Search

Background: Increasingly, preterm-born children are entering adulthood as survival at earlier gestational ages improves. However, there is little understanding of the lived experience in preterm-born adults., Methods: A cross-sectional descriptive study was conducted including young adults from a regional birth cohort of infants born <33 weeks in Western Australia. Participants provided written reflections of their experiences growing up and included messages for future families experiencing preterm birth. Content analysis was conducted according to SRQR (Standards for Reporting Qualitative Research) guidelines. Ethics approval was granted by the Women and Newborn Health Service Ethics Committee., Results: Forty-one adults reflected on their life experiences, and 31 included messages for future families. Two predominant themes were (1) neonatal experiences and (2) experiences from childhood and adulthood which were divided into 'positive' and 'negative' subthemes. Participants made 44 references to the neonatal period: 31 (70.5%) 'challenging' including sickness (17, 54.8%), uncertainty (10, 32.3%), family separation (4, 12.9%); and 13 (29.5%) 'positive' including survival (6, 46.2%), support (5, 38.5%), strength (2, 15.4%). Childhood and adulthood was described as 'positive' in 119 (73.5%) references including a good life (41, 33.3%), supportive family (20, 16.3%), success (18, 14.6%), strength (18, 14.6%), gratitude (15, 12.2%), positive self-talk (7, 5.7%); and 'negative' in 43 (26.5%) including health challenges (19, 44.2%), school difficulties (10, 23.3%), family difficulties (9, 20.9%). Messages for future families included what to expect (56, 75.7%) and helpful advice (18, 24.3%)., Conclusion: Our preterm-born young adults predominantly describe positive life experiences of childhood and adulthood balanced with an awareness of particular challenges., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

In perinatal medicine, the number of babies with life-limiting or life-threatening conditions is increasing and the benefits of providing palliative care with a holistic, interdisciplinary approach are well documented. It can be particularly challenging, however, to integrate palliative care into routine care where there exists uncertainty about a baby's diagnosis or potential outcome.This framework, developed collaboratively by the British Association of Perinatal Medicine (BAPM) and the Association of Paediatric Palliative Medicine (APPM), offers supportive guidance for all healthcare professionals working in perinatal medicine across antenatal and neonatal services. It explicitly acknowledges that palliative care is not just for babies who are dying or who will certainly die in early life; incorporating a palliative approach into antenatal and neonatal care for all babies with an uncertain outcome can be particularly valuable. The framework provides guidance on recognising babies who may benefit from palliative care and outlines the key elements of perinatal palliative care: holistic family support, empowering parents to be parents, parallel planning, symptom management and loss and bereavement care. It provides recommendations for the delivery of palliative care services, advocating for a unified approach that involves all members of the perinatal team, supported by specialist services as needed.This framework calls for a shift in the philosophy and practice of perinatal care to integrate palliative care into the everyday and to recognise and embrace the challenge of uncertain prognosis., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: Early hypoglycaemia at the time of neonatal intensive care unit (NICU) admission is common in very/extreme preterm infants. This study aimed to determine whether buccal dextrose gel in the delivery room (DR) would improve rates of early hypoglycaemia in this population., Design: Randomised, blinded, placebo-controlled trial., Setting: Four level-3 and one level-2 neonatal units., Patients: Inborn infants≤32+0 weeks gestational age (GA)., Interventions: Infants were randomised to 40% dextrose or placebo gel in the DR (≤29+0 GA: 0.5 mL gel, ≥29+1 GA: 1 mL gel)., Main Outcome Measure: Hypoglycaemia (<1.8 mmol/L) measured at the time of first intravenous access at NICU admission., Results: Between November 2020 and August 2022, the recruitment rate was slow (impacted by the requirement for antenatal consent). This fact, coupled with finite research resources, led to a decision to end recruitment early. Data analysis of 169 newborns (33% of target sample size) showed no significant difference in the frequency of the primary outcome between dextrose 24/84 (29%) and placebo 25/85 (29%) groups (OR 0.95; 95% CI 0.49 to 1.86; p=0.88). A post-hoc analysis indicated that the trial had a low (47% conditional power) chance of detecting a statistically significant benefit from the intervention (had the target sample been achieved)., Conclusions: This study showed no evidence of benefit of 40% dextrose gel on rates of hypoglycaemia at NICU admission. Management of these vulnerable newborns should continue to focus on vascular access and commencement of dextrose-containing intravenous fluids as early as possible., Trial Registration Number: NCT04353713., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: The objectives are to assess the effectiveness of a modified and adapted oral sensorimotor intervention (MA-OSMI) protocol for infants in India on the rate and performance of breastfeeding among preterm (PT) infants at discharge., Design: Single-centre randomised control trial., Setting: Level III B neonatal intensive care unit in a quaternary care hospital in South India., Patients: A total of 76 PT infants born between 26 and 33 +6 weeks of gestational age, stratified into <30 weeks and 30-33 +6 weeks, were randomised to intervention group (MA-OSMI) or standard care (SC)., Interventions: MA-OSMI in addition to SC versus SC alone. The stimulation included 12 techniques administered by the principal investigator. SC included kangaroo mother care and non-nutritive sucking., Outcome Measures: Exclusive breastfeeding (EBF) rate and breastfeeding performance at the time of discharge, assessed using standardised tools by clinician and mothers., Results: Infants in MA-OSMI group (66%) had significantly higher EBF rate compared with the SC group (16%) (OR: 10.25; 95% CI: 3.41 to 30.80). Improved breastfeeding performance was noted as per the clinician's observation. Significantly lower scores for MA-OSMI groups (63.42±36.43) than SC groups (126.61±60.94) on mothers' ratings suggested better feeding skills., Conclusion: Prefeeding oral stimulation contributed significantly to the achievement of EBF among PT infants at discharge. The present findings may benefit speech-language pathologists, paediatricians/neonatologists and nurses in the intervention of oral feeding among neonates., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Competing Interests: Competing interests: None declared.

Objective: Human milk composition is dynamic. While extensive research has focused on its macronutrient concentrations during the first 6 months of lactation, limited research exists for extended lactation periods. This study aims to examine the nutritional composition of human milk during these longer lactation phases., Design: A retrospective longitudinal cohort study performed within the National Dutch Human Milk Bank., Participants: We selected donors who had provided milk donations at least once after the 6-month postpartum mark., Main Outcome Measures: The Miris Human Milk Analyser was used to analyse macronutrient concentrations in the milk samples. Linear mixed models were used for longitudinal analysis of these concentrations, factoring in time variables established for six sequential lactation periods., Results: We analysed 820 milk samples from 86 women, collected between 5 weeks and 28 months postpartum. Initially, milk protein concentrations dropped over the first 8 months of lactation (diff = -0.19 g/dL, p<0.001) and stabilised between 8 and 18 months before increasing again by 0.21 (95% CI 0.06-0.21) g/dL. Carbohydrate concentrations remained steady throughout the study period. Fat concentrations were stable for the first 8 months but saw an increase afterwards. Post 18 months, the fat content saw a rise of 1.90 (95% CI 1.59-2.21) g/dL. The caloric density mirrored the pattern of the fat concentrations., Conclusion: The nutritional content of human milk does not decrease after 6 months of lactation. Therefore, human milk banks may accept donations from mothers up to 2 years post-birth., Competing Interests: Competing interests: JM, JIAL, JWRT, BJvK, AS: All report no conflict of interest. JBvG: Member of the Dutch National Health Institute and founder and director of the Dutch National Human Milk Bank. CHPVDA: Reports receipt of speakers and consultancy honoraria from Nestlé Nutrition Institute, Nutricia Early Life Nutrition and Baxter., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: To characterise perinatal, clinical and neuroimaging patterns and aetiology of perinatal intracranial haemorrhage (pICH), and to assess potential differences between cases diagnosed antenatally and postnatally., Methods: Prospective, observational, single-centre study of 110 consecutive cases of pICH identified in the fetal or neonatal period or diagnosed with presumed pICH between 2014 and 2023. Prematurity-related cases were excluded. Antenatal and postnatal MRI data were analysed for patterns and mechanisms of haemorrhage and their potential aetiology. Potential associations between pICH with perinatal and clinical risk factors were also explored., Results: Fifty-nine of the 110 included cases (53.6%) were diagnosed antenatally (termination of pregnancy, n=22), and postnatal data on 81/88 (92%) children were available. Intraventricular haemorrhage (IVH) was the most common haemorrhage type (83/110 (75.5%)) and was more common prenatally (p=0.004). Subpial haemorrhage was exclusively diagnosed postnatally (p<0.001), and it was more commonly detected in primigravida women (p=0.013). The germinal matrix was the most common origin of IVH (n=56, 50.9%) occuring more frequently prenatally (p<0.001), whereas sinus venous thrombosis-related IVH was more commonly detected postnatally (p=0.002). Subdural haemorrhage was associated with haematological abnormalities (p=0.023). Genetic disorders caused 31.9% of the cases (15 of 47 tested cases). Genetic disorders and associated congenital anomalies were more common in the prenatally diagnosed group (p=0.038 and p=0.04, respectively)., Conclusions: The patterns and pathogenesis of pICH appear to be different for prenatally and postnatally diagnosed cases and for types of haemorrhages. Given the important role of genetic factors in prenatal intracranial haemorrhage, next-generation sequencing is indicated in these cases., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: Women with sickle cell disease (SCD) have adverse maternal and infant outcomes. Our aim was to determine whether the outcomes of SCD mothers and their infants differed from African or Caribbean women not affected by SCD and whether there were differences between SCD individuals with the haemoglobin SS (HbSS) or haemoglobin SC (HbSC) genotypes. Furthermore, we wished to determine if any differences related to deprivation., Design: A matched cohort study., Setting: Tertiary perinatal centre in London PATIENTS: 4964 African or Caribbean women without SCD and 148 with SCD., Main Outcome Measures: Mode of delivery, maternal exchange transfusion, birthweight, neonatal unit admission, neonatal death and deprivation indices RESULTS: SCD women were more likely to be delivered by caesarean section (p<0.001) and had babies of lower birthweight (p<0.001). Their infants were no more likely to be admitted to neonatal intensive care unit or suffer a neonatal death. There were no significant differences between the SCD women and those without SCD in their deprivation index or deprivation decile. The women with the HbSS genotype compared to those with the HbSC genotype were more anaemic (p<0.02), required more exchange transfusions (p<0.001) and were more likely to be delivered by caesarean section (p=0.008). The infant outcomes did not differ significantly between the genotypes., Conclusions: Although, the SCD women, particularly those with the HbSS genotype, had greater morbidity, infant morbidity, and mortality was similar in mothers with the HbSS or HbSC genotypes and those without SCD., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: To evaluate whether kangaroo mother care (KMC) in preterm infants on non-invasive respiratory support improves indices of cardiorespiratory wellbeing., Study Design: Prospective quasi-experimental observational study., Setting: Tertiary perinatal neonatal unit., Patients: 50 very preterm infants being managed with nasal continuous positive airway pressure., Interventions: Continuous high-resolution preductal pulse-oximetry recordings using Masimo Radical-7 oximeter for 1 hour (incubator care) followed by 1 hour during KMC performed on the same day., Main Outcome Measures: Measures of cardiorespiratory stability (dips in oxygen saturations (SpO 2 )) of ≥5% less than baseline, % time spent with oxygen saturations <90%, SpO 2 variability and heart rate fluctuation and incidence of bradycardias., Results: The gestational age and birth weight of the cohort were 28.4±2.1 weeks and 1137±301 g, respectively. Dips in SpO 2 of ≥5% less than baseline were significantly fewer with KMC, median (IQR) 24 (12 to 42) vs 13 (3 to 25), p=0.001. SpO 2 variability (Delta 12 s and 2 s), (1.24±0.6 vs 0.9±0.4, p=0.005 and 4.1±1.7 vs 2.8±1.2, p<0.0001) and rapid resaturation and desaturation indices were significantly lower during KMC, compared with incubator care. Percentage time spent in oxygen saturations <90% was less with KMC (7.5% vs 2.7%, p=0.04). Mean heart rate was comparable although fluctuations in heart rate (rise by >8 bpm) were lower with KMC (43±22 vs 33±20, p=0.03). Seven (14%) infants had bradycardias during incubator care and none during KMC, p=0.012., Conclusions: KMC improves cardiorespiratory stability in ventilated preterm infants. Regular KMC has the potential to improve clinical outcomes in this vulnerable cohort., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: To evaluate the impact of a quality improvement project of the adoption of standard parenteral nutrition (SPN) in preterm infants., Design: Retrospective, multicentre, whole-population, non-concurrent control study using data from the UK National Neonatal Research Database between 1 January 2014 and 31 December 2020., Setting: Neonatal units in London UK organised by geographical network., Patients: Preterm infants <31 weeks' gestation., Interventions: Introduction of two SPN formulations previously tested in randomised controlled trials (NEON and SCAMP). SCAMP delivers a higher target macronutrient intake., Main Outcome Measures: The primary outcome was survival to discharge from neonatal care without major morbidities. Secondary outcomes included the individual components of the primary outcome and a comparison of outcomes between the NEON and the SCAMP formulations., Results: Of 6538 eligible infants, 4693 were admitted to neonatal care before and 1845 after the adoption of SPN. Morbidity-free survival decreased by an average of 8.6% (95% CI 5.8% to 11.4%, p<0.0001) following adoption. The effect varied by type of formulation; the cohort that adopted NEON showed no difference in morbidity-free survival, whereas the cohort that adopted SCAMP showed a statistically significant decrease in morbidity-free survival. Overall survival decreased by an average of 2.0% (95% CI 0.01% to 4.0%, p=0.048)., Conclusions: Research is urgently needed to identify the optimal composition of parenteral nutrition for preterm babies. This study also adds to the growing body of evidence that suggests that early and high intakes of macronutrients in preterm babies may be harmful., Competing Interests: Competing interests: Members of this research group (SNU and NM) were investigators of the NEON trial. SNU was a committee member of the UK NICE guideline on neonatal parenteral nutrition and the QI implementation programme of SPN that is the subject of this paper., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: To examine the feasibility of early and extended erythropoietin monotherapy after hypoxic ischaemic encephalopathy (HIE)., Design: Double-blind pilot randomised controlled trial., Setting: Eight neonatal units in South Asia., Patients: Neonates (≥36 weeks) with moderate or severe HIE admitted between 31 December 2022 and 3 May 2023., Interventions: Erythropoietin (500 U/kg daily) or to the placebo (sham injections using a screen) within 6 hours of birth and continued for 9 days. MRI at 2 weeks of age., Main Outcomes and Measures: Feasibility of randomisation, drug administration and assessment of brain injury using MRI., Results: Of the 154 neonates screened, 56 were eligible; 6 declined consent and 50 were recruited; 43 (86%) were inborn. Mean (SD) age at first dose was 4.4 (1.2) hours in erythropoietin and 4.1 (1.0) hours in placebo. Overall mortality at hospital discharge occurred in 5 (19%) vs 11 (46%) (p=0.06), and 3 (13%) vs 9 (40.9%) (p=0.04) among those with moderate encephalopathy in the erythropoietin and placebo groups. Moderate or severe injury to basal ganglia, white matter and cortex occurred in 5 (25%) vs 5 (38.5%); 14 (70%) vs 11 (85%); and 6 (30%) vs 2 (15.4%) in the erythropoietin and placebo group, respectively. Sinus venous thrombosis was seen in two (10%) neonates in the erythropoietin group and none in the control group., Conclusions: Brain injury and mortality after moderate or severe HIE are high in South Asia. Evaluation of erythropoietin monotherapy using MRI to examine treatment effects is feasible in these settings., Trial Registration Number: NCT05395195., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: To compare reintubation rates after planned extubation and unplanned extubation (UE) in patients in neonatal intensive care units (NICUs), to analyse risk factors for reintubation after UE and to compare outcomes in patients with and without UE., Design: Prospective, observational study nested in a randomised controlled trial (SEPREVEN/Study on Epidemiology and PRevention of adverse EVEnts in Neonates). Outcomes were expected to be independent of the intervention tested., Setting: 12 NICUs in France with a 20-month follow-up, starting November 2015., Patients: n=2280 patients with a NICU stay >2 days, postmenstrual age ≤42 weeks on admission., Interventions/exposure: Characteristics of UE (context, timing, sedative administration in the preceding 6 hours, weaning from ventilation at time of UE) and patients., Main Outcome Measures: Healthcare professional-reported UE rates, reintubation/timing after extubation, duration of mechanical ventilation, mortality and bronchopulmonary dysplasia (BPD)., Results: There were 162 episodes of UE (139 patients, median gestational age (IQR) 27.3 (25.6-31.7) weeks). Cumulative reintubation rates within 24 hours and 7 days of UE were, respectively, 50.0% and 57.5%, compared with 5.5% and 12.3% after a planned extubation. Independent risk factors for reintubation within 7 days included absence of weaning at the time of UE (HR, 95% CI) and sedatives in the preceding 6 hours (HR 1.93, 95% CI 1.04 to 3.60). Mortality at discharge did not differ between patients with planned extubation or UE. UE was associated with a higher risk of BPD., Conclusion: In the SEPREVEN trial, reintubation followed UE in 58% of the cases, compared with 12% after planned extubation., Trial Registration Number: NCT02598609., Competing Interests: Competing interests: TD, FC, HY, EA, RL and LS have no conflict of interest to declare. MT declared consulting fees from Pfizer and payments for honoraria and lectures from Gennisium Pharma and Pfizer. LC declares honoraria from Chiesi for lectures unrelated to this topic. CJ declares payment or honoraria for lectures or presentations for Nestlé and Menarini unrelated to this topic. XD declares personal payment for lectures, presentations, speakers bureaus, manuscript writing or educational events from AstraZeneca and from Gennisium Pharma, and support for attending meetings and/or travel (launch congress organisers, launch meeting 2023, European Society for Pediatric Research, Abbott). HY declares support for attending meetings and/or travel from Duomed, Guigoz and Chiesi., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Competing Interests: Competing interests: None declared.

Objective: To assess the effect of a non-noxious vibratory stimulus on noxious-evoked cortical responses to skin puncture and to determine whether the presence of certain behavioural components may be used to predict such cortical responses., Design: Randomised controlled trial., Setting: Level IV neonatal intensive care unit at a stand-alone children's hospital., Patients: 134 hospitalised infants between 36 and 52 weeks' postmenstrual age and ordered to receive a clinically required laboratory draw., Interventions: Infants randomised to receive the intervention, a vibratory stimulus at the site of skin puncture beginning 10 s prior to a heel stick, or the control, no vibration., Main Outcome Measures: Electroencephalography and video recording time-locked to the deployment of the lancet for the skin puncture. Noxious-evoked cortical responses were measured by the area under the curve in the somatosensory region contralateral to the skin puncture. Behavioural responses were coded through video analysis., Results: Noxious-evoked cortical responses were significantly reduced in participants receiving the vibratory stimulus compared with the control (frontal, p<0.0001; central, p = 0.0088; central-parietal, p = 0.0111). There were no significant differences in behavioural responses between groups (all p>0.05)., Conclusions: A non-noxious vibratory stimulus presented prior to and continuing simultaneously with skin puncture significantly mitigates nociception in hospitalised infants. The presence or absence of facial expression components is inadequate to reliably predict pain signalling in the brain., Trial Registration Number: NCT04050384., Competing Interests: Competing interests: NM holds equity in Thrive Neuromedical. CPK was previously a consultant for Thrive Neuromedical. The remaining authors declare no competing interests., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: To determine the accuracy of two developmental screening questionnaires to detect cognitive or language delay, defined using the Bayley Scales of Infant and Toddler Development-Third Edition (Bayley-III), in children born extremely preterm (EP: <28 weeks' gestation) or extremely low birth weight (ELBW: <1000 g)., Design: Prospective cohort study., Setting: State of Victoria, Australia., Patients: 211 infants born EP/ELBW assessed at 2 years' corrected age (mean 2.2, SD 0.2)., Main Outcome Measures: Cognitive and language delay (<-1 SD) on the Bayley-III. The screening questionnaires were the Parent Report of Children's Abilities-Revised (PARCA-R) and the Ages & Stages Questionnaires Third Edition (ASQ-3)., Results: The PARCA-R performed better than the ASQ-3, but neither questionnaire had substantial agreement with the Bayley-III to detect cognitive delay; kappa (95% CI): PARCA-R 0.43 (0.23, 0.63); ASQ-3 0.15 (-0.05, 0.35); sensitivity (95% CI): PARCA-R 70% (53%, 84%) ASQ-3 62% (47%, 76%); specificity (95% CI): PARCA-R 73% (60%, 84%) ASQ-3 53% (38%, 68%). When both tools were used in combination (below cut-off on at least one assessment), sensitivity increased to 78% (60%, 91%) but specificity fell to 45% (29%, 62%). Similar trends were noted for language delay on the Bayley-III, although kappa values were better than for cognitive delay., Conclusions: Neither screening questionnaire identified cognitive delay well, but both were better at identifying language delay. The PARCA-R detects delay on the Bayley-III more accurately than the ASQ-3. Sensitivity for detecting delay is greatest when the PARCA-R and ASQ-3 were used in combination, but resulted in lower specificity., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: There is insufficient evidence to determine if non-invasive transcutaneous bilirubin (TcB) measurement can replace serum bilirubin (SBR) in assessing rebound hyperbilirubinaemia after phototherapy., Objective: To investigate if TcB can safely guide management of neonates after phototherapy., Subjects: 100 well neonates ≥35 weeks' gestation who had received inpatient phototherapy., Method: Measurement of both helix (manufacturer's recommendation) and earlobe TcB coincidentally with routine SBR 12 hours after cessation of phototherapy. All mothers gave written informed consent., Results: Gestation ranged from 35 +0 to 41 +5 (median 37 +6 ) weeks; birth weight 2018-4566 (median 3230) g; age 55-222 (median 109) hours at testing. 86% neonates were Caucasian. Outcomes determined by SBR included restarting phototherapy (n=0), repeat SBR next day (n=29), no further routine follow-up (n=71).TcB and SBR measurements were unpredictably inconsistent. Helix TcB tended to underestimate SBR (mean difference 50.1 (95% CI 113.9 to -13.7) μmols/L); for earlobe TcB mean difference was -13.4 (95% CI 46.3 to -73.2) μmols/L (overestimate), but bias was greater over the range of mean differences. No demographic factor predicted consistency between TcB and SBR. TcB was 25% (helix) and 76% (earlobe) sensitive in predicting repeat phototherapy and/or repeat SBR; specificities were 92% and 58%, respectively. Adding a safety margin of 120 μmols/L to helix TcB value could have safely avoided invasive SBR measurement in 50/98 (51%) babies., Conclusions: Consistency between TcB and rebound SBR is unpredictable in well neonates > 35 weeks' gestation but adopting a wide safety margin has potential to reduce blood sampling. Recommencement of phototherapy is uncommon in this population., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Planned caesarean section (CS) is a risk factor for neonatal respiratory distress caused by a greater volume of airway liquid in the absence of uterine contractions.Performing a newly conceptualised knee-to-chest flexion (KCF) manoeuvre at birth, mimicking uterine contraction-induced flexion may aid in expelling excess lung liquid., Objectives: To test whether performing a KCF manoeuvre at birth is feasible in infants born after planned CS and to test whether KCF leads to visible expulsion of lung liquid., Methods: Single-centre prospective interventional study in term infants born by planned CS at Leiden University Medical Centre, Netherlands. KCF was performed for a maximum of 45 s. Baseline characteristics were collected, primary outcome was ability to perform KCF and secondary outcome was any visible expulsion of fluid., Results: In 39 infants (mean (SD) gestational age 38.0 (0.7) weeks, birth weight 3537 (440) g), KCF could be performed in 21/39 (54%), whereas 18/39 (46.2%) starting vigorous breathing before KCF could be performed. Notably, visible lung liquid expulsion occurred in 9/21 (43%) infants. KCF duration averaged 29 (18) s. In 13/21 (62 %), KCF was not performed as per standard operating procedure. No adverse events were reported., Conclusion: It is feasible to perform KCF at birth in a large proportion of term infants born by planned CS, with visible expulsion of liquid in a significant proportion of these infants. Training healthcare providers to perform a standardised KCF could increase feasibility and success. Further studies are needed to assess feasibility and effectiveness of KCF., Trial Registration Number: NL74285.058.20., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: To describe strategies used to maximise follow-up after a neonatal randomised trial, how these differed for families of different ethnicity, socioeconomic status and urban versus rural residence and investigate relationships between the difficulty of follow-up and rate of neurosensory impairment., Method: hPOD was a multicentre randomised trial assessing oral dextrose gel prophylaxis for neonatal hypoglycaemia. Follow-up at 2 years was conducted from 2017 to 2021. We analysed all recorded contacts between the research team and participants' families. Neurosensory impairment was defined as blindness, deafness, cerebral palsy, developmental delay or executive function impairment., Results: Of 1321 eligible participants, 1197 were assessed (91%) and 236/1194 (19.8%) had neurosensory impairment. Participants received a median of five contacts from the research team (range 1-23). Those from more deprived areas and specific ethnicities received more contacts, particularly home tracking visits and home assessments. Impairment was more common among participants receiving more contacts (relative risk 1.81, 95% CI 1.34 to 2.44 for ≥7 contacts vs <7 contacts), and among those assessed after the intended age (76/318, 23.9% if >25 months vs 160/876, 18.3% if ≤25 months)., Conclusions: Varied contact strategies and long timeframes are required to achieve a high follow-up rate. Without these, the sociodemographics of children assessed would not have been representative of the entire cohort, and the rate of neurosensory impairment would have been underestimated. To maximise follow-up after randomised trials, substantial effort and resources are needed to ensure that data are useful for clinical decision-making., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: To determine the factors associated with second attempt success and the risk of adverse events following a failed first attempt at neonatal tracheal intubation., Design: Retrospective analysis of prospectively collected data on intubations performed in the neonatal intensive care unit (NICU) and delivery room from the National Emergency Airway Registry for Neonates (NEAR4NEOS)., Setting: Eighteen academic NICUs in NEAR4NEOS., Patients: Neonates requiring two or more attempts at intubation between October 2014 and December 2021., Main Outcome Measures: The primary outcome was successful intubation on the second attempt, with severe tracheal intubation-associated events (TIAEs) or severe desaturation (≥20% decline in oxygen saturation) being secondary outcomes. Multivariate regression examined the associations between these outcomes and patient characteristics and changes in intubation practice., Results: 5805 of 13 126 (44%) encounters required two or more intubation attempts, with 3156 (54%) successful on the second attempt. Second attempt success was more likely with changes in any of the following: intubator (OR 1.80, 95% CI 1.56 to 2.07), stylet use (OR 1.65, 95% CI 1.36 to 2.01) or endotracheal tube (ETT) size (OR 2.11, 95% CI 1.74 to 2.56). Changes in stylet use were associated with a reduced chance of severe desaturation (OR 0.74, 95% CI 0.61 to 0.90), but changes in intubator, laryngoscope type or ETT size were not; no changes in intubator or equipment were associated with severe TIAEs., Conclusions: Successful neonatal intubation on a second attempt was more likely with a change in intubator, stylet use or ETT size., Competing Interests: Competing interests: VN serves as the President of the Society of Critical Care Medicine (SCCM) 2023–2024. The views expressed in this manuscript are his and not intended to represent the opinions of the SCCM., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: The Glucose in Well Babies (GLOW) Study showed that there are two phases of low glucose concentrations in healthy newborn infants: an initial phase in which plasma concentrations of ketones are low; and a second phase in which low glucose concentrations are accompanied by elevated concentrations of ketones. The implications of these two phases for the brain differ depending on whether ketones are available as alternative substrate for brain metabolism. The purpose of this study was to estimate the duration of these two phases of neonatal low glucose concentrations in 66 healthy breastfed newborns from the GLOW Study during the first 5 days of life., Methods: The sum of glucose and beta-hydroxybutyrate (BOHB) was used as a proxy for the total concentrations of insulin-dependent fuels for the brain; a threshold value below 4 mmol/L was taken to indicate the presence of relative hyperinsulinism and a BOHB concentration above 0.5 mmol/L to indicate ketonaemia., Results: The first phase of low glucose concentrations lasted a median of 40 hours and in 15% of infants, this persisted beyond 60 hours. Fifty (76%) of the 66 infants subsequently had ketonaemia, which resolved at a median age of 76 hours (range 41->120 hours)., Conclusions: These data suggest that monitoring BOHB concentrations may be useful for interpreting glucose concentrations in newborns and screening for persistent hyperinsulinism., Competing Interests: Competing interests: DDDL has received consulting fees from Zealand Pharma, Crinetics Pharmaceuticals, Hanmi Pharmaceuticals, Eiger Pharma, Twist Biosciences and Rhythm Pharmaceuticals; has received research funding from Zealand Pharma, Rezolute, Crinetics Pharmaceuticals, Hanmi Pharmaceuticals, Twist Biosciences, Eiger Pharma and Ultragenyx for studies not discussed in this manuscript. CAS serves on the Data and Safety Monitoring Board for Zealand Pharma clinical trials in hyperinsulinism. DDDL and CAS serve on the Scientific Advisory Board for Congenital Hyperinsulinism International., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Competing Interests: Competing interests: None declared.

Objective: Caffeine is widely used in preterm infants to prevent or treat apnoea of prematurity. Adverse gastrointestinal effects of caffeine have not been thoroughly researched in preterm infants. With this systematic review and meta-analysis, we aim to summarise the results of trials on the gastrointestinal effects of caffeine in preterm infants., Design: We searched MEDLINE, Web of Science, Scopus and ClinicalTrials.gov up to 21 April 2023. We included randomised controlled trials assessing caffeine versus placebo in preterm neonates and reporting gastrointestinal side effects. Risk of bias was assessed using the Cochrane Risk of Bias tool. A Bayesian meta-analysis was performed to estimate the pooled OR of gastrointestinal side effects., Results: Nine trials involving 2746 preterm infants were analysed. Seven trials assessing necrotising enterocolitis and four trials assessing feeding intolerance in our meta-analysis found no differences between caffeine and placebo (OR=1.007 (95% credible interval 0.021, 5.462), I 2 =97.4%, and OR=1.266 (95% credible interval 0.064, 28.326), I 2 =84.8%, respectively). Four trials assessed the outcomes spontaneous intestinal perforation, constipation, gastrointestinal disorder (composite outcome: gastro-oesophageal regurgitation or dilated bowel loops), age at oral feeding and cholestasis syndrome and found no differences between groups. One trial assessed the outcomes gastro-oesophageal symptoms and duration of tube feeding and found that caffeine was associated with a reduced burden of gastro-oesophageal reflux symptoms at 2 weeks (p<0.05), but not at term., Conclusions: According to this systematic review and meta-analysis, the use of caffeine at usual doses in preterm infants does not seem to be associated with significant gastrointestinal adverse effects., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: Regarding the use of lung ultrasound (LU) in neonatal intensive care units (NICUs) across Europe, to assess how widely it is used, for what indications and how its implementation might be improved., Design and Intervention: International online survey., Results: Replies were received from 560 NICUs in 24 countries between January and May 2023. LU uptake varied considerably (20%-98% of NICUs) between countries. In 428 units (76%), LU was used for clinical indications, while 34 units (6%) only used it for research purposes. One-third of units had <2 years of experience, and only 71 units (13%) had >5 years of experience. LU was mainly performed by neonatologists. LU was most frequently used to diagnose respiratory diseases (68%), to evaluate an infant experiencing acute clinical deterioration (53%) and to guide surfactant treatment (39%). The main pathologies diagnosed by LU were pleural effusion, pneumothorax, transient tachypnoea of the newborn and respiratory distress syndrome. The main barriers for implementation were lack of experience with technical aspects and/or image interpretation. Most units indicated that specific courses and an international guideline on neonatal LU could promote uptake of this technique., Conclusions: Although LU has been adopted in neonatal care in most European countries, the uptake is highly variable. The main indications are diagnosis of lung disease, evaluation of acute clinical deterioration and guidance of surfactant. Implementation may be improved by developing courses and publishing an international guideline., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: To investigate the risk for sensorineural hearing impairment (SNHI) in preterm infants, and to what extent the risk is attributed to perinatal morbidities and therapies., Design: Population-based cohort study using data from several nationwide registries., Setting: Norwegian birth cohort 1999-2014, with data on SNHI until 2019., Participants: 60 023 live-born preterm infants, divided in moderate-late preterm (MLP) infants (32-36 weeks), very preterm (VP) infants (28-31 weeks) and extremely preterm (EP) infants (22-27 weeks), and a reference group with all 869 797 term-born infants from the study period., Main Outcome Measures: SNHI defined by selected ICD-10 codes, recorded during minimum 5-year observation period after birth., Results: The overall SNHI prevalence in the preterm cohort was 1.4% compared with 0.7% in the reference group. The adjusted risk ratios (95% CIs) for SNHI were 1.7 (1.5-1.8) in MLP infants, 3.3 (2.8-3.9) in VP infants and 7.6 (6.3-9.1) in EP infants. Among EP infants, decreasing gestational age was associated with a steep increase in the risk ratio of SNHI reaching 14.8 (7.7-28.7) if born at 22-23 weeks gestation. Among the VP and MLP infants, mechanical ventilation and antibiotic therapy had strongest association with increased risk of SNHI, but infants not receiving these therapies remained at increased risk. Among EP infants intracranial haemorrhage increased the already high risk for SNHI. We found no signs of delayed or late-onset SNHI in preterm infants., Conclusion: Preterm birth is an independent risk factor for SNHI. Invasive therapies and comorbidities increase the risk, predominantly in infants born after 28 weeks gestation., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: The rPAP respiratory support system, used for delivery room stabilisation with nasal prongs, has been shown to reduce the need for intubation in extremely preterm infants. A simplified version of the system has been developed. The purpose of this study was to determine the feasibility of providing uninterrupted respiratory support with the simplified rPAP from birth up to 4 hours of life and to assess ease of use for skin-to skin stabilisation., Methods: This was a non-randomised feasibility study conducted at Karolinska University Hospital, Sweden. Respiratory support with continuous positive airway pressure (CPAP) and positive pressure ventilation if needed was given with the simplified rPAP using heated humidified gases. Respiratory support was provided in the delivery room, during transportation and in the neonatal unit, for a maximum of 4 hours., Results: 32 preterm infants with a mean (SD) gestational age of 33.4 weeks (±1.2) were included. Of 17 infants born vaginally, 13 were stabilised skin-to-skin. The remaining infants were stabilised on a resuscitation table. All infants received CPAP and nine received positive pressure ventilation. 31 infants received continued support during transport and after arrival in the neonatal unit. Minor interruptions in CPAP support occurred in all infants. The study did not reveal problems with usability of the system., Conclusion: It is feasible to stabilise preterm infants with the simplified respiratory support system both skin-to-skin and on a resuscitation table, and to provide continued respiratory support with the same system during transportation and in the neonatal unit., Trial Registration Number: NCT04244890., Competing Interests: Competing interests: TD is one of the designers of the original and simplified rPAP respiratory support system., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: To determine if combining high-frequency oscillatory ventilation (HFOV) with additional sigh breaths would improve end-expiratory lung volume (EELV) and oxygenation in preterm infants., Design: Prospective interventional crossover study., Setting: Neonatal intensive care unit., Patients: Ventilated preterm infants <36 weeks corrected gestational age receiving HFOV., Interventions: Infants were randomly assigned to receive HFOV with sigh breaths followed by HFOV-only (or vice versa) for four alternating periods. Sigh breaths were delivered with an inspiratory time of 1 s, peak inspiratory pressure of 30 cmH 2 0 and frequency of three breaths/min., Main Outcome Measures: Electrical impedance tomography measured the effect of sigh breaths on EELV and ventilation distribution. Physiological variables were recorded to monitor oxygenation. Measurements were taken at 30 and 60 min postchange of HFOV mode and compared with baseline., Results: Sixteen infants (10 males, 6 females) with a median (range) gestational age at birth of 25.5 weeks (23-31), study weight of 950 g (660-1920) and a postnatal age of 25 days (3-49) were included in the study. The addition of sigh breaths resulted in a significantly higher global EELV (mean difference±95% CI) (0.06±0.05; p=0.04), with increased ventilation occurring in the posterior (dependent) and left lung segments, and improved oxygen saturations (3.31±2.10; p<0.01)., Conclusion: Intermittent sigh breaths during HFOV were associated in the short-term with an increased EELV in the posterior and left lungs, and improved oxygen saturations in preterm infants., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Milk curd obstruction (MCO), in which milk becomes inspissated, is a rare, serious, complication of preterm birth. Case reports implicate male sex and bovine-derived human milk fortifier (HMF) use as predisposing factors. We investigated this through a case-control study., Methods: MCO cases in the Starship Child Health neonatal database between 2008 and 2020 were matched with controls in a 1:2 ratio based on gestational age (±1 week), birth weight (±200 g) and date of birth (±1 month). Data were analysed using the Student's t-test, Mann-Whitney U-test or χ² test as appropriate. Data are median (IQR) or n (%)., Results: Of 20 MCO cases, gestation was 26.1 (24.5-28.1) weeks, birth weight was 822 (713-961) g, 15 (75%) were male. 40 controls were well-matched for gestation (26.1 (24.8-27.9) weeks) and birth weight (849 (690-1066) g) but only 18 (45%) were male (p=0.05). MCO occurred at 21 (15-33) days; 6 (30%) cases died compared with 3 (7.5%) controls (p=0.06). HMF was commenced at 243 (150-309) hours in cases and 224 (172-321) hours in controls (p=0.95); full-fortification (manufacturer's recommended dose) was achieved in 8 (40%) cases and 27 (68%) controls (p=0.08). In cases, MCO occurred 10 (7-17) days after commencing HMF. Medically/surgically-managed gut pathology occurred in 7 (35%) cases prior to MCO but in no controls (p<0.001)., Conclusions: Our data support male sex but not HMF use as a predisposition to MCO. Evidence of prior medical/surgical gut pathology may be a premonition for MCO; however, further research is required to confirm this., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Prematurity is a significant risk for bronchopulmonary dysplasia related pulmonary artery pressure., Objective: To determine the association between pulmonary artery pressure in the early days of life and the development of bronchopulmonary dysplasia or mortality., Methods: This prospective observational cohort study included infants born at <32 weeks and weighing <1500 g. Pulmonary artery pressure was measured between postnatal days 3 and 7. Pulmonary hypertension was defined as systolic pulmonary artery pressure ≥40 mm Hg or systolic pulmonary artery pressure/systolic blood pressure >0.5 (pulmonary hypertension criterion-1). Infants were categorised into pulmonary hypertension and non-pulmonary hypertension groups. The primary endpoint was bronchopulmonary dysplasia or mortality. Receiver operating characteristic analysis established a new threshold value for predicting bronchopulmonary dysplasia or mortality (pulmonary hypertension criterion-2). Infants were reanalysed according to new criteria., Results: A total of 329 infants were included in this study. Moderate-to-severe pulmonary hypertension was identified in 24% (n=79) of the infants. The pulmonary hypertension group exhibited a significantly lower gestational age, lower birth weight and a higher incidence of small for gestational age. Systolic pulmonary artery pressure >25 mm Hg or systolic pulmonary artery pressure/systolic blood pressure >0.35 was defined as the pulmonary hypertension criterion-2. Logistic regression analysis identified pulmonary hypertension criterion-2 as an independent risk factor for moderate-to-severe bronchopulmonary dysplasia or mortality (OR 2.67, 95% CI 1.3 to 5.51, p<0.01)., Conclusion: Pulmonary artery pressure exceeding 25 mm Hg in the early days of life may be considered a potential risk factor for bronchopulmonary dysplasia or mortality., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Less invasive surfactant administration (LISA) is an increasingly popular technique to deliver surfactant to spontaneously breathing preterm infants with respiratory distress syndrome. The optimal method of alleviating the pain and discomfort associated with LISA, either pharmacological or non-pharmacological, while maintaining spontaneous respiration remains unclear. There is limited evidence to guide clinicians, resulting in wide variations in practice. The aim of this article is to summarise the current knowledge and evidence gaps regarding the use of premedication prior to LISA., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: This study investigates whether and to what extent cerebral injury is associated with bilateral blindness in extremely preterm infants, which has been attributed mainly to retinopathy of prematurity (ROP)., Design: Multicentre analysis of children born from 1994 to 2021 at gestational age 22 0/7 to 28 6/7 weeks with follow-up at 18-26 months. Logistic regression examined the adjusted association of bilateral blindness with severe ROP and/or cerebral injury among extremely preterm infants., Exposures: Severe ROP and cerebral injury, the latter defined as any of the following on cranial imaging: ventriculomegaly; blood/increased echogenicity in the parenchyma; cystic periventricular leukomalacia., Main Outcome Measures: Bilateral blindness, defined as a follow-up examination meeting criteria of 'blind-some functional vision' or 'blind-no useful vision' in both eyes., Results: The 19 863 children included had a mean gestational age of 25.6±1.7 weeks, mean birth weight of 782±158 g and 213 (1%) had bilateral blindness. Multiplicative interaction between ROP and cerebral injury was statistically significant. For infants with only severe ROP (n=3130), odds of blindness were 8.14 times higher (95% CI 4.52 to 14.65), and for those with only cerebral injury (n=2836), odds were 8.38 times higher (95% CI 5.28 to 13.28), compared with the reference group without either condition. Risks were not synergistic for infants with both severe ROP and cerebral injury (n=1438, adjusted OR=28.7, 95% CI 16.0 to 51.7, p<0.0001)., Conclusions: In a group of extremely preterm infants, severe ROP and cerebral injury were equally important risk factors for blindness. Besides ROP, clinicians should consider cerebral injury as a cause of blindness in children born extremely preterm., Trial Registration Number: NCT00063063., Competing Interests: Competing interests: NA is an advisor to ResBiotic and Alveolus Bio and serves on the Data and Safety Monitoring Board for Shire/Oak Hill Bio. CMC has a consulting agreement with ReAlta Life Sciences (for a new drug in clinical trials for hypoxic ischaemic encephalopathy), and IP in a company, CryoCell (for a cell therapy for HIE). AD has a grant from the Neonatal Research Network (NRN). CPT is supported by grants from the National Institutes of Health (K23HL157618). CPT is supported by a grant from Owlet Baby Care for an investigator-initiated study (ClinicalTrials.gov identifier: NCT05774470) and also has a patent application pending for a bradycardia predictor and interrupter. VVS is supported by a grant from the American Heart Association (23CDA1048106)., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

ObjectiveGlobally, demand for donor human milk (DHM) is increasing with WHO guidelines recommending DHM as the first line nutrition for premature infants in the absence or shortfall of maternal milk. Policymakers and clinicians currently have limited knowledge regarding costs incurred by human milk banks (HMBs) making the planning and resourcing of these services challenging. This study aimed to evaluate costs in a national network of HMBs in the UK., Design and Setting: All 14 UK HMBS were invited to complete a bottom-up microcosting survey from 1 April 2021 to 31 March 2022 covering four key areas: Staffing, equipment, donor screening and incidental costs. Total annual salary costs included on-costs (ie, national insurance, pensions), qualifications, overheads (ie, non-staff costs) and capital overheads. The annual equivalent costs for each equipment item were based on the total cost over its useful life and discounted at 3.5%., Results: 10 out of 14 milk banks provided responses with more complete datasets returned by larger milk banks. Staffing costs ranged from £24 983 to £476 194 (n=9, mean: £159 798) and considerable expertise was provided voluntarily or from non-costed staffing. Other costs included equipment (n=7, range: £2600-£51 453, mean: £19 279), donor screening (n=6, range: £925-£38 057, mean: £18 570), incidentals (n=6, range: £650-£109 996, mean: £23 774). The total annual cost of operating a milk bank annually was £202 719 (range, £27 583-£675 699) to provide between 205 and 3495 litres of DHM. The cost per litre averaged £173.49 (range, £95.94-£274.88)., Conclusions: The average cost of DHM is currently higher than current cost recovery tariffs and this study likely under-represents total costs. This study provides useful benchmarking data for future economic analyses, trial development and service planning., Competing Interests: Competing interests: NS and GW are co-founders of and consultants for the Human Milk Foundation, a charity dedicated to research, education and equitable access to donor human milk., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

Objective: To investigate the relationship between the fraction of fetal haemoglobin (HbF(%)) and oxygen requirement as determined by the fraction of inspired oxygen (FiO 2 ) and alveolar-arterial gradient (A-a gradient). Increased alveolar exposure to oxygen may explain the association between decreased HbF(%) and the development of bronchopulmonary dysplasia (BPD)., Design: Longitudinal, retrospective, observational study., Setting: Tertiary-level neonatal intensive care unit, referral centre for southern Sweden., Patients: Four hundred forty very preterm infants born before gestational week 30, 2009-2015., Intervention: Regular clinical practice., Main Outcome Measures: The FiO 2 and A-a gradient were determined at the time-point of 10 015 arterial blood gas analyses obtained during postnatal days 1-7. The relationship between HbF(%) and FiO 2 and A-a gradient and the modifying influence of other factors affecting haemoglobin oxygen affinity were evaluated., Results: We found a significant relationship between a low fraction of HbF and an increase in FiO 2 and A-a gradient, respectively. These relationships remained significant after adjusting for pH, pCO 2 , postnatal age, gestational age and sex., Conclusion: These high-resolution data show that decreased HbF(%) during the first postnatal week is associated with increased FiO 2 and A-a gradient in very preterm infants. Increased alveolar exposure to oxygen and resulting oxidative stress may, at least partly, explain the previously reported associations between decreased HbF, blood transfusions and the development of BPD in preterm infants., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

Objective: To validate a hypoxic ischaemic encephalopathy (HIE) prediction algorithm to identify infants at risk of HIE immediately after birth using readily available clinical data., Design: Secondary review of electronic health record data of term deliveries from January 2017 to December 2021., Setting: A tertiary maternity hospital., Patients: Infants >36 weeks' gestation with the following clinical variables available: Apgar Score at 1 min and 5 min, postnatal pH, base deficit, and lactate values taken within 1 hour of birth INTERVENTIONS: Previously trained open-source logistic regression and random forest (RF) prediction algorithms were used to calculate a probability index (PI) for each infant for the occurrence of HIE., Main Outcome: Validation of a machine learning algorithm to identify infants at risk of HIE in the immediate postnatal period., Results: 1081 had a complete data set available within 1 hour of birth: 76 (6.95%) with HIE and 1005 non-HIE. Of the 76 infants with HIE, 37 were classified as mild, 29 moderate and 10 severe. The best overall accuracy was seen with the RF model. Median (IQR) PI in the HIE group was 0.70 (0.53-0.86) vs 0.05 (0.02-0.15), (p<0.001) in the non-HIE group. The area under the receiver operating characteristics curve for prediction of HIE=0.926 (0.893-0.959, p<0.001). Using a PI cut-off to optimise sensitivity of 0.30, 936 of the 1081 (86.5%) infants were correctly classified., Conclusion: In a large unseen data set an open-source algorithm could identify infants at risk of HIE in the immediate postnatal period. This may aid focused clinical examination, transfer to tertiary care (if necessary) and timely intervention., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: To examine whether changes in survival without moderate or severe neurodevelopmental impairment (NDI) at 18-26 months' corrected age from 1999 to 2018 differed between male and female infants., Design: This retrospective cohort study used data from the NICHD Neonatal Research Network hospitals. Robust Poisson regression models were used to estimate adjusted relative risks (aRRs) and 95% CIs for survival without moderate or severe NDI between males and females. Interactions between sex and time were assessed to evaluate temporal differences in the outcome by sex. Variables adjusted for included centre, maternal age, ethnicity/race, gestational age and small for gestational age., Patients: Inborn infants with gestational age of 22-26 weeks at NICHD Neonatal Research Network hospitals from 1999 to 2018., Main Outcome Measure: Change over time in survival without moderate or severe NDI at 18-26 months' corrected age between male and female infants., Results: Of 26 307 infants, 13 045 (49.6%) were male. Survival without moderate or severe NDI declined for both sexes over time, from 32.9% to 30.6% for males and from 47.4% to 40.0% for females, between 1999-2003 and 2014-2018. Males were less likely than females to survive without moderate or severe NDI (aRR=0.80; 95% CI 0.78 to 0.83). Changes in survival without moderate or severe NDI did not differ between males and females., Conclusion: There were no differential changes in survival without moderate or severe NDI between male and female infants., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: Reports of hyperinsulinism typically focus on infants managed by highly specialised services. However, neonates with hyperinsulinism are initially managed by neonatologists and often not referred to specialists. This study aimed to characterise the diversity in presentation and management of these infants., Setting: Level 3 neonatal intensive care., Patients: Neonates with hyperinsulinism, defined as blood glucose <2.8 mmol/mL and insulin level >6 pmol/L., Design: 7-year retrospective study (January 2015-December 2021)., Results: 99 cases were identified: severe -treated with diazoxide (20%), moderate -clinically concerning hyperinsulinism not treated with diazoxide (30%), mild -biochemical hyperinsulinism (50%). Birth weight z-score was -1.02±2.30 (mean±SD), 42% were preterm, but neither variable correlated with clinical severity. The severe group received a higher concentration of intravenous glucose (27±12%) compared with the moderate (15±7%) and mild (16±10%) groups (p<0.001). At diagnosis, the intravenous glucose intake was similar in the severe (7.43±5.95 mg/kg/min) and moderate (5.09±3.86 mg/kg/min) groups, but higher compared with the mild group (3.05+/2.21 mg/kg/min) (p<0.001). In the severe group, term infants started diazoxide earlier (9.9±4.3 days) compared with preterm (37±26 days) (p=0.002). The national congenital hyperinsulinism service was consulted for 23% of infants, and 3% were transferred., Conclusions: This study highlights the diversity in clinical presentation, severity and prognosis of neonatal hyperinsulinism, irrespective of birth weight and gestational age. More infants were small rather than large for gestational age, and the majority had transient hyperinsulinism and were not referred to the national centre, or treated with diazoxide. Further research is required to understand the breadth of neonatal hyperinsulinism and optimal management., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: Neonatal meningitis significantly contributes to neonatal morbidity and mortality, yet large-scale epidemiological data in developing countries, particularly among very preterm infants (VPIs), remain sparse. This study aimed to describe the epidemiology of meningitis among VPIs in China., Design: Cross-sectional study using the Chinese Neonatal Network database from 2019 to 2021., Setting: 79 tertiary neonatal intensive care units in China., Patients: Infants with gestational age <32 weeks or birth weight <1500 g., Main Outcome Measures: Incidence, pathogen distribution, antimicrobial use and outcomes of bacterial and fungal meningitis., Results: Of 31 915 VPIs admitted, 122 (0.38%) infants were diagnosed with culture-confirmed meningitis, with 14 (11.5%) being early-onset (≤6 days of age) and 108 (88.5%) being late-onset (>6 days of age). The overall in-hospital mortality was 18.0% (22/122). A total of 127 pathogens were identified, among which 63.8% (81/127) were Gram-negative bacteria, 24.4% (31/127) were Gram-positive bacteria and 11.8% (15/127) were fungi. In terms of empirical therapy (on the day of the first lumbar puncture), the most commonly used antibiotic was meropenem (54.9%, 67/122). For definitive therapy (on the sixth day following the first lumbar puncture, 86 cases with available antibiotic data), meropenem (60.3%, 35/58) and vancomycin (57.1%, 16/28) were the most used antibiotics for Gram-negative and Gram-positive bacterial meningitis, respectively. 44% of infants with Gram-positive bacterial meningitis and 52% with Gram-negative bacterial meningitis received antibiotics for more than 3 weeks., Conclusion: 0.38% of VPIs in Chinese neonatal intensive care units were diagnosed with meningitis, experiencing significant mortality and inappropriate antibiotic therapy. Gram-negative bacteria were the predominant pathogens, with fungi emerging as a significant cause., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Competing Interests: Competing interests: None declared.

Cystic fibrosis (CF) is common, multisystem, life-limiting genetic condition, predominantly in the Caucasian population. There have been recent advances in the management of CF, in particular in the last 5 years following approval of cystic fibrosis transmembrane conductance regulator (CFTR) protein modulators by the National Health Service (NHS) for use in people with CF (pwCF).Traditionally, almost 40% of female patients with CF (fwCF) and over 95% of male patients with CF (mwCF) have issues with subfertility or infertility. CFTR modulators have transformed the lives of pwCF who have the specific genetic variants that respond to the treatment.Women taking CFTR modulators, particularly highly effective CFTR modulators (elexacaftor, tezacaftor and ivacaftor), have shown resolution of infertility and successful pregnancies without fertility treatment. At present male patients taking CFTR modulators have not shown improvement in infertility. Unplanned pregnancies are on the increase in fwCF. fwCF have had significantly improved general health when taking CFTR modulators. Subsequently many fwCF now become pregnant and choose to continue their pregnancies to term, with positive outcomes.Clinical and biochemical status of the newborn babies with CF, who are born to fwCF on CFTR modulators, can be very different when compared with the other babies with CF who are unexposed to CFTR modulators in utero.New opportunities bring new challenges. This review highlights how infants exposed to CFTR modulators in utero can be affected, and suggests how they should be monitored., Competing Interests: Competing interests: HSK has received speaker honorarium from Vertex Pharmaceuticals (Europe) Limited for an educational non-promotional talk., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: T-piece is recommended for respiratory support during neonatal stabilisation. Bench studies have shown a delay >30 s in achieving changes in fraction of inspired oxygen (FiO 2 ) at the airway when using the T-piece. Using a face mask adds dead space (DS) to the patient airway. We hypothesised that adding face mask to T-piece systems adversely affects the time required for a change in FiO 2 to reach the patient., Methods: Neopuff (Fisher and Paykel, Auckland, New Zealand) and rPAP (Inspiration Healthcare, Croydon, UK) were used to ventilate a test lung. DS equivalent to neonatal face masks was added between the T-piece and test lung. Additionally, rPAP was tested with nasal prongs. Time course for change in FiO 2 to be achieved at the airway was measured for increase (0.3-0.6) and decrease (1.0-0.5) in FiO 2 . Primary outcome was time to reach FiO 2 +/-0.05 of the set target. One-way analysis of variance was used to compare mean time to reach the primary outcome between different DS volumes., Results: In all experiments, the mean time to reach the primary outcome was significantly shorter for rPAP with prongs compared with Neopuff and rPAP with face mask DS (p<0.001). The largest observed difference occurred when testing a decrease in FiO 2 with 10 mL tidal volume (TV) without leakage (18.3 s for rPAP with prongs vs 153.4 s for Neopuff with face mask DS). The shortest observed time was 13.3 s when increasing FiO 2 with 10 mL TV with prongs with leakage and the longest time was 172.7 s when decreasing FiO 2 with 4 mL TV and added face mask DS without leak., Conclusion: There was a delay in achieving changes in oxygen delivery at the airway during simulated ventilation attributable to the mask volume. This delay was greatly reduced when using nasal prongs as an interface. This should be examined in clinical trials., Competing Interests: Competing interests: TD is one of the designers of the original rPAP respiratory support system., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: Intravenous epinephrine administration is preferred during neonatal resuscitation, but may not always be rapidly administered due to lack of equipment or trained staff. We aimed to compare the time to return of spontaneous circulation (ROSC) and post-ROSC haemodynamics between intravenous, endotracheal (ET) and intranasal (IN) epinephrine in severely asphyxic, bradycardic newborn lambs., Methods: After instrumentation, severe asphyxia (heart rate <60 bpm, blood pressure ~10 mm Hg) was induced by clamping the cord in near-term lambs. Resuscitation was initiated with ventilation followed by chest compressions. Lambs were randomly assigned to receive intravenous (0.02 mg/kg), ET (0.1 mg/kg) or IN (0.1 mg/kg) epinephrine. If ROSC was not achieved after three allocated treatment doses, rescue intravenous epinephrine was administered. After ROSC, lambs were ventilated for 60 min., Results: ROSC in response to allocated treatment occurred in 8/8 (100%) intravenous lambs, 4/7 (57%) ET lambs and 5/7 (71%) IN lambs. Mean (SD) time to ROSC was 173 (32) seconds in the intravenous group, 360 (211) seconds in the ET group and 401 (175) seconds in the IN group (p<0.05 intravenous vs IN). Blood pressure and cerebral oxygen delivery were highest in the intravenous group immediately post-ROSC (p<0.05), whereas the ET group sustained the highest blood pressure over the 60-min observation (p<0.05)., Conclusion: Our study supports neonatal resuscitation guidelines, highlighting intravenous administration as the most effective route for epinephrine. ET and IN epinephrine should only be considered when intravenous access is delayed or not feasible., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

Rationale: Preterm neonates needing rescue treatments with inotropes and/or inhaled nitric oxide (iNO) (acute critical illnesses, ACIs) in neonatal intensive care units (NICUs) are at high risk of mortality. While targeted neonatal echocardiography consultations (TNE) are increasingly used to guide management, its clinical impact need evaluation., Objectives: To investigate clinical outcomes in relation to TNE utilisation during episodes of ACIs among preterm neonates., Methods: This retrospective cohort study, conducted at two tertiary NICUs over 10 years, included neonates<37 weeks gestational age (GA) who developed ACIs. Patients receiving TNE-guided care (TNE within 24 hours of treatment initiation) were compared with non-TNE management. Outcomes included predischarge mortality, episode-related mortality (<7 days) and a new diagnosis of intraventricular haemorrhage≥grade 3 (IVH-3). Inverse probability of treatment weighting (IPTW) using propensity score was used to account for confounders, including site, birth years and baseline illness severity., Measurements and Main Results: Of 622 included patients, 297 (48%) had TNE; median (IQR) GA at ACI was 26.4 (25.0-28.4) weeks. TNE group demonstrated higher baseline mean airway pressure, oxygen requirement and heart rate and frequently received both inotrope and iNO during ACI. IPTW analysis revealed TNE was associated with lower mortality (adjusted OR (95% CI) 0.75 (0.59 to 0.95)), episode-related mortality (0.54 (0.40 to 0.72)) and death or IVH-3 (0.78 (0.62 to 0.99)). TNE group received more varied inotropic agents, demonstrated earlier improvements in blood pressures, without increasing overall inotrpoic burden., Conclusions: Among preterm neonates requiring rescue treatments with inotropes/iNO, TNE utilisation to guide clinical management may be associated with improved survival., Competing Interests: Competing interests: All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest and do not have any conflict of interest., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)