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ObjectiveThere is a paucity of data relating to neurodevelopmental outcomes in infants born late and moderately preterm (LMPT; 32+0–36+6 weeks). This paper present the results of a prospective, population-based study of 2-year outcomes following LMPT birth.Design1130 LMPT and 1255 term-born children were recruited at birth. At 2 years corrected age, parents completed a questionnaire to assess neurosensory (vision, hearing, motor) impairments and the Parent Report of Children's Abilities-Revised to identify cognitive impairment. Relative risks for adverse outcomes were adjusted for sex, socio-economic status and small for gestational age, and weighted to account for over-sampling of term-born multiples. Risk factors for cognitive impairment were explored using multivariable analyses.ResultsParents of 638 (57%) LMPT infants and 765 (62%) controls completed questionnaires. Among LMPT infants, 1.6% had neurosensory impairment compared with 0.3% of controls (RR 4.89, 95% CI 1.07 to 22.25). Cognitive impairments were the most common adverse outcome: LMPT 6.3%; controls 2.4% (RR 2.09, 95% CI 1.19 to 3.64). LMPT infants were at twice the risk for neurodevelopmental disability (RR 2.19, 95% CI 1.27 to 3.75). Independent risk factors for cognitive impairment in LMPT infants were male sex, socio-economic disadvantage, non-white ethnicity, preeclampsia and not receiving breast milk at discharge.ConclusionsCompared with term-born peers, LMPT infants are at double the risk for neurodevelopmental disability at 2 years of age, with the majority of impairments observed in the cognitive domain. Male sex, socio-economic disadvantage and preeclampsia are independent predictors of low cognitive scores following LMPT birth.

Introduction Published prevalence rates of congenital diaphragmatic hernia (CDH) vary. This study aims to describe the epidemiology of CDH using data from high-quality, population-based registers belonging to the European Surveillance of Congenital Anomalies (EUROCAT). Methods Cases of CDH delivered between 1980 and 2009 notified to 31 EUROCAT registers formed the population-based case series. Prevalence over time was estimated using multilevel Poisson regression, and heterogeneity between registers was evaluated from the random component of the intercept. Results There were 3373 CDH cases reported among 12 155 491 registered births. Of 3131 singleton cases, 353 (10.4%) were associated with a chromosomal anomaly, genetic syndrome or microdeletion, 784 (28.2%) were associated with other major structural anomalies. The male to female ratio of CDH cases overall was 1:0.69. Total prevalence was 2.3 (95% CI 2.2 to 2.4) per 10 000 births and 1.6 (95% CI 1.6 to 1.7) for isolated CDH cases. There was a small but significant increase (relative risk (per year)=1.01, 95% credible interval 1.00–1.01; p=0.030) in the prevalence of total CDH over time but there was no significant increase for isolated cases (ie, CDH cases that did not occur with any other congenital anomaly). There was significant variation in total and isolated CDH prevalence between registers. The proportion of cases that survived to 1 week was 69.3% (1392 cases) for total CDH cases and 72.7% (1107) for isolated cases. Conclusions This large population-based study found an increase in total CDH prevalence over time. CDH prevalence also varied significantly according to geographical location. No significant association was found with maternal age.

Background To undertake a systematic review of studies describing the proportion of children admitted to a paediatric intensive care unit (PICU) for respiratory syncytial virus (RSV) and/or bronchiolitis who were born preterm, and compare their outcomes in PICU with children born at term. Methods We searched Medline, Embase and Scopus. Citations and references of included articles were searched . We included studies published from the year 2000 onwards, from high-income countries, that examined children 0–18 years of age, admitted to PICU from the year 2000 onwards for RSV and/or bronchiolitis. The primary outcome was the percentage of PICU admissions born preterm, and secondary outcomes were observed relative risks of invasive mechanical ventilation and mortality within PICU. We used the Joanna Briggs Institute Checklist for Analytical Cross-Sectional Studies to assess risk of bias. Results We included 31 studies, from 16 countries, including a total of 18,331 children. Following meta-analysis, the pooled estimate for percentage of PICU admissions for RSV/bronchiolitis who were born preterm was 31% (95% confidence interval: 27% to 35%). Children born preterm had a greater risk of requiring invasive ventilation compared to children born at term (relative risk 1.57, 95% confidence interval 1.25 to 1.97, I 2  = 38%). However, we did not observe a significant increase in the relative risk for mortality within PICU for preterm-born children (relative risk 1.10, 95% confidence interval: 0.70 to 1.72, I 2  = 0%), although the mortality rate was low across both groups. The majority of studies ( n  = 26, 84%) were at high risk of bias. Conclusions Among PICU admissions for bronchiolitis, preterm-born children are over-represented compared with the preterm birth rate (preterm birth rate 4.4% to 14.4% across countries included in review). Preterm-born children are at higher risk of mechanical ventilation compared to those born at term.

ObjectivesTo investigate inequalities in stillbirth rates by ethnicity to facilitate development of initiatives to target those at highest risk.DesignPopulation-based perinatal mortality surveillance linked to national birth and death registration (Mothers and Babies: Reducing Risk through Audits and Confidential Enquiries across the UK).SettingUK.Participants4 391 569 singleton births at ≥24+0 weeks gestation between 2014 and 2019.Main outcome measuresStillbirth rate difference per 1000 total births by ethnicity.ResultsAdjusted absolute differences in stillbirth rates were higher for babies of black African (3.83, 95% CI 3.35 to 4.32), black Caribbean (3.60, 95% CI 2.65 to 4.55) and Pakistani (2.99, 95% CI 2.58 to 3.40) ethnicities compared with white ethnicities. Higher proportions of babies of Bangladeshi (42%), black African (39%), other black (39%) and black Caribbean (37%) ethnicities were from most deprived areas, which were associated with an additional risk of 1.50 stillbirths per 1000 births (95% CI 1.32 to 1.67). Exploring primary cause of death, higher stillbirth rates due to congenital anomalies were observed in babies of Pakistani, Bangladeshi and black African ethnicities (range 0.63–1.05 per 1000 births) and more placental causes in black ethnicities (range 1.97 to 2.24 per 1000 births). For the whole population, over 40% of stillbirths were of unknown cause; however, this was particularly high for babies of other Asian (60%), Bangladeshi (58%) and Indian (52%) ethnicities.ConclusionsStillbirth rates declined in the UK, but substantial excess risk of stillbirth persists among babies of black and Asian ethnicities. The combined disadvantage for black, Pakistani and Bangladeshi ethnicities who are more likely to live in most deprived areas is associated with considerably higher rates. Key causes of death were congenital anomalies and placental causes. Improved strategies for investigation of stillbirth causes are needed to reduce unexplained deaths so that interventions can be targeted to reduce stillbirths.

Background Newborns may be affected by maternal SARS-CoV-2 infection during pregnancy. We aimed to describe the epidemiology, clinical course and short-term outcomes of babies admitted to a neonatal unit (NNU) following birth to a mother with confirmed SARS-CoV-2 infection within 7 days of birth. Methods This is a UK prospective cohort study; all NHS NNUs, 1 March 2020 to 31 August 2020. Cases were identified via British Paediatric Surveillance Unit with linkage to national obstetric surveillance data. Reporting clinicians completed data forms. Population data were extracted from the National Neonatal Research Database. Results A total of 111 NNU admissions (1.98 per 1000 of all NNU admissions) involved 2456 days of neonatal care (median 13 [IQR 5, 34] care days per admission). A total of 74 (67%) babies were preterm. In all, 76 (68%) received respiratory support; 30 were mechanically ventilated. Four term babies received therapeutic hypothermia for hypoxic ischaemic encephalopathy. Twenty-eight mothers received intensive care, with four dying of COVID-19. Eleven (10%) babies were SARS-CoV-2 positive. A total of 105 (95%) babies were discharged home; none of the three deaths before discharge was attributed to SARS-CoV-2. Conclusion Babies born to mothers with SARS-CoV-2 infection around the time of birth accounted for a low proportion of total NNU admissions over the first 6 months of the UK pandemic. Neonatal SARS-CoV-2 was uncommon. Study registration ISRCTN60033461; protocol available at http://www.npeu.ox.ac.uk/pru-mnhc/research-themes/theme-4/covid-19 . Impact Neonatal unit admissions of babies born to mothers with SARS-CoV-2 infection comprised only a small proportion of total neonatal admissions in the first 6 months of the pandemic. A high proportion of babies requiring neonatal admission who were born to mothers with confirmed SARS-CoV-2 infection were preterm and had neonatal SARS-CoV-2 infection and/or other conditions associated with long-term sequelae. Adverse neonatal conditions were more common in babies whose SARS-CoV-2-positive mothers required intensive care compared to those whose SARS-CoV-2-positive mothers who did not.

Background The coronavirus disease-19 (COVID-19) pandemic had a relatively minimal direct impact on critical illness in children compared to adults. However, children and paediatric intensive care units (PICUs) were affected indirectly. We analysed the impact of the pandemic on PICU admission patterns and patient characteristics in the UK and Ireland. Methods We performed a retrospective cohort study of all admissions to PICUs in children < 18 years during Jan–Dec 2020, using data collected from 32 PICUs via a central database (PICANet). Admission patterns, case-mix, resource use, and outcomes were compared with the four preceding years (2016–2019) based on the date of admission. Results There were 16,941 admissions in 2020 compared to an annual average of 20,643 (range 20,340–20,868) from 2016 to 2019. During 2020, there was a reduction in all PICU admissions (18%), unplanned admissions (20%), planned admissions (15%), and bed days (25%). There was a 41% reduction in respiratory admissions, and a 60% reduction in children admitted with bronchiolitis but an 84% increase in admissions for diabetic ketoacidosis during 2020 compared to the previous years. There were 420 admissions (2.4%) with either PIMS-TS or COVID-19 during 2020. Age and sex adjusted prevalence of unplanned PICU admission reduced from 79.7 (2016–2019) to 63.1 per 100,000 in 2020. Median probability of death [1.2 (0.5–3.4) vs. 1.2 (0.5–3.4) %], length of stay [2.3 (1.0–5.5) vs. 2.4 (1.0–5.7) days] and mortality rates [3.4 vs. 3.6%, (risk-adjusted OR 1.00 [0.91–1.11, p  = 0.93])] were similar between 2016–2019 and 2020. There were 106 fewer in-PICU deaths in 2020 ( n  = 605) compared with 2016–2019 ( n  = 711). Conclusions The use of a high-quality international database allowed robust comparisons between admission data prior to and during the COVID-19 pandemic. A significant reduction in prevalence of unplanned admissions, respiratory diseases, and fewer child deaths in PICU observed may be related to the targeted COVID-19 public health interventions during the pandemic. However, analysis of wider and longer-term societal impact of the pandemic and public health interventions on physical and mental health of children is required.

Objectives To provide contemporary estimates of the prevalence of microcephaly in Europe, determine if the diagnosis of microcephaly is consistent across Europe, and evaluate whether changes in prevalence would be detected using the current European surveillance performed by EUROCAT (the European Surveillance of Congenital Anomalies).Design Questionnaire and population based observational study.Setting 24 EUROCAT registries covering 570 000 births annually in 15 countries.Participants Cases of microcephaly not associated with a genetic condition among live births, fetal deaths from 20 weeks’ gestation, and terminations of pregnancy for fetal anomaly at any gestation.Main outcome measures Prevalence of microcephaly (1 Jan 2003-31 Dec 2012) analysed with random effects Poisson regression models to account for heterogeneity across registries.Results 16 registries responded to the questionnaire, of which 44% (7/16) used the EUROCAT definition of microcephaly (a reduction in the size of the brain with a skull circumference more than 3 SD below the mean for sex, age, and ethnic origin), 19% (3/16) used a 2 SD cut off, 31% (5/16) were reliant on the criteria used by individual clinicians, and one changed criteria between 2003 and 2012. Prevalence of microcephaly in Europe was 1.53 (95% confidence interval 1.16 to 1.96) per 10 000 births, with registries varying from 0.4 (0.2 to 0.7) to 4.3 (3.6 to 5.0) per 10 000 (χ2=338, df=23, I2=93%). Registries with a 3 SD cut off reported a prevalence of 1.74 per 10 000 (0.86 to 2.93) compared with those with the less stringent 2 SD cut off of 1.21 per 10 000 (0.21 to 2.93). The prevalence of microcephaly would need to increase in one year by over 35% in Europe or by over 300% in a single registry to reach statistical significance (P<0.01).Conclusions EUROCAT could detect increases in the prevalence of microcephaly from the Zika virus of a similar magnitude to those observed in Brazil. Because of the rarity of microcephaly and discrepant diagnostic criteria, however, the smaller increases expected in Europe would probably not be detected. Clear diagnostic criteria for microcephaly must be adopted across Europe.

Observational studies have generated conflicting evidence on the effects of moderate maternal alcohol consumption during pregnancy on offspring cognition mainly reflecting problems of confounding. Among mothers who drink during pregnancy fetal alcohol exposure is influenced not only by mother's intake but also by genetic variants carried by both the mother and the fetus. Associations between children's cognitive function and both maternal and child genotype at these loci can shed light on the effects of maternal alcohol consumption on offspring cognitive development. We used a large population based study of women recruited during pregnancy to determine whether genetic variants in alcohol metabolising genes in this cohort of women and their children were related to the child's cognitive score (measured by the Weschler Intelligence Scale) at age 8. We found that four genetic variants in alcohol metabolising genes in 4167 children were strongly related to lower IQ at age 8, as was a risk allele score based on these 4 variants. This effect was only seen amongst the offspring of mothers who were moderate drinkers (1-6 units alcohol per week during pregnancy (per allele effect estimates were -1.80 (95% CI= -2.63 to -0.97) p=0.00002, with no effect among children whose mothers abstained during pregnancy (0.16 (95%CI= -1.05 to 1.36) p=0.80), p-value for interaction  =0.009). A further genetic variant associated with alcohol metabolism in mothers was associated with their child's IQ, but again only among mothers who drank during pregnancy.

Intensive care services for children have undergone substantial centralisation in the UK. Along with the establishment of regional paediatric intensive care units (PICUs), specialist retrieval teams were set up to transport critically ill children from other hospitals. We studied the outcome of children transferred from local hospitals to PICUs. We analysed data that were gathered for a cohort of children (≤16 years) admitted consecutively to 29 PICUs in England and Wales during 4 years (Jan 1, 2005, to Dec 31, 2008). We compared unplanned admissions from wards within the same hospital as the PICU and from other hospitals; interhospital transfers by non-specialist and specialist retrieval teams; and patients transferred to their nearest PICU and those who were not. Primary outcome measures were mortality rate in PICU and length of stay in PICU. We analysed data by use of logistic regression analysis. There were 57 997 admissions to PICUs during the study. Nearly half of unplanned admissions (17 649 [53%] of 33 492) were from other hospitals. Although children admitted from other hospitals were younger (median 10 months [IQR 1–55] vs 18 months [3–85]), sicker at admission (median predicted risk of mortality 6% [4–10] vs 4% [2–7]), stayed longer in PICUs (75 h [33–153] vs 43 h [18–116]), and had higher crude mortality rates (1384 [8%] of 17 649 vs 996 [6%] of 15 843; odds ratio 1·27, 95% CI 1·16–1·38), the risk-adjusted mortality rate in PICUs was lower than among children admitted from within the same hospital (0·65, 0·53–0·80). In a multivariable analysis, use of a specialist retrieval team for transfer was associated with improved survival (0·58, 0·39–0·87). These findings support the policy of combining centralisation of intensive care services for children with transfer by specialist retrieval teams. National Clinical Audit and Patient Outcomes Programme through Healthcare Quality Improvement Partnership, Health Commission Wales Specialised Services, National Health Service (NHS) Lothian and National Service Division NHS Scotland, the Royal Belfast Hospital for Sick Children, and the Pan Thames PICU Commissioning Consortium.

ObjectiveTo explore international variations in the management and survival of extremely low gestational age and birthweight births.DesignArea-based prospective cohort of birthsSetting12 regions across Belgium, France, Italy, Portugal and the UKParticipants1449 live births and fetal deaths between 22+0 and 25+6 weeks gestation born in 2011–2012.Main outcome measuresPercentage of births; recorded live born; provided antenatal steroids or respiratory support; surviving to discharge (with/without severe morbidities).ResultsThe percentage of births recorded as live born was consistently low at 22 weeks and consistently high at 25 weeks but varied internationally at 23 weeks for those weighing 500 g and over (range 33%–70%) and at 24 weeks for those under 500 g (range 5%–71%). Antenatal steroids and provision of respiratory support at 22–24 weeks gestation varied between countries, but were consistently high for babies born at 25 weeks. Survival to discharge was universally poor at 22 weeks gestation (0%) and at any gestation with birth weight <500 g, irrespective of treatment provision. In contrast, births at 23 and 24 weeks weighing 500 g and over showed significant international variation in survival (23 weeks: range: 0%–25%; 24 weeks range: 21%–50%), reflecting levels of treatment provision.ConclusionsWide international variation exists in the management and survival of extremely preterm births at 22–24 weeks gestation. Universally poor outcomes for babies at 22 weeks and for those weighing under 500 g suggest little impact of intervention and support the inclusion of birth weight along with gestational age in ethical decision-making guidelines.