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Background: The findings of individual epidemiological studies that suggest an association between some Persistent Organic Pollutants (POPs) and Gestational Diabetes Mellitus (GDM) are inconclusive. Objectives: To estimate the strength of the association between POPs exposure and GDM in a systematic review with meta-analysis. Search strategy: MEDLINE, Scopus, and Web of Science were searched until 2022. Selection criteria: Cohort and case-control studies analyzing the association between POPs and GDM in healthy pregnant women. Data collection and analysis: Quality was assessed using QUIPS scale and standardized mean differences (SMD) and 95% confidence intervals (CI) was pooled using random-effect model. Main results: Fourteen articles including 11,422 participants were selected. The risk of bias of included studies was high in 4 (28.6%), moderate in 9 (64.3%) and low in 1 (7.14%). Only six POPs showed a significative SMD between GDM cases and controls: Perfluorobutanesulfonic acid (PFBS) 0.33 (95% CI 0.23, 0.43; I2=0%); Perfluorodecanoic acid (PFDA) -0.11 (95% CI -0.20, -0.01, I2 = 0.0%); 2,2’,3,4,4’,5,5’-Heptachlorobiphenyl (PCB 180) 0.37 (95% CI 0.19, 0.56; I2=25.3%); 2,2’,4,4’,5-Decabromodiphenyl ether (BDE 99) 0.36 (95% CI 0.14, 0.59; I2=0%); 2,2’,4,4’,6-Decabromodiphenyl ether (BDE 100) 0.42 (95% CI 0.19, 0.38; I2=0%); and, Hexachlorobenzene (HCB) 0.22 (95% CI 0.01, 0.42, I2=39.6%). For other POPs, no statistically significant association was observed. Conclusion: The available evidence is variable on quality and results were heterogeneous making impossible to establish a clear association between POPs exposure and risk of GDM. Improve the methodology of epidemiological studies assessing the association of POPs and risk of adverse clinical outcomes are needed.

Background Mother-to-baby transmission of group B Streptococcus (Streptococcus agalactiae) is the main cause of early-onset infection. Objectives We investigated if intrapartum antibiotic prophylaxis directed by a rapid intrapartum test reduces maternal and neonatal antibiotic use, compared with usual care (i.e. risk factor-directed antibiotics), among women with risk factors for vertical group B Streptococcus transmission, and examined the accuracy and cost-effectiveness of the rapid test. Design An unblinded cluster randomised controlled trial with a nested test accuracy study, an economic evaluation and a microbiology substudy. Setting UK maternity units were randomised to either a strategy of rapid test or usual care. Participants Vaginal and rectal swabs were taken from women with risk factors for vertical group B Streptococcus transmission in established term labour. The accuracy of the GeneXpert® Dx IV GBS rapid testing system (Cepheid, Maurens-Scopont, France) was compared with the standard of selective enrichment culture in diagnosing maternal group B Streptococcus colonisation. Main outcome measures Primary outcomes were rates of intrapartum antibiotic prophylaxis administered to prevent early-onset group B Streptococcus infection and accuracy estimates of the rapid test. Secondary outcomes were maternal antibiotics for any indication, neonatal antibiotic exposure, maternal antibiotic duration, neonatal group B Streptococcus colonisation, maternal and neonatal antibiotic resistance, neonatal morbidity and mortality, and cost-effectiveness of the strategies. Results Twenty-two maternity units were randomised and 20 were recruited. A total of 722 mothers (749 babies) participated in rapid test units and 906 mothers (951 babies) participated in usual-care units. There were no differences in the rates of intrapartum antibiotic prophylaxis for preventing early-onset group B Streptococcus infection in the rapid test units (41%, 297/716) compared with the usual-care units (36%, 328/906) (risk ratio 1.16, 95% confidence interval 0.83 to 1.64). There were no differences between the groups in intrapartum antibiotic administration for any indication (risk ratio 0.99, 95% confidence interval 0.81 to 1.21). Babies born in the rapid test units were 29% less likely to receive antibiotics (risk ratio 0.71, 95% confidence interval 0.54 to 0.95) than those born in usual-care units. The sensitivity and specificity of the rapid test were 86% (95% confidence interval 81% to 91%) and 89% (95% confidence interval 85% to 92%), respectively. In 14% of women (99/710), the rapid test was invalid or the machine failed to provide a result. In the economic analysis, the rapid test was shown to be both less effective and more costly and, therefore, dominated by usual care. Sensitivity analysis indicated potential lower costs for the rapid test strategy when neonatal costs were included. No serious adverse events were reported. Conclusions The Group B Streptococcus 2 (GBS2) trial found no evidence that the rapid test reduces the rates of intrapartum antibiotic prophylaxis administered to prevent early-onset group B Streptococcus infection. The rapid test has the potential to reduce neonatal exposure to antibiotics, but economically is dominated by usual care. The accuracy of the test is within acceptable limits. Future work The role of routine testing for prevention of neonatal infection requires evaluation in a randomised controlled trial. Trial registration Current Controlled Trials ISRCTN74746075. Funding This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 26, No. 12. See the NIHR Journals Library website for further project information.

Objectives Lifestyle interventions during pregnancy improve maternal and infant outcomes. We aimed to compare the cost-effectiveness of 4 antenatal lifestyle intervention types with standard care. Methods A decision tree model was constructed to compare lifestyle intervention effects from a novel meta-analysis. The target population was women with singleton pregnancies and births at more than 20 weeks’ gestation. Interventions were categorized as diet, diet with physical activity, physical activity, and mixed (lacking structured diet and, or, physical activity components). The outcome of interest was cost per case prevented (gestational diabetes, hypertensive disorders in pregnancy, cesarean birth) expressed as an incremental cost-effectiveness ratio (ICER) from the Australian public healthcare perspective. Scenario analyses were included for all structured interventions combined and by adding neonatal intensive care unit costs. Costs were estimated from published data and consultations with experts and updated to 2019 values. Discounting was not applied owing to the short time horizon. Results Physical activity interventions reduced adverse maternal events by 4.2% in the intervention group compared with standard care and could be cost saving. Diet and diet with physical activity interventions reduced events by 3.5% (ICER = A$4882) and 2.9% (ICER = A$2020), respectively. Mixed interventions did not reduce events and were dominated by standard care. In scenario analysis, all structured interventions combined and all interventions when including neonatal intensive care unit costs (except mixed) may be cost saving. Probabilistic sensitivity analysis showed that for physical activity and all structured interventions combined, the probability of being cost saving was 58% and 41%, respectively. Conclusions Governments can expect a good return on investment and cost savings when implementing effective lifestyle interventions population-wide.

IntroductionWith good medical care, most pregnancy complications like pre-eclampsia, gestational diabetes, etc resolve after childbirth. However, pregnancy complications are known to be associated with an increased risk of new long-term health conditions for women later in life, such as cardiovascular disease. These umbrella reviews aim to summarise systematic reviews evaluating the association between pregnancy complications and five groups of long-term health conditions: autoimmune conditions, cancers, functional disorders, mental health conditions and metabolic health conditions (diabetes and hypertension).Methods and analysisWe will conduct searches in Medline, Embase and the Cochrane database of systematic reviews without any language restrictions. We will include systematic reviews with or without meta-analyses that studied the association between pregnancy complications and the future risk of the five groups of long-term health conditions in women. Pregnancy complications were identified from existing core outcome sets for pregnancy and after consultation with experts. Two reviewers will independently screen the articles. Data will be synthesised with both narrative and quantitative methods. Where a meta-analysis has been carried out, we will report the combined effect size from individual studies. For binary data, pooled ORs with 95% CIs will be presented. For continuous data, we will use the mean difference with 95% CIs. The findings will be presented in forest plots to assess heterogeneity. The methodological quality of the studies will be evaluated with the AMSTAR 2 tool or the Cochrane risk of bias tool. The corrected covered area method will be used to assess the impact of overlap in reviews. The findings will be used to inform the design of prediction models, which will predict the risk of women developing these five group of health conditions following a pregnancy complication.Ethics and disseminationNo ethical approvals required. Findings will be disseminated through publications in peer-reviewed journals and conference presentations.

The ability to calculate the absolute risk of adverse pregnancy outcomes for an individual woman with gestational diabetes mellitus (GDM) would allow preventative and therapeutic interventions to be delivered to women at high-risk, sparing women at low-risk from unnecessary care. We aimed to develop, validate and evaluate the clinical utility of a prediction model for adverse pregnancy outcomes in women with GDM.A prediction model development and validation study was conducted on data from a observational cohort. Participants included all women with GDM from three metropolitan tertiary teaching hospitals in Melbourne, Australia. The development cohort comprised those who delivered between 1 July 2017 to 30 June 2018 and the validation cohort those who delivered between 1 July 2018 to 31 December 2018. The main outcome was a composite of critically important maternal and perinatal complications (hypertensive disorders of pregnancy, large-for-gestational age neonate, neonatal hypoglycaemia requiring intravenous therapy, shoulder dystocia, perinatal death, neonatal bone fracture and nerve palsy). Model performance was measured in terms of discrimination and calibration and clinical utility evaluated using decision curve analysis.The final PeRSonal (Prediction for Risk Stratified care for women with GDM) model included body mass index, maternal age, fasting and 1-hour glucose values (75-g oral glucose tolerance test), gestational age at GDM diagnosis, Southern and Central Asian ethnicity, East Asian ethnicity, nulliparity, past delivery of an large-for-gestational age neonate, past pre-eclampsia, GWG until GDM diagnosis, and family history of diabetes. The composite adverse pregnancy outcome occurred in 27% (476/1747) of women in the development (1747 women) and in 26% (244/955) in the validation (955 women) cohorts. The model showed excellent calibration with slope of 0.99 (95% CI 0.75 to 1.23) and acceptable discrimination (The PeRSonal GDM model comprising of routinely available clinical data shows compelling performance, is transportable across time, and has clinical utility across a range of predicted probabilities. Further external validation of the model to a more disparate population is now needed to assess the generalisability to different centres, community based care and low resource settings, other healthcare systems and to different GDM diagnostic criteria.This work is supported by the Mothers and Gestational Diabetes in Australia 2 NHMRC funded project #1170847.

Purpose of review To review the various classification systems for mother-to-child transmission (MTCT) of SARS-CoV-2 and collate existing evidence on systematic reviews of MTCT of SARS-CoV-2. Recent findings To-date, there are three classification systems for MTCT of SARS-CoV-2, including the WHO classification developed by expert consensus, based on in-utero, intrapartum and postnatal exposure of the babies to the virus. The systems variously classify babies tested for suspected SARS-CoV-2 infection as confirmed, probable, possible, indeterminate and unlikely for MTCT. To-date, 68 systematic reviews have been published between December 2019 and March 2021 on SARS-CoV-2 MTCT. Most of the reviews included cases series and case reports in their pooling of data, and often used SARS-CoV-2 infection and test positivity interchangeably. Summary Several classification systems are available to assist in determining the timing of SARS-CoV-2 infection in new-borns. Existing reviews of MTCT are of poor quality and report variable rates of SARS-CoV-2 positivity. A high-quality systematic review is needed on the extent of confirmed vertical transmission of SARS-CoV-2, risk factors for MTCT of SARS-CoV-2, the prevalence and persistence of viral particles or immunological response in reported biological samples. Primary studies should categorize MTCT using classifications, such as WHO classification system that considers the strength of the timing of classification and persistence of positivity, taking into account the sterility of the collected samples.

The coronavirus disease-19 (COVID-19) pandemic has directly and indirectly impacted pregnant women with co-morbidities or antenatal medical complications, through vulnerability to the severe effects of COVID-19 and service reconfiguration. Women with diabetes or hypertension in pregnancy are at higher risk of admission to intensive care, need for invasive ventilation and death from COVID-19. Suggested service modifications specific to maternal medicine services include home measurement of blood glucose or blood pressure, the use of risk calculators, adaptations to screening criteria for gestational diabetes and monitoring of obstetric cholestasis. Neither the added risk of COVID-19 on pregnant women with medical comorbidities nor the impact of maternal medicine service modifications has yet been established.

Background Polycystic ovary syndrome (PCOS) affects up to one in five women of childbearing age. Observational studies assessing the association between maternal PCOS and adverse obstetric outcomes have reported varying results, depending on patient population, diagnostic criteria for PCOS and covariates accounted for in their analyses. We aimed to assess the risk of obstetric outcomes among a population-based representative cohort of women with PCOS compared to an age-matched cohort of women without PCOS. Methods A retrospective cohort study was conducted of pregnancies of women in England aged 15–49 years identified from the Clinical Practice Research Datalink (CPRD) GOLD pregnancy register and linked Hospital Episodes Statistic (HES) data between March 1997 and March 2020. Pregnancies from the register that had a linked HES delivery record were included. Linked CPRD primary care data was used to ascertain maternal PCOS exposure prior to pregnancy. To improve detection of PCOS, in addition to PCOS diagnostic codes, codes for (1) polycystic ovaries or (2) hyperandrogenism and anovulation together were also considered. Sensitivity analysis was limited to only pregnant women with a diagnostic code for PCOS. Primary outcomes ascertained from linked HES data were (1) preterm delivery (gestation 4000 g) or low birthweight ( Conditional logistic regression models were performed adjusting for age, ethnicity, deprivation, dysglycaemia, hypertension, thyroid disorders, number of babies born at index pregnancy, and pre-gravid BMI. Multiple imputation was performed for missing outcome data. Results 27,586 deliveries with maternal PCOS were matched for age (± 1 year) to 110,344 deliveries without PCOS. In the fully adjusted models, maternal PCOS was associated with an increased risk of (1) preterm birth [aOR: 1.11 (95% CI 1.06–1.17)], and (2) emergency caesarean, elective caesarean and instrumental vaginal compared to spontaneous delivery [aOR: 1.10 (1.05–1.15), 1.07 (1.03–1.12) and 1.04 (1.00–1.09), respectively]. There was absence of association with low birthweight, high birthweight and stillbirth. In the sensitivity analysis, the association with preterm birth [aOR: 1.31 (95% CI 1.13–1.52)], emergency caesarean [aOR: 1.15 (95% CI 1.02–1.30)], and elective caesarean [aOR: 1.03 (95% CI 1.02–1.03)] remained. While there was no significant association with any of the secondary outcomes in the primary analysis, in the sensitivity analysis maternal PCOS was associated with increased risk of extremely preterm delivery [aOR: 1.86 (95% CI 1.31–2.65)], and lower risk of small for gestational age babies [aOR: 0.74 (95% CI 0.59–0.94)]. Conclusions Maternal PCOS was associated with increased risk of preterm and caesarean delivery. Association with low birthweight may be largely mediated by lower gestational age at birth.

IntroductionOne in five pregnant women have multiple long-term conditions in the United Kingdom (UK). Studies have shown that maternal multiple long-term conditions are associated with adverse outcomes. This observational study aims to compare maternal and children’s outcome for pregnant women with multiple long-term to those without multiple long-term conditions.Methods and analysisPregnant women aged 15 to 49 years old with a conception date between 2000 and 2019 in the UK will be included. The data source will be routine health records from all four UK nations (Clinical Practice Research Datalink [CPRD, England], Secure Anonymised Information Linkage [SAIL, Wales], Scotland routine health records and Northern Ireland Maternity System [NIMATS]), and the Born in Bradford prospective birth cohort.The exposure of two or more pre-existing, long-term physical or mental health conditions will be defined from a list of health conditions predetermined by women and clinicians. The association of maternal multiple long-term conditions with (i) antenatal, (ii) peripartum, (iii) postnatal and long-term, and (iv) mental health outcomes, for both women and their children will be examined. Outcomes of interest will be guided by a core outcome set.Comparisons will be made between pregnant women with and without multiple long-term conditions using logistic and Cox regression. Generalised estimating equation will account for the clustering effect of women who had more than one pregnancy episode. Where appropriate, multiple imputation with chained equation will be used for missing data. Federated analysis will be conducted for each dataset and results will be pooled using meta-analysis.Ethics and disseminationApproval has been obtained from the respective data sources in each UK nation: CPRD: Independent Scientific Advisory Committee (reference: 20_181R); SAIL: Information Governance Review Panel; Scotland: National Health Service Scotland Public Benefit and Privacy Panel for Health and Social Care (HSC-PBPP), The University Teaching and Research Ethics Committee (UTREC) from the University of St Andrews; NIMATS: Honest Broker Service Governance Board; Born in Bradford: Bradford National Health Service Research Ethics Committee (ref 07/H1302/112).Study findings will be submitted for publications in peer reviewed journals and presented at key conferences for health and social care professionals involved in the care of pregnant women with multiple long-term conditions and their children.ARTICLE SUMMARYStrengths and limitations of this studyThe study will utilise rich data sources from routine health records from all four UK nations and a birth cohort.Beyond examining maternal outcomes, linked mother baby data and the birth cohort data will allow for the exploration of children’s outcomes.Key limitations include missing data, misclassification bias due to inaccurate clinical coding and residual confounding.

IntroductionThe prevalence of COVID-19 and its impact varied between countries and regions. Pregnant women are at high risk of COVID-19 complications compared with non-pregnant women. The magnitude of variations, if any, in SARS-CoV-2 infection rates and its health outcomes among pregnant women by geographical regions and country’s income level is not known.MethodsWe performed a random-effects meta-analysis as part of the ongoing PregCOV-19 living systematic review (December 2019 to April 2021). We included cohort studies on pregnant women with COVID-19 reporting maternal (mortality, intensive care admission and preterm birth) and offspring (mortality, stillbirth, neonatal intensive care admission) outcomes and grouped them by World Bank geographical region and income level. We reported results as proportions with 95% confidence intervals (CI).ResultsWe included 311 studies (2 003 724 pregnant women, 57 countries). The rates of SARS-CoV-2 infection in pregnant women varied significantly by region (pConclusionThe rates of SARS-CoV-2 infection in pregnant women vary globally, and its health outcomes mirror the COVID-19 burden and global maternal and offspring inequalities.PROSPERO registration numberCRD42020178076.

IntroductionLow dietary calcium intake is a risk factor for pre-eclampsia, a major contributor to maternal and perinatal mortality and morbidity worldwide. Calcium supplementation can prevent pre-eclampsia in women with low dietary calcium. However, the optimal dose and timing of calcium supplementation are not known. We plan to undertake an individual participant data (IPD) meta-analysis of randomised trials to determine the effects of various calcium supplementation regimens in preventing pre-eclampsia and its complications and rank these by effectiveness. We also aim to evaluate the cost-effectiveness of calcium supplementation to prevent pre-eclampsia.Methods and analysisWe will identify randomised trials on calcium supplementation before and during pregnancy by searching major electronic databases including Embase, CINAHL, MEDLINE, CENTRAL, PubMed, Scopus, AMED, LILACS, POPLINE, AIM, IMSEAR, ClinicalTrials.gov and the WHO International Clinical Trials Registry Platform, without language restrictions, from inception to February 2022. Primary researchers of the identified trials will be invited to join the International Calcium in Pregnancy Collaborative Network and share their IPD. We will check each study’s IPD for consistency with the original authors before standardising and harmonising the data. We will perform a series of one-stage and two-stage IPD random-effect meta-analyses to obtain the summary intervention effects on pre-eclampsia with 95% CIs and summary treatment–covariate interactions (maternal risk status, dietary intake, timing of intervention, daily dose of calcium prescribed and total intake of calcium). Heterogeneity will be summarised using tau2, I2and 95% prediction intervals for effect in a new study. Sensitivity analysis to explore robustness of statistical and clinical assumptions will be carried out. Minor study effects (potential publication bias) will be investigated using funnel plots. A decision analytical model for use in low-income and middle-income countries will assess the cost-effectiveness of calcium supplementation to prevent pre-eclampsia.Ethics and disseminationNo ethical approvals are required. We will store the data in a secure repository in an anonymised format. The results will be published in peer-reviewed journals.PROSPERO registration numberCRD42021231276.

Context The incidence of gestational diabetes mellitus (GDM) has been on the rise, driven by maternal obesity. In parallel, pubertal tempo has increased in the general population, driven by childhood obesity. Objective To evaluate the available evidence on pubertal timing of boys and girls born to mothers with GDM. Data sources We searched MEDLINE, EMBASE, CINAHL Plus, Cochrane library and grey literature for observational studies up to October 2019. Study selection and extraction Two reviewers independently selected studies, collected data and appraised the studies for risk of bias. Results were tabulated and narratively described as reported in the primary studies. Results Seven articles (six for girls and four for boys) were included. Study quality score was mostly moderate (ranging from 4 to 10 out of 11). In girls born to mothers with GDM, estimates suggest earlier timing of pubarche, thelarche and menarche although for each of these outcomes only one study each showed a statistically significant association. In boys, there was some association between maternal GDM and earlier pubarche, but inconsistency in the direction of shift of age at onset of genital and testicular development and first ejaculation. Only a single study analysed growth patterns in children of mothers with GDM, describing a 3-month advancement in the age of attainment of peak height velocity and a slight increase in pubertal tempo. Conclusions Pubertal timing may be influenced by the presence of maternal GDM, though current evidence is sparse and of limited quality. Prospective cohort studies should be conducted, ideally coupled with objective biochemical tests.

Investing in clinical research and evidence-based medicine has helped to improve the care for women with polycystic ovary syndrome (PCOS). However, several important questions remain unanswered on the optimal prevention and management strategies for PCOS. Addressing this uncertainty is often hindered by suboptimal research conduct leading to inefficient evidence synthesis and research wastage. PCOS research is often practised by varied specialized teams in silo leading to disharmonious and fragmented efforts neglecting the lifelong impact of PCOS on women’s wellbeing. Poor engagement among key stakeholders and lay consumers continues to limit the impact and benefits of research to society. Selective reporting on surrogate outcomes with a ‘significant’ P-value is a common malpractice in PCOS outputs. Effective adoption of the harmonizing research outcomes for PCOS (HARP) core outcome set is needed to minimize heterogeneity in reporting and promote research excellence. Small single-centre studies offer limited value to assess the varied PCOS phenotypes. Efficient large scale data-sharing is needed to address complex research questions and glean the benefits of big data research. We propose a roadmap to address these challenges and remedy future research need by promoting patient and public involvement in PCOS research to guide research efforts and address real patients’ needs; engaging all key stakeholder groups to promote a multi-disciplinary lifelong approach to new research; continuously refining research needs and priorities to revise the knowledge gap and allocate resources judiciously; standardizing outcomes definitions and measurement tools to harmonize reporting and promote excellence in research; and by investing in large data-sharing infrastructure to facilitate big data research and govern ethical data sharing.

To map the care provided to pregnant women with epilepsy in UK maternity units and identify future research priorities by conducting a nationwide survey of healthcare professionals.A prospective cross-sectional electronic survey was conducted between 29 April and 30 October 2021. The survey included 23 questions developed and refined with relevant stakeholders, including a woman with lived experience of epilepsy and pregnancy. We used descriptive analyses to summarise responses and estimated proportions with medians and interquartile ranges.144 individual healthcare professionals from 94 hospitals, representing 77 NHS Trusts, participated in the survey. Obstetricians were the most common responders (45%, 65/144) and almost half (47%, 7/15) of regions had a survey response rate per NHS Trust greater than 50%. Six pregnant women with epilepsy, on average, were booked into antenatal care per hospital per month, and 49% (46/94) of hospitals saw women for specialist antenatal care in the first trimester. The care provided across healthcare systems varied, with multiple pathways for referral to specialist care within regions. Midwife referral was the most used care pathway (80%, 75/94). Less than a third of hospitals (31%, 29/94) ran joint obstetric/neurology clinics for pregnant women with epilepsy. Most survey respondents (81%, 117/144) were confident talking to pregnant women about their risk of seizures but only a minority (20%, 29/144) used validated calculators to assess this risk. There was broad agreement across healthcare professionals that the priorities for research should focus on how to improve communication and address pregnant women's concerns regarding epilepsy and pregnancy, and to develop further understanding on the optimal use and long-term effects of anti-seizure medication.Our UK nationwide survey of hospital-based maternity services for pregnant women with epilepsy identified wide variation in when, how and by whom these women are seen, with differences between and within the UK regions. This survey highlights areas for improvement in the care of pregnant women with epilepsy.

Safety and effectiveness of COVID-19 vaccines during pregnancy is a particular concern affecting vaccination uptake by this vulnerable group. Here we evaluated evidence from 23 studies including 117,552 COVID-19 vaccinated pregnant people, almost exclusively with mRNA vaccines. We show that the effectiveness of mRNA vaccination against RT-PCR confirmed SARS-CoV-2 infection 7 days after second dose was 89·5% (95% CI 69·0-96·4%, 18,828 vaccinated pregnant people, I2 = 73·9%). The risk of stillbirth was significantly lower in the vaccinated cohort by 15% (pooled OR 0·85; 95% CI 0·73–0·99, 66,067 vaccinated vs. 424,624 unvaccinated, I2 = 93·9%). There was no evidence of a higher risk of adverse outcomes including miscarriage, earlier gestation at birth, placental abruption, pulmonary embolism, postpartum haemorrhage, maternal death, intensive care unit admission, lower birthweight Z-score, or neonatal intensive care unit admission (p > 0.05 for all). COVID-19 mRNA vaccination in pregnancy appears to be safe and is associated with a reduction in stillbirth.

IntroductionGlobally, tuberculosis (TB) is a leading cause of death in women of reproductive age and there is high risk of reactivation of latent tuberculosis infection (LTBI) in pregnancy. The uptake of routine screening of migrants for LTBI in the UK in primary care is low. Antenatal care is a novel setting which could improve uptake and can lend insight into the feasibility and acceptability of offering opt-out screening for LTBI.Methods and analysisThis is an observational feasibility study with a nested qualitative component. The setting will be the antenatal clinics in three hospitals in East London, UK . Inclusion criteria are pregnant migrant women aged 16–35 years attending antenatal clinics who are from countries with a TB incidence of greater than 150/100 000 including sub-Saharan Africa, and who have been in the UK for less than 5 years. Participants will be offered LTBI screening with an opt-out interferon gamma release assay blood test, and be invited to complete a questionnaire. Both participants and healthcare providers will be invited to participate in semistructured interviews or focus groups to evaluate understanding, feasibility and acceptability of routine opt-out LTBI screening. The primary analysis will focus on estimating the uptake of the screening programme along with the corresponding 95% CI. Secondary analysis will focus on estimating the test positivity. Qualitative analysis will evaluate the acceptability of offering routine opt-out LTBI screening to participants and healthcare providers.Ethics and disseminationThe study has received the following approvals: Health Research Authority (IRAS 247388) and National Health Service Ethics Committee (19/LO/0557). The results will be made available locally to antenatal clinics and primary care physicians, nationally to NHS England and Public Health England and internationally through conferences and journals.Trial registration numberNCT04098341.

Women's blood pressure (BP) changes throughout pregnancy. The effect of BP trajectories on preterm delivery is not clear. The authors aim to evaluate the association between maternal BP trajectories during pregnancy and preterm delivery. The authors studied pregnant women included in the Born in Guangzhou Cohort Study in China between February 2012 and June 2016. Maternal BP was measured at antenatal visits between 13 and 40 gestational weeks, and gestational age of delivery data was collected. The authors used linear mixed models to capture the BP trajectories of women with term, and spontaneous and iatrogenic preterm delivery. BP trajectories of women with various gestational lengths (34, 35, 36, 37, 38, 39, 40 weeks) were compared. Of the 17 426 women included in the analysis, 618 (3.55%) had spontaneous preterm delivery; 158 (.91%) had iatrogenic preterm delivery; and 16 650 (95.55%) women delivered at term. The BP trajectories were all J-shaped curves for different delivery types. Women with iatrogenic preterm delivery had the highest mean BP from 13 weeks till delivery, followed by those with spontaneous preterm delivery and term delivery (p .001). Trajectory analysis stratified by maternal parity showed similar results for nulliparous and multiparous women. Excluding women with pre-eclampsia and gestational hypertension (GH) significantly attenuated the aforementioned association. Also, women with shorter gestational length tend to have higher BP trajectories during pregnancy. In conclusion, Women with spontaneous preterm delivery have a higher BP from 13 weeks till delivery than women with term delivery, while women with iatrogenic preterm delivery have the highest BP.

ObjectivesTo assess the rates of SARS-CoV-2 positivity in babies born to mothers with SARS-CoV-2 infection, the timing of mother-to-child transmission and perinatal outcomes, and factors associated with SARS-CoV-2 status in offspring.DesignLiving systematic review and meta-analysis.Data sourcesMajor databases between 1 December 2019 and 3 August 2021.Study selectionCohort studies of pregnant and recently pregnant women (including after abortion or miscarriage) who sought hospital care for any reason and had a diagnosis of SARS-CoV-2 infection, and also provided data on offspring SARS-CoV-2 status and risk factors for positivity. Case series and case reports were also included to assess the timing and likelihood of mother-to-child transmission in SARS-CoV-2 positive babies.Data extractionTwo reviewers independently extracted data and assessed study quality. A random effects model was used to synthesise data for rates, with associations reported using odds ratios and 95% confidence intervals. Narrative syntheses were performed when meta-analysis was inappropriate. The World Health Organization classification was used to categorise the timing of mother-to-child transmission (in utero, intrapartum, early postnatal).Results472 studies (206 cohort studies, 266 case series and case reports; 28 952 mothers, 18 237 babies) were included. Overall, 1.8% (95% confidence interval 1.2% to 2.5%; 140 studies) of the 14 271 babies born to mothers with SARS-CoV-2 infection tested positive for the virus with reverse transcriptase polymerase chain reaction (RT-PCR). Of the 592 SARS-CoV-2 positive babies with data on the timing of exposure and type and timing of tests, 14 had confirmed mother-to-child transmission: seven in utero (448 assessed), two intrapartum (18 assessed), and five during the early postnatal period (70 assessed). Of the 800 SARS-CoV-2 positive babies with outcome data, 20 were stillbirths, 23 were neonatal deaths, and eight were early pregnancy losses; 749 babies were alive at the end of follow-up. Severe maternal covid-19 (odds ratio 2.4, 95% confidence interval 1.3 to 4.4), maternal death (14.1, 4.1 to 48.0), maternal admission to an intensive care unit (3.5, 1.7 to 6.9), and maternal postnatal infection (5.0, 1.2 to 20.1) were associated with SARS-CoV-2 positivity in offspring. Positivity rates using RT-PCR varied between regions, ranging from 0.1% (95% confidence interval 0.0% to 0.3%) in studies from North America to 5.7% (3.2% to 8.7%) in studies from Latin America and the Caribbean.ConclusionSARS-CoV-2 positivity rates were found to be low in babies born to mothers with SARS-CoV-2 infection. Evidence suggests confirmed vertical transmission of SARS-CoV-2, although this is likely to be rare. Severity of maternal covid-19 appears to be associated with SARS-CoV-2 positivity in offspring.Systematic review registrationPROSPERO CRD42020178076.Readers’ noteThis article is a living systematic review that will be updated to reflect emerging evidence. Updates may occur for up to two years from the date of original publication.

Background Stillbirth accounts for over 2 million deaths a year worldwide and rates remains stubbornly high. Multivariable prediction models may be key to individualised monitoring, intervention or early birth in pregnancy to prevent stillbirth. Objectives To collate and evaluate systematic reviews of factors associated with stillbirth in order to identify variables relevant to prediction model development. Search strategy MEDLINE, Embase, DARE and Cochrane Library databases and reference lists were searched up to November 2019. Selection criteria We included systematic reviews of association of individual variables with stillbirth without language restriction. Data collection and analysis Abstract screening and data extraction were conducted in duplicate. Methodological quality was assessed using AMSTAR and QUIPS criteria. The evidence supporting association with each variable was graded. Results The search identified 1198 citations. Sixty-nine systematic reviews reporting 64 variables were included. The most frequently reported were maternal age (n = 5), body mass index (n = 6) and maternal diabetes (n = 5). Uterine artery Doppler appeared to have the best performance of any single test for stillbirth. The strongest evidence of association was for nulliparity and pre-existing hypertension. Conclusion We have identified variables relevant to the development of prediction models for stillbirth. Age, parity and prior adverse pregnancy outcomes had a more convincing association than the best performing tests, which were PAPP-A, PlGF and UtAD. The evidence was limited by high heterogeneity and lack of data on intervention bias. Tweetable abstract Review shows key predictors for use in developing models predicting stillbirth include age, prior pregnancy outcome and PAPP-A, PLGF and Uterine artery Doppler.

Background Obstetric anal sphincter injuries (OASIS) are the commonest cause of anal incontinence in women of reproductive age. We determined the risk of anal sphincter defects diagnosed by ultrasound, and the risk of anal incontinence in (i) all women who deliver vaginally, (ii) in women without clinical suspicion of OASIS, and (iii) after primary repair of sphincter injury, by systematic review. Methods We searched major databases until June 2018, without language restrictions. Random effects meta-analysis was used to obtain pooled estimates of ultrasound diagnosed OASIS and risk of anal incontinence symptoms at various time points after delivery, and of persistent sphincter defects after primary repair. We reported the association between ultrasound diagnosed OASIS and anal incontinence symptoms using relative risk (RR) with 95 % CI. Results We included 103 studies involving 16,110 women. Of all women who delivered vaginally, OASIS were diagnosed on ultrasound in 26 % (95 %CI, 21–30, I2 = 91 %), and 19 % experienced anal incontinence (95 %CI, 14–25, I2 = 92 %). In women without clinical suspicion of OASIS (n = 3688), sphincter defects were observed in 13 % (10–17, I2 = 89 %) and anal incontinence experienced by 14 % (95 % CI: 6–24, I2 = 95 %). Following primary repair of OASIS, 55 % (46–63, I2 = 98 %) of 7549 women had persistent sphincter defect with 38 % experiencing anal incontinence (33–43, I2 = 92 %). There was a significant association between ultrasound diagnosed OASIS and anal incontinence (RR 3.74, 2.17−6.45, I2 = 98 %). Interpretation Women and clinicians should be aware of the high risk for sphincter defects following vaginal delivery even when clinically unsuspected. This underlines the need of careful and systematic perineal assessment after birth to mitigate the risk of missing OASIS. We also noted a high rate of persistent defects and symptoms following primary repair of OASIS. This dictates the need for provision of robust training for clinicians to achieve proficiency and sustain competency in repairing OASIS.

The COVID-19 pandemic has required rapid transformation and adaptation of healthcare services. Women with gestational diabetes mellitus (GDM) are one of the largest high-risk groups accessing antenatal care. In reformulating the care offered to those with GDM, there is a need to balance the sometimes competing requirement of lowering the risk of direct viral transmission against the potential adverse impact of service changes. We suggest pragmatic options for screening of GDM in a pandemic setting based on blood tests, and risk calculators applied to underlying risk factors. Alternative models for antenatal care provision for women with GDM, including targeting high-risk groups, early lifestyle interventions and remote monitoring are provided. Testing options and their timing for postpartum screening in women who had GDM are also considered. Our suggestions are only applicable in a pandemic scenario, and usual guidelines and care pathways should be re-implemented as soon as possible and appropriate.

Objective To describe the prevalence of and factors associated with different thyroid dysfunction phenotypes in women who are asymptomatic preconception. Design Observational cohort study. Setting A total of 49 hospitals across the United Kingdom between 2011 and 2016. Participants Women aged 16 to 41years with history of miscarriage or subfertility trying for a pregnancy. Methods Prevalences and 95% confidence intervals (CIs) were estimated using the binomial exact method. Multivariate logistic regression analyses were conducted to identify risk factors for thyroid disease. Intervention None. Main Outcome Measure Rates of thyroid dysfunction. Results Thyroid function and thyroid peroxidase antibody (TPOAb) data were available for 19213 and 19237 women, respectively. The prevalence of abnormal thyroid function was 4.8% (95% CI, 4.5-5.1); euthyroidism was defined as levels of thyroid-stimulating hormone (TSH) of 0.44 to 4.50 mIU/L and free thyroxine (fT4) of 10 to 21 pmol/L. Overt hypothyroidism (TSH > 4.50 mIU/L, fT4 < 10 pmol/L) was present in 0.2% of women (95% CI, 0.1-0.3) and overt hyperthyroidism (TSH < 0.44 mIU/L, fT4 > 21 pmol/L) was present in 0.3% (95% CI, 0.2-0.3). The prevalence of subclinical hypothyroidism (SCH) using an upper TSH concentration of 4.50 mIU/L was 2.4% (95% CI, 2.1-2.6). Lowering the upper TSH to 2.50 mIU/L resulted in higher rates of SCH, 19.9% (95% CI, 19.3-20.5). Multiple regression analyses showed increased odds of SCH (TSH > 4.50 mIU/L) with body mass index (BMI) ≥ 35.0 kg/m2 (adjusted odds ratio [aOR] 1.71; 95% CI, 1.13-2.57; P = 0.01) and Asian ethnicity (aOR 1.76; 95% CI, 1.31-2.37; P < 0.001), and increased odds of SCH (TSH ≥ 2.50 mIU/L) with subfertility (aOR 1.16; 95% CI, 1.04-1.29; P = 0.008). TPOAb positivity was prevalent in 9.5% of women (95% CI, 9.1-9.9). Conclusions The prevalence of undiagnosed overt thyroid disease is low. SCH and TPOAb are common, particularly in women with higher BMI or of Asian ethnicity. A TSH cutoff of 2.50 mIU/L to define SCH results in a significant proportion of women potentially requiring levothyroxine treatment.

Fibrinogen levels drop early in postpartum hemorrhage (PPH), and low fibrinogen levels predict outcomes. There is increasing interest in replacing fibrinogen early in severe PPH and this systematic review's aim was to assess if early fibrinogen replacement therapy improves outcomes in severe PPH. We searched the following databases from inception to June 2019: CDSR and CENTRAL (The Cochrane Library), MEDLINE, Embase, CINAHL, PubMed, Transfusion Evidence Library, LILACS, Web of Science Conference Proceedings Citation Index-Science, ClinicalTrials.gov and the WHO International Clinical Trials Registry Portal. We included randomized (RCT) and well-designed controlled observational studies where fibrinogen replacement therapy was given early (within 90 minutes of bleeding) compared with standard protocol in pregnant women > 24 weeks' gestation who developed PPH, defined as estimated blood loss ≥500 mL up to 24 hours post-delivery. Two independent reviewers extracted and reviewed the data on the primary outcome of allogeneic blood transfusion at 24 hours after intervention and secondary outcomes including all-cause mortality, rate of thrombosis, and the need for surgical and non-surgical interventions. We identified 5 eligible studies: 2 completed (total of 299 women) RCTs comparing fibrinogen concentrate with placebo, and 3 ongoing RCTs. There was no completed study assessing cryoprecipitate transfusion. There was variation of: timings of intervention administration; severity of PPH; fibrinogen doses and use of tranexamic acid. There was insufficient evidence that early administration of fibrinogen in PPH reduces the need for allogeneic blood transfusion at 24 hours (risk ratio 0.83 (95% CI 0.54-1.26), P = 0.38) (2 trials, 299 participants) or improves other outcomes. Both studies were underpowered to answer our outcomes. There is a lack of evidence that early fibrinogen replacement therapy improves outcomes in PPH. Future studies are needed to address this, underpinned by data on the optimal fibrinogen dose, protocol-driven approaches versus targeted therapy, and cost-effectiveness of cryoprecipitate versus fibrinogen concentrate therapy in PPH.

Background Lifestyle interventions (diet, physical activity and/or behavioural) to optimise gestational weight gain can prevent adverse maternal outcomes such as gestational diabetes, pre-eclampsia and caesarean section. Objective We aimed to model the cost effectiveness of lifestyle interventions during pregnancy on reducing adverse maternal outcomes. Methods Decision tree modelling was used to determine the cost effectiveness of lifestyle interventions compared with usual care on preventing cases of gestational diabetes and hypertensive disease in pregnancy. Participants were pregnant women receiving routine antenatal care in secondary and tertiary care hospitals. The main outcome measures were cases of gestational diabetes and/or hypertensive disease in pregnancy prevented, costs, and incremental cost-effectiveness ratios. Analysis was conducted from the perspective of the Australian healthcare system, with a time horizon of early pregnancy to discharge after birth. Results Women in the intervention group were 2.25% less likely to have gestational diabetes and/or hypertensive disease in pregnancy (9.53%) compared with the control group (11.78%). Intervention costs were Australian dollars (AUD) 228 per person. Costs were AUD33 per person higher in the intervention group (AUD8281) than the control group (AUD8248). The incremental cost-effectiveness ratio was AUD1470 per case prevented. Sensitivity analysis showed that base-case results were robust. In the probabilistic sensitivity analysis, 44.8% of data points fell within the north-east quadrant, and 52.2% in the south-east quadrant (cost saving), with a 95% confidence interval ranging from AUD − 50,018 to 32,779 per case prevented. Conclusions While there is no formally accepted cost-effectiveness threshold for willingness-to-pay to prevent an adverse maternal event, the cost per person receiving a lifestyle intervention compared with controls was close to neutral, and therefore likely to be cost effective. Exploration of the cost effectiveness of different lifestyle delivery modes across various models of antenatal care is now required. Future cost-effectiveness studies should investigate longer time horizons, quality-adjusted life-years and productivity loss. Trial Registration Not applicable. Electronic supplementary material The online version of this article (10.1007/s41669-020-00197-9) contains supplementary material, which is available to authorized users.

Polycystic ovary syndrome (PCOS) is a common, complex condition that affects up to 18% of reproductive- aged women, causing reproductive, metabolic and psychological dysfunctions. We performed an overview and appraisal of methodological quality of systematic reviews that assessed medical and surgical treatments for reproductive outcomes in women with PCOS. Databases (MEDLINE, EMBASE, CINAHL PLUS and PROSPERO) were searched on the 15th of September 2017. We included any systematic review that assessed the effect of medical or surgical management of PCOS on reproductive, pregnancy and neonatal outcomes. Eligibility assessment, data extraction and quality assessment by the Assessing the Methodological Quality of Systematic Reviews (AMSTAR) tool were performed in duplicate. We identified 53 reviews comprising 44 reviews included in this overview; the majority were moderate to high quality. In unselected women with PCOS, letrozole was associated with a higher live birth rate than clomiphene citrate (CC), while CC was better than metformin or placebo. In women with CC-resistant PCOS, gonadotrophins were associated with a higher live birth rate than CC plus metformin, which was better than laparoscopic ovarian drilling (LOD). LOD was associated with lower multiple pregnancy rates than other medical treatments. In women with PCOS undergo- ing in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI), the addition of metformin to gonadotro- phins resulted in less ovarian hyperstimulation syndrome (OHSS), and higher pregnancy and live birth rates than gonadotrophins alone. Gonadotrophin releasing hormone (GnRH) antagonist was associated with less OHSS, gonadotrophin units and shorter stimulation length than GnRH agonist. Letrozole appears to be a good first line treatment and gonadotrophins, as a second line treatment, for anovulatory women with PCOS. LOD results in lower multiple pregnancy rates. However, due to the heterogeneous nature of the included popula- tions of women with PCOS, further larger scale trials are needed with more precise assessment of treatments according to heterogeneous variants of PCOS.

GBS2 was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme (13/82/04). The funder had no role in the design and conduct of the study; the collection, management, analysis and interpretation of the data; the writing of the manuscript; or the decision to submit the manuscript for publication. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health and Social Care. JJD is supported by the NIHR Birmingham Biomedical Research Centre at the University Hospitals Birmingham NHS Foundation Trust and the University of Birmingham. KSK is a Distinguished Investigator funded by the Beatriz Galindo (senor modality) Program grant given to the University of Granada by the Ministry of Science, Innovation, and Universities of the Spanish Government., Background: Mother-to-baby transmission of group B Streptococcus (GBS) is the main cause of early-onset infection. We evaluated whether, in women with clinical risk factors for early neonatal infection, the use of point-ofcare rapid intrapartum test to detect maternal GBS colonisation reduces maternal antibiotic exposure compared with usual care, where antibiotics are administered due to those risk factors. We assessed the accuracy of the rapid test in diagnosing maternal GBS colonisation, against the reference standard of selective enrichment culture. Methods: We undertook a parallel-group cluster randomised trial, with nested test accuracy study and microbiological sub-study. UK maternity units were randomised to a strategy of rapid test (GeneXpert GBS system, Cepheid) or usual care. Within units assigned to rapid testing, vaginal-rectal swabs were taken from women with risk factors for vertical GBS transmission in established term labour. The trial primary outcome was the proportion of women receiving intrapartum antibiotics to prevent neonatal early-onset GBS infection. The accuracy of the rapid test was compared against the standard of selective enrichment culture in diagnosing maternal GBS colonisation. Antibiotic resistance profiles were determined in paired maternal and infant samples. Results: Twenty-two maternity units were randomised and 20 were recruited. A total of 722 mothers (749 babies) participated in rapid test units; 906 mothers (951 babies) were in usual care units. There was no evidence of a difference in the rates of intrapartum antibiotic prophylaxis (relative risk 1.16, 95% CI 0.83 to 1.64) between the rapid test (41%, 297/716) and usual care (36%, 328/906) units. No serious adverse events were reported. The sensitivity and specificity measures of the rapid test were 86% (95% CI 81 to 91%) and 89% (95% CI 85 to 92%), respectively. Babies born to mothers who carried antibiotic-resistant Escherichia coli were more likely to be colonised with antibiotic-resistant strains than those born to mothers with antibiotic-susceptible E. coli. Conclusion: The use of intrapartum rapid test to diagnose maternal GBS colonisation did not reduce the rates of antibiotics administered for preventing neonatal early-onset GBS infection than usual care, although with considerable uncertainty. The accuracy of the rapid test is within acceptable limits., National Institute for Health Research (NIHR) 13/82/04, NIHR Birmingham Biomedical Research Centre at the University Hospitals Birmingham NHS Foundation Trust University of Birmingham, Beatriz Galindo (senor modality) Program

Background: Existing evidence on the effects of race and ethnicity on pregnancy outcomes is restricted to individual studies done within specific countries and health systems. We aimed to assess the impact of race and ethnicity on perinatal outcomes in high-income and upper-middle-income countries, and to ascertain whether the magnitude of disparities, if any, varied across geographical regions. Methods: For this individual participant data (IPD) meta-analysis we used data from the International Prediction of Pregnancy Complications (IPPIC) Network of studies on pregnancy complications; the full dataset comprised 94 studies, 53 countries, and 4 539 640 pregnancies. We included studies that reported perinatal outcomes (neonatal death, stillbirth, preterm birth, and small-for-gestational-age babies) in at least two racial or ethnic groups (White, Black, south Asian, Hispanic, or other). For our two-step random-effects IPD meta-analysis, we did multiple imputations for confounder variables (maternal age, BMI, parity, and level of maternal education) selected with a directed acyclic graph. The primary outcomes were neonatal mortality and stillbirth. Secondary outcomes were preterm birth and a small-for-gestational-age baby. We estimated the association of race and ethnicity with perinatal outcomes using a multivariate logistic regression model and reported this association with odds ratios (ORs) and 95% CIs. We also did a subgroup analysis of studies by geographical region. Findings: 51 studies from 20 high-income and upper-middle-income countries, comprising 2 198 655 pregnancies, were eligible for inclusion in this IPD meta-analysis. Neonatal death was twice as likely in babies born to Black women than in babies born to White women (OR 2·00, 95% CI 1·44–2·78), as was stillbirth (2·16, 1·46–3·19), and babies born to Black women were at increased risk of preterm birth (1·65, 1·46–1·88) and being small for gestational age (1·39, 1·13–1·72). Babies of women categorised as Hispanic had a three-times increased risk of neonatal death (OR 3·34, 95% CI 2·77–4·02) than did those born to White women, and those born to south Asian women were at increased risk of preterm birth (OR 1·26, 95% CI 1·07–1·48) and being small for gestational age (1·61, 1·32–1·95). The effects of race and ethnicity on preterm birth and small-for-gestational-age babies did not vary across regions. Interpretation: Globally, among underserved groups, babies born to Black women had consistently poorer perinatal outcomes than White women after adjusting for maternal characteristics, although the risks varied for other groups. The effects of race and ethnicity on adverse perinatal outcomes did not vary by region. Funding: National Institute for Health and Care Research, Wellbeing of Women.

ObjectiveTo synthesise the evidence from studies that implemented interventions to increase/reintroduce the use of assisted vaginal births (AVB).DesignSystematic review.Eligibility criteriaWe included experimental, semi-experimental and observational studies that reported any intervention to reintroduce/increase AVB use.Data sourcesWe searched PubMed, EMBASE, CINAHL, LILACS, Scopus, Cochrane, WHO Library, Web of Science, ClinicalTrials.gov and WHO.int/ictrp through September 2021.Risk of biasFor trials, we used the Cochrane Effective Practice and Organisation of Care tool; for other designs we used Risk of Bias for Non-Randomised Studies of Interventions.Data extraction and synthesisDue to heterogeneity in interventions, we did not conduct meta-analyses. We present data descriptively, grouping studies according to settings: high-income countries (HICs) or low/middle-income countries (LMICs). We classified direction of intervention effects as (a) statistically significant increase or decrease, (b) no statistically significant change or (c) statistical significance not reported in primary study. We provide qualitative syntheses of the main barriers and enablers for success of the intervention.ResultsWe included 16 studies (10 from LMICs), mostly of low or moderate methodological quality, which described interventions with various components (eg, didactic sessions, simulation, hands-on training, guidelines, audit/feedback). All HICs studies described isolated initiatives to increase AVB use; 9/10 LMIC studies tested initiatives to increase AVB use as part of larger multicomponent interventions to improve maternal/perinatal healthcare. No study assessed women’s views or designed interventions using behavioural theories. Overall, interventions were less successful in LMICs than in HICs. Increase in AVB use was not associated with significant increase in adverse maternal or perinatal outcomes. The main barriers to the successful implementation of the initiatives were related to staff and hospital environment.ConclusionsThere is insufficient evidence to indicate which intervention, or combination of interventions, is more effective to safely increase AVB use. More research is needed, especially in LMICs, including studies that design interventions taking into account theories of behaviour change.PROSPERO registration numberCRD42020215224.

IntroductionWomen with gestational diabetes are at increased risk of developing type 2 diabetes later in life. In at-risk general populations, Mediterranean-style diet helps prevent type 2 diabetes. But its effect on postnatal women with a history of gestational diabetes is not known. Prior to a full-scale trial on Mediterranean-style diet in the postnatal period to prevent type 2 diabetes, a feasibility study is required to assess the acceptability of the diet and evaluate the trial processes.Methods and analysisMEditerranean diet for pReventIon of type 2 diabeTes is a single-arm feasibility study (65 women) with qualitative evaluation of women who have recently given birth and had gestational diabetes. The intervention is a Mediterranean-style diet supplemented with nuts and olive oil, with dietary advice and an action plan. A dedicated Health Coach will interact with participants through an interactive lifestyle App. Women will follow the intervention from 6 to 13 weeks post partum until 1 year post partum. The primary outcomes are rates of recruitment, follow-up, adherence and attrition. The secondary outcomes are maternal dysglycaemia, cost and quality of life outcomes, and acceptability of the intervention to participants, and to healthcare professionals delivering the intervention. Feasibility outcomes will be reported using descriptive statistics.Ethics and disseminationEthical approval was obtained through the South Central—Berkshire Research Ethics Committee (19/SC/0064). Study findings will be disseminated via publication in peer-reviewed journals, as well as via newsletters made available to participants and members of Katie’s Team (a women’s health patient and public advisory group).Trial registration numberISRCTN40582975.

There is an increase in maternal metabolic burden due to the rise in pregnancies complicated by obesity, gestational diabetes, type 2 diabetes and polycystic ovary syndrome. Metabolic dysfunction during pregnancy is associated with increased risks of long-term morbidity and mortality for women and their offspring. Lifestyle interventions in pregnancy in women at risk of metabolic dysfunction have demonstrated short-term improvements such as reduced gestational weight gain and lowered risk of gestational diabetes. It is not known whether these interventions lead to sustained improvements in the metabolic health of the mother and baby. Pharmacological interventions have also shown benefits for the mother and baby in pregnancy, including improvements in glycaemic control, reduction in gestational weight gain and reduction in large for gestational age infants; however, there remains uncertainty over long-term outcomes for mother and child. Existing studies on interventions targeting metabolic health are limited to selected populations in the preconception and postpartum periods and lack follow-up beyond delivery of the intervention. The COVID-19 pandemic has refocused our attention on the effects of maternal metabolic ill-health that play a role in contributing to premature morbidity and mortality. There is an urgent need for strategies to accurately identify the growing number of women and offspring at risk of long-term adverse metabolic health. Strategies which focus on early identification and risk stratification using individualised risk scores in the pre and inter-conception periods must take priority if we are to target and improve the metabolic health of women and their offspring who are at highest risk.

OBJECTIVE: Clinical trials evaluating pharmacological and non-pharmacological treatment of COVID-19, either excluded pregnant women or included very few women. Unlike the numerous systematic reviews on prevalence, symptoms and adverse outcomes of COVID-19 in pregnancy, there are very few on the effects of treatment on maternal and neonatal outcomes in pregnancy. We undertook a systematic review of all published and unpublished studies on the effects of pharmacological and non-pharmacological interventions for COVID-19 on maternal and neonatal pregnancy outcomes. DATA SOURCES: We performed a systematic literature search of the following databases: Medline, Embase, Cochrane database, WHO (World Health Organization) COVID-19 database, China National Knowledge Infrastructure (CNKI), and Wanfang databases from 1 December 2019 to 1 December 2020. STUDY ELIGIBILITY CRITERIA: Studies were only included if they involved pregnant or postnatal women who were exposed to pregnancy specific interventions like the mode of delivery and type of anaesthesia, pharmacological or non-pharmacological interventions. STUDY APPRAISAL AND SYNTHESIS METHODS: We first screened the titles and abstracts of studies and then assessed the full text of the selected studies in detail for eligibility. Data on study design, population, type of screening for COVID-19, country, hospital, country status (high or low and middle income), treatment given (mode of delivery, type of anaesthesia, type of pharmacological and non-pharmacological treatment was extracted. The pre-defined maternal outcomes we collected were mode of delivery (vaginal or by caesarean section), severe or critical COVID-19 (as defined by the authors), symptomatic COVID-19, maternal death, maternal hospital admission, ICU admission, mechanical ventilation, ECMO and maternal pneumonia. The pre-defined neonatal outcomes we extracted were preterm birth (

Background Obesity is a leading cause of preventable deaths from cardiometabolic diseases worldwide. About two-thirds of all individuals with obesity live in low- and middle-income countries (LMICs), facing an epidemiological transition from predominantly infectious to non-communicable diseases burden. The magnitude of sex-related disparities in the risk of obesity and cardiometabolic diseases in LMICs, and if these vary by region, country's income status, setting, and time is unclear. We undertook a systematic review and meta-analysis to assess the magnitude of sex-specific disparities in the prevalence of obesity and cardiometabolic diseases in LMICs, their burden on women, and variations by region, country's income status, setting, and time. Methods We searched MEDLINE and EMBASE (from inception to September 2021). Two independent reviewers selected the studies, assessed their quality, and performed data extraction. We used a random-effects model to obtain pooled estimates of odds ratios and 95% confidence interval (95%CI) for the association between sex and obesity and cardiometabolic diseases and rates of relevant outcomes. Results We included 287 studies (2,624,289 individuals). The risk of obesity was 2.72-fold (OR 2.72, 95% CI 2.54-2.91) higher in women than men, independent of age. The sex-specific disparities varied by World Bank region, with the greatest difference in Sub-Saharan Africa (OR 3.70, 95% CI 2.25-6.08), but it did not vary by the country's income status, setting, or overtime. There were no differences between the sexes in the type 2 diabetes or hypertension rates. Amongst women in LMICs, 22% (95% CI 0.20-0.24) had obesity, 27% (95% CI 0.24-0.30) hypertension, and 7% (95% CI 0.06-0.09) type 2 diabetes. The rates of obesity, hypertension and type 2 diabetes in women varied by region and country's income status, with the highest rates in the Middle East and North-Africa, and in upper-middle-income countries; obesity and type 2 diabetes rates were highest in urban settings. The odds of hypertension (OR 2.43, 95% CI 2.9-2.80) and type 2 diabetes (OR 2.84, 95% CI 2.16-3·74) were doubled in women with vs without obesity. Conclusions Women are disproportionately affected by obesity compared to men in LMICs, with the greatest disparity observed in the Sub-Saharan region. Obesity rates were consistently higher in women than men irrespective of the country's income status (low, low-middle, upper-middle), setting (rural, urban) or overtime. Amongst women, obesity and cardiometabolic diseases prevalence vary by World Bank region and country's income status. Obesity doubles the risk of hypertension and type 2 diabetes in women in LMICs. Our findings call for urgent sex-specific and region-stratified actions targeting obesity awareness, prevention, treatment, and control in women in LMICs. Implementing cost-effective and sustainable programmes specific to women and addressing obesity's burden should be an urgent public health priority in LMICs. Presentation: Saturday, June 11, 2022 1:12 p.m. - 1:17 p.m., Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m.

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Background: Cervical cerclage is a recognised treatment to prevent late miscarriage and pre-term birth (PTB). Emergency cervical cerclage (ECC) for cervical dilatation with exposed unruptured membranes is less common and the potential benefits of cerclage are less certain. A randomised control trial is needed to accurately assess the effectiveness of ECC in preventing pregnancy loss compared to an expectant approach.Methods: C-STICH2 is a multicentre randomised controlled trial in which women presenting with cervical dilatation and unruptured exposed membranes at 16+0 to 27+6 weeks gestation are randomised to ECC or expectant management. Trial design includes: 18 month internal pilot with embedded qualitative process evaluation; minimal data set; and a within-trial health economic analysis. Inclusion criteria are: ≥16 years, singleton pregnancy, exposed membranes at the external os, gestation 16+0-27+6 weeks, informed consent. Exclusion criteria are: contraindication to cerclage, cerclage in situ or previous cerclage in this pregnancy.Randomisation occurs via an online service in a 1:1 ratio, using a minimisation algorithm to reduce chance imbalances in key prognostic variables (site, gestation and dilatation). Primary outcome is pregnancy loss; a composite including miscarriage, termination of pregnancy and perinatal mortality defined as stillbirth and neonatal death in the first week of life. Secondary outcomes include all core outcomes for PTB. Two year development outcomes will be assessed using general health and Parent Report of Children's Abilities-Revised (PARCA-R) questionnaires. Intended sample size is 260 participants (130 each arm) based on 60% rate of pregnancy loss in the expectant management arm and 40% in the ECC arm, with 90% power and alpha 0.05. Analysis will be by intention-to-treat.Discussion: To date there has been one small trial of ECC in 23 participants which included twin and singleton pregnancies. This small trial along with the largest observational study (n=161) found ECC to prolong pregnancy duration and reduce deliveries before 34 weeks gestation. It is important to generate high quality evidence on the effectiveness of ECC in preventing pregnancy loss, and improve understanding of the prevalence of the condition and frequency of complications associated with ECC. An adequately powered RCT will provide the highest quality evidence regarding optimum care for these women and their babies. Trial registration: ISRCTN12981869 Registered on 13th June 2018

Background: The COVID-19 pandemic has had a profound impact on healthcare systems globally, with a worrying increase in adverse maternal and foetal outcomes. We aimed to assess the changes in maternity healthcare provision and healthcare-seeking by pregnant women during the COVID-19 pandemic.Methods: We performed a systematic review and meta-analysis of studies of the effects of the pandemic on provision of, access to and attendance at maternity services (CRD42020211753). We searched MEDLINE and Embase in accordance with PRISMA guidelines from January 1st, 2020 to April 17th 2021 for controlled observational studies and research letters reporting primary data comparing maternity healthcare-seeking and healthcare delivery during compared to before the COVID-19 pandemic. Case reports and series, systematic literature reviews, and pre-print studies were excluded. Meta-analysis was performed on comparable outcomes that were reported in two or more studies. Data were combined using random-effects meta-analysis, using risk ratios (RR) or incidence rate ratios (IRR) with 95% confidence intervals (CI).Findings: Of 4743 citations identified, 56 were included in the systematic review, and 21 in the meta-analysis. We identified a significant decrease in the number of antenatal clinic visits (IRR 0614, 95% CI 0486-0776, PInterpretation: Reduced maternity healthcare-seeking and healthcare provision during the COVID-19 pandemic has been global, and must be considered as potentially contributing to worsening of pregnancy outcomes observed during the pandemic.

Background The impact of maternal obesity extends beyond birth, being independently associated with an increased risk of child obesity. Current evidence demonstrates that women provided with a dietary intervention during pregnancy improve their dietary quality and have a modest reduction in gestational weight gain. However, the effect of this on longer-term childhood obesity-related outcomes is unknown. Methods We conducted an individual participant data meta-analysis from RCTs in which women with a singleton, live gestation between 10+0 and 20+0 weeks and body mass index (BMI) ≥ 25 kg/m2 in early pregnancy were randomised to a diet and/or lifestyle intervention or continued standard antenatal care and in which longer-term maternal and child follow-up at 3–5 years of age had been undertaken. The primary childhood outcome was BMI z-score above the 90th percentile. Secondary childhood outcomes included skinfold thickness measurements and body circumferences, fat-free mass, dietary and physical activity patterns, blood pressure, and neurodevelopment. Results Seven primary trials where follow-up of participants occurred were identified by a systematic literature search within the International Weight Management in Pregnancy (i-WIP) Collaborative Group collaboration, with six providing individual participant data. No additional studies were identified after a systematic literature search. A total of 2529 children and 2383 women contributed data. Approximately 30% of all child participants had a BMI z-score above the 90th percentile, with no significant difference between the intervention and control groups (aRR 0.97; 95% CI 0.87, 1.08; p=0.610). There were no statistically significant differences identified for any of the secondary outcome measures. Conclusions In overweight and obese pregnant women, we found no evidence that maternal dietary and/or lifestyle intervention during pregnancy modifies the risk of early childhood obesity. Future research may need to target the pre-conception period in women and early childhood interventions. Trial registration PROSPERO, CRD42016047165

Background Polycystic ovary syndrome (PCOS) is complex with reproductive, metabolic and psychological features. Infertility is a prevalent presenting feature of PCOS with approximately 75% of these women suffering infertility due to anovulation, making PCOS by far the most common cause of anovulatory infertility. Previous guidelines either lacked rigorous evidence-based processes, did not engage consumer and international multidisciplinary perspectives, or were outdated. Aims This review paper aims to provide a brief update on the best available and most current research evidence supporting the treatment of PCOS which informed the recommendations in the assessment and treatment of infertility section of the international evidence-based guideline on PCOS 2018. Materials and methods International evidence-based guideline development engaged professional societies and consumer organisations with multidisciplinary experts and women with PCOS directly involved at all stages. Results Lifestyle change alone is considered the first-line treatment for the management of infertile anovulatory PCOS women who are overweight or obese. Letrozole should now be considered first-line pharmacological treatment for ovulation induction to improve fertility outcomes. Clomiphene citrate alone and metformin alone could also be used as first-line pharmacological therapy, although both are less effective than letrozole and metformin is less effective than clomiphene citrate in obese women. Gonadotrophins or laparoscopic ovarian surgery are usually second-line ovulation induction therapies. In the absence of an absolute indication for in vitro fertilisation (IVF) / intracytoplasmic sperm injection, women with PCOS and anovulatory infertility could be offered IVF as third-line therapy where first- or second-line ovulation induction therapies have failed. Conclusion This review provides the best available evidence informing recommendations (along with clinical expertise and consumer preference) which provide clinicians with clear advice on best practice for the management of infertile women with PCOS.

Aims/hypothesis Gestational diabetes mellitus (GDM) is linked with a higher lifetime risk for the development of impaired fasting glucose, impaired glucose tolerance, type 2 diabetes, the metabolic syndrome, cardiovascular disease, postpartum depression and tumours. Despite this, there is no consistency in the long-term follow-up of women with a previous diagnosis of GDM. Further, the outcomes selected and reported in the research involving this population are heterogeneous and lack standardisation. This amplifies the risk of reporting bias and diminishes the likelihood of significant comparisons between studies. The aim of this study is to develop a core outcome set (COS) for RCTs and other studies evaluating the long-term follow-up at 1 year and beyond of women with previous GDM treated with insulin and/oral glucose-lowering agents. Methods The study consisted of three work packages: (1) a systematic review of the outcomes reported in previous RCTs of the follow-up at 1 year and beyond of women with GDM treated with insulin and/or oral glucose-lowering agents; (2) a three-round online Delphi survey with key stakeholders to prioritise these outcomes; and (3) a consensus meeting where the final COS was decided. Results Of 3344 abstracts identified and evaluated, 62 papers were retrieved and 25/62 papers were included in this review. A total of 121 outcomes were identified and included in the Delphi survey. Delphi round 1 was emailed to 835 participants and 288 (34.5%) responded. In round 2, 190 of 288 (65.9%) participants responded and in round 3, 165 of 190 (86.8%) participants responded. In total, nine outcomes were selected and agreed for inclusion in the final COS: assessment of glycaemic status; diagnosis of type 2 diabetes since the index pregnancy; number of pregnancies since the index pregnancy; number of pregnancies with a diagnosis of GDM since the index pregnancy; diagnosis of prediabetes since the index pregnancy; BMI; post-pregnancy weight retention; resting blood pressure; and breastfeeding. Conclusions/interpretation This study identified a COS that will help bring consistency and uniformity to outcome selection and reporting in clinical trials and other studies involving the follow-up at 1 year and beyond of women diagnosed with GDM treated with insulin and/or oral glucose-lowering agents during pregnancy. Electronic supplementary material The online version of this article (10.1007/s00125-019-4935-9) contains peer-reviewed but unedited supplementary material, which is available to authorised users.

OBJECTIVE: To determine the effects on the vaginal microbiota of an oral probiotic preparation administered from early pregnancy. \ud \ud DESIGN: Randomised, double blind, placebo-controlled trial. \ud \ud SETTING: Four maternity units in the UK. \ud \ud POPULATION: Women aged 16 years or older recruited at 9-14 weeks' gestation. \ud \ud METHODS: Participants were randomly allocated to receive oral capsules of probiotic containing Lactobacillus rhamnosus GR-1 and Lactobacillus reuteri RC-14 each at 2.5 × 109 colony-forming units (CFUs) or placebo once daily from recruitment until the end of pregnancy. \ud \ud MAIN OUTCOME MEASURE: Rates of bacterial vaginosis (BV, defined as Nugent score ≥7) at 18-20 weeks' gestation compared by logistic regression adjusted for possible confounders. \ud \ud RESULTS: The primary analysis included 78% (238/304) of participants who initially consented (probiotic group 123, placebo group 115). Of these participants, 95% (227/238) reported an intake of 93% or more of the required number of capsules. The rates of BV did not differ between groups at 18-20 weeks' gestation (15% (19/123) in the probiotic group vs. 9% (10/115) in the placebo group, adjusted odds ratio 1.82, 95% confidence interval 0.64-5.19). There were also no differences between the groups in the proportion of women colonised with the probiotic strains, Escherichia coli, Group B streptococci or other vaginal microbiota. There were no differences in the alpha diversity or composition of the bacterial communities between or within the probiotic and placebo groups at 9-14 and 18-20 weeks' gestation. \ud \ud CONCLUSIONS: Oral probiotics taken from early pregnancy did not modify the vaginal microbiota. \ud \ud TWEETABLE ABSTRACT: The oral probiotic preparation used in this study does not prevent BV in pregnant women.

Background Pre-eclampsia affects around 2–3% of all pregnancies, and is associated with potential serious complications for the woman and the baby. Once diagnosed, progression of the syndrome can be unpredictable, and decisions around timing of delivery need to take into account evolving maternal complications and perinatal morbidity. Novel prognostic models and blood biomarkers for determination of need for delivery in pregnancies with pre-eclampsia are now emerging. Objective The objective of the study was to establish a prognostic model to inform optimal timing of delivery in women with late preterm pre-eclampsia (34+ 0 to 36+ 6 weeks’ gestation), comparing novel candidate biomarkers (e.g. placental growth factor) with clinical and routinely collected blood/urinary parameters [incorporated into the PREP-S (Prediction models for Risk of Early-onset Pre-eclampsia – Survival) model] to determine clinically indicated need for delivery for pre-eclampsia (or related complications) within 7 days of assessment. Methods Prospective recruitment of women in whom blood samples for placental growth factor and soluble fms-like tyrosine kinase-1 testing was obtained, alongside clinical data, for use within the PREP-S model. Candidate variables were compared using standard methods (sensitivity, specificity, receiver operator curve areas). Estimated probability of early delivery from PREP-S was compared with actual event rates by calibration. Setting The PEACOCK (Prognostic indicators of severe disEAse in women with late preterm pre-eClampsia tO guide deCision maKing on timing of delivery) study was a prospective cohort study, nested within the PHOENIX (Pre-eclampsia in HOspital: Early iNductIon or eXpectant management) trial. Participants Women between 34+ 0 and 36+ 6 weeks’ gestation, with a diagnosis of pre-eclampsia, in whom a plasma (ethylenediaminetetraacetic acid) blood sample for placental growth factor testing was obtained, alongside clinical data for the assessment of variables in a prognostic model. Main outcome measures Clinically indicated need for delivery for pre-eclampsia within 7 days of assessment. Statistical analysis: both PREP-S and placental growth factor were assessed and compared using standard methods (sensitivity and specificity for placental growth factor thresholds of 100 pg/ml and Results Between 27 April 2016 and 24 December 2018, 501 women were recruited to the study. Although placental growth factor testing had high sensitivity (97.9%) for delivery within 7 days, the negative predictive value was only 71.4% and the specificity was low (8.4%). The area under the curve for the clinical prediction model (PREP-S) and placental growth factor in this cohort in determining need for delivery within 7 days was 0.64 (standard error 0.03) and 0.60 (standard error 0.03), respectively, and 0.65 (standard error 0.03) in combination. Limitations A high proportion of women in this cohort already had low placental growth factor concentrations at the time of confirmed diagnosis, which reduced the ability of the biomarker to further predict adverse outcomes. Conclusions In this group of women with late preterm pre-eclampsia, placental growth factor measurement is not likely to add to the current clinical assessment to help plan care for late preterm pre-eclampsia regarding timing of delivery. Existing models developed in women with early-onset pre-eclampsia to predict complications cannot be used to predict clinically indicated need for delivery in women with late preterm pre-eclampsia. Future work Further statistical modelling and subgroup analysis is being considered to assess if improved model performance in the whole cohort or a subgroup can be achieved. Addition of other biomarkers to the model may also be of use and will be explored. Trial registration Current Controlled Trials ISRCTN01879376. Funding This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 25, No. 30. See the NIHR Journals Library website for further project information.

Bassel Al Wattar holds a personal Academic Clinical Lectureship from the UK National Health Institute of Research. Khalid Khan is a Distinguished Investigator funded by the Beatriz Galindo (senior modality) Program Grant given to the University of Granada by the Ministry of Science, Innovation, and Universities of the Spanish Government., BACKGROUND: Cesarean delivery is the most common surgical procedure worldwide. Intrapartum fetal surveillance is routinely offered to improve neonatal outcomes, but the effects of different methods on the risk of emergency cesarean deliveries remains uncertain. We conducted a systematic review and network meta-analysis to evaluate the effectiveness of different types of fetal surveillance. METHODS: We searched MEDLINE, Embase and CENTRAL until June 1, 2020, for randomized trials evaluating any intrapartum fetal surveillance method. We performed a network meta-analysis within a frequentist framework. We assessed the quality and network inconsistency of trials. We reported primarily on intrapartum emergency cesarean deliveries and other secondary maternal and neonatal outcomes using risk ratios (RRs) and 95% confidence intervals (CIs). RESULTS: We included 33 trials (118 863 patients) evaluating intermittent auscultation with Pinard stethoscope/handheld Doppler (IA), cardiotocography (CTG), computerized cardiotocography (cCTG), CTG with fetal scalp lactate (CTG-lactate), CTG with fetal scalp pH analysis (CTG-FBS), CTG with fetal pulse oximetry (FPO-CTG), CTG with fetal heart electrocardiogram (CTG-STAN) and their combinations. Intermittent auscultation reduced the risk of emergency cesarean deliveries compared with other types of surveillance (IA v. CTG: RR 0.83, 95% CI 0.72-0.97; IA v. CTG-FBS: RR 0.71, 95% CI 0.63-0.80; IA v.CTG-lactate: RR 0.77, 95% CI 0.64-0.92; IA v. FPO-CTG: RR 0.75, 95% CI 0.65-0.87; IA v.FPO-CTG-FBS: RR 0.81, 95% CI 0.67-0.99; cCTG-FBS v. IA: RR 1.21, 95% CI 1.04-1.42), except STAN-CTG-FBS (RR 1.17, 95% CI 0.98-1.40). There was a similar reduction observed for emergency cesarean deliveries for fetal distress. None of the evaluated methods was associated with a reduced risk of neonatal acidemia, neonatal unit admissions, Apgar scores or perinatal death. INTERPRETATION: Compared with other types of fetal surveillance, intermittent auscultation seems to reduce emergency cesarean deliveries in labour without increasing adverse neonatal and maternal outcomes., Beatriz Galindo (senior modality) Program Grant by Ministry of Science, Innovation, and Universities of the Spanish Government

AIMS To develop a core outcome set for trials investigating interventions to prevent stillbirth. MATERIALS & METHODS Outcomes identified from a systematic literature review and semi-structured interviews with parents in Australia and the UK were entered into a two-round online Delphi survey and focus group/consensus meetings. RESULTS A core outcome set containing 11 outcomes in two categories. Five outcomes were related to the mother; fetal loss, onset of and mode of delivery, maternal mortality or near miss, psychological and social impact on the women, women's knowledge. Six outcomes were related to the baby; timing of stillbirth, neonatal mortality, gestational age at delivery, birthweight, congenital anomaly, NICU/SCBU or other higher-level neonatal care length of stay. CONCLUSIONS Implementation and dissemination of this core outcome set in future trials will contribute towards coordinated outcome reporting and advancing usefulness of research to guide clinical practice.