Finally, a SMART approach for the PDA?

One of the thorniest topics in neonatology currently. Some experts seem certain that we can define PDAs that benefit from early treatment. In contrast, the recent trials don't show any clinical benefit in early treated groups compared to controls, and indeed usually show an increase in BPD with early treatment, and an increase in mortality with very early treatment. I have posted many times over the last few years about trials of PDA closure. See here and here and here and here Bedside echocardiography has been used to try and define characteristics of the baby and the ductus that might benefit from treatment, but the difficulties in interpretation mean that most of the trials have either just confirmed patency, or have just measured ductus diameter (which isn't much above the limits of resolution of the devices) as a criterion for entry into the trial.

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A new standard for NOWS

Neonatal Opioid Withdrawal is a major public health problem in the world. Large numbers of infants born after fetal exposure to opioids experience unpleasant symptoms, requiring non-pharmacologic and pharmacologic intervention. Studies of different approaches for symptom control have the potential to improve outcomes for this fragile population. To go back in the history a bit, the Finnegan scale was developed as a research tool, it is fairly cumbersome, with 21 items, several of which are rather subjective, and some are frequent in babies without opioid exposure. The threshold for treatment, of a score of 8, was entirely arbitrary, and has never been adequately tested or compared to other thresholds.

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Neonatal Research Shorts : March 2026

Pineda R, et al. Language and sound exposure across neonatal intensive care hospitalization and relationships with early outcome. J Perinatol 2026. In this short term outcome study, 64 very preterm infants <29 weeks GA were evaluated at near-term age with the Neonatal Neurobehavioural Score (NNNS). They had previously had a recording of the ambient noise for 4 separate 16 hour periods during their NICU stay, which was analysed to determine the exposure to any noise, including electronic sounds (which I guess means alarms, and monitors beeping), or meaningful language or distant voices.

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Steroids and BPD, what do we really know?

My first foray into systematic review and meta-analysis was about 25 years ago with this article Barrington KJ. The adverse neuro-developmental effects of postnatal steroids in the preterm infant: a systematic review of RCTs. BMC Pediatr. 2001;1:1. As you can see it was the very first article in the new journal BMC Pediatrics, I had submitted to BioMed Central, BMC, because it was a new open access model of publishing, (which authors didn't have to pay for!) and then they asked me if I minded them transferring it to BMC Pediatrics.

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Registration of clinical trials.

Since 2005 the International Committee of Medical Journal Editors has required that a condition of publication of a prospective controlled trial is that it should be registered in an accessible database prior to starting the trial. It is understandable that for a few years afterwards, trials that had been commenced prior to this standard might not have been pre-registered. I don't think there is any reasonable excuse for not pre-registering prospective trials in more recent years. Since 2013, the World Medical Association's declaration of Helsinki has also clearly stated "Every research study involving human subjects must be registered in a publicly accessible database before recruitment of the first subject".

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Neonatal Acute Respiratory Distress Syndrome, what is it and how should we treat it?

ARDS is a fairly common problem in the adult and the paediatric ICU; following trauma, or systemic sepsis, or other extrapulmonary insults, usually inflammatory in nature, or as a complication of direct pulmonary insults, such as pneumonia or aspiration of gastric contents. It is characterised by acute respiratory distress, diffuse pulmonary infiltrates on the x-ray, without signs of cardiac compromise, an oxygenation defect, and a major decrease in lung compliance. Various definitions have been proposed, none of which are entirely satisfactory, but many cases in the PICU are fairly clear.

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Neonatal Research Shorts : February 2026

Dereymaeker A, et al. Neonatal sleep physiology and early executive functioning in preterm children. Pediatr Res. 2026. In this observational study, the authors recorded sleep architecture overnight shortly prior to discharge of 76 preterm infants, averaging 30 weeks GA. The main finding was that infants with less sleep time (as a percentage of the recording) had more executive function problems. This was a single recording prior to discharge, and might not reflect total sleep problems during the hospitalisation, but is certainly suggestive that preterms need their sleep. Take Home Message…

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Optimizing ventilation in established BPD

Babies with established BPD (I won't worry about the exact diagnostic criteria here, but very preterm infants who are still ventilated as they approach term are the group I am talking about) have somewhat reduced compliance, increased airways resistance, leading to long time constants, and rather heterogeneous lungs, often with apical emphysema and basal atelectasis. Ventilatory requirements are different to infants with, for example, HMD, who have predominately atelectatic lung disease, very low compliance, and airways resistance which is largely normal, apart from the resistance due to the endotracheal tube; such infants have very short time constants, so can be ventilated with very short expiratory times, and respond to increased PEEP with improving oxygenation.

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Managing Post-Haemorrhagic Hydrocephalus

PHH, as I will call it, is an extremely important determinant of outcomes in a small subgroup of preterm infants. Infants with severe IVH who don't develop PHH have outcomes that are little affected. As our group reviewed, even grade 4 IVH, if unilateral, and affecting 1 or 2 of the Bassan zones, has little impact on motor or cognitive outcomes unless complicated by PHH. Andrew Whitelaw died recently (a touching eulogy is on the site of the Newborn Brain Society), I knew him personally, having worked as his resident during a summer in Jersey (Channel Isles, UK), when he covered for my consultant during their vacation.

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Give your opinion: what should we call the most immature babies?

There is an upcoming workshop, sponsored by the AAP, and other groups, that is investigating what shared language should be used for the babies of less than 25 weeks gestation. At present there are not as many responses as they would like from families, or from former preterm infants. I would encourage any readers of the blog, and especially those from the 2 groups I just mentioned, a few of whom, I know, follow this blog, to participate.

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Automated oxygen control; is it worth it?

The history of automated controls of inspired oxygen goes back many decades, to before the invention of pulse oximetry. The first studies I remember used transcutaneous PO2 as the target variable, which had major limitations, as well as the advantage of being better at detecting hyperoxia, at least when it was working well. There are numerous recent publications about automated FiO2 control, at the end of this post I have put a list of a selection of publications from the last 8 years or so.

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Prophylactic acetaminophen in the preterm

In a newly published trial (Roze JC, et al. Prophylactic Treatment of Patent Ductus Arteriosus With Acetaminophen: A Randomized Clinical Trial. JAMA Pediatr. 2026) nearly 800 infants of 23 to <29 weeks GA were randomized within 12 hours of birth. There were few exclusions, basically only congenital anomalies and Twtin-Twin transfusion syndrome. The doses were different among the 27-28 weeks infants compared to those more immature, and continued for 5 days in both groups. The primary outcome variable was survival without "severe morbidity" which was any one of : severe bronchopulmonary dysplasia, stage II or III NEC, grade III or IV IVH, or cystic leukomalacia.

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Not just neonatology, trip to Rwanda

I was very fortunate to be able to take a trip to Rwanda to participate in their neonatal training scheme, in what was termed a "respiratory bootcamp". Rwanda is a small country of 23000 km2, with a young population of over 14 million, and 400,000 births annually. Which I can't help comparing to Quebec, with an area of 1.5 million km2, a population of 9 million and annual births of 80,000. There has been remarkable progress in perinatal health care and outcomes over the last decade, with a marked improvement in the proportion of deliveries attended by a trained birth assistant, and taking place in an institution (now >95%), with a dramatic reduction in maternal mortality from over 1000 to about 300/100,000 births.

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How much oxygen for the resuscitation of the preterm?

I like a good acronym, so my initial response to the new TORPIDO trial was very positive! TORPIDO 30/60 was a large multicentre RCT comparing initial FiO2 concentrations for resuscitation of the preterm infant (Oei JL, et al. Targeted Oxygen for Initial Resuscitation of Preterm Infants: The TORPIDO 30/60 Randomized Clinical Trial. JAMA. United States2025). The first TORPIDO study (Targeted Oxygen in the Resuscitation of Preterm Infants and their Developmental Outcomes) was a comparison in 290 infants <32 weeks GA, of 21% starting O2 concentration vs 100% starting concentration (

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Universal Neonatal Genome sequencing?

It is over 2 years since I posted about this issue, in the meantime there have been a number of new initiatives, and several review articles and opinion pieces. Including a JAMA, "research of the year" article". I was triggered to return to this issue by a recent example of such an editorial which claimed that universal neonatal genome sequencing (UNGS) "pilot programmes like the Generation Study by Genomics England, which showed that whole-genome sequencing could identify rare, treatable conditions in about one in every 200 babies." (Of note there is no author given for this editorial, perhaps it was generated by AI, interestingly…

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Why doesn’t closing the PDA help preterm infants?

I have been continuing to think about this issue, so will subject you all to some of my thoughts. The large RCTs of medication for closure of the PDA show no benefit, and some evidence of harms, but we all know that the PDA usually closes shortly after birth in the term infant, and there is a statistical association between a persistently patent ductus in the very preterm infant and several neonatal complications. So why don't babies benefit from closure of the PDA? I think there are 2 possibilities. One is that the medications are the problem.

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Should we ever close the PDA?

The latest large multicentre RCT has just been published. Laughon MM, et al. Expectant Management vs Medication for Patent Ductus Arteriosus in Preterm Infants. JAMA. 2025. In this trial, infants of 22 to 28 weeks GA were randomized at between 48 hours and 21 days of life after an echocardiogram. They were classified into: 1. no or asymptomatic PDA; 2.symptomatic PDA; or 3. cardiopulmonary compromise. Only group 2 were randomized. The definitions are shown below, including, at the bottom of the figure, the definition of group 2. Of note, infants receiving hydrocortisone were ineligible.

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Is this article trustworthy?

There are many ways that an article in the medical literature may not be worthy of trust, and whose results may be unreliable. I remember one of my own trials, LACUNA, which was a pilot RCT of lactoferrin supplementation to prevent late-onset sepsis (LOS). As a pilot. the primary outcome was feasibility of a larger trial, but the clinical outcomes that I reported included the incidence of culture-positive sepsis.

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Hope for HIE

I was struck this morning by a new article in Pediatric Research a "Family Perspectives" written by the founder of the organisation that has the same name as the title of this post, "Hope for HIE", Betsy Pilon (Pilon B. Family reflections: what’s next for hypoxic-ischemic encephalopathy (HIE)—a patient advocacy perspective. Pediatr Res. 2025). It is an eloquent cri-de-coeur, demanding a greater voice for parents of infants with HIE: …

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Longer term outcomes after cooling

One of the numerous major advances in neonatology during my career has been the introduction of therapeutic hypothermia for infants with Hypoxic Ischemic Encephalopathy (HIE). Mortality is decreased, by about 25%, and long term morbidity among survivors is also decreased, by about 33%. Those estimates of effect size come from the Cochrane review, which provides the following Forest plot (I'm sorry about the quality of the image, the version in the pdf of the review is much clearer, but it extends over 2 pages, with a page break in the middle).

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Face masks for resuscitation?

Blank DA, et al. Face mask versus nasal mask device use for initial resuscitation in extremely and very preterm infants (FONDUE): an open-label, single-centre, randomised, controlled trial. Lancet Child Adolesc Health. 2025;9(10):715–23. An excellent acronym for this trial. Hopefully it will lead to a trend in acronyms based on European culinary specialities. Very preterm infants, n=151, of 23 to 32 weeks GA were randomized to receive delivery room CPAP with a face mask, or with a nasal mask in a single centre study from Monash in Melbourne. Delayed clamping was attempted, without respiratory support, or immediate clamping if the baby needed intervention.

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Beware articles written by AI

I subscribe to Google alerts, which sends me an email whenever the phrase "neonatal research" appears on a new website or a new post. I was interested, therefore to receive an alert about an article which, according the blog "Bioengineer.org", showed a major genetic contribution to the occurrence of Necrotising Enterocolitis. The blog post includes the following quote "Bai et al.’s study represents a landmark in neonatal research by providing compelling evidence for the heritability of necrotizing enterocolitis in very preterm infants. The twin study design elegantly disentangles genetic predisposition from environmental influences and firmly establishes a genetic foundation for this complex disease".

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Neonatal Research Shorts : November 2025

Ybarra M, et al. Low-Grade Germinal Matrix Hemorrhage-Intraventricular Hemorrhage and Concomitant Preterm Brain Injuries: Neurodevelopmental Outcomes at 3 Years of Age. J Pediatr. 2025:114713. Previous studies of the long term outcome of infants with germinal matrix or low grade IVH have been inconsistent. Some have shown an association with poorer developmental progress, and others have shown no impact. Some of this variability may be due to uncertainty about diagnostic criteria, with slightly larger amounts of intraventricular blood being classified differently. Some is probably due to the variable association with other brain injury, not readily seen on ultrasound, such as white matter injury, or cerebellar haemorrhages.

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Clinical examination and treatment of septic shock. Not neonatology.

Andromeda-Shock-2 Investigators for the Andromeda Research Network SSoAR, et al. Personalized Hemodynamic Resuscitation Targeting Capillary Refill Time in Early Septic Shock: The ANDROMEDA-SHOCK-2 Randomized Clinical Trial. JAMA. 2025. This is a very interesting trial evaluating the usefulness of clinical assessment of the circulation in adults with septic shock in a large international multicentre trial. Patients with suspected sepsis, who required norepinephrine after 1 litre fluid bolus, and had an elevated serum lactate, were randomized. A standardized method of measuring capillary refill time was agreed upon, CRT was assessed by applying firm pressure to the ventral surface of the distal phalanx of a finger, using a glass microscope slide.

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Lactoferrin supplementation does not prevent late-onset sepsis in the preterm… or is it more complicated that that?

Many of my readers will remember the impressive results of the high-quality study by Paolo Manzoni, Manzoni P, et al. Bovine lactoferrin supplementation for prevention of late-onset sepsis in very low-birth-weight neonates: a randomized trial. JAMA. 2009;302(13):1421–8) which showed that routine supplementation of preterm infants with bovine lactoferrin (bLF) dramatically reduced late-onset sepsis. Many of us were quite excited with this finding, and launched our own studies, I performed a pilot in my NICU, hoping to use the data to get funding for a confirmatory trial (Barrington KJ, et al.

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Return to the Regression to the Mean

After my post on regression to the mean, and its importance in studies of apnoea therapy, I was thinking of other examples. Some which have been most evident to me are those which impact on areas of medicine that I have researched myself. One example, from many years ago now, looked at the haemodynamic effects of dopamine in sick preterm infants. Seri I, et al. Regional hemodynamic effects of dopamine in the sick preterm neonate. J Pediatr. 1998;133(6):728–34. This study was performed during the 1st 2 days of life, a period when blood pressure normally gradually increases, and when renal vascular resistance falls dramatically.

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Beware of meta-analysis factories

I mentioned in my previous post, an issue with meta-analyses; there have been several I have read recently which are very problematic. They seem to be produced by groups that have little concern for the quality of their product. This recent meta-analysis, for example, of transfusion thresholds in the preterm, stated that they found 12 RCTs (Fu et al Ann Hematol 2023).

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Do blood transfusions treat apnoea of prematurity?

There has for a long time been a thought that anemic babies with many apnoeas could benefit from a blood transfusion which would decrease their apnoeic spells. This idea has never been directly tested by an RCT. That is, a trial in which infants with apnoea were randomized to receive a transfusion or control, and the response accurately determined. I actually started such a trial when I was in San Diego, but only enrolled a tiny number of babies before leaving to return to Canada; the fellow who was involved finished at about the same time as me, and the project was sadly terminated.

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Non-invasive high-frequency oscillation; worth the hassle?

Non-invasive HFOV can be delivered by a variety of different equipment and interfaces. The high flows and upper airway turbulence probably have an impact on gas exchange; It appears that the effective dead space of the oro-nasopharynx is washed out (De Luca D, Dell'Orto V. Non-invasive high-frequency oscillatory ventilation in neonates: review of physiology, biology and clinical data. Arch Dis Child Fetal Neonatal Ed. 2016;101(6):F565–F70), but how much transmission of the oscillatory pressures to the lung occurs is uncertain. Transmission does occur under some circumstances, however, as several groups have shown.

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Avoiding IVs in moderately preterm babies

A new very large (for neonatology) RCT has just been published. Ojha S, et al. Full exclusively enteral fluids from day 1 versus gradual feeding in preterm infants (FEED1): a open-label, parallel-group, multicentre, randomised, superiority trial. Lancet Child Adolesc Health. 2025. Mothers were approached prior to preterm delivery, and babies were enrolled if they delivered between 30 and >33 weeks gestation, and were deemed clinically stable, prior to 3 hours of age. Prior to delivery the mothers either gave full written signed consent, or they verbally agreed to the study, in which case they had a full written consent later.

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