Characteristics of children requiring admission to neonatal care and paediatric intensive care before the age of 2 years in England and Wales: a data linkage study.

OBJECTIVE: To quantify the characteristics of children admitted to neonatal units (NNUs) and paediatric intensive care units (PICUs) before the age of 2 years. DESIGN: A data linkage study of routinely collected data. SETTING: National Health Service NNUs and PICUs in England and Wales PATIENTS: Children born from 2013 to 2018. INTERVENTIONS: None. MAIN OUTCOME MEASURE: Admission to PICU before the age of 2 years. RESULTS: A total of 384 747 babies were admitted to an NNU and 4.8% (n=18 343) were also admitted to PICU before the age of 2 years. Approximately half of all children admitted to PICU under the age of 2 years born in the same time window (n=18 343/37 549) had previously been cared for in an NNU.The main reasons for first admission to PICU were cardiac (n=7138) and respiratory conditions (n=5386). Cardiac admissions were primarily from children born at term (n=5146), while respiratory admissions were primarily from children born preterm (<37 weeks' gestational age, n=3550). A third of children admitted to PICU had more than one admission. CONCLUSIONS: Healthcare professionals caring for babies and children in NNU and PICU see some of the same children in the first 2 years of life. While some children are following established care pathways (eg, staged cardiac surgery), the small proportion of children needing NNU care subsequently requiring PICU care account for a large proportion of the total PICU population. These differences may affect perceptions of risk for this group of children between NNU and PICU teams.

Primary Classic Kaposi Sarcoma of the Parotid Gland in an HIV-Negative Patient.

This case report describes an HIV-negative man in his 60s of Mediterranean descent with hypertension, Hashimoto thyroiditis, nephrolithiasis, and gout who presented with a lump on the right side of his face and was subsequently diagnosed with Kaposi sarcoma.

Understanding the co-construction of safety in the paediatric intensive care unit: A meta-ethnography of parents' experiences.

BACKGROUND: Children experiencing critical illness or injury may require admission to a paediatric intensive care unit (PICU) to receive life-sustaining or life-saving treatment. Studies have explored the experience of parents with a child in PICU but tend to focus on subgroups of children or specific healthcare systems. Therefore, we aimed to undertake a meta-ethnography to draw together the published research. METHODS: A systematic search strategy was developed to identify qualitative studies, which had explored the experiences of parents with a critically ill child treated in a PICU. A meta-ethnography was undertaken following the structured steps of identifying the topic; undertaking a systematic search; reading the research; determining how the studies relate and translate into each other; and synthesising and expressing the results. RESULTS: We identified 2989 articles from our search and after a systematic series of exclusions, 15 papers remaining for inclusion. We explored the original parent voices (first order) and the interpretation of the study authors (second order) to identify three third-order concepts (our interpretation of the findings), which related to technical, relational and temporal factors. These factors influenced parents' experiences, providing both barriers and facilitators to how parents and caregivers experienced the time their child was in the PICU. The dynamic and co-constructed nature of safety provided an analytical overarching frame of reference. CONCLUSION: This synthesis demonstrates novel ways in which parents and caregivers can contribute to the vital role of ensuring a co-created safe healthcare environment for their child when receiving life-saving care within the PICU.

Conservative versus liberal oxygenation targets in critically ill children (Oxy-PICU): a UK multicentre, open, parallel-group, randomised clinical trial.

BACKGROUND: The optimal target for systemic oxygenation in critically ill children is unknown. Liberal oxygenation is widely practiced, but has been associated with harm in paediatric patients. We aimed to evaluate whether conservative oxygenation would reduce duration of organ support or incidence of death compared to standard care. METHODS: Oxy-PICU was a pragmatic, multicentre, open-label, randomised controlled trial in 15 UK paediatric intensive care units (PICUs). Children admitted as an emergency, who were older than 38 weeks corrected gestational age and younger than 16 years receiving invasive ventilation and supplemental oxygen were randomly allocated in a 1:1 ratio via a concealed, central, web-based randomisation system to conservative peripheral oxygen saturations ([SpO2] 88-92%) or liberal (SpO2 >94%) targets. The primary outcome was the duration of organ support at 30 days following random allocation, a rank-based endpoint with death either on or before day 30 as the worst outcome (a score equating to 31 days of organ support), with survivors assigned a score between 1 and 30 depending on the number of calendar days of organ support received. The primary effect estimate was the probabilistic index, a value greater than 0·5 indicating more than 50% probability that conservative oxygenation is superior to liberal oxygenation for a randomly selected patient. All participants in whom consent was available were included in the intention-to-treat analysis. The completed study was registered with the ISRCTN registry (ISRCTN92103439). FINDINGS: Between Sept 1, 2020, and May 15, 2022, 2040 children were randomly allocated to conservative or liberal oxygenation groups. Consent was available for 1872 (92%) of 2040 children. The conservative oxygenation group comprised 939 children (528 [57%] of 927 were female and 399 [43%] of 927 were male) and the liberal oxygenation group included 933 children (511 [56%] of 920 were female and 409 [45%] of 920 were male). Duration of organ support or death in the first 30 days was significantly lower in the conservative oxygenation group (probabilistic index 0·53, 95% CI 0·50-0·55; p=0·04 Wilcoxon rank-sum test, adjusted odds ratio 0·84 [95% CI 0·72-0·99]). Prespecified adverse events were reported in 24 (3%) of 939 patients in the conservative oxygenation group and 36 (4%) of 933 patients in the liberal oxygenation group. INTERPRETATION: Among invasively ventilated children who were admitted as an emergency to a PICU receiving supplemental oxygen, a conservative oxygenation target resulted in a small, but significant, greater probability of a better outcome in terms of duration of organ support at 30 days or death when compared with a liberal oxygenation target. Widespread adoption of a conservative oxygenation saturation target (SpO2 88-92%) could help improve outcomes and reduce costs for the sickest children admitted to PICUs. FUNDING: UK National Institute for Health and Care Research Health Technology Assessment Programme.

Variation in follow-up for children born very preterm in Europe.

BACKGROUND: Children born very preterm (<32 weeks of gestation) face high risks of neurodevelopmental and health difficulties compared with children born at term. Follow-up after discharge from the neonatal intensive care unit is essential to ensure early detection and intervention, but data on policy approaches are sparse. METHODS: We investigated the characteristics of follow-up policy and programmes in 11 European countries from 2011 to 2022 using healthcare informant questionnaires and the published/grey literature. We further explored how one aspect of follow-up, its recommended duration, may be reflected in the percent of parents reporting that their children are receiving follow-up services at 5 years of age in these countries using data from an area-based cohort of very preterm births in 2011/12 (N = 3635). RESULTS: Between 2011/12 and 22, the number of countries with follow-up policies or programmes increased from 6 to 11. The policies and programmes were heterogeneous in eligibility criteria, duration and content. In countries that recommended longer follow-up, parent-reported follow-up rates at 5 years of age were higher, especially among the highest risk children, born <28 weeks' gestation or with birthweight <1000 g: between 42.1% and 70.1%, vs. <20% in most countries without recommendations. CONCLUSIONS: Large variations exist in follow-up policies and programmes for children born very preterm in Europe; differences in recommended duration translate into cross-country disparities in reported follow-up at 5 years of age.

Prevalence of neural tube defects in England prior to the mandatory fortification of non-wholemeal wheat flour with folic acid: a population-based cohort study.

OBJECTIVES: To determine the baseline trends in the total birth prevalence of neural tube defects (NTDs) in England (2000-2019) to enable the impact of folic acid fortification of non-wholemeal wheat flour to be monitored. DESIGN: Population-based, observational study using congenital anomaly (CA) registration data for England curated by the National Congenital Anomaly and Rare Disease Registration Service (NCARDRS). SETTING: Regions of England with active registration in the time period. PARTICIPANTS: Babies that were liveborn or stillborn and pregnancies that resulted in a termination of pregnancy or a late miscarriage (20-23 weeks' gestation) with an NTD. MAIN OUTCOME MEASURES: Total birth prevalence of anencephaly, spina bifida and all NTDs in England. Poisson regression analysis was used to evaluate time trends with regional register as a random effect. The progress of national registration across England was assessed. RESULTS: There were 4541 NTD pregnancies out of 3 637 842 births in England; 1982 anencephaly and 2127 spina bifida. NTD prevalence was 12.5 (95% CI 12.1 to 12.9) per 10 000 total births. NTD prevalence per 10 000 total births was significantly higher in 2015-2019 (13.6, 95% CI 12.9 to 14.4) compared with 2010-2014 (12.1, 95% CI 11.7 to 12.5). An increasing trend in NTDs overall was detected (incidence rate ratio (IRR) 1.01, 1.00 to 1.02), although further analysis determined this effect was confined to 2015-2019 (compared against 2000-2004, IRR 1.14, 1.04 to 1.24). The birth prevalence of anencephaly reflected this pattern. The prevalence of spina bifida remained relatively stable over time. CONCLUSIONS: Baseline NTD prevalence for England has been established. National and standardised CA registration is in place, facilitating the systematic and consistent monitoring of pre-fortification and post-fortification NTD trends and evaluating the impact of fortification on NTD prevalence.

Paediatric intensive care admissions of preterm children born <32 weeks gestation: a national retrospective cohort study using data linkage.

OBJECTIVE: Survival of babies born very preterm (<32 weeks gestational age) has increased, although preterm-born children may have ongoing morbidity. We aimed to investigate the risk of admission to paediatric intensive care units (PICUs) of children born very preterm following discharge home from neonatal care. DESIGN: Retrospective cohort study, using data linkage of National Neonatal Research Database and the Paediatric Intensive Care Audit Network datasets. SETTING: All neonatal units and PICUs in England and Wales. PATIENTS: Children born very preterm between 1 January 2013 and 31 December 2018 and admitted to neonatal units. MAIN OUTCOME MEASURES: Admission to PICU after discharge home from neonatal care, before 2 years of age. RESULTS: Of the 40 690 children discharged home from neonatal care, there were 2308 children (5.7%) with at least one admission to PICU after discharge. Of these children, there were 1901 whose first PICU admission after discharge was unplanned.The percentage of children with unplanned PICU admission varied by gestation, from 10.2% of children born <24 weeks to 3.3% born at 31 weeks.Following adjustment, unplanned PICU admission was associated with lower gestation, male sex (adjusted OR (aOR) 0.79), bronchopulmonary dysplasia (aOR 1.37), necrotising enterocolitis requiring surgery (aOR 1.39) and brain injury (aOR 1.42). For each week of increased gestation, the aOR was 0.90. CONCLUSIONS: Most babies born <32 weeks and discharged home from neonatal care do not require PICU admission in the first 2 years. The odds of unplanned admissions to PICU were greater in the most preterm and those with significant neonatal morbidity.

Characteristics and outcomes of neonates hospitalised with SARS-CoV-2 infection in the UK by variant: a prospective national cohort study.

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.

Apgar Score and Neurodevelopmental Outcomes at Age 5 Years in Infants Born Extremely Preterm.

Importance: The Apgar score is used worldwide as an assessment tool to estimate the vitality of newborns in their first minutes of life. Its applicability to estimate neurodevelopmental outcomes in infants born extremely preterm (EPT; <28 weeks' gestation) is not well established. Objective: To investigate the association between the Apgar score and neurodevelopmental outcomes in infants born EPT. Design, Setting, and Participants: This cohort study was conducted using data from the Effective Perinatal Intensive Care in Europe-Screening to Improve Health in Very Preterm Infants in Europe (EPICE-SHIPS) study, a population-based cohort in 19 regions of 11 European countries in 2011 to 2012. Clinical assessments of cognition and motor function at age 5 years were performed in infants born EPT and analyzed in January to July 2023. Exposures: Apgar score at 5 minutes of life categorized into 4 groups (0-3, 4-6, 7-8, and 9-10 points). Main Outcomes and Measures: Cognitive and motor outcomes were assessed using the Wechsler Preschool and Primary Scale of Intelligence test of IQ derived from locally normed versions by country and the Movement Assessment Battery for Children-Second Edition. Parents additionally provided information on communication and problem-solving skills using the Ages and Stages Questionnaire, third edition (ASQ-3). All outcomes were measured as continuous variables. Results: From the total cohort of 4395 infants born EPT, 2522 infants were live born, 1654 infants survived to age 5 years, and 996 infants (478 females [48.0%]) followed up had at least 1 of 3 outcome measures. After adjusting for sociodemographic variables, perinatal factors, and severe neonatal morbidities, there was no association of Apgar score with IQ, even for scores of 3 or less (ß = -3.3; 95% CI, -10.5 to 3.8) compared with the score 9 to 10 category. Similarly, no association was found for ASQ-3 (ß = -2.1; 95% CI, -24.6 to 20.4). Congruent results for Apgar scores of 3 or less were obtained for motor function scores for all children (ß = -4.0; 95% CI, -20.1 to 12.1) and excluding children with a diagnosis of cerebral palsy (ß = 0.8, 95% CI -11.7 to 13.3). Conclusions and Relevance: This study found that low Apgar scores were not associated with longer-term outcomes in infants born EPT. This finding may be associated with high interobserver variability in Apgar scoring, reduced vitality signs and poorer responses to resuscitation after birth among infants born EPT, and the association of more deleterious exposures in the neonatal intensive care unit or of socioeconomic factors with greater changes in outcomes during the first 5 years of life.

Impact of prematurity on long-stay paediatric intensive care unit admissions in England 2008-2018.

BACKGROUND: Survival following extreme preterm birth has improved, potentially increasing the number of children with ongoing morbidity requiring intensive care in childhood. Previous single-centre studies have suggested that long-stay admissions in paediatric intensive care units (PICUs) are increasing. We aimed to examine trends in long-stay admissions (≥28 days) to PICUs in England, outcomes for this group (including mortality and PICU readmission), and to determine the contribution of preterm-born children to the long-stay population, in children aged <2 years. METHODS: Data was obtained from the Paediatric Intensive Care Audit Network (PICANet) for all children <2 years admitted to National Health Service PICUs from 1/1/2008 to 31/12/2018 in England. We performed descriptive analysis of child characteristics and PICU outcomes. RESULTS: There were 99,057 admissions from 67,615 children. 2,693 children (4.0%) had 3,127 long-stays. Between 2008 and 2018 the annual number of long-stay admissions increased from 225 (2.7%) to 355 (4.0%), and the proportion of bed days in PICUs occupied by long-stay admissions increased from 24.2% to 33.2%. Of children with long-stays, 33.5% were born preterm, 53.5% were born at term, and 13.1% had missing data for gestational age. A considerable proportion of long-stay children required PICU readmission before two years of age (76.3% for preterm-born children). Observed mortality during any admission was also disproportionately greater for long-stay children (26.5% for term-born, 24.8% for preterm-born) than the overall rate (6.3%). CONCLUSIONS: Long-stays accounted for an increasing proportion of PICU activity in England between 2008 and 2018. Children born preterm were over-represented in the long-stay population compared to the national preterm birth rate (8%). These results have significant implications for future research into paediatric morbidity, and for planning future PICU service provision.

Pediatric Hospitalizations and ICU Admissions Due to COVID-19 and Pediatric Inflammatory Multisystem Syndrome Temporally Associated With SARS-CoV-2 in England.

Importance: Investigating how the risk of serious illness after SARS-CoV-2 infection in children and adolescents has changed as new variants have emerged is essential to inform public health interventions and clinical guidance. Objective: To examine risk factors associated with hospitalization for COVID-19 or pediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 (PIMS-TS) among children and adolescents during the first 2 years of the COVID-19 pandemic and change in risk factors over time. Design, Setting, and Participants: This population-level analysis of hospitalizations after SARS-CoV-2 infection in England among children and adolescents aged 0 to 17 years was conducted from February 1, 2020, to January 31, 2022. National data on hospital activity were linked with data on SARS-CoV-2 testing, SARS-CoV-2 vaccination, pediatric intensive care unit (PICU) admissions, and mortality. Children and adolescents hospitalized with COVID-19 or PIMS-TS during this time were included. Maternal, elective, and injury-related hospitalizations were excluded. Exposures: Previous medical comorbidities, sociodemographic factors, and timing of hospitalization when different SARS-CoV-2 variants (ie, wild type, Alpha, Delta, and Omicron) were dominant in England. Main Outcomes: PICU admission and death within 28 days of hospitalization with COVID-19 or PIMS-TS. Results: A total of 10 540 hospitalizations due to COVID-19 and 997 due to PIMS-TS were identified within 1 125 010 emergency hospitalizations for other causes. The number of hospitalizations due to COVID-19 and PIMS-TS per new SARS-CoV-2 infections in England declined during the second year of the COVID-19 pandemic. Among 10 540 hospitalized children and adolescents, 448 (4.3%) required PICU admission due to COVID-19, declining from 162 of 1635 (9.9%) with wild type, 98 of 1616 (6.1%) with Alpha, and 129 of 3789 (3.4%) with Delta to 59 of 3500 (1.7%) with Omicron. Forty-eight children and adolescents died within 28 days of hospitalization due to COVID-19, and no children died of PIMS-TS (PIMS-S data were limited to November 2020 onward). Risk of severe COVID-19 in children and adolescents was associated with medical comorbidities and neurodisability regardless of SARS-CoV-2 variant. Results were similar when children and adolescents with prior SARS-CoV-2 exposure or vaccination were excluded. Conclusions: In this study of data across the first 2 years of the COVID-19 pandemic, risk of severe disease from SARS-CoV-2 infection in children and adolescents in England remained low. Children and adolescents with multiple medical problems, particularly neurodisability, were at increased risk and should be central to public health measures as further variants emerge.

Comparing behavioural outcomes in children born extremely preterm between 2006 and 1995: the EPICure studies.

BACKGROUND: Children born extremely preterm (EP) are at increased risk of neurocognitive and behavioural morbidity. Here, we investigate whether behavioural outcomes have changed over time concomitant with increasing survival following EP birth. METHODS: Comparison of outcomes at 11 years of age for two prospective national cohorts of children born EP in 1995 (EPICure) and 2006 (EPICure2), assessed alongside term-born children. Behavioural outcomes were assessed using the parent-completed Strengths and Difficulties Questionnaire (SDQ), DuPaul Attention-Deficit/Hyperactivity Disorder Rating Scale (ADHD-RS), and Social Communication Questionnaire (SCQ). RESULTS: In EPICure, 176 EP and 153 term-born children were assessed (mean age: 10.9 years); in EPICure2, 112 EP and 143 term-born children were assessed (mean age: 11.8 years). In both cohorts, EP children had higher mean scores and more clinically significant difficulties than term-born children on almost all measures. Comparing outcomes for EP children in the two cohorts, there were no significant differences in mean scores or in the proportion of children with clinically significant difficulties after adjustment for confounders. Using term-born children as reference, EP children in EPICure2 had significantly higher SDQ total difficulties and ADHD-RS hyperactivity impulsivity z-scores than EP children in EPICure. CONCLUSIONS: Behavioural outcomes have not improved for EP children born in 2006 compared with those born in 1995. Relative to term-born peers, EP children born in 2006 had worse outcomes than those born in 1995. There is an ongoing need for long-term clinical follow-up and psychological support for children born EP.

Ending preventable stillbirths and improving bereavement care: a scorecard for high- and upper-middle income countries.

BACKGROUND: Despite progress, stillbirth rates in many high- and upper-middle income countries remain high, and the majority of these deaths are preventable. We introduce the Ending Preventable Stillbirths (EPS) Scorecard for High- and Upper Middle-Income Countries, a tool to track progress against the Lancet's 2016 EPS Series Call to Action, fostering transparency, consistency and accountability. METHODS: The Scorecard for EPS in High- and Upper-Middle Income Countries was adapted from the Scorecard for EPS in Low-Income Countries, which includes 20 indicators to track progress against the eight Call to Action targets. The Scorecard for High- and Upper-Middle Income Countries includes 23 indicators tracking progress against these same Call to Action targets. For this inaugural version of the Scorecard, 13 high- and upper-middle income countries supplied data. Data were collated and compared between and within countries. RESULTS: Data were complete for 15 of 23 indicators (65%). Five key issues were identified: (1) there is wide variation in stillbirth rates and related perinatal outcomes, (2) definitions of stillbirth and related perinatal outcomes vary widely across countries, (3) data on key risk factors for stillbirth are often missing and equity is not consistently tracked, (4) most countries lack guidelines and targets for critical areas for stillbirth prevention and care after stillbirth and have not set a national stillbirth rate target, and (5) most countries do not have mechanisms in place for reduction of stigma or guidelines around bereavement care. CONCLUSIONS: This inaugural version of the Scorecard for High- and Upper-Middle Income Countries highlights important gaps in performance indicators for stillbirth both between and within countries. The Scorecard provides a basis for future assessment of progress and can be used to help hold individual countries accountable, especially for reducing stillbirth inequities in disadvantaged groups.

Children born preterm admitted to paediatric intensive care for bronchiolitis: a systematic review and meta-analysis.

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, I2 = 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, I2 = 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.

Neonatal mortality risk for vulnerable newborn types in 15 countries using 125.5 million nationwide birth outcome records, 2000-2020.

OBJECTIVE: To compare neonatal mortality associated with six novel vulnerable newborn types in 125.5 million live births across 15 countries, 2000-2020. DESIGN: Population-based, multi-country study. SETTING: National data systems in 15 middle- and high-income countries. METHODS: We used individual-level data sets identified for the Vulnerable Newborn Measurement Collaboration. We examined the contribution to neonatal mortality of six newborn types combining gestational age (preterm [PT] versus term [T]) and size-for-gestational age (small [SGA], <10th centile, appropriate [AGA], 10th-90th centile or large [LGA], >90th centile) according to INTERGROWTH-21st newborn standards. Newborn babies with PT or SGA were defined as small and T + LGA was considered as large. We calculated risk ratios (RRs) and population attributable risks (PAR%) for the six newborn types. MAIN OUTCOME MEASURES: Mortality of six newborn types. RESULTS: Of 125.5 million live births analysed, risk ratios were highest among PT + SGA (median 67.2, interquartile range [IQR] 45.6-73.9), PT + AGA (median 34.3, IQR 23.9-37.5) and PT + LGA (median 28.3, IQR 18.4-32.3). At the population level, PT + AGA was the greatest contributor to newborn mortality (median PAR% 53.7, IQR 44.5-54.9). Mortality risk was highest among newborns born before 28 weeks (median RR 279.5, IQR 234.2-388.5) compared with babies born between 37 and 42 completed weeks or with a birthweight less than 1000 g (median RR 282.8, IQR 194.7-342.8) compared with those between 2500 g and 4000 g as a reference group. CONCLUSION: Preterm newborn types were the most vulnerable, and associated with the highest mortality, particularly with co-existence of preterm and SGA. As PT + AGA is more prevalent, it is responsible for the greatest burden of neonatal deaths at population level.

Estimated neonatal survival of very preterm births across the care pathway: a UK cohort 2016-2020.

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.

Postnatal growth restriction and neurodevelopment at 5 years of age: a European extremely preterm birth cohort study.

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.

Neonatal outcomes of maternal SARS-CoV-2 infection in the UK: a prospective cohort study using active surveillance.

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.

Amniotic band syndrome and limb body wall complex in Europe 1980-2019.

Amniotic band syndrome (ABS) and limb body wall complex (LBWC) have an overlapping phenotype of multiple congenital anomalies and their etiology is unknown. We aimed to determine the prevalence of ABS and LBWC in Europe from 1980 to 2019 and to describe the spectrum of congenital anomalies. In addition, we investigated maternal age and multiple birth as possible risk factors for the occurrence of ABS and LBWC. We used data from the European surveillance of congenital anomalies (EUROCAT) network including data from 30 registries over 1980-2019. We included all pregnancy outcomes, including live births, stillbirths, and terminations of pregnancy for fetal anomalies. ABS and LBWC cases were extracted from the central EUROCAT database using coding information responses from the registries. In total, 866 ABS cases and 451 LBWC cases were included in this study. The mean prevalence was 0.53/10,000 births for ABS and 0.34/10,000 births for LBWC during the 40 years. Prevalence of both ABS and LBWC was lower in the 1980s and higher in the United Kingdom. Limb anomalies and neural tube defects were commonly seen in ABS, whereas in LBWC abdominal and thoracic wall defects and limb anomalies were most prevalent. Twinning was confirmed as a risk factor for both ABS and LBWC. This study includes the largest cohort of ABS and LBWC cases ever reported over a large time period using standardized EUROCAT data. Prevalence, clinical characteristics, and the phenotypic spectrum are described, and twinning is confirmed as a risk factor.

Epidemiology of aplasia cutis congenita: A population-based study in Europe.

BACKGROUND: Aplasia cutis congenita (ACC) is a rare congenital anomaly characterized by localized or widespread absence of skin at birth, mainly affecting the scalp. Most information about ACC exists as individual case reports and medium-sized studies. OBJECTIVES: This study aimed to investigate the epidemiology of ACC, using data from a large European network of population-based registries for congenital anomalies (EUROCAT). METHODS: Twenty-eight EUROCAT population-based registries in 16 European countries were involved. Poisson regression models were exploited to estimate the overall and live birth prevalence, to test time trends in prevalence between four 5-year periods and to evaluate the impact of the change of coding for ACC from the unspecific ICD9-BPA code to the specific ICD10 code. Proportions of ACC cases associated with other anomalies were reported. RESULTS: Five hundred cases were identified in the period 1998-2017 (prevalence: 5.10 per 100,000 births). Prevalence across 5-year periods did not differ significantly and no significant differences were evident due to the change from ICD9 to ICD10 in ACC coding. Heterogeneity in prevalence was observed across registries. The scalp was the most common site for ACC (96.4%) and associated congenital anomalies were present in 33.8% of cases. Patau and Adams-Oliver syndromes were the most frequent among the associated chromosomal anomalies (88.3%) and the associated genetic syndromes (57.7%), respectively. 16% of cases were associated with limb anomalies and 15.4% with congenital heart defects. A family history of ACC was found in 2% of cases. CONCLUSION: To our knowledge, this is the only population-based study on ACC. The EUROCAT methodologies provide reliable prevalence estimates and proportions of associated anomalies.