The reasons for international variation in NEC incidence are an important area for future research. Reliable inferences require clarity in defining population coverage and consistency in the case definition applied. PROSPERO INTERNATIONAL PROSPECTIVE REGISTER OF SYSTEMATIC REVIEWS REGISTRATION NUMBER: CRD42015030046.

ObjectiveTo analyse survival trends and regional variation for very preterm infants admitted to neonatal care.SettingAll neonatal units in England.PatientsInfants born at 22+0–31+6 weeks+daysgestational age (GA) over 2008–2014 and admitted to neonatal care; published data for admitted infants 22+0–25+6 weeks+days GA in 1995 and 2006, and for live births at 22+0–31+6 weeks+days GA in 2013.MethodsWe obtained data from the National Neonatal Research Database. We used logistic regression to model survival probability with birth weight, GA, sex, antenatal steroid exposure and multiple birth included in the risk adjustment model and calculated annualpercentage change (APC) for trends using joinpoint regression. We evaluated survival over a 20-year period for infants <26 weeks’ GA using additional published data from the EPICure studies.ResultsWe identified 50 112 eligible infants. There was an increase in survival over 2008–2014 (2008: 88.0%; 2014: 91.3%; adjusted APC 0.46% (95% CI 0.30 to 0.62) p<0.001). The greatest improvement was at 22+0–23+6 weeks (APC 6.03% (95% CI 2.47 to 3.53) p=0.002). Improvement largely occurred in London and South of England (APC: London 1.26% (95% CI 0.60 to 1.96); South of England 1.09% (95% CI 0.36 to 1.82); Midlands and East of England 0.15% (95% CI −0.56 to 0.86); and North of England 0.26% (95% CI −0.54 to 1.07)). Survival at the earliest gestations improved at a similar rate over 1995–2014 (22+0–25+6 weeks, APC 2.73% (95% CI 2.35 to 3.12), p value for change=0.25).ConclusionsContinued national improvement in the survival of very preterm admissions masks important regional variation. Timely assessment of preterm survival is feasible using electronic records.

Aim: This review examined how applicable national and regional clinical practice guidelines and recommendations for managing neonates born to mothers with COVID-19 mothers were to the evolving pandemic. Methods: A systematic search and review identified 20 guidelines and recommendations that had been published by May 25, 2020. We analysed documents from 17 countries: Australia,

BackgroundThe National Neonatal Research Database (NNRD) is a rich repository of pre-defined clinical data extracted at regular intervals from point-of-care, clinician-entered electronic patient records on all admissions to National Health Service neonatal units in England, Wales, and Scotland. We describe population coverage for England and assess data completeness and accuracy.MethodsWe determined population coverage of the NNRD in 2008–2014 through comparison with data on live births in England from the Office for National Statistics. We determined the completeness of seven data items on the NNRD. We assessed the accuracy of 44 data items (16 patient characteristics, 17 processes, 11 clinical outcomes) for infants enrolled in the multi-centre randomised controlled trial, Probiotics in Preterm Study (PiPs). We compared NNRD to PiPs data, the gold standard, and calculated discordancy rates using predefined criteria, and sensitivity, specificity and positive predictive values (PPV) of binary outcomes.ResultsThe NNRD holds complete population data for England for infants born alive from 25+0 to 31+6 (completed weeks) of gestation; and 70% and 90% for those born at 23 and 24 weeks respectively. Completeness of patient characteristics was over 90%. Data were linked for 2257 episodes of care received by 1258 of the 1310 babies recruited to PiPs. Discordancy rates were <5% for 13/16 patient characteristics (exceptions: mode of delivery 8.7%; maternal ethnicity 10.2%, Lower layer Super Output Area 16.5%); <5% for 9/16 processes (exceptions: medical treatment for Patent ductus arteriosus 6.1%, high-dependency days 10.2%, central line days 11.2%, type of first milk 22.3%; and during first 14 days, summary of types of milk 13.8%; number of days of antibiotics 9.0%; whether antacid given 5.1%); and <5% for 10/11 clinical outcomes (exception: Bronchopulmonary dysplasia, defined as oxygen dependency at 36 weeks postmenstrual age 3.3%). The specificity of NNRD data was >85% for all outcomes; sensitivity ranged from 50–100%; PPV ranged from 58.8 (95% CI 40.8–75.4%) for porencephalic cyst to 99.7 (95% CI 99.2, 99.9%) for survival to discharge.ConclusionsThe completeness and quality of data held in the NNRD is high, providing assurance in relation to use for multiple purposes, including national audit, health service evaluations, quality improvement, and research.

Word count: Abstract (300 /300w) Background: Necrotising enterocolitis (NEC), a feared neonatal gastrointestinal inflammatory disease with high mortality and morbidity, is growing in global relevance as birth rates and early survival of low gestational age (GA) infants increases. Population data are scant and pathogenesis is incompletely understood but enteral feed exposures are believed to influence risk. Methods:We conducted a two-year national surveillance study to quantify the total population burden of severe NEC (confirmed at laparotomy and/or leading to death) in England, and a propensity score analysis of the impact of early feeds of maternal milk (MM), and avoidance of bovine-origin formula (BOF) and milk fortifier (BMF), on NEC risk in very preterm infants. Findings:During the study period 118,073 infants (14,678 <32w GA) were admitted to 163 neonatal units across 23 networks; 531 (462 <32w GA) developed severe NEC; 247 died, 139 following laparotomy. Among infants <32w GA the adjusted network incidence ranged from 2·51% to 3·85% with no evidence of unusual variation in relation to the national incidence of 3·13% (95%CI 2·85, 3·42) despite variation in feeding practices. Also among infants <32w GA, commencing any MM within seven postnatal days resulted in an Absolute Risk Difference (ARD) of -0·88% (95% CI -1·15, -0·61), Relative Risk (RR) 0·69 (95% CI 0·60, 0·78), and Number Needed to Treat (NNT) 114 (95% CI 87, 136); equivalent figures for infants receiving no, compared to any bovine-origin products within 14 postnatal days were ARD -0·65% (95% CI -1·01, -0·29), RR 0·61 (95% CI 0·39, 0·83), NNT 154 (95% CI 94, 345). Interpretation:Commencing MM early and avoiding bovine-origin products may reduce NEC but absolute risk reductions appear small. The rarity of severe NEC requires national and international collaboration for adequately powered preventive trials.Funding: This study represents independent research funded by the National Institute for Health Research (NIHR). Research in contextEvidence before this study Necrotising enterocolitis (NEC) is a feared, acute neonatal gastrointestinal inflammatory disease with high mortality and morbidity. Reliable population incidence data are necessary for designing preventive and treatment studies. Enteral feeding stratagems are widely believed to influence NEC risk. When maternal milk (MM) is insufficient or unavailable some clinicians prefer pasteurised human donor milk (HDM) over bovine-origin formula (BOF) in the hope that avoidance of bovine-origin products will be protective and/or pasteurised HDM will retain some of the protective properties of MM. Others prefer BOF to HDM as the composition of the former is consistent, nutrient density is higher, and costs are lower. Other uncertainties relate to the timing of introduction of milk feeds in very preterm infants, and use of bovineorigin fortifier (BMF) (additional vitamins, minerals, and nutrients added to human milk).We conducted a systematic search of studies from the 34 countries in the Organisation fo...

Importance: Necrotising Enterocolitis (NEC) is a major cause of neonatal morbidity and mortality. Preventive and therapeutic research, surveillance and quality improvement initiatives, are hindered by variations in case-definitions. Objective: To develop a gestational age (GA) specific case-definition for NEC. Design, Setting, and Participants: We conducted a prospective 34 month population study using clinician-recorded findings between December 2011 and September 2014 across all 163 neonatal units in England. Exposure: Abdominal X-ray (AXR) performed to investigate clinical concerns. Main outcomes and measures: Ordinal NEC likelihood score, dichotomous casedefinition, and GA-specific probability plots. We secured clinician commitment to record data prospectively into each infant's Electronic Patient Record (EPR). We obtained study data from the UK National Neonatal Research Database that holds information extracted regularly from the neonatal EPR. We split study data into test and validation datasets. We entered GA, birth-weight z score, clinical and AXR findings as candidate variables in a logistic regression model, performed model fitting 1000 times, averaged the predictions, and used estimates from the fitted model to develop an ordinal NEC score, and cut-points to develop a dichotomous case-definition based upon the highest area under the receiver operating characteristic curves and positive predictive values. Results: We included data from 3866 infants (2978 without and 888 with NEC). Less mature infants were less likely to present with pneumatosis, blood or mucus in stools, and were more likely to have a gasless AXR. In the ordinal NEC score analysis we allocated three points to pneumatosis, two points to blood in stools. One point each was allocated to: abdominal tenderness;abdominal discolouration; the composite of increased and/or bilious aspirates AND abdominal distension;one or more of pneumoperitoneum, fixed loop and portal venous gas. The cutoff scores for the dichotomous gestational age-specific case-definition were ≥2 (<30 weeks GA); ≥3 (30 to <37 weeks); ≥4 (≥37 weeks). The ordinal NEC score and dichotomous case-definition discriminated well between infants with and without NEC (AUC 87% and 80% respectively). Conclusions and relevance: NEC risk and clinical presentation are related to GA. Adoption of a consistent GA-specific case-definition would strengthen global efforts to reduce the population burden of this devastating neonatal disease.

ObjectiveTo identify the primary reasons for term admissions to neonatal units in England, to determine risk factors for admissions for jaundice and to estimate the proportion who can be cared for in a transitional setting without separation of mother and baby.DesignRetrospective observational study using neonatal unit admission data from the National Neonatal Research Database and data of live births in England from the Office for National Statistics.SettingAll 163 neonatal units in England 2011–2013.Participants133 691 term babies born ≥37 weeks gestational age and admitted to neonatal units in England.Primary and secondary outcomesPrimary reasons for admission, term babies admitted for the primary reason of jaundice, patient characteristics, postnatal age at admission, total length of stay, phototherapy, intravenous fluids, exchange transfusion and kernicterus.ResultsRespiratory disease was the most common reason for admission overall, although jaundice was the most common reason for admission from home (22% home vs 5% hospital). Risk factors for admission for jaundice include male, born at 37 weeks gestation, Asian ethnicity and multiple birth. The majority of babies received only a brief period of phototherapy, and only a third received intravenous fluids, suggesting that some may be appropriately managed without separation of mother and baby. Admission from home was significantly later (3.9 days) compared with those admitted from elsewhere in the hospital (1.7 days) (p<0.001).ConclusionAround two-thirds of term admissions for jaundice may be appropriately managed in a transitional care setting, avoiding separation of mother and baby. Babies with risk factors may benefit from a community midwife postnatal visit around the third day of life to enable early referral if necessary. We recommend further work at the national level to examine provision and barriers to transitional care, referral pathways between primary and secondary care, and community postnatal care.

CONTEXT: Preterm brain injuries are common; neurodevelopmental outcomes following contemporary neonatal care are continually evolving. OBJECTIVE: To systematically review and meta-analyze neurodevelopmental outcomes among preterm infants after intraventricular hemorrhage (IVH) and white matter injury (WMI). DATA SOURCES: Published and gray literature were searched across 10 databases between 2000 and 2021. STUDY SELECTION: Observational studies reporting 3-year neurodevelopmental outcomes for preterm infants with IVH or WMI compared with preterm infants without injury. DATA EXTRACTION: Study characteristics, population characteristics, and outcome data were extracted. RESULTS: Thirty eight studies were included. There was an increased adjusted risk of moderate-severe neurodevelopmental impairment after IVH grade 1 to 2 (adjusted odds ratio 1.35 [95% confidence interval 1.05–1.75]) and IVH grade 3 to 4 (adjusted odds ratio 4.26 [3.25–5.59]). Children with IVH grade 1 to 2 had higher risks of cerebral palsy (odds ratio [OR] 1.76 [1.39–2.24]), cognitive (OR 1.79 [1.09–2.95]), hearing (OR 1.83 [1.03–3.24]), and visual impairment (OR 1.77 [1.08–2.9]). Children with IVH grade 3 to 4 had markedly higher risks of cerebral palsy (OR 4.98 [4.13–6.00]), motor (OR 2.7 [1.52–4.8]), cognitive (OR 2.3 [1.67–3.15]), hearing (OR 2.44 [1.42–4.2]), and visual impairment (OR 5.42 [2.77–10.58]). Children with WMI had much higher risks of cerebral palsy (OR 14.91 [7.3–30.46]), motor (OR 5.3 [3–9.36]), and cognitive impairment (OR 3.48 [2.18–5.53]). LIMITATIONS: Heterogeneity of outcome data. CONCLUSIONS: Mild IVH, severe IVH, and WMI are associated with adverse neurodevelopmental outcomes. Utilization of core outcome sets and availability of open-access study data would improve our understanding of the nuances of these outcomes.