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Objective: Neonatal infection with wildtype SARS-CoV-2 is rare and good outcomes predominate. We investigated neonatal outcomes using national population-level data to describe the impact of different SARS-CoV-2 variants., Design: Prospective population-based cohort study., Setting: Neonatal, paediatric and paediatric intensive care inpatient care settings in the UK., Patients: Neonates (first 28 days after birth) with confirmed SARS-CoV-2 infection who received inpatient care, March 2020 to April 2022. Neonates were identified through active national surveillance with linkage to national SARS-CoV-2 testing data, routinely recorded neonatal data, paediatric intensive care data and obstetric and perinatal mortality surveillance data., Outcomes: Presenting signs, clinical course, severe disease requiring respiratory support are presented by the dominant SARS-CoV-2 variant in circulation at the time., Results: 344 neonates with SARS-CoV-2 infection received inpatient care; breakdown by dominant variant: 146 wildtype, 123 alpha, 57 delta and 18 omicron. Overall, 44.7% (153/342) neonates required respiratory support; short-term outcomes were good with 93.6% (322/344) of neonates discharged home. Eleven neonates died: seven unrelated to SARS-CoV-2 infection, four were attributed to neonatal SARS-CoV-2 infection (case fatality 4/344, 1.2% 95% CI 0.3% to 3.0%) of which three were born preterm due to maternal COVID-19. More neonates were born very preterm (23/54) and required invasive ventilation (27/57) when delta variant was predominant, and all four SARS-CoV-2-related deaths occurred in this period., Conclusions: Inpatient care for neonates with SARS-CoV-2 was uncommon. Although rare, severe neonatal illness was more common during the delta variant period, potentially reflecting more severe maternal disease and associated preterm birth., Trial Registration Number: ISRCTN60033461., Competing Interests: Competing interests: MK, MAQ, CG and JJK received grants from the UK NIHR Policy Research Programme in relation to the submitted work. KEF, AM, MH, AP, SNL, ESD, DS, CD and HM declare no competing interests., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

Objective: Currently used estimates of survival are nearly 10 years old and relate to only those babies admitted for neonatal care. Due to ongoing improvements in neonatal care, here we update estimates of survival for singleton and multiple births at 22 +0 to 31 +6 weeks gestational age across the perinatal care pathway by gestational age and birth weight., Design: Retrospective analysis of routinely collected data., Setting: A national cohort from the UK and British Crown Dependencies., Patients: Babies born at 22 +0 to 31 +6 weeks gestational age from 1 January 2016 to 31 December 2020., Interventions: None., Main Outcome Measures: Survival to 28 days., Results: Estimates of neonatal survival are provided for babies: (1) alive at the onset of care during the birthing process (n=43 763); (2) babies where survival-focused care was initiated (n=42 004); and (3) babies admitted for neonatal care (n=41 158). We have produced easy-to-use survival charts for singleton and multiple births. Generally, survival increased with increasing gestational age at birth and with increasing birth weight. For all births with a birthweight over 1000 g, survival was 90% or higher at all three stages of care., Conclusions: Survival estimates are a vital tool to support and supplement clinical judgement within perinatal care. These up-to-date, national estimates of survival to 28 days are provided based on three stages of the perinatal care pathway to support ongoing clinical care. These novel results are a key resource for policy and practice including counselling parents and informing care provision., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: To investigate whether extrauterine growth restriction (EUGR) during the neonatal hospitalisation by sex among extremely preterm (EPT) infants is associated with cerebral palsy (CP) and cognitive and motor abilities at 5 years of age., Study Design: Population-based cohort of births <28 weeks of gestation with data from obstetric and neonatal records and parental questionnaires and clinical assessments at 5 years of age., Setting: 11 European countries., Patients: 957 EPT infants born in 2011-2012., Main Outcomes: EUGR at discharge from the neonatal unit was defined as (1) the difference between Z-scores at birth and discharge with <-2 SD as severe, -2 to -1 SD as moderate using Fenton's growth charts (Fenton) and (2) average weight-gain velocity using Patel's formula in grams (g) per kilogram per day (Patel) with <11.2 g (first quartile) as severe, 11.2-12.5 g (median) as moderate. Five-year outcomes were: a CP diagnosis, intelligence quotient (IQ) using the Wechsler Preschool and Primary Scales of Intelligence tests and motor function using the Movement Assessment Battery for Children, second edition., Results: 40.1% and 33.9% children were classified as having moderate and severe EUGR, respectively, by Fenton and 23.8% and 26.3% by Patel. Among children without CP, those with severe EUGR had lower IQ than children without EUGR (-3.9 points, 95% Confidence Interval (CI)=-7.2 to -0.6 for Fenton and -5.0 points, 95% CI=-8.2 to -1.8 for Patel), with no interaction by sex. No significant associations were observed between motor function and CP., Conclusions: Severe EUGR among EPT infants was associated with decreased IQ at 5 years of age., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: To assess the impact of public health measures taken during the COVID-19 pandemic on perinatal health indicators., Design: Interrupted time series analysis comparing periods of the pandemic with the previous 5 years., Setting: Yorkshire and the Humber region, England (2015-2020)., Main Outcome Measures: Relative risk (RR) of stillbirth, extreme preterm (EPT, <27 weeks' gestational age) delivery, hypoxic ischaemic encephalopathy (HIE) and meconium aspiration syndrome (MAS), antenatal transfer for threatened EPT delivery and postnatal transfer for EPT birth, HIE or MAS., Results: Stillbirths fell from 3.7/1000 deliveries prepandemic to 2.9/1000 afterwards; EPT births decreased from 2.5/1000 to 1.8/1000 live births. Following adjustment, during the first lockdown there were decreased antenatal transfers (RR 0.74, 95% CI 0.57 to 0.94) with non-statistically significant increased stillbirth (RR 1.08, 95% CI 0.78 to 1.51) and decreased EPT admissions (RR 0.88, 95% CI 0.60 to 1.29). Over the entire pandemic period, antenatal transfer (RR 0.64, 95% CI 0.55 to 0.76) and EPT birth (RR 0.73, 95% CI 0.56 to 0.94) decreased; stillbirths showed non-statistically significant increases overall (RR 1.21, 95% CI 0.98 to 1.49) but with increasing trend through the pandemic (RR 1.11, 95% CI 1.00 to 1.22). No changes were seen for HIE, MAS, postnatal transfers or in subgroup analyses by ethnicity., Conclusions: Lower rates of antenatal transfer and extreme preterm birth were identified, alongside an apparent increase in stillbirth over time. The findings provide evidence that effects on perinatal activity related to the pandemic changed over time., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: To identify factors associated with the offer of and consent to perinatal post-mortem., Design: National population-based cohort study SETTING: The UK., Population: 26 578 perinatal deaths born between 1 January 2013 and 31 December 2017., Main Outcome Measures: Postmortem offer by clinical staff; parental consent to post-mortem., Results: Postmortem offer rates were high but varied significantly with time of death from 97.8% for antepartum deaths to 88.4% for neonatal deaths following neonatal admission. Offer rates did not significantly vary by gestation, year of birth, mother's socioeconomic deprivation, ethnicity or age. Only 44.5% of parents consented to a postmortem. Mothers from the most deprived areas were less likely to consent than those from the least deprived areas (relative risk (RR)=0.76, 95% CI 0.71 to 0.80). Consent rates were similar for mothers of white, mixed, Asian Indian, black Caribbean and black African ethnicity (43%-47%), but significantly lower for mothers of Asian Pakistani (20%) and Asian Bangladeshi (18%) ethnicity. Consent increased with increasing gestation (p<0.001) and was lower for deaths following neonatal unit admission than for antepartum death (RR 0.71, 95% CI 0.67 to 0.75)., Conclusions: The current profile of cause of perinatal deaths in the UK is likely to be biased with less postmortem information available for babies dying in the neonatal period and those born to mothers from deprived areas and of Asian Pakistani or Asian Bangladeshi ethnicity. Such bias severely limits the design of effective strategies for reducing mortality in these high-risk groups. These findings have implications for high-income countries seeking to explore and improve the understanding of perinatal deaths., Competing Interests: Competing interests: ED reports grants from HQIP. LS reports grants from HQIP and NIHR., (© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: To determine whether the variation in neurodevelopmental disability rates between populations persists after adjustment for demographic, maternal and infant characteristics for an international very preterm (VPT) birth cohort using a standardised approach to neurodevelopmental assessment at 2 years of age., Design: Prospective standardised cohort study., Setting: 15 regions in 10 European countries., Patients: VPT births: 22 +0 -31 +6 weeks of gestation., Data Collection: Standardised data collection tools relating to pregnancy, birth and neonatal care and developmental outcomes at 2 years corrected age using a validated parent completed questionnaire., Main Outcome Measures: Crude and standardised prevalence ratios calculated to compare rates of moderate to severe neurodevelopmental impairment between regions grouped by country using fixed effects models., Results: Parent reported rates of moderate or severe neurodevelopmental impairment for the cohort were: 17.3% (ranging 10.2%-26.1% between regions grouped by country) with crude standardised prevalence ratios ranging from 0.60 to 1.53. Adjustment for population, maternal and infant factors resulted in a small reduction in the overall variation (ranging from 0.65 to 1.30)., Conclusion: There is wide variation in the rates of moderate to severe neurodevelopmental impairment for VPT cohorts across Europe, much of which persists following adjustment for known population, maternal and infant factors. Further work is needed to investigate whether other factors including quality of care and evidence-based practice have an effect on neurodevelopmental outcomes for these children., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Competing Interests: Competing interests: All authors are investigators on the BPSU Neonatal Complications of COVID-19 study.

Objective: To investigate socioeconomic inequalities in cause-specific stillbirth and neonatal mortality to identify key areas of focus for future intervention strategies to achieve government ambitions to reduce mortality rates., Design: Retrospective cohort study., Setting: England, Wales, Scotland and the UK Crown Dependencies., Participants: All singleton births between 1 January 2014 and 31 December 2015 at ≥24 weeks' gestation., Main Outcome Measure: Cause-specific stillbirth or neonatal death (0-27 days after birth) per 10 000 births by deprivation quintile., Results: Data on 5694 stillbirths (38.1 per 10 000 total births) and 2368 neonatal deaths (15.9 per 10 000 live births) were obtained from Mothers and Babies: Reducing Risk through Audits and Confidential Enquiries across the UK (MBRRACE-UK). Women from the most deprived areas were 1.68 (95% CI 1.56 to 1.81) times more likely to experience a stillbirth and 1.67 (95% CI 1.48 to 1.87) times more likely to experience a neonatal death than those from the least deprived areas, equating to an excess of 690 stillbirths and 231 neonatal deaths per year associated with deprivation. Small for gestational age (SGA) unexplained antepartum stillbirth was the greatest contributor to excess stillbirths accounting for 33% of the deprivation gap in stillbirths. Congenital anomalies accounted for the majority (59%) of the deprivation gap in neonatal deaths, followed by preterm birth not SGA (24-27 weeks, 27%)., Conclusions: Cause-specific mortality rates at a national level allow identification of key areas of focus for future intervention strategies to reduce mortality. Despite a reduction in the deprivation gap for stillbirths and neonatal deaths, public health interventions should primarily focus on socioeconomic determinants of SGA stillbirth and congenital anomalies., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Competing Interests: Competing interests: None declared.

Objective: To predict length of stay in neonatal care for all admissions of very preterm singleton babies., Setting: All neonatal units in England., Patients: Singleton babies born at 24-31 weeks gestational age from 2011 to 2014. Data were extracted from the National Neonatal Research Database., Methods: Competing risks methods were used to investigate the competing outcomes of death in neonatal care or discharge from the neonatal unit. The occurrence of one event prevents the other from occurring. This approach can be used to estimate the percentage of babies alive, or who have been discharged, over time., Results: A total of 20 571 very preterm babies were included. In the competing risks model, gestational age was adjusted for as a time-varying covariate, allowing the difference between weeks of gestational age to vary over time. The predicted percentage of death or discharge from the neonatal unit were estimated and presented graphically by week of gestational age. From these percentages, estimates of length of stay are provided as the number of days following birth and corrected gestational age at discharge., Conclusions: These results can be used in the counselling of parents about length of stay and the risk of mortality., Competing Interests: Competing interests: SS is funded by a National Institute for Health Research Doctoral Research Fellowship award (DRF-2013-06-011). KA is partially supported by the National Institute for Health Research (NIHR) as a senior investigator (NF-SI-0512-10159)., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2019. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Objective: To investigate the variation in severe neonatal morbidity among very preterm (VPT) infants across European regions and whether morbidity rates are higher in regions with low compared with high mortality rates., Design: Area-based cohort study of all births before 32 weeks of gestational age., Setting: 16 regions in 11 European countries in 2011/2012., Patients: Survivors to discharge from neonatal care (n=6422)., Main Outcome Measures: Severe neonatal morbidity was defined as intraventricular haemorrhage grades III and IV, cystic periventricular leukomalacia, surgical necrotizing enterocolitis and retinopathy of prematurity grades ≥3. A secondary outcome included severe bronchopulmonary dysplasia (BPD), data available in 14 regions. Common definitions for neonatal morbidities were established before data abstraction from medical records. Regional severe neonatal morbidity rates were correlated with regional in-hospital mortality rates for live births after adjustment on maternal and neonatal characteristics., Results: 10.6% of survivors had a severe neonatal morbidity without severe BPD (regional range 6.4%-23.5%) and 13.8% including severe BPD (regional range 10.0%-23.5%). Adjusted inhospital mortality was 13.7% (regional range 8.4%-18.8%). Differences between regions remained significant after consideration of maternal and neonatal characteristics (P<0.001) and severe neonatal morbidity rates were not correlated with mortality rates (P=0.50)., Conclusion: Severe neonatal morbidity rates for VPT survivors varied widely across European regions and were independent of mortality rates., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2019. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Objectives: Construct updated birth weight-for-gestational age centile charts for use in the UK and compare these to the currently used UK-WHO charts., Design: Secondary analysis of national birth data., Participants: Centiles were constructed using 1 269 403 singleton births occurring in England and Wales in 2013-2014 as part of the MBRRACE-UK national perinatal surveillance programme. These were then validated using 642 737 singleton births occurring in England and Wales in 2015., Main Outcome Measures: Sex-specific birth weight-for-gestational age centiles. Centiles were created using the lambda-mu-sigma method via the GAMLSS package in R. This method transforms the skewed birth weight distribution to approximate a normal distribution, allowing any birth weight centile to be produced., Results: The new centiles performed well in the validation sample, with the observed and expected proportion of births below a given centile in agreement. Overall, driven by the predominance of term births, the UK-WHO charts classify a smaller proportion of infants as below a given centile. For example, the UK-WHO estimates classified only 1.32% (8035/606 430) of term infants born in 2015 as below the second centile, compared with 1.97% (11 975/606 430) using the new MBRRACE-UK centiles. At the earliest gestational ages, however, the opposite is observed, with the UK-WHO classifying a larger proportion of infants as below a given centile, particularly at the lower end of the birthweight distribution., Conclusions: We have constructed and validated updated birth weight-for-gestational age centiles using a contemporary sample of births occurring in England and Wales. The benefits of these updated centiles will be first to assist the national surveillance of perinatal mortality programme by improving the identification of the proportion of stillbirths and neonatal deaths affected by intrauterine growth restriction and, second, to aid clinicians by more accurately identifying babies who require increased monitoring in the period immediately following birth., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Objectives:  To evaluate the implementation of four high evidence practices for the care of very preterm infants to assess their use and impact in routine clinical practice and whether they constitute a driver for reducing mortality and neonatal morbidity., Design:  Prospective multinational population based observational study., Setting:  19 regions from 11 European countries covering 850 000 annual births participating in the EPICE (Effective Perinatal Intensive Care in Europe for very preterm births) project., Participants:  7336 infants born between 24+0 and 31+6 weeks' gestation in 2011/12 without serious congenital anomalies and surviving to neonatal admission., Main Outcome Measures:  Combined use of four evidence based practices for infants born before 28 weeks' gestation using an "all or none" approach: delivery in a maternity unit with appropriate level of neonatal care; administration of antenatal corticosteroids; prevention of hypothermia (temperature on admission to neonatal unit ≥36°C); surfactant used within two hours of birth or early nasal continuous positive airway pressure. Infant outcomes were in-hospital mortality, severe neonatal morbidity at discharge, and a composite measure of death or severe morbidity, or both. We modelled associations using risk ratios, with propensity score weighting to account for potential confounding bias. Analyses were adjusted for clustering within delivery hospital., Results:  Only 58.3% (n=4275) of infants received all evidence based practices for which they were eligible. Infants with low gestational age, growth restriction, low Apgar scores, and who were born on the day of maternal admission to hospital were less likely to receive evidence based care. After adjustment, evidence based care was associated with lower in-hospital mortality (risk ratio 0.72, 95% confidence interval 0.60 to 0.87) and in-hospital mortality or severe morbidity, or both (0.82, 0.73 to 0.92), corresponding to an estimated 18% decrease in all deaths without an increase in severe morbidity if these interventions had been provided to all infants., Conclusions:  More comprehensive use of evidence based practices in perinatal medicine could result in considerable gains for very preterm infants, in terms of increased survival without severe morbidity., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Background: Routine comparable outcome data collection relating to the later health status of babies born very preterm has long been considered important, but has not been achieved in the UK., Aim: To test the potential for a parental questionnaire to provide these data for all eligible babies from a geographical population., Methods: Consent for follow-up by questionnaire (using the Parent Report of Children's Abilities-Revised combined with questions derived from the Oxford minimum dataset) was sought for all babies ≤30 weeks of gestation, discharged from a hospital in the East Midlands and Yorkshire regions of the UK, having been born between 1 January 2007 and 31 December 2011., Results: The rate of consent to participate in follow-up showed a steady increase over time to 83.1% in 2011. However, the response rate in terms of completion and return of the questionnaire at 2 years, as a proportion of those eligible, showed little change over time, varying between 42% and 46%. Among those children where a questionnaire was returned, the rate of disability was broadly consistent over time: lowest in 2009, 21.0% (95% CI 16.8% to 25.6%) and highest in 2011, 25.5% (95% CI 21.5% to 31.2%). The instruments used appeared effective with the capability of discriminating between children with physical and/or cognitive disability., Conclusions: The overall response rate in terms of returned questionnaires was disappointing and inadequate to recommend for implementation. It is possible that response rates would have been higher had clinical follow-up been linked to the data obtained from the questionnaires rather than running as a parallel process., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)

Objective: To estimate the effect of the provision of a one-to-one nurse-to-patient ratio on mortality rates in neonatal intensive care units., Design: A population-based analysis of operational clinical data using an instrumental variable method., Setting: National Health Service neonatal units in England contributing data to the National Neonatal Research Database at the Neonatal Data Analysis Unit and participating in the Neonatal Economic, Staffing, and Clinical Outcomes Project., Participants: 43 tertiary-level neonatal units observed monthly over the period January 2008 to December 2012., Intervention: Proportion of neonatal intensive care days or proportion of intensive care admissions for which one-to-one nursing was provided., Outcomes: Monthly in-hospital intensive care mortality rate., Results: Over the study period, the provision of one-to-one nursing in tertiary neonatal units declined from a median of 9.1% of intensive care days in 2008 to 5.9% in 2012. A 10 percentage point decrease in the proportion of intensive care days on which one-to-one nursing was provided was associated with an increase in the in-hospital mortality rate of 0.6 (95% CI 1.2 to 0.0) deaths per 100 infants receiving neonatal intensive care per month compared with a median monthly mortality rate of 4.5 deaths per 100 infants per month. The results remained robust to sensitivity analyses that varied the estimation sample of units, the choice of instrumental variables, unit classification and the selection of control variables., Conclusions: Our study suggests that decreases in the provision of one-to-one nursing in tertiary-level neonatal intensive care units increase the in-hospital mortality rate., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)

Objective: To describe neonatal outcomes and explore variation in delivery of care for infants born late (34-36  weeks) and moderately (32-33 weeks) preterm (LMPT)., Design/setting: Prospective population-based study comprising births in four major maternity centres, one midwifery-led unit and at home between September 2009 and December 2010. Data were obtained from maternal and neonatal records., Participants: All LMPT infants were eligible. A random sample of term-born infants (≥37 weeks) acted as controls., Outcome Measures: Neonatal unit (NNU) admission, respiratory and nutritional support, neonatal morbidities, investigations, length of stay and postnatal ward care were measured. Differences between centres were explored., Results: 1146 (83%) LMPT and 1258 (79% of eligible) term-born infants were recruited. LMPT infants were significantly more likely to receive resuscitation at birth (17.5% vs 7.4%), respiratory (11.8% vs 0.9%) and nutritional support (3.5% vs 0.3%) and were less likely to be fed breast milk (64.2% vs 72.2%) than term infants. For all interventions and morbidities, a gradient of increasing risk with decreasing gestation was evident. Although 60% of late preterm infants were never admitted to a NNU, 83% required medical input on postnatal wards. Clinical management differed significantly between services., Conclusions: LMPT infants place high demands on specialist neonatal services. A substantial amount of previously unreported specialist input is provided in postnatal wards, beyond normal newborn care. Appropriate expertise and planning of early care are essential if such infants are managed away from specialised neonatal settings. Further research is required to clarify optimal and cost-effective postnatal management for LMPT babies., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Objective: This study explores the associations between lifestyle factors and late and moderate preterm birth (LMPT: 32(+0)-36(+6) weeks' gestation), a relatively under-researched group., Study Design: A population-based case-cohort study was undertaken involving 922 LMPT and 965 term (37+ weeks' gestation) singleton live and stillbirths born between 1 September 2009 and 31 December 2010 to women residing in Leicestershire and Nottinghamshire, UK. Poisson multivariable regression models were fitted to estimate relative risks (RR) of LMPT birth associated with maternal smoking, alcohol and recreational drug use, and diet., Results: Women who smoked during pregnancy were at 38% increased risk of LMPT birth compared with non-smokers (RR 1.38, 95% CI (1.04 to 1.84)). Low consumption of fruit and vegetables was associated with a 31% increased risk compared with those who reported eating higher consumption levels (RR 1.31 (1.03 to 1.66)). Women who did not have any aspects of a Mediterranean diet were nearly twice as likely to deliver LMPT compared with those whose diet included more Mediterranean characteristics (RR 1.81 (1.04 to 3.14)). Women who smoked and consumed low levels of fruit and vegetables (5% of women) were at particularly high risk (RR=1.81 (1.29 to 2.55)). There was no significant effect of alcohol or recreational drug use on LMPT birth., Conclusions: Smoking and poor diet during pregnancy, factors that strongly impact on very preterm birth, are also important at later gestations and experienced together are associated with an elevated rate of risk. Our findings suggest early cessation of smoking during pregnancy may be an effective strategy to reduce LMPT births., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Objective: To investigate socioeconomic inequalities in outcome of pregnancy associated with Down syndrome (DS) compared with other congenital anomalies screened for during pregnancy., Design and Setting: Retrospective population-based registry study (East Midlands & South Yorkshire in England)., Participants: All registered cases of DS and nine selected congenital anomalies with poor prognostic outcome (the UK Fetal Anomaly Screening Programme (FASP)9) with an end of pregnancy date between 1 January 1998 and 31 December 2007., Main Outcome Measures: Poisson regression models were used to explore outcome measures, including socioeconomic variation in rates of anomaly; antenatal detection; pregnancy outcome; live birth incidence and neonatal mortality. Deprivation was measured using the Index of Multiple Deprivation 2004 at super output area level., Results: There were 1151 cases of DS and 1572 cases of the nine severe anomalies combined. The overall rate of antenatal detection was 57% for DS, which decreased with increasing deprivation (rate ratio comparing the most deprived tenth with the least deprived: 0.76 (0.60 to 0.97)). Antenatal detection rates were considerably higher for FASP9 anomalies (86%), with no evidence of a trend with deprivation (0.99 95% CI (0.84 to 1.17)). The termination of pregnancy rate following antenatal diagnosis was higher for DS (86%) than the FASP9 anomalies (70%). Both groups showed wide socioeconomic variation in the termination of pregnancy rate (rate ratio: DS: 0.76 (0.58 to 0.99); FASP9 anomalies: 0.80 (0.65 to 0.97)). Consequently, socioeconomic inequalities in live birth and neonatal mortality rates associated with these anomalies arise that were not observed in utero., Conclusions: Socioeconomic inequalities exist in the antenatal detection of DS, and subsequent termination rates are much higher for DS than other anomalies. Termination rates for all anomalies are lower in more deprived areas leading to wide socioeconomic inequalities in live born infants with a congenital anomaly, particularly DS, and subsequent neonatal mortality., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Objective: There 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., Design: 1130 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., Results: Parents 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., Conclusions: Compared 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., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

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., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Background: Partial urorectal septum malformation (pURSM) sequence (or 'persistent cloaca') is a rare congenital anomaly characterised by a joining of the urethral, anal, and genital openings into a single common channel. This study describes the epidemiology of pURSM sequence in England and Wales including prevalence, additional anomalies, and pregnancy outcomes., Methods: All cases of pURSM sequence prospectively notified to seven congenital anomaly registers in England and Wales during 1985-2010, whether delivered as live births, spontaneous fetal deaths (≥20 weeks' gestation), or elective terminations of pregnancy for fetal anomaly (TOPFA, any gestation), formed this population-based cohort. The risks of spontaneous fetal and infant death were examined by Kaplan-Meier analysis. Differences in prevalence over time, and between regions, were examined by multilevel Poisson regression., Results: 117 cases were recorded among 4,251,241 total births. Six (5%) pregnancies resulted in spontaneous fetal deaths, 53 (45%) in TOPFA, and 58 (50%) in live births. The prevalence was 2.8 (95% CI 2.3 to 3.4) per 100,000 total births, increasing significantly over time (p=0.002) and differing significantly between regions (p=0.005). 77 cases (66%) had at least one additional major congenital anomaly outside the perineum, including 67 (57%) renal, 29 (25%) musculoskeletal, 26 (23%) digestive system, and 24 (21%) cardiovascular anomalies. The risks of spontaneous fetal and infant death were estimated as 8.9% (95% CI 4.1 to 18.8) and 26.3% (95% CI 15.1 to 43.4) respectively., Conclusions: This is the largest study of the epidemiology of pURSM sequence. The information will be valuable for families and health professionals whenever a case of pURSM sequence is diagnosed., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Background: Expertise and resources may be important determinants of outcome for extremely preterm babies. We evaluated the effect of place of birth and perinatal transfer on survival and neonatal morbidity within a prospective cohort of births between 22 and 26 weeks of gestation in England during 2006., Methods: We studied the whole population of 2460 births where the fetus was alive at the admission of the mother to hospital for delivery. Outcomes to discharge were compared between level 3 (most intensive) and level 2 maternity services, with and without transfers, and by activity level of level 3 neonatal unit; ORs were adjusted for gestation at birth and birthweight for gestation (adjusted ORs (aOR))., Findings: Of this national birth cohort, 56% were born in maternity services with level 3 and 34% with level 2 neonatal units; 10% were born in a setting without ongoing intensive care facilities (level 1). When compared with level 2 settings, risk of death in level 3 services was reduced (aOR 0.73 (95% CI 0.59 to 0.90)), but the proportion surviving without neonatal morbidity was similar (aOR 1.27 (0.93 to 1.74)). Analysis by intended hospital of birth confirmed reduced mortality in level 3 services. Following antenatal transfer into a level 3 setting, there were fewer intrapartum or labour ward deaths, and overall mortality was higher for those remaining in level 2 services (aOR 1.44 (1.09 to 1.90)). Among level 3 services, those with higher activity had fewer deaths overall (aOR 0.68 (0.52 to 0.89))., Interpretation: Despite national policy, only 56% of births between 22 and 26 weeks of gestation occurred in maternity services with a level 3 neonatal facility. Survival was significantly enhanced following birth in level 3 services, particularly those with high activity; this was not at the cost of increased neonatal morbidity.

Objective: To investigate regional variation in the registration of preterm births <24 weeks of gestation and the impact on infant death rates for English Primary Care Trusts (PCTs)., Design: Cohort study., Setting: England., Participants: All registered births (1 January 2005-31 December 2008) by gestational age and PCT (147 trusts) linked to infant deaths (up to 1 year of life). Late-fetal deaths at 22 and 23 weeks gestation (1 January 2005-31 December 2006)., Main Outcome Measures: Extremely preterm (<24 weeks) birth rate per 1000 live births and percentage of births registered as live born by PCT. Infant death rate and rank of mortality for (1) all live births and (2) live births over 24 weeks gestation by PCT., Results: Wide between-PCT variation existed in extremely preterm birth (<24 weeks) rates (per 1000 births) (90% central range (0.31, 1.91)) and percentages of births <24 weeks of gestation registered as live born (median 52.6%, 90% central range (26.3%, 79.5%)). Consequently, the percentage of infant deaths arising from these births varied (90% central range (6.7%, 31.9%)). Excluding births <24 weeks, led to significant changes in infant mortality rankings of PCTs, with a median worsening of 12 places for PCTs with low rates of live born preterm births <24 weeks of gestation compared with a median improvement of four ranks for those with higher live birth registration rates., Conclusions: Infant death rates in PCTs in England are influenced by variation in the registration of births where viability is uncertain. It is vital that this variation is minimised before infant mortality is used as indicator for monitoring health and performance and targeting interventions.

Objective: To assess the care given to the babies born at the threshold of viability over the last 20 years using regional and national data., Design: Population-based retrospective study., Setting: Former 'Trent' health region., Participants: Babies born between 1 January 1991 and 31 December 2010 at 22(+0) to 25(+6) weeks gestational age., Main Outcome Measure: Survival and use of respiratory support., Methods: Data of all babies born between 1 January 1991 and 31 December 2010 with a gestational age of 22(+0) to 25(+6) weeks and admitted to a neonatal unit were extracted from The Neonatal Survey. Use of respiratory support in terms of ventilation and continuous positive airway pressure (CPAP) for this group of babies was calculated as a proportion of the total used by the whole neonatal intensive care population within the defined study area., Results: The proportion of babies surviving to discharge increased significantly over time in those born at 24 and 25 weeks (p<0.01) but failed to achieve statistical significance for those at 23 weeks (p=0.08). No babies born at 22 weeks survived. The babies born at 22-25 weeks accounted for 26.3% of all ventilation and 21.5% of CPAP given., Conclusion: Our work concurs with the current UK guidelines. There could be advantages in focusing the care of babies born at 23 weeks to a small number of intensive care units to allow specialist expertise to develop in all aspects of the management of these babies. However, focusing care will not necessarily improve survival or reduce morbidity.

Objective: To determine survival and neonatal morbidity for babies born between 22 and 26 weeks' gestation in England during 2006, and to evaluate changes in outcome since 1995 for babies born between 22 and 25 weeks' gestation., Design: Prospective national cohort studies., Setting: Maternity and neonatal units in England., Participants: 3133 births between 22 and 26 weeks' gestation in 2006; 666 admissions to neonatal units in 1995 and 1115 in 2006 of babies born between 22 and 25 weeks' gestation., Main Outcome Measures: Survival to discharge from hospital, pregnancy and delivery outcomes, infant morbidity until discharge., Results: In 2006, survival of live born babies was 2% (n=3) for those born at 22 weeks' gestation, 19% (n=66) at 23 weeks, 40% (n=178) at 24 weeks, 66% (n=346) at 25 weeks, and 77% (n=448) at 26 weeks (P<0.001). At discharge from hospital, 68% (n=705) of survivors had bronchopulmonary dysplasia (receiving supplemental oxygen at 36 weeks postmenstrual age), 13% (n=135) had evidence of serious abnormality on cerebral ultrasonography, and 16% (n=166) had laser treatment for retinopathy of prematurity. For babies born between 22 and 25 weeks' gestation from March to December, the number of admissions for neonatal care increased by 44%, from 666 in 1995 to 959 in 2006. By 2006 adherence to evidence based practice associated with improved outcome had significantly increased. Survival increased from 40% to 53% (P<0.001) overall and at each week of gestation: by 9.5% (confidence interval -0.1% to 19%) at 23 weeks, 12% (4% to 20%) at 24 weeks, and 16% (9% to 23%) at 25 weeks. The proportions of babies surviving in 2006 with bronchopulmonary dysplasia, major cerebral scan abnormality, or weight and/or head circumference <-2 SD were similar to those in 1995, but the proportion treated for retinopathy of prematurity had increased from 13% to 22% (P=0.006). Predictors of mortality and morbidity were similar in both cohorts., Conclusion: Survival of babies born between 22 and 25 weeks' gestation has increased since 1995 but the pattern of major neonatal morbidity and the proportion of survivors affected are unchanged. These observations reflect an important increase in the number of preterm survivors at risk of later health problems.

Objective: To determine outcomes at age 3 years in babies born before 27 completed weeks' gestation in 2006, and to evaluate changes in outcome since 1995 for babies born between 22 and 25 weeks' gestation., Design: Prospective national cohort studies, EPICure and EPICure 2., Setting: Hospital and home based evaluations, England., Participants: 1031 surviving babies born in 2006 before 27 completed weeks' gestation. Outcomes for 584 babies born at 22-25 weeks' gestation were compared with those of 260 surviving babies of the same gestational age born in 1995., Main Outcome Measures: Survival to age 3 years, impairment (2008 consensus definitions), and developmental scores. Multiple imputation was used to account for the high proportion of missing data in the 2006 cohort., Results: Of the 576 babies evaluated after birth in 2006, 13.4% (n=77) were categorised as having severe impairment and 11.8% (n=68) moderate impairment. The prevalence of neurodevelopmental impairment was significantly associated with length of gestation, with greater impairment as gestational age decreased: 45% at 22-23 weeks, 30% at 24 weeks, 25% at 25 weeks, and 20% at 26 weeks (P<0.001). Cerebral palsy was present in 83 (14%) survivors. Mean developmental quotients were lower than those of the general population (normal values 100 (SD 15)) and showed a direct relation with gestational age: 80 (SD 21) at 22-23 weeks, 87 (19) at 24 weeks, 88 (19) at 25 weeks, and 91 (18) at 26 weeks. These results did not differ significantly after imputation. Comparing imputed outcomes between the 2006 and 1995 cohorts, the proportion of survivors born between 22 and 25 weeks' gestation with severe disability, using 1995 definitions, was 18% (95% confidence interval 14% to 24%) in 1995 and 19% (14% to 23%) in 2006. Fewer survivors had shunted hydrocephalus or seizures. Survival of babies admitted for neonatal care increased from 39% (35% to 43%) in 1995 to 52% (49% to 55%) in 2006, an increase of 13% (8% to 18%), and survival without disability increased from 23% (20% to 26%) in 1995 to 34% (31% to 37%) in 2006, an increase of 11% (6% to 16%)., Conclusion: Survival and impairment in early childhood are both closely related to gestational age for babies born at less than 27 weeks' gestation. Using multiple imputation to account for the high proportion of missing values, a higher proportion of babies admitted for neonatal care now survive without disability, particularly those born at gestational ages 24 and 25 weeks.

Objective: To describe one year outcomes for a national cohort of infants with gastroschisis., Design: Population based cohort study of all liveborn infants with gastroschisis born in the United Kingdom and Ireland from October 2006 to March 2008., Setting: All 28 paediatric surgical centres in the UK and Ireland., Participants: 301 infants (77%) from an original cohort of 393., Main Outcome Measures: Duration of parenteral nutrition and stay in hospital; time to establish full enteral feeding; rates of intestinal failure, liver disease associated with intestinal failure, unplanned reoperation; case fatality., Results: Compared with infants with simple gastroschisis (intact, uncompromised, continuous bowel), those with complex gastroschisis (bowel perforation, necrosis, or atresia) took longer to reach full enteral feeding (median difference 21 days, 95% confidence interval 9 to 39 days); required a longer duration of parenteral nutrition (median difference 25 days, 9 to 46 days) and a longer stay in hospital (median difference 57 days, 29 to 95 days); were more likely to develop intestinal failure (81% (25 infants) v 41% (102); relative risk 1.96, 1.56 to 2.46) and liver disease associated with intestinal failure (23% (7) v 4% (11); 5.13, 2.15 to 12.3); and were more likely to require unplanned reoperation (42% (13) v 10% (24); 4.39, 2.50 to 7.70). Compared with infants managed with primary fascial closure, those managed with preformed silos took longer to reach full enteral feeding (median difference 5 days, 1 to 9) and had an increased risk of intestinal failure (52% (50) v 32% (38); 1.61, 1.17 to 2.24). Event rates for the other outcomes were low, and there were no other significant differences between these management groups. Twelve infants died (4%)., Conclusions: This nationally representative study provides a benchmark against which individual centres can measure outcome and performance. Stratifying neonates with gastroschisis into simple and complex groups reliably predicts outcome at one year. There is sufficient clinical equipoise concerning the initial management strategy to embark on a multicentre randomised controlled trial comparing primary fascial closure with preformed silos in infants suitable at presentation for either treatment to determine the optimal initial management strategy and define algorithms of care.

Objectives: To provide survival data and rates of severe disability at 2 years of corrected age in infants born prior to 26 weeks' gestation in 2001-2003 and to compare these outcomes with an earlier cohort from 1991 to 1993., Design: Population-based prospective cohort study., Setting: Former Trent region of UK covering a population of approximately five million and around 55 000 births per annum., Participants: The authors identified a 3-year cohort of infants born before 26 weeks' gestation between 1 January 2001 and 31 December 2003 from The Neonatal Survey (TNS). Questionnaires based on the Oxford minimum dataset were completed., Main Outcome Measures: Survival, service use and disability levels were compared between the 2001- 2003 cohort and the cohort from 1991 to 1993., Results: In 2001-2003, 0%, 18% and 35% of live born babies were alive at 2 years without any evidence of severe disability at 23, 24 and 25 weeks' gestation, respectively. Overall, of those children admitted to neonatal care, the proportion with no evidence of severe disability at 2 years corrected age improved from 14.5% in 1991-1993 to 26.5% in 2001-2003. There was an increase in the proportion of children with at least one severe disability, out of total admissions to neonatal unit (8% vs 17%) and of those assessed at 2 years (35% vs 39%)., Conclusions: This study has shown an improvement in survival to discharge in babies admitted for neonatal care. However, this improved survival has been associated with an increase in the proportion of children with at least one severe disability at a corrected age of 2 years.

Objectives: To investigate socioeconomic inequalities in outcome of pregnancy and neonatal mortality associated with congenital anomalies., Design: Retrospective population based registry study., Setting: East Midlands and South Yorkshire regions of England (representing about 10% of births in England and Wales)., Participants: All registered cases of nine selected congenital anomalies with poor prognostic outcome audited as part of the United Kingdom's fetal anomaly screening programme with an end of pregnancy date between 1 January 1998 and 31 December 2007., Main Outcome Measures: Socioeconomic variation in the risk of selected congenital anomalies; outcome of pregnancy; incidence of live birth and neonatal mortality over time. Deprivation measured with the index of multiple deprivation 2004 at super output area level., Results: There were 1579 fetuses registered with one of the nine selected congenital anomalies. There was no evidence of variation in the overall risk of these anomalies with deprivation (rate ratio for the most deprived 10th with the least deprived 10th: 1.05, 95% confidence interval 0.89 to 1.23). The rate ratio varied with type of anomaly and maternal age (deprivation rate ratio adjusted for maternal age: 1.43 (1.17 to 1.74) for non-chromosomal anomalies; 0.85 (0.63 to 1.15) for chromosomal anomalies). Of the nine anomalies, 86% were detected in the antenatal period, and there was no evidence that this varied with deprivation (rate ratio 0.99, 0.84 to 1.17). The rate of termination after antenatal diagnosis of a congenital anomaly was lower in the most deprived areas compared with the least deprived areas (63% v 79%; rate ratio 0.80, 0.65 to 0.97). Consequently there were significant socioeconomic inequalities in the rate of live birth and neonatal mortality associated with the presence of any of these nine anomalies. Compared with the least deprived areas, the most deprived areas had a 61% higher rate of live births (1.61, 1.21 to 2.15) and a 98% higher neonatal mortality rate (1.98, 1.20 to 3.27) associated with a congenital anomaly., Conclusions: Antenatal screening for congenital anomalies has reduced neonatal mortality through termination of pregnancy. Socioeconomic variation in decisions regarding termination of pregnancy after antenatal detection, however, has resulted in wide socioeconomic inequalities in liveborn infants with a congenital anomaly and subsequent neonatal mortality.

Objective: To investigate time trends in socioeconomic inequalities in cause specific neonatal mortality in order to assess changing patterns in mortality due to different causes, particularly prematurity, and identify key areas of focus for future intervention strategies., Design: Retrospective cohort study., Setting: England., Participants: All neonatal deaths in singleton infants born between 1 January 1997 and 31 December 2007., Main Outcome Measure: Cause specific neonatal mortality per 10 000 births by deprivation tenth (deprivation measured with UK index of multiple deprivation 2004 at super output area level)., Results: 18 524 neonatal deaths occurred in singleton infants born in the 11 year study period. Neonatal mortality fell between 1997-9 and 2006-7 (from 31.4 to 25.1 per 10 000 live births). The relative deprivation gap (ratio of mortality in the most deprived tenth compared with the least deprived tenth) increased from 2.08 in 1997-9 to 2.68 in 2003-5, before a fall to 2.35 in 2006-7. The most common causes of death were immaturity and congenital anomalies. Mortality due to immaturity before 24 weeks' gestation did not decrease over time and showed the widest relative deprivation gap (2.98 in 1997-9; 4.14 in 2003-5; 3.16 in 2006-7). Mortality rates for all other causes fell over time. For congenital anomalies, immaturity, and accidents and other specific causes, the relative deprivation gap widened between 1997-9 and 2003-5, before a slight fall in 2006-7. For intrapartum events and sudden infant deaths (only 13.5% of deaths) the relative deprivation gap narrowed slightly., Conclusions: Almost 80% of the relative deprivation gap in all cause mortality was explained by premature birth and congenital anomalies. To reduce socioeconomic inequalities in mortality, a change in focus is needed to concentrate on these two influential causes of death. Understanding the link between deprivation and preterm birth should be a major research priority to identify interventions to reduce preterm birth.

Objective: To describe simple estimates of likely duration of stay for very premature babies born in the UK and discharged home., Design: Statistical modelling of data from thirty neonatal units in a geographically defined region of the UK., Participants: All babies born at 23 to 32 completed weeks of gestation in 2005, 2006 and 2007 who were discharged home with the expectation that they would survive., Main Outcome Measure: Total duration of stay in the neonatal service., Results: 5528 babies were initially identified. 558 (10.1%) who died or who did not follow a normal care pathway were excluded. In a further 27, data were either missing or inadequate, leaving a study population of 4702 babies. As expected, gestation and birthweight exhibited strong influence on length of stay. Of the other variables tested, initial reason for admission (need for early respiratory support) showed the most consistent association. These factors were combined to produce predictive tables. The predictive performance of the tables was found to fit the data well for various groups, with the exception of multiple births who tended to have longer stays. However, when tested against individual units, much greater variation was seen independent of unit size and case mix., Conclusion: The prediction tables should permit parents to make sensible estimates about the duration of their baby's stay in the neonatal service; however, there appear to be important differences between units. The variation noted in length of stay between otherwise similar units merits further investigation.

Objective: To validate Clinical Risk Index for Babies (CRIB) and CRIB II mortality prediction scores in a UK population of infants born at

Objectives: To assess socioeconomic inequalities in survival and provision of neonatal care among very preterm infants., Design: Prospective cohort study in a geographically defined population., Setting: Former Trent health region of the United Kingdom (covering about a twelfth of UK births)., Participants: All infants born between 22+0 and 32+6 weeks' gestation from 1 January 1998 to 31 December 2007 who were alive at the onset of labour and followed until discharge from neonatal care., Main Outcome Measures: Survival to discharge from neonatal care per 1000 total births and per 1000 very preterm births. Neonatal care provision for very preterm infants surviving to discharge measured with length of stay, provision of ventilation, and respiratory support. Deprivation measured with the UK index of multiple deprivation 2004 score at super output area level., Results: 7449 very preterm singleton infants were born in the 10 year period. The incidence of very preterm birth was nearly twice as high in the most deprived areas compared with the least deprived areas. Consequently rates of mortality due to very preterm birth per 1000 total births were almost twice as high in the most deprived areas compared with the least deprived (incidence rate ratio 1.94, 95% confidence interval 1.62 to 2.32). Mortality rates per 1000 very preterm births, however, showed little variation across all deprivation fifths (incidence rate ratio for most deprived fifth versus least deprived 1.02, 0.86 to 1.20). For infants surviving to discharge from neonatal care, measures of length of stay and provision of ventilation and respiratory support were similar across all deprivation fifths., Conclusions: The burden of mortality and morbidity is greater among babies born to women from deprived areas because of increased rates of very preterm birth. After very preterm birth, however, survival rates and neonatal care provision is similar for infants from all areas.

Objective: To estimate the influence of variation in the rate of very preterm delivery on the reported rate of neonatal death in 10 European regions., Design: Comparison of 10 separate geographically defined European populations, from nine European countries, over a 1-year period (7 months in one region)., Participants: All births that occurred between 22(+0) and 31(+6) weeks of gestation in 2003., Main Outcome Measure: Neonatal death rate adjusted for rate of delivery at this gestation., Results: Rate of delivery of all births at 22(+0)-31(+6) weeks of gestation and live births only were calculated for each region. Two regions had significantly higher rates of very preterm delivery per 1000 births: Trent UK (16.8, 95% CI 15.7 to 17.9) and Northern UK (17.1, 95% CI 15.6 to 18.6); group mean 13.2 (95% CI 12.9 to 13.5). Four regions had rates significantly below the group average: Portugal North (10.7, 95% CI 9.6 to 11.8), Eastern and Central Netherlands (10.6, 95% CI 9.7 to 11.6), Eastern Denmark (11.2, 95% CI 10.1 to 12.4) and Lazio in Italy (11.0, 95% CI 10.1 to 11.9). Similar trends were seen in live birth data. Published rates of neonatal death for each region were then adjusted by applying (a) a standardised rate of very preterm delivery and (b) the existing death rate for babies born at this gestation in the individual region. This produced much greater homogeneity in terms of neonatal mortality., Conclusions: Variation in the rate of very preterm delivery has a major influence on reported neonatal death rates.

Objective: To investigate the variation in the survival rate and the mortality rates for very preterm infants across Europe., Design: A prospective birth cohort of very preterm infants for 10 geographically defined European regions during 2003, followed to discharge home from hospital., Participants: All deliveries from 22 + 0 to 31 + 6 weeks' gestation., Main Outcome Measure: All outcomes of pregnancy by gestational age group, including termination of pregnancy for congenital anomalies and other reasons, antepartum stillbirth, intrapartum stillbirth, labour ward death, death after admission to a neonatal intensive care unit (NICU) and survival to discharge., Results: Overall the proportion of this very preterm cohort who survived to discharge from neonatal care was 89.5%, varying from 93.2% to 74.8% across the regions. Less than 2% of infants <24 weeks' gestation and approximately half of the infants from 24 to 27 weeks' gestation survived to discharge home from the NICU. However large variations were seen in the timing of the deaths by region. Among all fetuses alive at onset of labour of 24-27 weeks' gestation, between 84.0% and 98.9% were born alive and between 64.6% and 97.8% were admitted to the NICU. For babies <24 weeks' gestation, between 0% and 79.6% of babies alive at onset of labour were admitted to neonatal intensive care., Conclusions: There are wide variations in the survival rates to discharge from neonatal intensive care for very preterm deliveries and in the timing of death across the MOSAIC regions. In order to directly compare international statistics for mortality in very preterm infants, data collection needs to be standardised. We believe that the standard point of comparison should be using all those infants alive at the onset of labour as the denominator for comparisons of mortality rates for very preterm infants analysing the cohort by gestational age band.

Objective: To assess changes in survival for infants born before 26 completed weeks of gestation., Design: Prospective cohort study in a geographically defined population., Setting: Former Trent health region of the United Kingdom., Subjects: All infants born at 22+0 to 25+6 weeks' gestation to mothers living in the region. Terminations were excluded but all other births of babies alive at the onset of labour or the delivery process were included., Main Outcome Measures: Outcome for all infants was categorised as stillbirth, death without admission to neonatal intensive care, death before discharge from neonatal intensive care, and survival to discharge home in two time periods: 1994-9 and 2000-5 inclusive., Results: The proportion of infants dying in delivery rooms was similar in the two periods, but a significant improvement was seen in the number of infants surviving to discharge (P<0.001). Of 497 infants admitted to neonatal intensive care in 2000-5, 236 (47%) survived to discharge compared with 174/490 (36%) in 1994. These changes were attributable to substantial improvements in the survival of infants born at 24 and 25 weeks. During the 12 years of the study none of the 150 infants born at 22 weeks' gestation survived. Of the infants born at 23 weeks who were admitted to intensive care, there was no significant improvement in survival to discharge in 2000-5 (12/65 (18%) in 2000-5 v 15/81 (19%) in 1994-9)., Conclusions: Survival of infants born at 24 and 25 weeks of gestation has significantly increased. Although over half the cohort of infants born at 23 weeks was admitted to neonatal intensive care, there was no improvement in survival at this gestation. Care for infants born at 22 weeks remained unsuccessful.

Background: Comparisons of national perinatal and neonatal mortality often neglect the underlying causes., Objective: To assess effects of very-preterm births in the UK and Australia., Setting: Two geographically defined populations: the former Trent Health Region of the UK and New South Wales (NSW)/the Australian Capital Territory (ACT), Australia., Method: All births 22(+0) to 31(+6) weeks in 2000, 2001 and 2002 were identified by established surveys of perinatal care. Rates of birth and death were compared., Results: The population of NSW/ACT was 35% higher and there were 66% more births than in Trent (273 495 vs 164 824). The proportion of liveborn infants between 22 and 31 weeks gestation was about 25% higher in Trent (NSW/ACT 2945, rate per 1000 live births 10.82 (95% CI 10.43 to 11.22); Trent 2208, rate per 1000 live births 13.47 (95% CI 12.92 to 14.05)). The proportion of these infants admitted to a neonatal unit was also higher in Trent (91.2% vs 94.4%; OR 1.63 (95% CI 1.30 to 2.05)). Unadjusted mortality in infants admitted to a neonatal unit was similar: NSW/ACT 332/2686 (12.4%); Trent 284/2085 (13.6%); unadjusted OR 1.12 (95% CI 0.94 to 1.33; p = 0.21)., Conclusions: The higher rates of very premature birth and more ready admission to neonatal intensive care for infants in the UK may help to explain why perinatal and neonatal mortality are higher there than in Australia. Efforts to understand why the rate of premature birth in the UK is so high should be a national priority.

Objective: To explore the differences in outcome of very preterm pregnancies between two geographically defined populations in Europe with similar socioeconomic characteristics and healthcare provision but different organisational arrangements for perinatal care., Design: Prospective cohort study., Setting: Nord Pas-de-Calais (NPC), France, and Trent, UK., Participants: All pregnancy outcomes 22(+0) to 32(+6) weeks' gestational age for resident mothers., Outcome Measures: Mortality patterns (antepartum death, intrapartum death, labour ward death and neonatal unit death) among very preterm babies were analysed by region. Multinomial logistic regression was used to model regional differences for a variety of pregnancy outcomes and to adjust for regional differences in the organisation of perinatal care., Results: Delivery of very preterm infants was significantly higher in Trent compared with NPC (1.9% v 1.5% of all births, respectively (p<0.001)). Stillbirth rate was significantly higher in NPC than in Trent (23.0%, 95% CI 20.0% to 26.5% v 14.4%, 95% CI 12.3% to 16.6%, respectively (p<0.001)) and survival to discharge was higher in Trent than in NPC (74.6%, 95% CI 71.9% to 77.1% v 66.7%, 95% CI 63.3% to 69.9%, respectively (p<0.001)). Probability of intrapartum and labour ward death in NPC was more than five times higher than Trent (relative risk 5.3, 95% CI 2.2 to 13.1 (p<0.001))., Conclusion: The high rate of very preterm deliveries and the larger proportion of these infants recorded as live born in Trent appear to be the cause of the excess neonatal mortality seen in the routine statistics. Information about very preterm babies (not usually included in routine statistics) is vital to avoid inappropriate interpretation of international perinatal and infant data. This study highlights the importance of including deaths before transfer to neonatal care and emphasises the need to include the outcome of all pregnancies in a population in any comparative analysis.

Aims: To investigate the extent of socioeconomic inequalities in the incidence of very preterm birth over the past decade., Methods: Ecological study of all 549 618 births in the former Trent health region, UK, from 1 January 1994 to 31 December 2003. All singleton births of 22(+0) to 32(+6) weeks gestation (7 185 births) were identified from population surveys of neonatal services and stillbirths. Poisson regression was used to calculate incidence of very preterm birth (22-32 weeks) and extremely preterm birth (22-28 weeks) by year of birth and decile of deprivation (child poverty section of the Index of Multiple Deprivation)., Results: Incidence of very preterm singleton birth rose from 11.9 per 1000 births in 1994 to 13.7 per 1000 births in 2003. Those from the most deprived decile were at nearly twice the risk of very preterm birth compared with those from the least deprived decile, with 16.4 per 1000 births in the most deprived decile compared with 8.5 per 1000 births in the least deprived decile (incidence rate ratio 1.94; 95% CI (1.73 to 2.17)). This deprivation gap remained unchanged throughout the 10-year period. The magnitude of socio-economic inequalities was the same for extremely preterm births (22-28 weeks incidence rate ratio 1.94; 95% CI (1.62 to 2.32))., Conclusions: This large, unique dataset of very preterm births shows wide socio-economic inequalities that persist over time. These findings are likely to have consequences on the burden of long-term morbidity. Our research can assist future healthcare planning, the monitoring of socio-economic inequalities and the targeting of interventions in order to reduce this persistent deprivation gap.

Background: The outcome in late childhood for children entered into a randomised trial of continuous negative extrathoracic pressure (CNEP) versus standard respiratory management for the treatment of neonatal respiratory distress was studied. In the original trial, there were advantages in the duration of oxygen and the prevalence of chronic lung disease for those assigned to receive CNEP., Aim: To determine whether the above differences had persisted into childhood., Methods: Outpatient evaluation of children by a paediatrician using Spirometry (Vitalograph Spirometer 2120, Ennis, Ireland) and MicroRint (Micro Medical, Rochester, Kent, UK) techniques independently of the original trial. Parents completed questionnaires about their child's respiratory history and social-demographic information., Results: 133 (65%) survivors were evaluated at 9.6-14.9 years of age. The group examined were representative of the original cohort and no significant baseline differences were observed between children evaluated who had been allocated to CNEP or standard treatments. We compared Rint (before and after bronchodilator) and forced expiratory flow, volume and vital capacity between the two study groups; none were significant. Children in the standard group had received paediatric intensive care more often (p = 0.19) and were more likely to be receiving inhaled drugs for asthma (p = 0.19; all not significant)., Conclusions: No important differences were found at follow-up in late childhood in respiratory outcomes for children treated with neonatal CNEP or standard treatment. Caution should be exercised, as the original trial was not powered to show these differences, but there seems to be no long-term detriment in respiratory outcomes for children treated with CNEP in the neonatal period.

Background: Adverse cognitive and educational outcomes are often ascribed to perinatal hypoxia without good evidence., Objective: To investigate neurocognitive and behavioural outcomes after neonatal encephalopathy., Methods: Sixty five children with neonatal encephalopathy, identified using the Trent Neonatal Survey database for 1992-1994, were followed up at the age of 7 years. They were examined at school, with a classmate for those in mainstream school, by a paediatrician and a psychologist. Neonatal encephalopathy was graded as moderate or severe using published definitions., Findings: Fifteen children had major disability, all with cerebral palsy; eight were in special school with severe cognitive impairment (IQ<55). Disability was present in 6% of the moderate and 42% of the severe encephalopathy group. Of the 50 children without motor disability, cognitive scores were lowest in the severe group (mean IQ difference from peers -11.3 points (95% confidence interval (CI) -19.0 to -3.6) and with similar scores for the moderate group compared with classmates (mean difference -1.7 points (95% CI -7.3 to +3.9). Neuropsychological testing showed similar findings in all domains. In particular, memory and attention/executive functions were impaired in the severe group. Despite relatively small differences in performance of the moderate group, special educational needs were identified more often in both encephalopathy groups, associated with lower achievement on national curriculum attainment targets., Interpretation: After neonatal encephalopathy, subtle cognitive impairments are found in the absence of neuromotor impairment. Subtle impairments are found more commonly after a more severe clinical course. Studies of brain protection strategies require long term follow up to study effects on cognitive outcome.

Objectives: To investigate the feasibility of obtaining signed consent for submission of patient identifiable data to a national clinical audit database and to identify factors influencing the consent process and its success., Design: Feasibility study., Setting: Seven paediatric intensive care units in England., Participants: Parents/guardians of patients, or patients aged 12-16 years old, approached consecutively over three months for signed consent for submission of patient identifiable data to the national clinical audit database the Paediatric Intensive Care Audit Network (PICANet)., Main Outcome Measures: The numbers and proportions of admissions for which signed consent was given, refused, or not obtained (form not returned or form partially completed but not signed), by age, sex, level of deprivation, ethnicity (South Asian or not), paediatric index of mortality score, length of hospital stay (days in paediatric intensive care)., Results: One unit did not start and one did not fully implement the protocol, so analysis excluded these two units. Consent was obtained for 182 of 422 admissions (43%) (range by unit 9% to 84%). Most (101/182; 55%) consents were taken by staff nurses. One refusal (0.2%) was received. Consent rates were significantly better for children who were more severely ill on admission and for hospital stays of six days or more, and significantly poorer for children aged 10-14 years. Long hospital stays and children aged 10-14 years remained significant in a stepwise regression model of the factors that were significant in the univariate model., Conclusion: Systematically obtaining individual signed consent for sharing patient identifiable information with an externally located clinical audit database is difficult. Obtaining such consent is unlikely to be successful unless additional resources are specifically allocated to training, staff time, and administrative support.