research paper topics on neonatology

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Neonatology articles from across Nature Portfolio

Latest research and reviews.

Global longitudinal strain is an informative index of left ventricular performance in neonates receiving intensive care

Enrico Petoello
Alice Iride Flore
Benjamim Ficial

Long-term impact of late pulmonary hypertension requiring medication in extremely preterm infants with severe bronchopulmonary dysplasia

Yun Sil Chang

Application of machine learning algorithms for accurate determination of bilirubin level on in vitro engineered tissue phantom images

Jiayao Huang

Impact of intrapartum oxytocin administration on neonatal sucking behavior and breastfeeding

Machiko Omaru
Setsu Kajiwara
Seiichi Morokuma

A Time-of-Flight and Radar Dataset of a neonatal Thorax Simulator with synchronized Reference Sensor Signals for respiratory Rate Detection

Johanna Gleichauf
Sven Herrmann
Alexander Koelpin

Prenatal tobacco smoke exposure and risk for cognitive delays in infants born very premature

E. Melinda Mahabee-Gittens
Nusrat Harun
Weihong Yuan

News and Comment

Prenatal treatment for Pompe’s disease

To prevent irreversible organ damage, an infant with early-onset Pompe’s disease was treated in utero; early data suggest improved outcomes and safety of this approach.

Karen O’Leary

First step to cell therapy for ischemic stroke in newborns

In a first-in-human study, intranasal transplantation of mesenchymal stromal cells was safe and well-tolerated in newborns who had suffered a stroke — laying the foundation for large-scale clinical trials.

Genetic testing in the neonatal ICU

First-line whole-genome sequencing may lead to more-focused clinical management for infants with a suspected genetic disease.

Bending the arc for the extremely low gestational age newborn

DeWayne M Pursley
Marie C McCormick

Hope vs. caution: ethical and regulatory considerations for neonatal stem cell therapies

Naomi T Laventhal
Scott A Rivkees
Valerie P Opipari

Biomarkers for neonatal therapeutic studies: time for a public–private partnership

Scott C Denne
Jonathan M Davis

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Neonatology

Explore the latest in neonatology, including advances in fetal surgery and in the care of preterm and extremely low-birth-weight infants.

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This cohort study examines the association between fertility treatment and multifetal pregnancy rates in a publicly funded fertility program in Ontario, Canada, from 2006 to 2021.

This prospective follow-up study of a randomized clinical trial evaluates whether antenatal corticosteroids administered to birthing parents at risk of late preterm delivery were associated with adverse neurodevelopmental effects on their offspring.

Late Preterm Corticosteroids Exposure and Neurodevelopmental Outcomes JAMA Opinion April 24, 2024 Women's Health Reproductive Health Obstetrics Obstetrics and Gynecology Pediatrics Full Text | pdf link PDF

This cohort study assesses the association between severe maternal morbidity after a first delivery and risk of hospitalization or emergency department (ED) visits for a mental health condition over a 13-year period.

This randomized clinical trial examines whether breast milk enemas can shorten the time to complete meconium evacuation and achievement of full enteral feeding for infants born preterm in China.

Study: Younger Deaths Driving Maternal Mortality Increase JAMA News April 19, 2024 Pediatrics Pregnancy Obstetrics Women's Health Obstetrics and Gynecology Full Text | pdf link PDF free

This case report describes a diagnosis of morning glory syndrome in a 2-week-old infant who presented with divergent strabismus, cleft lip, and hypertelorism.

This cohort study investigates the association of immune checkpoint inhibitor (ICI) treatment for cancer during pregnancy with adverse outcomes in mothers and newborns.

Pregnancy and Cancer—Navigating Impossible Decisions JAMA Network Open Opinion April 17, 2024 Oncology Pediatrics Targeted and Immune Therapy Reproductive Health Women's Health Full Text | pdf link PDF open access

This Viewpoint discusses the need for universal standards of recording and measuring phototherapy administered to infants to monitor for potential adverse effects in the long term.

This cohort study aims to determine long-term mortality risks associated with 5 major adverse pregnancy outcomes in a large population-based cohort of women.

This randomized clinical trial examines data for infants pharmacologically treated for neonatal opioid withdrawal in a subgroup analysis to evaluate differences in opioid exposure and length of hospital stay comparing a function-based care approach vs usual care.

This cohort study examines cervical length trajectories and their association with risk of spontaneous preterm birth in individuals with singleton and twin pregnancies.

Spontaneous Preterm Birth Phenotyping Based on Cervical Length and Immune-Mediated Factors JAMA Network Open Opinion April 11, 2024 Obstetrics and Gynecology Reproductive Health Pregnancy Obstetrics Women's Health Full Text | pdf link PDF open access
Paid Family Leave Programs—Understanding the Consequences for Infant Health JAMA Pediatrics Opinion April 8, 2024 Pediatrics Pregnancy Obstetrics Obstetrics and Gynecology Reproductive Health Full Text | pdf link PDF

This cross-sectional study uses an interrupted time series analysis to assess whether an association exists between Swedish speed premium family policies protecting parental leave payment levels in short birth intervals and perinatal health outcomes among infants.

This cross-sectional study investigates perioperative oxygen saturation differences in Black and White infants with single ventricles undergoing stage 1 palliation.

This cross-sectional study conducted in 6 states and New York City estimates the prevalence of mistreatment by health care professionals during childbirth among a representative multistate sample and identifies patient characteristics associated with mistreatment experiences.

This secondary analysis of a randomized clinical trial investigated the association of gonadotropin dosage and duration with embryonic genetic status and pregnancy outcomes among pregnant individuals who underwent euploidy embryo transfer.

This cohort study evaluates whether neonates with risk factors for hypoglycemia have higher catecholamine concentrations in umbilical cord blood and/or amniotic fluid and whether catecholamines are correlated with postnatal glycemia.

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Neonatal sepsis: a systematic review of core outcomes from randomised clinical trials

Affiliations.

1 Discipline of Paediatrics, Trinity College Dublin, The University of Dublin & Children's Hospital Ireland (CHI) at Tallaght, Dublin, Ireland.
2 John Stearne Medical Library, Trinity College Dublin, St. James' Hospital, Dublin, Ireland.
3 Trinity Translational Medicine Institute, St. James Hospital, Dublin, Ireland.
4 Trinity Research in Childhood Centre (TRiCC), Trinity College Dublin, Dublin, Ireland.
5 Department of Pediatrics and Adolescence Medicine, University Hospital of North Norway, Tromsø, Norway.
6 Paediatric Research Group, Faculty of Health Sciences, UiT-The Arctic University of Norway, Tromsø, Norway.
7 School of Nursing and Midwifery, Faculty of Health, University of Plymouth, Plymouth, UK.
8 Division of Woman and Baby, Department of Neonatology, Wilhelmina Children's Hospital (part of UMC Utrecht) and University of Utrecht, Utrecht, The Netherlands.
9 Neonatal Health and Development, Telethon Kids Institute, Perth, WA, Australia.
10 Neonatal Directorate, King Edward Memorial Hospital for Women, Perth, WA, Australia.
11 Clinic of Neonatology, Department Mother-Woman-Child, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.
12 Paediatric Critical Care Research Group, Child Health Research Centre, University of Queensland, Brisbane, QLD, Australia.
13 Paediatric Intensive Care Unit, Queensland Children's Hospital, Brisbane, QLD, Australia.
14 Department of Pediatrics, Bern University Hospital, University of Bern, Bern, Switzerland.
15 Department of Neonatology, Pirogov Russian National Research Medical University, Moscow, Russia.
16 Department of Paediatrics, Tergooi Hospital, Blaricum, The Netherlands.
17 Department of Paediatrics, Amsterdam UMC, Emma Children's Hospital, University of Amsterdam, Amsterdam, The Netherlands.
18 Department of Neonatology, Radboud Institute for Health Sciences, Radboud University Medical Center, Amalia Children's Hospital, Nijmegen, The Netherlands.
19 Karolinska University Hospital and Karolinska Institutet, Stockholm, Sweden.
20 Department of Paediatrics, University of Florida, Gainesville, FL, USA.
21 Department of Pathology, Immunology, and Laboratory Medicine, University of Florida, Gainesville, FY, USA.
22 Department of Neonatology, Clinic for Paediatric Cardiology, Intensive Care and Neonatology, University Medical Centre Göttingen, Göttingen, Germany.
23 Neonatal Unit, Department of Obstetrics and Gynecology, Motol University Hospital and Second Faculty of Medicine, Prague, Czech Republic.
24 Institute of Pathological Physiology, First Faculty of Medicine, Charles University, Prague, Czech Republic.
25 Department of Pediatrics, Division of Neonatology, Erasmus MC-Sophia Children's Hospital, Rotterdam, The Netherlands.
26 Department of Pediatrics, Women & Infants Hospital of Rhode Island, Alpert Medical School of Brown University, Providence, RI, USA.
27 Division of Neonatal-Perinatal Medicine, Department of Pediatrics, Columbia University Medical Center, New York City, NY, USA.
28 Division of Neonatology, Edward Doisy Research Center, Saint Louis University, St. Louis, MO, USA.
29 Institute of Translational Medicine, University of Liverpool, Centre for Women's Health Research, Liverpool Women's Hospital, Liverpool, UK.
30 Department of Neonatal Medicine, School of Public Health, Faculty of Medicine, Imperial College London, Chelsea and Westminster Campus, London, UK.
31 Discipline of Paediatrics, Trinity College Dublin, The University of Dublin & Children's Hospital Ireland (CHI) at Tallaght, Dublin, Ireland. [email protected].
32 Trinity Translational Medicine Institute, St. James Hospital, Dublin, Ireland. [email protected].
33 Trinity Research in Childhood Centre (TRiCC), Trinity College Dublin, Dublin, Ireland. [email protected].
34 Department of Paediatrics, Coombe Women's and Infant's University Hospital, Dublin, Ireland. [email protected].
35 Department of Neonatology, CHI at Crumlin, Dublin, Ireland. [email protected].
PMID: 34997225
PMCID: PMC9064797
DOI: 10.1038/s41390-021-01883-y

Background: The lack of a consensus definition of neonatal sepsis and a core outcome set (COS) proves a substantial impediment to research that influences policy and practice relevant to key stakeholders, patients and parents.

Methods: A systematic review of the literature was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. In the included studies, the described outcomes were extracted in accordance with the provisions of the Core Outcome Measures in Effectiveness Trials (COMET) handbook and registered.

Results: Among 884 abstracts identified, 90 randomised controlled trials (RCTs) were included in this review. Only 30 manuscripts explicitly stated the primary and/or secondary outcomes. A total of 88 distinct outcomes were recorded across all 90 studies included. These were then assigned to seven different domains in line with the taxonomy for classification proposed by the COMET initiative. The most frequently reported outcome was survival with 74% (n = 67) of the studies reporting an outcome within this domain.

Conclusions: This systematic review constitutes one of the initial phases in the protocol for developing a COS in neonatal sepsis. The paucity of standardised outcome reporting in neonatal sepsis hinders comparison and synthesis of data. The final phase will involve a Delphi Survey to generate a COS in neonatal sepsis by consensus recommendation.

Impact: This systematic review identified a wide variation of outcomes reported among published RCTs on the management of neonatal sepsis. The paucity of standardised outcome reporting hinders comparison and synthesis of data and future meta-analyses with conclusive recommendations on the management of neonatal sepsis are unlikely. The final phase will involve a Delphi Survey to determine a COS by consensus recommendation with input from all relevant stakeholders.

Publication types

Systematic Review
Research Support, Non-U.S. Gov't
Delphi Technique
Infant, Newborn
Neonatal Sepsis* / diagnosis
Neonatal Sepsis* / therapy
Outcome Assessment, Health Care
Randomized Controlled Trials as Topic
Research Design*
Treatment Outcome

Grants and funding

MR/N008405/1/MRC_/Medical Research Council/United Kingdom

Editorial: Case reports in neonatology 2022

Sascha meyer.

1 Department of General Pediatrics and Neonatology, Franz-Lust Klinik für Kinder und Jugendliche, Karlsruhe, Germany

Michael Wagner

2 Department of Neonatology, Medical University of Vienna, Vienna, Austria

Merih Cetinkaya

3 Department of Neonatology, University of Health Sciences, Istanbul, Türkiye

Editorial on the Research Topic Case reports in neonatology 2022

This Research Topic publishes high-quality case reports and case series in the field of neonatology, ranging from lethal poisoning, adverse drug reactions, congenital pathologies, neonatal metabolic disease, survival and care practices of periviable births to malignancies in newborns ( Baptiste et al. Cheng et al. Gaertner et al. Boddu et al. Chen et al. Yan et al. ). Case reports provide important insights into the differential diagnosis, decision making, and clinical management of unusual cases. They provide a valuable tool for (a) recognizing new or rare diseases, (b) evaluating therapeutic effects, adverse events, and costs of interventions; as well as (c) improving problem-based medical education in a real-world clinical setting, Conversely, randomized clinical trials generate evidence for the efficacy of interventions in a controlled setting. Undoubtedly, both types of reports are necessary and complementary in modern medicine. Of note, case reports today make up a substantial proportion of articles published in medical journals, and they continue to further our understanding of a great variety of diseases. Consequently, case reports are an important contributor to and driver of medical progress. The CARE guidelines help increase the completeness, accuracy, and transparency of published case reports ( 1 ).

The importance of having access to case reports in our continuously changing modern world is key in the provision of best clinical care. In the immortal words of the famous Canadian physician, first Professor of Medicine and founder of the Medical Service at Johns Hopkins Hospital, Sir William Osler (July 12, 1849 to December 29, 1919): “Always note and record the unusual … Publish it. Save it on a permanent record as a short, concise note. Such communications are always of value” ( 2 ).

No doubt, the value of case reports may be underestimated compared to other publications that are more detailed and supported by evidence (eg, randomized controlled clinical trials). Nevertheless, this experience-based informative method has nowadays been transformed into an accepted academic form of communication and publication, thus contributing to the rapid dissemination of medical knowledge to a wide medical professional audience, including neonatologists.

Therefore, we hope that this Special Collection is both informative and stresses the importance and role of case reports in the field of neonatology, and will also translate into improved neonatal care practices around the world.

Author contributions

This editorial was jointly conceptualized and written together. All authors contributed to the article and approved the submitted version.

Conflict of interest

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Publisher's note

All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.

Emerging Topics and Controversies in Neonatology

© 2020
Elaine M. Boyle 0 ,
Jonathan Cusack 1

Department of Health Sciences, George Davies Centre for Medicine, University of Leicester, Leicester, UK

You can also search for this editor in PubMed Google Scholar

Adopts an evidence-based approach to controversial neonatal problems

Aligned with the curriculum for senior trainees in neonatal medicine, but also of interest to early career neonatologists and established neonatologists

Provides a broad focus, and as well as addressing specific clinical problems, also addresses common practical issues (eg. ethics, counselling, education and training).

Includes section by parents who have experience of their baby in neonatal intensive care

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Table of contents (34 chapters)

Front matter, pregnancy–related complications and preterm delivery.

Suzanna Dunkerton, Penny C. McParland

Maternal Chronic Conditions and the Fetus

Kate Jones, Abigail Anness, Farah Siddiqui

Artificial Gestation

Dominic Wilkinson, Lydia Di Stefano

The Term Infant: Evidence-Based Approach to Management

Management of the depressed newborn; to cool or not to cool.

Divyen K. Shah

Neonatal Hypotonia

Robin Miralles, Deepa Panjwani

Critical Congenital Heart Disease

Katie Linter, Thomas Mukasa

Evidence Based Approach to the Management of Persistent Pulmonary Hypertension of the Newborn (PPHN)

Venkatesh Kairamkonda, Sumit Mittal

Neonatal Surgical Conditions: Congenital Diaphragmatic Hernia and Short Bowel Syndrome

Yew-Wei Tan, Andrew Currie, Bala Eradi

Managing the Difficult Airway in a Neonate

James Blythe, Jonathan Cusack

Sudden Unexpected Postnatal Collapse

Vix Monnelly, Julie-Clare Becher

The Very Preterm Infant: Controversies in Postnatal Management

Mechanical ventilation of the preterm infant.

Kate Hodgson, Peter Davis, Louise Owen

Non-invasive Respiratory Support

Charles Christoph Roehr

Oxygen Management in Neonatal Care

Ben Stenson

Patent Ductus Arteriosus: The Conundrum and Management Options

Kiran More, Samir Gupta

Glucocorticoid Treatment for Bronchopulmonary Dysplasia

Tanja Restin, Dirk Bassler

Feeding and Nutrition

Nicholas D. Embleton
term infant
pre-term infant
prematurity
neontatal care
preterm birth
neonatal intensive care

About this book

This textbook addresses the themes that are at the forefront of neonatal clinical care and research, based on natural divisions in care during pregnancy, and postnatally by gestational age at birth. The book offers a unique approach, in that it proposes discussion of important general principles underpinning neonatal care that are not addressed in most general neonatology textbooks, such as ethical issues, counselling, effective training methods, quality and safety, among other subjects. These are fundamental aspects and challenges that need to be appreciated by senior clinicians. A chapter authored by parents describing their perspectives of neonatal intensive care is unique and will be highly educational, with the potential to influence the way in which individuals view and deliver neonatal care.

The authors discuss common and important conditions, to promote adoption of sound evidenced based practice where this is available. However, where evidence is limited, as is the case in many areas of neonatal practice, the authors aim to encourage critical thinking and evidence appraisal, which are necessary skills for busy clinicians wishing to filter evidence to guide delivery of care.

Editors and Affiliations

Elaine M. Boyle, Jonathan Cusack

About the editors

Dr Elaine Boyle is a clinical academic in neonatal medicine at the University of Leicester. She graduated in Medicine from the University of Sheffield and obtained MSc, MD and PhD from the University of Edinburgh. Elaine is active in both clinical neonatology and neonatal research. Her main research interest is late preterm and moderately preterm birth, and she led the Late And Moderately preterm Birth Study (LAMBS), the first large UK population based study of birth at 32-36 weeks gestation. Other research interests include the assessment and management of neonatal pain and infant feeding, which were the focus of her MD and PhD theses respectively. Elaine has a large number of research publications and has contributed chapters to a number of medical texts.

Bibliographic Information

Book Title : Emerging Topics and Controversies in Neonatology

Editors : Elaine M. Boyle, Jonathan Cusack

DOI : https://doi.org/10.1007/978-3-030-28829-7

Publisher : Springer Cham

eBook Packages : Medicine , Medicine (R0)

Hardcover ISBN : 978-3-030-28828-0 Published: 06 February 2020

Softcover ISBN : 978-3-030-28831-0 Published: 26 August 2021

eBook ISBN : 978-3-030-28829-7 Published: 05 February 2020

Edition Number : 1

Number of Pages : VII, 597

Number of Illustrations : 8 b/w illustrations, 58 illustrations in colour

Topics : Pediatrics , Intensive / Critical Care Medicine

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Selected Topics in Neonatal Care

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Austral University of Chile , Chile

Published 27 June 2018

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ISBN 978-1-78923-363-6

Print ISBN 978-1-78923-362-9

eBook (PDF) ISBN 978-1-83881-248-5

Number of pages 248

Neonatology is one of the areas of greatest development and evolution within pediatrics. The technoscientific advances in this area have led to an increase in the survival of premature infants who sometimes require sophisticated care. However, there is essential care that must be included in all centers that care for high-risk babies. This book includes important topics related to neonatal care grouped into four sections. In 14 chapters that address relevant issues about neonatal care, the book seeks to contribute to the clinical work of the health teams of neonatal units. Specialists in the field of neonatology from different countries have developed these chapters and through them they hope to share part of their experience.

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Présentations françaises
Publications
How should we pasteurize donor breast milk?

The standard method of pasteurization of donor breast milk, and I believe the only method approved by HMBANA (the human milk banking association of north america), is similar to what Louis Pasteur himself came up with a couple of centuries ago (in about 1865). I’m not sure why its called Holder pasteurization, it may be because the temperature is “held” at 62.5 degrees for 30 minutes, or maybe it’s named after someone. In any case, it is effective in killing most bacteria, not including spore-bearing forms (like Bacillus cereus), but, unfortunately, inactivates white cells, kills probiotic organisms and denatures many large molecules, especially proteins.

Some of the advantages of human milk are therefore impacted by Holder pasteurization (HP), and there are a few review articles available (including this one from the European MBA) which discuss the available pasteurization methods. Other means of pasteurization that have been evaluated, include ultraviolet treatment , high hydrostatic pressure , and most particularly High Temperature Short Time (HTST) which uses temperatures of about 72 degrees for 15 seconds. All the alternative methods seem to be equally good at inactivating bacteria, and many viruses, but the alternatives have much less negative impact on the other beneficial components of milk (Oligosaccharides are relatively unaffected by HP). The major current problem with changing over to alternatives are the new equipment that will be required, and the lack of good evidence that it actually makes a clinical difference.

A recent RCT from 2 NICUs in Madrid compared supplementing mothers milk with pasteurized donor milk that used one of 2 different pasteurization methods, HP and HTST. They enrolled 213 and analyzed results from 160 ELBW infants, with the primary outcome being the occurrence of CLABSI, or a positive blood culture in an infant who had a central line in place for more than 48 hours, and in whom the culture was drawn during catheter use or within 48 hours after.

The most striking result is the enormously high frequency of CLABSI in those units, in both groups, 42% with the HTST and 46% in the HP group. There was no statistical difference between groups, but the study was designed to have 150 babies per group, and powered for a 33% reduction in the outcome. They stopped adding patients after 160 were actually enrolled, which is never really explained, the confidence intervals for the relative risk of catheter related sepsis were 0.68-1.26 with HTST compared to HP, so a large potential benefit is consistent with this null result.

The definition of late-onset sepsis is quite rigorous, and required a positive blood culture, after 72 hours of life, with a central catheter in place (or removed <48 h) and at least 2 of a sequence of clinical signs, or in the case of CoNS also other lab results (CBC results or CrP raised). When expressed per 1000 catheter days, the incidence in the two groups was about 18/1000 catheter days.

As a comparison, among babies <1kg birth weight in the CNN, all LOS combined (which is any positive blood culture, not requiring any other criteria, either with or without a central catheter in place) was 28%. In a publication from the German Neonatal Network , they showed “only 45% of primary BSI were CVC related in the <1000 g birthweight group” in other words, only about half of LOS was catheter related. That percentage is going to vary a great deal, depending on how central catheters are used, and the GNN also showed also a large variation in use. Nevertheless, the infections reported by this new Spanish study are only a subgroup of all the LOS in their infants; again in comparison with the Canadian Network, among infants <33 weeks the incidence of CLABSI was about 7.5/1000 catheter days.

As far as I can tell, the Spanish study did not enrol particularly high-risk babies, some were eliminated because of a “risk of early death”, they seem to be a group with relatively standard risk profile.

I think that different ways to try and preserve the advantages of human milk, by using different pasteurization methods is really important. However, by themselves, such improvements will not be likely to have a huge impact on LOS rates, especially when only a small proportion of the milk received is the donor milk. Enteral colonization with pathogenic, mostly Gram negative, organisms is a known common occurrence prior to blood stream infection. This recent publication for example, Schwartz DJ, et al. Gut pathogen colonization precedes bloodstream infection in the neonatal intensive care unit. Sci Transl Med. 2023;15(694):eadg5562 , showed that GI colonization with the same organisms was very common, and that the pathogens were more abundant, in babies who later developed LOS. The anti-infective properties of milk will have an impact on gut colonization, and it is likely that different pasteurization methods will have an impact on those benefits.

There are many other things we do that can affect the incidence of LOS, I note that in the Spanish trial the use of “anti-acid” medications was very common at 20 to 30%, there are no details, and they may have been given after the episodes of sepsis, but I think there is very little indication for the use of such medications, which clearly can increase gut colonization by reducing one of the important barriers.

I just hope this new study doesn’t discourage the on-going development of better ways to pasteurize donor human milk which preserve more of the advantages. I think we need more, adequately powered studies to, firstly, show impacts on the intestinal microbiome of different pasteurization methods, and, if possible, following that, the clinical benefits. But we must take into account the large number of other risk factors for LOS, and reinforce quality control. Stringent quality improvement methods can reduce LOS in the very preterm, and have to be a priority wherever ELBW infants are cared for.

Time to open the DOOR

I have written many times about the problems with classical composite outcomes in neonatal research. “Death or BPD”, “death or NDI”, or sometimes “death or NEC or Sepsis or BPD or severe IVH” have been used as a way of combining adverse outcomes that we want to avoid, and accounting for the fact that death is a competing outcome for many negative outcomes. The enormous problems with such composites is that they give equal weight, when evaluating an intervention, to the components of the composite. A baby who survives to 36 weeks but needs oxygen is considered equivalent, in terms of the analysis of the results, to a baby who dies.

This has led to a number of serious problems in interpretation of results, to the extent that interventions may, for example, decrease mortality, but if they have no impact on BPD the results may be considered null and “not statistically significant”. Composite outcomes have sometimes been used as a way of increasing power, but in reality they do not necessarily increase power. Especially if the components change in different directions, or if the most important outcome is less frequent than the less important components; in such instances power may actually be decreased.

I have suggested, in the past the Win Ratio approach, one way of planning and analyzing trials, in which outcomes are evaluated in a prioritised fashion, and death is considered the worst outcome, followed by survival with very severe BPD, followed by survival with less severe BPD… etc. Subjects can be compared in pairs to see which has the better outcome, this Win Ratio approach has been used in some trials, especially in adult cardiology studies. It is an approach which is most easily used if subjects are randomized in pairs. In more standard large RCTs, each subject in group 1 has to be compared to every subject in group 2, and the maths and the statistical analysis becomes more complex.

An alternative which has been used mostly, I think, in infectious disease research, is called the Desirability Of Outcomes Ranking. This article, for example, discusses how to design and analyze a trial using this approach ( Ong SWX, et al. Unlocking the DOOR-how to design, apply, analyse, and interpret desirability of outcome ranking endpoints in infectious diseases clinical trials. Clin Microbiol Infect. 2023;29(8):1024-30 ). It was designed as a way of analyzing trials where there are a few deaths, some patients survive with complications, and others survive without serious complications. Ranking these outcomes according to their desirability. Exactly how to rank the outcomes, which also include, for example, treatment failure where the antibiotics don’t eliminate the infection, is an ongoing question, but should include important input from patients, or in our case, parents.

As usual, Anup Katheria is ahead of the game, and he has just published a reanalysis of the MINVI trial. This was a cluster randomized trial of cord-milking in term and near-term babies who were non-vigorous at 15 seconds of life. A cartoon of the protocol, from the original publication ( Katheria AC, et al. Umbilical cord milking in non-vigorous infants: A cluster-randomized crossover trial. Am J Obstet Gynecol. 2022) is reproduced below.

The primary outcome of the MINVI trial was NICU admission for any of the following reasons “respiratory distress (tachypnea, grunting, or retractions), bradycardia or tachycardia, hypotonia, lethargy or difﬁculty arousing, hypertonia or irritability, poor feeding or emesis, hypoglycemia, oxygen desaturations or cyanosis, need for oxygen, apnea, seizures or seizure-like activity, hyperbilirubinemia, and/or temperature instability”. Although there were some apparent benefits of cord milking in the results, the primary outcome was 23% (cord milking) vs 28% (early cord clamping) and considered not ‘statistically significant’. Many of the individual reasons for NICU admission were slightly lower in the cord milking group.

This reanalysis ( Katheria AC, et al. Application of desirability of outcome ranking to the milking in non-vigorous infants trial. Early Hum Dev. 2024;189:105928 ) used a DOOR approach. Which depends on a list of ranked outcomes which are shown below in the first column of the table; the table also shows the numbers and proportion of babies in each of the two groups, Umbilical Cord Milking (UCM) and Early Cord Clamping (ECC) who have that outcome as their worst outcome.

The DOOR analysis entails a calculation of how likely it is that a member of the UCM group will have a better outcome than a member of the ECC group. If the interventions are equivalent, then the possibility will be 50%, 95% confidence intervals can be calculated, and if they do not include 50%, then you can conclude, with 95% confidence, that the results are different. You can see in the figure below that the overall DOOR ranking was more likely to favour ECM, with the percentage of the comparisons between UCM and ECC babies favouring UCM being 56%, with 95% CI of 53 to 59%, and each component of the score favouring UCM, except for mild HIE being equivalent.

The last author of this new paper with Anup Katheria has been heavily involved in developing this approach in infections disease research, and they have an extra twist in those studies, that, if there is a tie in outcomes, you can take into account the duration of antibiotic use. Getting an equally good clinical outcome with a shorter course of antibiotics is considered an advantage. I think they mostly invented this wrinkle for the cute acronym RADAR (Response Adjusted for the Duration of Antibiotic Risk) Evans SR, et al. Desirability of Outcome Ranking (DOOR) and Response Adjusted for Duration of Antibiotic Risk (RADAR). Clin Infect Dis. 2015;61(5):800-6 . I’m not sure how this could be adapted to our population, but I like the idea that if you get equally good outcomes with less intervention, that is a good thing.

I know there are other groups that are already considering this approach, which I think could be easily adapted to be a much better primary outcome variable for clinical trials in neonatology. It clarifies the difference in outcomes between groups, giving greater weight to worse outcomes. How to develop the prioritised list of outcomes, and what order to place them in, should definitely be done in collaboration with parents.

To bolus or not to bolus? Not really a question…

Many preterm babies receive boluses of normal saline, often during the first 24 hours when their blood pressure is lower than desired. I have 3 serious questions about this.

Are they indicated?
Do they work?
Are there adverse effects?
Do hypotensive newborn infants have low blood volume?

The rationale for giving a fluid bolus is that the infant may be hypovolaemic, if they are, then you really don’t want to start other therapies if you could simply correct the hypovolaemia. I have some sympathy with this idea, I certainly wouldn’t want to start an epinephrine infusion if all the baby needed was to have 10 mL/kg of saline. But what is the likelihood that a hypotensive very preterm baby may have a low blood volume? There are a couple of studies that have attempted to measure circulating blood volumes in preterm babies, neither show any correlation between volume and BP, or volume and the occurrence of hypotension. Both studies were performed before widespread use of delayed cord clamping, which is very likely to make the association even rarer.

Generally then, no; preterm babies with hypotension are unlikely to be hypovolaemic, and after DCC extremely unlikely to be hypovolaemic. Unless the baby had a cord prolapse, vasa praevia, or was unable to have DCC for some reason, I don’t think we should even consider hypovolaemia. It is a rare reason for babies to be hypotensive after birth.

What about sepsis?

This is a trickier issue, the haemodynamics of neonatal sepsis have not been studied in as much detail as I would like, there are a few studies, which have studied mostly infants with Gran-negative sepsis, who may develop shock from the haemodynamic responses to endotoxins, or as a result of systemic inflammation.

It has become a sort of gospel in treatment of sepsis in older patients that they need huge amounts of fluids, 60 ml/kg is often given before patients are considered fluid unresponsive, at which time inotropes may be added to their therapy (this is what the current CPS recommendations for sepsis treatment in children state). But more recent trials in adults with septic shock are casting doubt on this approach. Two new large RCTs ( here and here ) have shown no harm from a restrictive approach to fluid management compared to liberal fluids. Admittedly to be enrolled in those trial the adults had to have already received a litre of fluid, but that is an awful lot less than 60 mL/kg. An updated meta-analysis including those trials confirmed a lack of difference with liberal compared to restrictive fluid management. Indeed the only large RCT I am aware of in children with septic shock showed an increase in mortality with fluid boluses.

As there is no good data in babies with septic shock, I think that an initial bolus of 10 mL/kg is reasonable, but may not actually turn out to be a good idea, after that the approach should be based on improving overall perfusion if it is impaired, increasing BP, if it is low and associated with poor perfusion, and/or improving perfusion of vital regions. Overall haemodynamic evaluation with functional echo, and regional evaluation with NIRS might help, but that is about as evidence-based as one can get. I start steroids early in treatment of septic shock, although I don’t know for sure that is right, 2 to 6 hours after starting hydrocortisone at lowish dose (2-3 mg/kg/day) things are usually getting better.

2. Do fluid boluses increase BP?

To return to our hypotensive preterm without evidence of sepsis, there is very little evidence that boluses even increase blood pressure. With the knowledge that BP is likely to trend upward anyway, you can only really answer this question with an RCT, but to my knowledge there has never been an RCT of bolus vs no bolus in hypotensive preterms.

Years ago, I did a little before and after study where we gave 15 mL/kg of 5% albumin to hypotensive preterms, and showed that mean BP increased by a mean of 2 mmHg for about 20 minutes, before returning to baseline, echocardiography at the time showed an increase in left ventricular output, but not right ventricular output, which means, in preterm babies with an open PDA, that the only thing the boluses did was to increase ductal shunting without improving systemic flow.

There are a few other short term haemodynamic studies showing very similar findings, i.e. increase in ductal shunt, little or no effect on BP.

3. Are there adverse effects?

This new publication ( Sehgal A, Gauli B. Changes in respiratory mechanics in response to crystalloid infusions in extremely premature infants. Am J Physiol Lung Cell Mol Physiol. 2023;325(6):L819-L25 ) is what triggered this blog post, Arvind Sehgal and Bishal Gauli from Monash in Melbourne, recorded dynamic pulmonary mechanics from the VN500 ventilator before, during and after administration of a crystalloid bolus that had been prescribed by the clinical team.

Ventilator setting remained the same in these babies <29 weeks who were on volume guarantee ventilation. So a change in dynamic lung compliance will lead to a change in peak inspiratory pressure if the baby’s efforts remain similar.

There was a trivial increase in BP with the boluses, 2 mmHg, which may well have been due to the variable nature of BP. As you can see, there was a worsening of dynamic compliance, leading to an increase in PIP, associated with an increase in FiO2.

The most likely explanation is an increase in pulmonary interstitial liquid, perhaps secondary to the increase in ductal shunting.

In view of the lack of evidence of hypovolaemia, the lack of response in BP, and the adverse effects, fluid boluses should generally be avoided in hypotensive preterm infants.

Early routine surfactant, method and outcomes

Two important new studies of the use of very early routine surfactant, compared to later selective surfactant if necessary. The first I will discuss is the one that didn’t seem to improve any important clinical outcomes ( Murphy MC, et al. Prophylactic Oropharyngeal Surfactant for Preterm Newborns at Birth: A Randomized Clinical Trial. JAMA Pediatr. 2023 the POPART trial). 252 infants of less than 29 weeks (mean GA 26 weeks) were randomized prior to birth in 9 university hospitals in 6 European countries, co-ordinated by Colm O’Donnell in Dublin. The intervention was the instillation of 120 mg of Poractant into the pharynx for infants <26 weeks, and 240 mg for those 26-28, this was done without any suctioning, and prior to any positive pressure, ideally before clamping of the cord at 30 to 60 seconds after delivery. Only a small number of babies were protocol violations, being intubated outside of protocol defined indications. After the oro-pharyngeal surfactant, babies followed standard stabilisation, including intubation if required, and any baby thought to need surfactant was treated with the usual surfactant dose thereafter (either by intubation or LISA).

The primary outcome was intubation for respiratory failure in the 1st 120 hours of life, with fairly objective criteria, even though the intervention was, unsurprisingly, unmasked. As you can see here, there isn’t a hint of a difference between groups.

The only difference in secondary outcomes was an increase in pneumothoraces in the surfactant group, 17% vs 6%, not likely to be a random difference. Clinical BPD (70 vs 69%) and physiologic BPD were also just about identical, there was a minor difference in NEC, favouring the control group, and in home oxygen, favouring the surfactant group. Mortality was identical also, 18% in each group.

The rationale for the trial was based on previous pre-clinical data in rabbits showing that the administration method does lead to pulmonary surfactant deposition, and an old RCT in 328 babies of 25 to 29 weeks GA, with a dry powder surfactant which is no longer available, called ALEC (Artifical Lung Expanding Compound, which was developed by Colin Morley) in the Ten centre trial of artificial surfactant in very premature babies. ( Ten Centre Study Group. Br Med J (Clin Res Ed). 1987;294(6578):991-6 ). In that study the prophylactic administration was performed in the delivery room, in a similar way to the POPART trial. In the Ten Centre trial, mortality was lower with surfactant. ALEC was a mixture of two phospholipids, DPPC and PG, and was eventually taken off the market as it was, overall, somewhat less effective than liquid surfactants containing protein.

Why ALEC would work, and lead to lower mortality, but poractant would not, and lead to increased pneumothorax, is not clear to me. Clearly, in the last 35 years many things have changed in neonatology, (I have witnessed all of them!) the Ten Centre group studied 328 babies of 25 to 29 weeks gestation, of whom 19% of the ALEC group and 30% of the controls died, with an overall mean GA of just under 28 weeks. Unfortunately there are some problems with the study design of that trial, it started as a much smaller pilot trial published in the widely circulated journal (!) known as “Colloids and Surfaces”, the results of which were published after about 35 babies of 25 to 29 weeks were reported, and there were 5 deaths in the control group, and 0 in the ALEC group. The later publication in the BMJ appears to have included and re-reported the outcomes of those pilot trial babies, as well as a much larger group added on after the initial benefit was shown. Routine early CPAP was not typically used in the Ten Centre study, perhaps that is why early prophylactic ALEC surfactant was effective, in comparison to standard care, which did not include routine early CPAP.

The mortality is overall about 50% higher in the old study, despite a substantially lower GA in the new trial, demonstrating some of the amazing improvements in survival over this time period. Overall respiratory and ICU management is so much better, that there are no apparent benefits from this intra-pharyngeal prophylactic approach. The controls in the older study did not receive routine CPAP, but in both control groups in the 2 new studies, controls routinely were supported with CPAP.

One thing which is not mentioned in the POPART manuscript, or in the protocol, is the use of caffeine, which although frequently given early, is not often given in very early life.

That is one of the 2 major differences between PROPART and CaLI, the routine administration of intravenous caffeine in the 1st 2 hours of life, the other difference being direct intra-tracheal surfactant administration by the LISA procedure, after the caffeine.

In the CaLI trial, which is unfortunately not open access ( Katheria A, et al. Caffeine and Less Invasive Surfactant Administration for Respiratory Distress Syndrome of the Newborn. NEJM Evidence. 2023;2(12 )), it was funded by Chiesi, I would have thought they could pay for open access as well! 180 babies between 24 and <29 weeks were randomized. The protocol was as briefly outlined above, Caffeine and CPAP versus Caffeine, LISA, and CPAP. To be enrolled, babies had to be breathing and stable at 5 to 60 minutes of age, if enrolled, babies were then weighed and had IV access inserted. LISA followed at least 5 minutes after the 20 mg/kg load of caffeine citrate. In the CPAP group, early postnatal caffeine was also given, which was intended to be before 2 hours of age in both groups.

Randomization was performed at an average of 7 minutes of age, the caffeine was given at a median of about 50 to 60 minutes, and the LISA performed in the LISA group at a median of 1.5 hours, IQR 0.9 to 2. The primary outcome of the trial was the diagnosis of respiratory failure in the first 72 hours of life, the criteria for which were an FiO2 of >40%, respiratory acidosis with a PCO2 >65 on 2 gases, or lots of apneas.

The primary outcome was dramatically reduced by Caffeine plus LISA, compared to Caffeine alone. 23% vs 53%, the benefit was very similar in the 2 GA strata, 44% vs 80% in the 24 to 26 wk group and 14% vs 51% in the 27 to 29 weeks group.

I am actually a bit confused about what exactly was the primary outcome. In the text of the document it is written, “The primary outcome of the trial was the frequency of neonates requiring endotracheal intubation or meeting respiratory failure criteria between the two groups (caffeine and LISA vs. caffeine and CPAP) within the ﬁrst 72 HoL” but then the tables just mention intubation, and babies in the caffeine plus CPAP group could have had LISA without necessarily being intubated. In the table showing the primary outcome results,

the implication is that all the babies counted were actually intubated, even though LISA was permitted in the caffeine alone group. LISA is not much used in the USA currently, so perhaps all the “intubation or respiratory failure” babies were actually intubated. There were only 3 deaths, all in the CPAP without LISA group.

Among other outcomes, there was no sign of adverse effects, and the proportion of babies in oxygen at 36 weeks fell from 35 to 21% in the LISA group. I previously discussed the presentation of these results at the PAS earlier this year, and how Anup Katheria, the first author and PI, put the results together with the OPTIMIST trial. There aren’t yet any data on more clinically important long-term respiratory outcomes with the CaLI approach, but follow up is planned, and, if such outcomes are improved, we will have to figure out the best way to implement the approach. I’d love to figure out how to reduce the discomfort/pain of laryngoscopy, without any respiratory depression, and be more comfortable at performing LISA in the 50% of babies who would never have needed intubation.

CORRECTION: post changed 15 December 2023: The post initially read that the protocol violations in POPART were of babies “being intubated before the POPART intervention”. Colm O’Donnell has informed me that I misinterpreted the violations, the protocol violations were all babies who received the intervention, but were intubated outside of protocol indications, such as because they were “very small” or “needing a lot of oxygen”. As Colm also points out, if there was insufficient surfactant reaching the lungs to improve lung function, then how could the increase in pneumothoraces be blamed on the intervention? (I paraphrase), he is right of course, it doesn’t make much sense, so I guess the difference in pneumothorax rates may just be an accidental occurrence. As for caffeine timing, it isn’t known exactly when the babies in POPART received their caffeine, but they probably mostly received it quite early….

Umbilical cord management at birth for preterm infants

The Lancet just published back-to-back articles from the iCOMP collaborative reporting the results of the Individual Patient Data Meta-analysis of trials of differing cord management techniques in preterm infants. There were 48 trials with a total of 7000 patients in the IPD which made 3 comparisons Delayed compared to immediate clamping, and each approach compared to cord milking. Seidler AL, et al. Deferred cord clamping, cord milking, and immediate cord clamping at preterm birth: a systematic review and individual participant data meta-analysis. Lancet. 2023 .

The data were analysed by subgroups above and below 32 weeks. Above 32 weeks there was very little evident impact on the outcomes that they analyzed, IVH, need for transfusion, NICU admission, and temperature on admission; which is what you would expect. The advantages in larger babies are probably more long term, with higher iron stores and less later anaemia.

Below 32 weeks the results can be seen below: clear advantages of DCC compared to ICC; no major advantages of cord milking compared to ICC; and the major difference between DCC and milking being more severe IVH with cord milking.

For the first comparison, 80% of the weight of the meta-analysis of mortality comes from 3 trials, APTS 58%, a trial from Egypt which is inaccessible, (not listed on Pubmed, or in Embase, and the journal does not appear to have a website, so I am unsure how iCOMP even found it!), weight 14%, and the UK CORD pilot trial (8% weight). The remaining are all small trials with between 4 and 50 per group. The CORD pilot trial was a trial of at least 2 minutes of DCC, with resuscitation, if needed, with the cord intact.

Other analyses performed included the impact of multiple delivery (only available for 4 trials, many trials have excluded multiples) and of gestational age. Neither of these factors appear to have an impact on the advantages of DCC.

The second paper tries to evaluate the data regarding how long to delay cord clamping ( Seidler AL, et al. Short, medium, and long deferral of umbilical cord clamping compared with umbilical cord milking and immediate clamping at preterm birth: a systematic review and network meta-analysis with individual participant data. Lancet. 2023 ), dividing the studies up into 3 groups, 15 to 45 seconds, 45 seconds to less than 120 seconds, and 120 seconds or more. Almost all of the information for the longest delayed group comes from the same UK CORD pilot trial, the other trials with longer delays had more predominantly mature infants, and therefore few events. In particular there were very few severe IVH, so they don’t even report that, in the UK trial there were 6 and 7 severe IVH in the two groups, and the other trials had tiny numbers of babies at risk, or excluded the most immature, or had 0 events.

The analysis of the longest duration of delay therefore relies almost entirely on the results of the CORD pilot trial, which was a well-done trial, delaying cord clamping for at least 2 minutes, and even longer if the physicians felt comfortable waiting for longer, up until there was no evident pulsation. Babies needing resuscitation were treated next to the mother on a hard surface. Many babies in the DCC group actually had clamping earlier as can be seen here:

Many of the early clamped babies in the DCC group of the CORD pilot trial had good reason for early clamping, such as abruption, or the baby being born with the placenta, but many were because the “cord was too short” which, the authors note, became less frequent with time, or for “clinical decision”, which is not further explained.

I remain somewhat sceptical about Network Meta-Analyses, especially for indirect comparisons, where interventions that have not been directly compared are evaluated against each other as if they had been. The huge advantage of a true RCT, that all confounding variables tend to even out, those which you know about as well as those you don’t, is lost with an indirect comparison, such as in an NMA. No matter how much effort is put into correction for baseline imbalances, there always will remain the possibility of residual confounding.

The results of the NMA for these 3 outcomes (all are compared to ICC as the reference group) suggest that the longest delay gives the most mortality benefit. But I don’t think that this should lead to everyone aiming for 2 minutes in every baby. Only one tiny trial directly compared short duration DCC to longer duration. But the NMA, showing the biggest reduction in mortality with the longer delay, is mostly dependent on the trial of Duley, which, individually, showed a small reduction in mortality with longer delay in clamping, which may have been due to random variability. Although this trial had more deaths in the ICC group, the difference in deaths was almost entirely among larger babies of 26 to 32 weeks (8/108 deaths compared to 1/107) and may have been a random occurrence in a smallish trial.

The NMA gives sufficient evidence that further trials examining the relative impacts of 60 to >120 seconds of DCC are warranted. The ABC3 trial was presented recently at the JENS meeting in Rome, it was a trial in very preterm infants comparing an approach similar to what many are currently doing, that is, immediate clamping if the baby needs intervention and DCC of 30 to 60 seconds if the baby is doing well. This approach was compared to DCC and clamping being performed after the baby was stabilised, with a good heart rate and oxygenation, resuscitation if needed was performed with the cord intact, and clamping could be delayed up to 10 minutes. There were no differences in the outcomes reported at presentation of the results, mortality or IVH. I think we should therefore wait until this, and other ongoing trials are published, before longer delays in clamping, and resuscitation with an intact cord becomes the standard.

Take home messages: for mildly preterm infants at low risk of IVH, DCC is preferable to ICC, but milking may be a reasonable option if DCC is not feasible; for very preterm infants at risk of mortality or IVH, DCC is preferable to either ICC or milking. Longer durations of DCC, with resuscitation on an intact umbilical circulation, are not yet proven to further improve mortality or other clinically important outcomes.

Which Probiotic is Preferable?

The word “probiotic” is defined rather vaguely as a micro-organism which has beneficial health impacts. I think it is obvious that there is a huge difference between fungi that are found in the intestinal microbiome of adults, and the lactic acid bacteria which are major components in the young infant.

Even that term “lactic acid bacteria” includes organisms which are dramatically different. Lactobacilli, of the phylum Firmicutes (also called Bacillota), are gram positive rods which are facultative anaerobes, and have limited synthetic capacity, fermenting hexoses to produce lactic acid. Bifidobacteria are Bifid gram positive rods, hence the name, they are often portrayed as tiny little ‘Y’s, and are from a different phylum, the Actinobacteria (or Actinomycetota). They are obligate anaerobes, and have varying abilities to metabolise Hexoses, but remarkable abilities to metabolise oligosaccharides (Human Milk Oligosaccharides, HMOs) that are present in large quantities in breastmilk, but which humans lack the ability to digest.

The only reason these HMOs are present in breastmilk is to feed the Bifidobacteria, which, when they are established and reproduce, come to dominate the intestinal microbiome of the breastfed baby. In particular, a subspecies of B Longum , known as Bifidobacterium Longum ssp Infantis , is a micro-organism that seems to have co-evolved with humans, and is able to digest just about the entire range of HMOs, of which there may be over 200. ( Underwood MA, et al. Bifidobacterium longum subspecies infantis: champion colonizer of the infant gut. Pediatr Res. 2015;77(1-2):229-35 ). HMO composition of human milk is variable, but B Infantis has 24 glycoside hydrolase genes and, alone among GI commensals, possesses sialidases and fucosidases allowing it to digest all types of HMOs.

I don’t for a minute think that breastmilk composition and B infantis evolved in this symbiotic manner in order to prevent NEC! But the GI tract of the full term newborn, who had a possibility of survival, is a haven for nasty pathogens, that can thrive if they have access to food, and which sometimes need access to iron. Hence the presence of Lactoferrin in substantial quantities in breastmilk, which binds iron to keep it out of the clutches of certain Gram negatives, and allows very high bioavailability of breastmilk iron, shuttling it into enterocytes, via specific human lactoferrin receptors, that strip off the iron and resecrete the lactoferrin. Hence the presence of those HMOs, which feed bifidobacteria but for which many pathogens, such as E Coli , Clostridia, Enterobacter and Staphylococci, completely lack the enzymes required to feed on them.

During the evolution of humanity it looks like the constant pressure to avoid GI and systemic infections, in order to survive to be able to pass on our genes, led to this symbiotic relationship between breastmilk and B Infantis . It led to the evolution of breastmilk that is packed with molecules that can only be utilised by Bifidobacteria, and specifically with a high degree of activity by B Infantis. B Infantis can inhibit the growth of other organisms, as well as starving them by eating up all the HMOs, and reduces inflammation by damping down the activity of the TLR4. TLR4 has an affinity for G negative LPS endotoxin, and seems (probably, I guess, by accident) to be overexpressed in the very immature bowel (Meng D, et al. Toll-like receptor-4 in human and mouse colonic epithelium is developmentally regulated: a possible role in necrotizing enterocolitis. Pediatr Res. 2015;77(3):416-24 ).

B Infantis also seems to decrease gut permeability and translocation of pathogens, at least in part by stabilising tight junction proteins. ( Bergmann KR, et al. Bifidobacteria stabilize claudins at tight junctions and prevent intestinal barrier dysfunction in mouse necrotizing enterocolitis. Am J Pathol. 2013;182(5):1595-606. )

When there are a lot of B Infantis about, their metabolic activity leads to production of acids, lactate and acetate, and other short chain fatty acids. Which leads to a low stool pH. A fascinating study published 5 years ago ( Henrick BM, et al. Elevated Fecal pH Indicates a Profound Change in the Breastfed Infant Gut Microbiome Due to Reduction of Bifidobacterium over the Past Century. mSphere. 2018;3(2):10.1128/msphere.00041-18 ) traced the changes in stool pH over the last century, as recorded in various publications, and showed that stool pH in breast fed babies used to be as low as 5, and has increased to as high as 6.5. There is a clear correlation between this increase and lower colonization by Bifidobacteria.

The intestinal protection afforded by this normal microbiome is the reason behind the use of probiotics, my micro-review suggests strongly that B Infantis is the most promising candidate of all the strains.

Sanjay Patole and others in Perth have performed a number of meta-analyses of the clinical trials of probiotics in the preterm, and the most recent focuses on the trials that have used B Infantis , as either the sole probiotic, or as a component of a mixed probiotic preparation. ( Batta VK, et al. Bifidobacterium infantis as a probiotic in preterm infants: a systematic review and meta-analysis. Pediatr Res. 2023 ).

As you can see from this Forest plot, there are a large number of trials, including B Infantis or without, with a total of over 14,000 babies. The trials which included a B Infantis in the treatment group had a reduction in NEC with the RR of 0.38 (0.27, 0.55 95% CI) compared to those with other organisms which had an RR of 0.59 (0.50, 0.70). The statistical test for subgroup differences suggest that this differential impact is unlikely to be due to random effects.

That SR also includes similar plots for overall mortality, preparations with B Infantis RR=0.65 (0.48, 0.88) compared to placebo, preparations without B Infantis compared to placebo, RR= 0.78 (0.67, 0.91). For Late-Onset Sepsis, RR=0.8 (0.63, 1.01) with B Infantis , compared to 0.86 (0.77, 0.97) without B Infantis .

The minor problem with this SR is that, as mentioned B Infantis is a subspecies of B Longum , the other subspecies being B Longum ssp Longum . A few RCTs have stated that they used B Longum , without specifying the subspecies, at least one of them used a mixture “Restore” that they report as including B Longum , when I went on the website of the company that produces Restore, they state that it is a B Longum ssp Infantis . However, the study had so few cases of NEC, 2 vs 1, (and is so badly written that I cannot tell whether group A or group B received the probiotics!) that it would make no difference to the meta-analysis. Another small trial used a mixture containing B Longum, but neither the publication nor the website of the company states which subspecies is in the mixture “Darolac”.

Indeed, this is a major problem in many parts of the world, the quality control standards and certainty of the identification of the strains in the various available products are often very poor. Mixtures may contain no live organisms, different organisms to those claimed, and/or pathogens. It is essential to find a preparation with the production standards required to ensure that you are really giving the organisms you want, and not others.

If B infantis , or other “probiotic” organisms, are able to enter the blood stream, which usually occurs only when the intestinal barrier has been breached, they do not produce lipopolysaccharide endotoxins, as do most pathogenic Gram negatives, which are responsible for much of the inflammation. Nor do they produce any exotoxins, as does Group B streptococcus and some Gram negatives. Which is why most of the babies described in the literature have had minor illness when they have a bacteraemia with these organisms, they just are not very pathogenic. It really is essential to make sure that you are not giving any of the bad bugs when you try and supplement with the good guys.

The most likely candidate, as a single strain of organism that could vigorously colonise the preterm intestine, digest HMOs, decrease inflammation, decrease intestinal permeability, inhibit the growth of pathogens, and has been shown to be a preferentially effective probiotic against NEC in this species selective Systematic Review is B Infantis . The very organism that the FDA has just forced off the market.

UPDATE: of note, David Mills, a real expert in this subject, sent a comment (and a reference ) pointing out that many commercial probiotic preparations, that are supposed to contain B Infantis often do not! There may be other Bifidobacteria, such as a B Infantis that turned out to be B lactis , and there is even variation from lot to lot. This casts a shadow over the meta-analysis above, as it is possible that some of the preparations in the B Infantis group may not actually have contained B Infantis , clearly, all future studies must reliably ascertain the strain used.

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Brain organoids and assembloids are new models for elucidating, treating neurodevelopmental disorders

Stanford Medicine research on Timothy syndrome — which predisposes newborns to autism and epilepsy — may extend well beyond the rare genetic disorder to schizophrenia and other conditions.

April 24, 2024 - By Bruce Goldman, Erin Digitale

In this 2019 photo, Timothy syndrome patient Holden Hulet, left, rides in a side-by-side ATV driven by his dad, Kelby Hulet, at sand dunes near their home in southern Utah. Courtesy of the Hulet family

For a long time, no one understood that Holden Hulet was having seizures.

“He would just say ‘I feel tingly, and my vision kind of goes blurry,’” said Holden’s mom, JJ Hulet. “But he couldn’t communicate exactly what was going on.”

JJ and Kelby Hulet could see their son was having short spells of incoherent speech, rapid back-and-forth eye movements and odd physical changes. “He’d kind of go — I don’t want to say ‘limp’ because he would stand just fine — but his body would just be in zombie mode,” JJ said. The episodes lasted less than a minute.

The parents were puzzled and worried, as they had been many times since Holden was born in 2008 and they learned that their newborn had an extremely rare genetic disease. “I was thinking it was his heart,” Kelby Hulet, Holden’s dad, said.

Holden’s condition, Timothy syndrome, causes long, irregular gaps in heart rhythm. He spent his first six months hospitalized in a neonatal intensive care unit in his family’s home state of Utah while he grew big enough to receive an implantable cardioverter defibrillator. The device sends an electrical signal to restart his heart when it pauses for too long.

As a small child, Holden would sometimes pass out before the defibrillator shocked his heart back into action. When Holden started telling his parents about the blurry-vision episodes at age 6, Kelby initially believed it was a new version of the same problem, and he kept a time stamp on his phone for each episode. But the records from Holden’s defibrillator showed that these times did not line up with any heart-rhythm problems.

The family’s pediatrician was confused, too. Perhaps Holden was having periods of low blood sugar, another possible Timothy syndrome complication, he suggested. Initial testing at the local medical center did not turn up clear answers.

But Kelby, who was training to become an operating room nurse, realized Holden’s episodes reminded him of what he was learning about warning signs for stroke. JJ called Holden’s cardiologist in Utah and asked for a detailed neurologic evaluation, which enabled the mysterious episodes to be diagnosed as seizures. Holden began taking anti-seizure medication, which helped, to his parents’ great relief.

Researching a rare disease

A few months after Holden was born, Sergiu Pasca , MD, arrived at Stanford Medicine to pursue a postdoctoral fellowship in the lab of Ricardo Dolmetsch, PhD, then an assistant professor of neurobiology, who was redirecting his research to autism spectrum disorder. At the time, Pasca did not know the Hulet family. But his work soon became focused on the disorder that has shaped Holden’s life.

Caused by a defective gene on the 12th chromosome, Timothy syndrome is vanishingly rare, with no more than 70 diagnosed cases. Children with this disorder rarely survive to late adolescence. It is caused by a mutation in the gene coding for a type of calcium channel — a protein containing a pore that selectively opens or closes, respectively permitting or blocking the flow of calcium across cells’ membranes. While a prominent feature — severe heart malfunction — can be tackled with a pacemaker, most children with Timothy syndrome will end up with lifelong brain disorders including autism, epilepsy and schizophrenia.

By mid-2009, Pasca had succeeded in generating nerve cells from induced pluripotent stem cells (which can be induced to form virtually any of the body’s numerous cell types). These included cells derived from the skin of two patients with Timothy syndrome. Later that year he observed defects in how the patient-derived neurons were handling calcium. This advance — the creation of one of the initial in-a-dish models of brain disease, built from neurons with defects that precisely mirrored those of a patient’s brain — was published in Nature Medicine in 2011.

Pasca and colleagues continued to monitor these Timothy-syndrome neurons in standard two-dimensional culture — growing as single layers in petri dishes — over the next few years. While this two-dimensional culture method was limited in its ability to sustain viable neurons, it was soon superseded by a genuine scientific breakthrough.

Pioneering the first assembloids

The constraints of two-dimensional culture, including the inability to keep these neurons for long periods of time so that they could reach key stages of neural development, prompted Pasca in 2011 to start developing an unprecedented three-dimensional method. The novel technology produced what came to be known as brain organoids. These constructs recapitulated some of the architecture and physiology of the human cerebral cortex. The organoids can survive for several years in culture, enabling neuroscientists to view, non-invasively, the developing human brain up close and in real time. The scientists wrote a seminal Nature Methods paper , published in 2015, that described their discovery.

Pasca’s group subsequently showed that culturing brain organoids in different ways could generate organoids representing different brain regions (in this case, the cerebral cortex and a fetal structure called the subpallium). In a breakthrough set of experiments, Pasca’s team found ways to bring these organoids into contact so that they fuse and forge complex neuronal connections mimicking those that arise during natural fetal and neonatal development. Pasca named such constructs assembloids.

In their paper on the research, which was published in Nature in 2017, Pasca’s team showed that after fusion, a class of inhibitory neurons originating in the subpallium migrates to the cortex, proceeding in discrete, stuttering jumps. (See animation .) These migrating neurons, called interneurons, upon reaching their destinations — excitatory neurons of the cortex — form complex circuits with those cortical neurons.

But in assembloids derived from Timothy syndrome patients, the motion of interneurons as they migrate from the subpallium is impaired — they jump forward more often, but each jump is considerably shorter, so they fail to integrate into the appropriate circuitry in the cortex. This wreaks havoc with signaling in cortical circuits. Pasca’s team tied this aberrant neuronal behavior on the part of Timothy syndrome neurons to the key molecular consequence of the genetic defect responsible for the condition: namely, malfunction of the critical channels through which calcium must pass to cross neurons’ outer membranes.

A family’s struggles

While Pasca was developing assembloids, the Hulet family was progressing through their own journey of discovery with Holden. They faced painful uncertainty at every stage, starting when Holden was discharged from the NICU in the summer of 2009, after several months of hospitalization and multiple heart surgeries.

“Even when we brought him home, [his doctors] said ‘Don’t get your hopes up. We don’t usually see them make it past age 2,” JJ recalled. Many children with Timothy syndrome die from cardiac failure in early life.

“It’s really hard to be positive in that kind of situation, and for a long time I did let it get to me,” JJ said. “I finally got to a point where I said, ‘I have to live my life and we just keep fighting.’”

JJ runs a child care center and has years of experience working with special-needs kids, which motivated her to push for an autism evaluation when she saw signs of autism in Holden. He’s much more verbal than many children with autism, which paradoxically made it more difficult to get an official diagnosis.

“That was frustrating,” JJ said. Although the family’s pediatric cardiologist in Salt Lake City was familiar with the vagaries of Timothy syndrome, their local caregivers in the small town where they live in southern Utah were not. “They kept saying ‘Oh, no, it’s just developmental delays because he was so premature,’” she said. She wonders whether it would have been easier to have Holden’s autism diagnosed had more been known about Timothy syndrome at the time.

“I think research is important so that parents and children have the support they need,” she said, noting how lonely and painful it can be to advocate for a child when his condition is poorly understood — and when, as a parent, you may be doubted by medical professionals. “It’s a really hard thing to deal with.”

Her voice breaks briefly. She continues, “I think research brings validity to that.”

Sergiu Pasca

Implanting organoids

In 2022, Pasca published a study in Nature describing the transplantation of human cortical organoids into neonatal rats’ brains, which resulted in the integration of human neurons along with supporting brain cells into the brain tissue of rats to form hybridized working circuits. The implanted human organoids survived, thrived and grew. Individual neurons from the human organoids integrated into young rats’ brains were at least six times as big as those — generated the same way, at the same time — that remained in a dish. The transplanted neurons also exhibited much more sophisticated branching patterns. Pasca and his colleagues observed marked differences in the electrical activity of, on one hand, human neurons generated from a Timothy syndrome patient, cultured as organoids and transplanted into one side of a rat’s brain, and, on the other hand, those generated from a healthy individual and transplanted, as an organoid, into the corresponding spot on the other side of the same rat’s brain. The Timothy syndrome neurons were also much smaller and were deficient in sprouting branching, brush-like extensions called dendrites, which act as antennae for input from nearby neurons.

“We’ve learned a lot about Timothy syndrome by studying organoids and assembloids kept in a dish,” Pasca said. “But only with transplantation were we able to convincingly see these neuronal-activity-related differences.”

That same year, the FDA Modernization Act 2.0 was signed into law, exempting certain categories of new drug-development protocols from previously mandated animal testing. The act was predicated on the understanding that recent advancements in science offer increasingly viable alternatives to animal testing, so the findings based on the organoid- and assembloid-culture technologies may be adequate to justify clinical trials in some neurodevelopmental conditions.

Most recently, in a Nature paper published April 24, Pasca and his colleagues demonstrated, in principle, the ability of antisense oligonucleotides (ASOs) to correct the fundamental defects that lead to Timothy syndrome by nudging calcium-channel production toward another form of the gene that does not carry the disease-causing mutation. Using ASOs to guide production of the functional rather than defective form of this channel reversed the defect’s detrimental downstream effects: Interneuronal migration proceeded similarly to that procedure in healthy brains, and the altered electrical properties of the calcium channel reverted to normalcy. This therapeutic correction was demonstrated in a lab dish — and, critically, in rat-transplantation experiments, suggesting that this therapeutic approach can work in a living organism.

Pasca is now actively searching the globe for carriers of the genetic defect, in preparation for the pursuit of a clinical trial at Stanford Medicine to test the safety and therapeutic potential of ASOs in mitigating the pathological features of Timothy syndrome.

“We are also actively engaged in conversations with other scientists, clinicians in the field and ethicists about the best way to move forward and safely bring this therapeutic approach into the clinic,” he said.

Pasca added that the calcium channel that is mutated in Timothy syndrome is, in fact, “the hub” of several neuropsychiatric diseases including schizophrenia and bipolar disorder. So it may be that the lessons learned — and the therapies derived — from his 15-year focus on a rare disease may have broad application in a number of widespread and troubling psychiatric conditions.

‘Amazing’ teenager

Today, in defiance of his doctors’ warning that he might not live past age 2, Holden Hulet is 15 years old and doing well.

“I think a lot of times, autism is perceived as ‘They’re not neurotypical and they’re not capable of certain things.’ But he is brilliant,” JJ said. “He’s amazing with techie stuff or Legos. He’s funny and super honest and very self-aware.”

Kelby often takes Holden to visit the farm where he grew up. Holden loves to ride the farm equipment and enjoys hanging out with the animals, especially the farm dogs and calves. Like a lot of kids, he keeps an eye out for good rocks, Kelby said with a chuckle.

“He’s always either throwing them or collecting them,” JJ said. “That’s something I really like about him: He’s always got a pocket full of something.”

Although navigating a rare disease is one of the most challenging things they have faced, the Hulets see light in their situation, and would offer encouragement to any family facing a new Timothy syndrome diagnosis.

“There is hope,” JJ said. “There are people out there who care, people out there who fight for you who don’t even know you. I think that’s what is so important about research — that you’re fighting a battle for people you don’t even know.”

The study published April 24 was supported by the National Institute of Mental Health (grants R01 MH115012 and K99 MH119319P), the Wu Tsai Neuroscience Institute, the Autism Speaks Postdoctoral Fellowship, the Kwan Funds, the Senkut Funds, the Coates Foundation, the Ludwig Family Foundation, the Alfred E. Mann Foundation, and the Stanford Maternal and Child Health Research Institute Postdoctoral Fellowship.

About Stanford Medicine

Stanford Medicine is an integrated academic health system comprising the Stanford School of Medicine and adult and pediatric health care delivery systems. Together, they harness the full potential of biomedicine through collaborative research, education and clinical care for patients. For more information, please visit med.stanford.edu .

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Neonatal Nursing Research Paper Topics

Neonatal nursing research paper topics are a critical area of study due to the sensitive and crucial nature of neonatal care. Neonatal nursing focuses on providing care for newborn infants during their first 28 days of life, a period that is often marked by various health challenges. This field of nursing encompasses a wide range of topics including neonatal respiratory care, nutrition, developmental care, and ethical issues, among others. Conducting research on these topics helps in developing evidence-based practices and interventions that can improve the quality of care provided to neonates and their families.

100 Neonatal Nursing Research Paper Topics

Neonatal nursing is a specialty that focuses on the care of newborn infants who have a variety of medical needs, ranging from being born prematurely to having congenital abnormalities or infections. Neonatal nursing research paper topics are diverse and comprehensive as they cover a wide range of areas that are critical to the field. These topics are essential in helping researchers and practitioners develop effective strategies for providing the best possible care to these vulnerable infants. It is important for students, professionals, and researchers to delve into these topics to better understand the challenges faced in neonatal nursing and develop innovative solutions.

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Neonatal Respiratory Care

The effectiveness of different ventilation strategies for neonates with respiratory distress syndrome.
The role of surfactant therapy in the management of neonatal respiratory distress syndrome.
The impact of maternal smoking on neonatal respiratory outcomes.
Strategies for preventing bronchopulmonary dysplasia in preterm infants.
The role of non-invasive ventilation in neonatal respiratory care.
Evaluation of the effectiveness of pulmonary function tests in neonates.
The impact of infection on neonatal respiratory outcomes.
The use of nitric oxide in the management of persistent pulmonary hypertension of the newborn.
The role of antenatal corticosteroids in improving neonatal respiratory outcomes.
Strategies for managing apnea of prematurity.

Infection and Immunization in Neonates

The effectiveness of different vaccination schedules in neonates.
The impact of maternal infections on neonatal outcomes.
Strategies for preventing nosocomial infections in the neonatal intensive care unit.
The role of antibiotics in the management of neonatal sepsis.
The impact of maternal immunization on neonatal infection rates.
Strategies for managing neonatal herpes simplex virus infection.
The effectiveness of intravenous immunoglobulin in the management of neonatal infections.
The role of probiotics in the prevention of necrotizing enterocolitis.
Strategies for managing congenital cytomegalovirus infection.
The impact of breastfeeding on neonatal infection rates.

Neonatal Nutrition

The impact of maternal nutrition on neonatal outcomes.
The effectiveness of different feeding strategies for preterm infants.
The role of human milk fortifiers in the nutrition of preterm infants.
Strategies for managing neonatal hypoglycemia.
The impact of early enteral feeding on the outcomes of preterm infants.
The role of parenteral nutrition in the management of critically ill neonates.
Strategies for managing neonatal hyperbilirubinemia.
The impact of breastfeeding on the long-term outcomes of neonates.
The role of vitamin D supplementation in the prevention of rickets in neonates.
Strategies for managing neonatal gastroesophageal reflux disease.

Developmental Care in Neonatology

The impact of early intervention programs on the developmental outcomes of preterm infants.
The effectiveness of kangaroo mother care in the management of preterm infants.
The role of music therapy in the development of neonates in the NICU.
Strategies for managing neonatal sleep disorders.
The impact of light and noise levels on the developmental outcomes of neonates in the NICU.
The role of touch and massage therapy in the development of neonates.
Strategies for managing neonatal stress and pain.
The impact of parental involvement on the developmental outcomes of neonates in the NICU.
The role of physical therapy in the development of neonates with congenital abnormalities.
Strategies for managing developmental delays in neonates.

Ethical Issues in Neonatal Care

The ethics of resuscitating extremely preterm infants.
The role of parents in decision-making for critically ill neonates.
Strategies for managing conflicts between healthcare providers and parents in the NICU.
The ethics of organ donation from neonates.
The impact of religious and cultural beliefs on decision-making in neonatal care.
The role of palliative care in the management of critically ill neonates.
Strategies for managing ethical dilemmas in neonatal research.
The impact of resource limitations on decision-making in neonatal care.
The role of advance directives in the management of critically ill neonates.
Strategies for managing ethical dilemmas in the use of experimental therapies in neonates.

Parental Involvement and Support

The impact of parental involvement on the outcomes of neonates in the NICU.
Strategies for improving communication between healthcare providers and parents in the NICU.
The role of peer support in the mental health of parents of neonates in the NICU.
Strategies for managing parental stress and anxiety in the NICU.
The impact of parental education on the outcomes of neonates in the NICU.
The role of family-centered care in the management of neonates in the NICU.
Strategies for managing parental grief and loss in the NICU.
The impact of parental mental health on the developmental outcomes of neonates.
The role of social support in the mental health of parents of neonates in the NICU.
Strategies for managing parental expectations in the NICU.

Neonatal Intensive Care Unit (NICU) Management

The impact of nurse staffing levels on the outcomes of neonates in the NICU.
Strategies for preventing medication errors in the NICU.
The role of simulation training in improving the skills of healthcare providers in the NICU.
Strategies for managing neonatal transport between hospitals.
The impact of telemedicine on the management of neonates in the NICU.
The role of continuous quality improvement in the management of the NICU.
Strategies for managing conflicts between healthcare providers in the NICU.
The impact of electronic health records on the management of neonates in the NICU.
The role of multidisciplinary teams in the management of neonates in the NICU.
Strategies for managing ethical dilemmas in the allocation of resources in the NICU.

Neonatal Pain Management

The effectiveness of different pain assessment tools in neonates.
Strategies for managing pain in neonates undergoing surgery.
The role of non-pharmacological interventions in the management of neonatal pain.
Strategies for managing pain in neonates with opioid withdrawal.
The impact of maternal analgesia on neonatal pain outcomes.
The role of parental involvement in the management of neonatal pain.
Strategies for managing pain in neonates with chronic illnesses.
The impact of pain management on the developmental outcomes of neonates.
The role of acupuncture in the management of neonatal pain.
Strategies for managing pain in neonates undergoing invasive procedures.

Technological Advancements in Neonatal Care

The impact of telemedicine on the management of neonatal illnesses.
Strategies for using wearable technology in the monitoring of neonates.
The role of artificial intelligence in the diagnosis and management of neonatal diseases.
Strategies for using electronic health records to improve the outcomes of neonates.
The impact of simulation training on the skills of healthcare providers in neonatal care.
The role of point-of-care ultrasound in the diagnosis and management of neonatal illnesses.
Strategies for using mobile applications to improve communication between healthcare providers and parents of neonates.
The impact of virtual reality on the training of healthcare providers in neonatal care.
The role of remote monitoring in the management of neonates with chronic illnesses.
Strategies for using 3D printing in the management of neonatal congenital abnormalities.

Long-term Outcomes of Premature Infants

The impact of early intervention programs on the long-term developmental outcomes of premature infants.
Strategies for managing long-term respiratory complications in premature infants.
The role of nutritional interventions in the long-term outcomes of premature infants.
Strategies for managing long-term neurodevelopmental complications in premature infants.
The impact of parental involvement on the long-term outcomes of premature infants.
The role of physical therapy in the long-term outcomes of premature infants with congenital abnormalities.
Strategies for managing long-term mental health complications in premature infants.
The impact of early socialization on the long-term outcomes of premature infants.
The role of educational interventions in the long-term outcomes of premature infants.
Strategies for managing long-term metabolic complications in premature infants.

Neonatal nursing is a critical and evolving field that requires continuous research and development. The neonatal nursing research paper topics provided above offer a comprehensive list of areas that can be explored by students, professionals, and researchers alike. These topics are essential for developing evidence-based practices and interventions that can improve the quality of care provided to neonates and their families. It is encouraged that those in the field of neonatal nursing explore these topics and contribute to the body of knowledge that is essential for the growth and development of this important field.

The Range of Neonatal Nursing Research Paper Topics

Neonatal nursing is a specialized area of nursing that focuses on providing care for newborn infants during their first 28 days of life, a critical period that sets the foundation for a child’s future health and well-being. This field of nursing is incredibly significant as it involves caring for the most vulnerable patients – newborns who are experiencing a variety of health challenges, from prematurity and low birth weight to congenital abnormalities and infections. Neonatal nurses play a crucial role in not only providing immediate care for these infants but also in educating and supporting their families during this stressful time. Due to the diverse and complex nature of neonatal care, there are a plethora of neonatal nursing research paper topics that can be explored to develop new insights and improve current practices.

One important aspect of neonatal nursing is neonatal respiratory care. Respiratory distress is common in newborns, particularly in premature infants whose lungs may not be fully developed. Neonatal nurses must be well-versed in the various interventions and technologies used to support neonatal respiratory function, from supplemental oxygen and mechanical ventilation to surfactant therapy and non-invasive ventilation techniques. Research in this area is crucial to developing new strategies for preventing and managing respiratory distress in neonates, as well as for evaluating the long-term outcomes of different interventions. For example, a neonatal nursing research paper topic in this area could focus on comparing the effectiveness of different ventilation strategies in neonates with respiratory distress syndrome or evaluating the long-term outcomes of neonates treated with surfactant therapy.

Another key aspect of neonatal nursing is the prevention and management of infections and the administration of immunizations in neonates. Neonates, especially those born prematurely, have an immature immune system and are at a higher risk of developing infections. Therefore, it is crucial for neonatal nurses to have a thorough understanding of the common infections that affect neonates, the strategies for preventing these infections, and the appropriate immunizations that should be administered. Neonatal nursing research paper topics in this area could focus on evaluating the effectiveness of different strategies for preventing nosocomial infections in the neonatal intensive care unit (NICU), or assessing the impact of maternal immunization on neonatal infection rates.

Parental involvement and support are also crucial aspects of neonatal nursing. The birth of a child is a significant event in a family’s life, and it can be particularly stressful when the child is ill or requires specialized care in the NICU. Neonatal nurses play a critical role in supporting parents during this time, by providing education about their infant’s condition and care, facilitating bonding between the infant and parents, and providing emotional support. Research in this area is important for developing strategies to improve parental involvement and support in the NICU, as well as for evaluating the impact of these strategies on neonatal and parental outcomes. For instance, a neonatal nursing research paper topic in this area could focus on assessing the impact of family-centered care interventions on parental stress and anxiety levels in the NICU.

In addition to these specific areas, there are many other neonatal nursing research paper topics that can be explored. For example, research could focus on evaluating the effectiveness of different pain assessment and management strategies in neonates, assessing the impact of developmental care interventions on the long-term outcomes of preterm infants, or evaluating the ethical dilemmas that arise in the care of critically ill neonates. Ultimately, research in all of these areas is crucial for developing evidence-based practices and interventions that can improve the quality of care provided to neonates and their families.

In conclusion, neonatal nursing is a critical field that involves caring for the most vulnerable patients and supporting their families during a stressful time. There are a wide range of neonatal nursing research paper topics that can be explored to develop new insights and improve current practices in various aspects of neonatal nursing, such as neonatal respiratory care, infection and immunization in neonates, and parental involvement and support. It is encouraged that those in the field of neonatal nursing explore these topics and contribute to the body of knowledge that is essential for the growth and development of this important field.

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NICU Research Ideas & Topics to Consider

Nicu practice and evidence-based research is constantly changing. many of the practices i have seen over the past 9+ years have changed with updates, new technology, procedures, and treatments, with a movement to push our patient population forward with improved outcomes.

Here are a few topics to consider when searching for a research project, paper, or developing an abstract for your project! Many of these are controversial with a lot of different research supporting various outcomes.

NICU Research Project Ideas

Double jeopardy. what do we know and what can we do.

Common comorbidities of prematurity.

Intraventricular hemorrhage

Bronchopulmonary Dysplasia

Necrotizing Enertocolities

Retinopathy of Prematurity

Congenital heart Disease (CHD)

NEC! WHAT FACTORS INCREASE THE RISK OF NEC?

Standardization of assessments and treatments, Pneumoatosis, Is Clonic Pneumotosis real?, Treatment and feeding decisions, Guidelines, Antibiotics, Parenteral Nutrition, Vascular Access, Imaging Modalities, Hemodynamics, disease entity, restriction of systemic blood flow, generalized cyanotic state, Congenital Heart Disease (CHD).

https://www.nature.com/articles/pr2016215

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6181543/

SMALL BABY STANDARDIZATION OF CARE

The formation and focus on standardizing ELBW and VLBW care. Guidelines, standardization, and streamlined care. Feedings, humidity, positioning, weights, lab draws central line management, RDS management, guidelines for incubations/extubations, weaning from isolette to crib, developmental considerations by gestational age.

https://engagegrowthrive.com/small-baby-care-specialist-program/

https://pubmed.ncbi.nlm.nih.gov/34330869/

PROBIOTICS!

The use of probiotics in practice (to use or not to use them). Gut flora. The pros and cons. Latest research in preventing NEC. Is this a preventative measure? Which probiotic products to consider? Lactobacillus, dual strains, and possible side effects or contraindications.

https://www.sciencedirect.com/science/article/abs/pii/S0378378219302932

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7303425/

https://www.degruyter.com/document/doi/10.1515/jpm-2019-0268/html

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6805101/

PDA TREATMENT

Treatment of PDA. When to treat it and what modalities to treat it with…Indomethacin, PICCOLO PDA closure device, PEEP, etc). Risk vs Benefit. Clinical signs and symptoms.

https://www.sciencedirect.com/science/article/abs/pii/S0022347618309181

https://www.sciencedirect.com/science/article/abs/pii/S0146000518300326

SKIN TO SKIN

Skin to skin (myth-busting nicu dynamics when parents can’t hold). Developmental considerations. How to support families during the initial times with inability to hold baby.

https://www.sciencedirect.com/science/article/abs/pii/S1751485118302356

https://connect.springerpub.com/content/sgrnn/37/6/343.abstract?implicit-login=true

https://connect.springerpub.com/content/sgrnn/36/2/89?implicit-login=true

PAIN MANAGEMENT IN THE NEONATE

Anesthesia / Sedation! What is too much? What is not enough? Neurodevelopment perspectives with Gestational age & disease process. Nociceptive stimuli. Neuroapoptosis. Pain consequences with unrelieved pain, sleep, fatigue, and inflammatory response. Pre and Post-op considerations. The first line of pain relief modalities. Benzodiazepines, Opiates, Alpha 2 Agonists (Dexmedetomidine, Clonadine), Sweeties, Positioning etc.

https://journals.lww.com/advancesinneonatalcare/Abstract/2009/12000/Exploring_Barriers_to_Pain_Management_in_Newborn.10.aspx

https://www.nature.com/articles/jp201788

https://www.sciencedirect.com/science/article/abs/pii/S0146000516301161

BLOOD PRESSURE GOALS & STANDARDIZATION

Lack of standardization within the NICU patient population. What is too low? What is too high? Treating symptoms. What line of hemodynamic modalities to turn to? (Epi / Vasopressin / Dopamine)

https://www.thieme-connect.com/products/ejournals/abstract/10.1055/s-0041-1726123

https://www.sciencedirect.com/science/article/abs/pii/S0022347620302869

VENTILATOR STRATEGIES

Specific considerations for Gestational age, disease-specific treatments. Optimal PEEP, Low peak inflation/TV. Use of surfactant. Surfactant deficiencies (RDS), Corticosteroids, Alkalosis etc.

https://www.nature.com/articles/s41372-022-01399-1

SATURATION TARGET GOALS

Optimizing neurodevelopment, Target pre ductal SpO2. Oxygen should be used like any other drug; with potential benefits and side effects. Positioning considerations.

https://fn.bmj.com/content/96/2/F93.short

https://publications.aap.org/pediatrics/article-abstract/136/2/e496/33808/Balancing-the-Tension-Between-Hyperoxia-Prevention

PALLIATIVE CARE

Multidisciplinary approach. Women facing pregnancies with a diagnosis of complex congenital or life-threatening conditions. Limitations in choices. Support during pregnancy, delivery, post-partum, and beyond.

https://journals.lww.com/advancesinneonatalcare/Abstract/2020/04000/Preparing_Nurses_for_Palliative_Care_in_the_NICU.9.aspx?context=LatestArticles

https://journals.lww.com/co-pediatrics/Abstract/2017/04000/Neonatal_palliative_care.3.aspx

PRETERM INFANTS WITH CHD

Congenital Heart Disease issues. Cyanosis (TOF & TGA), pulmonary venous obstruction, (TAPVD, MS), Preoperative care, Preoperative pulmonary vasculature/reactivity (Trisomy 21, post RSV, transitional circulation). Neurodevelopment risk associated with prematurity. Restricted oxygen and insufficient nutrient delivery in utero.

https://assets.researchsquare.com/files/rs-1741684/v1/9490f182-82ce-4cc9-b3f9-40689bd5b67c.pdf?c=1655971172

BREAST MILK PRODUCTION & BREASTFEEDING INITIATIVES

The push for breast is best (doesn’t always work in the NICU). Breast milk production, the latest Evidence-Based Research to support mothers.

Hope this list helps you in your NICU Research! These are all very relevant in our NICU care with continued improvements in Evidence-Based Research! The more minds and research we can put to these topics the better. Feel free to drop your suggestions and comments below!

Tori Meskin BSN RNC-NIC. Nurse. Blogger. Podcaster. Tori has been a clinician since 2012 and works in acute care/inpatient NICU & Pediatric settings in southern California. She is a blogger, podcaster, NICU & Pediatric Critical Care RN, S ponsored Capella University MSN student , & Brave beginnings Ambassador. She has obtained her National NICU Nurse Certification (RNC-NIC) & has previously worked as a travel nurse, pursuing bedside experiences in several NICU settings. Follow her as she shares her NICU journey in married life & juggles work, school, and content creation, & brings you top notch Tips & Tricks along the way. Find her at www.tipsfromtori.com or [email protected]

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70+ research topics on neonatal nursing: a complete guide, carla johnson.

August 25, 2023
Essay Topics and Ideas

Neonatal nursing is a pillar of hope and care for the most delicate and vulnerable members of society – newborn babies. Aspiring nurses embarking on this journey may encounter challenges and rewards unlike any other. This article provides several research topics on neonatal nursing , project ideas, and questions for comprehensive research papers.

What You'll Learn

Understanding Neonatal Nursing

Neonatal nursing is a specialized branch that focuses on the care of newborn infants, particularly those born prematurely, have medical complications, or require surgical interventions. The neonatal nurse’s role extends beyond medical care, encompassing emotional support for infants and their families. These nurses work in neonatal intensive care units (NICUs), providing round-the-clock monitoring, administering treatments, and ensuring the optimal growth and development of the infants.

Exploring PICOT Questions in Neonatal Nursing

P: Preterm infants in the NICU; I: Implementation of developmental care techniques; C: Conventional care methods; O: Enhanced neurodevelopmental outcomes; T: 12 months. In the realm of neonatal care , how does the implementation of developmental care techniques in the NICU affect the neurodevelopmental outcomes of preterm infants compared to conventional care methods over a period of 12 months?
P: Neonates with neonatal abstinence syndrome; I: Breast milk feeding with pharmacological treatment; C: Formula feeding with pharmacological treatment; O: Duration of treatment and weight gain; T: 3 weeks. For neonates suffering from neonatal abstinence syndrome, what is the impact of breast milk feeding along with pharmacological treatment on the duration of treatment and weight gain compared to formula feeding with pharmacological treatment within a span of 3 weeks?
P: Newborns with congenital heart defects; I: Early surgical intervention; C: Delayed surgical intervention; O: Mortality rate and postoperative complications; T: 6 months. Among newborns diagnosed with congenital heart defects, how does the timing of surgical intervention (early vs. delayed) relate to mortality rate and postoperative complications over a period of 6 months?
P: Low birth weight infants; I: Implementation of skin-to-skin contact; C: Traditional incubator care; O: Temperature regulation and weight gain; T: 4 weeks. In the case of low birth weight infants, what is the effect of implementing skin-to-skin contact in comparison to traditional incubator care on temperature regulation and weight gain over a span of 4 weeks?
P: Neonates on mechanical ventilation; I: Nurse-led sedation management; C: Physician-led sedation management; O: Duration of mechanical ventilation and sedation-related complications; T: Until extubation. For neonates receiving mechanical ventilation, how does nurse-led sedation management influence the duration of mechanical ventilation and the occurrence of sedation-related complications as compared to physician-led management until extubation?
P: Newborns with hypoglycemia; I: Use of early breastfeeding ; C: Delayed breastfeeding initiation; O: Blood glucose levels and length of hospital stay; T: 48 hours. Among newborns diagnosed with hypoglycemia, what is the impact of early breastfeeding initiation on blood glucose levels and length of hospital stay compared to delayed breastfeeding initiation within the first 48 hours of life?
P: Infants exposed to maternal smoking during pregnancy; I: Nicotine replacement therapy for mothers; C: No nicotine replacement therapy; O: Incidence of neonatal withdrawal symptoms; T: 2 weeks. For infants exposed to maternal smoking during pregnancy, how does the administration of nicotine replacement therapy for mothers affect the incidence of neonatal withdrawal symptoms compared to cases where no nicotine replacement therapy is provided over a period of 2 weeks?
P: Late preterm infants; I: Exclusive breastfeeding; C: Mixed feeding (breast milk and formula); O: Rates of hospital readmission due to feeding-related issues; T: 1 month. Among late preterm infants, what is the association between exclusive breastfeeding and mixed feeding with rates of hospital readmission due to feeding-related issues within the first month of life?
P: Neonates undergoing therapeutic hypothermia; I: Parental involvement in care; C: Standard nursing care; O: Parent-infant bonding and long-term neurodevelopmental outcomes; T: 2 years. When neonates are subjected to therapeutic hypothermia, how does parental involvement in care compared to standard nursing care influence parent-infant bonding and long-term neurodevelopmental outcomes over a span of 2 years?
P: Infants born to mothers with gestational diabetes; I: Blood glucose monitoring for neonates; C: No blood glucose monitoring; O: Incidence of hypoglycemia and length of hospital stay; T: Until discharge. In the case of infants born to mothers with gestational diabetes, what is the effect of blood glucose monitoring for neonates on the incidence of hypoglycemia and the length of hospital stay compared to cases where no blood glucose monitoring is performed until discharge?

10 EBP Project Ideas in Neonatal Nursing

Assessing the impact of kangaroo care on preterm infants’ weight gain.
Evaluating the effectiveness of music therapy in reducing pain perception among neonates undergoing procedures.
Implementing a standardized protocol for the management of neonatal sepsis.
Investigating the influence of noise reduction strategies on the neurodevelopment of NICU infants.
Developing guidelines for safe transport of critically ill neonates between hospitals.
Creating an educational program for parents of NICU graduates to enhance developmental outcomes.
Examining the effects of neonatal massage on neonates’ growth and overall well-being.
Investigating the role of neonatal nurses in promoting family-centered care in the NICU.
Developing a pain assessment tool specifically tailored for neonates.
Exploring the benefits of using breast milk fortifiers in improving the nutritional status of preterm infants.

Neonatal Nursing Capstone Project Ideas

Designing a comprehensive training program for neonatal nurses on caring for infants with complex congenital anomalies.
Evaluating the implementation of individualized developmental care plans in the NICU and their impact on outcomes.
Creating a resource guide for parents of premature infants, addressing their emotional and informational needs.
Developing a communication strategy for effective interdisciplinary collaboration in the neonatal intensive care unit.
Investigating the long-term effects of neonatal pain management techniques on later developmental milestones.
Designing a protocol for early identification and management of neonatal withdrawal symptoms.
Exploring the ethical considerations in decision-making for extremely premature infants.
Developing guidelines for supporting neonates’ transition from NICU to home care .
Assessing the utilization of technology in enhancing parent-infant bonding in the NICU.
Creating an educational module on neonatal palliative care for healthcare providers.

10 Nursing Research Paper Topics in Neonatal Nursing

Impact of neonatal skin-to-skin contact on maternal mental health.
Comparative analysis of the nutritional content of human milk and formula for preterm infants.
Neonatal pain assessment tools: A critical review.
Factors influencing parental stress in the NICU.
Neuroprotective strategies for preventing brain injury in neonates.
Trends in neonatal mortality rates and contributing factors.
The role of neonatal nurses in promoting breastfeeding in the NICU.
Addressing cultural disparities in neonatal care outcomes.
Parental experiences of having a newborn in the NICU: A qualitative exploration.
Long-term cognitive and developmental outcomes of extremely low birth weight infants.

Neonatal Nursing Research Questions

How do parental socioeconomic factors impact neonatal outcomes in the NICU?
What are the challenges and benefits of implementing family-centered care in the NICU?
How does kangaroo care influence the physiological stability of preterm infants?
What interventions are most effective in preventing hospital-acquired infections among neonates?
What are the experiences of neonatal nurses in providing end-of-life care?
How does the type of feeding (breast milk vs. formula) affect the microbiome of premature infants?
What are the long-term effects of maternal substance abuse on neonatal development?
How can neonatal nurses contribute to the prevention of retinopathy of prematurity?
What are the psychological impacts of prolonged NICU stays on parents?
How does noise exposure in the NICU impact neonatal stress levels and neurodevelopment?

20 Neonatal Nursing Essay Topic Ideas & Examples

The Role of Neonatal Nurses in Promoting Bonding Between Parents and Infants in the NICU.
Ethical Dilemmas in Neonatal Palliative Care: Navigating Complex Decision-Making.
Neonatal Abstinence Syndrome: A Comprehensive Review of Treatment Strategies.
Prematurity and Neurodevelopmental Outcomes: Exploring the Link.
Cultural Competence in Neonatal Nursing: Providing Care Across Diverse Backgrounds.
Neonatal Pain Management: Challenges and Innovations.
The Impact of NICU Design on Neonatal Development and Outcomes.
Neonatal Infections: Causes, Prevention, and Treatment Approaches.
The Role of Neonatal Nurses in Supporting Breastfeeding for Premature Infants.
Neonatal Transport: Ensuring Safe Passage for Critically Ill Infants.
Neonatal Nutrition: Breast Milk vs. Formula for Preterm Infants.
Parental Experiences of Having a Newborn in the NICU: A Personal Perspective.
Promoting Neuroprotection in Neonatal Care: Strategies and Best Practices.
Neonatal Hearing Screening Programs: Identifying Hearing Impairments Early.
Neonatal Pain Assessment : Tools, Challenges, and Future Directions.
Neonatal Abandonment: Addressing Legal and Ethical Considerations.
Neonatal Resuscitation: Techniques, Guidelines, and Training.
Neonatal Brain Development: The Role of Early Intervention Programs.
Neonatal Jaundice: Causes, Complications, and Phototherapy Interventions.
Maternal and Neonatal Health Disparities : Strategies for Improvement.

As you delve into neonatal nursing, you embark on a journey requiring empathy, resilience, and dedication. The countless lives you’ll touch, and the positive impact you’ll make are immeasurable. To further enhance your understanding and contribution to neonatal care, consider exploring these research avenues and project ideas. However, if the demands of academic life become overwhelming, remember that seeking assistance is a sign of wisdom. Our writing services provide the support you need, allowing you to focus on honing your skills and knowledge as a future neonatal nurse. Your commitment to neonatal nursing is a testament to your passion for making a difference in the lives of the tiniest and most precious beings. Embrace this journey with an open heart and a determination to nurture the future, one baby at a time.

Frequently Asked Questions (FAQs) About Neonatal Nursing

Q: What is another name for a neonatal nurse? A: Neonatal nurses are also called NICU nurses, which stands for Neonatal Intensive Care Unit nurses.

Q: What is the difference between pediatric and neonatal nurses? A: While pediatric nurses and neonatal nurses work with children, pediatric nurses generally care for children from infancy through adolescence, while neonatal nurses specialize in caring for newborn infants, particularly those who are ill or premature.

Q: What is the study of neonatology called? A: Neonatology is the medical subspecialty that focuses on the care and treatment of newborn infants, particularly those born prematurely or with medical complications.

Q: Why is neonatal nursing important? A: Neonatal nursing is vital because it provides specialized care to the most vulnerable and fragile newborns. Neonatal nurses are critical in monitoring and supporting premature and sick infants’ growth, development, and health during their initial days, weeks, and sometimes months of life.

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Voluntary corporate emissions targets not enough to create real climate action

Companies' emissions reduction targets should not be the sole measure of corporate climate ambition, according to a new perspective paper.

Relying on emissions can favour more established companies and hinder innovation, say the authors, who suggest updating regulations to improve corporate climate action.

The paper, published today in Science , is by an international team led by Utrecht University, which includes Imperial College London researchers.

Lead author of the study Dr Yann Robiou Du Pont, from the Copernicus Institute of Sustainable Development at Utrecht University, said: "Assessing the climate ambition of companies based only on their emissions reductions may not be meaningful for emerging companies working on green innovation."

Companies can set individual climate goals, typically commitments to reduce greenhouse gas emissions from their activities -- not unlike national governments. To indicate how ambitious these voluntary commitments are, businesses can get them validated as 'Paris-aligned' under the Science Based Targets initiative (SBTi), a collaboration that started in 2015.

This validation means SBTi considers their targets to be aligned to the Paris Agreement, which aims to limit global temperature increase to well below 2°C above preindustrial levels and pursue efforts to limit it to 1.5°C.

The new paper says this approach may inadvertently favour larger existing companies, stifling innovation and skewing the playing field against emerging competitors. This is because Paris-aligned targets for larger, established companies often assume that they can simply keep their current market share of emissions, leaving no capacity for emissions from the activities of emerging companies.

For example, a new solar panel manufacturer that needs to grow its emissions ten years from now while it scales up a new, highly efficient method of building those panels, may be squeezed out of the market because, in this model, their operation would mean overshooting the Paris-aligned climate goal.

Dr Robiou Du Pont said: "These voluntary corporate targets may have been useful to achieve some progress on emissions reduction in the largest companies. But our paper shows that this approach is not sufficient to guide the corporate sector and cannot be the sole basis for regulations assessing if businesses are Paris-compliant."

To level the playing field, the authors say corporate climate targets could be based on other factors than reductions in emissions, such as emissions intensity per unit of economic or physical output. These types of targets however are harder to align to Paris Agreement targets, as they don't cap absolute emissions.

The study also highlights that adopting a target doesn't necessarily cause a drop in actual emissions, as voluntary targets are just that. The authors point to evidence that corporations are already using these voluntary targets, often of questionable credibility, as justification for watering down or delaying mandatory regulations.

Co-author Professor Joeri Rogelj, from the Centre for Environmental Policy and Director of Research at the Grantham Institute at Imperial College London, said: "Companies setting their own individual targets risk complacency that we can't afford. The window to keep the planet to 1.5°C warming is rapidly closing, and even for keeping warming well below the upper Paris limit of 2°C we need concerted action to reduce greenhouse gas emissions now. Voluntary corporate emissions targets alone are not enough for rapid global decarbonization and certainly not a substitute for regulation."

The authors conclude that governments or intergovernmental organisations need to introduce legal frameworks based on a range of indicators that encourage best practices and innovation, as well as stringent requirements on transparency for any assessments.

The toolkit for building those frameworks exists, argue the authors, including carbon pricing, green subsidies and demand-side measures. Regulators should also consider the usefulness of the products that companies produce in the green transition, not only their emissions. Under a revised framework, the more efficient solar panel manufacturer would not have to constrain production, allowing for needed innovation with spillover effects in the future.

Co-author Professor Detlef van Vuuren, also from the Copernicus Institute of Sustainable Development at Utrecht University, said: "Our research underscores the urgent need for robust regulatory frameworks and transparent oversight to guide corporate climate action. Voluntary targets, while commendable, are not a substitute for mandatory regulations that ensure accountability and drive innovation across all sectors."

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Yann Robiou du Pont, Joeri Rogelj, Angel Hsu, Detlef van Vuuren, Andreas G. F. Hoepner. Corporate emissions targets and the neglect of future innovators . Science , 2024; 384 (6694): 388 DOI: 10.1126/science.adl5081

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Researchers detect a new molecule in space

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New research from the group of MIT Professor Brett McGuire has revealed the presence of a previously unknown molecule in space. The team's open-access paper, “ Rotational Spectrum and First Interstellar Detection of 2-Methoxyethanol Using ALMA Observations of NGC 6334I ,” appears in April 12 issue of The Astrophysical Journal Letters .

Zachary T.P. Fried , a graduate student in the McGuire group and the lead author of the publication, worked to assemble a puzzle comprised of pieces collected from across the globe, extending beyond MIT to France, Florida, Virginia, and Copenhagen, to achieve this exciting discovery.

“Our group tries to understand what molecules are present in regions of space where stars and solar systems will eventually take shape,” explains Fried. “This allows us to piece together how chemistry evolves alongside the process of star and planet formation. We do this by looking at the rotational spectra of molecules, the unique patterns of light they give off as they tumble end-over-end in space. These patterns are fingerprints (barcodes) for molecules. To detect new molecules in space, we first must have an idea of what molecule we want to look for, then we can record its spectrum in the lab here on Earth, and then finally we look for that spectrum in space using telescopes.”

Searching for molecules in space

The McGuire Group has recently begun to utilize machine learning to suggest good target molecules to search for. In 2023, one of these machine learning models suggested the researchers target a molecule known as 2-methoxyethanol.

“There are a number of 'methoxy' molecules in space, like dimethyl ether, methoxymethanol, ethyl methyl ether, and methyl formate, but 2-methoxyethanol would be the largest and most complex ever seen,” says Fried. To detect this molecule using radiotelescope observations, the group first needed to measure and analyze its rotational spectrum on Earth. The researchers combined experiments from the University of Lille (Lille, France), the New College of Florida (Sarasota, Florida), and the McGuire lab at MIT to measure this spectrum over a broadband region of frequencies ranging from the microwave to sub-millimeter wave regimes (approximately 8 to 500 gigahertz).

The data gleaned from these measurements permitted a search for the molecule using Atacama Large Millimeter/submillimeter Array (ALMA) observations toward two separate star-forming regions: NGC 6334I and IRAS 16293-2422B. Members of the McGuire group analyzed these telescope observations alongside researchers at the National Radio Astronomy Observatory (Charlottesville, Virginia) and the University of Copenhagen, Denmark.

“Ultimately, we observed 25 rotational lines of 2-methoxyethanol that lined up with the molecular signal observed toward NGC 6334I (the barcode matched!), thus resulting in a secure detection of 2-methoxyethanol in this source,” says Fried. “This allowed us to then derive physical parameters of the molecule toward NGC 6334I, such as its abundance and excitation temperature. It also enabled an investigation of the possible chemical formation pathways from known interstellar precursors.”

Looking forward

Molecular discoveries like this one help the researchers to better understand the development of molecular complexity in space during the star formation process. 2-methoxyethanol, which contains 13 atoms, is quite large for interstellar standards — as of 2021, only six species larger than 13 atoms were detected outside the solar system , many by McGuire’s group, and all of them existing as ringed structures.

“Continued observations of large molecules and subsequent derivations of their abundances allows us to advance our knowledge of how efficiently large molecules can form and by which specific reactions they may be produced,” says Fried. “Additionally, since we detected this molecule in NGC 6334I but not in IRAS 16293-2422B, we were presented with a unique opportunity to look into how the differing physical conditions of these two sources may be affecting the chemistry that can occur.”

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How Pew Research Center will report on generations moving forward

Journalists, researchers and the public often look at society through the lens of generation, using terms like Millennial or Gen Z to describe groups of similarly aged people. This approach can help readers see themselves in the data and assess where we are and where we’re headed as a country.

Pew Research Center has been at the forefront of generational research over the years, telling the story of Millennials as they came of age politically and as they moved more firmly into adult life . In recent years, we’ve also been eager to learn about Gen Z as the leading edge of this generation moves into adulthood.

But generational research has become a crowded arena. The field has been flooded with content that’s often sold as research but is more like clickbait or marketing mythology. There’s also been a growing chorus of criticism about generational research and generational labels in particular.

Recently, as we were preparing to embark on a major research project related to Gen Z, we decided to take a step back and consider how we can study generations in a way that aligns with our values of accuracy, rigor and providing a foundation of facts that enriches the public dialogue.

A typical generation spans 15 to 18 years. As many critics of generational research point out, there is great diversity of thought, experience and behavior within generations.

We set out on a yearlong process of assessing the landscape of generational research. We spoke with experts from outside Pew Research Center, including those who have been publicly critical of our generational analysis, to get their take on the pros and cons of this type of work. We invested in methodological testing to determine whether we could compare findings from our earlier telephone surveys to the online ones we’re conducting now. And we experimented with higher-level statistical analyses that would allow us to isolate the effect of generation.

What emerged from this process was a set of clear guidelines that will help frame our approach going forward. Many of these are principles we’ve always adhered to , but others will require us to change the way we’ve been doing things in recent years.

Here’s a short overview of how we’ll approach generational research in the future:

We’ll only do generational analysis when we have historical data that allows us to compare generations at similar stages of life. When comparing generations, it’s crucial to control for age. In other words, researchers need to look at each generation or age cohort at a similar point in the life cycle. (“Age cohort” is a fancy way of referring to a group of people who were born around the same time.)

When doing this kind of research, the question isn’t whether young adults today are different from middle-aged or older adults today. The question is whether young adults today are different from young adults at some specific point in the past.

To answer this question, it’s necessary to have data that’s been collected over a considerable amount of time – think decades. Standard surveys don’t allow for this type of analysis. We can look at differences across age groups, but we can’t compare age groups over time.

Another complication is that the surveys we conducted 20 or 30 years ago aren’t usually comparable enough to the surveys we’re doing today. Our earlier surveys were done over the phone, and we’ve since transitioned to our nationally representative online survey panel , the American Trends Panel . Our internal testing showed that on many topics, respondents answer questions differently depending on the way they’re being interviewed. So we can’t use most of our surveys from the late 1980s and early 2000s to compare Gen Z with Millennials and Gen Xers at a similar stage of life.

This means that most generational analysis we do will use datasets that have employed similar methodologies over a long period of time, such as surveys from the U.S. Census Bureau. A good example is our 2020 report on Millennial families , which used census data going back to the late 1960s. The report showed that Millennials are marrying and forming families at a much different pace than the generations that came before them.

Even when we have historical data, we will attempt to control for other factors beyond age in making generational comparisons. If we accept that there are real differences across generations, we’re basically saying that people who were born around the same time share certain attitudes or beliefs – and that their views have been influenced by external forces that uniquely shaped them during their formative years. Those forces may have been social changes, economic circumstances, technological advances or political movements.

When we see that younger adults have different views than their older counterparts, it may be driven by their demographic traits rather than the fact that they belong to a particular generation.

The tricky part is isolating those forces from events or circumstances that have affected all age groups, not just one generation. These are often called “period effects.” An example of a period effect is the Watergate scandal, which drove down trust in government among all age groups. Differences in trust across age groups in the wake of Watergate shouldn’t be attributed to the outsize impact that event had on one age group or another, because the change occurred across the board.

Changing demographics also may play a role in patterns that might at first seem like generational differences. We know that the United States has become more racially and ethnically diverse in recent decades, and that race and ethnicity are linked with certain key social and political views. When we see that younger adults have different views than their older counterparts, it may be driven by their demographic traits rather than the fact that they belong to a particular generation.

Controlling for these factors can involve complicated statistical analysis that helps determine whether the differences we see across age groups are indeed due to generation or not. This additional step adds rigor to the process. Unfortunately, it’s often absent from current discussions about Gen Z, Millennials and other generations.

When we can’t do generational analysis, we still see value in looking at differences by age and will do so where it makes sense. Age is one of the most common predictors of differences in attitudes and behaviors. And even if age gaps aren’t rooted in generational differences, they can still be illuminating. They help us understand how people across the age spectrum are responding to key trends, technological breakthroughs and historical events.

Each stage of life comes with a unique set of experiences. Young adults are often at the leading edge of changing attitudes on emerging social trends. Take views on same-sex marriage , for example, or attitudes about gender identity .

Many middle-aged adults, in turn, face the challenge of raising children while also providing care and support to their aging parents. And older adults have their own obstacles and opportunities. All of these stories – rooted in the life cycle, not in generations – are important and compelling, and we can tell them by analyzing our surveys at any given point in time.

When we do have the data to study groups of similarly aged people over time, we won’t always default to using the standard generational definitions and labels. While generational labels are simple and catchy, there are other ways to analyze age cohorts. For example, some observers have suggested grouping people by the decade in which they were born. This would create narrower cohorts in which the members may share more in common. People could also be grouped relative to their age during key historical events (such as the Great Recession or the COVID-19 pandemic) or technological innovations (like the invention of the iPhone).

By choosing not to use the standard generational labels when they’re not appropriate, we can avoid reinforcing harmful stereotypes or oversimplifying people’s complex lived experiences.

Existing generational definitions also may be too broad and arbitrary to capture differences that exist among narrower cohorts. A typical generation spans 15 to 18 years. As many critics of generational research point out, there is great diversity of thought, experience and behavior within generations. The key is to pick a lens that’s most appropriate for the research question that’s being studied. If we’re looking at political views and how they’ve shifted over time, for example, we might group people together according to the first presidential election in which they were eligible to vote.

With these considerations in mind, our audiences should not expect to see a lot of new research coming out of Pew Research Center that uses the generational lens. We’ll only talk about generations when it adds value, advances important national debates and highlights meaningful societal trends.

Age & Generations
Demographic Research
Generation X
Generation Z
Generations
Greatest Generation
Methodological Research
Millennials
Silent Generation

Kim Parker is director of social trends research at Pew Research Center

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ABOUT PEW RESEARCH CENTER Pew Research Center is a nonpartisan fact tank that informs the public about the issues, attitudes and trends shaping the world. It conducts public opinion polling, demographic research, media content analysis and other empirical social science research. Pew Research Center does not take policy positions. It is a subsidiary of The Pew Charitable Trusts .

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