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Reply that please (classmate’s response, Yolanny Ramirez)

Reply to the student no less than 200 words using 1 APA reference

Current Policies Related to Medicinal Marijuana

Medicinal marijuana policies in the United States vary quite significantly among states and have significantly changed over the past years. They outline issues such as legality, qualifying conditions, prescription processes, and distribution methods.

Federal Policy vs. State Policies

Despite this, marijuana remains classified under the federal Controlled Substances Act as a Schedule I controlled substance. It is therefore considered to have a high potential for abuse and no accepted medical use. This creates several problems for research and medical use, greatly compounding the legal situation for states in which medicinal marijuana has been legalized.

Although the use of medicinal marijuana remains restricted under federal law, many states have enacted laws that permit such use. By 2024, 38 states, the District of Columbia, and several U.S. territories had implemented comprehensive medical marijuana programs. Many of these programs identify certain specific conditions that are to be treated with medicinal marijuana. These most commonly include "chronic pain, epilepsy, multiple sclerosis, cancer, and HIV/AIDS."

Qualifying Conditions and Prescription Processes

State policy thus dictates what types of medical conditions qualify a patient to use medicinal marijuana. Chronic pain would be a fairly common qualifying condition in most of these states; where it differs is whether it includes Glaucoma, Crohn's Disease, or even Post-Traumatic Stress Disorder. Different qualifying conditions within the various conditions present variations reflective of differing views as to what types of medical use may be considered legitimate.

Prescription processes vary as well. In most states, the patient must get a recommendation from an approved health professional, provide clearance, and register their status with that state's medical marijuana program. In some cases, requirements under the state program include the need to update registration annually along with continued supervision by one's health care provider. Measurement

Distribution and Access

Another area of policy divergence regards access to medicinal marijuana. Most states ought to regulate cultivation, distribution, and sale through licensed dispensaries. For instance, some states allow the cultivation at home of a few plants for personal medical use, while others exercise rigorous control over the supplies through state-monitored dispensaries.

Another difference is how policies vary concerning the forms of medicinal marijuana allowed. Some states allow for smokable marijuana, while others restrict use to non-smokable forms, like edibles, oils, or tinctures.

Policy Challenges and Considerations

One of the bigger challenges facing medicinal marijuana policy is the inconsistency between federal and state laws, thus posing a series of legal and logistical problems for patients, providers, and research. Furthermore, there is nonuniformity in regulation between states, which would almost imply different access and quality to medicinal marijuana.

Another critical area affected by current policies is research. Federal Schedule I puts a damper on thorough research into the efficacy and safety of medicinal marijuana. Lacking rigorous scientific evidence, policymakers and healthcare providers are often left making decisions based upon limited or anecdotal evidence, which negatively affects clinical decision-making and patient outcomes.

Contemporary policies regarding medicinal marijuana resemble a patchwork of state laws operating within the constraints of federal prohibition. In large part, these policies reflect ongoing debates about the medical utility and safety, along with regulatory frameworks necessary for managing medicinal marijuana use. Continued evaluation and harmonization of policies inrente, along with rigorous research to address complexities to maximize the therapeutic potential of medicinal marijuana.

References

National Conference of State Legislatures. (2024). State Medical Cannabis Laws. Retrieved from https://www.ncsl.org/research/health/state-medical-marijuana-laws.aspx

Pacula, R. L., Smart, R., & Kilmer, B. (2022). The evolving policies on cannabis legalization and their effects. Annual Review of Law and Social Science, 18, 121-138.

Affordable Care Act

Do you believe that the Affordable Care Act (ObamaCare) should be repealed, replaced with something else, or stay in its current form? Why or why not?

Where should we place the blame for the Great Depression?

Where should we place the blame? Economists believe the Great Depression was caused by the weaknesses in the 1920s economy, but the person whose name will be forever linked to the depression is President Herbert Hoover. Personally blaming him for the crisis, Americans started to call the shantytowns set up by unemployed people "Hoovervilles."

no more than 150 words please

America's Great Depression – Causes and Cures (amatecon.com)

Microsoft Word – 9.prosperity_depression.doc.doc (uh.edu)

Hoover's presidency will be forever shadowed by the Great Depression. Is it fair to blame Hoover's actions or inaction for the Great Depression?

The_Unfinished_Nation_6e_the_great_depression.pdf

The Unfinished Nation: A Concise History of the American People, 6/e

Alan Brinkley, Columbia University

Debating the Past

Chapter Twenty-Five: The Great Depression

Where Historians Disagree – Causes of the Great Depression

What were the causes of the Great Depression? Economists and historians have debated

this question since the economic collapse began and still have not reached anything close to

agreement on it. In the process, however, they have illustrated several very different

theories about how a modern economy works.

During the Depression itself, different groups offered interpretations of the crisis that fit

comfortably with their own self-interests. Some corporate leaders claimed that the

Depression was the result of a lack of "business confidence," that businessmen were

reluctant to invest because they feared government regulation and high taxes. The Hoover

administrations blamed international economic forces and sought, therefore, to stabilize

world currencies and debt structures. New Dealers, determined to find a domestic solution

to the crisis, argued that the Depression was a crisis of "underconsumption," that low wages

and high prices had made it too difficult to buy the products of the industrial economy; and

that a lack of demand had led to the economic collapse.

Scholars in the years since the Great Depression have also created interpretations that fit

their view of how the economy works. One of the first important postwar interpretations

came from the economists Milton Friedman and Anna Schwartz, in their Monetary History of

the United States (1963). In a chapter entitled "The Great Contractions," they argued for

what has become known as the "monetary" interpretation. The Depression, they claimed,

was a result of a drastic contraction of the currency (a result of mistaken decisions by the

Federal Reserve Board, which raised interest rates when it should have lowered them).

These deflationary measures turned an ordinary recession into the Great Depression. The

monetary argument fits comfortably with the ideas that Milton Friedman, in particular, has

advocated for many years: that sound monetary policy is the best way to solve economic problems–as opposed to fiscal policies, such as taxation and spending.

A second, very different argument is known as the "spending" interpretation, an

interpretation supported by many liberal, Keynesian economists. It is identified with, among

others, the economist Peter Temin, and his book Did Monetary Forces Cause the Great

Depression? (1976). Temin's answer to his own question is "no." The cause of the crisis was

not monetary contraction (although the contraction made it worse), but a drop in

investment and consumer spending, which preceded the decline in the money supply and

helped to cause it. Here again, there are obvious political implications. If a decline in

spending was the cause of the Depression, then the proper response was an effort to

stimulate demand–raising government spending, increasing purchasing power,

redistributing wealth. The New Deal never ended the Depression because it did not spend

enough. World War II did end it because it pumped so much public money into the economy.

Another important explanation comes from the historian Michael Bernstein. In The Great

Depression (1987) he avoids trying to explain why the economic downturn occurred and

asks, instead, why it lasted so long. The reason the recession of 1929 became the

Depression of the 1930s, he argues, was the timing of the collapse. The recession began as

an ordinary cyclical downturn. Had it begun a few years earlier, the basic strength of the

automobile and construction industries in the 1920s would have led to a reasonably speedy

recovery. Had it begun a few years later, a group of newer, emerging industries would have

helped produce a recovery in a reasonably short time. But the recession began in 1929, too

late for the automobile and construction industries to help and too soon for emerging new

industries–aviation, petrochemicals and plastics, aluminum, and others–to help, since they

were still in their infancies.

The political implications of this argument are less obvious than those of some other

interpretations. But one possible conclusion is that if economic growth depends on the

successful development of new industries to replace declining ones, then the most sensible

economic policy for government is to target investment and other policies toward the

growth of new economic sectors. One of the reasons World War II was so important to the

long-term recovery of the U.S. economy, Bernstein's argument suggests, was not just that

it pumped money into the economy, but that much of that money contributed to developing

new industries. This is, in other words, an explanation of the Depression that seems to

support some of the economic ideas that became popular in the 1980s and 1990s calling for a more direct government role in stimulating the growth of new industries.

In the end, however, no single explanation of the Great Depression has ever seemed

adequate to most scholars. The event, the economist Robert Lucas once argued, is simply

"inexplicable" by any rational calculation. There is no one, wholly persuasive answer to the question of

The decision to drop the atomic bomb

Hiroshima: Harry Truman on Trial | History News Network (hnn.us)

Critics have charged that the United States was morally irresponsible in using atomic weapons against Japan during World War II. Were the United States' actions justified?

What are the arguments that have been presented against using the atomic bomb? What is your response to these arguments? Make sure that you provide specific support from your readings.

no more than 150 words please

The_Unfinished_Nation_dropping_the_bomb.pdf

The Unfinished Nation: A Concise History of the American People, 5/e

Alan Brinkley, Columbia University

Debating the Past

Chapter Twenty-Eight: America in a World at War

Where Historians Disagree – The Decision to Drop the Atomic Bomb

There has been continuing disagreement since 1945 among historians–and among many others–

about how to explain and evaluate President Truman's decision to use the atomic bomb in the war against Japan.

Truman himself, both at the time and in his 1955 memoirs, and many of his contemporaries insisted

that the decision was a simple and straightforward one. The alternative to using atomic weapons, he claimed, was an American invasion of mainland Japan that might have cost as many as a million lives. That view has received considerable support from historians. Herbert Feis argued in The Atomic Bomb and the End of World War II (1966) that Truman made his decision on purely military grounds–to ensure a speedy American victory. David McCullough, the author of an enormously popular biography of Truman published in 1992, also accepted Truman's own account of his actions largely uncritically,

as did Alonzo L. Hamby in Man of the People (1995), an important scholarly study of Truman. "One consideration weighed most heavily on Truman," Hamby concluded. "The longer the war lasted, the more Americans killed."

Others have strongly disagreed. As early as 1948, a British physicist, P.M.S. Blackett, wrote in Fear, War, and the Bomb that the destruction of Hiroshima and Nagasaki was "not so much the last military act of the second World War as the first major operation of the cold diplomatic war with Russia." The most important critic of Truman's decision is the historian Gar Alperovitz, the author of two influential books on the subject: Atomic Diplomacy: Hiroshima and Potsdam (1965) and The Decision to Use the

Atomic Bomb (1995). Alperovitz dismissed the argument that the bomb was used to shorten the war

and save lives. Japan was likely to have surrendered soon even if the bomb had not been used, he claimed. Instead, he argued, the United States used the bomb less to influence Japan than to intimidate the Soviet Union, "to make Russia more manageable in Europe."

John W. Dower's War Without Mercy (1986) contributed, by implication at least, to another controversial explanation of the American decision: racism. The Japanese, many Americans came to believe during the war, were almost a subhuman species. Even many of Truman's harshest critics, however, note that it is, as Alperovitz has written, "all but impossible to find specific evidence that racism was an important factor in the decision to attack Hiroshima and Nagasaki."

The debate over the decision to drop the atomic bomb is an unusually emotional one, and it has inspired bitter professional and personal attacks on advocates of almost every position. It illustrates clearly how history has often been, and remains, a powerful force in the way societies define themselves.

How has the automobile impacted American society?

In the 1950s the United States enjoyed a broad-based, unprecedented level of prosperity. Rising purchasing power, expanding credit, and a rapidly growing advertising industry stimulated consumerism. One industry that rapidly developed and expanded was the automobile industry. During the 1950s, Americans purchased 58 million cars. By 1960, 75 percent of American families owned one. The automobile created mobility on a scale not known before, and the automobile industry became a vital element in the economy. It became one of the world's major manufacturing industries. The automobile dramatically impacted American society, whether you owned one or not.

Discuss how the automobile positively or negatively impacted American society.
Do you agree or disagree with the assessment that has been made on the importance of the automobile?

no more than 100 words

PLAAFP

The details communicated in a Present Level of Academic Achievement and Functional Performance (PLAAFP) statement are part of an IEP and address the areas affected by the disability and the effect on academic progress. Because the PLAAFP provides a focus to the overall IEP, it is important to have a strong working knowledge about the information that is required to ensure the IEP is properly structured and best meets the needs of the student.

Review the “Sample PLAAFP” and “Present Level of Academic Achievement and Functional Performance (PLAAFP)” documents to become familiar with the content and structure of the PLAAFP. Review the “Charley” case study below to inform a PLAAFP that would guide the development of his IEP.

Case Study: Charley

Preschool, Age 4

Charley is an energetic 4-year-old preschool student with cerebral palsy. He is in his second year of preschool. His mother experienced a difficult pregnancy with him, and she had an emergency C-section due to the umbilical cord being wrapped around his neck. Charley was diagnosed with cerebral palsy at 18 months of age. He began receiving services in home at the age of 2.

Charley typically speaks in two-word sentences. He indicates his wants and needs by pointing. He gets frustrated when he is unable to communicate quickly. He prefers to do things independently. Charley was evaluated by a speech pathologist who determined he would benefit from a speech device. He began using the speech device, both at home and school, at the beginning of the school year. He is still learning to use it consistently. Charley tries to communicate without the speech device but will use it when asked. The parents are consistent with using the speech device at home.

Charley is in a wheelchair and has limited use of his arms. He can bunny hop on the floor. He needs some assistance with feeding and is still in diapers. He receives physical and occupational therapy twice a week. Charley demonstrates frustration when he is not able to be with the other students due to these activities.

Charley loves going to school. He interacts well with all of the students and teachers. He actively participates in all activities. He tends to shut down when the content of the lesson is too difficult for him. Charley can match objects to colors and can point to 17 of the letters of the alphabet and the numbers 1-10. He requires assistance with tasks such as cutting, gluing, etc. but he is able to use larger pencils and markers for some activities.

Charley’s parents are very involved in his school. His mother volunteers in the classroom once a week, and both parents have volunteered for field trips. They are Charley’s biggest cheerleaders! They help him when he needs it, but also push him to be as independent as he can. They have expressed concern about Charley’s future in school. They would like for him to be in a general education classroom when he begins kindergarten.

As Charley’s teacher, it is your responsibility to complete the subsections included in the PLAAFP section of an IEP. Using the “IEP Template,” provide the following information to complete “Section 3: Present Level of Academic Achievement and Functional Performance” for Charley’s IEP.

Cognitive (academic performance in content areas)
Physical (gross and fine motor, vision, and hearing)
Oral Language and Communication
Social and Emotional Behavior
Adaptive
Current Classroom-Based Data
Family Input on Student’s Current Performance
Summary of Work Habits

APA format is not required, but solid academic writing is expected.

This assignment uses a rubric. Review the rubric prior to beginning the assignment to become familiar with the expectations for successful completion.

You are required to submit this assignment to LopesWrite. A link to the LopesWrite technical support articles is located in Class Resources if you need assistance.

ECS-520_RS_Sample_PLAAFP2.docx

Present Level of Academic Achievement and Functional Performance (PLAAFP)

Special Education Department

Individualized Education Program (IEP)

Student Name: Lesley Jones Student Data/Cover Sheet (Form B) IEP Meeting Date: 02/10/21

Student ID: 22567876 DOB: 01/12/14

PRESENT LEVEL OF ACADEMIC ACHIEVEMENT AND FUNCTIONAL PERFORMANCE (PLAAFP)

Section 1: Current IEP Information

Summarize special education services the student is receiving:

Lesley is in 2nd grade. She receives special education services for a learning disability in reading fluency and reading comprehension.

Section 2: Evaluation Information

Lesley was evaluated in 1st grade, and it was determined that she was showing signs of dyslexia.

Areas of Eligibility:

Special Education Primary Category: Specific Learning Disability

For students with SLD only, the following area(s) of eligibility was previously determined:

reading fluency and reading comprehension

State and District Assessment Scores:

Lesley is falling far below the standard in Reading. In Math and Writing, she is approaching standard on the AIMS Assessment.

Section 3: Present Level of Academic Achievement and Functional Performance

A. Cognitive (academic performance in content areas, e.g., ELA/reading/writing, math, science, social studies, technology and fine arts, as applicable)

Reading

Areas of Strength: Lesley is currently reading at a pre-k level. She can identify all of the letters and their sounds but struggles with putting sounds together to form words. She does enjoy reading books with more pictures.

Areas of Need: Lesley struggles with answering questions about a text she has read, but does better when there are pictures to choose from to answer the questions.

Writing

Areas of Strength: Lesley's handwriting is very legible, but she does not enjoy writing. Lesley can write a complete sentence independently. She can use appropriate punctuation in her writing. She is beginning to combine her thoughts to develop a full paragraph.

Areas of Need: Lesley is unable to write a well-structured paragraph aligned with a given writing prompt.

Math

Areas of Strength: Lesley does very well with basic math skills. She enjoys math and enjoys using manipulatives to complete her work. She can add and subtract double digits with regrouping. She draws pictures to solve word problems. She is beginning to work on basic multiplication and division.

Areas of Need: Lesley struggles with determining the needed computation steps to solve word problems independently.

B. Physical (gross motor, fine motor, vision, and hearing)

Area of Strength:

Areas of Need: Lesley currently has no needs in this area.

C. Oral Language and Communication

Areas of Strength: Lesley can communicate well verbally,

Areas of Need: Lesley struggles with oral presentations in front of a group.

D. Social and Emotional Behavior

Areas of Strength: Lesley follows direction well from teachers and adults.

Areas of Need: Lesley's only health concern is her asthma, which can, at times, limit her ability to participate in physical activity. She takes medication for both asthma and depression. The depression medication can sometimes make her feel drowsy.

At times, Lesley exhibits inappropriate behavior with friends and classmates. She can be easily distracted and then she becomes upset when she misses information, resulting in a conflict with either the teacher or a classmate.

Since the Behavior Intervention Plan (BIP) has been set up, her attendance to classes where conflict existed has increased. She does not have any tardies at this time. Her time outs are self- monitored. Behavior does significantly and adversely impact the progress in the general curriculum.

E. Adaptive

Areas of Strength: Not applicable at this time.

Areas of Need: Not applicable at this time.

Current Classroom-Based Data:

All of Lesley's teachers enjoy having her in class. She completes assignments in a timely manner and never overextends her allowed extra time.

Family Input on Student’s Current Performance:

· Lesley's parents are very satisfied with her current academic achievement. They are happy that she is getting good grades in all her subjects with little support.

· Lesley's parents are impressed with Lesley's Functional Achievement as it relates to behavior.

Summary of Work Habits:

· Lesley learns best in a classroom environment with activities that she can see and work on independently.

· Lesley can use a computer well.

· Test taking can require a little extra time for Lesley.

Summary of Educational Needs:

Based on the information from the current multidisciplinary evaluation, academic achievement, functional performance, and transition-based data (if applicable), the IEP team has determined that the student has educational needs in the following areas:

· Reading fluency and reading comprehension.

She will receive support in the resource classroom.

image1.jpeg

Nursing Wk 1 Assignment

Please do not plagiarize Follow instructions provided Pay attention to the due date Answer each bullet point Topic Attached! 5 References needed

Nursing Introduction & PICOT Question Assignment

Introduction for the project

2-3 PAGES IN LENGTH

******TOPIC IS INFECTION CONTROL AND PREVENTION IN THE NICUs*********

Introduction includes:

Your PICOT question. (SUGGESTED TIME FRAME FOR (T) IS 3-6 MONTHS)
Purpose of / or rationale for the scholarly project:
- Evidence-based explanation of why it is necessary to complete your scholarly project and what benefit will be gained (health promotion, fiscal, and efficiency).
Background on the problem or population of interest:
- Using primary sources, provide data on your topic.
- Providing the background will demonstrate the focused need for your project.
Significance of the problem to nursing and health care:
- How your problem or population of interest aligns with the larger interest of health care in the community.
- context as to why your topic is important.
Benefit of the project to nursing practice:
- what will be gained from your project.
- what are the expected outcomes of your project to practice within your population and setting.
- compare the outcomes to evidence-based guidelines and outcomes.
- how your project may influence other populations or settings.

Instructions:

must be submitted via Turnitin and not exceed 20% score for AI and similarity.

***************PLEASE INCLUDE AI AND PLAGIARISM REPORTS**********

The introduction is original work and logically organized.
must be 2-3 pages in length and follows current APA7 format including citation of references.
Incorporate a minimum of 4 current (published within the last five years) scholarly journal articles or primary legal sources (statutes, court opinions) within your work.
USE THE SAME 4 ARTICLES AS IN THE PREVIOUS ASSIGNMENTS (ARTICLES ATTACHED )
Journal articles and books should be referenced according to the current APA style (the library has a copy of the APA Manual).

S26 | www.pidj.com The Pediatric Infectious Disease Journal • Volume 41, Number 3S, March 2022

ISSN: 0891-3668/22/4101-0S26 DOI: 10.1097/INF.0000000000003320

Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc. This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY- NCND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commer- cially without permission from the journal.

Supplement

The Impact of Interventions to Prevent Neonatal Healthcare-associated Infections in Low- and Middle-income

Countries: A Systematic Review Felicity C. Fitzgerald, PhD,*† Walter Zingg, PhD,‡ Gwendoline Chimhini, MMED, MPH,§ Simbarashe Chimhuya, MMED,§ Stefanie Wittmann, MD,¶ Helen Brotherton, MBChB,¶‖

Ioana D. Olaru, MBBS,†¶ Samuel R. Neal, MRes,* Neal Russell, MBBS,** André Ricardo Araujo da Silva, PhD,†† Mike Sharland, FRCPCH,** Anna C. Seale, DPhil,¶

Mark F. Cotton, M.Med, PhD,‡‡ Susan Coffin, MD,§§ and Angela Dramowski, PhD‡‡

Background: Clinically suspected and laboratory-confirmed bloodstream infections are frequent causes of morbidity and mortality during neonatal care. The most effective infection prevention and control interventions for neonates in low- and middle-income countries (LMIC) are unknown. Aim: To identify effective interventions in the prevention of hospital- acquired bloodstream infections in LMIC neonatal units. Methods: Medline, PUBMED, the Cochrane Database of Systematic Reviews, EMBASE and PsychInfo (January 2003 to October 2020) were searched to identify studies reporting single or bundled interventions for prevention of bloodstream infections in LMIC neonatal units. Results: Our initial search identified 5206 articles; following application of fil- ters, 27 publications met the inclusion and Integrated Quality Criteria for the Review of Multiple Study Designs assessment criteria and were summarized in the final analysis. No studies were carried out in low-income countries, only 1 in Sub-Saharan Africa and just 2 in multiple countries. Of the 18 single-interven- tion studies, most targeted skin (n = 4) and gastrointestinal mucosal integrity (n = 5). Whereas emollient therapy and lactoferrin achieved significant reductions in proven neonatal infection, glutamine and mixed probiotics showed no ben- efit. Chlorhexidine gluconate for cord care and kangaroo mother care reduced

infection in individual single-center studies. Of the 9 studies evaluating bundles, most focused on prevention of device-associated infections and achieved sig- nificant reductions in catheter- and ventilator-associated infections. Conclusions: There is a limited evidence base for the effectiveness of infec- tion prevention and control interventions in LMIC neonatal units; bundled interventions targeting device-associated infections were most effective. More multisite studies with robust study designs are needed to inform infection pre- vention and control intervention strategies in low-resource neonatal units.

Key Words: Infection prevention and control, low-and-middle income countries, systematic review, neonatal infection, hospital-acquired infection

(Pediatr Infect Dis J 2022;41:S26–S35)

The World Health Organization estimates that bacterial infec- tions cause ≈25% of the 2.8 million annual neonatal deaths and

long-term neurodevelopmental disabilities in survivors.1 Hospital- acquired infection (HAI) is a major cause of neonatal morbidity and mortality with prevalence ratios in low- and middle-income countries (LMICs) 3–20× higher than high-income countries.2 Tra- ditional definitions, applied in high-income countries, use a 72-hour cutoff to differentiate early- from late-onset infection: the former associated with vertical transmission of pathogens such as group B Streptococcus, the latter with horizontal transmission of hospital- acquired pathogens, often associated with prematurity and invasive procedures such as intravenous catheterization. However, particu- larly in LMICs, there is recognition that facility-based delivery is itself a risk for HAIs, with pathogens such as Klebsiella pneumoniae (previously associated with late-onset infection) commonly isolated in the first 24 hours of life.2,3 This observation informs the Strength- ening the Reporting of Observational Studies in Epidemiology for Newborn Infection guidelines, which recommend recording the tim- ing of symptom onset rather than the binary early/late-onset dico- hotomy.1 It also raises questions about fundamental differences in the mechanisms of neonatal infections in LMICs, as compared with high-income countries. The leading neonatal pathogens are increas- ingly resistant to first- and second-line antimicrobials, with substan- tial resistance to commonly used agents including ampicillin (89% of Escherichia coli), ceftriaxone (49% of Klebsiella spp. isolates) and cloxacillin (40% of Staphylococcus aureus).3

In this context, effective, feasible and affordable interventions to enhance infection prevention and control (IPC) in LMIC neonatal units are critical to prevent both neonatal mortality and emerging antimicro- bial resistance. However, even in high-income settings, implementing effective prevention measures is challenging, and a robust evidence base on what tools to use is limited. Randomized controlled trials are considered the gold standard for generating evidence in general. How- ever, best practice procedures and quality improvement interventions

Accepted for publication August 12, 2021 From the *Department of Infection, Immunity and Inflammation, UCL Great

Ormond Street Institute of Child Health, London, United Kingdom, †Bio- medical Research and Training Institute, Harare, Zimbabwe, ‡Department of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, University of Zurich, Zurich, Switzerland, §Department of Paediat- rics and Child Health, University of Zimbabwe College of Health Sciences, Zimbabwe, ¶Clinical Research Department, London School of Hygiene and Tropical Medicine, London, United Kingdom, ‖MRC Unit, The Gambia at the London School of Hygiene & Tropical Medicine, Fajara, The Gambia, **Paediatric Infectious Diseases Research Group, St George’s University of London, United Kingdom, ††Laboratory of Teaching of Prevention and Control of Healthcare-Associated Infections, Federal Fluminense University, Brazil, ‡‡Department of Paediatrics and Child Health, Division of Paediatric Infectious Diseases, Stellenbosch University, South Africa, and §§Children’s Hospital of Philadelphia, Pennsylvania, Philadelphia.

F.C.F. is supported by the Academy of Medical Sciences, the funders of the Starter Grant for Clinical Lecturers scheme and UCL Great Ormond Street NIHR Biomedical Research Centre. A.D. is supported by the Fogarty Inter- national Center of the National Institutes of Health, Emerging Global Leader Award Number K43-TW010682.

Address for correspondence: Angela Dramowski, PhD, Department of Paediat- rics and Child Health, Division of Paediatric Infectious Diseases, Stellen- bosch University, South Africa. E-mail: [email protected]

Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s website (www.pidj.com)

mailto:[email protected]

www.pidj.com

The Pediatric Infectious Disease Journal • Volume 41, Number 3S, March 2022 Low-income Neonatal Units: Infection Prevention

must be contextual for maximum impact. As interventions are seldom identical across trial sites, patient-level randomization is often not possi- ble. Trials within hospitals (randomizing wards for example) are at risk of bias due to movement between wards of staff and patients. Further- more, matching hospitals for randomization can be complex.4

To address these methodologic challenges, new study designs, such as interrupted time series for cohorts and hospital-level stepped- wedge cluster randomization, have been adopted. In addition, qualita- tive research aiming at understanding behavior change is increasingly used to complement quantitative data.4 For neonates in LMICs, vari- ous HAI prevention strategies have been suggested but only studied in small and single-center studies. To date, the evidence base in these settings has not yet been systematically assessed. We set out to review a broad range of potential interventions (both single and bundled), aiming to reduce healthcare-associated infections, with a focus on bloodstream infections (BSIs) in LMIC neonatal units.

METHODS This systematic review was conducted in adherence with

the Preferred Reporting Items for Systematic Reviews and Meta- Analyses statements of evaluations of healthcare interventions.5 We registered the search strategy on the international prospective register of systematic reviews (CRD42018112346 on International prospective register of systematic reviews; see Supplemental Digi- tal Content, http://links.lww.com/INF/E517).

Search Strategy We searched Medline, the Cochrane Database of Systematic

Reviews, EMBASE and PsychInfo (January 1, 2003, to October 31, 2020) to identify studies reporting on the effectiveness of interven- tions to prevent infections in LMIC neonatal wards and neonatal intensive care units. We selected the year 2003 to reflect the rapid evolution and spread of resistant bacteria causing HAIs in the last 17 years. IPC interventions were defined as any intervention aiming to prevent the development of a healthcare-associated bacterial or fun- gal infection such as BSI, meningitis, laboratory-confirmed urinary tract infection or clinically suspected but culture-negative infections.

We limited results by age [neonates 0–27 days or 0–89 days if admitted on a neonatal ward or neonatal intensive care unit (NICU)], location (LMIC as defined by the 2021 World Bank classification6), language (articles written in English, German, French, Italian, Portu- guese and Spanish were included) and by relevant filters as per exclu- sion criteria (for a full list of terms and filters, see Supplemental Digital Content, http://links.lww.com/INF/E517). Our primary outcome was the effect of the interventions on (1) incidence of infection or (2) attrib- utable mortality, depending on study definitions. Fungal or bacterial hospital-acquired invasive infections in hospitalized neonates were the primary events for study. Secondary outcomes included impact on incidence of laboratory-confirmed urinary tract infection, throm- bophlebitis, necrotizing enterocolitis (NEC), device-associated infec- tions (clinically suspected or culture proven) and clinically suspected infection where laboratory cultures were negative or not available.

Inclusion Criteria Studies were eligible for full-text review if conducted in hos-

pitalized neonates, including neonatal ward and/or NICU settings, with a detailed description of the intervention. We included both single interventions [eg, probiotics, kangaroo mother care (KMC), breastfeeding, fluconazole prophylaxis] and bundled interventions (eg, vascular device care, hand hygiene and healthcare worker edu- cation combined). Studies conducted in several countries includ- ing both high-income countries and LMICs (as per the World Bank 2021 regions) could be included if possible, to extract data from the LMIC settings. Study designs included randomized controlled

trials, controlled and noncontrolled before-after, controlled and noncontrolled interrupted time series and cohort studies.

Exclusion Criteria We excluded letters, opinion articles and reviews that did

not report primary data. IPC interventions conducted during mater- nal care, in community-based settings and during outbreaks, were excluded. We also excluded studies conducted exclusively in high- income countries as per the World Bank 2021 regions.6 Interven- tions targeting viral infections (including HIV), infants older than 3 months or involving vaccination, diagnostic tools, infection predic- tion scores were excluded. We also excluded studies addressing IPC interventions on mixed neonatal/pediatric populations where extrac- tion of neonatal data was not possible and where only abstracts were available despite contacting the corresponding author. Finally, we excluded studies where bacterial colonization as opposed to invasive infection was the outcome, if BSI was not also included.

Study Selection Process The initial eligibility assessment of titles and abstracts identified

by our search was conducted independently by F.C.F. and A.D. using the predetermined inclusion and exclusion criteria. Disagreements on eligibility were resolved by consensus, if needed by consulting a third party. The reference lists of all eligible publications were screened for cross-referencing. After finalizing articles for full-text review, 2 authors evaluated the quality of each eligible publication using the Integrated Quality Criteria for the Review of Multiple Study Designs (ICROMS) tool,7 with disagreements resolved as explained above. The ICROMS tool was designed to allow the systematic integration and assessment of differing study types including both quantitative and qualitative designs for reviews of public health interventions such as those targeting IPC.7 The ICROMS tool provides a list of quality criteria with a set of require- ments specific for the study design. Studies are evaluated by a “decision matrix” where mandatory criteria must be met. The robustness of the study is measured by a score (see Tables, Supplemental Digital Content, http://links.lww.com/INF/E517, for criteria and scoring). To pass to the final analysis, studies must meet the minimum score and the mandatory ICROMS criteria, after duplicate review.

Data Abstraction We extracted data using a standardized data collection form

already independently piloted by F.C.F. and A.D. on a representa- tive sample of studies. Study details collected on the form included author(s), year of publication, country or countries where the study was performed, study design, study time frame, setting (neonatal ward, NICU or both), intervention type, intervention details and effect. We grouped studies by intervention type: IPC bundles, catheter care, skin integrity and bacterial colonization (umbilical cord care, skin cleansing, emollients and/or massage), fluconazole prophylaxis, hand hygiene, KMC, rooming-in/parental involvement in neonatal care and gastrointestinal integrity (probiotics and feeding practices). Data synthesis involved the collation and tabulation of results by interven- tion type, summarizing the key interventions and their effectiveness in IPC for hospitalized neonates (using either relative risk, odds ratios or hazard ratios as reported by each study). We did not undertake a meta- analysis due to diversity of study type, interventions and outcomes; although all studies targeted reduction of neonatal infections, each study had different modes of action for the intervention and/or major differences in study design that precluded combining data.

RESULTS We identified 5206 articles on initial searching, after

removal of duplicates (Fig. 1). Filter application (see Appendix,

http://links.lww.com/INF/E517

The Pediatric Infectious Disease Journal • Volume 41, Number 3S, March 2022

Fitzgerald et al

Supplemental Digital Content, http://links.lww.com/INF/E517) reduced this to 1799 titles and abstracts then reviewed indepen- dently by 2 study authors (F.C.F. and A.D.) for relevance. Of these,

124 were selected for full-text review in duplicate and ICROMS scoring, leading to another 97 exclusions and 27 selected for inclu- sion in the final review (Tables 1 and 2). Forty studies were excluded

FIGURE 1. Search strategy for the identification and selection of publications reporting the effectiveness of interventions to prevent infections in neonatal wards and intensive care (January 2003–October 2020).

http://links.lww.com/INF/E517

The Pediatric Infectious Disease Journal • Volume 41, Number 3S, March 2022

Low-income Neonatal Units: Infection Prevention T

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(C on

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)

The Pediatric Infectious Disease Journal • Volume 41, Number 3S, March 2022

Fitzgerald et al

G at

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9/ 38

2 (i

n te

rv en

– ti

on )

vs . 4

4/ 36

4 (c

on tr

ol s)

b u

t m

or e

m il

d/ m

od er

at e

in fe

ct io

u s

ep is

od es

( 7%

in te

rv en

ti on

s vs

3 %

c on

tr ol

s) ,

ab so

lu te

fi gu

re s

n ot

g iv

en . R

ed u

ct io

n in

n os

oc om

ia l

in fe

ct io

n s:

8 %

v s.

4 %

in in

te rv

en ti

on s/

co n

tr ol

(P =

0 .0

26 )

ab so

lu te

fi gu

re s

n ot

g iv

en L

i e t

al 23

N C

B A

C h

in a

S ta

bl e

n eo

n at

>1 50

0 g

in 1

N N

U 14

46 R

oo m

in g-

in N

eo n

at es

m ov

ed t

o R

oo m

-i n

f ro

m N

IC U

= 1

01 8)

v s.

t h

os e

el ig

ib le

t o

m ov

e bu

t st

ay in

g in

N IC

(n =

4 28

). 62

9 ad

m it

te d

di re

ct ly

t o

R oo

m -i

M or

ta li

ty , g

ro w

th , d

u ra

ti on

a dm

is si

on . s

ec on

da ry

tc om

es : n

os oc

om ia

l i n

fe c –

ti on

a n

d N

E C

( u

n cl

ea r

h ow

fi n

ed )

N o

di ff

er en

ce in

n os

oc om

ia l i

n fe

ct io

n : 1

00 /1

08 1

vs . 4

8/ 42

8 in

in te

rv en

ti on

s vs

. c on

tr ol

s; P

= 0

.4 1;

f ew

er n

eo n

at es

t h

e in

te rv

en ti

on g

ro u

p w

it h

N E

C : 7

/1 08

1 vs

. 8 /4

(P =

0 .0

4) .

R ed

u ct

io n

in m

or ta

li ty

: 2 %

v s.

0 %

; P <

0 .0

P ar

ik h

a l25

R C

T In

di a

P re

te rm

n eo

n at

<1 50

0 g

ad m

it te

d to

te rt

ia ry

N N

12 0

F lu

co n

az ol

e pr

op h

y- la

xi s

F lu

co na

zo le

p ro

ph yl

ax is

it hi

n th

e fir

st 3

d t

o da

y 28

o r

di sc

ha rg

e/ de

at h

if s

oo ne

r (n

= 6

vs . p

la ce

bo (n

= 6

F u

n ga

l c ol

on iz

at io

n a

n d

in va

si ve

f u

n ga

l i n

fe ct

io n

lt u

re s

ta ke

n o

n d

ay s

1– 3,

1 4,

2 1

an d

N o

re du

ct io

n in

in va

si ve

c an

di da

in fe

ct io

n d

et ec

te d

bl oo

d cu

lt u

re s:

1 6/

60 e

pi so

de s

vs . 1

5/ 60

in in

te rv

en ti

vs . c

on tr

ol ; P

= 0

.8 35

; o f

n ot

e, 3

0/ 31

o f

in va

si ve

s pe

ci es

er e

n on

-a lb

ic an

s sp

ec ie

B ar

re ra

a l21

C oh

or t

C ol

om bi

a A

ll n

eo n

at es

m it

te d

to 1

N N

U 66

55 H

an d

h yg

ie n

e In

tr od

u ct

io n

o f A

B H

di sp

en se

rs ; i

n it

ia l

ed u

ca ti

on ; d

ai ly

rv ei

ll an

ce , q

u ar

te rl

y fe

ed ba

H A

I, C

L A

B S

I, V

A P

a n

d U

T I

as p

er C

D C

d efi

n it

io n

s 12

60 p

at ie

n ts

w it

h H

A I,

7 24

/1 84

8 ep

is od

es c

on fi

rm ed

c u

lt u

re . T

re n

d in

r ed

u ct

io n

o f

M et

h ic

il li

n -r

es is

ta n

t S

ta ph

yl oc

oc cu

s au

re u

s, 2

.2 –0

.6 in

fe ct

io n

s/ 10

00 p

at ie

n t-

da ys

in f

ro m

2 00

1– 20

05 , −

30 %

, P =

0 .0

01 N

o tr

en d

in r

ed u

ct io

n o

f A

ci n

et ob

ac te

r ba

u m

an n

ii (

0. 6–

0. 2/

10 00

p at

ie n

t- da

ys ; P

v al

u e

n ot

g iv

en )

S ig

n ifi

ca n

t in

cr ea

se in

u se

o f

al co

h ol

-b as

ed h

an d

ru b

M en

de s

an d

P ro

– ci

an oy

R C

T B

ra zi

l 1

N IC

U , a

ll n

eo n

at es

≤3

2 w

ee ks

’ G A

a n

d 75

0– 15

00 g

10 4

M as

sa ge

er ap

y M

as sa

ge t

h er

ap y

(t ac

ti le

– ki

n es

th et

ic s

ti m

u la

– ti

on , n

= 5

2) v

s. n

o in

te rv

en ti

(n =

5 2)

P ri

m ar

y ou

tc om

e: le

ng th

o f N

N U

ay ; s

ec on

da ry

o ut

co m

es :

w ei

gh t g

ai n,

ti m

e to

e nt

er al

ed s,

ti m

e to

o ra

l f ee

ds ,

in ci

de nc

e of

L O

S (c

lin ic

al ly

d bl

oo d

cu lt

ur e

co nfi

rm ed

), in

ci de

nc e

of N

E C

(c lin

ic al

a nd

di ol

og ic

c on

fir m

at io

L ow

er in

ci de

n ce

L O

S in

in te

rv en

ti on

v s.

c on

tr ol

s (5

/4 6

vs . 1

8/ 47

; P =

0 .0

05 );

8 vs

. 2 2

pa th

og en

s id

en ti

fi ed

cu lt

u re

s (u

n cl

ea r

h ow

m an

y cu

lt u

re s

h ad

m u

lt ip

pa th

og en

s) .

B ar

rí a

a l24

R C

T C

h il

e “h

ig h

-r is

k” n

eo n

at es

m it

te d

to 1

N U

74 In

tr av

en ou

s ca

th et

er i-

za ti

P er

ip h

er al

ly in

se rt

ce n

tr al

c at

h et

er s

= 3

7) v

s. s

ta n

da rd

ri ph

er al

in tr

av en

ou s

ca th

et er

s (n

= 3

L en

gt h

o f

n eo

n at

al in

te n

si ve

re u

n it

s ta

y an

d in

ci de

n ce

in fe

ct io

n a

n d

ph le

bi ti

N o

di ff

er en

ce in

in ci

de n

ce o

f su

sp ec

te d

in fe

ct io

n b

et w

ee n

ou ps

: 1 4/

37 v

s. 8

/3 7;

P =

0 .1

27 O

r cu

lt u

re -p

ro ve

n in

fe ct

io n

: 1 /3

7 vs

. 2 /3

7; P

= 0

.5 3.

R ed

u c –

ti on

in p

h le

bi ti

s: 4

/3 7

vs . 1

5/ 37

; P =

0 .0

07 . n

o di

ff er

en ce

t h

e le

n gt

h o

f st

ay : m

ed ia

n , 2

0 vs

. 1 7

d in

in te

rv en

– ti

on /c

on tr

ol g

ro u

ps ; P

= 0

.1 58

A B

H R

in di

ca te

s al

co h

ol -b

as ed

h an

d ru

b; C

A -B

S I,

c at

h et

er -a

ss oc

ia te

d bl

oo d

st re

am in

fe ct

io n

s; C

B A

, c on

tr ol

le d

be fo

re a

n d

af te

r; C

L A

B S

I, c

en tr

al li

n e–

as so

ci at

ed b

lo od

st re

am in

fe ct

io n

; C V

C , c

en tr

al v

en ou

s ca

th et

er s;

I T

S, in

te rr

u pt

ti m

e se

ri es

; I R

R , i

n ci

de n

t ra

te r

at io

; L O

S, la

te -o

n se

t in

fe ct

io n

; N C

B A

, n on

co n

tr ol

le d

be fo

re a

n d

af te

T A

B L

E 1

. (C

on ti

n u

ed ).

A u

th or

S tu

D es

ig n

* C

ou n

tr y

P op

u la

ti on

/S et

ti n

g S

am pl

e S

iz e

In te

rv en

ti on

pe In

te rv

en ti

on O

u tc

om e

K ey

F in

di n

The Pediatric Infectious Disease Journal • Volume 41, Number 3S, March 2022

Low-income Neonatal Units: Infection Prevention T

A B

L E

2 .

B u

n dl

ed I

n te

rv en

ti on

s fo

r th

e P

re ve

n ti

on o

f H

os pi

ta l-

A cq

u ir

ed N

eo n

at al

B lo

od st

re am

I n

fe ct

io n

s an

d C

li n

ic al

ly S

u sp

ec te

d In

fe ct

io n

L ow

-r es

ou rc

e S

et ti

n gs

( Ja

n u

ar y

20 03

t o

S ep

te m

be r

20 18

)

A u

th or

S tu

D es

ig n

C ou

n tr

y P

op u

la ti

on /

S et

ti n

g S

am pl

e S

iz e

B u

n dl

e E

le m

en ts

O u

tc om

e( s)

K ey

F in

di n

A za

b et

a l26

N C

B A

E gy

pt 1

N IC

U , a

N IC

ad m

is –

si on

s w

it h

ra ti

of in

va si

ve n

ti la

ti on

8 h

62 v

s. 8

1 V

A P

p re

ve n

ti on

b u

n dl

e +

ro u

ti n

e IP

C m

ea su

re s:

h ea

d- of

-b ed

ev at

io n

, h an

d h

yg ie

n e,

s te

ri le

ct io

n in

g, s

tr ic

t in

di ca

ti on

s fo

r in

tu ba

ti on

, r ei

n tu

ba ti

on a

n d

su c-

ti on

in g,

v en

ti la

to r

ci rc

u it

c h

an ge

v is

ib ly

s oi

le d

or m

al fu

n ct

io n

in g,

ou th

c ar

e, d

ai ly

e va

lu at

io n

f or

ad in

es s

fo r

ex tu

ba ti

on , s

ed at

io n

ca ti

on s

V A

P e

pi so

de s

pe r

10 00

ec h

an ic

al v

en ti

la to

r da

V A

P r

at e

re du

ce d

fr om

3 6.

4 to

2 3

ep is

od es

/1 00

0 M

da ys

( R

R 0

.5 65

; 9 5%

C I

0. 40

8– 0.

78 2;

P =

0 .0

00 6)

d re

du ce

d M

V d

ay s/

ca se

in t

h e

po st

in te

rv en

ti on

ri od

( 21

.5 0

± 7.

6 to

1 0.

36 ±

5 .2

d ; P

= 0

.0 00

1) .

T re

n d

to w

ar d

re du

ct io

n in

N IC

U L

O S

( 23

.9 ±

1 0.

3 to

2 2.

8 ±

9. 6

d; P

= 0

.5 6)

a n

d ov

er al

l m or

ta li

(2 5%

–1 7.

3% ; P

= 0

.2 15

)

L en

gt h

o f

st ay

in N

IC U

O ve

ra ll

m or

ta li

G il

be rt

a l32

N C

I T

S B

ra zi

l 5

N N

U s,

a ll

m is

si on

s <1

50 0

67 9

vs . 5

63 N

u rs

e tr

ai n

in g

pa ck

ag e,

in cl

u di

n g

IP C

m ea

su re

s M

or ta

li ty

in V

L B

W n

eo –

n at

es (

pr im

ar y

ou tc

om e)

D es

pi te

im pr

ov em

en t

in n

u rs

es ’ k

n ow

le dg

e an

d pr

ac ti

ce s,

t h

er e

w as

n o

ch an

ge in

s u

rv iv

al (

pr e-

tr ai

n in

g, 8

0% ; p

os t-

tr ai

n in

g, 7

8. 2%

), se

ve re

R O

(1 .6

v s.

2 .8

% ),

la te

-o n

se t

in fe

ct io

n (

11 .3

v s.

1 2.

3 ca

se s/

10 00

in fa

n t

da ys

) or

o th

er o

u tc

om es

In ci

de n

ce o

f la

te -o

n se

t in

fe ct

io n

, N E

C a

n d

ot h

se co

n da

ry o

u tc

om es

G il

l e t

al 31

N C

B A

P h

il ip

pi n

es 2

N IC

U s,

a ll

m is

si on

s be

tw ee

20 03

a n

d 20

04 .

ph as

e 1,

9 25

; ph

as e

2, 9

02 B

u n

dl e

w it

h b

lo od

c u

lt u

re q

u al

– it

y im

pr ov

em en

t, p

ro vi

si on

o f

al co

h ol

h an

d ru

b, in

fe ct

io n

a n

d H

H s

u rv

ei ll

an ce

, e du

ca ti

on , c

as e

di sc

u ss

io n

s, in

fe ct

io n

c on

tr ol

ec kl

is ts

P ro

po rt

io n

o f

n eo

n at

n ew

ly c

ol on

iz ed

w it

re si

st an

t pa

th og

en s.

ec on

da ry

o u

tc om

in cl

u de

d ba

ct er

em ia

te s,

c u

m u

la ti

m or

ta li

ty in

N IC

U a

n d

h an

d h

yg ie

n e

co m

pl i-

an ce

r at

R at

es o

f co

lo n

iz at

io n

w it

h d

ru g-

re si

st an

t pa

th og

en s

an d

ra te

s of

in fe

ct io

n d

id n

ot c

h an

ge s

ig n

ifi ca

n tl

S ta

ff h

an d

h yg

ie n

e co

m pl

ia n

ce im

pr ov

ed c

om pa

re d

w it

h t

h e

co n

tr ol

p er

io d

(N IC

U 1:

R R

1 .3

; 9 5%

C I

1. 1–

1. 5;

N IC

U 2:

R R

1 .6

; 9 5%

C I

1. 4–

2. 0)

. O ve

ra ll

or ta

li ty

d ec

re as

ed (

N IC

U 1:

R R

0 .5

; 9 5%

C I

0. 4–

0. 6;

N IC

U 2:

R R

0 .8

; 9 5%

C I

0. 7–

0. 9)

L en

g et

a l33

C oh

or t

C h

in a

1 N

N U

, co

n se

cu ti

ou tb

or n

eo n

at es

50 0

86 v

s. 8

6 H

yp ot

h er

m ia

p re

ve n

ti on

b u

n dl

e in

cl u

di n

g st

an da

rd iz

ed t

ra n

sp or

t pr

oc ed

u re

s, s

ki ll

ed t

ra n

sf er

am s,

p ro

ce ss

r ev

ie w

s w

it h

ed ba

A xi

ll ar

y te

m pe

ra tu

on a

rr iv

al (

pr im

ar y

ou tc

om e)

M ea

n d

el iv

er y

ro om

a n

d N

IC U

a dm

is si

on t

em pe

ra –

tu re

s ro

se f

ro m

3 5.

5 to

3 6.

1 °C

a n

d fr

om 3

4. 6

36 .2

°C (

P <

0 .0

1) , w

it h

s ig

n ifi

ca n

tl y

de cr

ea se

d m

or ta

li ty

( P

< 0

.0 2)

. T h

er e

w as

n o

di ff

er en

ce in

t h

e in

ci de

n ce

o f

N E

C a

n d

in fe

ct io

n f

ol lo

w in

g im

pl e-

m en

ta ti

on o

f th

e in

te rv

en ti

on .

D es

cr ip

ti on

o f

ra te

s of

E C

, e ar

ly –

an d

la te

– on

se t

n eo

n at

al in

fe ct

io n

M w

an an

– ya

n da

a l34

C oh

or t

Z am

bi a

A ll

ad m

is si

on s

to 1

N N

U 26

69 : 8

ba se

li n

e, 2

im pl

em en

ta –

ti on

, 1 54

9 in

te rv

en ti

ev al

u at

io n

IP C

t ra

in in

g, t

ex t

m es

sa ge

r em

in d-

er s,

a lc

oh ol

h an

d ru

b, e

n h

an ce

d en

vi ro

n m

en ta

l c le

an in

g an

d w

ee kl

y ba

th in

g of

n eo

n at

≥1 .5

k g

w it

h 2

% c

h lo

rh ex

id in

e gl

u co

n at

M or

ta li

ty p

ri m

ar y

ou t-

co m

e, H

A I,

B S

I se

co n

d- ar

y ou

tc om

A bs

ol u

te m

ea n

m on

th ly

m or

ta li

ty r

ed u

ct io

n , –

(9 5%

C I

–1 1

to –

7) ; o

ve ra

ll r

el at

iv e

m or

ta li

ty r

is k

re du

ct io

n , 2

1% (

R R

0 .7

9; 9

5% C

I 0.

76 –0

.8 3)

In ci

de n

ce r

at e

ra ti

o of

s u

sp ec

te d

in fe

ct io

n (

0. 48

–0 .6

an d

pa th

og en

-i de

n ti

fi ed

( 0.

28 –0

.6 2)

d ec

re as

ed f

al l w

ei gh

t gr

ou ps

e xc

ep t

<1 k

g su

sp ec

te d

in fe

ct io

(1 .3

8; P

= 0

.5 3;

P v

al u

es f

or o

th er

s, a

ll <

0. 00

1) R

es en

et a

l30 N

C B

A B

ra zi

l A

ll ad

m is

si on

s to

1 N

N U

25 1

C at

h et

er b

u n

dl e:

s u

rv ei

ll an

ce ,

fe ed

ba ck

o f

C A

-B S

I; e

du ca

ti on

, tr

ai n

in g,

p os

te rs

, h an

d h

yg ie

n e;

ll -b

ar ri

er p

re ca

u ti

on s

du ri

n g

C V

C in

se rt

io n

; c h

lo rh

ex id

in e

sk in

ea n

in g;

a vo

id in

g fe

m or

al s

it e;

m ov

in g

u n

n ec

es sa

ry c

at h

et er

B S

I ra

te s

pr e/

po st

-i n

te r-

ve n

ti on

R ed

u ct

io n

in c

u lt

u re

-p ro

ve n

C A

-B S

I in

ci de

n ce

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Fitzgerald et al

for either missing mandatory ICROMS criteria or ICROMS scores below the cutoff for the particular study design. Of the included studies, 8 were conducted in lower middle-income countries and 19 in upper middle-income countries (only 2 studies were multicoun- try). None were conducted in low-income countries. Including mul- tisite studies and using the 2021 World Bank regions, 14 study sites were in Latin America/Caribbean, 14 in South-East Asia/Pacific, 5 in the Middle East/North Africa, 3 in Europe/Central Asia and 1 in Sub-Saharan Africa.6 Eighteen studies evaluated single interven- tions and 9 evaluated bundled interventions (two of which were conducted in multiple countries).

Single-Intervention Studies Of the single interventions (Table 1), probiotics/feeding

interventions were the most commonly evaluated (5), followed by emollients (4), chlorhexidine cord cleansing (2) and KMC (2).

Three of the 5 probiotic/feeding interventions evaluated oral bovine lactoferrin versus placebo in a total of 370 neonates with birth weights <2500 g.8–10 Varying bovine lactoferrin dosage (from 80 to 200 mg/kg/day) and weight/gestational age thresholds made data incomparable and meta-analysis inappropriate. Two studies showed reduction in HAI in the intervention groups, one document- ing 4.4 infections per 1000 patient-days in the intervention arm ver- sus 17.3 (P = 0.007), the other finding a risk ratio of 0.211 (95% CIs, 0.044–1.019; P = 0.036), in those receiving the intervention versus placebo.8,9 Two studies evaluated enteral supplements but neither reduced infection incidence [parenteral glutamine supplementation (P = 0.518)11 or mixed probiotic administration (P = 0.4)12].

For emollients, one group conducted 2 studies using sun- flower seed oil in 103 Egyptian and 497 Bangladeshi neonates <72 hours of age, born at <34 or <33 weeks’ gestational age, respec- tively.13,14 Both studies found that sunflower seed oil massage was associated with a significant decrease in the adjusted incidence rate ratio (aIRR, adjusted for weight on admission, gestational age and sex) of culture-proven BSI than control (aIRR 0.46; 95% CI 0.26–0.81 and aIRR 0.59; 95% CI 0.37–0.96). Notably, the Bangla- deshi study showed no difference in the rate of clinically suspected infection triggering taking of blood cultures or antibiotic treatment rates between groups, although culture-proven BSI decreased in the intervention arm. Topical coconut oil was used in a Pakistani study in 270 neonates (26–34 weeks gestational age), first in the neonatal unit (NNU) and then at home.15 Neonates randomized to the con- trol arm had an increased risk of hospital-acquired BSI (adjusted hazard ratio, 6.0; 95% CI 2.3–16). A Turkish study of 197 preterm neonates (<34 weeks’ gestation and <24 hours old) found no dif- ference in mortality, incidence of culture-proven or clinically sus- pected infection in patients randomized to receive aquaphor emol- lient versus standard skin care.16

Two studies from India examined the impact of topical application of chlorhexidine gluconate; one in 140 neonates ≥32 weeks’ gestational age and ≥1500 g using chlorhexidine 2.5% to clean the umbilical stump; the other in 140 neonates compar- ing whole-body cleansing with chlorhexidine 0.25% versus tepid water.17,18 The first demonstrated a significant decrease in culture- proven BSI with chlorhexidine cord care (2 vs. 15; P = 0.02; absolute risk, 21% vs. 3%; absolute risk reduction, 19%; CIs not shown), although clinically suspected infections increased in inter- vention versus control subjects (Table 1).17 The second study found a nonsignificant decrease in blood culture positivity with whole- body cleansing (6/168 blood cultures positive in the intervention group vs. 12/175; P = 0.195), possibly owing to a small sample size and that blood cultures were taken at set intervals regardless of clinical indication.18

Studies on KMC were carried out in Colombia and Malaysia, in 746 neonates <2000 g and 126 neonates <1500 g, respectively.19,20

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Low-income Neonatal Units: Infection Prevention

These studies evaluated substantially different KMC interventions (≈24 hours per day of KMC vs. ≥1 hour per day of KMC; Table 1). The Colombian study found similar numbers of infectious epi- sodes [49/382 (intervention) vs. 44/364 (controls)], although they describe a milder phenotype in the intervention arm and a reduction in nosocomial infections (8% vs. 4% in interventions/controls; P = 0.026; absolute figures not given), without a clear distinction of the definition of “nosocomial” versus other infections. In the Malay- sian study, there were 2/64 infections in the intervention group ver- sus 1/64 controls (P = 1.0).

A large cohort study in Colombia (6655 neonates) evaluat- ing a hand hygiene intervention (alcohol-based hand rub dispens- ers, daily surveillance and quarterly feedback) found a decreased incidence density of neonatal methicillin-resistant Staphylococ- cus aureus BSIs (from 2.2 to 0.6 per 1000 patient-days; P = 0.01), although no decrease in Acinetobacter baumannii21 (0.6–0.2 per 1000 patient-days; P not given).

A small Brazilian study of massage therapy versus no inter- vention (n = 104) reported lower incidence of late-onset infections in the intervention versus control groups.22

No study evaluating “rooming-in” (defined as continuous presence of parent caregivers in the neonatal unit23), peripherally inserted central catheters versus standard intravenous catheters24 and fluconazole prophylaxis25 found differences in infection rates between the study arms (Table 1).

Bundled Interventions Five of the 9 studies reporting the impact of IPC bundles

(Table 2) focused on preventing device-associated infection.26–30 One small, single-center study in an Egyptian NICU achieved significant reduction in ventilator-associated pneumonia (VAP) rates and mechan- ical ventilation days, with a trend toward reduction in NICU length of stay and overall mortality.26 A multicountry study in 10 NICUs dem- onstrated significant reduction in VAP rates (RR 0.67; 95% CI 0.50– 0.91), after implementation of a multimodal strategy including hand hygiene, oral antiseptics, ventilator circuit management and enhanced infection surveillance.27 A tertiary hospital, 50-bed NICU in China, significantly reduced VAP rates, as well as overall mortality following implementation of a bundle including hand hygiene, ventilator disin- fection, education and rational antibiotic use.28

Two studies targeted prevention of central line–associated BSI. A multicountry study in 4 NICUs demonstrated significant reduction in central line–associated BSI rates following a multimodal intervention strategy including education, enhanced process and outcome surveil- lance and staff feedback (rate ratio, 0.45; 95% CI 0.33–0.63).29 A sin- gle-center Brazilian NICU significantly reduced central line–associated BSI rates (24 vs. 15 per 1000 catheter days; P = 0.04) following imple- mentation of a bundle including education, hand hygiene, chlorhexidine gluconate skin preparation and removal of unnecessary catheters.30

The first of two studies utilizing education/training inter- ventions was a noncontrolled “before-after” study conducted in 2 NICUs in the Philippines. The bundle focused on quality improve- ment in blood culture collection, hand hygiene compliance, use of infection control checklists and staff education. Although there was no change in the primary outcome (proportion of neonates newly colonized with resistant pathogens) or in the secondary outcome of bacteremia, the study achieved improved hand hygiene compli- ance rates and reduction in overall mortality.31 A Brazilian study in 5 neonatal units conducted an interrupted time series analysis following introduction of a nurse training package including IPC measures. Despite improvement in nurses’ knowledge and prac- tices, there was no change in mortality or rates of hospital-acquired BSI (11.3 vs. 12.3 cases/1000 infant days).32

A single-center cohort study at a large, academic center NICU in China enrolled outborn neonates <1500 g to assess the

impact of a hypothermia prevention bundle on admission tem- perature, rates of NEC and neonatal infection. Mean axillary tem- perature on arrival increased, and overall mortality rates decreased significantly; however, there was no difference in either NEC or infection incidence following the intervention.33

A recent, large cohort study in a Zambian neonatal unit evaluated the impact of IPC training, text message reminders for staff, hand hygiene promotion with alcohol-based hand rub, enhanced environmental cleaning and weekly whole-body bathing of neonates ≥1.5 kg with 2% chlorhexidine gluconate. The bundle achieved significant reduction in overall mortality, clinically sus- pected infection and culture-proven BSI for all birth weight groups except those <1 kg.34 In a subsequent subanalysis of the interven- tion group data, chlorhexidine gluconate bathing reduced the haz- ard rate of BSI among inborn babies ≥1.5 kg by a factor of 0.58 (P = 0.10; 95% CI 0.31–1.11).35

DISCUSSION Although infection is the most frequent complication of hos-

pitalization in LMIC neonates, the most effective IPC interventions remain unknown. We, therefore, conducted a systematic review of published studies describing the impact of various IPC inter- ventions on healthcare-associated infection rates in LMIC NNUs. We identified 27 eligible publications that assessed single (n = 18) and bundled IPC interventions (n = 9). None were carried out in low-income countries, only 1 in Sub-Saharan Africa and just 2 had sites in multiple countries. We found considerable heterogeneity of study design, analysis and outcomes selected, as well as diversity in the modes of infection prevention targeted (skin and gastroin- testinal mucosal integrity, promotion of normal flora acquisition and reduction of bacterial pathogen colonization). The evidence base we have identified for the effectiveness of IPC interventions in LMIC neonatal units is limited but appears most promising for bundled interventions targeting device-associated infections.

Limitations of this review include the paucity of published research on neonatal IPC from LMIC, the lack of multicenter stud- ies or large sample sizes and the failure to use optimal study inter- ventional study designs. Although we endeavored to be as inclusive as possible in our search terms, we only searched 4 databases and in 6 languages, so it is possible that we missed some relevant studies. It was not appropriate to do meta-analyses due to heterogeneity of both interventions and outcomes. Most studies were carried out in tertiary or academic neonatal units, which further limits the gener- alizability of the findings. Of note, although our initial search cap- tured a large number of potentially eligible studies, full-text review led to 40/120 (33%) papers being excluded due to not including mandatory criteria required by ICROMS or having a low score for study design/analysis quality. Thus, some geographic areas were not well represented, in particular, Sub-Saharan Africa with only one study included.34 This highlights the challenges for clinicians in LMIC settings to identify and implement contextually appropri- ate evidence-based guidelines. It also demonstrates the difficulties of designing and analyzing high-quality IPC studies where facility, laboratory and statistical support may be lacking.

IPC studies are notoriously complex to design and imple- ment, with issues of contamination between arms, the need for large-scale randomization (eg, cluster randomization of hospitals) and use of study designs unfamiliar to many academic clinicians, for example, interrupted time series analysis. IPC interventions also frequently involve behavior change, which does not lend itself to RCT evaluation. In recognition of the importance of evaluating effective behavior change in interventions in fields such as IPC, the UK Medical Research Council has developed guidance on how these studies should be designed and implemented.36 Similarly, the

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ICROMS score was developed to allow the inclusion of studies such as controlled before-after studies, noncontrolled before-after studies and qualitative studies in assessing evidence, the exclusion of which from standard systematic reviews undermines their poten- tial contribution to the evidence base.7

A major challenge in selecting the primary end point for neonatal IPC studies is the very low yield of blood cultures (the current gold standard for confirmation of BSI) in both high- and low-income settings. This necessitates recruitment of large num- bers of neonates to conclusively demonstrate an intervention’s impact, which is often particularly challenging in LMIC owing to budgetary and logistic constraints. Sensitive and specific neo- natal infection diagnostic tools that are accessible and affordable in LMIC settings are needed. In addition, standardized and vali- dated definitions for clinically suspected, culture-negative neona- tal infections are required, to allow for comparison of findings across study sites. Use of multiple study outcomes (proven infec- tion, clinically suspected infection and mortality) may compli- cate interpretation of findings, particularly where the results are discrepant.14 Until there is consensus on definitions of clinically suspected neonatal infection, particularly in settings where cul- tures have limited availability, the issue of quantifying reduction in infection rates will persist.

Despite these inherent limitations in the available data, end point definitions and study methodologies used, we have conducted the first systematic review of IPC interventions for LMIC NNUs. We used a robust search strategy, long inclusion time frame and ICROMS quality assessment to ensure we have identified all rel- evant and rigorously conducted research on this topic.

Among the single-intervention studies, emollient therapy (sunflower oil) in low-birth-weight babies had the strongest evidence supporting its use, demonstrating reduced healthcare-associated infection rates in both studies.13,14 There was also evidence to support the use of oral bovine lactoferrin, although the studies were small and there was inconsistency in dosage used. This finding is echoed in a recent Cochrane review of studies in high- and low-resource settings, which concluded there was low-certainty evidence that lactoferrin supplementation could reduce late-onset sepsis, though not NEC or all-cause mortality.37 Contrary to another previous Cochrane review, we did not find strong evidence for KMC as an intervention to reduce BSI in LMICs—only 2 studies fulfilled the ICROMS criteria and only 1 had some evidence of impact on BSI.20,38 For studies that ana- lyzed the impact of bundled interventions, the strongest evidence was generated from studies aiming to prevent device-associated infec- tion. Bundles incorporating other interventions (education, infection surveillance with feedback, hand hygiene promotion and chlorhex- idine gluconate bathing) were also effective, but the evidence was generated from single-center or small studies.

Particular areas that appear promising for future research on neonatal IPC in LMIC are the use of chlorhexidine gluconate body washing and/or emollient therapy. Bundles that target neonatal BSI (the most common neonatal HAI) should be developed, utilizing les- sons learned from the success of bundles targeting device-associated infections. The ideal bundled intervention should target all portals of entry for pathogenic bacteria causing neonatal BSI. It could include avoidance of hospitalization and/or invasive procedures, promotion of mucosal integrity (gut and skin), promotion of colonization with normal flora and reduced colonization with pathogenic bacteria.

Future studies in LMICs should utilize multinational col- laborations, standardize definitions (or at least clearly elucidate what criteria have been used) and use robust study designs, for example, individual randomized or cluster-randomized con- trolled trials and interrupted time series analysis to generate evidence for IPC interventions that can be adopted in neonatal practice. Wherever possible, guidelines such as Strengthening

the Reporting of Observational Studies in Epidemiology for Newborn Infection should be followed to allow for future com- parisons between studies.1

CONCLUSIONS There is a limited evidence base for IPC interventions in

LMIC neonatal units. Overall, bundled interventions targeting pre- vention of device-associated infection are supported by the strong- est evidence to date. More multisite studies using standardized neonatal infection definitions and robust study designs are needed to inform IPC interventions for use in low-resource neonatal units.

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Publications Reporting Infection in Newborns Globally) Group. Strengthening the Reporting of Observational Studies in Epidemiology for Newborn Infection (STROBE-NI): an extension of the STROBE statement for neonatal infection research. Lancet Infect Dis. 2016;16:e202–e213.

2. Zaidi AK, Huskins WC, Thaver D, et al. Hospital-acquired neonatal infec- tions in developing countries. Lancet. 2005;365:1175–1188.

3. Okomo U, Akpalu ENK, Le Doare K, et al. Aetiology of invasive bacterial infection and antimicrobial resistance in neonates in sub-Saharan Africa: a systematic review and meta-analysis in line with the STROBE-NI reporting guidelines. Lancet Infect Dis. 2019;19:1219–1234.

4. Gould DJ, Creedon S, Jeanes A, et al. Impact of observing hand hygiene in practice and research: a methodological reconsideration. J Hosp Infect. 2017;95:169–174.

5. Liberati A, Altman DG, Tetzlaff J, et al. The PRISMA statement for report- ing systematic reviews and meta-analyses of studies that evaluate healthcare interventions: explanation and elaboration. BMJ. 2009;339:b2700.

6. World Bank. World Bank Country and Lending Groups. Available at: https:// datahelpdesk.worldbank.org/knowledgebase/articles/906519-world-bank- country-and-lending-groups. Accessed November 2020.

7. Zingg W, Castro-Sanchez E, Secci FV, et al. Innovative tools for quality assessment: integrated quality criteria for review of multiple study designs (ICROMS). Public Health. 2016;133:19–37.

8. Akin IM, Atasay B, Dogu F, et al. Oral lactoferrin to prevent nosocomial sepsis and necrotizing enterocolitis of premature neonates and effect on T-regulatory cells. Am J Perinatol. 2014;31:1111–1120.

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10. Ochoa TJ, Zegarra J, Cam L, et al; NEOLACTO Research Group. Randomized controlled trial of lactoferrin for prevention of sepsis in peru- vian neonates less than 2500 g. Pediatr Infect Dis J. 2015;34:571–576.

11. Li ZH, Wang DH, Dong M. Effect of parenteral glutamine supplementation in premature infants. Chin Med J (Engl). 2007;120:140–144.

12. Wang Y, Gao L, Zhang YH, et al. Efficacy of probiotic therapy in full-term infants with critical illness. Asia Pac J Clin Nutr. 2014;23:575–580.

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14. Darmstadt GL, Saha SK, Ahmed AS, et al. Effect of topical treatment with skin barrier-enhancing emollients on nosocomial infections in preterm infants in Bangladesh: a randomised controlled trial. Lancet. 2005;365:1039–1045.

15. Salam RA, Darmstadt GL, Bhutta ZA. Effect of emollient therapy on clini- cal outcomes in preterm neonates in Pakistan: a randomised controlled trial. Arch Dis Child Fetal Neonatal Ed. 2015;100:F210–F215.

16. Erdemir A, Kahramaner Z, Yuksel Y, et al. The effect of topical ointment on neonatal sepsis in preterm infants. J Matern Fetal Neonatal Med. 2015;28:33–36.

17. Gathwala G, Sharma D, Bhakhri Bk. Effect of topical application of chlo- rhexidine for umbilical cord care in comparison with conventional dry cord care on the risk of neonatal sepsis: a randomized controlled trial. J Trop Pediatr. 2013;59:209–213.

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20. Charpak N, Ruiz-Peláez JG, Figueroa de C Z, et al. Kangaroo mother versus traditional care for newborn infants </=2000 grams: a randomized, con- trolled trial. Pediatrics. 1997;100:682–688.

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38. Conde-Agudelo A, Diaz-Rossello JL. Kangaroo mother care to reduce mor- bidity and mortality in low birthweight infants. Cochrane Database Syst Rev. 2016;2016:CD002771.

Original Investigation | Pediatrics

Assessment of Neonatal Intensive Care Unit Practices, Morbidity, and Mortality Among Very Preterm Infants in China Yun Cao, MD, PhD; Siyuan Jiang, MD, PhD; Jianhua Sun, MD; Mingyan Hei, MD, PhD; Laishuan Wang, MD, PhD; Huayan Zhang, MD; Xiaolu Ma, MD; Hui Wu, MD, PhD; Xiaoying Li, MD, PhD; Huiqing Sun, MD, PhD; Wei Zhou, MD, PhD; Yuan Shi, MD, PhD; Yanchen Wang, MSC; Xinyue Gu, MSC; Tongling Yang, RN; Yulan Lu, PhD; Lizhong Du, MD, PhD; Chao Chen, MD, PhD; Shoo K. Lee, PhD; Wenhao Zhou, MD, PhD; for the Chinese Neonatal Network

Abstract

IMPORTANCE The Chinese Neonatal Network was established in 2018 and maintains a standardized national clinical database of very preterm or very low-birth-weight infants in tertiary neonatal intensive care units (NICUs) throughout China. National-level data on outcomes and care practices of very preterm infants (VPIs) in China are lacking.

OBJECTIVE To assess the care practices in NICUs and outcomes among VPIs in China.

DESIGN, SETTING, AND PARTICIPANTS A cohort study was conducted comprising 57 tertiary hospitals from 25 provinces throughout China. All infants with gestational age (GA) less than 32 weeks who were admitted to the 57 NICUs between January 1 and December 31, 2019, were included.

MAIN OUTCOMES AND MEASURES Care practices, morbidities, and survival were the primary outcomes of the study. Major morbidities included bronchopulmonary dysplasia, severe intraventricular hemorrhage (grade �3) and/or periventricular leukomalacia, necrotizing enterocolitis (stage �2), sepsis, and severe retinopathy of prematurity (stage �3).

RESULTS A total of 9552 VPIs were included, with mean (SD) GA of 29.5 (1.7) weeks and mean (SD) birth weight of 1321 (321) g; 5404 infants (56.6%) were male. Antenatal corticosteroids were used in 75.6% (6505 of 8601) of VPIs, and 54.8% (5211 of 9503)were born through cesarean delivery. In the delivery room, 12.1% of VPIs received continuous positive airway pressure and 26.7% (2378 or 8923) were intubated. Surfactant was prescribed for 52.7% of the infants, and postnatal dexamethasone was prescribed to 9.5% (636 of 6675) of the infants. A total of 85.5% (8171) of the infants received complete care, and 14.5% (1381) were discharged against medical advice. The incidences of the major morbidities were bronchopulmonary dysplasia, 29.2% (2379 of 8148); severe intraventricular hemorrhage and/or periventricular leukomalacia, 10.4% (745 of 7189); necrotizing enterocolitis, 4.9% (403 of 8171 ); sepsis, 9.4% (764 of 8171); and severe retinopathy of prematurity, 4.3% (296 of 6851) among infants who received complete care. Among VPIs with complete care, 95.4% (7792 of 8171) survived: 65.6% (155 of 236) at 25 weeks’ or less GA, 89.0% (880 of 988) at 26 to 27 weeks’ GA, 94.9% (2635 of 2755)at 28 to 29 weeks’ GA, and 98.3% (4122 of 4192) at 30 to 31 weeks’ GA. Only 57.2% (4677 of 8171) of infants survived without major morbidity: 10.5% (25 of 236) at 25 weeks’ or less GA, 26.8% (48 of 179) at 26 to 27 weeks’ GA, 51.1% (1409 of 2755) at 28 to 29 weeks’ GA, and 69.3% (2904 of 4192) at 30 to 31 weeks’ GA. Among all infants admitted, the survival rate was 87.6% (8370 of 9552)and survival without major morbidities was 51.8% (4947 of 9552).

(continued)

Key Points Question What are the care practices

and outcomes for very preterm infants

in Chinese neonatal intensive care units?

Findings In this cohort study of 9552

very preterm infants from 57 tertiary

neonatal intensive care units throughout

China in 2019, 86% received complete

care, among whom 95% survived and

57% survived without major

morbidities. Only 76% of the infants

received antenatal corticosteroids, and

12% of the infants received delivery

room continuous positive airway

pressure.

Meaning The findings of this study

suggest that survival and survival

without major morbidity of very preterm

infants in Chinese neonatal intensive

care units remain lower than in high-

income countries and clinical quality

improvement as well as systems and

health services reorganization are

needed to improve outcomes.

+ Invited Commentary

+ Supplemental content

Author affiliations and article information are listed at the end of this article.

Open Access. This is an open access article distributed under the terms of the CC-BY License.

JAMA Network Open. 2021;4(8):e2118904. doi:10.1001/jamanetworkopen.2021.18904 (Reprinted) August 2, 2021 1/13

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Abstract (continued)

CONCLUSIONS AND RELEVANCE The findings of this study suggest that survival and survival without major morbidity of VPIs in Chinese NICUs have improved but remain lower than in high- income countries. Comprehensive and targeted quality improvement efforts are needed to provide complete care for all VPIs, optimize obstetrical and neonatal care practices, and improve outcomes.

JAMA Network Open. 2021;4(8):e2118904. doi:10.1001/jamanetworkopen.2021.18904

Introduction

In recent decades, there have been major advances in perinatal and neonatal intensive care in China.1,2 Neonatal mortality has been reduced substantially, but preterm birth has become the leading cause of neonatal death.3 There are approximately 0.2 million very preterm infants (VPIs) (<32 weeks’ gestational age [GA]) born every year in China.4,5 Although steady improvements in outcomes have been reported, VPIs in China continue to contribute disproportionately to the burden of neonatal death and long-term developmental disability. Currently, national-level data on outcomes and care practices for VPIs in China are lacking. Information on care practices, morbidity, and mortality of VPIs is essential to benchmark outcomes for institutions to evaluate their performance, identify deficiencies in care, facilitate quality improvement, improve health services delivery, and support parental counseling and clinical decision-making.

The Chinese Neonatal Network (CHNN) was founded in 2018 and has established a standardized national clinical database of VPIs in tertiary neonatal intensive care units (NICUs) throughout China to monitor outcomes and changes in care practices and explore potential strategies for improving neonatal care. The CHNN database was launched with prospective data collection starting from January 1, 2019. To our knowledge, the present study is the first full-year report of the CHNN database assessing the outcomes and care practices of VPIs in Chinese NICUs in 2019, aiming to profile the current state of care and outcomes for VPIs in Chinese tertiary NICUs.

Methods

Design The CHNN hospitals are tertiary referral institutions with large neonatal services and recognized expertise in caring for high-risk neonates and were selected to be representative of different regions of the country. A total of 58 hospitals from 25 provinces throughout China participated in the CHNN in 2019 (eFigure in the Supplement), caring for approximately 5% of all VPIs in China. These hospitals included all government-designated neonatal centers of excellence in China, including 4 national children’s medical centers, 5 regional children’s medical centers, and 30 provincial perinatal or children’s medical centers. The other 19 hospitals were major referral centers in large cities across China. Fifty-seven hospitals collected whole-year data of VPIs admitted to their NICUs in 2019 and were enrolled in this study (1 hospital was excluded because of incomplete data for logistical reasons but will be included in future studies). Forty-three hospitals were perinatal centers with birthing facilities, and 14 hospitals were freestanding children’s hospitals that admitted only outborn infants. The median number of NICU beds was 40 (interquartile range [IQR], 30-62), and the median number of intermediate-level and continuing care neonatal beds was 66 (IQR, 40-91). For perinatal centers, the median number of annual deliveries was 10 280 (IQR, 6273-15 423). The median number of full- time equivalent neonatologists was 19 (IQR, 12-27), and the median number of NICU nurses was 42 (IQR, 30-65). All hospitals had facilities to provide long-term invasive or noninvasive ventilation support. General surgery was available in 47 hospitals, patent ductus arteriosus ligation in 45 hospitals, and cardiac surgeries requiring extracorporeal circulation in 35 hospitals. All hospitals could perform bedside head ultrasonography, and 55 hospitals could perform magnetic resonance imaging

JAMA Network Open | Pediatrics Neonatal Intensive Care Unit Practices and Outcomes Among Very Preterm Infants in China

JAMA Network Open. 2021;4(8):e2118904. doi:10.1001/jamanetworkopen.2021.18904 (Reprinted) August 2, 2021 2/13

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examination. All hospitals performed onsite screening for retinopathy of prematurity (ROP), and 47 performed ROP treatment. All hospitals provided mother’s milk for feeding, and 20 hospitals provided donor milk.

This study was approved by the ethics review board of Children’s Hospital of Fudan University, which was recognized by all participating hospitals. Waiver of consent was granted at all sites owing to the use of deidentified patient data. This study followed the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) reporting guideline for cohort studies.

This was a hospital-based cohort. The CHNN database includes all infants with less than 32 weeks’ GA or with birth weight less than 1500 g and admitted to participating NICUs. Stillbirths, delivery room deaths, and infants transferred to nonparticipating hospitals within 24 hours after birth are not captured by the database. Readmissions and transfers between participating hospitals were tracked as data from the same infants. Infants were followed up until NICU discharge or transfer or death. In this study, we included all infants with less than 32 weeks’ GA and admitted to participating NICUs between January 1 and December 31, 2019, without exclusion.

Trained data abstractors were responsible for data acquisition in each hospital. Data were directly entered into a customized database with built-in error checking and a standard manual of operations and definitions. Data were electronically transmitted to the CHNN coordinating center in Children’s Hospital of Fudan University with patient identity kept confidential. Quarterly data checks were performed by the coordinating center for quality and completeness. Quarterly site-specific data quality reports were given to each site, and data records were returned for corrections if needed. Data quality audit using data reabstraction was performed annually. Site investigators were responsible for data quality control in each site.

Outcomes Care practices were chosen based on their association with neonatal outcomes or because they were important indicators of quality of care. The care practices included antenatal corticosteroids, antenatal antibiotics, cesarean delivery, delivery room resuscitation, surfactant therapy, respiratory support, postnatal corticosteroids, and breast milk feeding. Antenatal corticosteroids were defined as a partial or complete course of antenatal corticosteroids. Surfactants included those used both in delivery rooms and in NICUs. Postnatal corticosteroids referred to intravenous dexamethasone used for bronchopulmonary dysplasia (BPD). Invasive ventilation included high-frequency and conventional ventilation via endotracheal tubes. Noninvasive respiratory support included noninvasive high-frequency ventilation, noninvasive positive pressure ventilation, nasal continuous positive airway pressure, and high-flow oxygen.

Morbidities included intraventricular hemorrhage (IVH) (grade �3) and/or cystic periventricular leukomalacia (PVL), necrotizing enterocolitis (NEC) (stage �2), sepsis, ROP (stage �3), and BPD. Intraventricular hemorrhage was defined as greater than or equal to grade 3 according to the Papile criteria.6 Cystic PVL was defined as the presence of periventricular cysts identified on cranial ultrasonography or magnetic resonance imaging. Necrotizing enterocolitis was defined according to Bell criteria.7,8 Sepsis was defined as positive blood or cerebrospinal fluid culture and antibiotic therapy or intent of antibiotic therapy for 5 days or longer.9 Retinopathy of prematurity was diagnosed according to the International Classification of Retinopathy of Prematurity.10

Bronchopulmonary dysplasia was defined as ventilation or oxygen dependency at 36 weeks’ corrected age or at discharge, transfer, or death before 36 weeks.11 Survival and survival without major morbidities (IVH grade �3 or PVL, NEC stage �2, sepsis, ROP stage �3, and BPD) were studied.

A large proportion of VPIs were discharged against medical advice (DAMA), which meant parents terminated treatment before the treating physicians recommended discharge. DAMA substantially compromised the survival of VPIs and influenced the morbidities. The poorer outcomes of DAMA infants may be attributable to infant characteristics and perinatal care practices or early termination of appropriate medical treatment. Therefore, we studied morbidities and survival among

JAMA Network Open | Pediatrics Neonatal Intensive Care Unit Practices and Outcomes Among Very Preterm Infants in China

JAMA Network Open. 2021;4(8):e2118904. doi:10.1001/jamanetworkopen.2021.18904 (Reprinted) August 2, 2021 3/13

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infants with complete care, DAMA infants, and all admitted infants separately. Morbidities and survival among infants with complete care may reflect the quality of care more accurately by excluding the influence of termination of care against medical advice on the outcomes. Outcomes of all infants reflected the general survival status of all infants admitted to CHNN NICUs, regardless of whether care was terminated against medical advice. We used predefined criteria to make assumptions about survival of DAMA infants, as we were unable to determine the survival of these infants after discharge because of logistical constraints. If DAMA infants required invasive or noninvasive mechanical ventilation, inotropes infusion, or total parenteral nutrition (no enteral feeds initiated) on the day of discharge, we assumed that they would not survive after discharge.

Gestational age was determined using the hierarchy of best obstetric estimate based on prenatal ultrasonography, menstrual history, obstetric examination, or all 3 factors. If the obstetric estimate was not available or was different from the postnatal estimate of gestation by more than 2 weeks, the GA was estimated using the Ballard score.12 Small for gestational age was defined as birth weight less than the 10th percentile for the GA according to the Chinese neonatal birth weight values.13 Prenatal care was defined as 1 or more pregnancy-related hospital visit during pregnancy. The Transport Risk Index of Physiologic Stability score14,15 was used as an illness severity score on NICU admission.

Statistical Analysis Demographic variables, care practices, morbidities, and mortality are summarized using descriptive statistics without comparison. Statistical results are presented by frequency (percentages) for categorical variables and means (SDs) or medians (IQRs) for continuous variables. The results are displayed by each week of GA. Survival rates and morbidities of DAMA and complete-care infants were compared using χ2 tests. Statistical analysis was performed using Stata, version 15.0 (StataCorp LLC).

Results

A total of 9552 VPIs with the mean (SD) GA of 29.5 (1.7) weeks and the mean (SD) birth weight of 1321 (321) g composed our study population, after excluding 1271 infants with GA greater than or equal to 32 weeks from the total 2019 CHNN cohort of 10 823 infants, which enrolled all infants admitted to 57 participating NICUs with gestational age less than 32 weeks or birth weight less than 1500 g.

Among 9552 VPIs included in our study, only 3.7% (353) were 25 weeks’ GA or less and 13.5% (1293) were 26 to 27 weeks’ GA. Most infants were 28 to 31 weeks’ GA (Table 1). A total of 56.6% (5404) of VPIs were male, 43.4% (4148) were female, 30.0% (2870 of 9552) were multiple births, and 36.5% (3482 of 9552) were outborn. The mean maternal age was 30.8 (5.0) years. Overall, 99.0% (9114 of 9209) of mothers received prenatal care, 18.8% (1761 of 9372) were diagnosed with hypertension, and 17.1% (1600 of 9353) were diagnosed with any type of diabetes.

Care Practices Overall, 75.6% (6505 of 8601) of infants received at least 1 dose of antenatal corticosteroids, and the incidence of use increased with GA (Table 2): 37.0% (10 of 27) at 23 weeks’ GA or less, 68.1% (196 of 288) at 24 to 25 weeks’ GA, 73.7% (825 of 1135) at 26 to 27 weeks’ GA, and 76.5% (5474 of 7151) at 28 to 31 weeks’ GA. Cesarean birth was the mode of delivery for 54.8% (5211 of 9503) of all infants, but only 17.1% (60 of 351) for infants 25 weeks’ GA or less and 31.0% (398 of 1283) for infants 26 to 27 weeks’ GA.

Only 12.1% (1080 of 8923) of infants received continuous positive airway pressure in delivery rooms, with similar rates across different gestational ages, but 26.7% (2378 of 8923) of the infants were intubated in the delivery room (Table 2). Delayed cord clamping was performed in 22.8% (1446 of 6354) of the infants.

JAMA Network Open | Pediatrics Neonatal Intensive Care Unit Practices and Outcomes Among Very Preterm Infants in China

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JAMA Network Open | Pediatrics Neonatal Intensive Care Unit Practices and Outcomes Among Very Preterm Infants in China

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JAMA Network Open | Pediatrics Neonatal Intensive Care Unit Practices and Outcomes Among Very Preterm Infants in China

JAMA Network Open. 2021;4(8):e2118904. doi:10.1001/jamanetworkopen.2021.18904 (Reprinted) August 2, 2021 6/13

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Respiratory treatments were evaluated for 6675 infants who were admitted to participating NICUs within 7 days after birth, received complete care, and survived to discharge (Table 2). Overall, 52.7% (3518 of 6675) of infants received surfactant, with the incidence decreasing with increasing GA: 89.9% (98 of 109) at 25 weeks’ GA or less, 75.7% (523 of 691) at 26 to 27 weeks’ GA, 63.1% (1412 of 2236) at 28 to 29 weeks’ GA, and 40.8% (1485 of 3639) at 30 to 31 weeks’ GA. A total of 9.5% (636 of 6675) of infants were prescribed postnatal corticosteroids: 53.2% (58 of 109) at 25 weeks’ GA or less, 25.5% (176 of 691) at 26 to 27 weeks’ GA, 11.9% (267 of 2236) at 28 to 29 weeks’ GA, and 3.7% (136 of 3639) at 30 to 31 weeks’ GA. Overall, 38.8% (2591 of 6675) of infants received invasive ventilation: 64.7% (447 of 691) at 26 to 27 weeks’ GA, 44.6% (997 of 2236) at 28 to 29 weeks’ GA, and 29.1% (1058 of 3638) at 30 to 31 weeks’ GA. Noninvasive respiratory support was provided to 91.4% (6104 of 6675) infants. Among infants with enteral feeds initiated during hospitalization, 70.8% (6300 of 8897) of infants received breast milk.

Morbidities A total of 14.5% (1381) VPIs were DAMA and 85.5% (8171) of the infants received complete care in NICUs. Among infants with complete care, oxygen or respiratory support was needed for 29.2% (2379 of 8148) of VPIs at 36 weeks’ corrected GA or at discharge. The incidences of BPD were 74.2% (173 of 233) at 25 weeks’ GA or less, 51.9% (513 of 988) at 26 to 27 weeks’ GA, 33.4% (918 of 2747) at 28 to 29 weeks’ GA, and 19.3% (805 of 4180) at 30 to 31 weeks’ GA. Overall, 10.4% (745 of 7189) of the infants were diagnosed with IVH (grade �3) or cystic PVL (Table 3). The incidence of severe brain injury decreased with increasing GA: 26.8% (48 of 179) at 25 weeks’ GA or less, 16.9% (145 of 858) at 26 to 27 weeks’ GA, 11.0% (273 of 2471) at 28 to 29 weeks’ GA, and 7.6% (279 of 3681) at 30 to 31 weeks’ GA. Necrotizing enterocolitis was diagnosed in 4.9% (403 of 8171) of the infants and culture-proven sepsis in 9.4% (764 of 8171). Severe ROP was present in 4.3% (296 of 6851) of the infants.

Morbidities among DAMA infants and all infants admitted are reported in eTable 1 and eTable 2 in the Supplement. DAMA infants had higher incidences of IVH grade 3 or greater or cystic PVL, BPD, and NEC compared with infants who received complete care.

Survival and Survival Without Major Morbidities Among 8171 infants who received complete care, the survival rate was 95.4% (7792 of 8171) for all VPIs, 65.6% (155 of 236) at 25 weeks’ GA or less, 89.0% (880 of 988) at 26 to 27 weeks’ GA, 94.9% (2635 of 2755) at 28 to 29 weeks’ GA, and 98.3% (4122 of 4192) at 30 to 31 weeks’ GA (Table 4 and Figure). The rate of survival without major morbidity was 57.2% (4677 of 8171) for all VPIs with complete care, 10.5% (25 of 236) at 25 weeks’ GA or less, 26.8% (265 of 988) at 26 to 27 weeks’ GA, 51.1% (1409 of 2755) at 28 to 29 weeks’ GA, and 69.3% (2904 of 4192) at 30 to 31 weeks’ GA.

Among all VPIs admitted, including DAMA infants, 87.6% (8370 of 9552) survived (eTable 3 in the Supplement). A total of 58.1% (803 of 1381) of DAMA infants were expected to die after discharge, accounting for 67.9% (803 of 1182) of all deaths. The survival rate was 67.7% (1115 of 1646) for infants at less than 28 weeks’ GA (15.6% [5 of 32] at �23 weeks’ GA, 48.6% [156 of 321] at 24 to 25 weeks’ GA, and 73.8% [954 of 1293] at 26 to 27 weeks’ GA), 88.2% (2828 of 3207) at 28 to 29 weeks’ GA, and 94.2% (4427 of 4699) at 30 to 31 weeks’ GA. Survival without major morbidity was 51.8% (4947 of 9552) for all VPIs, and the rates increased with increasing gestational age: 7.4% (26 of 353) at 25 weeks’ GA or less, 27.2% (352 of 1293) at 26 to 27 weeks’ GA, 46.6% (1494 of 3207) at 28 to 29 weeks’ GA, and 65.4% (3075 of 4699) at 30 to 31 weeks’ GA.

Discussion

To our knowledge, this study of VPIs admitted to 57 tertiary NICUs throughout China is the first national-level comprehensive assessment of care practices, morbidities, and mortality of VPIs in Chinese NICUs and serves to fill a gap in our knowledge of the current status of neonatal intensive

JAMA Network Open | Pediatrics Neonatal Intensive Care Unit Practices and Outcomes Among Very Preterm Infants in China

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JAMA Network Open | Pediatrics Neonatal Intensive Care Unit Practices and Outcomes Among Very Preterm Infants in China

JAMA Network Open. 2021;4(8):e2118904. doi:10.1001/jamanetworkopen.2021.18904 (Reprinted) August 2, 2021 8/13

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care in China. The study identifies opportunities for improving outcomes of VPIs in China and may enable us to prioritize and target specific areas of care practices for change.

The survival rate of VPIs in our study was 87.6% among all infants admitted to NICUs and 95.4% among infants who received complete care. Our results suggest substantial improvement in survival rates compared with previous reports from China.16-19 Wu et al16 reported that the survival rate among 2051 infants with less than 28 weeks’ GA and admitted to NICUs from Guangdong province improved from 36.2% in 2008 to 59.3% in 2017, compared with 67.7% in our study in 2019. Our results also compare favorably with those of Jiang et al,17 who reported survival rates among 25 Chinese NICUs for infants with complete care in 2015-2016 of 47% vs 65.6% in our study for infants at 25 weeks’ GA or less, 79% vs 89.0% for infants 26 to 27 weeks’ GA, and 96% vs 97.3% for infants at 28 to 31 weeks’ GA. However, despite the improvement, our outcomes continue to lag behind those of high-income countries. For instance, our current survival rates are comparable only with those of the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network (NICHD) in 2003-2007.18 Compared with the Canadian Neonatal Network in 2018, our survival rates for all NICU admissions were approximately 40% lower for infants at 24 weeks’ GA, 25% lower at 25 to 26 weeks’ GA, 15% lower at 27 to 28 weeks’ GA, and 5% lower at 29 to 31 weeks’ GA.19 The difference indicates substantial room for improvement.

One unique problem in China is that a large proportion of infants did not receive complete care and were DAMA. In our study, only 85.5% of VPIs received complete care, which is an improvement over previous reports of less than 80% of VPIs during the past decade.17,20 Nevertheless, DAMA remains a factor associated with mortality in VPIs, and we estimated that it accounted for 67.9% (803 of 1182) of deaths in our study. However, DAMA infants also presented higher incidences of morbidities than infants with complete care. Therefore, DAMA infants should be taken into consideration when looking into overall outcomes of preterm infants in China to avoid underestimation. In addition, the high proportion of DAMA in China may be partially due to societal attitudes and lack of social supports for handicapped individuals or to lack of comprehensive health

Table 4. Survival to Discharge for Very Preterm Infants (<32 Weeks' Gestation) Admitted to 57 Chinese Neonatal Intensive Care Units and Receiving Complete Care

Variable Total

Gestational age, No. (%), wk

≤23 24 25 26 27 28 29 30 31 No. 8171 23 52 161 325 663 1185 1570 1917 2275

Survival 7792 (95.4) 5 (21.7) 29 (55.8) 121 (75.2) 285 (87.7) 595 (89.7) 1113 (93.9) 1522 (96.9) 1883 (98.2) 2239 (98.4)

Survival without major morbidity

4677 (57.2) 0 (0.0) 4 (7.7) 21 (13.0) 82 (25.2) 257 (38.8) 533 (45.0) 876 (55.8) 1250 (65.2) 1654 (72.7)

Figure. Survival and Survival Without Major Morbidity of Very Preterm Infants (<32 Weeks' Gestation) Admitted to 57 Chinese Neonatal Intensive Care Units and Receiving Complete Care

100

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Survival among infants with complete care Survival without morbidities among infants with complete care

Whiskers indicate 95% CIs.

JAMA Network Open | Pediatrics Neonatal Intensive Care Unit Practices and Outcomes Among Very Preterm Infants in China

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insurance coverage and a high burden of cost to families. Given the high proportion of DAMA and its association with overall outcomes, reduction of DAMA and ensuring that all VPIs receive appropriate care should be one of the priorities for China.

Survival without major morbidity is even more important than survival because it has consequences for long-term developmental outcomes.21-23 Although overall, 87.6% of infants survived, only 51.8% of infants survived without major morbidity. Among infants with complete care, the discrepancy between survival and survival without major morbidity remained substantial. Although the discrepancy between survival and survival without major morbidity was largest among infants with the lowest gestational age, it remained large among infants with greater gestational age. As survival improves, reducing morbidities and improving quality of life will become increasingly important, and neonatal follow-up, early intervention, and developmental care should be appropriately developed in China.

Among the major morbidities, BPD was the most common in our cohort, occurring in more than one-third of VPIs, and approximately 20% higher than the rates reported by NICHD NICUs in 2008- 2012 for each gestational age group.18 Addressing BPD through quality improvement measures should be a priority for Chinese NICUs. Our data provide some insights into potential reasons and remedies. For example, only 12.1% of VPIs received continuous positive airway pressure and 26.7% were intubated in the delivery room, suggesting that there may be opportunities for more use of less- invasive strategies in delivery rooms. The second most common morbidity was severe brain injury, which is associated with long-term neurodevelopmental delay.21-24 Interventions such as use of antenatal corticosteroids, maternal rather than infant transport, and elective cesarean delivery for VPIs have been associated with reduced risk of brain injury, and implementation of appropriate practice guidelines could be approaches to reducing severe brain injury.25

Another important finding is the high incidence of perinatal risk factors and suboptimal adherence to prenatal care practices that may improve neonatal outcomes. The outborn rate in our study was 36.5%, which is much higher than the 5% to 20% rate reported by most high-income countries,26 indicating the need for development of an appropriate perinatal regionalization system, which is lacking in China. Our finding of 75.6% antenatal corticosteroid use is an improvement over previous reports from China (39% in 2008-2012,27 56% in 2013-2014,28 and 64% in 2015-201617) but remains much lower than the 80% to 90% rate in high-income countries and indicates a need for better implementation of optimal care guidelines.18,29 We also found that the cesarean delivery rates were lower for VPIs in China than in high-income countries, especially among the infants with the lowest GA.18 Only 17.1% of infants at 25 weeks’ GA or less and 31.0% of those at 26 to 27 weeks’ GA were born by cesarean delivery in our study. This low rate may reflect parental decision-making, but it may also indicate a need for better communication and discussion between obstetricians, neonatologists, and parents when making active decisions in complex perinatal situations.

Limitations Our study had several limitations. The data are from a select group of large tertiary NICUs with the highest level of neonatal care in China and may not be representative of the general population. Our cohort was hospital based rather than population based; in addition, delivery room deaths and infants who were not admitted to NICUs were not included in our study. There was a large predominance of male infants in groups with the lowest gestational ages; one possible cause might be selection bias from our hospital-based design. We made assumptions about mortality of DAMA infants based on predetermined criteria but we did not validate these assumptions by following up the infants after discharge.

Conclusions

The findings from this study provide national data about outcomes and clinical practices in NICUs and potential strategies for improving care and counseling families in China. Although substantially

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improved, outcomes of VPIs in China continue to lag behind those of high-income countries. In the future, it may be useful to coordinate efforts in multiple domains, including clinical quality improvement, systems and health services reorganization, strengthening financial and social supports for families, and addressing social determinants of maternal and infant health.

ARTICLE INFORMATION Accepted for Publication: April 28, 2021.

Published: August 2, 2021. doi:10.1001/jamanetworkopen.2021.18904

Corresponding Authors: Wenhao Zhou, MD, PhD, Division of Neonatology, Children’s Hospital of Fudan University, 399 Wanyuan Rd, Minhang District, Shanghai, China, 201102 ([email protected]); Shoo K. Lee, PhD, Maternal-Infant Care Research Centre and Department of Pediatrics, Mount Sinai Hospital, 600 University Ave, Room 19-231M, Toronto, Ontario M5G 1X5, Canada ([email protected]).

Author Affiliations: Division of Neonatology, Children’s Hospital of Fudan University, Shanghai, China (Cao, Jiang, L. Wang, Yang, Chen, Wenhao Zhou); Division of Neonatology, Shanghai Children’s Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China (J. Sun); Neonatal Center, Beijing Children's Hospital, Capital Medical University, Beijing, China (Hei); Division of Neonatology, Division of Neonatology and Center for Newborn Care, Guangzhou Women and Children’s Medical Center, Guangdong, China (Zhang, Wei Zhou); Department of Pediatrics, Children’s Hospital of Philadelphia and University of Pennsylvania Perelman School of Medicine, Philadelphia (Zhang); Division of Neonatology, The Children’s Hospital Zhejiang University School of Medicine, Zhejiang, China (Ma, Du); Division of Neonatology, The First Bethune Hospital of Jilin University, Jilin, China (Wu); Division of Neonatology, Qilu Children’s Hospital of Shandong University, Shandong, China (Li); Division of Neonatology, Children’s Hospital Affiliated with Zhengzhou University, Children’s Hospital of Henan Zhengzhou, Hennan, China (H. Sun); Division of Neonatology, Children’s Hospital of Chongqing Medical University, Chongqing, China (Shi); NHC Key Laboratory of Neonatal Diseases, Fudan University, Children’s Hospital of Fudan University, Shanghai, China (Y. Wang, Gu); Center for Molecular Medicine, Pediatrics Research Institute, Children’s Hospital of Fudan University, Shanghai, China (Lu); Maternal-Infant Care Research Centre and Department of Pediatrics, Mount Sinai Hospital, Toronto, Ontario, Canada (Lee); Department of Pediatrics, University of Toronto, Toronto, Ontario, Canada (Lee); Department of Obstetrics and Gynecology and Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada (Lee).

Author Contributions: Drs Cao and Wenhao Zhou had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.

Concept and design: Cao, L. Wang, Ma, Wu, Li, Shi, Chen, Lee, Wenhao Zhou.

Acquisition, analysis, or interpretation of data: Cao, Jiang, J. Sun, Hei, Zhang, Li, H. Sun, Wei Zhou, Y. Wang, Gu, Yang, Lu, Du, Wenhao Zhou.

Drafting of the manuscript: Cao, Jiang, Li.

Critical revision of the manuscript for important intellectual content: All authors.

Statistical analysis: Li, Y. Wang, Gu, Lu.

Obtained funding: Li, Lee, Wenhao Zhou.

Administrative, technical, or material support: L. Wang, Zhang, Ma, Wu, Li, H. Sun, Wei Zhou, Shi, Yang, Lu, Du, Wenhao Zhou.

Supervision: Cao, L. Wang, Li, Chen, Lee, Wenhao Zhou.

Conflict of Interest Disclosures: Dr Lee reported receiving grants from Canadian Institutes of Health Research during the conduct of the study. No other disclosures were reported.

Funding/Support: Dr Lee is supported by the Canadian Institutes of Health Research (grant CTP87518).

Role of the Funder/Sponsor: The funding organization had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

Group Information: The Chinese Neonatal Network members are listed in Supplement 2.

Meeting Presentation: The results of the study were presented at Pediatric Academic Societies 2021 Virtual Meeting; May 4, 2021.

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SUPPLEMENT 1. eFigure. Map of 58 Participating Hospitals in Chinese Neonatal Network eTable 1. Morbidities of Very Preterm Infants (<32 Weeks' Gestation) Admitted to 57 Chinese NICUs and Discharged Against Medical Advice eTable 2. Morbidities of All Very Preterm Infants (<32 Weeks' Gestation) Admitted to 57 Chinese NICUs eTable 3. Survival to Discharge for All Very Preterm Infants (<32 Weeks' Gestation) Admitted to 57 Chinese NICUs

SUPPLEMENT 2. Nonauthor Collaborators. The Chinese Neonatal Network

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RESEARCH ARTICLE

Infection prevention and control in neonatal

units: An ethnographic study of social and

clinical interactions among healthcare

providers and mothers in Ghana

Gifty Sunkwa-MillsID 1,2*, Kodjo Senah3, Britt Pinkowski Tersbøl2

1 Ghana Health Service, Central Region, Kasoa, Ghana, 2 Global Health Section, Department of Public

Health, University of Copenhagen, Copenhagen, Denmark, 3 Department of Sociology, University of Ghana,

Accra, Ghana

* [email protected]

Abstract

Introduction

Healthcare-associated infections (HAIs) are a global health challenge, particularly in low-

and middle-income countries (LMICs). Infection prevention and control (IPC) remains an

important strategy for preventing HAIs and improving the quality of care in hospital wards.

The social environment and interactions in hospital wards are important in the quest to

improve IPC. This study explored care practices and the interactions between healthcare

providers and mothers in the neonatal intensive care units (NICU) in two Ghanaian hospitals

and discusses the relevance for IPC.

Methodology

This study draws on data from an ethnographic study using in-depth interviews, focus group

discussions involving 43 healthcare providers and 72 mothers, and participant observations

in the wards between September 2017 and June 2019. The qualitative data were analysed

thematically using NVivo 12 to facilitate coding.

Findings

Mothers of hospitalized babies faced various challenges in coping with the hospital environ-

ment. Mothers received sparse information about their babies’ medical conditions and felt

intimidated in the contact with providers. Mothers strategically positioned themselves as

learners, guardians, and peers to enable them to navigate the clinical and social environ-

ment of the wards. Mothers feared that persistent requests for information might result in

their being labelled “difficult mothers” or might impact the care provided to their babies.

Healthcare providers also shifted between various positionings as professionals, caregivers,

and gatekeepers, with the tendency to exercise power and maintain control over activities

on the ward.

PLOS ONE

PLOS ONE | https://doi.org/10.1371/journal.pone.0283647 July 7, 2023 1 / 22

a1111111111

OPEN ACCESS

Citation: Sunkwa-Mills G, Senah K, Tersbøl BP

(2023) Infection prevention and control in neonatal

units: An ethnographic study of social and clinical

interactions among healthcare providers and

mothers in Ghana. PLoS ONE 18(7): e0283647.

https://doi.org/10.1371/journal.pone.0283647

Editor: Kahabi Ganka Isangula, Agha Khan

University, UNITED REPUBLIC OF TANZANIA

Received: July 28, 2021

Accepted: March 14, 2023

Published: July 7, 2023

open access article distributed under the terms of

the Creative Commons Attribution License, which

permits unrestricted use, distribution, and

reproduction in any medium, provided the original

author and source are credited.

Data Availability Statement: All relevant data are

within the manuscript and its Supporting

Information files.

Funding: This study was supported by the Danish

Ministry of Foreign Affairs as part of the HAI-Ghana

project (DANIDA grant number 16-PO1-GHA). The

funders played no direct role in the study design or

preparation of the manuscript.

Competing interests: The authors have declared

that no competing interests exist.

https://orcid.org/0000-0001-8342-4877

https://doi.org/10.1371/journal.pone.0283647

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https://doi.org/10.1371/journal.pone.0283647

http://creativecommons.org/licenses/by/4.0/

Conclusion

The socio-cultural environment of the wards, with the patterns of interaction and power,

reduces priority to IPC as a form of care. Effective promotion and maintenance of hygiene

practices require cooperation, and that healthcare providers and mothers find common

grounds from which to leverage mutual support and respect, and through this enhance care

for mothers and babies, and develop stronger motivation for promoting IPC.

Introduction

Healthcare-associated infections (HAIs) remain a global health challenge [1, 2], with associ-

ated direct and indirect costs to health institutions, families, and individuals [3, 4]. Neonatal

intensive care units (NICUs), with neonates receiving complex medical therapy in a highly

technical environment, are challenging environments in which to maintain patient safety [5].

HAIs are responsible for more than a quarter of the estimated neonatal deaths in hospitals in

LMICs [6]. In Ghana, the overall HAI prevalence rate is 8.2% among hospitalized patients [7].

In the NICU, mothers of babies on admission are important stakeholders, and their

involvement is critical in improving the quality of care [8, 9]. Although mothers are not solely

responsible for the care of their babies, their constant presence in the therapeutic space renders

them important stakeholders in care, whose concerns and roles need to be considered [8, 9].

This also requires that the underlying social relations of power are recognized and considered

[10]. The medical encounter has been portrayed as a place where patients are subordinated to

physicians’ domination. The unequal power relationships between healthcare providers (HPs)

and clients (including patients, caretakers, and mothers) are a central factor at the core of

addressing quality of care [11–15]. The differences in provider and client access to power and

decision-making are further accentuated by the different statuses of providers and clients [16].

In Ghana, research has shown how power relationships affect the quality of care women

receive during childbirth [17, 18]. HPs play a key role in involving and empowering mothers.

However, mothers’ reliance on the perceived expertise of HPs enforces unequal power rela-

tions [12, 19].

The joint endeavour of meaningful collaboration between HPs and mothers in managing

the risk of infection in this context is complex and compounded with challenges [20–22]. In

this context, HPs are often more focused on the provision of clinical care and are uncertain

about how to engage parents and relatives in care delivery [8, 9]. Although IPC as a form of

care may seem less of a priority to HPs, management of the risk of infection constitutes a cru-

cial aspect of care.

Limited research exists on the social environments of NICUs in low- and middle-income

settings including the interaction between HPs and mothers [23–26]. Using Positioning The-

ory, this ethnographic study explores care practices in two NICU wards in Ghana, to identify

challenges and opportunities for improved IPC.

Conceptual framework

Positioning Theory is a psycho-sociological concept of how people position themselves and

others within society and in institutions [27–29]. It is concerned with revealing the patterns of

reasoning that underlie how people behave toward one another [28]. This theory has been

applied to workplace interactions in fields ranging from public relations [30, 31] to

PLOS ONE Infection prevention and control in the neonatal unit

PLOS ONE | https://doi.org/10.1371/journal.pone.0283647 July 7, 2023 2 / 22

Abbreviations: FA, Facility A (Tertiary Hospital; FB,

Facility B (Secondary Hospital; FGD, Focus Group

Discussions; GHS, Ghana Health Service; HAIs,

Healthcare-Associated Infections; HPs, Healthcare

providers; IDIs, In-depth interviews; IPC, Infection

Prevention and Control; LMICS, Low-and middle-

income countries; MOH, Ministry of Health; NICU,

Neonatal Intensive Care Unit; WHO, World Health

Organization.

https://doi.org/10.1371/journal.pone.0283647

interprofessional relations in healthcare, including how HPs see themselves in relation to

other colleagues, patients and their relatives [32, 33]. Harré and colleagues explain that "posi-

tioning theory studies refer to cognitive processes that are instrumental in supporting the

actions people undertake, particularly by fixing for this moment and this situation what these

actions mean" [28].

HPs orient themselves to the hierarchies and duties attached to their professional functions

in the hospital setting. Communication and negotiations about hygiene and IPC compliance

also take place in this context [32]. Among HPs, collaboration across organisational bound-

aries remains challenging, and power dynamics affect the strategic choices about how and with

whom to collaborate [13]. Positioning theory [28, 30, 34] is employed to shed light on the

necessity and functionality of positions in this context.

Positioning theory has been used to examine how people produce and explain their behav-

iour and that of others, and how positions are invoked and negotiated [29, 34–37]. Positioning

and other-positioning may result in marginalization, decreased opportunities, and exclusion

[38]. HPs are continuously engaged with mothers in the NICU context, with its characteristic

structural and socio-cultural working conditions. Focusing on the positionings of HPs and

mothers, the relevant factors and the framework within which care is delivered are explored.

From the Foucauldian perspective, the hospital ward can be described as a ‘heterotopia’, a

relatively segregated place in which several spatial arrangements and rules co-exist, practices

and power structures interconnect, and various lines of interest, identity, authority, and activ-

ity intersect [39]. Doctors, nurses, administrators, patients, and families, who are involved in

this space subscribe to a set of cultural norms and base their expectations and decisions on

professional information, knowledge, and background [40–42].

Power shapes social inequalities experienced by individuals and communities as well as

health collaboration, participation, and ownership [43]. In hospital settings, where there is an

asymmetrical power difference between clients and HPs [11, 44], any form of collaboration

toward improving the quality of care is associated with complexities. Continuous attention

should be focused on the care practices in such contexts [45]. Using positioning theory, we

explore the potential to attend to and strengthen care practices in hospital wards.

Methodology

Study setting

Ghana is a West African country with a population of about 30.3 million and is divided into 16

regions, constituting the northern, middle, and southern zones [46]. Ghana has 10 regional-

level hospitals which form secondary-level referral points from primary care centres, and 5

teaching hospitals providing tertiary-level care in the public sector [47]. This study occurred in

two purposively selected hospitals in southern Ghana: the Greater Accra region and the East-

ern region. The Greater Accra region was selected because it is the national capital and has

some of the largest health facilities in the country. The Eastern region was selected due to logis-

tical reasons, with its proximity to the national capital. This study was conducted in the NICU

of a tertiary-level hospital and a secondary-level hospital, which were purposively selected as

part of a larger field study on HAIs in Ghana [7, 47]. The two hospitals selected for this study

have an average HAI prevalence rate of 10.2%, which is above the overall HAI prevalence rate

of 8.2% among hospitalized patients in Ghana [7].

The tertiary-level hospital (hereafter referred to as Facility A or FA) is a 2,000-bed hospital

in Accra in the Greater Accra region and serves as a referral centre for most hospitals in the

southern zone and beyond. FA has a 55-bed NICU and a 261-bed maternity unit. The NICU

admits approximately 2400 neonates yearly. The secondary-level hospital (hereafter, FB) is in

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Koforidua in the Eastern region and has a 356-bed capacity that serves the population of the

Eastern and other nearby regions. FB has a 30-bed NICU and a 54-bed maternity unit. The

NICU admits about 1000 neonates yearly.

Study design

We used an ethnographic approach involving qualitative in-depth interviews, focus group dis-

cussions (FGDs), and participant observations to collect data between September 2017 and

June 2019. Ethnographic research emphasizes "being there" and gaining an insider perspective

by observing and interacting with people in the setting, as participants become more comfort-

able with the researchers’ presence [48]. Ethnographic studies require long periods in the field

to experience the everyday lives of participants [49, 50]. This can provide a deeper insight into

social phenomena, and help in understanding the organisational and cultural aspects of patient

safety research [51].

Multiple data collection methods were employed as the hallmark of a good qualitative study

[52, 53] and to present an in-depth understanding of the topic under study. FGDs help to gain

an understanding of how individuals collectively construct meanings and provide deeper and

richer data due to group dynamics [43]. Participant observation was done to familiarize with

the care processes and appreciate the relationships and interactions between the various partic-

ipants. The first author (GSM) conducted most of the in-depth interviews and FGDs, with the

help of two trained research assistants, who have degrees in health-related fields and experi-

ence in qualitative research.

The first author (GSM) is a female medical doctor and Ph.D. researcher with a background

in anthropology and public health. GSM, under the guidance of the Ph.D. supervisors, BPT

(last author, an associate professor of public health with a background in anthropology and

qualitative research), and KS (second author, a professor of social science with decades of expe-

rience in qualitative research) trained the research assistants and also supervised them during

data collection. The researchers were not familiar with the participants before the study.

Recruitment and data collection

Purposive sampling was used to recruit HPs working in the two hospitals. We considered the

various categories of HPs on the wards during the selection, to achieve diversity in terms of

staff cadre and level of experience. HPs were approached during their break period, informed

about the research, and invited to participate. The study included doctors, nurses, auxiliary

nurses, midwives, hospital managers, IPC coordinators, and ward in-charges at the maternal

and NICU wards with more than 6 months of experience in the hospital. The study excluded

HPs working in the outpatient departments and those who were on study leave or transfer at

the time of the study. Forty-three HPs participated in in-depth interviews.

Women 15 years and older, whose babies had been admitted to the NICU for a minimum

of 48 hours were eligible to participate in the study. The mothers were selected purposively to

ensure that they had spent different periods in the NICU so they could share their varied per-

spectives on care. Mothers were recruited from the maternity and NICU wards, as some moth-

ers spent their time between the two wards. Mothers were approached, informed about the

study, and invited to participate. None of the participants who were invited refused to partici-

pate in the study. A total of 32 mothers participated in the in-depth interviews, and a conve-

nience sample of 40 eligible mothers participated in 6 FGDs, 3 in each hospital, with 6–8

women per group.

Interviews lasted 45 to 60 minutes and FGDs lasted 60 to 90 minutes. Interviews were con-

ducted face-to-face in the hospital, and in quiet side rooms on the wards, or in available

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conference rooms or meeting rooms. Demographic information was collected. A semi-struc-

tured interview guide (S1 Appendix) which had been pilot-tested was used to capture partici-

pants’ experiences with ward interactions and IPC compliance, but it was open to include

other perspectives. Some mothers’ interviews were conducted in English and others in Twi.

At the point of data saturation, no new information was generated from the interviews. We

conducted 6 FGDs with 40 mothers. We considered this sample size sufficient to fulfil the

objectives of this study, based on a predicted thematic saturation after 5 FGDs, with an allow-

ance for an extra FGD after data saturation.

Participants were provided refreshments (drinks and snacks) during the interviews.

The first author and 2 research assistants conducted participant observations intermittently

in the two hospitals. The observations were done on the wards during both the day and night

shifts, using an observation guide (S2 Appendix). This was done on 2 or more days in a week

in each hospital over the period of the research. The combination of participant observation

and interviews provided insight into how perceptions were translated into action [52–54].

During participant observations, researchers participated in activities, assisted by handing

over items during procedures, and supported HPs when they needed help to fetch items or to

arrange the wards. Informal conversations were held with HPs during work or while they were

on break. We took down observation notes and documented any interesting incidents during

the observation period. Observation notes were taken during participant observation (S3 File).

Data analysis

Interviews were audio-recorded and transcribed verbatim. Interviews conducted in Twi were

translated into the English language during transcription and then checked for accuracy. Data

were analysed thematically based on the objectives of the study [55, 56]. Relevant contextual

information from interview notes and field notes were incorporated for further ethnographic

analyses [50]. The transcripts were uploaded to QSR N Vivo 12 to support coding and analysis.

The data was triangulated, and similar codes were grouped into categories. Initial codes were

descriptive and close to the data [57]. The categories were then regrouped into subthemes and

themes. Our theoretical orientation was drawn from the positioning theory [28, 34] which

informed the framework for analysis. The initial reading of the transcripts was done by all

authors. GSM conducted the majority of the analysis; however, the co-authors (KS and BPT)

read and coded several interviews. During data analysis the developing themes were also dis-

cussed with the co-authors and other researchers including conflicting perspectives which rep-

resent the complexity of social life and interactions on the ward. The second author (KS) was

engaged to resolve any discrepancies. To maintain rigor in the analysis, we aimed for reflexiv-

ity by having a research team with diverse backgrounds. Team discussions were held to incor-

porate diverse perspectives while interpreting the findings to maintain objectivity in the

research. We used the COREQ checklist (Tong et al., 2007) [58] to report our research as it is

the standard guide for reporting qualitative research studies.

Ethical approval and considerations

Ethics approval for this study was obtained from the Ethical Review Committee (GHS-ERC

07/03/2017) of the Ghana Health Service. Written and verbal information and explanation

about the research objectives were given to participants before each interview. The interview-

ees all gave written informed consent by signing a consent form after they had been informed

about the study and assured of confidentiality and anonymity. Pseudonyms were used to

ensure the anonymity of participants.

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Findings

HPs were aged between 20 and 59 years and worked in various capacities in the hospital

(Table 1). The mothers who participated in this study were representative of postnatal mothers

in the selected wards (Table 2).

Navigating the NICU

The NICUs of the two hospitals had many similarities in terms of organization of care, proce-

dures, and routines. The number of HPs on the wards changed constantly due to the shift sys-

tem, regular reshuffling, and the presence of medical and nursing students on rotations and

internships.

In FA, the NICU consists of three cubicles. Babies are admitted to cubicle 1 when they are

severely ill. Cubicle 1 has more incubators and radiant warmers, and usually has the attention

of more nurses as the babies are critically ill. The babies are moved to cubicle 2 when their clin-

ical condition improves, and then to cubicle 3 prior to discharge.

Most mothers move between the maternity ward and the NICU to feed their babies at

scheduled times. Other mothers commute from home or a nearby hostel to feed their babies

every 2–3 hours.

In FB, the NICU has two cubicles—one for babies born within the hospital and the other

for babies referred from external health facilities. Mothers come in to attend to their babies

2–3 hourly, and when specifically requested by HPs. In the initial stages of treatment, babies

are placed in open cots, under radiant warmers, or in specialized incubators that monitor their

Table 1. Characteristics of healthcare providers who participated in the study (n = 43).

Demographic characteristics Number (%)

Age

20–30 22 51

30–39 18 42

>40 3 7

Marital Status

Single 14 33

Married/ Partner 28 65

Divorced 1 2

Staff cadre

Manager 4 9

Doctor 8 19

IPC Coordinator 2 5

Nurse/Midwife 24 56

Other 5 12

Years in current position

< 5 35 81

6–10 7 16

> 10 1 2

Location/ Service level

Tertiary (FA) 18 42

Regional (FB) 25 58

Gender

Male 10 23

Female 33 77

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oxygen level, temperature, respiration, and other vital signs. It is common to hear beeping

alarms and humming sounds from machines in the NICU environment.

HPs maintain a constant presence in the NICU, overseeing the contact between mothers

and babies. Experienced HPs are familiar with the ward setting, routines, and technology;

however, mothers often find this space alienating. In FA, mothers sit in compactly arranged

plastic chairs in an open space in the middle of each cubicle when they come in to care for

their babies. In FB, mothers sit by their babies’ cots to care for and breastfeed them. Outside

the scheduled hours for contact with their babies, mothers often remain in the background try-

ing to understand what is going on while keeping an eye on their babies from a distance. In

trying to cope with this situation and find their place as part of the ward community, mothers

positioned themselves as learners, guardians, and peers.

Mothers’ position as learners. Mothers consistently mentioned that they were neither

introduced to the routines of the ward nor their roles in the care of their babies. A young

mother who had been referred to FA from a smaller hospital narrated how she waited all night

to be attended to by a doctor.

“It was a little bit frustrating because the ambulance brought me in around 10:30 pm. . .. on Thursday evening . . . and by the time I got a bed it was 4:00 am on Friday. You can imagine! There’s no chair to sit on, nowhere to lie. The ambulance had left. . . .they took me to the emergency. . . then they left me hanging till they were ready for me (MT1)

After she had delivered through a caesarean section, her baby was transferred to the NICU

and was kept in a cot near the nurses’ station until a doctor was available to conduct an assess-

ment of the baby. Her husband did the initial follow-up on the baby’s condition, and she only

saw her baby a few days later, while recovering from surgery. She lamented that she received

little information about the condition and progress of her baby. More than half of the mothers

Table 2. Characteristics of mothers who participated in the study (n = 72).

Demographic characteristics Number (%)

Age

15–19 4 6

20–29 29 40

30–39 25 35

40–49 14 19

Marital Status

Single/Other 25 35

Married 47 65

Education

None 10 14

Primary 26 36

Secondary 19 27

Tertiary 14 19

Postgraduate 3 4

Number of days on admission

<14 51 71

15–28 17 24

>28 4 5

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interviewed shared similar experiences reflecting poor communication and ensuing feelings of

marginalization.

About a third of the mothers mentioned that they were uncertain about who would address

their concerns. These mothers also mentioned that they felt uncomfortable asking questions

about their babies.

“What will I ask? I am neither a doctor nor a nurse. I do not understand what is going on”.

(MT10)

Struggling with information deprivation, mothers said they felt relieved when they received

information about their baby’s treatment or progress.

“I remember one of the doctors. . .he came to tell me the following day. . .that my baby was alright. And I thanked him for the information he brought to me, but I still didn’t know where exactly they had sent my baby.” (MT9)

Mothers were anxious about the lack of bonding with their babies through skin-to-skin

closeness. Mothers with critically ill babies had to wait longer to embrace their babies, who

were often attached to tubes and machines. Mothers became fast ‘learners’, as they observed

and tried to understand routines and activities in care and how HPs handled the babies. Moth-

ers negotiated with nurses to be allowed to do more, such as changing diapers and bathing

their baby as the baby’s medical condition improved. Mothers took these initiatives with care-

ful consideration of the potential negative reactions of HPs, to avoid being reproached for

engaging with their babies without permission to do so.

In all FGDs, mothers mentioned that they were grateful and relieved whenever HPs offered

guidance on how to care for their babies. They appreciated it when HPs encouraged and

empowered them to participate in caring for their babies. Mothers underlined the importance

of HPs’ support in helping them to understand the invasive procedures, changes in weight,

and other concerning aspects of the baby’s condition. Mothers acknowledged that although it

was a stressful time, support and feedback from HPs could help them have a more positive

experience.

“I take a lot of interest in what is going on. I ask a lot of questions. . .I get very interactive with the nurses when they are not busy. . .if they are busy, I don’t stress them. . . I can imagine their frustrations . . . I mean if they can’t answer my questions at the time, they would get back to me later.” (MT17)

Although there seemed to be no clear role for mothers in many scenarios, they made them-

selves available to learn and perform any tasks related to the care of their babies. They would

typically ask a lot of questions, which met a wide range of responses from the nurses, some-

times favourable, and other times discouraging.

“When they come around to do their work, I ask them questions. . . .. Some smile and talk to me, others don’t.” (MT18)

During the FGDs, mothers made comments such as:

“They do not even exercise patience to listen . . . when we ask questions, they do not take their time to explain things well to us.” (MT45)

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“Sometimes they come and tell you that today, your baby will be under the light, but they do not explain why. Is the light supposed to help the baby improve? Is there something wrong? They do not say anything to us.” (MT52)

Mothers’ position as guardians. Mothers generally perceived the hospital as a stressful

environment. Some mothers speculated about the potential risk of infection. They mentioned

the inadequate provisions available for them and often complained that the time allotted for

them to be with their babies was inadequate. A mother mentioned that the associated anxiety

made her so stressed that she often could not sleep well at night.

Mothers longed to be fully informed about their baby’s progress and have opportunities to

raise questions about care, especially when they perceived their babies to be at risk. A mother

indicated that she did not fully trust HPs with the care of her babies, due to previous experiences.

“I find myself being nosy. . . I would like to know when they are administering the med- ication. . . when I come, I want to follow up on it. . . please, did you give this medication at this time to my baby? There have been more than four occasions when it hasn’t been adminis- tered. . . because we are many, and probably. . . they forgot. . . but once you remind them, they do it.” (MT1)

Mothers reported how they sought to watch their babies closely whenever they had the

opportunity so that they could detect any issues with their baby’s condition and bring it to the

attention of HPs.

A mother mentioned that at one point, she alerted a nurse about her baby’s intravenous

line that had come off, but was dissatisfied with the apathetic response she received.

When mothers felt that HPs were not keeping up with the babies’ needs, they worried that

it would affect the baby’s condition. This, they said, was especially so during the night duties,

when there were fewer doctors and nurses on duty.

“While some mothers at the ward have their babies close by, mine is lying so far away. I can- not leave him there and go to sleep, so I sit by his bedside and sleep in the chair if I feel tired”. (MT20)

If permitted to do so, mothers assumed some of the nursing tasks, once their babies were

stable. Nurses would correct mothers to have procedures and tasks done according to how

things, in their view, should be done. Mothers who adapted, felt better accepted by the HPs.

Thus, mothers are directed to be ‘good mothers’. Mothers who do not adjust or who ques-

tioned or confronted HPs on the informal or formal rules of the ward risk being labelled as

‘difficult’ by HPs.

In FA, a mother expressed concern about the risk of infection due to the close arrangement

of cots and incubators, which also left little room to perform care activities or have any privacy.

“I think they can have another place for us the mothers to breastfeed instead of being in the same room with the incubators and other machines. . . the place is small, and the mothers are many. . . we can even spread infection to the babies”. (MT9)

Mothers also paid attention to spaces reserved for medical procedures. HPs took laboratory

samples from the babies and performed other procedures on a designated table with a linen

cover. Mothers sometimes complained that the linen cover on the table was not changed

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frequently, thereby posing a risk of infection. A mother also complained that she had noticed

ants in her baby’s cot and expressed worry about the dilapidated state of the mattress.

As guardians, mothers paid attention to hygiene in the NICU. A mother said:

“I just had my own way of extra sanitizing my hands. I pick the chair with my elbow because I don’t want to infect my hands so that I don’t defeat the purpose.” (MT32)

Mothers’ position as peers. Mothers in the NICU did not have direct access to any official

structured guidance or support systems provided by the hospital. Collective instructions, ori-

entation, and support were not routine procedures on the wards, so mothers generally received

sparse instructions about how to act and cope on the ward during this stressful time. Instead,

important information, instruction, and advice were provided by other mothers, a form of

improvised and unofficial peer education in the NICU. Mothers discretely established net-

works with peers and offered advice right from the first days in the NICU to help others find

their way in the opaque rules and norms of the wards.

Mothers described watching other mothers closely and that this interaction helped them in

attempting to become more “competent” in the gaze of HPs. Sharing experiences with other

NICU mothers was an important source of emotional support. Mothers created and facilitated

an informal platform to share experiences. Mothers who had stayed longer in the NICU often

became unofficial teachers, with the new incoming mothers literally calling themselves “stu-

dents.” The “students” typically observed what their peer mentors were doing and took cues

from their approaches.

“For me, I have not started breastfeeding my baby, but sometimes when I see people breast- feeding their babies, I observe” (MT37)

Peer support also reminded mothers of routine hand hygiene practices as the experienced

mothers were already used to this. The mothers relied heavily on the support and advice gener-

ated by this association. When mothers were not informed about the purpose of specific medi-

cal procedures or equipment that their baby was exposed to, they relied on more experienced

mothers who could provide comfort by giving them some insights:

“When I came and noticed my baby had been put under the light for phototherapy, I was scared . . . I was confused and was crying until another mother whose baby had previously been put under the light called me, and explained to me that it was going to help my baby. She assured me that my baby was going to be ok” (MT30)

Some mothers also depended on the support and encouragement from family members

and friends to help them during the period of hospitalization. Although relatives came around

to support them, there were visiting restrictions that prevented them from having access to the

NICU. HPs explained that they had concerns about too many relatives coming in, as it would

increase the risk of infection for the babies. Some mothers were however displeased with the

restrictions as it left them feeling even more lonely and excluded.

Positionings of healthcare providers

In the following, we describe the ways in which HPs positioned themselves.

Healthcare providers as professionals. The major professionals in the hospital wards

include doctors, nurses, and other clinical and non-clinical staff. Both hospitals have an IPC

coordinator—a nurse with the task of supporting, communicating, and facilitating hygiene

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procedures in the wards. The IPC coordinator worked across professional groups and tasks. In

terms of responsibility for implementing HAI prevention strategies, HPs maintained that it

should be done by everyone including clinical staff, non-clinical staff, and mothers.

As professionals, HPs placed themselves in a position as knowledgeable and powerholders,

legitimated by their educational and professional qualifications and the hierarchical structures

of the hospital. HPs felt the need to make their authority known and tangible to mothers and

established boundaries to control the daily routines on the ward. One HP said:

“Sometimes you’re busy trying to set a line for a baby, only for a mother to tap you on the shoulder trying to find out what is wrong with their baby; it can be really distracting. . . but it’s ok, because sometimes we also need them to be around to give us information about the babies”(D7)

These boundaries were not only of a clinical nature but focused on controlling social inter-

action, to maintain order in interactions with mothers and their relatives. Sometimes, when

convenient for HPs, they would disregard these boundaries and allow mothers or family mem-

bers into the ward outside the designated visiting hours to assist in carrying specimens to the

laboratory or purchasing medicines from the pharmacy.

Although communication with mothers was often done in an authoritarian way, there were

also instances of kind and empathetic communication. HPs would encourage mothers to take

care of their health and advise on when and what to eat to have a good flow of breastmilk. HPs

focused on clinically authorized standards, levels, and measurables, for example, they expected

mothers to sometimes express and measure breastmilk for babies who had to take specified

amounts at a time. Mothers were expected to relate to these clinical objectives and remain

cooperative, even though this was sometimes challenging for some mothers.

Healthcare professionals as caregivers. The position of the clinical caregiver was central

in the NICU. HPs conducted physical examination, set intravenous lines, suctioned and resus-

citated babies among many other tasks, and they monitored babies in critical conditions and

performed other routine tasks in the NICU. HPs also provided other forms of care including

feeding, cleaning babies, changing diapers, and assisting mothers who attempted to breastfeed

their babies:

“It is her first time having a baby, and sometimes even handling the baby is a problem . . . the idea that her baby is in NICU, the anxiety is already high, so even touching or holding the baby is another problem; so, she will ask you to do it for her. You have to encourage them and let them know that they are babies, and they will go home with them so bit by bit . . . they are able to grasp everything you say, and as time goes on, you will see them positioning the baby to the breast and breastfeeding them” (N15)

HPs admitted that they did not always have enough time to explain things to mothers, and they

did not always prioritize it; the busy workload, large number of babies, and rapid patient turnover

were described as overwhelming. The night shifts were perceived to be more demanding.

“The night shift is more tedious. . . and there are limited staff too. . . .And because the mothers do not come up to breastfeed during the night, the workload is increased. . . you have to do everything by yourself” (N14)

We noted from our observations that the night shifts usually involved fewer administrative

tasks and social activities, but nurses had to do more work, as there were fewer nurses assigned

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to care for the same number of babies during the night. Senior consultants did not work on

night shifts and had to be contacted on the phone if there were critical issues or a baby was in a

critical condition and the doctor on duty needed direction.

HPs described their challenges in coping with the demands of caring for severely ill babies

while attempting to address the physical and emotional needs of mothers. Therefore, they

mostly focussed on the babies, despite the opportunities to address mothers’ worries and

engage mothers in a participatory role in care.

All HPs associated some aspects of their work as caregivers with a risk of infection, given

the regular exposure to body fluids and ‘unseen’ microorganisms.

Healthcare providers as gatekeepers. HPs determined the extent to which mothers could

participate in the care of their babies. For extremely ill babies, nurses were observed guiding

the mother to hold or hand over materials during procedures. Nurses, however, positioned

themselves as ‘gatekeepers’ by restricting the amount of time mothers had direct physical con-

tact with the delicate preterms, and explained that this was to ensure the baby’s safety. Moth-

ers’ participation in caring for babies was particularly limited during these periods. When

mothers were allowed to hold their babies and carry out different care tasks, HPs felt the need

to control how mothers handled their babies due to their vulnerability.

A nurse mentioned that mothers were sometimes inattentive or slow to respond to instruc-

tions, and this increased the work of HPs as they had to supervise such mothers to ensure

timely responses to instructions such as purchasing drugs or following up on laboratory speci-

men results, in the interest of the baby’s health. During our observations and interactions, one

doctor described a practice of ‘covering’ babies by administering antibiotics as ‘prophylaxis’ to

babies who were perceived to be at risk of infection from a clinical perspective, or from the

environment when they are paired with other babies in the same cot when the NICU was full.

When discussing IPC, HPs highlighted that mothers need to maintain a minimum level of

hand hygiene—with emphasis on washing hands at the entrance of the NICU, and after chang-

ing the baby’s diapers. HPs directed mothers to follow instructions through posters, e.g.,

proper handwashing, not handling of mobile phones while breastfeeding, not picking things

from the floor, etc. Mothers were often instructed ’not to touch’. One mother said:

"Over here you don’t take something for someone. You can’t take anything for someone, even if it’s a cot sheet. . . even if you want something, you have to tell the nurse, especially with the cups that we express the milk into. They take the cup themselves, you don’t have to touch it" (M21).

HPs worked within an environment with both human resource and supply constraints.

One HP noted:

“. . . ermmm sometimes the workload alone overwhelms you, so I won’t say you tend to forget your hand hygiene, but it comes as if it’s a burden or something of that sort.” (N28)

HPs were expected to maintain clinical standards with limited equipment and materials.

Cots, phototherapy machines, radiant warmers, and apnoea monitors were available but not in

sufficient numbers for the care of neonates admitted. Various professionals sometimes com-

peted for resources, and glove use was monitored by ward matrons and used sparingly.

In gatekeeping, HPs controlled resources available to mothers too. For example, limited

quantities of hand towels were kept at the entrance where mothers wash their hands, and liq-

uid soap was disbursed in diluted quantities in bottles as a strategy to minimize wastage.

Some HPs in FA expressed concerns about overcrowding in the NICU as it made it difficult

to monitor mothers adequately, especially during feeding times. HPs mentioned that they

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expect mothers to cooperate with them as they the HPs oversee the health needs of their babies.

A nurse indicated that ‘difficult mothers’ do not comply with nurses’ instructions.

“Err. . . Ideally, there should be a nurse at the entrance during the time that the mothers come, to supervise them to wash their hands at the proper place when they enter and when they are leaving. . . but for some time now . . . we do not have a permanent public health nurse who will assist with those things. . . so one of the nurses speaks to the mothers at the gate . . .so they wash their hands before they enter the cubicle, but when they are going most of them don’t wash their hands.” (N3)

This nurse here also indicated that instruction to mothers regarding IPC is ideally the role

of a public health nurse, rather than the responsibility of all staff.

Collaboration to improve hand hygiene

HPs in this study appreciated and discussed the relationship between HAIs and poor adher-

ence to IPC protocols, especially hand hygiene. One doctor mentioned that HAI is not pro-

jected enough among HPs, and that more evidence must be demonstrated to convince HPs of

the significant impact of hand hygiene on preventing HAIs. One HP admitted to neglecting

hand hygiene protocols in circumstances that require unusual responses such as emergencies

where time is of essence.

HPs mentioned that the frequent lack of materials for hand hygiene makes IPC compliance

challenging, especially in FA where the handwashing sinks in the cubicles were often out of

order or had no water flowing.

“Yeah, sometimes you might come and there wouldn’t be soap so you would have to go and get some from somewhere else, and also sometimes it is not practical for me. . . for example, if I’m going to examine like 15 to 20 babies, I can’t wash my hands after everyone.” (D1)

HPs indicated that they needed more commitment from those at the management level to

help address gaps in IPC on the wards.

“There is no allocation of funds for IPC to the best of my knowledge. . . so anytime you request for funds. . . then you hear the complaints of no funds . . .there is no money." (N23)

Although HPs might be called for IPC training, IPC-related materials were routinely lacking:

"For instance, when we went for the workshop, they taught us a lot of things, but when we come to the ward, we don’t get the items. For instance, when decontaminating or washing bed- sheets you need to wear utility gloves. They will say it, but it’s not available." (N18).

Although HPs did not actively engage mothers in conversations on hand hygiene or infec-

tion control, mothers who took the initiative to follow protocols were often encouraged by the

HPs.

“Some mothers were also very cautious to the extent that if they pick a chair with their hand, you see them rubbing their hands with the sanitizer before they touch the baby. It was impres- sive. It was very good.” (N6)

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During observations, HPs were seen monitoring each other and commenting on who was

observing IPC protocols or performing hand hygiene appropriately. One HP said:

“When I come on a shift and a staff is performing a delivery without an apron, I would quickly go for an apron and come and put it on for her.” (N41).

HPs also considered it important to support and look out for each other:

“If you see a colleague who has taken off the gloves and the hands are very soiled. . . and he or she just wants to move to the next thing by just sanitizing, you prompt them “you can see your hand is visibly soiled, so what do you”? Then the person will say “handwashing”, and the per- son goes to wash their hands. So, like everybody is prompting someone and we are all on the same page.” (N18)

Discussing the challenges of IPC implementation, a HP commented on the difficulty in

reaching management with suggestions of improvement due to ’lines of command’.

“The challenges have to do with the structure. . . if I identify something that I think can help improve IPC, I have to communicate that to somebody. . .the head of the department. . . who will then have to discuss it at the management meeting. . . and once I’m not there to articulate and explain what it is, the person’s interest will influence the outcome of this idea. . . so if he doesn’t see the need for what you are saying, what it means is that your idea is already aborted prematurely.”(N22)

During interactions with one HP who was also a manager, we asked about how sustainabil-

ity of an IPC intervention could be secured. He promptly responded that we should “forget

about sustainability” and added that even if we "just provide the gloves, cleaning agents, and

other IPC supplies" for a few months, some babies would still benefit, even if it is not sustain-

able. The HP continued to describe his own efforts to secure running water in the ward, ’chas-

ing the engineers. . .spending hours looking for them.’ He added that they eventually came and

fixed the pipes, but two days later, there was no running water. "I don’t have the time to chase

engineers", the HP concluded.

Discussion

This study used an ethnographic qualitative methodology to assess IPC efforts in the clinical

and social environment of two NICUs in Ghana. Inspired by the positioning theory, we

explored how healthcare providers and mothers positioned themselves opposite each other in

the social field of the hospital and navigated their roles in the hospital setting. We focused on

key aspects of the positionings of HPs and mothers, and how this helps us understand the social

environment and the "positioning" of IPC in this setting. Research participants make sense of

their experiences and actions and also justify their positions and practices by reference to other

people, processes, and hospital structures surrounding them in the ward environment.

Mothers’ positioning as a form of agency

The hospital and its organizational and staff structure is an arena of asymmetrical roles and

power dynamics [59, 60]. HPs have a high status due to their education and position in the

hospital, while mothers are expected to be compliant with the priorities of clinical manage-

ment. These asymmetrical power dynamics lead to the strategic positioning of the HPs and

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mothers. The interactions between HPs and mothers are of great importance in improving the

quality of clinical decision-making and ultimately maternal and new-born health outcomes

[26, 61–63]. Researchers have demonstrated a need to support bonding between mothers and

their babies through early and repeated physical contact [64, 65]. Mothers experience distress

when restricted from physical contact with their babies. Early separation from the mothers is

also a significant stressor for neonates, influencing emotional and cognitive development with

possible long-term health consequences [66]. Similar to our findings, mothers have reported

feelings of neglect and lack of supportive treatment in hospital wards in other settings [67].

Other studies have reported that powerful HPs can frustrate less powerful mothers through

neglect or withholding required services [60, 68].

Parental presence in NICU, together with support and education by nursing staff reduces

the stress that parents experience [69]. Implementing initiatives in this direction in low-income

settings to improve the level of satisfaction with care would demand resources and a shift of the

culture and practices shaping social interaction and positioning on the ward [61, 67].

In our data, mothers positioning as guardians was fuelled by lack of information and lack of

trust in the dedication of HPs to ensure the best possible care. As guardians, mothers’ agency

was limited. They could watch their baby if they were allowed in the ward, but they could not

interfere with the clinical care. Notification about a drip that had fallen out or other unin-

tended clinical events not addressed by HPs, would possibly spur irritation from HPs.

However, the mothers exercised agency in other ways: positioning themselves as compliant

learners aimed to pave the way for goodwill, information and up-dates from HPs. As ‘good

mothers’, they avoided interfering with the routines of HP and they could carefully time their

request for information, attention to a drip out of place, or being granted more time next to

their babies’ incubators.

Mothers also exercised agency as they teamed up and offered or received peer guidance.

Mothers demonstrated their emic insight and capacity in their support to new mothers. This

way, the experienced mothers inherently also supported the HPs’ routines on the ward. Peer

networks have shown themselves to be beneficial in care, and helpful in allaying the concerns

and experiences of marginalization in terms of clinical care and hygiene [70–72].

HPs’ positioning as a form of self-protection

As HPs positioned themselves as professionals and gate keepers, they continuously refer to a

need to maintain control and power over the presence and actions of mothers and relatives, so

as to be able to focus on clinical tasks and prevent unforeseen events that would steal time.

HPs justify this with reference to the supreme priority of clinical tasks. This tendency is com-

pounded by the fact that work at the NICU is challenged by a patient-load above ward capacity

and staff numbers that do not match the patient-load. One HP described how contributing to

innovation is difficult because the distance to decision-makers where suggestions could be

heard and discussed is too great, which indicates that HPs sometimes feel disempowered.

HPs communicated with authority, provided limited information on conditions of the neo-

nates and sought to maintain a focus on clinical care and outcomes, similar to findings in

other studies [73, 74]. Although HPs had opportunities to engage mothers to partner with

them in caring for the babies and in promoting IPC, the stressful situations in the NICU did

not encourage an interactive and collaborative approach, and there is a possibility that HPs

were concerned that this would affect their authority. Other studies have reported that HPs felt

that engaging with families created additional demands on their time [75, 76]. However, non-

clinical care, such as communication with and support to parents and relatives has been

shown to influence perceptions of the quality of care [77, 78].

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One HP mentioned the practice of "covering babies"- providing preventive treatment with

antibiotics to babies who were perceived to be at risk of infection from overcrowding or the gen-

eral ward environment- which can be viewed as "an extension of infection prevention and con-

trol measures". Willis and Chandler have raised concerns about treating infections as a quick

fix, rather than addressing the underlying factors of poor hygiene among others. They further

noted that antibiotics have become a ‘quick fix’ in fractured health systems, being used as a sub-

stitute for hygiene in resource-constrained settings [79]. Labi et al argue for continuous surveil-

lance of infections in the NICU to guide antibiotic treatment guidelines and improve neonatal

morbidity and mortality [80]. The positioning of HPs could be described as a response to orga-

nisational ‘injustice’ [81] where HPs feel exploited and disenfranchised from influences in their

workplace, as shown in our findings. Arnold et al noted that HPs in Afghan hospitals were frus-

trated by the injustices they experienced as a result of their own powerlessness within the health-

care system [82]. Aberese-Ako et al [81] emphasise the need to develop health care

organisations that are able to produce people-centred care and continuous quality improve-

ment. Our data points to this need as well. Organisations that cannot protect and care for their

own people, can hardly provide quality care for clients. In principle, IPC constitutes a form of

mutual care—a care practice that should be prioritized to keep babies, mothers, and HPs safe.

Strengths and limitations

The study involved long durations of immersion in the hospital wards to mitigate observation

biases and using interviews to gain a better understanding of the topic under exploration. This

strengthens our understanding of how positioning intersects with the HPs’ and mothers’ expe-

riences in the hospital context and how this affects care delivery. The inclusion of mothers’

perspectives further strengthens the findings of this study.

Some mothers were interviewed in Twi. It is possible that there may have been translational

variability, and that nuances in the language could have been missed in the process of interview-

ing, transcription and analysis. To mitigate this, researchers carefully considered the approach

to phrasing interview questions to facilitate easy comprehension. Researchers were also skilled

in interviewing and established a good rapport with participants which made the sharing of

information easier. Transcripts were checked against the original audio files to ensure the

nuances of the local language had been well captured, to limit translational variability.

Questions to participants were not always phrased or probed the same way. The findings

are therefore informed by the experiences of the participants and the researchers. However,

researchers were reflexive, and there were constant discussions between researchers to ensure

that the objectives of the study were understood.

Conclusion

This study shed light on issues in the socio-cultural environment of the wards which reduce

priority to IPC. The research demonstrates the need for HPs and mothers to reflect on their

positionings in relation to each other, to promote better communication and collaboration.

These positionings have provided an analytical construct by which we capture patterns of

interaction and power. While Harré et al. speak of "fixing for this moment the meaning of

actions" [28], we consider the positionings expressed in our data to be of a more lasting nature.

This is because the organisational and societal context that co-create these positions are more

or less unchanging and the stressors and dilemmas of both HPs and mothers present on the

ward, are therefore continuously reproduced.

The WHO global report on infection prevention and control [83] indicates that IPC inter-

ventions can reduce HAI rates HAIs by 35–70%. There is however a need to put in more effort

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to ensure that IPC is placed at the centre of hospital care alongside clinical care, in sustainable

ways, with full-time professionals dedicated to IPC, allocated IPC budget, surveillance, and a

suitable patient-staff ratio. While human resources and other resources and materials for IPC

are important, the social environment and interactions in hospital wards are also fundamen-

tally important. To improve IPC in a sustainable way at the health facility level, an enabling

environment must be created, as well as an institutional culture that considers important

socio-cultural processes that impact care practices including IPC-related care.

Effective promotion and maintenance of hygiene practices requires cooperation between

HPs and mothers, and the need to find common grounds from which to leverage mutual sup-

port and develop a stronger motivation for preventing HAIs.

This requires a shift in emphasis from the biomedical focus to collaborative practice in the

appropriate socio-cultural context, with a facilitating environment that also supports mothers’

confidence as stakeholders. A better understanding of mothers’ experiences helps identify

strategies to involve them as partners in care delivery. Further research into strategic

approaches towards a partnership to improve the quality of care would be beneficial in ensur-

ing that mothers receive quality care for themselves and their babies.

In addition to training and capacity building for HPs, the organisational culture in hospitals

should prioritise IPC as a form of care for both HPs and clients. IPC knowledge, skills, and

tools should be accessible to both HPs and clients to facilitate best practices. Withholding

knowledge or skills as a way of maintaining power, respect, or superiority [82] should be dis-

couraged. Rather, HPs should be empowered through an enabling environment to maximise

the provision of quality care.

This study explores the positionings of HPs and mothers and focused less on actual cases of

HAIs. An important next step would be to link positioning, perspectives, and practices to the

occurrence of HAIs.

Supporting information

S1 Checklist. COREQ (COnsolidated criteria for REporting Qualitative research) check-

list.

(PDF)

S1 Appendix. Interview questions.

(DOCX)

S2 Appendix. Participant observation guide.

(DOCX)

S1 File. Quotes reflecting mothers positioning.

(DOCX)

S2 File. Quotes reflecting HPs positioning.

(DOC)

S3 File. Participant observation notes.

(DOCX)

Acknowledgments

We thank the informants who participated in this study for their willingness to share their

knowledge. We are grateful to the healthcare providers and mothers in this study, and we

thank everyone who has contributed to the research. We appreciate the dedication of our

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research assistants, Mavis Obeng-Kusi, Evelyn Larkai and Jessica Laryea. We are grateful to

Matilda Aberese-Ako for her constructive input on the manuscript. We wish to thank our

reviewers for their insightful comments. The research is under the HAI Ghana project, a proj-

ect aimed at reducing morbidity, mortality, and costs related to HAIs. The HAI Ghana project

is an international, multicentre, and interdisciplinary research network that brings together

post-Doctoral fellows and Ph.D. students under the supervision of Ghanaian and Danish

experts in various fields of academia.

Author Contributions

Conceptualization: Gifty Sunkwa-Mills, Kodjo Senah, Britt Pinkowski Tersbøl.

Data curation: Gifty Sunkwa-Mills.

Formal analysis: Gifty Sunkwa-Mills, Britt Pinkowski Tersbøl.

Investigation: Gifty Sunkwa-Mills.

Methodology: Gifty Sunkwa-Mills, Kodjo Senah, Britt Pinkowski Tersbøl.

Software: Gifty Sunkwa-Mills.

Supervision: Kodjo Senah, Britt Pinkowski Tersbøl.

Writing – original draft: Gifty Sunkwa-Mills, Britt Pinkowski Tersbøl.

Writing – review & editing: Gifty Sunkwa-Mills, Kodjo Senah, Britt Pinkowski Tersbøl.

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SHEA White Paper

SHEA Neonatal Intensive Care Unit (NICU) White Paper Series: Practical approaches for the prevention of central-line–associated bloodstream infections

Martha Muller MD1,2, Kristina A. Bryant MD3,4, Claudia Espinosa MD, MSC5, Jill A. Jones MS, APRN, NNP-BC6,

Caroline Quach MD, MSc, FRCPC7,8, Jessica R. Rindels MBA, BSN, RN, CIC9, Dan L. Stewart MD10,11,

Kenneth M. Zangwill MD12 and Pablo J. Sánchez MD13,14

1Pediatric Infectious Disease, University of New Mexico School of Medicine, Albuquerque, New Mexico, United States, 2UNM Health Sciences, Albuquerque, New Mexico, United States, 3Pediatric Infectious Diseases, University of Louisville, Louisville, Kentucky, United States, 4Norton Children’s Hospital, Louisville, Kentucky, United States, 5Pediatric Infectious Diseases, University of South Florida Morsani College of Medicine, Tampa, Florida, United States, 6Nationwide Children’s Hospital, Columbus, Ohio, United States, 7Departments of Microbiology, Infectious Diseases and Immunology and Pediatrics, University of Montreal, Montreal, Québec, Canada, 8Clinical Department of Laboratory Medicine, CHU Sainte-Justine, Québec, Canada, 9Children’s Mercy Hospital, Kansas City, Missouri, United States, 10Norton Children’s Hospital, Louisville, Kentucky, United States, 11University of Louisville School of Medicine, Louisville, Kentucky, United States, 12Division of Pediatric Infectious Diseases and Department of Infection Prevention and Control, Harbor-UCLA Medical Center, Torrance, California, United States, 13Divisions of Neonatology and Pediatric Infectious Diseases, Department of Pediatrics, Nationwide Children’s Hospital, Columbus, Ohio, United States and 14Center for Perinatal Research, Abigail Wexner Research Institute at Nationwide Children’s Hospital, The Ohio State University College of Medicine, Columbus, Ohio, United States

Abstract

This document is part of the “SHEA Neonatal Intensive Care Unit (NICU) White Paper Series.” It is intended to provide practical, expert opinion, and/or evidence-based answers to frequently asked questions about CLABSI detection and prevention in the NICU. This document serves as a companion to the CDC Healthcare Infection Control Practices Advisory Committee (HICPAC) Guideline for Prevention of Infections in Neonatal Intensive Care Unit Patients. Central line-associated bloodstream infections (CLABSIs) are among the most frequent invasive infections among infants in the NICU and contribute to substantial morbidity and mortality. Infants who survive CLABSIs have prolonged hospitalization resulting in increased healthcare costs and suffer greater comorbidities including worse neurodevelopmental and growth outcomes. A bundled approach to central line care practices in the NICU has reduced CLABSI rates, but challenges remain. This document was authored by pediatric infectious diseases specialists, neonatologists, advanced practice nurse practitioners, infection pre- ventionists, members of the HICPAC guideline-writing panel, and members of the SHEA Pediatric Leadership Council. For the selected topic areas, the authors provide practical approaches in question-and-answer format, with answers based on consensus expert opinion within the context of the literature search conducted for the companionHICPAC document and supplemented by other published information retrieved by the authors. Two documents in the series precede this one: “Practical approaches to Clostridioides difficile prevention” published in August 2018 and “Practical approaches to Staphylococcus aureus prevention,” published in September 2020.

(Received 22 February 2022; accepted 23 February 2022; electronically published 4 March 2022)

Central–line-associated bloodstream infections (CLABSIs) are among the most frequent invasive infections among infants in the NICU, and they contribute to substantial morbidity and mor- tality. Infants who develop CLABSIs have prolonged hospitaliza- tions, resulting in increased healthcare costs; these infants also suffer greater comorbidities, including worse neurodevelopmental and growth outcomes.1–3 A bundled approach to central-line care practices in the NICU has reduced CLABSI rates significantly,4–6

but challenges remain. A cross-sectional study using 2013–2018 Centers for Disease Control and Prevention (CDC) surveillance

data from 132 NICUs that report to the National Healthcare Safety Network (NHSN) suggested that previous improvements in CLABSI rates have plateaued.7 During the study period, CLABSI rates remained stable, with mean rates of 1.56 CLABSIs per 1,000 central venous catheter (CVC) days in NICU patients with birth weights ≤1,500 grams and 0.72 CLABSIs per 1,000 CVC days for those with birth weights >1,500 grams. Infants in the NICU have certain unmodifiable risk factors for infection (eg, an immature immune system), and they require life-sustaining invasive procedures (eg, endotracheal intubation and umbilical, central venous and arterial catheterization) that are essential for respiratory and nutritional support. Importantly, these infants often suffer from disruption in skin and intestinal integrity that may contribute to translocation of pathogens resulting in a diag- nosis of CLABSI. Nevertheless, adherence to proper insertion

Corresponding author:Kristina A. Bryant, MD, E-mail: [email protected] Cite this article: Muller M, Bryant KA, Espinosa C, et al. (2023). SHEA Neonatal

Intensive Care Unit (NICU) White Paper Series: Practical approaches for the prevention of central-line–associated bloodstream infections. Infect Control Hosp Epidemiol, 44: 550–564, doi: 10.1017/ice.2022.53

Infection Control & Hospital Epidemiology (2023), 44, 550–564

doi:10.1017/ice.2022.53

https://doi.org/10.1017/ice.2022.53 Published online by Cambridge University Press

mailto:[email protected]

https://doi.org/10.1017/ice.2022.53

http://crossmark.crossref.org/dialog?doi=https://doi.org/10.1017/ice.2022.53&domain=pdf

https://doi.org/10.1017/ice.2022.53

techniques andmanagement of the CVC can reduce CLABSI rates, even among the highest-risk infants. The CDC has recommended elements of insertion and maintenance bundles for all patients, although the nuances of care for NICU patients are not included (Table 3).8 This white paper provides clinicians with practical guid- ance on the implementation of strategies to prevent CLABSIs in NICU patients, including those strategies above and beyond the elements suggested by CDC.

Intended use

The Society for Healthcare Epidemiology of America (SHEA) intends for this document to serve as a companion to the CDC Healthcare Infection Control Practices Advisory Committee (HICPAC) Guideline for Prevention of Infections in Neonatal Intensive Care Unit Patients,9 and to provide practical, expert opin- ions, and/or evidence-based answers to frequently asked questions about CLABSI detection and prevention in the NICU. This docu- ment is not a comprehensive compilation of infection prevention strategies recommended for NICUs. Hand hygiene, environmental cleaning and disinfection, infection prevention education for fam- ily members and caregivers, and other core practices recom- mended by the CDC for all healthcare settings are essential to CLABSI prevention and are detailed elsewhere https://www.cdc. gov/hicpac/recommendations/core-practices.html.

The published literature related to the questions presented herein is not sufficient to meet Grading of Recommendations Assessment, Development and Evaluation (GRADE) standards9,10; therefore, the authors provide no evidence grading, and answers incorporate experts’ clinical experience. No guideline, expert guid- ance, or white paper can anticipate all situations. This document is meant to serve as an adjunct to individual judgment by qualified professionals. In general, these recommendations apply to nonout- break settings. Healthcare personnel (HCP) may implement addi- tional measures during an outbreak or other special clinical scenarios.

Methods

This document has been developed by pediatric infectious diseases specialists, neonatologists, advanced practice nurse practitioners, infection preventionists, and members of the HICPAC guide- line-writing panel, as well as members of the SHEA Pediatric Leadership Council, to identify and address practical questions anticipated from practitioners and infection prevention professionals. This document is part of the “SHEA Neonatal Intensive Care Unit (NICU) White Paper Series.” Two documents in the series precede this one: “Practical approaches to Clostridioides difficile prevention” published in August 201811

and “Practical approaches to Staphylococcus aureus prevention,” published in September 2020.12

Unlike the SHEA expert guidance format, this document is not based on a systematic literature search. Instead, for the selected topic areas, the authors provide practical approaches in question-and-answer format, with answers based on consen- sus expert opinion within the context of the literature search conducted for the companion HICPAC document and supple- mented by other published information retrieved by the authors.

The full white paper series is overseen by a group of experts in pediatrics, including pediatric infectious diseases specialists,

neonatologists, advanced practice nurse practitioners, and infec- tion preventionists, convened by SHEA, called the NICU Advisory Panel (see the Acknowledgments). The NICU Advisory Panel members serve as representatives for the following organizations: the American Hospital Association (AHA), the American Academy of Pediatrics (AAP), the Association for Professionals in Infection Control and Epidemiology (APIC), the Infectious Diseases Society of America (IDSA), The Joint Commission, the National Association of Neonatal Nurses (NANN), the Pediatric Infectious Diseases Society (PIDS), and the Vermont Oxford Network (VON). This document was reviewed by the NICU Advisory Panel member organizations, the SHEA Guidelines Committee, and the SHEA Publications Committee.

This white paper has been endorsed by SHEA, AHA, APIC, IDSA, The Joint Commission, NANN, and PIDS.

A list of abbreviations, including organization acronyms, is pro- vided in Table 1.

Authors

The authors include current and past members of the SHEA Guidelines Committee and the SHEA Pediatric Leadership Council, and representation from AAP and APIC. All authors

Table 1. Abbreviations

AAP American Academy of Pediatrics

AAP/ SOID

American Academy of Pediatrics Section on Infectious Diseases

AHA American Hospital Association

APIC Association for Professionals in Infection Control and Epidemiology

CDC US Centers for Disease Control and Prevention

CHG Chlorhexidine gluconate

CI Confidence Interval

CLABSI Central-line–associated bloodstream infection

CVC Central venous catheter

EBM Evidence-based medicine

FDA US Food and Drug Administration

HCP Healthcare personnel

IDSA Infectious Diseases Society of America

kg Kilogram

mg Milligram

mL Milliliter

NANN National Association of Neonatal Nurses

NICU Neonatal intensive care unit

NS Normal saline

OR Odds Ratio

PICC Peripherally inserted central catheter

PIDS Pediatric Infectious Diseases Society

SHEA Society for Healthcare Epidemiology of America

TPN Total parenteral nutrition

VAT Vascular access team

VON Vermont Oxford Network

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Table 2. Questions and Recommendations

# Question Answer

1 Which NICU patients are likely to benefit from use of chlorhexidine (CHG) skin antisepsis for CVC insertion and maintenance?

• Skin antisepsis should occur for all infants in the NICU and optimally should be performed with a CHG-containing product.

• For infants ≥8 weeks of age 2% CHG in 70% alcohol should be used. • For infants <8 weeks of age, the authors’ clinical experience shows that a CHG-containing product may be used safely. Additionally, FDA has stated that CHG may be “[used] with care in premature infants or infants under 2 months of age.”13

• For infants born at <28 weeks gestation, especially ≤7 days of age, NICUs may consider use of aqueous 2% CHG for skin antisepsis.

2 How often should CVC dressings be changed in NICU infants?

• To reduce skin barrier breakdown and the risk for dislodgement of the CVC, CVC dressings should be changed only if soiled, damp, or loose, regardless of gestational age (and not according to a specific interval of time, eg, every 7 days).

• The integrity of the CVC dressing should be inspected by designated HCP at least daily.

3 In which NICU patients should CHG-impregnated sponges or other CHG-impregnated dressings be used?

• CHG-impregnated dressings are associated with an increased risk of contact dermatitis in NICU infants. Benefits have not been demonstrated in NICU infants and these products are not recommended by the authors.25

• If other interventions have failed to reduce CLABSI in an infant in the NICU, or if there is an increase in the NICU’s baseline CLABSI rates, CHG- impregnated dressings may be considered in infants ≥28 weeks gestation and ≥7 days of age.

4 Should alcohol disinfectant caps be used in the NICU? • NICUs may consider use of disinfectant caps as an additional intervention to reduce CLABSI rates when other interventions have failed.

5 In which NICU patients are the benefits of CHG bathing likely to outweigh the risks?

• Routine CHG bathing is not recommended for all NICU infants. • In NICUs that have high CLABSI rates (see Question 10), despite implementation of other evidence-based strategies, CHG bathing may be used in the NICU for infants with CVCs. The optimal frequency of CHG- bathing has not been established and depends on chronological age and gestational age: o CHG bathing in term infants (≥37 weeks): may be performed from birth. o CHG bathing in preterm infants (<37 weeks gestation) may be considered beginning at 4 weeks of chronological age, recognizing the potential for skin irritation and systemic absorption (the latter being of unknown clinical significance).

o CHG bathing in preterm infants (<37 weeks gestation) and <4 weeks of age is not recommended due to potential adverse local and systemic effects. In these infants, an alternative approach of bathing with sterile water with or without mild soap may help decrease bacterial counts on skin.

• When CHG bathing is utilized, NICUs should ensure careful surveillance for local and systemic adverse effects, including allergic reactions.

6 What are practical strategies for minimizing central-line entry in NICU patients?

• NICUs should perform laboratory and diagnostic stewardship (ie, consolidation of necessary tests and elimination of those not clinically relevant).

• HCP should avoid using the CVC to obtain routine blood tests. • Although not a universal recommendation, NICUs may consider the use of closed blood sampling systems.

• The utility of obtaining blood cultures through an indwelling CVC remains an unresolved issue.

7 When and how should prophylactic antimicrobial lock therapy be implemented in NICU patients?

• Prophylactic antimicrobial lock therapy as a universal prevention measure is not recommended.

• Antimicrobial locks may be considered as an additional intervention in NICU infants with recurrent CLABSIs.

8 Should prophylactic antimicrobials be administered to a NICU patient at the time of PICC removal to reduce the incidence of CLABSI or culture-positive sepsis?

• Prophylactic antimicrobials are not recommended at the time of PICC removal.

9 What are practical considerations for the implementation of a neonatal vascular access team (VAT)?

• NICUs should consider use of a VAT. Such teams have demonstrated effectiveness in reducing catheter-related complications and are cost- effective.22,81–83

• VAT proceduralists should receive education and clinical training, and upon completion, demonstrate knowledge and proficiency in PICC insertion, care, and removal, and a commitment to the team-based approach.

• VAT proceduralists should successfully insert a predefined number of PICCs as defined by the local facility’s delineation of privileges.

• The team should monitor relevant quality measures (see Table 7).

(Continued)

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served as volunteers. At their respective institutions, the authors are directly involved or provide an advisory role in the develop- ment of policies pertaining to pediatric and/or neonatal infection prevention in the NICU.

The NICU Advisory Panel (see the Acknowledgments), a col- laborative group of pediatric and pathogen-specific experts con- vened by SHEA, provided oversight and review of the draft document.

Practical approaches: Questions and Answers

Questions and recommendations are listed in Table 2. Question 1: Which NICU patients are likely to benefit from use of chlorhexidine (CHG) skin antisepsis for CVC insertion and maintenance? Answer 1:

• Skin antisepsis should occur for all infants in the NICU and opti- mally should be performed with a CHG-containing product.

• For infants ≥8 weeks of age or older, 2% CHG in 70% alcohol should be used.

• For infants <8 weeks of age, the authors’ clinical experience shows that a CHG-containing product may be used safely. Additionally, the US Food and Drug Administration (FDA) has stated that CHG may be “[used] with care in premature infants or infants under 2 months of age.”13

• For infants born at <28 weeks gestation, especially ≤7 days of age, NICUs may consider use of aqueous 2% CHG for skin antisepsis.

A variety of antiseptics, containing differing amounts of CHG, with and without alcohol (aqueous CHG), are available. The use of a CHG-containing skin antiseptic, in combination with alcohol, for CVC insertion and maintenance is preferred, based on its efficacy in reducing CLABSI in populations outside the NICU. In the NICU, the optimal concentration of CHG-containing agent has

not been determined. Although the FDA has stated that CHG may be “[used] with care in premature infants or infants under 2 months of age,”13 the authors’ clinical experience shows that it may be used safely. Figure 1, from the Centre Hospitalier Universitaire (CHU) Sainte-Justine Hospital in Montreal, Canada details how one hospital has operationalized options for antisepsis for various procedures commonly performed in the NICU setting. Although more detailed than the recommendations provided in this document, it could serve as a useful model for NICUs seeking to implement the use of CHG. Infants (≥8 weeks of age) may benefit from a higher CHG concentration (ie, 2%) (Fig. 1).14 For CVC insertion, some centers use 2% aqueous rather than alcohol-based CHG in extremely preterm infants (<28 weeks gestation), but recommend that, once dried, CHG should be rinsed off the skin with sterile water to prevent burns. However, Garland et al15 showed that the application of 2% CHG in 70% isopropyl alcohol for skin antisepsis before CVC placement and with each weekly dressing change in infants weighing ≥1500 grams and ≥7 days of age was not associated with dermatitis although cuta- neous absorption of CHG occurred in 15% of infants.15

As an alternative to alcohol-based CHG solutions that may potentiate skin irritation and cutaneous CHG absorption, some NICUs use 1% or 2% aqueous CHG for skin antisepsis. In a ran- domized, blinded, non-inferiority trial of 308 infants who were 26– 42 weeks gestation, the use of 1% aqueous CHG for skin antisepsis was comparable to a 2% aqueous CHG solution when assessed by the proportion of negative skin swab cultures after skin antisep- sis.14 Overall, 93% of swabs were sterile in the 1% CHG group com- pared with 95.6% in the 2% CHG group (risk difference, −2.7%; 95% CI, −6.2 to þ0.8%). The lower bound of the 95% CI crossed the prespecified absolute non-inferiority limit of 5%. Mild derma- titis was identified in 2.3% of infants in each group, with the worst being transient slightly pink discoloration of the skin without edema. Percutaneous absorption of chlorhexidine occurred in all 59 sampled infants but did not differ by the concentration of the aqueous preparation with the median CHG concentration at

Table 2. (Continued )

# Question Answer

10 What threshold should prompt a NICU to consider implementing additional preventive measures?

• Zero CLABSIs is the aspirational and potentially achievable goal. • Although there is no nationally endorsed threshold above which additional CLABSI prevention measures should be implemented, a variety of quantitative or qualitative metrics may be utilized to identify CLABSI prevention success over time and determine when additional intervention is necessary.

• A decision to identify a threshold for action in an individual NICU should assess a variety of factors including: o An SIR or rate of CLABSI that is above goal or increasing despite the consistent implementation of current organizational interventions

o Local interest in setting a specific lower target with input from Infection Prevention and Control (infection preventionists, healthcare epidemiologist)

o Patient mix and clinical acuity, which may predict general likelihood of CLABSI

o Resource and personnel capacity for initiation and/or maintenance of specific interventions and practice processes.

• Any quantitative or qualitative metric that is defined should be developed and accepted by all stakeholders.

11 What preventive bundle elements, above and beyond those recommended by CDC, could be considered by a NICU experiencing ongoing CLABSIs?

• Additional practices that lack robust evidence may be effective. NICUs may consider many different products, technologies, and processes, some of which are described below.

• Implementation of an expanded NICU central-line care bundle should take into account the risks and benefits of additional measures, as well as the needs, resources, and local expertise at individual institutions.

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24 hours being 19.6 ng/mL and 12.6 ng/mL in the 1% and 2% aque- ous CHG group, respectively.14 Therefore, use of the lower CHG concentration does not offer any substantial safety advantage.

CHG skin antisepsis is commonly used in many NICUs. In 2016, a survey of 58 academic NICUs in the United States found that CHG was used by 86% of centers, mostly for skin antisepsis at the time of CVC insertion, CVC dressing changes, CVC mainte- nance, and peripheral intravenous catheter insertion. In NICUs where CHG was restricted by age or weight, the most common requirements for CHG use were gestational age >28 weeks and weight >1000 grams.16

CHG-based skin antisepsis has demonstrated superiority com- pared to povidone-iodine in settings outside the NICU.17 Limited data from clinical trials in the NICU have failed to demonstrate superiority of either product from a safety and efficacy standpoint, although the use of povidone-iodine was associated with an increased risk of high thyroid stimulating hormone level requiring treatment.15,18 Recent guidelines from CDC for the prevention of CLABSIs in NICU patients advise to “consider the use of alcohol- containing chlorhexidine for skin antisepsis to prevent central- line–associated bloodstream infection (CLABSI) in neonatal inten- sive care unit (NICU) patients in whom the benefits are judged to outweigh the potential risks.”9 The consensus of the authors is that CHG-based skin antisepsis and not an iodine-based product is

optimal for all infants regardless of gestational age and birth weight.

Frequent inspection of the skin site where CHG has been applied is important to detect and manage cutaneous adverse effects including chemical burns.19 To decrease their occurrence, only the minimum amount of CHG-containing solution should be used, with removal of any excess solution, as well as any soaked materials or drapes, from the skin. Parents should be informed of the potential for CHG to cause skin irritation at the time consent for CVC placement is obtained.20 When severe dermatitis or chemical burns occur, temporary use of povidone-iodine or a lower concentration of aqueous CHGmay be needed until the skin injury is healed. Consultation with the NICU wound team or other spe- cialists such as burn and plastic surgeons may be necessary.

Question 2: How often should CVC dressings be changed in NICU infants?

Answer 2:

Fig. 1. Use of antiseptics in the NICU at CHU Sainte- Justine Hospital in Montreal, Canada.

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• The integrity of the CVC dressing should be inspected by des- ignated HCP at least daily.

Transparent CVC dressings have been recommended to be changed every 7 days, and more frequently if soiled, damp, or loose.21 However, it also is likely that in extremely preterm infants in particular (<28 weeks gestation), each dressing removal may result in skin barrier breakdown leading to an increased risk of CLABSI. Some NICUs will only change a transparent dressing if it is soiled, damp, or loose, and this is the authors’ consensus rec- ommendation for all NICU patients regardless of gestational or chronologic age or weight. Although the authors acknowledge that this is different than the CDC recommendation (Table 3), defer- ring changing dressings of NICU patients if they are intact has been recommended by other experts.17, 22, 23 Daily inspection of the dressing’s integrity, preferably by a dedicated team or trained bed- side nurse, is recommended.

Very limited data suggest that use of cyanoacrylate glue at the CVC insertion site may decrease bleeding and thus increase the time between dressing changes in extremely preterm infants. In one NICU the addition of cyanoacrylate glue to the insertion bun- dle for percutaneously placed CVCs significantly reduced acciden- tal catheter dislodgement and anecdotally reduced bleeding at the insertion site.24

Question 3: In which NICU patients should CHG-impregnated sponges or other CHG-impregnated dressings be used?

Answer 3:

• CHG-impregnated dressings are associated with an increased risk of contact dermatitis in NICU infants. Benefits have not

been demonstrated in NICU infants, and these products are not recommended by the authors.25

• If other interventions have failed to reduce CLABSI in an infant in the NICU, or if there is an increase in the NICU’s baseline CLABSI rates, CHG-impregnated dressings may be considered in infants ≥28 weeks gestation and ≥7 days of age.

Several types of dressings incorporate chlorhexidine, includ- ing CHG-impregnated sponges, transparent dressings, and films. A CHG-impregnated sponge, also called a patch or disk, is a device composed of sterile polyurethane foam impregnated with CHG. It is intended to be applied at the insertion site of a central line before a sterile, transparent dressing is placed. This device is designed to provide continuous protection from skin recoloniza- tion by slowly releasing CHG while also absorbing and drawing fluids away from the site.26 The use of CHG-impregnated sponges (eg, Biopatch Protective Disk with CHG, Ethicon, Raritan, NJ) has been shown to reduce CLABSIs in adults, but the benefits are less clear in pediatric patients.27 The National Health Service (NHS UK) recommends that if used, CHG-impregnated sponges should be restricted to infants ≥28 weeks gestation and ≥7 days of age and that pressure over the sponge be avoided to prevent skin necrosis.28 Adverse skin reactions, including derma- titis and cellulitis at the insertion site, may occur and may not be visible under the sponge, and this may be a deterrent to their use in some infants.

Dressings impregnated with antiseptics or antibiotics (ie, anti- microbial dressings) have also been studied in NICU infants.8,29 A Cochrane review evaluated the effectiveness and safety of antimi- crobial dressings used at the time of CVC insertion in reducing CLABSIs in the NICU. Compared to polyurethane dressing/

Table 3. Adapted CDC Checklist for Prevention of CLABSI*8,17

Insertion Maintenance

□ Perform hand hygiene before insertion. □ Perform hand hygiene.

□ Adhere to aseptic technique. □ Bathe ICU patients who are ≥2 months of age with CHG daily.

□ Use maximal sterile barrier precautions (i.e., mask, cap, gown, sterile gloves, and sterile full body drape).

□ Use only sterile devices to access catheters.

□ Choose the best insertion site to minimize infections and noninfectious complications based on individual patient characteristics.

□ Prepare the insertion site with >0.5% CHG with alcohol* (see Question/ Answer 1).

□ Scrub the access port or hub with friction immediately prior to each use with an appropriate antiseptic (CHG, povidone iodine, an iodophor, or 70% alcohol).

□ Place a sterile gauze dressing or a sterile, transparent, semipermeable dressing over the insertion.

□ For patients ≥18 years of age, use a CHG-impregnated dressing with an FDA cleared label that specifies a clinical indication for reducing CLABSI for short-term non-tunneled catheters unless the facility is demonstrating success at preventing CLABSI with baseline prevention practices*.

□ Immediately replace dressings that are wet, soiled, or dislodged. □ Perform routine dressing changes using aseptic technique with clean or

sterile gloves: □ Change gauze dressings at least every 2 days. □ Change semipermeable dressings at least every 7 days. □ For patients >18 years of age, use a chlorhexidine impregnated dressing

with an FDA cleared label that specifies a clinical indication for reducing CLABSI for short-term non-tunneled catheters unless the facility is demonstrating success at preventing CLABSI*.

□ Change administrations sets for continuous infusions no more frequently than every 4 days, but at least every 7 days.

□ If blood or blood products or fat emulsions are administered, change tubing every 24 hours.

□ If propofol is administered, change tubing every 6-12 hours or when the vial is changed.

□ Perform daily audits to assess if central line is still needed

*This is the complete CDC checklist. Some recommendations are different from those in this paper or are not pertinent because they are specific to older patients. The recommendations in this paper reflect the nuances of care in the NICU.

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povidone-iodine cleansing, CHG sponges/alcohol cleansing reduced catheter colonization (risk ratio [RR], 0.62; 95% CI, 0.45–0.86) but did not change the important outcomes of blood- stream infection (BSI; RR, 1.18; 95% CI, 0.53–2.65) or sepsis (RR, 1.06; 95% CI, 0.75–1.52).29 In addition, the use of CHG-impreg- nated dressings was associated with contact dermatitis in preterm infants (RR, 43.06; 95% CI, 2.61–710.44).29 The use of a silver-algi- nate patch appeared safe, but there was insufficient evidence of benefit.

The CDC Checklist for the Prevention of CLABSI does not recommend the use of CHG-impregnated dressings (including sponges) to protect the sites of short-term, nontunneled CVCs for premature infants due to the risk of serious adverse skin reactions. While recent guidance recommends the use of chlorhexidine-containing dressings for patients >2 months of age with CVCs, use of dressings in younger infants, particularly in pre-term or very low birthweight infants, remains an unresolved issue.17

Some NICUs utilize CHG dressings for selected infants. Of 50 neonatology training program directors in the United States who responded to a 2014 survey, 10 (20%) reported using impregnated dressings or disks (the survey did not differentiate between the products).16 A survey of SHEA Pediatric Leadership Council mem- bers in April 2014 revealed that 5 (19%) of 26 NICUs used a “CHG dressing” on infants with surgically placed CVCs but the criteria for use were variable and included infants who were >28 weeks gestation and weighing >1,000 grams, ≥34 weeks corrected age, or >2 months chronologic age. Only 3 (11%) of 27 NICUs used CHGdressings on similar infants with peripherally inserted central catheters (PICCs, also called percutaneously inserted CVCs).30 The survey did not differentiate between sponges and impregnated dressings.

Question 4: Should alcohol disinfectant caps be used in the NICU?

Answer 4:

• NICUs may consider use of disinfectant caps as an additional intervention to reduce CLABSI rates when other interventions have failed.

Access of pathogenic organisms to the bloodstream via a CVC is prevented in part by careful disinfection of the catheter hub. The manual “scrub-the-hub” process is time-consuming; thus, compli- ance byHCPmay be suboptimal. Disinfectant caps containing 70% isopropyl alcohol placed over intravenous needleless connectors act as antiseptic barriers by passive disinfection, decreasing hub colonization.31 Two in vitro studies found leakage of alcohol through the hub membrane,32, 33 but the potential clinical signifi- cance of this leakage is unknown. Adverse effects resulting from alcohol leakage in a clinical setting have not been identified. In vitro, alcohol leakage can vary by cap manufacturer and may be reduced by allowing the hub membrane to dry for 30 seconds prior to an infusion and limiting the number of days that the cap remains in place (ie, <7 days).

In pediatric patients, disinfectant caps have been used in many hospitals, usually as part of a bundle, with subsequent reduction in CLABSIs. In 2019, the National Institute of Health and Care Excellence (NICE) cited disinfectant caps as a potential interven- tion to reduce CLABSIs, but due to insufficient evidence, further research to assess their clinical benefit was recommended.34 A systematic review that included 9 studies comparing the effects of disinfectant caps (CurosTM and SwabCapTM) with manual

disinfection in multiple US and UK hospital settings (including 1 pediatric hospital) found that disinfectant caps effectively reduced CLABSIs (incidence rate ratio [IRR], 0.59; 95% CI, 0.45–0.77; P< .001) and were cost-saving.35, 36, In a prospective, single-center, pre- and post-observational study conducted in pediatric intensive care units (PICUs) and NICUs, CLABSI rates decreased by 22% with the use of disinfectant caps compared to the manual scrub-the-hub method, but the difference was not sta- tistically significant (95%CI, 34%–55%; P= .368).36 Among ambu- latory pediatric oncologic patients, a randomized controlled trial evaluating disinfectant caps did not demonstrate a significant reduction in CLABSI incidence.37

Despite the lack of supportive evidence in pediatrics, many NICUs utilize disinfectant caps without reporting clinically signifi- cant adverse effects. A survey conducted by the SHEA Pediatric Leadership Council in April 2014 showed that 9 (33%) of 27 par- ticipating NICUs used ethanol or alcohol caps on all hubs or ports of the intravenous administration set in all NICU patients.30

Question 5: In which NICU patients are the benefits of CHG bathing likely to outweigh the risks?

Answer 5:

from birth. o CHG bathing in preterm infants <37 weeks gestation may be

considered beginning at 4 weeks of chronological age, recog- nizing the potential for skin irritation and systemic absorption (the latter being of unknown clinical significance).

• When CHG bathing is utilized, NICUs should ensure careful surveillance for local and systemic adverse effects, including allergic reactions.

The use of CHG for skin antisepsis and the use of CHG for bath- ing are distinct interventions with unique sets of benefits and risks in NICU infants38. Daily bathing of ICU patients ≥8 weeks (ie, ≥2 months) is now considered to be standard infection prevention practice17 including patients in the NICU. With the exception of children with cancer or those undergoing hematopoietic stem cell transplantation, daily CHG bathing of children in the PICU who were ≥2 months of age (8 weeks) resulted in decreased bacteremia and CLABSIs.39 Recommendations for bathing younger infants, especially preterm infants, is more nuanced. Bathing infants with cloths infused with CHG decreases bacterial colony counts on skin transiently.40,41 Nonrandomized trials in NICU patients suggest a decrease in CLABSI rates in CHG-bathed neonates in the absence of observed adverse events.42,43 However, safety concerns persist, especially in very preterm infants whose poor skin integrity may predispose them to contact dermatitis, chemical burns, and sys- temic absorption.44 An additional concern comes from studies

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in pediatric and adult patients that have noted higher prevalence of reduced CHG susceptibility in organisms that cause CLABSIs in units that perform daily CHG bathing of patients.45 In adults, the potential development of cross resistance to other cell-envelope agents such as daptomycin and colistin has raised further concerns. These phenomena have not been evaluated in NICU patients.

For these reasons, CHG bathing has not been used routinely in extremely preterm (<28 weeks gestation) infants with birth weights of ≤1,000 grams who are <4 weeks of age, and alternate bathingmethods with sterile water and/ormild soap are advocated. However, based on decreases in CLABSI rates in CHG-bathed neo- nates as noted above, CHG bathing may be considered in more mature preterm and term infants between 4 and 8 weeks of age if CLABSI rates remain high despite implementation of other evi- dence-based interventions.

Question 6: What are practical strategies for minimizing cen- tral-line entry in NICU patients?

Answer 6:

• NICUs should perform laboratory and diagnostic stewardship (ie, consolidation of necessary tests and elimination of those not clinically relevant).

• HCP should avoid using the CVC to obtain routine blood tests. • Although not a universal recommendation, NICUs may con- sider the use of closed blood sampling systems.

• The utility of obtaining blood cultures through an indwelling CVC remains an unresolved issue.

Infants in the NICU require frequent blood draws for clinical monitoring. CDC guidelines for CLABSI prevention in NICU patients recommend minimizing the number of times central-line hubs are accessed, as well as minimizing blood sampling through central lines, even though high-quality data are lacking.9,46 Only 1 study among infants in the NICU reported an increased risk of CLABSI from procedures involving catheter manipulation such as disinfection of the catheter hub following disconnection of the CVC (OR, 1.2; 95% CI, 1.1–1.3) and blood sampling other than for blood gases (OR, 1.4; 95%CI, 1.1–1.8).47 The authors reported a cumulative dose-effect of the number of blood samples obtained from the CVC with an odds ratio (OR) of 1.04 for 1–7 blood sam- ples (95% CI, 0.33–3.27;P=0.95) to 8.4 (95% CI, 0–67.1;P=0.036) for>14 blood samples. Obtaining blood samples by other methods may also create risk. In an observational case-control study, there was an increased risk of CLABSI among NICU infants who had at least 3 capillary blood draws by heel punctures within 48 hours before CLABSI onset (OR, 5.36; 95% CI, 2.37–12.15).48 This retro- spective study could not confirm causality, but it is plausible that multiple skin breaks contributed to the development of bacteremia.

The first steps in decreasing the number of central-line system entries are (1) not using CVCs for routine blood draws and (2) per- forming laboratory and diagnostic stewardship to minimize tests that are not clinically relevant. Reducing laboratory testing is an achievable goal. After implementing a multifaceted quality improvement project that included guideline development, dash- board creation and distribution, electronic medical record optimi- zation, and expansion of noninvasive and point-of-care testing, one NICU achieved a 26.8% decrease in routine laboratory testing per 1,000 patient days over a 24-month period.49

The utility of obtaining blood cultures through an indwelling CVC remains controversial. In general, catheter-drawn blood cul- tures have higher rates of contamination (ie, false positives),50 and

some expert guidance recommends peripheral venipuncture as the preferred method for obtaining blood cultures.51 The Bright Star Collaborative is a multicenter quality improvement collaborative that includes children’s hospitals in 17 states across the United States.52 The mission of the group is to reduce bacterial culture overuse in critically ill children by implementing diagnostic stew- ardship interventions. Consensus recommendations from the group for PICU patients advise against obtaining blood cultures from every lumen of a CVC or from a peripheral intravenous cath- eter. The group did not reach consensus regarding the utility of a blood culture drawn from a CVC, since a positive culture cannot differentiate between catheter colonization or BSI.53 NICU-specific recommendations do not exist but the issues are likely to be similar.

The clinician must weigh practical considerations when deciding how to obtain blood cultures in a NICU patient. The NHSN surveil- lance definitions for CLABSI require 2 positive blood cultures, taken at different sites or at different times, when potential commensal bacteria (eg, coagulase-negative staphylococci) are detected to diag- nose a true device-associated infection. It may be difficult to obtain 2 separate samples by peripheral venipuncture in NICU infants. A CVC sample may be paired with a peripherally obtained sample to help differentiate between catheter colonization and a true BSI, especially when a commensal organism is isolated. A CVC culture is considered to have higher sensitivity compared to peripheral spec- imens, at the cost of lower specificity.54 Finally, HCP also may opt to draw a blood culture from a CVC tominimize painful procedures. A recent study conducted at a level IV NICU compared concurrently drawn peripheral and catheter blood cultures and found that most blood cultures were positive with the same organism fromboth sites, although a small but importantminority of episodes (12%) grew vir- ulent pathogens from either culture site alone.50 The authors con- cluded that while dual-site blood-culture practices may be useful, the gain in sensitivity of bacteremia detection should be weighed against additive contamination risk. Even whenHCPwant to obtain a blood culture from a CVC, it may not be feasible. Catheters with very small lumens may collapse when suction is applied during the blood draw.

Adopting the Bright Star Consensus Recommendations for PICU patients may reduce the total number of blood cultures ordered, as well as the number of samples obtained through the catheter. Before ordering a blood culture, HCP should review the patient’s clinical data, including previous cultures, and perform a physical examination, and they should discuss the patient’s status with the bedside nurse. If a blood culture needs to be drawn from the CVC, then additional blood draws can be performed at the same time or scheduled with other required laboratory tests to decrease system entry.53 Because bacteremia occurs before the onset of fever, once the fever has occurred, the timing of the blood culture is not as critical except in situations when obtaining a blood culture before a change in antimicrobial therapy informs antimi- crobial stewardship efforts.

Previous studies have shown that closed infusion systems are associated with a decrease in overall CLABSI rates compared to open-infusion systems. Other studies have proposed that closed blood-sampling systems, such as the venous arterial blood man- agement and protection (VAMPTM) and KidsKitTM systems, decrease system entry, blood waste, and microbial contamina- tion.55–57 A pediatric study evaluated both systems and compared implementation of the KidsKit system to the conventional 3-way stopcock methods used on umbilical arterial catheters in the PICU and NICU. The authors found a decrease in CLABSIs below the national benchmark.57 NICUs may consider use of a closed

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blood-sampling system as a potential intervention when CLABSI rates remain elevated despite high rates of compliance with inser- tion and maintenance bundles.

Question 7: When and how should prophylactic antimicrobial lock therapy be implemented in NICU patients?

Answer 7:

• Prophylactic antimicrobial lock therapy as a universal preven- tion measure is not recommended.

• Antimicrobial locks may be considered as an additional inter- vention in NICU infants with recurrent CLABSIs.

Antimicrobial locks are solutions used for prophylactic or adjunctive treatment of CLABSI when the catheter cannot be removed in the setting of bacteremia. They contain a solution of highly concentrated antimicrobial agent in combination with an anticoagulant that is inserted into the lumen of a CVC and removed after a specified period (dwell time). Three randomized controlled trials in NICU infants demonstrated that use of pro- phylactic antimicrobial lock therapy decreased CLABSIs in NICUs with high baseline CLABSI rates.58–60 These studies, how- ever, were conducted before routine implementation of insertion and maintenance bundles, which have reduced NICU CLABSI rates substantially. We do not, therefore, recommend prophylac- tic antimicrobial lock therapy as a universal prevention measure, although it may be considered in individual infants who experi- ence recurrent CLABSIs. The authors recommend collaboration with a pediatric infectious diseases specialist and the NICU vas- cular access team (VAT) before implementation of lock therapy.

NICUs will need to consider practical implementation chal- lenges, including that some catheters are not suitable for

antimicrobial locks and that the optimal minimum dwell time for lock therapy is 4 hours (Table 4).

There is no single preferred antimicrobial lock preparation. Several concentrations of antimicrobial agents and ethanol have been studied in combination with heparin and other anticoagulants (Table 5). When used, antimicrobial locks should have activity against common CLABSI pathogens, the ability to penetrate bio- films, compatibility with anticoagulants such as heparin or an alter- native ion chelator such as citrate, and prolonged stability.61 In addition, they should have low risk of toxicity and low potential for inducing antimicrobial resistance. Ampicillin and other β-lactam agents, with and without an extended spectrum, have been studied in combination with heparin and form stable locking solutions. Aminoglycosides and vancomycin have been studied with different additives such as heparin, citrate, and tissue plasminogen activator (TPA).61 In the NICU population, there is insufficient evidence for the effectiveness and safety of citrate locking solutions, although some institutions use sodium citrate 4% as the anticoagulant in the antimicrobial locks in combination with antimicrobial agents such as cefepime, vancomycin, or gentamicin.62

The safety and efficacy of ethanol locks have not been studied in NICU patients, but limited data exist on their use in infants with intestinal failure63 as young as 0.3 years and who weigh at least 5 kilograms.64–70 A recent systematic review and meta-analysis con- cluded that prophylactic ethanol locks in patients with intestinal failure reduced CLABSIs and catheter replacements but were asso- ciated with an increased need for catheter repair.71 The potential for alcohol-related toxicity was also assessed in a pilot study that enrolled 10 infants (mean age, 3.5 months; mean weight, 4.5 kg). Blood-alcohol concentrations were assessed 1 hour after a 0.4 mL dose of ethanol was flushed through the CVC, equivalent to the volume that would be used during ethanol lock therapy.72 At

Table 4. Considerations for Use of Lock Therapies in NICU Patients96

Prophylactic Antimicrobial Lock Therapy

Optimal Procedures: • Pharmacy-dispensed volume-specific syringes for each lumen • Minimum dwell time of 4 hours, without disruption, while all lumens are locked • Changing all line lock solutions inserted into ports every 24 hours • Routine administration of a thrombolytic drug other than saline or heparin to maintain catheter patency (e.g., alteplase). Each lumen of the catheter should be easy to flush and aspirate

• VAT evaluation and intervention if unable to withdraw antimicrobial lock from any lumen

Do not use for: • Infants with allergy to any component of antimicrobial lock therapy • 2 French or smaller PICCs, umbilical arterial and venous catheters, arterial lines, midline catheters, and peripheral intravenous catheters

• Infants who are receiving continuous infusions that require a dedicated lumen line (e.g., amiodarone, heparin, narcotics, pressors, and TPN)

• Obtaining antimicrobial levels

Do not use if: • Lock is incompatible with catheter being used • Patency of line cannot be assessed • Logistical challenges of rotating lumens when multiple lumens and/or catheters require antimicrobial lock therapy make use ineffective

Considerations for Ethanol Lock Therapy

Ethanol lock therapy has very limited use in the NICU65, 67, 70

Do not use in: • A non-silicone central catheter • A peripherally inserted central catheter

Do not use if: • The catheter has more than 1 lumen • The infant is less than 6 months of age • The infant weighs less than 5 kg • The infant is receiving continuous infusions. Ethanol may precipitate if in contact with TPN and cause catheter occlusion • Inability to maintain the lock for a minimum of 4 hours (optimal dwell time)

Do not mix with heparin

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5 minutes, 8 patients had undetectable blood alcohol concentra- tions and 2 patients had alcoholaemia of 0.011%. At 1 hour, blood alcohol concentrations were undetectable in all infants and there was no evidence of hepatic injury. No data are available on the repeated use of ethanol locks in the neonatal population. The cost and general availability of ethanol lock solutions many limit their potential use.

Practical guidance for implementation when the decision is made to use antimicrobial lock therapy is presented in Table 6.

Question 8: Should prophylactic antimicrobials be administered to a NICU patient at the time of PICC removal to reduce the incidence of CLABSI or culture-positive sepsis?

Answer 8:

• Prophylactic antimicrobials are not recommended at the time of PICC removal.

The proposed rationale for prophylactic antimicrobials admin- istered to NICU patients at the time of PICC removal is to mitigate the potential impact of dislodgement of intra- or extra-luminal bacterial biofilm and subsequent bacteremia that elevates the fre- quency of BSI or culture-positive sepsis in the days following cath- eter removal. The actual risk of BSI following catheter removal is not well described. One single-center, retrospective, cohort study of 101 preterm infants did not identify an increased risk of cath- eter-related BSI in the 48 hours following removal of PICCs.73 A second retrospective cohort study that included 1,002 PICCs in 856 infants did not find a difference in the prevalence of BSIs or culture-negative sepsis when comparing the 72 hours before PICC removal to the 72 hours after removal.74 However, for infants with birth weight <1,500 grams, the odds for culture-negative sep- sis increased 6.3-fold following removal of PICC not used for anti- microbial delivery (95% CI, 1.78–26.86; P< .01).74 A third retrospective cohort study conducted before the widespread imple- mentation of CVC insertion and maintenance bundles reported a high rate of culture-positive sepsis within 5 days of PICC removal (24 of 345, 7%).75 The incidence of sepsis was lower in infants who received antimicrobials at the time of catheter removal: 2 (1.5%) of 132 versus 22 (10.3%) of 213 (P= .002).

Subsequent studies have not demonstrated a benefit to prophy- lactic antimicrobials before PICC removal. One retrospective study identified no difference in clinical or culture-positive sepsis in 137 infants who received a single dose of vancomycin before PICC removal and 64 infants who received no antimicrobial.76 In a sec- ond retrospective cohort study of 216 NICU patients with PICCs, the occurrence of microbiologically proven (n= 6) or clinical sep- sis (n= 8) was uncommon within 5 days of catheter removal, and no benefit was identified with antimicrobial use at the time of PICC removal (OR, 0.6; 95%CI, 0.1–2.7; P= .74).77 A single randomized, unblinded trial enrolled 88 infants who received intravenous cefa- zolin administered 1 hour before or 12 hours after catheter removal.78 Although the authors reported a difference in cul- ture-positive sepsis within 48 hours (0% of treated infants vs 11% of controls, P= .021), there were significant methodological issues, and subsequent analyses suggested that this difference was not statistically significant (RR, 0.09; 95% CI, 0.01– 1.60).79,80 No studies have systematically evaluated potential harms of antimicrobial prophylaxis at the time of catheter removal, such as impact on the neonatal microbiome. A 2018 Cochrane review concluded that there is insufficient evidence to assess the efficacy or safety of antimicrobials given at the time of catheter removal.79

Question 9: What are practical considerations for the imple- mentation of a neonatal vascular access team (VAT)?

Answer 9:

• NICUs should consider use of a VAT. Such teams have demon- strated effectiveness in reducing catheter-related complications and are cost-effective.22,81–83

• VAT proceduralists should receive education and clinical train- ing, and upon completion, demonstrate knowledge and profi- ciency in PICC insertion, care, and removal, and a commitment to the team-based approach.

• VAT proceduralists should successfully insert a predefined number of PICCs as defined by the local facility’s delineation of privileges.

• The team should monitor relevant quality measures (see Table 7).

Table 5. Examples of Antimicrobial Locks96

Antimicrobial Lock Therapy Vial Concentration Vol. 1mL Vol. 2mL Vol. 3mL Vol. 5mL Final Concentration Stability

Vancomycin Vancomycin 50 mg/mL vial 0.2 0.4 0.6 1.0 10 mg/mL 7 days refrigerated 0.9% normal saline (NS) 0.8 1.6 2.4 4.4

Vancomycin 5 mg/mL solution (dilute with NS)

0.5 1.0 1.5 2.5 2.5 mg/mL

Heparin 100 units/mL 0.5 1.0 1.5 2.5 50 units/mL

Gentamicin Gentamicin 10 mg/mL vial 0.5 1.0 1.5 2.5 5 mg/mL 7 days refrigerated

0.9% NS 0.5 1.0 1.5 2.5

Ceftazidime Ceftazidime 100 mg/mL vial 0.1 0.2 0.3 0.5 10 mg/mL 7 days refrigerated

Heparin 100 units/mL 0.5 1.0 1.5 2.5 50 units/mL

0.9% NS 0.4 0.8 1.2 2.0 – Amphotericin B* Amphotericin B 5 mg/mL vial 0.5 1.0 1.5 2.5 2.5 mg/mL 7 days refrigerated

Heparin 100 units/mL 0.5 1.0 1.5 2.5 50 units/mL

*Rarely used since removal of catheter is recommended in the setting of fungemia.

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This document defines VAT as any organized group of HCP involved in the management of vascular access. Prevention of CLABSIs benefits from the establishment of a team dedicated to all aspects of intravenous therapy. A recommendation of the Consensus Conference on Prevention of Central-Line– Associated Bloodstream Infections was the establishment of dedicated intravenous therapy teams, citing studies that showed reductions in infections and complications from central and peripheral intravenous catheters.84 In practice, the duties of VATs toward the catheters they care for vary by institution. The authors suggest that the VAT’s responsibilities include catheter insertion, daily inspection, and maintenance, as well as development and education related to policies and

procedures. A dedicated team with expertise in PICC assess- ment, placement, and care can serve as an invaluable resource for the NICU. The VAT also can provide information to infec- tion preventionists in the form of data collection and identifica- tion of trends to inform quality improvement efforts. Including the teammembers in infection prevention meetings will assist in guiding the focus of prevention during insertion of the PICC. Duties may also include investigation of positive blood cultures, in conjunction with the healthcare epidemiology and infection prevention teams.85 This places the focus of the team on preven- tion rather than just job duties. In one medical center, including a VAT as part of a “better bundle” strategy was associated with a significant decrease in CLABSIs.85 Published guidelines state

Table 6. Antimicrobial Lock Implementation

Instilling an Antimicrobial Lock

1. Order the antimicrobial lock therapy through the electronic medical record system, if used in the facility, to avoid errors 2. Obtain pharmacy-dispensed volume-specific syringes for each lumen 3. Prepare for:

a. 4 hours of dwell time (optimal) b. Changing all line locks solutions inserted into ports every 24 hours

4. Flush each lumen with 0.9% sodium chloride before instilling the antimicrobial lock 5. At the end of the dwell time, withdraw the instilled antimicrobial lock priming volume and discard. Some institutions will withdraw an additional 0.1 mL, or an

additional percentage of the total volume 6. After removing and discarding the lock, flush the lumen(s) with 0.9% sodium chloride before infusion of other medications or fluids through the line 7. If patient is being transferred to a procedure area (line may be accessed), withdraw all lock solutions prior to patient leaving the unit 8. Obtain VAT evaluation and intervention if unable to withdraw antimicrobial lock from any lumen

Assessing Fill or Priming Volume of Existing CVCs

1. Perform hand hygiene 2. Disinfect cap/lumen connection with hospital-approved antiseptic 3. Clamp the lumen and remove existing needleless access device from the CVC hub of the lumen 4. Attach empty 3 mL luer-lock syringe directly to the hub of the lumen 5. Aspirate plunger slowly and gently until blood reaches the end of the hub 6. Clamp the line 7. Remove the syringe: the volume of fluid in the 3 mL syringe is the volume to be used for the lock volume 8. Flush the line

Table 7. Neonatal Vascular Access Team (VAT) Training, Evaluation, and Responsibilities15

After receiving training, who may be a proceduralist on a Neonatal VAT?

Neonatal nurse practitioners, registered nurses (in accordance with State Board of Nursing scope of practice), neonatal fellows with appropriate supervision, neonatologists

What should clinical training and education for proceduralists include?

• Indications and contraindications of PICC placement • Increased awareness of pain management • Knowledge of the anatomy of venous and arterial systems • Maintenance of the sterile insertion bundle

What knowledge and clinical competencies should a proceduralist be able to demonstrate after training?

• Knowledge of published guidelines and standards of infusion therapy • Appropriate catheter care and maintenance • Ability to recognize and manage complications • Successful placement of at least 5 PICC lines

How many procedures should a proceduralist perform to maintain competency?

Proceduralists should consistently perform a requisite number of procedures, as defined by the local facility’s delineation of privileges. At a minimum, a proceduralist should perform 5 successful PICC insertions per year

What are examples of quality measures that a VAT should monitor?

• Success rate of individual proceduralists • Rates of complications (CLABSI, thrombus, pericardial and pleural effusions, etc.) • Confirmation of final line location via radiographic imaging or point-of-care ultrasound

What additional responsibilities might a VAT handle? • Troubleshooting and managing complications • Providing formal and informal staff education related to care and maintenance of central lines

• Performing catheter site surveillance and dressing changes • Discussing removal of PICC line when patient reaches 120 ml/kg/day of enteral intake97

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that specialized “IV teams,” such as the VAT, have shown unequivo- cal effectiveness in reducing the incidence of catheter-related BSI (CR-BSI), associated complications, and costs.81

Proper sterile technique during the placement of CVCs remains paramount for reduction of CLABSIs. Standardization of proce- dures for long-termmaintenance of CVCs helps to reduce the inci- dence of CLABSIs in intensive-care patients.86 An identified VAT allows organizations to centralize the responsibility for PICC- related activities with a select group of proceduralists, thus enhanc- ing accountability and ultimately, clinical outcomes.83 The upfront investment in a VAT results in cost savings from a reduction in the number of CLABSIs and other CVC-related complications. In one NICU, the initiation of a dedicated PICC insertion and mainte- nance team resulted in a nearly 50% decrease in the risk of CLABSI in patients who required long-term central venous access (ie, >30 days).87

Additionally, by developing a VAT, a facility may reduce the resources spent training and retraining proceduralists and ancil- lary support staff in central-line insertion and maintenance.21

Regardless, standards for the training of proceduralists vary. A recent national survey showed that most proceduralists attend informal training sessions, with less stringent training require- ments for physicians than registered nurses or nurse practi- tioners.88 Many of proceduralists have <5 successful placements before being allowed to insert a PICC independently. Table 7 provides a list of recommended education, training, and competencies for members of a neonatal VAT.

Question 10:What threshold should prompt aNICU to consider implementing additional preventive measures?

Answer 10:

• Zero CLABSIs is the aspirational and potentially achievable goal. Although there is no nationally endorsed threshold above which additional CLABSI prevention measures should be imple- mented, a variety of quantitative or qualitative metrics may be utilized to identify CLABSI prevention success over time and determine when additional intervention is necessary.

• A decision to identify a threshold for action in an individual NICU should assess a variety of factors including the following: • An SIR or rate of CLABSI that is above goal or increasing despite the consistent implementation of current organiza- tional interventions

• Local interest in setting a specific lower target with input from Infection Prevention and Control (infection preventionists, healthcare epidemiologist)

• Patient mix and clinical acuity, which may predict general likelihood of CLABSI

• Resource and personnel capacity for initiation and/or mainte- nance of specific interventions and practice processes.

• Any quantitative or qualitative metric that is defined should be developed and accepted by all stakeholders.

CLABSI prevention should be a continuous goal and inte- grated into usual NICU practices and processes. Successful CLABSI prevention requires attention to the importance of prac- tices related to central-line insertion and maintenance over time and collaboration among a variety of stakeholders, including infection preventionists, nurses, physicians, advanced practice HCP, and educators, among others. The decision to increase infection prevention efforts requires the involvement of NICU leadership or a local champion to ensure that new processes

and education are prioritized within existing workflows. Individual units have achieved very low rates of CLABSIs–even zero CLABSIs–over sustained periods.6,22

A variety of quantitative metrics can be used to reveal a lapse in CLABSI prevention success. Quantitative metrics may include total NICU-wide CLABSI incidence over a predefined period, compared to a similar period that allows for adjustment for time-varying confounders (eg, season, census, staff short- ages, and turnover). Alternatively, an absolute number of CLABSIs may be deemed “acceptable” in a particular NICU for a given period or a given patient census. Either of these met- rics also may be considered for a subset of high-risk infants as a marker for general CLABSI prevention effectiveness (eg, post- operative patients, premature infants, and others). Lastly, a NICU may consider a predefined target standard infection ratio (SIR), a risk-adjusted metric generated by the CDC using NICU- specific surveillance data reported to NHSN (eg, SIR < 1.0).89

NICUs may also choose to increase CLABSI prevention efforts based upon rigorously evaluated or even anecdotal quali- tative observations in the unit. Qualitative observations can be performed actively on an ad hoc basis or via routine mecha- nisms such as team huddles with checklists or overt comprehen- sive audits of any or all practices. Real-time perceptions among staff of waning vigilance toward CVC maintenance practices or repeated breaches in protocol for specific practices related to line insertion or maintenance must be taken seriously and prop- erly investigated. Ultimately, any developed target metric that may trigger more intensive CLABSI prevention efforts should be acceptable to all a priori, particularly those involved with CVC use and CLABSI prevention at the bedside.

Before a decision is made to introduce new processes for CLABSI prevention, it is important to assess the adherence to existing prevention practices in the NICU in a systematic fashion, for example, through a quality improvement (QI) program. Such assessments should include direct input from infection preven- tionists, nurses, advance practice HCP, and physicians. If addi- tional CLABSI measures are deemed necessary, it is helpful to distinguish between those shown to be effective and those that are not proven robustly but may have an impact nonetheless. Known effective evidence-based interventions have been identi- fied by the CDC and other experts (Table 3).8,17

If an effort to enhance CLABSI prevention activities is deemed necessary, it must be recognized that staff at various levels of responsibility may have different attitudes or willingness to add tasks to the workflow.90 Simply having a written policy is insuffi- cient to effect practice change(s) that will lead to fewer CLABSIs. In 2011, a national survey noted that 84%–93% of NICUs had written policies for insertion checklist and for bundle practices, but ≥75% adherence for individual components was achieved only 68%–73% of the time for at least 1 component and only 28% for all monitored processes.91 Allowance for adaptations (dependent on local work- flows and priorities) is important, and quantitative metrics should be used as a guide to effectiveness.92

Question 11: What preventive bundle elements, above and beyond those recommended by the CDC, could be considered by a NICU experiencing ongoing CLABSIs?

Answer 11:

• Additional practices that lack robust evidence may be effective. NICUsmay consider many different products, technologies, and processes, some of which are described below.

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• If implemented, the impact of these practices should be evalu- ated by a multidisciplinary team.

Evidence-based care bundles effectively reduce CLABSIs in the NICU. A meta-analysis performed by Payne et al4 reported a 60% decrease in CLABSI rates after the introduction of a care bundle in neonatal units. Additionally, care bundles contribute to a reduction in total central-line use and duration. The CDC has recommended basic insertion and maintenance bundles for all patients with CVCs, including NICU patients (Table 3). Nevertheless, published reports suggest substantial variability in bundles utilized in NICUs and little consensus about what con- stitutes the optimal bundle. A variety of CLABSI prevention bun- dles with different individual components have been shown to minimize CLABSIs in NICU settings, although most include hand hygiene, maximal sterile barrier precautions, and effective skin antisepsis.93 Few studies have compared the effectiveness of different bundles in a way that permits assessment of individual bundle components.

Throughout this document, we have reviewed practices and products that could be added to basic prevention bundles, includ- ing CHG bathing, CHG-containing sponges at central-line inser- tion sites, ethanol disinfectant caps, and prophylactic antimicrobial locks. Additional practices may be effective and have been imple- mented by some NICUs, but they lack robust evidence and there- fore have not been reviewed in detail in these recommendations. Such practices include but are not limited to regular sharing of CLABSI incidence data with NICU staff, the use of nonsterile gloves for all central-line care,94 and a standard process for assess- ing when to discontinue a central line, such as when the infant is tolerating full enteral feeds andmedications can be provided enter- ally.22,95 For the assessment of continued need or discontinuation of a CVC, a short checklist in the daily note of the nurse or physi- cian with discussion on multidisciplinary patient rounds may be a useful tool.

Most studies of bundle effectiveness have been conducted in larger, higher level-of-care NICUs. Similar effectiveness is antici- pated in community NICUs that care for infants with CVCs.

Acknowledgments. The authors wish to thank NICU Advisory Panel Chairs, Drs. Alexis Elward and Deborah Yokoe. The authors thank Valerie Deloney, MBA and John Heys for their organizational expertise in the development of this manuscript.

NICU Advisory Panel : Kenneth M. Zangwill, MD, American Academy of Pediatrics Section on Infectious Diseases (AAP/SOID); Nancy Foster, American Hospital Association (AHA); Jessica R. Rindels, MBA, BSN, RN, CIC, Association for Professionals in Infection Control and Epidemiology (APIC); Jill Jones MS, APRN, NNP-BC, National Association of Neonatal Nurses (NANN); Pablo J. Sánchez, MD, Infectious Diseases Society of America (IDSA); Aaron M. Milstone, MD, Pediatric Infectious Diseases Society (PIDS); Margaret VanAmringe, MHS, The Joint Commission; Judith Guzman-Cottrill, DO, The Vermont Oxford Network (VON).

Conflicts of interest. The following disclosures are a reflection of what has been reported to SHEA. To provide thorough transparency, SHEA requires full disclosure of all relationships, regardless of relevancy to the guideline topic. Evaluation of such relationships as potential conflicts of interest is determined by a review process.

The assessment of disclosed relationships for possible conflicts of interest will be based on the relative weight of the financial relationship (ie, monetary amount) and the relevance of the relationship (ie, the degree to which an

association might reasonably be interpreted by an independent observer as related to the topic or recommendation of consideration). The reader of this guidance should be mindful of this when the list of disclosures is reviewed.

K.A.B. reports being a principal investigator on multicenter clinical trials funded by Pfizer, Gilead, and Enanta (payments made to institution) and serv- ing as Immediate Past President of the Pediatric Infectious Diseases Society. P.J.S. reports a grant for institution support from Merck (completed prior to publication) and current participation on the CDC Advisory Committee on Immunization Practices (ACIP). All other authors report no conflicts of interest relevant to this article.

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SHEA Neonatal Intensive Care Unit (NICU) White Paper Series: Practical approaches for the prevention of central-line-associated bloodstream infections