Association of antenatal or neonatal SARS-COV-2 exposure with developmental and respiratory outcomes, and healthcare usage in early childhood: a national prospective cohort study.

Background: Perinatal exposure to SARS-CoV-2 may affect neurodevelopment before 12 months of age, but longer-term outcomes remain unknown. We examined whether antenatal or neonatal SARS-CoV-2 exposure compared with non-exposure is associated with neurodevelopment, respiratory symptoms, and health care usage in early childhood. Methods: This prospective national population-based cohort study was conducted in England and Wales, United Kingdom. We enrolled term-born children (≥37 weeks' gestation) with and without antenatal or neonatal exposure to SARS-CoV-2 infection by approaching parents of eligible children who were cared for in 87 NHS hospitals. Potential participants were identified through the national active surveillance studies of pregnant women and newborn infants hospitalised with confirmed SARS-CoV-2 infection conducted through the UK Obstetric Surveillance System and the British Paediatric Surveillance Unit. We defined antenatal and neonatal SARS-CoV-2 exposure as infants born to mothers hospitalised with confirmed SARS-CoV-2 infection between 14 + 0 and 36 + 6 weeks gestation and infants admitted to hospital with confirmed SARS-CoV-2 infection within the first 28 days after birth. Children born preterm or with major congenital anomaly or who were not residing in the UK were excluded. We assessed children's development (Ages and Stages Questionnaire 3rd Edition (ASQ-3); Ages and Stages Questionnaire Social-Emotional 2nd Edition (ASQ:SE-2)), respiratory symptoms (Liverpool Respiratory Symptom Questionnaire (LRSQ)) and health care usage (parent-completed questionnaire) at 21-32 months of age. Primary outcome: total ASQ-3 score, converted to z-scores. Secondary outcomes: ASQ:SE-2 z-scores; risk of delay in ASQ-3 domains; total LRSQ scores, converted to z-scores. Analyses were adjusted for children's age, sex, maternal ethnicity, parental education, and index of multiple deprivation. Findings: Between October 20, 2021 and January 27, 2023, we approached 668 and 1877 families out of 712 and 1917 potentially eligible participants in the exposed and comparison cohort. Of the 125 and 306 participants who were enrolled to the exposed and comparison cohort 121 and 301 participants completed the questionnaires and 96 and 243 participants were included in the analysis. In the age adjusted analysis, the mean total ASQ-3 z-score was lower in the exposed than the comparison cohort (-0.3, 95% CI: -0.6 to -0.05), however, when adjusted for sex, parental education, ethnicity and IMD quintile, there was no significant difference (difference in mean z-score = -0.2 95% CI: -0.5 to 0.03). SARS-CoV-2 exposure was associated with increased risk of delayed personal-social skills (odds ratio = 3.81; 95% CI: 1.07-13.66), higher ASQ:SE-2 total z-scores (difference in mean z-score = 0.4; 95% CI: 0.2-0.6) and increased risk of delayed social-emotional development (OR = 3.58, 95% CI: 1.30-9.83), after adjusting for sex, age at assessment, parental education, ethnicity and IMD quintile. The exposed cohort had a higher mean total LRSQ z-score than the comparison cohort (0.3 95% CI: 0-0.6) and higher inpatient (38% vs. 21%, p = 0.0001), outpatient (38% vs. 30%, p = 0.0090), and General Practitioner appointments (60% vs. 50%, p = 0.021) than the comparison cohort, after adjusting for sex, age at assessment, parental education, ethnicity and IMD quintile. No differences in other secondary outcomes between the exposed and comparison cohorts were found. Interpretation: Although the exposed cohort did not differ from the comparison cohort on the primary outcome, total ASQ-3 score, the exposed cohort were at greater risk of delayed social-emotional development, had a greater prevalence of respiratory symptoms and increased health care usage relative to the comparison cohort. The study is limited by the smaller sample size due to the low response rate and lack of clinical developmental assessments. Given the association of poor social-emotional development with antenatal or neonatal SARS-CoV-2 exposure, developmental screening, and follow-up of children with confirmed antenatal or neonatal SARS-CoV-2 infection may be warranted to identify those in need of early intervention. Funding: Action Medical Research for Children.

Risk factors for labour induction and augmentation: a multicentre prospective cohort study in India.

Background: Guidelines for labour induction/augmentation involve evaluating maternal and fetal complications, and allowing informed decisions from pregnant women. This study aimed to comprehensively explore clinical and non-clinical factors influencing labour induction and augmentation in an Indian population. Methods: A prospective cohort study included 9305 pregnant women from 13 hospitals across India. Self-reported maternal socio-demographic and lifestyle factors, and maternal medical and obstetric histories from medical records were obtained at recruitment (≥28 weeks of gestation), and women were followed up within 48 h after childbirth. Maternal and fetal clinical information were classified based on guidelines into four groups of clinical factors: (i) ≥2 indications, (ii) one indication, (iii) no indication and (iv) contraindication. Associations of clinical and non-clinical factors (socio-demographic, healthcare utilisation and lifestyle related) with labour induction and augmentation were investigated using multivariable logistic regression analyses. Findings: Over two-fifths (n = 3936, 42.3%, 95% confidence interval [CI] 41.3-43.3%) of the study population experienced labour induction and more than a quarter (n = 2537, 27.3%, 95% CI 26.4-28.2%) experienced augmentation. Compared with women with ≥2 indications, those with one (adjusted odds ratio [aOR] 0.50, 95% CI 0.42-0.58) or no indication (aOR 0.24, 95% CI 0.20-0.28) or with contraindications (aOR 0.12, 95% CI 0.07-0.20) were less likely to be induced, adjusting for non-clinical characteristics. These associations were similar for labour augmentation. Notably, 34% of women who were induced or augmented did not have any clinical indication. Several maternal demographic (age at labour, parity and body mass index in early pregnancy), healthcare utilization (number of antenatal check-ups, duration of iron-folic acid supplementation and individuals managing childbirth) and socio-economic factors (religion, living below poverty line, maternal education and partner's occupation) were independently associated with labour induction and augmentation. Interpretation: Although decisions about induction and augmentation of labour in our study population in India were largely guided by clinical recommendations, we cannot ignore that more than a third of the women did not have an indication. Decisions could also be influenced by non-clinical factors which need further research. Funding: The MaatHRI platform is funded by a Medical Research Council Career Development Award (Grant Ref: MR/P022030/1) and a Transition Support Award (Grant Ref: MR/W029294/1).

Impact of maternal risk factors on ethnic disparities in maternal mortality: a national population-based cohort study.

Background: Ethnic disparities in maternal mortality are consistently reported. This study aimed to investigate the contribution of known risk factors including age, socioeconomic status, and medical comorbidities to observed ethnic disparities in the United Kingdom (UK). Methods: A cohort of all women who died during or up to six weeks after pregnancy in the UK 2009-2019 were identified through national surveillance. No single denominator population included data on all risk factors, therefore we used logistic regression modelling to compare to 1) routine population birth and demographic data (2015-19) (routine data comparator) and 2) combined control groups of four UK Obstetric Surveillance System studies (UKOSS) control comparator)). Findings: There were 801 maternal deaths in the UK between 2009 and 2019 (White: 70%, Asian: 13%, Black: 12%, Chinese/Other: 3%, Mixed: 2%). Using the routine data comparator (n = 3,519,931 maternities) to adjust for demographics, including social deprivation, women of Black ethnicity remained at significantly increased risk of maternal death compared with women of white ethnicity (adjusted OR 2.43 (95% Confidence Interval 1.92-3.08)). The risk was greatest in women of Caribbean ethnicity (aOR 3.55 (2.30-5.48)). Among women of White ethnicity, risk of mortality increased as deprivation increased, but women of Black ethnicity had greater risk irrespective of deprivation. Using the UKOSS control comparator (n = 2210), after multiple adjustments including smoking, body mass index, and comorbidities, women of Black and Asian ethnicity remained at increased risk (aOR 3.13 (2.21-4.43) and 1.57 (1.16-2.12) respectively). Interpretation: Known risk factors do not fully explain ethnic disparities in maternal mortality. The impact of socioeconomic deprivation appears to differ between ethnic groups. Funding: This research is funded by the National Institute for Health and Care Research (NIHR) Policy Research Programme, conducted through the Policy Research Unit in Maternal and Neonatal Health and Care, PR-PRU-127-21202.

Perinatal outcomes after admission with COVID-19 in pregnancy: a UK national cohort study.

There are few population-based studies of sufficient size and follow-up duration to have reliably assessed perinatal outcomes for pregnant women hospitalised with SARS-CoV-2 infection. The United Kingdom Obstetric Surveillance System (UKOSS) covers all 194 consultant-led UK maternity units and included all pregnant women admitted to hospital with an ongoing SARS-CoV-2 infection. Here we show that in this large national cohort comprising two years' active surveillance over four SARS-CoV-2 variant periods and with near complete follow-up of pregnancy outcomes for 16,627 included women, severe perinatal outcomes were more common in women with moderate to severe COVID-19, during the delta dominant period and among unvaccinated women. We provide strong evidence to recommend continuous surveillance of pregnancy outcomes in future pandemics and to continue to recommend SARS-CoV-2 vaccination in pregnancy to protect both mothers and babies.

Maternal and fetal factors associated with stillbirth in singleton pregnancies in 13 hospitals across six states in India: A prospective cohort study.

OBJECTIVE: This study aimed to investigate the incidence of and risk factors for stillbirth in an Indian population. METHODS: We conducted a secondary data analysis of a hospital-based cohort from the Maternal and Perinatal Health Research collaboration, India (MaatHRI), including pregnant women who gave birth between October 2018-September 2023. Data from 9823 singleton pregnancies recruited from 13 hospitals across six Indian states were included. Univariable and multivariable Poisson regression analysis were performed to examine the relationship between stillbirth and potential risk factors. Model prediction was assessed using the area under the receiver-operating characteristic (AUROC) curve. RESULTS: There were 216 stillbirths (48 antepartum and 168 intrapartum) in the study population, representing an overall stillbirth rate of 22.0 per 1000 total births (95% confidence interval [CI]: 19.2-25.1). Modifiable risk factors for stillbirth were: receiving less than four antenatal check-ups (adjusted relative risk [aRR]: 1.75, 95% CI: 1.25-2.47), not taking any iron and folic acid supplementation during pregnancy (aRR: 7.23, 95% CI: 2.12-45.33) and having severe anemia in the third trimester (aRR: 3.37, 95% CI: 1.97-6.11). Having pregnancy/fetal complications such as hypertensive disorders of pregnancy (aRR: 1.59, 95% CI: 1.03-2.36), preterm birth (aRR: 4.41, 95% CI: 3.21-6.08) and birth weight below the 10th percentile for gestational age (aRR: 1.35, 95% CI: 1.02-1.79) were also associated with an increased risk of stillbirth. Identified risk factors explained 78.2% (95% CI: 75.0%-81.4%) of the risk of stillbirth in the population. CONCLUSION: Addressing potentially modifiable antenatal factors could reduce the risk of stillbirths in India.

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.

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.

Effects of community-based interventions for stillbirths in sub-Saharan Africa: a systematic review and meta-analysis.

Background: Sub-Saharan Africa (SSA) alone contributed to 42% of global stillbirths in 2019, and the rate of stillbirth reduction has remained slow. There has been an increased uptake of community-based interventions to combat stillbirth in the region, but the effects of these interventions have been poorly assessed. Our objectives were to examine the effect of community-based interventions on stillbirth in SSA. Methods: In this systematic review and meta-analysis, we searched eight databases (MEDLINE [OvidSP], Embase [OvidSP], Cochrane Central Register of Controlled Trials, Global Health, Science Citation Index and Social Science Citation index [Web of Science Core Collection], CINAHL [EBSCOhost] and Global Index Medicus) and four grey literature sources from January 1, 2000 to July 7, 2023 for relevant studies from SSA. Community-based interventions targeting stillbirths solely or as part of complex interventions, with or without hospital interventions were included, while hospital-only interventions, microcredit schemes and maternity waiting home interventions were excluded. Study quality was assessed using the Cochrane risk of bias and National Heart, Lung and Blood Institute's tools. The study outcome was odds of stillbirth in intervention versus control communities. Pooled odds ratios (ORs) were estimated using random-effects models, and subgroup analyses were performed by intervention type and strategies. Publication bias was evaluated by funnel plot and Egger's test. This study is registered with PROSPERO, CRD42021296623. Findings: Of the 4223 records identified, seventeen studies from fifteen SSA countries were eligible for inclusion. One study had four arms (community only, hospital only, community and hospital, and control arms), so information was extracted from each arm. Analysis of 13 of the 17 studies which had community-only intervention showed that the odds of stillbirth did not vary significantly between community-based intervention and control groups (OR 0.96; 95% CI 0.78-1.17, I2 = 57%, p ≤ 0.01, n = 63,884). However, analysis of four (out of five) studies that included both community and health facility components found that in comparison with community only interventions, this combination strategy significantly reduced the odds of stillbirth by 17% (OR 0.83; 95% CI 0.79-0.87, I2 = 11%, p = 0.37, n = 244,868), after excluding a study with high risk of bias. The quality of the 17 studies were graded as poor (n = 2), fair (n = 9) and good (n = 6). Interpretation: Community-based interventions alone, without strengthening the quality and capacity of health facilities, are unlikely to have a substantial effect on reducing stillbirths in SSA. Funding: Nuffield Department of Population Health, Balliol College, the Clarendon Fund, Medical Research Council.

Antenatal and neonatal exposure to SARS-CoV-2 and children's development: a systematic review and meta-analysis.

OBJECTIVES: To conduct a systematic review of the impact of antenatal and neonatal exposure to SARS-CoV-2 on developmental outcomes in preterm and term-born infants. METHODS: We searched Embase, Emcare, MEDLINE, PsycINFO, Web of Science and grey literature on May 27, 2022 and updated on May 8, 2023. Studies defining exposure with a positive SARS-CoV-2 protein or genetic material, used a contemporaneous non-exposed cohort, and reported developmental outcomes up to 2 years of age were included. RESULTS: Four out of 828 screened studies were included. Meta-analysis included 815 infants screened for developmental delay (n = 306 exposed; n = 509 non-exposed) between 3- and 11-months of age. Among term-born infants, we did not find an increased risk of delay in communication (odd's ratio: 0.73 (95% CI: 0.24-2.24)), gross motor (1.50 (0.62, 3.62)), fine motor (2.90 (0.58, 14.43)), problem-solving (1.19 (0.54, 2.66)) or personal-social development (1.93 (0.78, 4.75)) in exposed infants. The number of preterm-born infants in the exposed (n = 37) and comparison cohorts (n = 41) were too few to report meaningful comparisons. CONCLUSION: Evidence regarding the potential impact of antenatal or neonatal exposure to SARS-CoV-2 infection on developmental outcomes in early infancy is limited and inconsistent. Larger cohorts with outcomes beyond the first year of life are needed. IMPACT: The current evidence examining associations between SARS-CoV-2 exposure during the neonatal period and developmental outcomes in infancy is limited by there being few studies with extremely small sample sizes. Based on sparse data there was no consistent association between antenatal or neonatal exposure to SARS-CoV-2 infection and an adverse impact on developmental outcomes below 12 months of age for babies born preterm or at term. This study highlights that larger cohorts with outcomes assessed beyond the first year are needed to determine the potential longer-term impact of SARS-CoV-2 infection exposure on child development.

Women's awareness of perinatal mental health conditions and the acceptability of being asked about mental health in two regions in India: a qualitative study.

BACKGROUND: Mental health conditions are common during pregnancy and the first year after childbirth. Early detection allows timely support and treatment to be offered, but identifying perinatal mental health conditions may be challenging due to stigma and under-recognition of symptoms. Asking about symptoms of mental health conditions during routine antenatal and postnatal appointments can help to identify women at risk. This study explores women's awareness of perinatal mental health conditions, their views on the acceptability of being asked about mental health and any preference for specific assessment tools in two regions in India. METHODS: Focus group discussions (FGDs) were conducted with pregnant, post-partum and non-perinatal women in Kangra, Himachal Pradesh (northern India) and Bengaluru, Karnataka (southern India). Settings included a hospital antenatal clinic and obstetric ward, Anganwadi Centres and Primary Health Centres. FGDs were facilitated, audio-recorded and transcribed. Narratives were coded for emerging themes and analysed using thematic analysis. RESULTS: Seven FGDs including 36 participants were conducted. Emerging themes were: manifestations of and contributors to mental health conditions; challenges in talking about mental health; and the acceptability of being asked about mental health. Difficult familial relationships, prioritising the needs of others and pressure to have a male infant were cited as key stressors. Being asked about mental health was generally reported to be acceptable, though some women felt uncomfortable with questions about suicidality. No preference for any specific assessment tool was reported. CONCLUSIONS: Women face many stressors during the perinatal period including difficult familial relationships and societal pressure to bear a male infant. Being asked about mental health was generally considered to be acceptable, but questions relating to suicidality may be challenging in a community setting, requiring sensitivity by the interviewer. Future studies should assess the acceptability of mental health assessments in 'real world' antenatal and postnatal clinics and explore ways of overcoming the associated challenges in resource-constrained settings.

Long-term healthcare utilization and costs of babies born after assisted reproductive technologies (ART): a record linkage study with 10-years' follow-up in England.

STUDY QUESTION: Is the long-term health care utilization of children born after ART more costly to the healthcare system in England than children born to mothers with no fertility problems? SUMMARY ANSWER: Children born after ART had significantly more general practitioner (GP) consultations and higher primary care costs up to 10 years after birth, and significantly higher hospital admission costs in the first year after birth, compared to children born to mothers with no fertility problems. WHAT IS KNOWN ALREADY: There is evidence that children born after ART are at an increased risk of adverse birth outcomes and a small increased risk of rare adverse outcomes in childhood. STUDY DESIGN, SIZE, DURATION: We conducted a longitudinal study of 368 088 mother and baby pairs in England using a bespoke linked dataset. Singleton babies born 1997-2018, and their mothers, who were registered at GP practices in England contributing data to the Clinical Practice Research Datalink (CPRD), were identified through the CPRD GOLD mother-baby dataset; this data was augmented with further linkage to the mothers' Human Fertilisation and Embryology Authority (HFEA) Register data. Four groups of babies were identified through the mothers' records: a 'fertile' comparison group, an 'untreated sub-fertile' group, an 'ovulation induction' group, and an ART group. Babies were followed-up from birth to 28 February 2021, unless censored due to loss to follow-up (e.g. leaving GP practice, emigration) or death. PARTICIPANTS/MATERIALS, SETTING, METHODS: The CPRD collects anonymized coded patient electronic health records from a network of GPs in the UK. We estimated primary care costs and hospital admission costs for babies in the four fertility groups using the CPRD GOLD data and the linked Hospital Episode Statistics (HES) Admitted Patient Care (APC) data. Linear regression was used to compare the care costs in the different groups. Inverse probability weights were generated and applied to adjust for potential bias caused by attrition due to loss to follow-up. MAIN RESULTS AND THE ROLE OF CHANCE: Children born to mothers with no fertility problems had significantly fewer consultations and lower primary care costs compared to the other groups throughout the 10-years' follow up. Regarding hospital costs, children born after ART had significantly higher hospital admission costs in the first year after birth compared to those born to mothers with no fertility problems (difference = £307 (95% CI: 153, 477)). The same pattern was observed in children born after untreated subfertility and ovulation induction. LIMITATIONS, REASONS FOR CAUTION: HFEA linkage uses non-donor data cycles only, and the introduction of consent for data use reduced the availability of HFEA records after 2009. The fertility groups were derived by augmenting HFEA data with evidence from primary care records; however, there remains some potential misclassification of exposure groups. The cost of neonatal critical care is not captured in the HES APC data, which may cause underestimation of the cost differences between the comparison group and the infertility groups. WIDER IMPLICATIONS OF THE FINDINGS: The findings can help anticipate the financial impact on the healthcare system associated with subfertility and ART, particularly as the demand for these treatments grows. STUDY FUNDING/COMPETING INTEREST(S): C.C. and this work were funded by a UK Medical Research Council Career Development Award [MR/L019671/1] and a UK MRC Transition Support Award [MR/W029286/1]. X.H. is an Australia National Health and Medical Research Council (NHMRC) Emerging Leadership Fellow [grant number 2009253]. The authors declare no competing interest. TRIAL REGISTRATION NUMBER: N/A.

Postpartum haemorrhage occurring in UK midwifery units: A national population-based case-control study to investigate incidence, risk factors and outcomes.

OBJECTIVES: To estimate the incidence of, and investigate risk factors for, postpartum haemorrhage (PPH) requiring transfer to obstetric care following birth in midwifery units (MU) in the UK; to describe outcomes for women who experience PPH requiring transfer to obstetric care. METHODS: We conducted a national population-based case-control study in all MUs in the UK using the UK Midwifery Study System (UKMidSS). Between September 2019 and February 2020, 1501 women with PPH requiring transfer to obstetric care following birth in an MU, and 1475 control women were identified. We used multivariable logistic regression, generating adjusted odds ratios (aORs) and 95% confidence intervals (CIs) to investigate risk factors for PPH requiring transfer to obstetric care. RESULTS: The incidence of PPH requiring transfer to obstetric care following birth in an MU was 3.7% (95% CI 3.6%-3.9%). Factors independently associated with PPH requiring transfer to obstetric care were smoking during pregnancy (aOR = 0.73; 95% CI 0.56-0.94), nulliparity (aOR = 1.96; 95% CI 1.66-2.30), previous PPH (aOR = 2.67; 95% CI 1.67-4.25), complications in a previous pregnancy other than PPH (aOR = 2.40; 95% CI 1.25-4.60), gestational age ≥41 weeks (aOR = 1.36; 95% CI 1.10-1.69), instrumental birth (aOR = 2.69; 95% CI 1.53-4.72), third stage of labour ≥60 minutes (aOR = 5.56; 95% CI 3.93-7.88), perineal trauma (aOR = 4.67; 95% CI 3.16-6.90), and birthweight 3500-3999g (aOR = 1.71; 95% CI 1.42-2.07) or ≥4000g (aOR = 2.31; 95% CI 1.78-3.00). One in ten (10.6%) cases received a blood transfusion and one in five (21.0%) were admitted to higher level care. CONCLUSIONS: The risk factors identified in this study align with those identified in previous research and with current guidelines for women planning birth in an MU in the UK. Maternal outcomes after PPH were broadly reassuring and indicative of appropriate management. NHS organisations should ensure that robust guidelines are in place to support management of PPH in MUs.

Types, reporting and acceptability of community-based interventions for stillbirth prevention in sub-Saharan Africa (SSA): a systematic review.

Background: Community-based interventions are increasingly being implemented in Sub-Saharan Africa (SSA) for stillbirth prevention, but the nature of these interventions, their reporting and acceptability are poorly assessed. In addition to understanding their effectiveness, complete reporting of the methods, results and intervention acceptability is essential as it could potentially reduce research waste from replication of inadequately implemented and unacceptable interventions. We conducted a systematic review to investigate these aspects of community-based interventions for preventing stillbirths in SSA. Methods: In this systematic review, eight databases (MEDLINE(OvidSP), Embase (OvidSP), Cochrane Central Register of Controlled Trials, Global Health, Science Citation Index and Social Science Citation index (Web of Science Core Collection), CINAHL (EBSCOhost) and Global Index Medicus) and four grey literature sources were searched from January 1, 2000 to July 7, 2023 for relevant quantitative and qualitative studies from SSA (PROSPERO-CRD42021296623). Following deduplication, abstract screening and full-text review, studies were included if the interventions were community-based with or without a health facility component. The main outcomes were types of community-based interventions, completeness of intervention reporting using the TIDier (Template for Intervention Description and replication) checklist, and themes related to intervention acceptability identified using a theoretical framework. Study quality was assessed using the Cochrane risk of bias and National Heart, Lung and Blood Institute's tools. Findings: Thirty-nine reports from thirty-four studies conducted in 18 SSA countries were eligible for inclusion. Four types of interventions were identified: nutritional, infection prevention, access to skilled childbirth attendants and health knowledge/behaviour of women. These interventions were implemented using nine strategies: mHealth (defined as the use of mobile and wireless technologies to support the achievement of health objectives), women's groups, community midwifery, home visits, mass media sensitisation, traditional birth attendant and community volunteer training, community mobilisation and transport vouchers. The completeness of reporting using the TIDier checklist varied across studies with a very low proportion of the included studies reporting the intervention intensity, dosing, tailoring and modification. The quality of the included studies were graded as poor (n = 6), fair (n = 14) and good (n = 18). Though interventions were acceptable, only 4 (out of 7) studies explored women's perceptions, mostly focusing on perceived intervention effects and how they felt, omitting key constructs like ethicality, opportunity cost and burden of participation. Interpretation: Different community-based interventions have been tried and evaluated for stillbirth prevention in SSA. The reproducibility and implementation scale-up of these interventions may be limited by incomplete intervention descriptions in the published literature. To strengthen impact, it is crucial to holistically explore the acceptability of these interventions among women and their families. Funding: Clarendon/Balliol/NDPH DPhil scholarship for UGA. MN is funded by a Medical Research Council Transition Support Award (MR/W029294/1).

Primary postpartum haemorrhage and longer-term physical, psychological, and psychosocial health outcomes for women and their partners in high income countries: A mixed-methods systematic review.

OBJECTIVES: Most research about outcomes following postpartum haemorrhage (PPH) has focused on immediate outcomes. There are fewer studies investigating longer-term maternal morbidity following PPH, resulting in a significant knowledge gap. This review aimed to synthesize the evidence about the longer-term physical and psychological consequences of primary PPH for women and their partners from high income settings. METHODS: The review was registered with PROSPERO and five electronic databases were searched. Studies were independently screened against the eligibility criteria by two reviewers and data were extracted from both quantitative and qualitative studies that reported non-immediate health outcomes of primary PPH. RESULTS: Data were included from 24 studies, of which 16 were quantitative, five were qualitative and three used mixed-methods. The included studies were of mixed methodological quality. Of the nine studies reporting outcomes beyond five years after birth, only two quantitative studies and one qualitative study had a follow-up period longer than ten years. Seven studies reported outcomes or experiences for partners. The evidence indicated that women with PPH were more likely to have persistent physical and psychological health problems after birth compared with women who did not have a PPH. These problems, including PTSD symptoms and cardiovascular disease, may be severe and extend for many years after birth and were more pronounced after a severe PPH, as indicated by a blood transfusion or hysterectomy. There was limited evidence about outcomes for partners after PPH, but conflicting evidence of association between PTSD and PPH among partners who witnessed PPH. CONCLUSION: This review explored existing evidence about longer-term physical and psychological health outcomes among women who had a primary PPH in high income countries, and their partners. While the evidence about health outcomes beyond five years after PPH is limited, our findings indicate that women can experience long lasting negative impacts after primary PPH, including PTSD symptoms and cardiovascular disease, extending for many years after birth. PROSPERO REGISTRATION: PROSPERO registration number: CRD42020161144.

Vulnerable newborn types: Analysis of population-based registries for 165 million births in 23 countries, 2000-2021.

OBJECTIVE: To examine the prevalence of novel newborn types among 165 million live births in 23 countries from 2000 to 2021. DESIGN: Population-based, multi-country analysis. SETTING: National data systems in 23 middle- and high-income countries. POPULATION: Liveborn infants. METHODS: Country teams with high-quality data were invited to be part of the Vulnerable Newborn Measurement Collaboration. We classified live births by six newborn types based on gestational age information (preterm <37 weeks versus term ≥37 weeks) and size for gestational age defined as small (SGA, <10th centile), appropriate (10th-90th centiles), or large (LGA, >90th centile) for gestational age, according to INTERGROWTH-21st standards. We considered small newborn types of any combination of preterm or SGA, and term + LGA was considered large. Time trends were analysed using 3-year moving averages for small and large types. MAIN OUTCOME MEASURES: Prevalence of six newborn types. RESULTS: We analysed 165 017 419 live births and the median prevalence of small types was 11.7% - highest in Malaysia (26%) and Qatar (15.7%). Overall, 18.1% of newborns were large (term + LGA) and was highest in Estonia 28.8% and Denmark 25.9%. Time trends of small and large infants were relatively stable in most countries. CONCLUSIONS: The distribution of newborn types varies across the 23 middle- and high-income countries. Small newborn types were highest in west Asian countries and large types were highest in Europe. To better understand the global patterns of these novel newborn types, more information is needed, especially from low- and middle-income countries.

Facility-based stillbirth review processes used in different countries across the world: a systematic review.

Background: Facility-based stillbirth review provides opportunities to estimate incidence, evaluate causes and risk factors for stillbirths, and identify any issues related to the quality of pregnancy and childbirth care which require improvement. Our aim was to systematically review all types and methods of facility-based stillbirth review processes used in different countries across the world, to examine how stillbirth reviews in facility settings are being conducted worldwide and to identify the outcomes of implementing the reviews. Moreover, to identify facilitators and barriers influencing the implementation of the identified facility-based stillbirth reviews processes by conducting subgroup analyses. Methods: A systematic review of published literature was conducted by searching MEDLINE (OvidSP) [1946-present], EMBASE (OvidSP) [1974-present], WHO Global Index Medicus (globalindexmedicus.net), Global Health (OvidSP) [1973-2022 Week 8] and CINAHL (EBSCOHost) [1982-present] from their inception until 11 January, 2023. For unpublished or grey literature, the WHO databases, Google Scholar and ProQuest Dissertations & Theses Global were searched, as well as hand searching the reference lists of included studies. MESH terms encompassing "∗Clinical Audit", "∗Perinatal Mortality", "Pregnancy Complications", and "Stillbirth" were used with Boolean operators. Studies that used a facility-based review process or any approach to evaluate care prior to stillbirth, and explained the methods used were included. Reviews and editorials were excluded. Three authors (YYB, UGA, and DBT) independently screened and extracted data, and assessed the risk of bias using an adapted JBI's Checklist for Case Series. A logic model was used to inform the narrative synthesis. The review protocol was registered with PROSPERO, CRD42022304239. Findings: A total of 68 studies from 17 high-income (HICs) and 22 low-and-middle-income countries (LMICs) met the inclusion criteria from a total of 7258 identified records. These were stillbirth reviews conducted at different levels: district, state, national, and international. Three types were identified: audit, review, and confidential enquiry, but not all desired components were included in most processes, which led to a mismatch between the description of the type and the actual method used. Routine data from hospital records was the most common data source for identifying stillbirths, and case assessment was based on stillbirth definition in 48 out of 68 studies. Hospital notes were the most common source of information about care received and causes/risk factors for stillbirth. Short-term and medium-term outcomes were reported in 14 studies, but impact of the review process on reducing stillbirth, which is more difficult to establish, was not reported in any study. Facilitators and barriers in implementing a successful stillbirth review process identified from 14 studies focused on three main themes: resources, expertise, and commitment. Interpretation: This systematic review's findings identified that there is a need for clear guidelines on how to measure the impact of implementation of changes based on outputs of stillbirth reviews and methods to enable effective dissemination of learning points in the future and promoting them through training platforms. In addition, there is a need to develop and adopt a universal definition of stillbirth to facilitate meaningful comparison of stillbirth rates between regions. The key limitation of this review is that while using a logic model for narrative synthesis was deemed most appropriate for this study, sequence of implementing a stillbirth review in the real world is not linear, and assumptions are often not met. Therefore, the logic model proposed in this study should be interpreted with flexibility when designing a stillbirth review process. The generated learnings from the stillbirth review processes inform the action plans and allow facilities to consider where the changes should happen to improve the quality of care in the facilities, enabling positive short-term and medium-term outcomes. Funding: Kellogg College, University of Oxford, Clarendon Fund, University of Oxford, Nuffield Department of Population Health, University of Oxford and Medical Research Council (MRC).

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.

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.

Gestational age and hospital admission costs from birth to childhood: a population-based record linkage study in England.

OBJECTIVE: To examine the association between gestational age at birth and hospital admission costs from birth to 8 years of age. DESIGN: Population-based, record linkage, cohort study in England. SETTING: National Health Service (NHS) hospitals in England, UK. PARTICIPANTS: 1 018 136 live, singleton births in NHS hospitals in England between 1 January 2005 and 31 December 2006. MAIN OUTCOME MEASURES: Hospital admission costs from birth to age 8 years, estimated by gestational age at birth (<28, 28-29, 30-31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41 and 42 weeks). RESULTS: Both birth admission and subsequent admission hospital costs decreased with increasing gestational age at birth. Differences in hospital admission costs between gestational age groups diminished with increasing age, particularly after the first 2 years following birth. Children born extremely preterm (<28 weeks) and very preterm (28-31 weeks) still had higher average hospital admission costs (£699 (95% CI £419 to £919) for <28 weeks; £434 (95% CI £305 to £563) for 28-31 weeks) during the eighth year of life compared with children born at 40 weeks (£109, 95% CI £104 to £114). Children born extremely preterm had the highest 8-year cumulative hospital admission costs per child (£80 559 (95% CI £79 238 to £82 019)), a large proportion of which was incurred during the first year after birth (£71 997 (95% CI £70 866 to £73 097)). CONCLUSIONS: The association between gestational age at birth and hospital admission costs persists into mid-childhood. The study results provide a useful costing resource for future economic evaluations focusing on preventive and treatment strategies for babies born preterm.

The impact of a universal late third-trimester scan for fetal growth restriction on perinatal outcomes in term singleton births: A prospective cohort study.

OBJECTIVE: To investigate perinatal mortality, morbidity and obstetric intervention following the introduction of a universal late third-trimester ultrasound scan for growth restriction. DESIGN: Prospective cohort study. SETTING: Oxfordshire (OUH), UK. POPULATION: Women with a non-anomalous singleton pregnancy undergoing pregnancy care and term delivery at OUH with an estimated due date (EDD) of birth between 1 January 2014 and 30 September 2019. METHODS: Universal ultrasound for fetal growth restriction between 35+0 and 36+6 weeks was introduced in 2016. The outcomes of the next 18 631 eligible term pregnancies were compared, adjusting for covariates and time, with the previous 18 636 who had clinically indicated ultrasounds only. 'Screen-positives' for growth restriction were managed according to a pre-determined protocol which included non-intervention for some small-for-gestational-age babies. MAIN OUTCOME MEASURES: Extended perinatal mortality, a composite of mortality or encephalopathy Grade II-III, and expedited birth. Other outcomes included composite adverse outcomes used elsewhere, detection of low birthweight and birth from 37+0 to 38+6 weeks. RESULTS: Extended perinatal deaths decreased 27% and severe morbidity decreased 33% but neither change was statistically significant (adjusted odd ratio [aOR] 0.53, 95% confidence interval [C1] 00.18-1.56 and aOR 0.71, 95% CI 0.31-1.63). Expedited births changed from 35.2% to 37.7% (aOR 0.99, 95% CI 0.92-1.06). Birthweight (<10th centile) detection using fetal biometry alone was 31.4% and rose to 40.5% if all abnormal scan parameters were used. CONCLUSION: Improvements in mortality and severe morbidity subsequent to introducing a universal ultrasound for growth restriction are encouraging but remain unclear. Little change in intervention is possible. The antenatal detection of low birthweight remains poor but improves where markers of growth restriction are used.