We used data from the National Neonatal Research Database on deaths in neonatal units in England, Wales and the Isle of Man (2017–2022). We used regression models to estimate rates of PM offer and completion and their association with selected clinical, socio-demographic and service-related variables. We report the relative risk (RR), with a p value <0.05 considered statistically significant.

PM offer and completion rates ranged from 56% to 62% and 15% to 18%, respectively. Compared with extremely preterm infants, term infants had higher PM completion rates (RR 2.25, 95% CI 1.94 to 2.62, p<0.001). PM completion was less likely for babies of Asian (RR 0.58, 95% CI 0.46 to 0.72, p<0.001) or black mothers (RR 0.78, 95% CI 0.60 to 0.99, p=0.04) when compared with babies of white mothers. Babies of mothers in the country’s least deprived decile were more likely to have a PM completed (RR 1.38, 95% CI 1.04 to 2.48, p=0.04), in comparison with the most deprived centile.

This national study provides a near-contemporaneous perspective on neonatal PM and adds to existing evidence of low rates. These data indicate the need to address the root causes of variation in PM completion to ensure equity in the care of families after a neonatal death.

National cohort study.

Sweden.

12-year follow-up of a cohort study, the Extremely Preterm Infants in Sweden Study, including children born EPT (n=449) and full-term controls (n=365).

Data on school grades (mathematics, Swedish and English) and special education school attendance were obtained from registers.

EPT group versus controls and subgroup analyses within the EPT group.

Compared with full-term controls, children born EPT more often attended special education schools (13.6% vs 0.5%; OR 28.5 (95% CI 6.9 to 117.5)) and those attending mainstream school more often received at least one failing grade (32.3% vs 5.2%; OR 8.7 (95% CI 5.2 to 14.5)). Of children with gestational age (GA) ≤23 weeks, 39% attended mainstream school and passed all three core subjects, compared with 65% of those born at 26 weeks (OR 0.34 (95% CI 0.17 to 0.62)). Among EPT children attending mainstream education, low GA, low maternal education, cognitive impairment and ADHD/ASD diagnosis increased the risk of poor academic achievement.

EPT birth was associated with poor academic achievement, but the risk varies substantially within the EPT group, primarily based on cognitive impairment, ADHD/ASD diagnosis and maternal education. However, the risk of poor academic achievement among children born EPT remained after adjusting for confounders and mediators.

Multicentre, open-label, parallel-design pilot randomised controlled trial

Seven tertiary/quaternary neonatal intensive care units.

Infants <26 weeks gestational age (GA) with a PDA diagnosed within 72 hours after birth.

Participants were randomised to an early echocardiographic screening within the first 72 hours followed by selective medical treatment (SMART) strategy of a moderate–severe PDA shunt or no intervention in the first 7 days.

The primary feasibility outcome was the proportion of eligible infants enrolled. Important secondary outcomes included a composite clinical endpoint of survival without major morbidity.

116 of 185 eligible infants were enrolled (63%, 95% CI 56% to 70%; SMART, n=51, Control, n=53). Of them, 104/116 (90%) (mean GA 24.3 weeks, birth weight 714 g) were randomised. Protocol deviation was 1.9%. Based on the treatment algorithm, 24% infants randomised to SMART never required treatment. Median treatment initiation age in the SMART arm was 2 days (IQR 1–2.5 days). The SMART strategy demonstrated an 85% probability of a better Win ratio (1.34, 95% CrIs 0.73 to 2.5) compared with control.

A trial of selective early PDA pharmacotherapy based on clinical and echocardiography grading of PDA shunt volume in the smallest infants is feasible with minimal protocol deviation. Early echocardiography screening and selective pharmacotherapy using the SMART-PDA algorithm may enhance the probability of survival with less morbidities in infants born <26 weeks GA.

NCT05011149.

Active surveillance (British Paediatric Surveillance Unit) study and meta-analysis of national surveillance studies.

UK and ROI.

Neonatal stroke presenting <90 days old in term and preterm infants between March 2022 and April 2023.

Reporting clinicians completed questionnaires and uploaded de-identified neuroimages via a purpose-built data platform.

68 neonatal stroke cases were reported in the UK and ROI. UK incidence was 9.0 per 100 000 live births (95% CI 6.9 to 11.6). Three-quarters were arterial ischaemic and unilateral. Arterial ischaemic and cerebral venous sinus thrombosis (CVST) strokes commonly presented with seizures at 2–3 days of age, while haemorrhagic stroke commonly presented with encephalopathy in the first ten days of age. Neonatal stroke was associated with fetal distress in utero. 61% of infants had an umbilical pH <7.25 and 28% required significant resuscitation at birth, respectively. A meta-analysis of 3 607 864 infants found our reported incidence and associated conditions were similar to surveillance studies in Germany and Australia.

Guidelines were available in a quarter of reporting hospitals. 87% of infants with arterial ischaemic and CVST stroke received antiseizure medications. 82% of infants were discharged home at 12 days old (median) with antiseizure medications (42%) alongside paediatric/neonatal (91%), physiotherapy (77%) and paediatric neurology (63%) follow-up.

Neonatal stroke is rare, with distinct subtypes associated with different presentations, timings and management strategies, highlighting the need to better understand this condition.

Using a modified Delphi approach with diverse stakeholders, we aimed to create recommendations for the use of alternative methods of consent in neonatal clinical trials.

Our process resulted in 21 recommendations within three categories. In ‘deciding whether to use alternative methods of consent’, we present five statements to guide whether alternative methods are appropriate. For example, heightened justification may be required for early phase research or allocation arms that are highly preference-sensitive for families. In ‘preallocation information and ability to opt-out’, we present 11 statements related to information sharing with families of potential participants. These include guidance on researcher communication and guidance for passive information sharing such as via flyers. In ‘postallocation information and decision to continue participation’, we present five statements to guide later information sharing. These focus on best practices for researcher communication postallocation. For two items, our Working Group could not reach consensus. These items were not included in our recommendations.

Our recommendations may guide researchers, clinicians, regulators and funders in the consideration and conduct of alternative methods of consent for neonatal clinical trials. Future work must evaluate these recommendations within neonatal clinical trials and the areas of lack of consensus among our Working Group.

Nationwide, population-based registry study.

All neonatal intensive care units (NICUs) in Norway.

All EPT (<28 weeks)/ELBW (<1000 g) infants born between 2014 and 2021, admitted to an NICU. Infants who within the first week of life died, underwent surgery for necrotising enterocolitis (NEC) or did not receive enteral feeds or started with probiotics after the first week of life were excluded from the main analyses. Logistic regression, propensity score matching, inverse probability of treatment weighting (IPTW) and clustering analyses were applied.

The primary outcome was all-cause mortality after the first week of life. Secondary outcomes were surgical NEC and late-onset sepsis after the first week of life, growth and probiotic sepsis.

Among 1596 live-born EPT/ELBW infants, 1268 were included in the main analysis and 676 (53.5%) started probiotics in the first week of life. Probiotics were associated with lower all-cause mortality (IPTW analysis; adjusted OR (aOR) 0.65, 95% CI 0.43 to 0.97), but no reduction in surgical NEC (aOR 0.83, 95% CI 0.49 to 1.43). However, in an emulated intention-to-treat scenario, high (>80%) probiotic use versus low (< 30%) was associated with a reduction in surgical NEC (aOR 0.40, 95% CI 0.19 to 0.86). We found no association between probiotics and sepsis or growth. 5 out of 858 infants (0.58%) exposed to probiotics developed probiotic-associated sepsis, all survived.

Probiotic supplementation to EPT/ELBW infants was associated with lower all-cause mortality and possibly reduced NEC.

HIE pathogenesis involves a cascade of metabolic, excitotoxic and inflammatory processes.1 The primary phase begins with ATP depletion, oxidative stress and excitotoxicity leading to neuronal death. This is followed by a latent phase (6–12 hours) of transient metabolic recovery providing a therapeutic window. Without intervention, a secondary phase ensues, characterised by mitochondrial dysfunction, apoptosis and inflammation. A tertiary phase may persist for weeks to months, marked by chronic neuroinflammation, gliosis and impaired repair.1

Chronic neuroinflammation is driven by persistent microglial and astrocytic activation, releasing cytokines such as interleukin-1 (IL-1), a key upstream inflammatory mediator. 2026-04-28T09:00:14-07:00 info:doi/10.1136/archdischild-2025-329808 hwp:master-id:fetalneonatal;archdischild-2025-329808 BMJ Publishing Group 2026-04-28 Viewpoint http://fn.bmj.com/cgi/content/short/archdischild-2025-330266v1?rss=1 Management of the patent ductus arteriosus (PDA) in preterm infants remains controversial. Randomised controlled trials (RCTs) have shown that administering pharmacotherapy, predominantly ibuprofen, a cyclooxygenase (COX) inhibitor, to infants selected based on the standard echocardiography approach to diagnosis (eg, duct diameter and shunt direction), does not improve outcomes and may lead to harm. It remains uncertain, however, whether eliminating or reducing PDA shunt volume using an intervention with higher efficacy and fewer adverse effects, or in a more selective population, would show different results. It is possible that an imprecise approach to patient selection exposes low-risk infants to the adverse effects of pharmacotherapy without benefit and high-risk infants to the synergistic adverse effects of pharmacotherapy and persistent high volume pathological shunt when treatment fails. Whether targeted management of moderate-high volume PDA shunts, informed by comprehensive echocardiography adjudication, in the highest risk infants is beneficial remains untested in an RCT setting. Furthermore, both pharmacological and non-pharmacological interventions warrant further investigation. High quality practice changing research requires a collaborative approach between haemodynamic specialists, epidemiologists and trial methodologists to (1) define the study population based on phenotypic profiles of high-risk infants; (2) enhance the choice and timing of intervention; and (3) identify outcome measures that are relevant and clinically meaningful to families. In this review, we summarise evidence from RCTs and observational studies by discerning discrepancies and exploring potential explanations. Such an approach is essential to establish whether active PDA treatment confers any measurable benefit for high-risk preterm infants.

Systematic review and meta-analysis.

MEDLINE, Embase, CINAHL and the Cochrane Library were searched to 16 April 2025. The review was registered on PROSPERO (CRD42023387592).

Prognostic studies of neonates ≥35 weeks’ gestation with HIE treated with TH, reporting short-term outcomes: death, abnormal brain MRI or a composite of both.

Data were extracted independently. Risk of bias was assessed using the Quality in Prognosis Studies tool. Pooled sensitivity, specificity, diagnostic OR (DOR) and area under the curve (AUC) were calculated using a random-effects model.

Thirty-seven studies (n=2836) were included; 26 (n=2268) contributed to meta-analyses. Abnormal aEEG background at 24 hours predicted abnormal MRI with sensitivity 0.76 (95% CI 0.38 to 0.94), specificity 0.70 (95% CI 0.43 to 0.87), DOR 5.91 (95% CI 2.00 to 17.49) and AUC 0.72. Abnormal cNIRS at 48 hours showed comparable prediction with sensitivity 0.77 (95% CI 0.57 to 0.89), specificity 0.61 (95% CI 0.19 to 0.91), DOR 8.38 (95% CI 2.02 to 34.66) and AUC 0.79. TnECHO-detected pulmonary hypertension had limited prognostic value with DOR 2.08 (95% CI 0.36 to 11.9) and AUC 0.62. Right ventricular function measures showed substantial heterogeneity in sensitivity and DOR.

aEEG and cNIRS between 24 hours and 48 hours could offer reasonable prognostic value for detecting brain injury in HIE. TnECHO has limited predictive utility in isolation. Multimodal approaches may enhance early risk stratification and should be explored in future studies.

We conducted a methodological systematic review of Cochrane and non-Cochrane systematic reviews. The search was conducted on 10 September 2024 in the Cochrane Database of Systematic Reviews and PubMed for articles published in the previous 12 months. Reviews were eligible if they involved randomised trials of interventions delivered in pregnancy or infancy, included multiple births and reported results of at least one aggregate data meta-analysis for an infant outcome.

After screening 222 articles, 39 had unclear eligibility due to making no mention of multiple births and nine met the eligibility criteria (five Cochrane and four non-Cochrane reviews). Multiple births were inconsistently handled across included reviews. The degree of clustering due to multiple births was poorly described and meta-analyses accounting for clustering were rarely reported (2/9 reviews; 22%). CIs around pooled treatment effect estimates were wider after accounting for clustering.

Clustering due to multiple births is a poorly recognised issue in systematic reviews and meta-analyses. Given the potential for this clustering to alter conclusions about the effectiveness of interventions, we recommend accounting for clustering due to multiple births in future meta-analyses.

This study investigated 5-week temporal changes in oxygen saturation indices in healthy moderate-late preterm (MLPT) (born between 32+0 weeks and 36+6 weeks of gestation) and term (born between 37+0 weeks and 41+6 weeks of gestation) infants.

MLPT and term infants’ sleeping postductal saturations were measured using nocturnal pulse oximetry at 7 days, 14 days, 21 days, 28 days and 35 days (±3 days) postnatal age. This recorded mean peripheral oxygen saturation (SpO₂), Oxygen Desaturation Indices (ODIs) 3, 4 and 10 (number of desaturations >3%, >4% and >10% per hour) and mean nadir SpO₂ >3%.

34 infants were studied (17 per group). The groups’ median gestations were 35+0 weeks and 39+5 weeks, respectively. Generalised linear mixed modelling indicated increasing mean saturations from 94.98% in week 1 to 96.68% in week 5 (p<0.001) for both groups together, with no significant group differences. MLPT infants’ average mean nadir SpO₂ >3% was 89.94% versus 91.55% for term infants (p=0.005), with both groups improving throughout the study (p=0.006). MLPT infants had 2.08 times more ODI3 dips/hour (p<0.001), 2.49 times more ODI4 dips/hour (p<0.001) and 6.66 times more ODI10 dips/hour (p=0.005) than term infants.

This study demonstrated significant differences in IH prevalence and severity between groups. Further research is needed to evaluate IH’s impact on neurodevelopmental outcomes in this population.

We retrospectively reviewed fetuses with ICH diagnosed prenatally at a single tertiary fetal centre between 2015 and 2025. Cases with a known mechanism at presentation were excluded. Ultrasound (US) and MRI images were reassessed by fetal medicine and neuroradiology specialists blinded to aetiology. Clinical, laboratory, genetic, autopsy and placental findings were integrated to determine underlying causes and assess imaging patterns.

Sixty-seven fetuses were included; a definitive aetiology was identified in 38.8% (26/67). Genetic aetiologies were detected in 27.7% (13/47) of cases with advanced genetic testing, most commonly associated with cerebral small vessel disease (CSVD). Other causes included infection (5/67, 7.5%), fetal anaemia (6/67, 9%), and coagulopathy (3/67, 4.5%, of which one was genetic). Twenty-one cases (31.3%) remained unexplained despite comprehensive investigation, and 20 (29.9%) had incomplete investigations. Intraventricular haemorrhage (IVH) was present in 91% (61/67), with periventricular haemorrhagic infarction (PVHI) in 55.2% (37/67). CSVD was associated with multifocal PVHI, porencephaly, white matter injury and frequent brainstem involvement. In fetal anaemia, cerebellar haemorrhage was common, with brainstem and vermian involvement predominantly in non-parvovirus cases. Intraparenchymal haemorrhage without IVH occurred mainly with coagulopathy or infection. Although some phenotypic clustering was observed, there was substantial overlap among aetiologic groups.

Genetic disorders, particularly CSVD, account for a significant proportion of prenatal ICH, supporting routine genomic testing. Imaging can suggest probable causes, but overlap limits its diagnostic specificity.

A retrospective study was conducted in a cohort of fetuses diagnosed with hepatic lesions between 2011 and 2023 at a tertiary referral center. Prenatal and postnatal data were collected, including lesion type, size, gestational age at detection, associated anomalies, genetic abnormalities, growth restriction and pregnancy outcomes. Postnatal follow-up included imaging, lesion resolution and overall health status.

65 fetuses were identified. Most lesions were echogenic (n=55); a minority were cystic (n=7), mixed (n=1) or subcapsular hematomas (n=2). Multiple lesions were present in 38%. Stillbirths, including fetal death and pregnancy termination, occurred in 18%, predominantly in the setting of major associated anomalies, fetal growth restriction and/or genetic abnormalities. Of 48 liveborn infants, 96% were healthy at discharge. Among 31 infants followed postnatally, 75% showed lesion resolution by 21 months. At the 5-year median follow-up, 79% were healthy. Echogenic lesions were more common in healthy infants, while a cystic component was associated with a higher rate of concurrent clinically significant health conditions, although liver function was typically normal.

Isolated small echogenic fetal hepatic lesions display a favorable prognosis with spontaneous resolution in most cases. Adverse pregnancy outcomes are common in cases with associated anomalies, fetal growth restriction and genetic abnormalities; therefore, counseling should be guided by a comprehensive anomaly assessment and appropriate genetic evaluation.

To compare the physical and functional characteristics of four commonly used neonatal VLs and assess user experience.

In this observational study, four VL systems—C-MAC, GlideScope, InfantView and NeoView were evaluated. A technical comparison of blade design and dimensions was performed across available blade sizes, alongside a conventional Miller blade. Medical professionals attending a neonatal airway workshop then used each device on neonatal manikins and rated their experience using a 4-point scale across six domains: ease of use, airway visualisation, ease of intubation, image quality, blade size and blade design.

A total of 23 participants with varied clinical backgrounds completed the evaluation. While 65% routinely performed neonatal intubations, 80% reported fewer than 10 intubations annually and 65% preferred conventional laryngoscopy. Following the trial, most participants favoured the C-MAC and NeoView VLs, and GlideScope was perceived to mimic conventional laryngoscope. The NeoView and C-MAC devices had the shortest distance between the camera and the distal blade tip. All VLs supported video and image capture. NeoView and GlideScope used disposable blades, while others employed reusable blades.

This study provides a systematic comparison of the physical features and user preferences for commonly available neonatal VLs. These insights can guide equipment selection, inform training programmes and promote safer neonatal airway management.

Randomised controlled trial.

Lamb delivery suite.

Term lambs in haemorrhagic, asphyxial cardiac arrest.

Fetal lambs were exsanguinated (~45 mL/kg) followed by umbilical cord occlusion to arrest. After 5 min of asystole, ventilation was followed by coordinated chest compressions. Asystolic lambs were randomised to epi-first (intravenous epinephrine, 0.02 mg/kg and if no ROSC, a 10 mL/kg saline bolus over 5 min), or bolus-first (10 mL/kg saline bolus over 2 min and if no ROSC, followed by intravenous epinephrine). Haemodynamics and blood gases were monitored.

In the epi-first group, none of the lambs achieved ROSC after epinephrine; ROSC occurred in 11/11 lambs during or immediately after saline bolus. In the bolus-first group, none of the lambs achieved ROSC with bolus alone and 8/9 lambs had ROSC after epinephrine. Mean time to ROSC from start of resuscitation was shorter in epi-first (4.9±1.3 vs 6.6±0.9 min, p=0.004), but time to ROSC from the time of epinephrine administration was shorter with bolus-first (86±43 vs 40±21 s, p=0.004). The fetal heart rate did not change significantly despite fetal blood loss.

Our findings support current neonatal resuscitation guidelines of intravenous epinephrine followed by a bolus in neonates with suspected hypovolaemic arrest. Early saline bolus delays epinephrine and ROSC. Careful clinical assessment of haemodynamics in the post-resuscitation phase is critical.

Prospective cohort pilot study conducted in two tertiary neonatal intensive care units. Sixty-seven neonates with suspected NEC underwent concurrent abdominal radiography and ultrasound assessments. Imaging studies were independently reviewed by masked investigators using pre-specified criteria to classify each study as reassuring or non-reassuring.

The main outcome measure was the need for surgical intervention. Imaging data were analysed using unsupervised k-means clustering (k=2): logistic regression—testing associations with surgery and principal component analysis (PCA)—to identify imaging features most contributing to group separation.

Ultrasounds were reassuring in all cases subsequently diagnosed with non-NEC, that is, feeding intolerance, whereas most radiographs in this group were non-reassuring. Clustering based on radiographs alone did not significantly discriminate surgical risk (58.8% vs 39.4%; p=0.11). Combined model (radiograph+ultrasound) produced two distinct clusters with significantly different surgical rates (78.3% vs 34.1%; OR 6.96, 95% CI 2.29 to 24.58). PCA highlighted complex ascites, absent peristalsis and abnormal bowel perfusion as key discriminating features.

Combining abdominal ultrasound with radiography improved the identification of neonates at high surgical risk from NEC, in our pilot study. A reassuring ultrasound reliably identified infants with feeding intolerance, suggesting potential to reduce unnecessary transfers and treatments. Larger multicentre studies are needed to validate these findings and inform development of a unified multimodal imaging score for NEC diagnosis.

Retrospective cohort study using data from the National Neonatal Research Database of all infants born at <30 weeks GA, admitted to neonatal units in England and Wales from 2016 to 2021.

Methods of respiratory support used in the delivery room and days 1 and 7 of care were determined. Success of the initial non-invasive respiratory support strategy was assessed by any use of mechanical ventilation in the first 7 days of care.

24 107 babies were included. Use of continuous positive airway pressure (CPAP) and high-flow nasal cannula (HFNC) as the highest method of respiratory support for stabilisation increased during the study period (CPAP: 17.3% to 28.8%; HFNC: 0% (first recorded in 2016) to 0.7%). CPAP use increased in the most preterm (<25 weeks GA; 0.7% to 4.8%), the extremely preterm (<28 weeks GA; 7.2% to 17.5%) and the very preterm (28–29 weeks GA; 29.3% to 44.1%) cohorts. Among those initially stabilised with non-invasive ventilation in this study, 2763 (48.0%) infants required mechanical ventilation in the first week.

In England and Wales, use of non-invasive respiratory support for initial stabilisation has increased among babies born at <30 weeks GA. 48% of those stabilised with non-invasive ventilation required mechanical ventilation in the first week. A higher quality evidence base for interventions that reduce mechanical ventilation could improve respiratory management in this population.

Concerns for the impact of oxygen toxicity on preterm retinal development date back to the 1940s prior to the availability of cardiorespiratory monitoring to assess oxygenation, with the first large cohort studies published in the early 1950s. One of these studies published in ADC in 19521 described potential risk factors for disease in 56 infants with retrolental fibroplasia (the first term for retinopathy of...]]> 2026-03-04T09:00:16-08:00 info:doi/10.1136/archdischild-2025-330066 hwp:master-id:fetalneonatal;archdischild-2025-330066 BMJ Publishing Group 2026-03-04 Original research http://fn.bmj.com/cgi/content/short/archdischild-2025-330160v1?rss=1 The International Liaison Committee on Resuscitation (ILCOR) recently issued a weak recommendation, based on low-certainty evidence, favouring intact umbilical cord milking (UCM) over early cord clamping (ECC) for term and late preterm infants who remain non-vigorous despite initial stimulation.1 This recommendation was primarily informed by evidence from a multicentre, cluster-randomised crossover trial that enrolled 1730 infants.2 The results of this pragmatic trial showed no significant difference in the primary outcome, ‘Neonatal intensive care unit (NICU) admission’, for which it was adequately powered. The ILCOR committee, however, based their recommendation on secondary findings, including a reduction in moderate or severe hypoxic-ischaemic encephalopathy (HIE), and improvement in early haemoglobin levels without adverse effects.

The incidence of moderate to severe HIE was 12/828 (1.4%) in the UCM versus 24/806 (3%) in the ECC group, yielding a crude OR of 0.48 (95% CI 0.24 to 0.96). It is important to note...]]> 2026-03-04T09:00:16-08:00 info:doi/10.1136/archdischild-2025-330160 hwp:master-id:fetalneonatal;archdischild-2025-330160 BMJ Publishing Group 2026-03-04 Letter http://fn.bmj.com/cgi/content/short/archdischild-2025-328568v1?rss=1 Despite a general understanding of the importance of docosahexaenoic acid (DHA) and arachidonic acid (ARA) in fetal development and the early postnatal deficits that result after preterm delivery, nutritional strategies to prevent postnatal DHA and ARA deficits and to harness the biological benefit of enteral replacement have been elusive. This shortcoming is critical given the clinical impact of these deficits in the risk of preterm disease in the neonatal intensive care unit.

In the past few years, there have been six meta-analyses to determine the health benefit and risk of enteral DHA with and without ARA supplementation. The recent publication of Dang et al is one of these studies.1–6 Dang et al report the results of a meta-analysis of DHA and/or ARA enteral supplementation in preterm infants which included data from 11 unique randomised clinical trials.6 The...]]> 2026-03-03T09:00:15-08:00 info:doi/10.1136/archdischild-2025-328568 hwp:master-id:fetalneonatal;archdischild-2025-328568 BMJ Publishing Group 2026-03-03 Editorials http://fn.bmj.com/cgi/content/short/archdischild-2024-327480v1?rss=1 Preterm birth affects around 7–8% of pregnancies in the UK. There are immunological consequences of preterm birth, epidemiological differences in infectious diseases in the preterm population and differences in immunity after vaccination, both following immunisations received in pregnancy and following vaccines administered to infants themselves. There are also often increased concerns about the side effects experienced by preterm infants following vaccination. It is important that health care professionals and parents are fully informed about the specific issues of vaccination in this group.

We recruited 800 healthy, term newborns from a tertiary referral obstetric department. Informed consent was obtained antenatally from expectant mothers on the labour ward. Those with known antenatal complications were excluded from the consent process. Those with postnatal admission to the neonatal unit or maternal admission...]]> 2026-02-25T09:00:19-08:00 info:doi/10.1136/archdischild-2025-329260 hwp:master-id:fetalneonatal;archdischild-2025-329260 BMJ Publishing Group 2026-02-25 Letter http://fn.bmj.com/cgi/content/short/archdischild-2025-328726v1?rss=1 Objective

To characterise white matter microstructural differences within very preterm (VPT; <33 weeks’ gestational age) infants that develop motor impairment in the first 2 years of life.

Cohort study, VPT infants (Cincinnati Infant Neurodevelopment Early Prediction Study) recruited from five level III/IV neonatal intensive care units in the greater Cincinnati area between September 2016 and November 2019.

Multicentre study; participants received MRI at term-equivalent age at Cincinnati Children’s Hospital Medical Center and were followed-up at 2 years corrected age to assess their motor performance.

Infants born before 33 weeks were eligible.

Composite motor scores at 2 years corrected age (CA) on the Bayley Scales of Infant and Toddler Development, III. Fractional anisotropy (FA) along the white matter tracts was used to measure white matter microstructure. Motor impairment was defined as Bayley-III motor score <85.

247 controls and 84 impaired infants were included in the study. Compared with the controls, infants with motor impairment were characterised by location-dependent credible group differences and significantly lower FA in both sensorimotor and non-sensorimotor tracts. A location-specific significant positive association between FA and Bayley scores in the impaired group was observed in multiple sensorimotor tracts and non-sensorimotor tracts. No significant associations were found between FA and Bayley scores in the controls.

VPT infants developing motor impairments show altered inter and intrahemispheric connectivity, with early indications of impaired visual-motor, sensorimotor and thalamo-cortical connectivity, extending beyond sensorimotor tracts.

A nationwide register-based cohort study was conducted including near-term to term children born between 1997 and 2013 with follow-up until 2021. Early-onset infection was defined as an invasive bacterial infection within the first week after birth defined by either physician-assigned diagnoses or bacterial pathogens cultured from blood or cerebrospinal fluid. Outcomes included diagnoses of intellectual disability and special educational needs. Associations were estimated by adjusted HRs (aHR) or unadjusted incidence rate ratios (IRR), when exposures and outcomes were rare. Additional analyses were conducted, including sibling-matched analyses and subgroup analyses considering only children with culture-positive infection.

Among 993 363 children, 8267 (0.8%) had sepsis and 152 (<0.1%) had meningitis. Of these, 260 had culture-positive sepsis and 31 had culture-positive meningitis. Early-onset sepsis was associated with an increased risk of intellectual disability (aHR: 2.24, 95% CI 1.93 to 2.59) and special educational needs (aHR: 1.49, 95% CI 1.40 to 1.59). Early-onset meningitis was associated with higher risks of both intellectual disability (IRR: 7.75, 95% CI 3.34 to 15.27) and special educational needs (aHR: 2.95, 95% CI 2.06 to 4.22). The associations remained consistent across multiple additional analyses, including sibling-matched analyses and subgroup analyses limited to culture-positive infections.

Early-onset neonatal infection in near-term to term children was associated with an increased risk of long-term cognitive impairment including both intellectual disability and special educational needs.

To evaluate whether high-frequency oscillatory ventilation (HFOV) initiated at birth facilitates lung aeration and reduces lung inflammation and injury, compared with conventional mechanical ventilation (CMV) in preterm lambs.

Preterm lambs (126±1 days’ gestation, term ~148 days) were instrumented to assess blood flow, pressure, oxygenation and blood gases. Lambs were allocated to HFOV (n=6), CMV (n=7) or unventilated control (UVC, n=8) groups. In ventilated groups, respiratory support was initiated during physiological-based cord clamping (PBCC). Lung aeration was assessed by lung ultrasound (LUS) in HFOV lambs. Postmortem lung tissues underwent histological and molecular analyses of inflammation and injury.

HFOV achieved effective respiratory stabilisation using significantly lower tidal volumes compared with CMV (1.7±0.4 vs 6.2±1.5 mL/kg, p<0.0001). LUS confirmed rapid lung aeration following HFOV. Histological analyses revealed significantly fewer CD45-positive and CD163-positive inflammatory cells in HFOV lungs compared with CMV (p<0.001 and p<0.05, respectively). Gene expression profiling demonstrated lower expression of key inflammatory and injury markers in HFOV versus CMV lambs, with some levels approaching those observed in UVC (p<0.05).

HFOV initiated during PBCC supports efficient lung aeration while minimising lung inflammation and injury in preterm lambs. These findings suggest that HFOV may reduce lung inflammation during initial respiratory stabilisation in preterm neonates.

Multicentre, double-blind, randomised crossover study.

Conducted online between February and April 2022 at the University Medical Centre Mainz, Germany.

Neonatal physicians from tertiary perinatal centres in Germany, Austria, Switzerland and Italy.

Participants viewed two scripted videos of a physician–parent conversation about a very preterm infant with severe intraventricular haemorrhage. Both conveyed identical numerical prognostic estimates but differed in framing: emphasising survival without disability (optimistic) or risk of death and impairment (pessimistic).

Primary outcome was framing preference. Secondary outcomes included Likert scale ratings of parental preparedness, physician professionalism and compassion, prognostic severity and optimism regarding survival and non-impairment, as well as free-text comments on challenges in prognostic communication.

Of 115 participants, 99 (86%) preferred the optimistic video (period-corrected preference odds (95% CI): 8.6 (7.4 to 9.7)). Optimistic framing was associated with higher ratings of parental preparedness and more favourable evaluations of the consulting physician, including professionalism and compassion, but had no effect on perceived prognostic severity, or optimism about survival or non-impairment. Communication was frequently described as an interpersonal challenge, involving the difficulty of maintaining trust, empathy and hope while communicating under prognostic uncertainty.

Neonatal physicians strongly preferred optimistic framing. Framing effects were primarily affective rather than cognitive and highlight implicit and complex framing biases in neonatal communication.

German Clinical Trials Register (DRKS), www.drks.de/DRKS00024466.

Retrospective observational cohort study, the UK National Neonatal Research Database.

Term infant NNU admissions in England and Wales, 2012–2020.

Term admission rate to NNU primarily for hypoglycaemia/1000 term live births. Change between epoch 1 (36 months before the publication of the British Association of Perinatal Medicine (BAPM) Framework in April 2017) and epoch 2 (36 months after the publication of the BAPM Framework in April 2017).

Term admissions primarily for hypoglycaemia decreased from 4.9 (95% CI 4.8 to 5.1) to 3.3 (95% CI 3.1 to 3.4) admissions/1000 term live births; proportion of potentially avoidable hypoglycaemia admissions (enteral feeds and special care only) decreased (from 12.8% (95% CI 12.1% to 13.4%) to 8.9% (95% CI 8.3% to 9.5%)), time to NNU admission and median length of stay were unchanged between epoch 1 and epoch 2. 46.5% (11 825/25 406) of infants admitted primarily for hypoglycaemia had one or more BAPM hypoglycaemia risk factors. Of infants with hypoglycaemia without BAPM risk factors, 44% (5990/13 581) had a birth weight above the 90th centile or between the 2nd centile and the 9.9th centile.

The publication of a national framework for term hypoglycaemia management was associated with a reduction in term NNU admission rates without delays in admission time or increased length of stay. One in two infants admitted for hypoglycaemia had no BAPM risk factors. Future research should explore birth weight between the 2nd centile and the 9.9th centile and above the 90th centile as additional factors that may further enhance hypoglycaemia risk stratification.

Web-based survey distributed to neonatologists at 258 NICUs across 15 countries in Europe, Australia, New Zealand and Canada, October 2023 and February 2024. Survey domains focused on availability of human milk, onset of enteral feeding, breast milk fortification (BMF), cytomegalovirus (CMV) screening and enteral supplements including probiotics. Results were compared with a similar survey performed in 2010.

Replies were received from 185 (72%) NICUs. Access to donor human milk (DHM) was high (91%). Across all NICUs, feeds were started on day 1 in 64%, 73% and 85% among infants born <25, 25–27 and 28–31 weeks’ gestation, respectively. Bovine milk-based BMF was routinely used in 88% of NICUs, with large variation in when it was commenced and discontinued. Routine use of human milk-based BMF was uncommon (4%). Maternal CMV status was routinely determined in 33% of all NICUs who then pasteurised or froze milk if the mother was CMV-seropositive. Probiotics were provided in 66% of the NICUs, with large variations in products and birth weight/gestational age criteria.

Compared with our survey from 2010, more NICUs now start feeding preterm infants on day 1, and DHM availability has increased in some countries. Substantial variation remains in the use of BMF, probiotics and CMV screening. A stronger evidence base is needed to update guidelines, aiming ultimately to improve growth and long-term neurodevelopment.

Systematic review and meta-analysis conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses of Diagnostic Test Accuracy guidelines. Eligible studies included infants born at term with NE who underwent amplitude-integrated EEG (aEEG) or EEG and MRI of the brain within the first month of life. Adverse outcomes, assessed at 18–36 months of age, were defined as cerebral palsy, postneonatal epilepsy, severe hearing or visual impairment, moderate-to-severe developmental delay, or death attributable to NE. Searches were conducted in MEDLINE, CINAHL, Embase and Web of Science from database inception to 10 June 2025; risk of bias of included studies was assessed using the Quality Assessment of Diagnostic Accuracy Studies-Comparative (QUADAS-C) tool.

Sensitivity, specificity and diagnostic odds ratio (DOR) of abnormal aEEG background, EEG background, EEG seizures and MRI injury, individually and in combination, for predicting adverse outcomes, pooled using Bayesian bivariate random effects meta-analyses.

27 studies including 1843 infants were analysed. MRI injury was the individual predictor with higher DOR estimate (31.01, 95% CI 15.07 to 72.82), followed by abnormal EEG background (16.84, 95% CI 5.88 to 50.59), while abnormal aEEG background and EEG seizures performed less well (7.99, 95% CI 2.40 to 33.00; 4.46, 95% CI 1.86 to 11.42). Combining EEG background with MRI injury improved DOR (78.59, 95% CI 19.72 to 321.36) and specificity (93.8%, 95% CI 85.2% to 97.9%) compared with MRI alone.

MRI is a strong individual predictor of adverse outcomes in NE. Combining it with early EEG improves prognostic accuracy and may better support clinical decision-making.

CRD42024585816.

This was an external validation study conducted on data collected from 2014 to 2021.

This was a retrospective, multicentre, population-level cohort with prospectively collected data.

Extremely low gestational age neonates recorded in the SwissNeoNet registry across all nine level III neonatal care units in Switzerland (n=1748) were included.

Recent BPD prediction models estimating the risk of BPD or death at 36 weeks postmenstrual age, based on predictors available within the first 24 hours of life.

The primary outcome was survival without BPD. A systematic literature search identified five eligible models, which were externally validated and recalibrated for the Swiss cohort. The most performant model was further optimised to improve local applicability.

Among 693 screened studies, five models based solely on perinatal variables were included. Without recalibration, models showed fair discrimination (area under the curve (AUC) 0.70–0.76) but variable calibration (observed/expected (O/E) 0.58–0.80). After recalibration, AUCs ranged from 0.69 to 0.76, and calibration improved (O/E 0.58–1.61). The optimised version of the best-performing model demonstrated improved calibration (O/E 1.03) and was validated in the Swiss population.

By comparing and externally validating existing BPD prediction models, we propose an optimised model using baseline variables at birth, enhancing its applicability to both the Swiss population and similar clinical contexts.

To assess changes in respiratory dynamics and physiological parameters in infants with and without respiratory distress in the delivery room and to determine the effect of continuous positive airway pressure (CPAP) support.

Electrical impedance tomography data were obtained from late preterm and term infants, born via caesarean section in a tertiary referral centre. Changes in the ratio of inspiratory to expiratory time (Ti/Te-ratio), end-expiratory lung impedance (EELI), oxygen saturation (SpO₂) and heart rate (HR) over the first 10 min as well as corresponding changes after CPAP application were assessed.

Of 73 infants, 18 (25%) received CPAP after birth (11 not admitted (CPAP group) and 7 admitted to the neonatal intensive care unit (CPAP/NICU)). Ti/Te ratio differed significantly between groups with the highest values in the CPAP/NICU group, mostly due to a reduced Te. There was no difference in EELI. Similarly, infants in the CPAP/NICU group had lower SpO₂ and HR trajectories over time than the other two groups. After CPAP application, EELI increased significantly. There were no changes in Ti/Te ratio, SpO₂ and HR after CPAP initiation.

In infants with more severe respiratory distress, Ti/Te ratio was increased, and SpO₂ and HR were reduced, suggesting that these parameters may serve as early predictors of respiratory failure. Application of CPAP resulted in an immediate increase in EELI, highlighting the importance of early CPAP initiation for infants with respiratory distress.

This was a mixed-methodology phenomenological study, using surveys. Statistical analysis was used for categorical data and thematic analysis for textual data.

Four tertiary or quaternary NICUs in Australia and Canada.

Parents of infants admitted to NICUs between July 2018 and August 2022 who engaged in decision-making in grey zones.

71 parents (80% mothers) completed the survey. 80% were bereaved.

Thematic analysis revealed five themes: (1) decision burdens, (2) internal tensions, (3) actualising beliefs and values through decision-making, (4) inauthentic shared decision-making (SDM) and (5) external factors that shaped decision-making.

Parents reported variable experiences of SDM. Despite decisions being described as burdensome, 89% wanted to be very involved in SDM, while 63% felt included. Actualisation of beliefs and values was important. Time pressures, competing interests and environmental factors influenced internal tensions experienced. Despite framing as SDM, some parents reported feeling coerced and experiences consistent with NMP.

Some parents do experience significant NMP during SDM in the grey zones of the NICU. Clinician awareness of NMP and their antecedents may enhance communication and the SDM process in this challenging setting.

We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension statement for network meta-analysis . We searched five medical databases for randomised controlled trials comparing different feeding approaches in preterm infants and their effects on growth, neonatal morbidities, mortality and NDO. The Cochrane Collaboration’s tool was used to assess the risk of bias. We used a random-effects model. Pooled mean differences (MD) or risk ratios with 95% CIs were calculated.

Ninety-five studies (9663 infants) were included.

Human milk (HM) with bovine milk fortifier (BMF) (adjusted according to blood urea nitrogen) achieved the best length increment (MD=0.56 cm/week; 95% CI 0.19 to 0.93). Notably, HM+BMF (3.5 gm/kg/d protein) showed the best head circumference growth (MD 0.46 cm/week; 95% CI 0.10 to 0.81) but no significant difference in weight gain. There were no significant differences in neonatal morbidities/mortality. While MOM|+PTF (supp) displayed significantly lower NDO delay in the domain of mild cognitive delay.

Overall, there is a lack of strong evidence to support a specific enteral feeding strategy and further high-quality research is required. Targeted HM fortification appears to improve head growth, while adjusted fortification enhances length. Given the significant inconsistency detected, which may compromise the reliability of the network estimates, these results must be interpreted carefully.

206 infants born at 22–28 weeks gestational age (GA) were randomised into intervention or control groups from three university hospitals in Sweden.

The intervention group received an oil with AA (100 mg/kg/d) and DHA (50 mg/kg/d) starting at birth until 40 weeks postmenstrual age (PMA) in addition to standard nutrition. Standard-of-care infants received standard nutrition according to national guidelines.

MRI volumetrics were defined a priori as a secondary outcome of the trial and included total brain, white and cortical grey matter, central structures and cerebellum. Univariable and multivariable linear regression models were used for comparisons.

MRI data in 117 infants had sufficient quality for inclusion (n=58 intervention). Birth weight, GA at birth, sex distribution, and PMA at MRI were similar in the groups. Infants receiving intervention had significantly larger white-matter volume at TEA, as compared with standard of care, in models adjusted for GA at birth, sex, study centre and PMA at MRI (β=6.8 cm³, 95% CI 0.7 to 12.9, p=0.028). The contribution of the intervention to white-matter volume corresponded to 10 days of prolonged gestation.

Our findings in this hypothesis-generating study suggest that AA+DHA promotes white matter growth, which may protect the developing brain in this vulnerable population.

NCT03201588.

Secondary analysis of the French EPIPAGE-2 cohort with children born between 24+0 weeks and 31+6 weeks of gestation, eligible for follow-up at 5.5 years. Children were classified into three VA groups: 5–6.3/10, 8/10 and 10/10 as reference group. Neurodevelopment was assessed with the Wechsler Preschool and Primary Scale of Intelligence-Fourth Edition, the Movement Assessment Battery for Children-II (MABC-2) and the Strengths and Difficulties Questionnaire (SDQ). Comparisons between groups were adjusted for neonatal and socioeconomic characteristics using generalised estimating equations models.

Among 1787 included children, 62% had suboptimal VA. Compared with the 10/10 VA group, the mean full-scale IQ decreased by –3.09 (95 % CI –4.75 to –1.42) and –4.97 (95 % CI –6.47 to –3.46) points, the mean MABC-2 total score by –0.66 (95 % CI –0.71 to –0.61) and –1.06 (95 % CI –1.09 to –1.00), and the mean total SDQ scores increased by 0.40 (95 % CI –0.16 to 0.94) and 0.60 (95 % CI 0.10 to 1.1) in groups with VA groups at 8/10 and 5–6.3/10, respectively.

In this French population-based cohort of children born preterm, suboptimal VA was frequent and associated with increased risk of neurodevelopmental difficulties. A comprehensive neurodevelopmental and neurovisual assessment is warranted in children born preterm with suboptimal VA.

Retrospective case series.

Tertiary referral centre.

Premature infants screened for ROP in a tertiary referral centre.

Vascular dilation and tortuosity on a scale from 1 to 5 were blindly labelled by three independent ROP experts using a 8 by 8 mm optic nerve-centred images. Images were automatically generated from images of the routine screening examinations.

A total of 278 patients (556 eyes) with a mean gestational age of 28.4±2.0 weeks and a mean birth weight of 1059.7±324.0 g were included. Treatment was needed in 49 eyes (8.8%) of 25 patients. A total of 1510 image sets centred on the optic disc were obtained and analysed. When the cut-off of the vascular dilatation and tortuosity rating was fixed at 3 (equivalent to a severe preplus disease), sensitivity and specificity for the detection of prethreshold type 1 ROP were 100% and 88.9%, respectively.

ROP screening using a single posterior pole image could reduce stress in premature infants without degrading the quality of screening, compare to iterative dilated complete fundus examination.

Observational genetic study using trio-based whole-exome sequencing (WES).

Multicentre study.

23 newborns diagnosed with idiopathic NAIS and their biological parents.

WES-trio with a customised workflow for filtering and interpreting variants in de novo autosomal dominant and recessive inheritance models.

Identification of pathogenic (P) or likely pathogenic (LP) variants potentially associated with NAIS.

We identified 28 unique rare de novo variants in 28 genes across 23 newborns with NAIS. Under the autosomal recessive model, no candidate genes were identified. No common P/LP variant across the 23 newborns was detected. In-silico predictors and comprehensive knowledge-driven analysis highlighted PIK3CD (p.Gln431Arg) as a candidate gene in one patient with perforant stroke. However, no more cases were identified with PIK3CD variants, and functional studies are warranted to assess its pathogenicity impact.

Trio-based WES did not identify a monogenic cause for idiopathic NAIS. Coding variants therefore appear unlikely to explain the underlying genetic base of the disease. Furthermore, PIK3CD (p.Gln431Arg) may contribute to perforant stroke, although it requires further association evidence. As the potential role of non-coding or structural variants in NAIS remains possible, genome-wide long-read sequencing approaches may provide further insights into the genetic architecture of this condition.