The Contribution of Hypertensive Disorders of Pregnancy to Neonatal Unit Admissions and Iatrogenic Preterm Delivery at < 34+0 Weeks' Gestation in the UK: A Population-Based Study Using the National Neonatal Research Database.

OBJECTIVES: The objectives of this study were to (i) quantify the contribution of maternal hypertensive disorders of pregnancy (HDP) to iatrogenic preterm birth (PTB) and neonatal unit (NNU) admissions < 34+0 weeks and (ii) describe short-term population-level outcomes for HDP infants, exploring ethnic disparities and comparing outcomes by HDP exposure. DESIGN: Retrospective population-based study using the National Neonatal Research Database. SETTING: England and Wales. POPULATION: Infants born < 34+0 weeks and admitted to NNU 2012-2020. METHODS: Descriptive statistics, linear and logistic regression models to compare outcomes between groups. MAIN OUTCOME MEASURES: Survival to discharge with/without comorbidity. RESULTS: 122 228 infants met inclusion criteria. Where collected, 49 839/114 164 (43.7%, 95% CI 43.4%-43.9%) of infants had an iatrogenic PTB. HDP was recorded in 16 510/122 228 (13.5%) of all infants and 13 560/49 839 (27.2%) of iatrogenic PTBs. HDP and/or foetal growth restriction (FGR) were recorded in 24 124/49 839 (48.4%) of iatrogenic PTBs. Singleton HDP infants < 10th BWC had ≥ 90% survival to discharge from 28 weeks' gestation, versus from 26 weeks' gestation for those born ≥ 10th BWC. In extreme preterm HDP infants (< 27 weeks), 27.3% of infants < 10th BWC died compared to 15.2% of those ≥ 10th BWC. Survival without comorbidity was ≥ 90% from 32 weeks' gestation in HDP infants across BWC. CONCLUSIONS: These contemporaneous population-level data show that almost one in two PTB < 34+0 weeks' gestation are iatrogenic, with HDP and/or FGR being the major contributors to iatrogenic prematurity. This has substantial implications for strategies to reduce preterm birth in the UK and internationally. The data further inform antenatal and at-birth counselling of HDP-exposed infants.

Preterm birth as a determinant of neurodevelopment and cognition in children (PRENCOG): protocol for an exposure-based cohort study in the UK.

INTRODUCTION: Preterm birth (PTB) is strongly associated with encephalopathy of prematurity (EoP) and neurocognitive impairment. The biological axes linking PTB with atypical brain development are uncertain. We aim to elucidate the roles of neuroendocrine stress activation and immune dysregulation in linking PTB with EoP. METHODS AND ANALYSIS: PRENCOG (PREterm birth as a determinant of Neurodevelopment and COGnition in children: mechanisms and causal evidence) is an exposure-based cohort study at the University of Edinburgh. Three hundred mother-infant dyads comprising 200 preterm births (gestational age, GA <32 weeks, exposed) and 100 term births (GA >37 weeks, non-exposed), will be recruited between January 2023 and December 2027. We will collect parental and infant medical, demographic, socioeconomic characteristics and biological data which include placental tissue, umbilical cord blood, maternal and infant hair, infant saliva, infant dried blood spots, faecal material, and structural and diffusion MRI. Infant biosamples will be collected between birth and 44 weeks GA.EoP will be characterised by MRI using morphometric similarity networks (MSNs), hierarchical complexity (HC) and magnetisation transfer saturation imaging (MTsat). We will conduct: first, multivariable regressions and statistical association assessments to test how PTB-associated risk factors (PTB-RFs) relate to MSNs, HC and or MTsat; second, structural equation modelling to investigate neuroendocrine stress activation and immune dysregulation as mediators of PTB-RFs on features of EoP. PTB-RF selection will be informed by the variables that predict real-world educational outcomes, ascertained by linking the UK National Neonatal Research Database with the National Pupil Database. ETHICS AND DISSEMINATION: A favourable ethical opinion has been given by the South East Scotland Research Ethics Committee 02 (23/SS/0067) and NHS Lothian Research and Development (2023/0150). Results will be reported to the Medical Research Council, in scientific media, via stakeholder partners and on a website in accessible language (https://www.ed.ac.uk/centre-reproductive-health/prencog).

Childhood Health and Educational outcomes afteR perinatal Brain injury (CHERuB): protocol for a population-matched cohort study.

INTRODUCTION: Over 3000 infants suffer a brain injury around the time of birth every year in England. Although these injuries can have important implications for children and their families, our understanding of how these injuries affect children's lives is limited. METHODS AND ANALYSIS: The aim of the CHERuB study (Childhood Health and Educational outcomes afteR perinatal Brain injury) is to investigate longitudinal childhood health and educational outcomes after perinatal brain injury through the creation of a population-matched cohort study. This study will use the Department of Health and Social Care definition of perinatal brain injury which includes infants with intracranial haemorrhage, preterm white matter injury, hypoxic ischaemic encephalopathy, perinatal stroke, central nervous system infections, seizures and kernicterus. All children born with a perinatal brain injury in England between 2008 and 2019 will be included (n=54 176) and two matched comparator groups of infants without brain injury will be created: a preterm control group identified from the National Neonatal Research Data Set and a term/late preterm control group identified using birth records. The national health, education and social care records of these infants will be linked to ascertain their longitudinal childhood outcomes between 2008 and 2023. This cohort will include approximately 170 000 children. The associations between perinatal brain injuries and survival without neurosensory impairment, neurodevelopmental impairments, chronic health conditions and mental health conditions throughout childhood will be examined using regression methods and time-to-event analyses. ETHICS AND DISSEMINATION: This study has West London Research Ethics Committee and Confidential Advisory Group approval (20/LO/1023 and 22/CAG/0068 issued 20/10/2022). Findings will be published in open-access journals and publicised via the CHERuB study website, social media accounts and our charity partners.

A protocol for neoWONDER: Neonatal whole population data linkage to improve long-term health and wellbeing of preterm and sick babies.

INTRODUCTION: Early-life medical and surgical interventions in babies born preterm and/or with surgical conditions influence later life health and educational outcomes. Obtaining long-term outcomes post-discharge to evaluate the impact of interventions is complex, expensive, and burdensome to families. Linkage of routinely collected data offers a feasible and cost-effective solution. The NeoWONDER research programme aims to describe the short and long-term health and educational outcomes for babies born preterm and/or with surgical conditions and evaluate the impact of neonatal care and interventions on later health and educational outcomes. METHODS AND ANALYSIS: We will include babies who received care in neonatal units in England and Wales, born between 2007-2020 with a gestational age below 32 weeks (approximately 100,000), and/or born between 2012-2020 (all gestations) with any of six surgical conditions: necrotising enterocolitis, Hirschsprung's disease, gastroschisis, oesophageal atresia, congenital diaphragmatic hernia, and posterior urethral valves (approximately 8,000). A detailed list of surgical condition codes is shown in S3 File. We will obtain long-term health and education outcomes through linkage of the National Neonatal Research Database, which contains routine data for all babies admitted to NHS neonatal units, to other existing health and educational datasets. For England, these are: Hospital Episode Statistics, the Office for National Statistics, Mental Health Services Dataset, Paediatric Intensive Care Audit Network, National Pupil Database; and for Wales, the Secure Anonymised Information Linkage databank. Analysis will be undertaken on de-identified linked datasets. Outcomes of interest for health include mortality, hospital admissions, diagnoses indicative of neurodisability and/or chronic illness, health care utilisation; and for education are attainment (using national curriculum assessments), school absence and special educational needs status.

UK neonatal stoma practice: a population study.

OBJECTIVE: The optimal time for neonatal stoma closure is unclear and there have been calls for a trial to compare early and late surgery. The feasibility of such a trial will depend on the population of eligible infants and acceptability to families and health professionals. In this study, we aimed to determine current UK practice and characteristics of those undergoing stoma surgery. DESIGN: A retrospective cohort study of neonates who had undergone stoma surgery (excluding anorectal malformations and Hirschsprung's disease) using three national databases: the National Neonatal Research Database (NNRD, 2012-2019), British Association of Paediatric Surgeons Congenital Anomalies Surveillance System (BAPS-CASS, 2013-2014) and Hospital Episode Statistics-Admitted Patient Care (HES-APC, 2011-2018). RESULTS: 1830 eligible neonates were identified from NNRD, 163 from BAPS-CASS, 2477 from HES-APC. Median (IQR) duration of stoma in days was 57 (36-80) in NNRD, 63 (41-130) in BAPS-CASS and 78 (55-122) for neonates identified from HES-APC. At the time of closure, there were low rates of invasive ventilation (13%), inotrope use (5%) and recent steroids use (4%). Infants who underwent earlier closure (<9 weeks) were less preterm (median 28 weeks vs 25 weeks), have higher birth weight (median 986 g vs 764 g) and more likely to have stoma complications (29% vs 5%). CONCLUSION: There are sufficient UK neonates undergoing stoma formation for a trial. Stoma closure is performed at around 2 months, with clinical stability, gestation, weight and stoma complications appearing to influence timing. The variation in practice we document indicates there is opportunity to optimise practice through a trial.

Methods of identifying surgical Necrotizing Enterocolitis-a systematic review and meta-analysis.

BACKGROUND: Current data suggests potential benefit of earlier surgery for necrotizing enterocolitis (NEC) however this requires accurate prognostication early in the disease course. This study aims to identify and determine the effectiveness of previously reported methods or tests for the identification of surgical NEC. METHODS: Systematic review and meta-analysis with registration on PROSPERO including articles describing a method of identifying surgical NEC. Outcomes of interest were effectiveness and repeatability of index test. RESULTS: Of the 190 full-text articles screened, 90 studies were included which contained 114 methods of identifying surgical NEC in 9546 infants. Of these methods, 44 were a scoring system, 37 a single biomarker, 24 an imaging method, and 9 an invasive method. Sensitivity and specificity ranged from 12.8-100% to 13-100%, respectively. Some methods (9.6%) provided insufficient methods for repeatability within clinical practice or research. Meta-analyses were possible for only 2 methods, the metabolic derangement 7 score and abdominal ultrasound. CONCLUSIONS: A range of methods for identifying surgical NEC have been identified with varying overall performance and uncertainties about reproducibility and superiority of any method. External validation in large multicentre datasets should allow direct comparison of accuracy and prospective study should evaluate impact on clinical outcomes. IMPACT: Earlier identification of need for surgery in necrotizing enterocolitis (NEC) has the potential to improve the unfavourable outcomes in this condition. As such, many methods have been developed and reported to allow earlier identification of surgical NEC. This study is the first synthesis of the literature which identifies previously reported methods and the effectiveness of these. Many methods, including scoring systems and biomarkers, appear effective for prognostication in NEC and external validation is now required in multicentre datasets prior to clinical utility.

Repeat Placental Growth Factor-Based Testing in Women With Suspected Preterm Preeclampsia: A Stratified Analysis of the PARROT-2 Trial.

BACKGROUND: PlGF (placental growth factor)-based testing reduces severe maternal adverse outcomes. Repeat PlGF-based testing is not associated with improved perinatal or maternal outcomes. This planned secondary analysis aimed to determine whether there is a subgroup of women who benefit from repeat testing. METHODS: Pregnant individuals with suspected preterm preeclampsia were randomized to repeat revealed PlGF-based testing, compared with usual care where testing was concealed. Perinatal and maternal outcomes were stratified by trial group, by initial PlGF-based test result, and by PlGF-based test type (PlGF or sFlt-1 [soluble fms-like tyrosine kinase-1]/PlGF ratio). RESULTS: A total of 1252 pregnant individuals were included. Abnormal initial PlGF-based test identified a more severe phenotype of preeclampsia, at increased risk of adverse maternal and perinatal outcomes. Repeat testing was not significantly associated with clinical benefit in women with abnormal initial results. Of women with a normal initial result, 20% developed preeclampsia, with the majority at least 3 to 4 weeks after initial presentation. Repeat test results were more likely to change from normal to abnormal in symptomatic women (112/415; 27%) compared with asymptomatic women (163/890; 18%). A higher proportion of symptomatic women who changed from normal to abnormal were diagnosed with preeclampsia, compared with asymptomatic women. CONCLUSIONS: Our results do not demonstrate evidence of the clinical benefit of repeating PlGF-based testing if the initial result is abnormal. Judicious use of repeat PlGF-based testing to stratify risk may be considered at least 2 weeks after a normal initial test result, particularly in women who have symptoms or signs of preeclampsia. REGISTRATION: URL: https://www.isrctn.com/ISRCTN85912420; Unique identifier: ISRCTN85912420.

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.

Place of birth and postnatal transfers in infants with congenital diaphragmatic hernia in England and Wales: a descriptive observational cohort study.

OBJECTIVE: To describe clinical pathways for infants with congenital diaphragmatic hernia (CDH) and short-term outcomes. DESIGN: Retrospective observational cohort study using the UK National Neonatal Research Database (NNRD). PATIENTS: Babies with a diagnosis of CDH admitted to a neonatal unit in England and Wales between 2012 and 2020. MAIN OUTCOME MEASURES: Clinical pathways defined by place of birth (with or without colocated neonatal and surgical facilities), transfers, clinical interventions, length of hospital stay and discharge outcome. RESULTS: There were 1319 babies with a diagnosis of CDH cared for in four clinical pathways: born in maternity units with (1) colocated tertiary neonatal and surgical units ('neonatal surgical units'), 50% (660/1319); (2) designated tertiary neonatal unit and transfer to stand-alone surgical centre ('tertiary designated'), 25% (337/1319); (3) non-designated tertiary neonatal unit ('tertiary non-designated'), 7% (89/1319); or (4) non-tertiary unit ('non-tertiary'), 18% (233/1319)-the latter three needing postnatal transfers. Infant characteristics were similar for infants born in neonatal surgical and tertiary designated units. Excluding 149 infants with minimal data due to early transfer (median (IQR) 2.2 (0.4-4.5) days) to other settings, survival to neonatal discharge was 73% (851/1170), with a median (IQR) stay of 26 (16-44) days. CONCLUSIONS: We found that half of the babies with CDH were born in hospitals that did not have on-site surgical services and required postnatal transfer. Similar characteristics between infants born in neonatal surgical units and tertiary designated units suggest that organisation rather than infant factors influence place of birth. Future work linking the NNRD to other datasets will enable comparisons between care pathways.

Repeat placental growth factor-based testing in women with suspected preterm pre-eclampsia (PARROT-2): a multicentre, parallel-group, superiority, randomised controlled trial.

BACKGROUND: Placental growth factor (PlGF)-based testing has high diagnostic accuracy for predicting pre-eclampsia needing delivery, significantly reducing time to diagnosis and severe maternal adverse outcomes. The clinical benefit of repeat PlGF-based testing is unclear. We aimed to determine whether repeat PlGF-based testing (using a clinical management algorithm and nationally recommended thresholds) reduces adverse perinatal outcomes in pregnant individuals with suspected preterm pre-eclampsia. METHODS: In this multicentre, parallel-group, superiority, randomised controlled trial, done in 22 maternity units across England, Scotland, and Wales, we recruited women aged 18 years or older with suspected pre-eclampsia between 22 weeks and 0 days of gestation and 35 weeks and 6 days of gestation. Women were randomly assigned (1:1) to revealed repeat PlGF-based testing or concealed repeat testing with usual care. The intervention was not masked to women or partners, or clinicians or data collectors, due to the nature of the trial. The trial statistician was masked to intervention allocation. The primary outcome was a perinatal composite of stillbirth, early neonatal death, or neonatal unit admission. The primary analysis was by the intention-to-treat principle, with a per-protocol analysis restricted to women managed according to their allocation group. The trial was prospectively registered with the ISRCTN registry, ISRCTN 85912420. FINDINGS: Between Dec 17, 2019, and Sept 30, 2022, 1253 pregnant women were recruited and randomly assigned treatment; one patient was excluded due to randomisation error. 625 women were allocated to revealed repeat PlGF-based testing and 627 women were allocated to usual care with concealed repeat PlGF-based testing (mean age 32·3 [SD 5·7] years; 879 [70%] white). One woman in the concealed repeat PlGF-based testing group was lost to follow-up. There was no significant difference in the primary perinatal composite outcome between the revealed repeat PlGF-based testing group (195 [31·2%]) of 625 women) compared with the concealed repeat PlGF-based testing group (174 [27·8%] of 626 women; relative risk 1·21 [95% CI 0·95-1·33]; p=0·18). The results from the per-protocol analysis were similar. There were four serious adverse events in the revealed repeat PlGF-based testing group and six in the concealed repeat PlGF-based testing group; all serious adverse events were deemed unrelated to the intervention by the site principal investigators and chief investigator. INTERPRETATION: Repeat PlGF-based testing in pregnant women with suspected pre-eclampsia was not associated with improved perinatal outcomes. In a high-income setting with a low prevalence of adverse outcomes, universal, routine repeat PlGF-based testing of all individuals with suspected pre-eclampsia is not recommended. FUNDING: Tommy's Charity, Jon Moulton Charitable Trust, and National Institute for Health and Care Research Guy's and St Thomas' Biomedical Research Centre.

Two-year neurodevelopmental data for preterm infants born over an 11-year period in England and Wales, 2008-2018: a retrospective study using the National Neonatal Research Database.

OBJECTIVE: United Kingdom guidelines recommend all infants born <30 weeks' gestation receive neurodevelopmental follow-up at 2 years corrected age. In this study, we describe completeness and results of 2-year neurodevelopmental records in the National Neonatal Research Database (NNRD). DESIGN: This retrospective cohort study uses data from the NNRD, which holds data on all neonatal admissions in England and Wales, including 2year follow-up status. PATIENTS: We included all preterm infants born <30 weeks' gestation between 1 January 2008 and 31 December 2018 in England and Wales, who survived to discharge from neonatal care. MAIN OUTCOME MEASURES: Presence of a 2-year neurodevelopmental assessment record in the NNRD, use of standardised assessment tools, results of functional 2-year neurodevelopmental assessments (visual, auditory, neuromotor, communication, overall development). RESULTS: Of the 41 505 infants included, 24 125 (58%) had a 2-year neurodevelopmental assessment recorded. This improved over time, from 32% to 71% for births in 2008 and 2018, respectively.Of those with available data: 0.4% were blind; 1% had a hearing impairment not correctable with aids; 13% had <5 meaningful words, vocalisations or signs; 8% could not walk without assistance and 9% had severe (≥12 months) developmental delay. CONCLUSIONS: The proportion of infants admitted to neonatal units in England and Wales with a 2-year neurodevelopmental record has improved over time. Rates of follow-up data from recent years are comparable to those of bespoke observational studies. With continual improvement in data completeness, the potential for use of NNRD as a source of longer-term outcome data can be realised.

Childhood outcomes after low-grade intraventricular haemorrhage: A systematic review and meta-analysis.

AIM: To undertake a systematic review and meta-analysis exploring school-age neurodevelopmental outcomes of children after low-grade intraventricular haemorrhage (IVH). METHOD: The published and grey literature was extensively searched to identify observational comparative studies exploring neurodevelopmental outcomes after IVH grades 1 and 2. Our primary outcome was neurodevelopmental impairment after 5 years of age, which included cognitive, motor, speech and language, behavioural, hearing, or visual impairments. RESULTS: This review included 12 studies and over 2036 infants born preterm with low grade IVH. Studies used 30 different neurodevelopmental tools to determine outcomes. There was conflicting evidence of the composite risk of neurodevelopmental impairment after low-grade IVH. There was evidence of an association between low-grade IVH and lower IQ at school age (-4.23, 95% confidence interval [CI] -7.53, -0.92, I2 = 0%) but impact on school performance was unclear. Studies reported an increased crude risk of cerebral palsy after low-grade IVH (odds ratio [OR] 2.92, 95% CI 1.95, 4.37, I2 = 41%). No increased risk of speech and language impairment or behavioural impairment was found. Few studies addressed hearing and visual impairment. INTERPRETATION: This systematic review presents evidence that low-grade IVH is associated with specific neurodevelopmental impairments at school age, lending support to the theory that low-grade IVH is not a benign condition. WHAT THIS PAPER ADDS: The functional impact of low-grade intraventricular haemorrhage (IVH) at school age is unknown. Low-grade IVH is associated with a lower IQ at school age. The risk of cerebral palsy is increased after low-grade IVH. Low-grade IVH is not associated with speech and language impairment.

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.

The contribution of hypertensive disorders of pregnancy to late preterm and term admissions to neonatal units in the UK 2012-2020 and opportunities to avoid admission: A population-based study using the National Neonatal Research Database.

OBJECTIVE: To quantify maternal hypertensive disorder of pregnancy (HDP) prevalence in late preterm and term infants admitted to neonatal units (NNU) and assess opportunities to avoid admissions. DESIGN: A retrospective population-based study using the National Neonatal Research Database. SETTING: England and Wales. POPULATION: Infants born ≥34 weeks' gestation admitted to NNU between 2012 and 2020. METHODS: Outcomes in HDP infants are compared with non-HDP infants using regression models. MAIN OUTCOME MEASURES: Hypertensive disorder of pregnancy, primary reason for admission, clinical diagnoses and resource use. RESULTS: 16 059/136 220 (11.8%) of late preterm (34+0 to 36+6 weeks' gestation) and 14 885/284 646 (5.2%) of term (≥37 weeks' gestation) admitted infants were exposed to maternal HDP. The most common primary reasons for HDP infant admission were respiratory disease (28.3%), prematurity (22.7%) and hypoglycaemia (16.4%). HDP infants were more likely to be admitted with primary hypoglycaemia than were non-HDP infants (odds ratio [OR] 2.1, 95% confidence interval [CI] 2.0-2.2, P < 0.0001). 64.5% of HDP infants received i.v. dextrose. 35.7% received mechanical or non-invasive ventilation. 8260/30 944 (26.7%) of HDP infants received intervention for hypoglycaemia alone (i.v. dextrose) with no other major intervention (respiratory support, parenteral nutrition, central line, arterial line or blood transfusion). CONCLUSIONS: The burden of maternal HDP on late preterm and term admissions to NNU is high, with hypoglycaemia and respiratory disease being the main drivers for admission. Over one in four were admitted solely for management of hypoglycaemia. Further research should determine whether maternal antihypertensive agent choice or postnatal pathways may reduce NNU admission.

Effect of national guidance on survival for babies born at 22 weeks' gestation in England and Wales: population based cohort study.

Objectives: To explore the effect of changes in national clinical recommendations in 2019 that extended provision of survival focused care to babies born at 22 weeks' gestation in England and Wales. Design: Population based cohort study. Setting: England and Wales, comprising routine data for births and hospital records. Participants: Babies alive at the onset of care in labour at 22 weeks+0 days to 22 weeks+6 days and at 23 weeks+0 days to 24 weeks+6 days for comparison purposes between 1 January 2018 and 31 December 2021. Main outcome measures: Percentage of babies given survival focused care (active respiratory support after birth), admitted to neonatal care, and surviving to discharge in 2018-19 and 2020-21. Results: For the 1001 babies alive at the onset of labour at 22 weeks' gestation, a threefold increase was noted in: survival focused care provision from 11.3% to 38.4% (risk ratio 3.41 (95% confidence interval 2.61 to 4.45)); admissions to neonatal units from 7.4% to 28.1% (3.77 (2.70 to 5.27)), and survival to discharge from neonatal care from 2.5% to 8.2% (3.29 (1.78 to 6.09)). More babies of lower birth weight and early gestational age received survival focused care in 2020-21 than 2018-19 (46% to 64% at <500g weight; 19% to 31% at 22 weeks+0 days to 22 weeks+3 days). Conclusions: A change in national guidance to recommend a risk based approach was associated with a threefold increase in 22 weeks' gestation babies receiving survival focused care. The number of babies being admitted to neonatal units and those surviving to discharge increased.

National Trends in Preterm Infant Mortality in the United States by Race and Socioeconomic Status, 1995-2020.

Importance: Inequalities in preterm infant mortality exist between population subgroups within the United States. Objective: To characterize trends in preterm infant mortality by maternal race and socioeconomic status to assess how inequalities in preterm mortality rates have changed over time. Design, Setting, and Participants: This was a retrospective longitudinal descriptive study using the US National Center for Health Statistics birth infant/death data set for 12 256 303 preterm infant births over 26 years, between 1995 and 2020. Data were analyzed from December 2022 to March 2023. Exposures: Maternal characteristics including race, smoking status, educational attainment, antenatal care, and insurance status were used as reported on an infant's US birth certificate. Main Outcomes and Measures: Preterm infant mortality rate was calculated for each year from 1995 to 2020 for all subgroups, with a trend regression coefficient calculated to describe the rate of change in preterm mortality. Results: The average US preterm infant mortality rate (IMR) decreased from 33.71 (95% CI, 33.71 to 34.04) per 1000 preterm births per year between 1995-1997, to 23.32 (95% CI, 23.05 to 23.58) between 2018-2020. Black non-Hispanic infants were more likely to die following preterm births than White non-Hispanic infants (IMR, 31.09; 95% CI, 30.44 to 31.74, vs 21.81; 95% CI, 21.43 to 22.18, in 2018-2020); however, once born, extremely prematurely Black and Hispanic infants had a narrow survival advantage (IMR rate ratio, 0.87; 95% CI, 0.84 to 0.91, in 2018-2020). The rate of decrease in preterm IMR was higher in Black infants (-0.015) than in White (-0.013) and Hispanic infants (-0.010); however, the relative risk of preterm IMR among Black infants compared with White infants remained the same between 1995-1997 vs 2018-2020 (relative risk, 1.40; 95% CI, 1.38 to 1.44, vs 1.43; 95% CI, 1.39 to 1.46). The rate of decrease in preterm IMR was higher in nonsmokers compared with smokers (-0.015 vs -0.010, respectively), in those with high levels of education compared with those with intermediate or low (-0.016 vs - 0.010 or -0.011, respectively), and in those who had received adequate antenatal care compared with those who did not (-0.014 vs -0.012 for intermediate and -0.013 for inadequate antenatal care). Over time, the relative risk of preterm mortality widened within each of these subgroups. Conclusions and Relevance: This study found that between 1995 and 2020, US preterm infant mortality improved among all categories of prematurity. Inequalities in preterm infant mortality based on maternal race and ethnicity have remained constant while socioeconomic disparities have widened over time.

A treatment strategy with nifedipine versus labetalol for women with pregnancy hypertension: study protocol for a randomised controlled trial (Giant PANDA).

BACKGROUND: Approximately one in ten women have high blood pressure during pregnancy. Hypertension is associated with adverse maternal and perinatal outcomes, and as treatment improves maternal outcomes, antihypertensive treatment is recommended. Previous trials have been unable to provide a definitive answer on which antihypertensive treatment is associated with optimal maternal and neonatal outcomes and the need for robust evidence evaluating maternal and infant benefits and risks remains an important, unanswered question for research and clinical communities. METHODS: The Giant PANDA study is a pragmatic, open-label, multicentre, randomised controlled trial of a treatment initiation strategy with nifedipine (calcium channel blocker), versus labetalol (mixed alpha/beta blocker) in 2300 women with pregnancy hypertension. The primary objective is to evaluate if treatment with nifedipine compared to labetalol in women with pregnancy hypertension reduces severe maternal hypertension without increasing fetal or neonatal death or neonatal unit admission. Subgroup analyses will be undertaken by hypertension type (chronic, gestational, pre-eclampsia), diabetes (yes, no), singleton (yes, no), self-reported ethnicity (Black, all other), and gestational age at randomisation categories (11 + 0 to 19 + 6, 20 + 0 to 27 + 6, 28 + 0 to 34 + 6 weeks). A cost-effectiveness analysis using an NHS perspective will be undertaken using a cost-consequence analysis up to postnatal hospital discharge and an extrapolation exercise with a lifetime horizon conditional on the results of the cost-consequence analysis. DISCUSSION: This trial aims to address the uncertainty of which antihypertensive treatment is associated with optimal maternal and neonatal outcomes. The trial results are intended to provide definitive evidence to inform guidelines and linked, shared decision-making tools, thus influencing clinical practice. TRIAL REGISTRATION: EudraCT number: 2020-003410-12, ISRCTN: 12,792,616 registered on 18 November 2020.

How frequent is routine use of probiotics in UK neonatal units?

OBJECTIVE: There is a lack of UK guidance regarding routine use of probiotics in preterm infants to prevent necrotising enterocolitis, late-onset sepsis and death. As practices can vary, we aimed to determine the current usage of probiotics within neonatal units in the UK. DESIGN AND SETTING: Using NeoTRIPS, a trainee-led neonatal research network, an online survey was disseminated to neonatal units of all service levels within England, Scotland, Northern Ireland and Wales in 2022. Trainees were requested to complete one survey per unit regarding routine probiotic administration. RESULTS: 161 of 188 (86%) neonatal units responded to the survey. 70 of 161 (44%) respondents routinely give probiotics to preterm infants. 45 of 70 (64%) use the probiotic product Lactobacillus acidophilus NCFM/Bifidobacterium bifidum Bb-06/B. infantis Bi-26 (Labinic™). 57 of 70 (81%) start probiotics in infants ≤32 weeks' gestation. 33 of 70 (47%) had microbiology departments that were aware of the use of probiotics and 64 of 70 (91%) had a guideline available. Commencing enteral feeds was a prerequisite to starting probiotics in 62 of 70 (89%) units. The majority would stop probiotics if enteral feeds were withheld (59 of 70; 84%) or if the infant was being treated for necrotising enterocolitis (69 of 70; 99%). 24 of 91 (26%) units that did not use probiotics at the time of the survey were planning to introduce them within the next 12 months. CONCLUSIONS: More than 40% of all UK neonatal units that responded are now routinely administering probiotics, with variability in the product used. With increased probiotic usage in recent years, there is a need to establish whether this translates to improved clinical outcomes.

Comparison of diagnoses of early-onset sepsis associated with use of Sepsis Risk Calculator versus NICE CG149: a prospective, population-wide cohort study in London, UK, 2020-2021.

OBJECTIVE: We sought to compare the incidence of early-onset sepsis (EOS) in infants ≥34 weeks' gestation identified >24 hours after birth, in hospitals using the Kaiser Permanente Sepsis Risk Calculator (SRC) with hospitals using the National Institute for Health and Care Excellence (NICE) guidance. DESIGN AND SETTING: Prospective observational population-wide cohort study involving all 26 hospitals with neonatal units colocated with maternity services across London (10 using SRC, 16 using NICE). PARTICIPANTS: All live births ≥34 weeks' gestation between September 2020 and August 2021. OUTCOME MEASURES: EOS was defined as isolation of a bacterial pathogen in the blood or cerebrospinal fluid (CSF) culture from birth to 7 days of age. We evaluated the incidence of EOS identified by culture obtained >24 hours to 7 days after birth. We also evaluated the rate empiric antibiotics were commenced >24 hours to 7 days after birth, for a duration of ≥5 days, with negative blood or CSF cultures. RESULTS: Of 99 683 live births, 42 952 (43%) were born in SRC hospitals and 56 731 (57%) in NICE hospitals. The overall incidence of EOS (<72 hours) was 0.64/1000 live births. The incidence of EOS identified >24 hours was 2.3/100 000 (n=1) for SRC vs 7.1/100 000 (n=4) for NICE (OR 0.5, 95% CI (0.1 to 2.7)). This corresponded to (1/20) 5% (SRC) vs (4/45) 8.9% (NICE) of EOS cases (χ=0.3, p=0.59). Empiric antibiotics were commenced >24 hours to 7 days after birth in 4.4/1000 (n=187) for SRC vs 2.9/1000 (n=158) for NICE (OR 1.5, 95% CI (1.2 to 1.9)). 3111 (7%) infants received antibiotics in the first 24 hours in SRC hospitals vs 8428 (15%) in NICE hospitals. CONCLUSION: There was no significant difference in the incidence of EOS identified >24 hours after birth between SRC and NICE hospitals. SRC use was associated with 50% fewer infants receiving antibiotics in the first 24 hours of life.

Association between birth location and short-term outcomes for babies with gastroschisis, congenital diaphragmatic hernia and oesophageal fistula: a systematic review.

BACKGROUND: Neonatal care is commonly regionalised, meaning specialist services are only available at certain units. Consequently, infants with surgical conditions needing specialist care who are born in non-surgical centres require postnatal transfer. Best practice models advocate for colocated maternity and surgical services as the place of birth for infants with antenatally diagnosed congenital conditions to avoid postnatal transfers. We conducted a systematic review to explore the association between location of birth and short-term outcomes of babies with gastroschisis, congenital diaphragmatic hernia (CDH) and oesophageal atresia with or without tracheo-oesophageal fistula (TOF/OA). METHODS: We searched MEDLINE, CINAHL, Web of Science and SCOPUS databases for studies from high income countries comparing outcomes for infants with gastroschisis, CDH or TOF/OA based on their place of delivery. Outcomes of interest included mortality, length of stay, age at first feed, comorbidities and duration of parenteral nutrition. We assessed study quality using the Newcastle-Ottawa Scale. We present a narrative synthesis of our findings. RESULTS: Nineteen cohort studies compared outcomes of babies with one of gastroschisis, CDH or TOF/OA. Heterogeneity across the studies precluded meta-analysis. Eight studies carried out case-mix adjustments. Overall, we found conflicting evidence. There is limited evidence to suggest that birth in a maternity unit with a colocated surgical centre was associated with a reduction in mortality for CDH and decreased length of stay for gastroschisis. CONCLUSIONS: There is little evidence to suggest that delivery in colocated maternity-surgical services may be associated with shortened length of stay and reduced mortality. Our findings are limited by significant heterogeneity, potential for bias and paucity of strong evidence. This supports the need for further research to investigate the impact of birth location on outcomes for babies with congenital surgical conditions and inform future design of neonatal care systems. PROSPERO REGISTRATION NUMBER: CRD42022329090.