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INTRODUCTION: Increasing the midwifery workforce has been identified as an evidence-based approach to decrease maternal mortality and reproductive health disparities worldwide. Concurrently, the profession of midwifery, as with all healthcare professions, has undergone a significant shift in practice with acceleration of telehealth use to expand access. We conducted a systematic literature review to identify and synthesize the existing evidence regarding how midwives experience, perceive and accept providing sexual and reproductive healthcare services at a distance with telehealth. METHODS: Five databases were searched, PubMed, CINHAL, PsychInfo, Embase and the Web of Science, using search terms related to midwives, telehealth and experience. Peer-reviewed studies with quantitative, qualitative or mixed methods designs published in English were retrieved and screened. Studies meeting the inclusion criteria were subjected to full-text data extraction and appraisal of quality. Using a convergent approach, the findings were synthesized into major themes and subthemes. RESULTS: After applying the inclusion/exclusion criteria, 10 articles on midwives experience of telehealth were reviewed. The major themes that emerged were summarized as integrating telehealth into clinical practice; balancing increased connectivity; challenges with building relationships via telehealth; centring some patients while distancing others; and experiences of telehealth by age and professional experience. CONCLUSIONS: Most current studies suggest that midwives experience of telehealth is deeply intertwined with midwives experience of the response to COVID-19 pandemic in general. More research is needed to understand how sustained use of telehealth or newer hybrid models of telehealth and in-person care are perceived by midwives.

This EBCOG guidance reviews the current and future status of genomics within fetal and maternal medicine. This document addresses the clinical uses of genetic testing in both screening and diagnostic testing prenatally. The role of genomics within fetal and maternal medicine is described. The research and future implications of genetic testing as well as the educational, ethical and economic implications of genomics are discussed. [ABSTRACT FROM AUTHOR]

Objective: In the present study we aimed to review the evolution and function of the maternal medicine multidisciplinary team (MMMDT) meeting of a maternal medicine service of a tertiary level stand‐alone maternity hospital. Methods: We conducted a retrospective descriptive study of all minutes of MMMDT meetings from 2014 to 2020, with the aim of evaluating meeting characteristics and patient demographics. Results: There were 575 multidisciplinary team (MDT) discussions of 486 women during 43 meetings in the 7 year period. On average, 13 (range 3–23; SD = 5.28) women were discussed at each meeting, attended by 17 (range: 11–27; SD = 4.26) attendees. There were 18 women discussed during successive pregnancies. When analyzing the 2017–2020 data, preconceptual discussions made up 7.3% (n = 42) of patients discussed, with 5.7% (n = 33) being postnatal. The mean maternal age was 32.5 years (range 15–48 years) and women were most likely to be discussed in the mid‐trimester period (21–24 weeks gestation). The top five primary specialities involved were hematology, neurology, rheumatology, neurosurgery and gastroenterology; however, 22 specialities were represented overall when classified by the primary medical condition. When examining the MDT input, hematology input was required in 144 patients (25.0%), radiology in 161 (28.0%) patients, and 117 in anesthesiology (20.3%). When examining the number of teams required to manage the patient, 80 women required the input of three specialities, with 16 women requiring the input of four specialities. Conclusion: We demonstrate the value and role of the MDT in the management of complex patients, providing a forum to discuss care in all phases of the obstetric journey. Synopsis: The maternal medicine MDT has evolved to become an essential part of practice, caring from women throughout the reproductive cycle. [ABSTRACT FROM AUTHOR]

Objective: To study the adverse maternal and perinatal outcomes in women with severe pre‐eclampsia (SPE) among different ranges of proteinuria. Methods: This prospective cohort study was conducted in Jawaharlal Institute of Postgraduate Medical Education and Research, India. After obtaining informed written consent, the 202 singleton women fulfilling the criteria of severe features of pre‐eclampsia were stratified based on the value of urine protein‐creatinine ratio (UPCR) as mild, moderate, severe, and massive proteinuria during pregnancy. Clinical outcomes were assessed and patients were followed up until 12 weeks postpartum to identify persistent proteinuria and hypertension. Results: Of the 202 women with SPE, adverse maternal outcomes were seen in 34.65% (n = 70) and adverse perinatal outcomes in 75.74% (n = 153). The demographic and clinical factors were similar among women with increasing severity of proteinuria, except for mean systolic blood pressure, serum creatinine and total serum protein. UPCR was found to have a significant correlation with composite adverse perinatal outcome (P < 0.001) and individual outcomes of neonatal intensive care unit admission for >48 h (P = 0.01) and neonatal sepsis (P = 0.02) but not adverse maternal outcomes (P = 0.201). The optimum UPCR cutoff for adverse perinatal outcomes was 1.6 (sensitivity, 73.2%; specificity, 52.7%). In addition, 14.85% of the women had a persistently elevated UPCR and 3.96% had hypertension at 3 months postpartum. Conclusion: In women with SPE, severe and massive proteinuria were related to composite adverse perinatal outcome but not composite adverse maternal outcome. Moreover, antenatal 24‐h proteinuria was significantly associated with persistent proteinuria. Significant proteinuria in women with SPE poses a risk for chronic renal dysfunction, requiring follow‐up. Synopsis: In women with severe pre‐eclampsia, high antenatal proteinuria was associated with adverse perinatal outcomes and persistent proteinuria, requiring long‐term renal follow‐up. [ABSTRACT FROM AUTHOR]

Background Obstetricians often times find themselves in a conflict of right and duty with their patients, when these patients refuse recommended treatment. On the one hand, the obstetrician, aiming to fulfil the duty of care, recommends a treatment in the best interest of the woman. The woman, on the other hand, exercising her right of self-determination and autonomy, declines the recommended treatment. Materials and Methods A search was conducted for literature, articles and case reports on the subject on PubMed/MEDLINE and Google Scholar using the keywords: medical ethics, medical law, obstetric mortality, maternal medicine, foetal medicine, patient autonomy, informed consent, right to life and right to liberty. Results Opinions have historically differed on whether maternal or foetal rights should be deferred to in situations where pregnant women refuse obstetric interventions. So also have legal decisions on the issue. The general consensus is, however, to respect a woman's refusal of recommended medical treatment, in deference to her right of self-determination and autonomy. The obstetric outcomes in such instances are however, often times, unfavourable. Conclusion The ethics of patient care in the face of conflicting rights deserves renewed examination and discourse. [ABSTRACT FROM AUTHOR]

ObjectiveTo evaluate neuromotor repertoires and developmental milestones in infants exposed to antenatal COVID-19.DesignLongitudinal cohort study.SettingHospital-based study in Los Angeles, USA and Rio de Janeiro, Brazil between March 2020 and December 2021.ParticipantsInfants born to mothers with COVID-19 during pregnancy and prepandemic control infants from the Graz University Database.InterventionsGeneral movement assessment (GMA) videos between 3 and 5 months post-term age were collected and clinical assessments/developmental milestones evaluated at 6-8 months of age. Cases were matched by gestational age, gender and post-term age to prepandemic neurotypical unexposed controls from the database.Main outcome measuresMotor Optimality Scores Revised (MOS-R) at 3-5 months. Presence of developmental delay (DD) at 6-8 months.Results239 infants were enrolled; 124 cases (83 in the USA/41 in Brazil) and 115 controls. GMA was assessed in 115 cases and 115 controls; 25% were preterm. Median MOS-R in cases was 23 (IQR 21-24, range 9-28) vs 25 (IQR 24-26, range 20-28) in controls, p

PurposePregnant and postpartum women living with HIV in South Africa are at high risk of dropping out of care, particularly after delivery. Population mobility may contribute to disruptions in HIV care, and postpartum women are known to be especially mobile. To improve engagement in HIV care during the peripartum period, we developed CareConekta, a smartphone application (app) that uses GPS coordinates to characterise mobility and allow for real-time intervention. We conducted a randomised controlled pilot study to assess feasibility, acceptability and initial efficacy of the app intervention to improve engagement in HIV care. This cohort profile describes participant enrolment and follow-up, describes the data collected and provides participant characteristics.ParticipantsWe enrolled 200 pregnant women living with HIV attending routine antenatal care at the Gugulethu Midwife Obstetric Unit in Cape Town, South Africa. Eligible women must have owned smartphones that met the app's technical requirements. Seven participants were withdrawn near enrolment, leaving 193 in the cohort.Findings to dateData were collected from detailed participant questionnaires at enrolment and follow-up (6 months after delivery), as well as GPS data from the app, and medical records. Follow-up is complete; initial analyses have explored smartphone ownership, preferences and patterns of use among women screened for eligibility and those enrolled in the study.Future plansAdditional planned analyses will characterise mobility in the population using the phone GPS data and participant self-reported data. We will assess the impact of mobility on engagement in care for the mother and infant. We also will describe the acceptability and feasibility of the study, including operational lessons learnt. By linking this cohort to the National Health Laboratory Service National HIV Cohort in South Africa, we will continue to assess engagement in care and mobility outcomes for years to come. Collaborations are welcome.Trial registration numberNCT03836625.

ObjectivesTo describe face mask use among pregnant women seeking antenatal care (ANC) in Kinshasa, Democratic Republic of Congo and to identify factors associated with masking adherence in this population.DesignFacility-based cross-sectional study nested within a prospective cohort study.SettingRandom sample of 10 health facilities, including 5 primary health centers and 5 secondary facilities or hospitals.ParticipantsA total of 934 pregnant women aged 18 years or above with a gestational age of at least 32 weeks were consecutively surveyed from 17 August 2020 to 31 January 2021.Primary and secondary outcome measuresWe estimated the proportions of pregnant women wearing a face mask and masking correctly (ie, over the mouth and nose), and assessed their knowledge regarding the COVID-19 pandemic. Multivariable logistic regression was employed to identify factors associated with overall and correct face mask use.ResultsOverall, 309 (33.1%) women wore a mask during the interview after their antenatal appointments, but only 33 (10.7%) wore a mask correctly. The odds of masking and correct mask use were significantly higher among women who had their ANC visit in a facility that provided COVID-19 care. Additionally, women who experienced COVID-19-like symptoms in the past 6 months had higher odds of wearing a mask correctly compared with those reporting no recent symptoms. Although 908 (97.2%) women were aware of the COVID-19 pandemic, only 611 (67.3%) thought that COVID-19 was circulating locally in Kinshasa.ConclusionOverall and correct face mask adherence levels were low among pregnant women attending ANC in Kinshasa. Our study highlights the need for improving adherence to correct face mask use in order to help control the spread of COVID-19 within Kinshasa alongside other control measures, like vaccination.

Venous thromboembolism (VTE) remains the leading cause of direct maternal death in the UK, despite the widespread use of personalised risk-stratified thromboprophylaxis in pregnancy. The primary risk factors associated with VTE are increasingly common, namely obesity, medical comorbidities and maternal age. Therefore, it is imperative that all clinicians seeing pregnant patients acutely can adequately assess, investigate and treat possible VTE. Clinical diagnosis of VTE is challenging due to its non-specific symptoms that mirror obstetric physiology. This article will consider the management of deep vein thrombosis (DVT), pulmonary embolism (PE) and cerebral venous thrombosis (CVT). Universally, prompt imaging and anticoagulation are required. The support of obstetric, haematology, medical, radiology and anaesthetic specialists is imperative for the complex or critically ill patient. Thrombolysis should be considered with massive PE associated with haemodynamic instability and not withheld due to pregnancy. Critically, these patients require multidisciplinary plans for delivery, contraception and future pregnancy. [ABSTRACT FROM AUTHOR]

Abstract Background Maternal hormonal contraception use has been associated with an increased risk of leukaemia and central nervous system (CNS) tumours in children. However, little is known about the association with other, less common childhood cancer types. We assessed associations between maternal hormonal contraceptive use and all main types of childhood cancer, excluding leukaemia and CNS tumours. Methods In this nationwide PECH cohort study, we followed all Danish children liveborn in 1996–2014 (n = 1 185 063) from birth until 2018. Registry information was extracted on maternal filled prescriptions of hormonal contraception and childhood cancer diagnoses (age at diagnosis

ObjectivesGlobally, hundreds of women die daily from preventable pregnancy-related causes, with the greatest burden in sub-Saharan Africa. Five key emergencies-bleeding, infections, high blood pressure, delivery complications and unsafe abortions-account for nearly 75% of these obstetric deaths. Skilled clinicians with strategic supplies could prevent most deaths. In this study, we (1) measured facility readiness to manage common obstetric emergencies using the clinical cascades and signal function tracers; (2) compared these readiness estimates by facility characteristics; and (3) measured cascading drop-offs in resources.DesignA facility-based cross-sectional analysis of resources for common obstetric emergencies.SettingData were collected in 2016 from 23 hospitals (10 designated comprehensive emergency obstetric care (CEmOC) facilities) in Migori County, western Kenya, and Busoga Region, eastern Uganda, in the Preterm Birth Initiative study in East Africa. Baseline data were used to estimate a facility's readiness to manage common obstetric emergencies using signal function tracers and the clinical cascade model. We compared emergency readiness using the proportion of facilities with tracers (signal functions) and the proportion with resources for identifying and treating the emergency (cascade stages 1 and 2).ResultsThe signal functions overestimated practical emergency readiness by 23 percentage points across five emergencies. Only 42% of CEmOC-designated facilities could perform basic emergency obstetric care. Across the three stages of care (identify, treat and monitor-modify) for five emergencies, there was a 28% pooled mean drop-off in readiness. Across emergencies, the largest drop-off occurred in the treatment stage. Patterns of drop-off remained largely consistent across facility characteristics.ConclusionsAccurate measurement of obstetric emergency readiness is a prerequisite for strengthening facilities' capacity to manage common emergencies. The cascades offer stepwise, emergency-specific readiness estimates designed to guide targeted maternal survival policies and programmes.Trial registration numberNCT03112018.

Background Induction of labor is performed for either maternal or fetal indications to reduce perinatal morbidity and mortality without increasing maternal morbidity. The aim of this study was to review the scientific literature regarding induction of labor in patients with full-term pregnancy and create a systematic review of the literature to answer the question: “In patients with full-term gestation - does combining the Foley balloon with dinoprostone for the artificial induction of labor - offer better perinatal results over time from the application of the labor induction method until birth?”. Methods A literature search was performed on 23/08/2023 in the PubMed database; only articles published within the past 5 years were considered. We included articles in which labor was triggered with a vaginal device with dinoprostone, oxytocin, and/or a Foley catheter in full-term patients who met the following criteria: monofetal pregnancy, cranial presentation, intact membranes, and no history of uterine scar. We used the keywords “induction,” “labour,” “term,” “Foley,” “dinoproston,” “oxytocin.” Results The Pubmed database currently has approximately 20,000 scientific papers about labor induction. Only two studies met the proposed criteria. Considering the small volume of eligible data for the proposed research, the main meta-analysis addressing the topic was also considered. Conclusions The use of dinoprostone and oxytocin infusion is effective for triggering labor under conditions of compliance with obstetrical indications and pharmacological characteristics. Studies that compare the success of artificial induction of labor with Foley balloon and Foley+dinoprostone in patients with full term gestation are limited, but nevertheless, the association of Foley balloon with artificial induction with dinoprostone seems to be a cost-effective method. The limited number of scientific studies on this topic determines a risk of bias, inconsistency and imprecision, and for the future, we propose to carry out a randomized prospective study to study the topic.

Abstract Introduction Anaemia during pregnancy is a significant global health problem, disproportionately affecting women in low‐ and middle‐income countries (LMICs). Oral iron is the standard of care; however, challenges exist regarding adherence and coverage. Increasingly, evidence demonstrates the superiority of intravenous (IV) iron over oral iron. Although clinical experience on IV iron for antenatal anaemia is growing, there remains little understanding regarding implementation. Our mixed‐method systematic review aims to identify barriers and facilitators to implementing an IV iron intervention for pregnant women with anaemia and implementation strategies. Methods Five bibliographic databases and grey literature were searched for studies. Barriers and facilitators were identified and mapped to the Consolidated Framework for Implementation Research (CFIR) and then matched to Expert Recommendations for Implementing Change (ERIC) strategies using the CFIR‐ERIC matching tool. Results The search identified six studies. Most studies captured the perspective of healthcare providers, with some studies capturing the perspective of pregnant women. Barriers and facilitators were mapped to the following CFIR constructs: (1) intervention characteristics—cost, complexity, evidence strength and quality, and relative advantage; (2) outer setting—patient needs and resources; (3) inner setting—culture, available resources and access to knowledge and information; (4) characteristics of individuals—knowledge and beliefs about the intervention; (5) process—champions. Matching ERIC strategies included identifying and preparing champions, conducting educational meetings and assessing for readiness and identifying barriers and facilitators. Conclusion Once tailored to each context, our findings can be used to improve the adoption, implementation, and sustainability of an IV iron programme for pregnant women with anaemia.

Abstract Background Breech presentation is observed in 3–4% at term of pregnancy and is one of the leading causes of cesarean section. There is no established treatment for breech presentation before 36 weeks. A retrospective cohort study was conducted to demonstrate that the lateral position is effective for breech presentation. However, there are no randomized controlled trials evaluating lateral position management for breech presentation. Here, we described the methodology of a randomized controlled trial of a cephalic version for breech presentation in the third trimester by lateral postural management (BRLT study). Methods The BRLT study is an open-label, randomized controlled trial with two parallel groups allocated in a 1:1 ratio to examine the lateral position management for breech presentation, as compared with expectant management care. An academic hospital in Japan will enroll 200 patients diagnosed with a breech presentation by ultrasonography between 28 + 0 weeks and 30 + 0 weeks. Participants in the intervention group will be instructed to lie on their right sides for 15 min three times per day if the fetal back was on the left side or lie on their left sides if the fetal back was on the right side. The instruction will be given every 2 weeks after confirmation of fetal position, and the lateral position will be instructed until the cephalic version, and after the cephalic version, the reverse lateral position will be instructed until delivery. The primary outcome is cephalic presentation at term. The secondary outcomes are cesarean delivery, cephalic presentation 2, 4, and 6 weeks after the instruction, and at delivery, recurrent breech presentation after cephalic version, and adverse effects. Discussion This trial will answer whether the lateral positioning technique is effective in treating breech presentation and, depending on the results, may provide a very simple, less painful, and safe option for treating breech presentation before 36 weeks, and it may impact breech presentation treatment. Trial registration UMIN Clinical Trials Registry UMIN000043613. Registered on 15 March 2021 https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000049800 .

Abstract Introduction To estimate the association between the severity of maternal SARS‐CoV2 disease and adversity of maternal and neonatal outcomes. Methods A retrospective single‐site descriptive study was conducted, where the records of pregnant women, universally screened for COVID‐19 infection, with laboratory‐confirmed SARS‐CoV2 disease during the period from March 2020 to March 2021 were reviewed. Patients were divided into two groups: an asymptomatic/mild disease group and a moderate/severe disease group. Maternal outcomes, including the incidence of pregnancy‐induced hypertension (PIH)/pre‐eclampsia, cesarean section (CS) rates, maternal intensive care unit (ICU) admission rates, and neonatal outcomes, including preterm birth, low birth weight, and neonatal ICU (NICU) admission rates, were compared in both study groups. Results A total of 352 patients were included with 87 (24.7%) having a moderate/severe disease. In this group, the incidence of preterm birth (

Abstract Background Sub-optimal medication adherence in pregnant women with chronic disease and pregnancy-related indications has the potential to adversely affect maternal and perinatal outcomes. Adherence to appropriate medications is advocated during and when planning pregnancy to reduce risk of adverse perinatal outcomes relating to chronic disease and pregnancy-related indications. We aimed to systematically identify effective interventions to promote medication adherence in women who are pregnant or planning to conceive and impact on perinatal, maternal disease-related and adherence outcomes. Methods Six bibliographic databases and two trial registries were searched from inception to 28th April 2022. We included quantitative studies evaluating medication adherence interventions in pregnant women and women planning pregnancy. Two reviewers selected studies and extracted data on study characteristics, outcomes, effectiveness, intervention description (TIDieR) and risk of bias (EPOC). Narrative synthesis was performed due to study population, intervention and outcome heterogeneity. Results Of 5614 citations, 13 were included. Five were RCTs, and eight non-randomised comparative studies. Participants had asthma (n = 2), HIV (n = 6), inflammatory bowel disease (IBD; n = 2), diabetes (n = 2) and risk of pre-eclampsia (n = 1). Interventions included education +/− counselling, financial incentives, text messaging, action plans, structured discussion and psychosocial support. One RCT found an effect of the tested intervention on self-reported antiretroviral adherence but not objective adherence. Clinical outcomes were not evaluated. Seven non-randomised comparative studies found an association between the tested intervention and at least one outcome of interest: four found an association between receiving the intervention and both improved clinical or perinatal outcomes and adherence in women with IBD, gestational diabetes mellitus (GDM), and asthma. One study in women with IBD reported an association between receiving the intervention and maternal outcomes but not for self-reported adherence. Two studies measured only adherence outcomes and reported an association between receiving the intervention and self-reported and/or objective adherence in women with HIV and risk of pre-eclampsia. All studies had high or unclear risk of bias. Intervention reporting was adequate for replication in two studies according to the TIDieR checklist. Conclusions There is a need for high-quality RCTs reporting replicable interventions to evaluate medication adherence interventions in pregnant women and those planning pregnancy. These should assess both clinical and adherence outcomes.

Background: Breech presentation is observed in 3–4% at term of pregnancy and is one of the leading causes of cesarean section. There is no established treatment for breech presentation before 36 weeks. A retrospective cohort study was conducted to demonstrate that the lateral position is effective for breech presentation. However, there are no randomized controlled trials evaluating lateral position management for breech presentation. Here, we described the methodology of a randomized controlled trial of a cephalic version for breech presentation in the third trimester by lateral postural management (BRLT study). Methods: The BRLT study is an open-label, randomized controlled trial with two parallel groups allocated in a 1:1 ratio to examine the lateral position management for breech presentation, as compared with expectant management care. An academic hospital in Japan will enroll 200 patients diagnosed with a breech presentation by ultrasonography between 28 + 0 weeks and 30 + 0 weeks. Participants in the intervention group will be instructed to lie on their right sides for 15 min three times per day if the fetal back was on the left side or lie on their left sides if the fetal back was on the right side. The instruction will be given every 2 weeks after confirmation of fetal position, and the lateral position will be instructed until the cephalic version, and after the cephalic version, the reverse lateral position will be instructed until delivery. The primary outcome is cephalic presentation at term. The secondary outcomes are cesarean delivery, cephalic presentation 2, 4, and 6 weeks after the instruction, and at delivery, recurrent breech presentation after cephalic version, and adverse effects. Discussion: This trial will answer whether the lateral positioning technique is effective in treating breech presentation and, depending on the results, may provide a very simple, less painful, and safe option for treating breech presentation before 36 weeks, and it may impact breech presentation treatment. Trial registration: UMIN Clinical Trials Registry UMIN000043613. Registered on 15 March 2021 https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000049800. [ABSTRACT FROM AUTHOR]

Objective: The Accelerating Innovation for Mothers project established a new database of candidate medicines under development between 2000 and 2021 for five pregnancy‐related conditions, including fetal growth restriction. The objective was to assess medicines for fetal growth restriction and their potential for clinical use globally. Design: Landscape analysis. Setting: Global (focus on low‐ and middle‐income countries, LMICs). Sample: Drugs, dietary supplements and biologics under investigation for prevention or treatment of fetal growth restriction. Methods: A research pipeline database of medicines was created through searching AdisInsight, PubMed and various grant and clinical trial databases. Analysis of clinical and preclinical candidates were descriptive. Main Outcomes Measures Fetal growth restriction candidates in clinical development were identified and ranked as high, medium or low potential based on prespecified criteria, including efficacy, safety and accessibility. Results: Of the 444 unique candidates in the database across all five pregnancy‐related conditions, 63 were for fetal growth restriction. Of these, 31 were in clinical development (phases I, II or III) and 32 were in preclinical development. Three candidates, aspirin, l‐arginine and vitamin D, were ranked as having high potential as preventive agents. There were no high‐potential candidates for treating fetal growth restriction, although five candidates were ranked as having medium potential: allylestrenol, dalteparin, omega‐3 fatty acids, tadalafil, and United Nations International Multiple Micronutrient Antenatal Preparation (UNIMMAP). Conclusions: l‐Arginine, aspirin and vitamin D are promising, high‐potential preventative agents for fetal growth restriction. Based on the medicines pipeline, new pharmacological agents for fetal growth restriction are unlikely to emerge in the near future. [ABSTRACT FROM AUTHOR]

IntroductionHealth interventions often target pregnant women and their unborn children. Interventions in rural India targeting pregnant women, however, often do not cover the critical early windows of susceptibility during the first trimester and parts of the second trimester. This pilot seeks to determine if targeting newlyweds could protect entire pregnancies with a clean stove and fuel intervention.MethodsWe recruited 50 newlywed couples who use biomass as a cooking fuel into a clean cooking intervention that included a liquefied petroleum gas (LPG) stove, two gas cylinders, a table to place the stove on and health education. We first evaluated whether community health workers in this region could identify and recruit couples at marriage. We quantified how many additional days of pregnancy could be covered by an intervention if we recruited at marriage versus recruiting after detection of pregnancy.ResultsOn average, we identified and visited newlywed couples within 40 (SD 21) days of marriage. Of the 50 couples recruited, 25 pregnancies and 18 deliveries were identified during this 1-year study. Due to challenges securing fuel from the LPG supply system, not all couples received their intervention prior to pregnancy. Regardless, couples recruited in the marriage arm had substantially more days with the intervention than couples recruited into a similar arm recruited at pregnancy (211 SD 46 vs 120 SD 45). At scale, a stove intervention targeting new marriages would cover about twice as many weeks of first pregnancies as an intervention recruiting after detection of pregnancy.ConclusionsWe were able to recruit in early marriage using existing community health workers. Households recruited early in marriage had more days with clean fuel coverage than those recruited at pregnancy. Our findings indicate that recruitment at marriage is feasible and warrants further exploration for stove and other interventions targeting pregnancy-related outcomes.

ObjectiveTo determine whether maternal cardiovascular disease (CVD) risk factors predict preterm birth.DesignCase control.SettingCalifornia hospitals.Participants868 mothers with linked demographic information and biospecimens who delivered singleton births from July 2009 to December 2010.MethodsLogistic regression analysis was employed to calculate odds ratios for the associations between maternal CVD risk factors before and during pregnancy (including diabetes, hypertensive disorders and cholesterol levels) and preterm birth outcomes.Primary outcomePreterm delivery status.ResultsAdjusting for the other maternal CVD risk factors of interest, all categories of hypertension led to increased odds of preterm birth, with the strongest magnitude observed in the pre-eclampsia group (adjusted OR (aOR), 13.49; 95% CI 6.01 to 30.27 for preterm birth; aOR, 10.62; 95% CI 4.58 to 24.60 for late preterm birth; aOR, 17.98; 95% CI 7.55 to 42.82 for early preterm birth) and chronic hypertension alone for early preterm birth (aOR, 4.58; 95% CI 1.40 to 15.05). Diabetes (types 1 and 2 and gestational) was also associated with threefold increased risk for preterm birth (aOR, 3.06; 95% CI 1.12 to 8.41). A significant and linear dose response was found between total and low-density lipoprotein (LDL) cholesterol and aORs for late and early preterm birth, with increasing cholesterol values associated with increased risk (likelihood χ2 differences of 8.422 and 8.019 for total cholesterol for late and early, and 9.169 and 10.896 for LDL for late and early, respectively). Receiver operating characteristic curves using these risk factors to predict late and early preterm birth produced C statistics of 0.601 and 0.686.ConclusionTraditional CVD risk factors are significantly associated with an increased risk of preterm birth; these findings reinforce the clinical importance of integrating obstetric and cardiovascular risk assessment across the healthcare continuum in women.

ObjectivesPreterm births (PTBs) represent significant health risks, and several studies have found associations between high outdoor temperatures and PTB. We estimated both the total and natural direct effects (independent of particulate matter, ozone and nitrogen dioxide air pollutants) of the prior 2-day mean apparent temperature (AT) on PTB. We evaluated effect modification by maternal age, race, education, smoking status and prenatal care.Design and settingWe obtained birth records and meteorological data for the Detroit, Michigan, USA area, for the warm months (May to September), 1991 to 2001. We used a time series Poisson regression with splines of AT, wind speed, solar radiation and citywide average precipitation to estimate total effects. To accommodate multiple mediators and exposure-mediator interactions, AT inverse odds weights, predicted by meteorological and air pollutant covariates, were added in a subsequent model to estimate direct effects.ResultsAt 24.9°C relative to 18.6°C, 10.6% (95% CI: 3.8% to 17.2%) of PTBs were attributable to the total effects of AT, and 10.4% (95% CI: 2.2% to 17.5%) to direct effects. Relative excess risks of interaction indicated that the risk of PTB with increasing temperature above 18.6°C was significantly lower among black mothers and higher among mothers less than 19, older than 30, with late or no prenatal care and who smoked.ConclusionThis additional evidence of a direct association between high temperature and PTB may motivate public health interventions to reduce extreme heat exposures among pregnant women, particularly among those who may have enhanced vulnerability.

Abstract Introduction The antibacterial agent was changed from cefepime to piperacillin and clindamycin for streptococcal toxic shock syndrome, and an emergency cesarean section was performed. Immunoglobulin was added on the first postoperative day. Group A Streptococcus was isolated on the second postoperative day. Case A 37‐year old woman visited her doctor with complaints of sore throat and fever at 32 weeks gestation, she visited her previous doctor for sore throat and fever. She was treated with cefepime and transported to hospital. Conclusion Antimicrobial therapy and combined immunoglobulin administration were continued. Both mother and infant survived.

Background: Sub-optimal medication adherence in pregnant women with chronic disease and pregnancy-related indications has the potential to adversely affect maternal and perinatal outcomes. Adherence to appropriate medications is advocated during and when planning pregnancy to reduce risk of adverse perinatal outcomes relating to chronic disease and pregnancy-related indications. We aimed to systematically identify effective interventions to promote medication adherence in women who are pregnant or planning to conceive and impact on perinatal, maternal disease-related and adherence outcomes. Methods: Six bibliographic databases and two trial registries were searched from inception to 28th April 2022. We included quantitative studies evaluating medication adherence interventions in pregnant women and women planning pregnancy. Two reviewers selected studies and extracted data on study characteristics, outcomes, effectiveness, intervention description (TIDieR) and risk of bias (EPOC). Narrative synthesis was performed due to study population, intervention and outcome heterogeneity. Results: Of 5614 citations, 13 were included. Five were RCTs, and eight non-randomised comparative studies. Participants had asthma (n = 2), HIV (n = 6), inflammatory bowel disease (IBD; n = 2), diabetes (n = 2) and risk of pre-eclampsia (n = 1). Interventions included education +/− counselling, financial incentives, text messaging, action plans, structured discussion and psychosocial support. One RCT found an effect of the tested intervention on self-reported antiretroviral adherence but not objective adherence. Clinical outcomes were not evaluated. Seven non-randomised comparative studies found an association between the tested intervention and at least one outcome of interest: four found an association between receiving the intervention and both improved clinical or perinatal outcomes and adherence in women with IBD, gestational diabetes mellitus (GDM), and asthma. One study in women with IBD reported an association between receiving the intervention and maternal outcomes but not for self-reported adherence. Two studies measured only adherence outcomes and reported an association between receiving the intervention and self-reported and/or objective adherence in women with HIV and risk of pre-eclampsia. All studies had high or unclear risk of bias. Intervention reporting was adequate for replication in two studies according to the TIDieR checklist. Conclusions: There is a need for high-quality RCTs reporting replicable interventions to evaluate medication adherence interventions in pregnant women and those planning pregnancy. These should assess both clinical and adherence outcomes. [ABSTRACT FROM AUTHOR]

(1) Background: Pregnant women are at risk of vitamin D deficiency. Data on pregnancy outcomes in women with vitamin D deficiency during pregnancy are controversial, and prospective longitudinal data on vitamin D deficiency with consistent definitions in pregnant women are scarce. (2) Methods: The aim of this prospective longitudinal cohort study was to investigate 25-hydroxyvitamin D levels over the course of pregnancy and postpartum in singleton and twin pregnancies with regard to dietary and supplemental vitamin D intake and environmental factors influencing vitamin D levels, evaluated by a standardized food frequency questionnaire. (3) Results: We included 198 healthy singleton and 51 twin pregnancies for analysis. A total of 967 study visits were performed over a 3-year period. Overall, 59.5% of pregnant women were classified as vitamin D deficient in the first trimester, 54.8% in the second trimester, 58.5% in the third trimester, 66.9% at birth, and 60% 12 weeks postpartum, even though 66.4% of the study population reported daily pregnancy vitamin intake containing vitamin D. Dietary vitamin D intake did not affect vitamin D levels significantly. (4) Conclusions: The majority of pregnant women evaluated in this study were vitamin D deficient, despite administration of pregnancy vitamins containing vitamin D. Individualized vitamin D assessment during pregnancy should be considered to ensure adequate supplementation and prevention of hypovitaminosis D. [ABSTRACT FROM AUTHOR]

Background: The Accelerating Innovation for Mothers (AIM) project established a database of candidate medicines in research and development (R&D) between 2000 and 2021 for five pregnancy-related conditions, including pre-eclampsia. In parallel, we published target product profiles (TPPs) that describe optimal characteristics of medicines for use in preventing/treating pre-eclampsia. The study objective was to use systematic double screening and extraction to identify all candidate medicines being investigated for pre-eclampsia prevention/treatment and rank their potential based on the TPPs.Methods: Adis Insight, Pharmaprojects, WHO international clinical trials registry platform (ICTRP), PubMed and grant databases were searched (Jan-May 2021). The AIM database was screened for all candidates being investigated for pre-eclampsia. Candidates in clinical development were evaluated against nine prespecified criteria from TPPs identified as key for wide-scale implementation, and classified as high, medium or low potential based on matching to the TPPs. Preclinical candidates were categorised by product type, archetype and medicine subclass.Results: The AIM database identified 153 candidates for pre-eclampsia. Of the 87 candidates in clinical development, seven were classified as high potential (prevention: esomeprazole, L-arginine, chloroquine, vitamin D and metformin; treatment: sulfasalazine and metformin) and eight as medium potential (prevention: probiotic lactobacilli, dalteparin, selenium and omega-3 fatty acid; treatment: sulforaphane, pravastatin, rosuvastatin and vitamin B3). Sixty-six candidates were in preclinical development, the most common being amino acid/peptides, siRNA-based medicines and polyphenols.Conclusions: This is a novel, evidence-informed approach to identifying promising candidates for pre-eclampsia prevention and treatment - a vital step in stimulating R&D of new medicines for pre-eclampsia suitable for real-world implementation. [ABSTRACT FROM AUTHOR]

Background: Maternal health in India is likely to move towards an obstetric transition, wherein there is sustained reduction of maternal mortality and focus shifts towards improving quality of care. In such a context, reproductive concerns of special populations gain prominence. One such population group is women with disability. What this review contains: This mini-review examines the incremental importance given to people with disabilities and the sparse data available on the topic of reproductive concerns among women with disability. The attitudes of the women with disability towards childbearing and the association between disability and obstetric problems are discussed. The limited available data on specific medical and obstetric problems among women with disability are reviewed. Conclusions: The article calls for all obstetricians to display increased sensitivity and heightened cognizance towards the reproductive concerns among women with disability. [ABSTRACT FROM AUTHOR]

To evaluate maternal serum pregnancy-associated plasma protein-A (PAPP-A) levels at 11-14 weeks of gestation and preeclampsia risk in women with common congenital anatomic uterine abnormalities (AUAs). First trimester screening markers were compared between 12 AUA pregnancies, 60 age matched controls and 12 cases of early preeclampsia. PAPP-A level and birth weight were significantly lower in AUA compared to control and early preeclampsia group (p<.001). Preeclampsia was absent in the AUAs pregnancies group. Birth weight were similar in AUA group when we compared AUA and control group regarding weeks of gestation at delivery and lower but not significantly, when we compared AUA and early preeclampsia group. Our findings suggest that AUA pregnancies are associated with low first trimester maternal serum PAPP-A concentrations not predictive of susceptibility to preeclampsia.Impact statementWhat is already known on this subject? During first trimester screening for preeclampsia based on maternal pregnancy-associated plasma protein A (PAPP-A) levels, various parameters are used, such as the somatometric characteristics of pregnant woman, single or multiple pregnancy, smoking status, family history, diabetes, hypertension and measurement of blood pressure and uterine artery Dopplers.What do the results of this study add? Our pioneer study revealed that there is drastic difference in PAPP-A concentration in women with common anatomic uterine abnormalities (AUAs), in comparison with their age matched control women with normal uterus.What are the implications of these findings for clinical practice and further research? Based on our results, uterine anatomical deviations, is another factor which must be taken in account for preeclampsia risk calculation and further clinical consultation and follow up in those pregnancies. Lower PAPP-A levels in AUA cases is a weak predictor of susceptibility to preeclampsia and could be associated to smaller placental size rather than poor placentation and in future research the calculation of the uterine cavity functional dimension may lead to a more accurate clinical assessment. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to assess 7-day perioperative maternal mortality and risk factors at Tibebe Ghion Specialized Hospital., Design: A single-centre prospective cohort study., Setting: A tertiary hospital in North-West Ethiopia, 01 June 2019 to 30 June 2021., Participants: A total of 979 pregnant mothers who underwent caesarean section were enrolled in this study. Mothers who did not have cellphones and who had incorrect information for follow-up were excluded from the study., Outcome Measure: Perioperative death measured from intraoperative time to the seventh day following caesarean section., Results: The most frequent indication for caesarean section was failure to progress, followed by fetal distress and elective caesarean delivery, accounting for 40.04%, 24.72% and 20.43% of all cases, respectively. The 7-day perioperative maternal mortality rate was 1.83%. Maternal bleeding (adjusted relative risk (ARR) = 11.80; 95% CI 1.12, 124.08) and not using the WHO surgical safety checklist (ARR = 6.88; 95% CI 3.14, 15.07) were independently associated with increased risk of 7-day perioperative mortality., Conclusion: In this study, mortality after caesarean section was higher than in high-income countries. Implementation of targeted interventions focusing on the prevention and management of maternal bleeding, along with the consistent use of the WHO surgical safety checklist, could potentially contribute to improving the overall safety and outcomes of caesarean sections., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: This systematic review evaluated the available evidence on the effects of proton pump inhibitors during pregnancy on preeclampsia and related maternal, fetal, and neonatal outcomes., Data Sources: Five electronic databases (MEDLINE, Embase, CINAHL, Cochrane Central Register of Controlled Trials, and Global Medicus Index) were searched on November 17, 2023., Study Eligibility Criteria: Randomized controlled trials of pregnant women who used any class or dose of proton pump inhibitor were eligible., Methods: A meta-analysis was conducted for all outcomes of interest using random-effects models. Results were presented as risk ratios or mean difference. Quality assessment was performed using the Risk of Bias 2 tool, and Grading of Recommendations, Assessment, Development, and Evaluations assessment was completed to evaluate the certainty of the evidence. The study was registered in the International Prospective Register of Systematic Reviews under identifier CRD42023423673., Results: Our search identified 3879 records that were screened independently by 2 authors. Nine reports (describing 8 trials) met our eligibility criteria, however, 6 trials were ultimately excluded from our analysis because women were only given proton pump inhibitors immediately before cesarean delivery for acid aspiration prevention. The 2 trials that were included in the meta-analysis evaluated the treatment of 177 women with diagnosed preeclampsia. For the primary outcomes, moderate-certainty evidence showed that the use of proton pump inhibitors likely has no effect on the risk for hemolysis, elevated liver enzymes, and low platelet count syndrome (risk ratio, 1.21; 95% confidence interval, 0.37-3.99; I²=0%) or perinatal mortality (risk ratio, 0.81; 95% confidence interval, 0.36-1.79; I²=0%), and there were insufficient data to conduct a meta-analysis on all other primary outcomes, including eclampsia and neonatal mortality. No trials investigated the use of proton pump inhibitors for the prevention of preeclampsia., Conclusion: Given the limited outcome data, we are uncertain about the effect of proton pump inhibitors on women with preeclampsia. Further trials are required to determine what (if any) effects proton pump inhibitors might have for preeclampsia prevention or treatment., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Introduction: Fetal growth restriction (FGR) affects about 3%-5% of term pregnancies. If prenatally detected and anterograde umbilical artery flow is preserved (stage I), it is recommended to deliver at term (≥ 37+0 weeks). In the absence of contraindications, the vaginal route is preferred, and labour induction is usually required. It has been postulated that mechanical methods for cervical ripening may have an optimal profile for the induction of term FGR fetuses since they are associated with less uterine stimulation than the standard pharmacological methods, and therefore, could be better tolerated by fetuses with reduced placental reserve. This study aims to evaluate whether cervical ripening with a Cook's balloon for the induction of labour from 37+0 weeks of gestation in the stage I FGR manages to increase the rate of vaginal delivery compared with vaginal dinoprostone., Methods and Analysis: This will be an open-labelled, randomised, parallel-group clinical trial to be held in five Spanish maternities. Women aged ≥18 years with singleton pregnancies complicated with stage I FGR (defined as the presence of at least one of these two criteria: (1) estimated fetal weight (EFW) <3rd percentile; (2) EFW <10th percentile and at least one of the following: (2.1.) umbilical artery pulsatility index >95th percentile and presence of antegrade end-diastolic flow or (2.2.) Cerebroplacental ratio <5th percentile), gestational age dated by first-trimester ultrasound ≥37+0 weeks at the time of labour induction, cephalic presentation, unfavourable cervix (Bishop score <7), intact fetal membranes, no previous caesarean section and no maternal or fetal contraindications for vaginal delivery or labour induction will be 1:1 randomised by centre to labour induction with Cook's balloon (experimental arm) or dinoprostone (control arm). FGR cases with evidence of non-placental origin (major structural fetal malformations, chromosomal anomalies or congenital infection) will be excluded. The primary outcome is the achievement of a vaginal delivery and it will be assessed by comparing the rates of vaginal delivery in each group using the one-sided χ 2 test at an alpha level of 0.025. The sample size has been estimated to observe an expected 84% of vaginal deliveries with Cook's balloon vs 62% with dinoprostone. Therefore, a total of 172 patients (86 per arm) are required (power of 90%, alpha level of 0.025, assuming a percentage of losses of 5%). The efficacy analysis will be performed in the intention-to-treat population. An interim analysis using a two-stage sequential design with the O'Brien-Fleming method will be applied., Ethics and Dissemination: The trial was registered in the European Union drug regulating authorities' clinical trials database (EUDRACT) (2021-001726-22) and received approval from the local Research Ethics Committee (21/728) and the Spanish Agency of Medicines and Medical Devices (AEMPS). AEMPS classified the study as a low-intervention trial. The study will be conducted in compliance with the principles of Good Clinical Practice. The study results will be disseminated through workshops and national/international conferences and published in peer-reviewed journals. In addition, they will be disclosed to patients and the public in understandable language through study newsletters and press releases to news and social media., Protocol Version: V.1.1, 18 May 2023., Trial Registration Numbers: EUDRACT 2021-001726-22 and NCT05774236., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Perinatal mortality is a major public health issue in sub-Saharan Africa, with Ghana experiencing consistently high rates. This poses challenges for achieving the maternal and child health-related sustainability development goals by 2030. While some studies have explored factors behind perinatal mortality in Ghana, a comprehensive analysis considering multifactorial predictors remains absent. This scoping review, guided by Anderson's framework of healthcare utilisation, aims to address this. The primary objective is to map the predictors of perinatal mortality in Ghana using Anderson's framework. It aims to identify interpersonal, social structural and health beliefs as predisposing factors; evaluate access to healthcare, social support and health literacy as enabling factors; and outline maternal and foetal conditions as need factors, concluding with identified knowledge gaps., Methods and Analysis: The Cochrane handbook for systematic reviews of interventions will be used to guide the conduct of this review. Four main electronic databases, PubMed, Web of Science, Scopus and Cumulative Index for Nursing and Allied Health Literature, will be searched. Eligible studies will be charted and synthesised, focussing on Anderson's primary domains: predisposing factors, enabling factors and need factors. Studies published in the English language from January 2000 to June 2024 will be included in the study to cover the most recent factors associated with perinatal mortality in Ghana., Ethics and Dissemination: This review will rely on already published peer-reviewed articles and therefore will not require ethical approval. The review results will be disseminated through peer-reviewed scientific publications and annual health services review conferences in Ghana., Prospero Registration Number: CRD42024564968., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Gestational diabetes mellitus (GDM) is one of the most common medical complications of pregnancy. Glycaemic control decreases the risk of adverse pregnancy outcomes for the affected pregnant individual and the infant exposed in utero. One in four individuals with GDM will require pharmacotherapy to achieve glycaemic control. Injectable insulin has been the mainstay of pharmacotherapy. Oral metformin is an alternative option increasingly used in clinical practice. Both insulin and metformin reduce the risk of adverse pregnancy outcomes, but comparative effectiveness data from a well-characterised, adequately powered study of a diverse US population remain lacking. Because metformin crosses the placenta, long-term safety data, in particular, the risk of childhood obesity, from exposed children are also needed. In addition, the patient-reported experiences of individuals with GDM requiring pharmacotherapy remain to be characterised, including barriers to and facilitators of metformin versus insulin use., Methods and Analysis: In a two-arm open-label, pragmatic comparative effectiveness randomised controlled trial, we will determine if metformin is not inferior to insulin in reducing adverse pregnancy outcomes, is comparably safe for exposed individuals and children, and if patient-reported factors, including facilitators of and barriers to use, differ between metformin and insulin. We plan to recruit 1572 pregnant individuals with GDM who need pharmacotherapy at 20 US sites using consistent diagnostic and treatment criteria for oral metformin versus injectable insulin and follow them and their children through delivery to 2 years post partum. More information is available at www.decidestudy.org., Ethics and Dissemination: The Institutional Review Board at The Ohio State University approved this study (IRB: 2024H0193; date: 7 December 2024). We plan to submit manuscripts describing the results of each study aim, including the pregnancy outcomes, the 2-year follow-up outcomes, and mixed-methods assessment of patient experiences for publication in peer-reviewed journals and presentations at international scientific meetings., Trial Registration Number: NCT06445946., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: The Rahima Moosa Mother and Child Hospital (RMMCH) maternal HIV cohort originated from data systems that were developed to support HIV-related birth care and track outcomes of a complete birth cohort of HIV-exposed infants at Rahima Moosa Hospital and their mothers living with HIV., Participants: Supported by the Empilweni Services and Research Unit, maternal and infant data from 13 654 pregnant women living with HIV who delivered their infants (and a subset also attended antenatal care) were collected at RMMCH in Johannesburg, South Africa since 2013. Maternal data were collected using counsellor-administered interviews and the 2013-2018 subset of this cohort was linked to the National Health Laboratory Services (NHLS) national HIV cohort-a longitudinal cohort of people living with HIV accessing care in the public sector antiretroviral therapy programme in South Africa that can observe national access to HIV care through laboratory testing data., Findings to Date: Topics addressed by the cohort include antenatal care history, HIV treatment exposure, delivery/birth management, prophylaxis and maternal blood results relevant to HIV captured at delivery. The cohort was also one of the first to describe implementation of early infant diagnosis procedures in South Africa including evaluations of novel point-of-care testing strategies demonstrating improvements in uptake of HIV care among infants accessing point-of-care services., Future Plans: Annual linkage of infant delivery and testing data to longitudinal laboratory test data in the NHLS national HIV cohort is planned to allow for analysis of both infant continuity of care outcomes and as well as evaluation of maternal-infant pair treatment and mobility outcomes in the post partum and later period., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Maternal suicide is a significant contributor to maternal mortality with devastating consequences for women, families and society. Maternal mortality reporting systems differ across countries and there is no up-to-date overview of maternal suicide deaths globally. This systematic review aims to synthesise the evidence on maternal suicide. The primary objective is to determine the contribution of suicide towards maternal mortality globally and explore differences between geographical regions. The secondary objectives are to summarise the availability and quality of data globally and to describe how suicide deaths are classified across different countries., Methods and Analysis: This protocol follows the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols guidelines. Medline, Embase, PsycINFO, Global Health and CINAHL databases and the grey literature were searched with no date or language restrictions. Observational studies, national surveys and reports that present data on maternal deaths due to suicide occurring during pregnancy, intrapartum and in the postpartum period will be included. Screening, data extraction and quality assessment will be conducted independently by two reviewers. Results will be summarised narratively. If sufficient outcome data are available, random-effects meta-analyses will be conducted to determine global pooled estimates of suicide-related maternal mortality rates and the proportion of maternal deaths attributable to suicide., Ethics and Dissemination: Ethical approval is not required for this systematic review. Results will be written up for publication in a peer-reviewed journal and findings will be shared at national and international conferences., Prospero Registration Number: CRD42023429072., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

Background: According to the WHO, obstetric fistula (OBF) is an abnormal connection between the genital tract and the urinary tract that occurs as the result of obstetric trauma, typically from prolonged obstructed labour. In 2018, globally, 50 000 and 100 000 cases of OBF are reported each year. The core of activities focused on reducing fistulas depends on a review of the disorder's knowledge and the features of women at risk of having a lack of understanding. The effect of community-level factors on awareness of OBF was not yet known in Nepal. Therefore, we aimed to investigate the community-level and individual-level factors of awareness of OBF among childbearing-aged women in Nepal., Methods: The 2022 Nepal Demographic and Health Survey data were used for this study. It included 14 845 childbearing-aged women. Because of the clustering effects of Demographic and Health Survey data and the binary nature of the outcome variable, a multilevel binary logistic regression model was applied. An adjusted OR (AOR) with a 95% CI was reported to declare the statistical significance. In addition, the model that had the lowest deviance was the one that best fit the data., Results: The overall prevalence of awareness of OBF among childbearing women in Nepal was 35.9% (95% CI 35.1%, 36.7%). Educational status (women who attended secondary education (AOR=1.65; 95% CI 1.41, 3.03) and higher education (AOR=4.29; 95% CI 1.14, 36.70)), currently working status (AOR=1.85; 95% CI 1.04, 3.30), birth history (AOR=2.23; 95% CI 1.48, 4.10), media exposure (AOR=1.54; 95% CI 1.07, 3.09) and women's age from 30 to 39 (AOR=3.38; 95% CI 1.35, 8.93) and 40 to 49 years old (AOR=4.68; 95% CI 1.60, 13.67) at the individual level, as well as urban residence (AOR=1.53; 95% CI 1.99, 2.87) and high community-level media exposure (AOR=2.05; 95% CI 1.67, 2.64) at the community level were statistically significant factors with awareness of OBF., Conclusion: Our study revealed that awareness of OBF among childbearing-aged women in Nepal was low (35.9%). The findings of this study will assist policymakers and public health programmers in understanding the magnitude of OBF awareness and the contributory factors. In addition, it will be useful to increasing awareness of OBF in the communities and promoting primary prevention approaches through education and motivation efforts., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: WHO recommends the use of the Robson's 'Ten Groups Classification' for monitoring and assessing caesarean section (CS) rates. The aim of this study was to investigate the rates, indications and outcomes of CS using Robson classification in a tertiary hospital in Sierra Leone., Design: Cross-sectional study., Setting: Princess Christian Maternity Hospital (PCMH), Freetown, Sierra Leone., Participants: All women who gave birth in PCMH from 1 October 2020 to 31 January 2021., Primary and Secondary Outcome Measures: Primary outcome: CS rate by Robson group., Secondary Outcomes: indications for CS and the newborn outcomes for each Robson group., Results: 1998 women gave birth during the study period and 992 CS were performed, with a CS rate of 49.6%. Perinatal mortality was 7.8% and maternal mortality accounted for 0.5%. Two-thirds of the women entered labour spontaneously and were considered at low risk (groups 1 and 3). CS rates in these groups were very high (43% group 1 and 33% group 3) with adverse outcomes (perinatal mortality, respectively, 4.1% and 6%). Dystocia was the leading indication for CS accounting for about two-thirds of the CS in groups 1 and 3. Almost all women with a previous CS underwent CS again (95%). The group of women who give birth before term (group 10) represents 5% of the population with high CS rate (50%) mainly because of emergency conditions., Conclusion: Our data reveals a notably high CS rate, particularly among low-risk groups according to the Robson classification. Interpretation must consider PCMH as a referral hospital within an extremely low-resourced healthcare system, centralising all the complicated deliveries from a vast catchment area. Further research is required to assess the impact of referred obstetrical complications on the CS rate and the feasibility of implementing measures to improve the management of women with dystocia and previous CS., Competing Interests: Competing interests: None declared., (© World Health Organization 2024. Licensee BMJ.)

Objectives: To characterise the exposure to valproate within a cohort of pregnant women using electronic health records (EHRs) from Catalonia (System for the Development of Research in Primary Care, SIDIAP)., Design: Drug-utilisation cohort study covering the period from January 2011 to June 2020. The study included pregnancy episodes of women from Catalonia identified by the algorithm., Setting: Data were sourced from SIDIAP, a comprehensive EHR repository that includes information from various data sources: recorded prescriptions (both hospital and primary care), diagnoses and sociodemographic characteristics identified by primary care physicians, and sexual and reproductive health data from ASSIR (used by gynaecologists and midwives)., Participants: Women aged 12-50 with at least one pregnancy episode occurred during January 2011-June 2020 and at least a prescription of valproate during pregnancy., Primary and Secondary Outcomes: Primary outcomes included valproate exposure, measured through prevalence and cumulative incidence in pregnancy episodes and by trimester. The impact of regulatory measures (risk mitigation measures, RMMs) was assessed, and prescriptions over time were analysed using interrupted time series analysis. Secondary outcomes included health issues, pregnancy outcomes, smoking habits and socioeconomic characteristics., Results: A total of 99 605 pregnancies were identified, with at least 3.03‰ (95% CI 2.69‰ to 3.39‰) exposed to valproate at some point (302 pregnancies, 276 women). The median pregnancy duration was 38.30 weeks (IQR 12.6-40.1), and the median age at pregnancy was 32.37 years (IQR 27.20-36.56). Epilepsy was the most frequent health issue. The prevalence and cumulative incidence of valproate prescriptions decreased during pregnancy and increased postpregnancy. The RMMs implemented in 2014 led to a reduction in monthly valproate prescriptions during pregnancy in this cohort., Conclusions: The study highlights the decline in valproate prescriptions during pregnancy due to RMMs and underscores the need for standardised methodologies in future studies to ensure the safety of pregnant patients and optimise scientific evidence., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

Introduction: Previous systematic reviews investigating the effects of green and blue space (GBS) on maternal and neonatal health have mainly focused on cross-sectional evidence, limiting potential causal inferences. The last review on the topic was published in January 2024. This review focused on residential greenness effects and neonatal health only but did not include other green/blue space measures, or maternal health outcomes. This review also only included papers published up to June 2023; discounting the 15 studies that have been published since. Thus, this study will capture the growing number of studies that generate causal evidence and aims to investigate the association between GBS and maternal and/or neonatal health., Methods and Analysis: The study protocol was developed with reference to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. This review will include study designs such as experiments, quasi-experiments, longitudinal studies and more. The study independent variable must be a GBS, green space and/or blue space measure. Eligible maternal health outcomes are those reported during pregnancy and up to 1 year after pregnancy. Neonatal health outcomes are limited to neonates no older than 28 days. A total of seven online databases will be searched: Medline, Scopus, Web of Science, PsycInfo, Embase, Environment Complete, and Maternity and Infant Care Database. Abstract and full-text screenings will be undertaken by three reviewers. Risk of bias assessment will be conducted based on the Risk of Bias in Non-randomized Studies-of Exposure framework.A narrative synthesis will be undertaken. If sufficiently comparable studies are identified, meta-analyses using random effects models will be conducted. We will explore heterogeneity using the I 2 test., Ethics and Dissemination: Ethical approval is not required as all the data will be derived from published primary studies that have already obtained ethical permissions. The findings will be disseminated through relevant conferences and peer-reviewed publications., Prospero Registration Number: CRD42023396372., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

Objectives: To investigate the association between multimorbidity during pregnancy and neurodevelopmental delay in offspring using data from a Japanese nationwide birth cohort study., Design: This study was a prospective birth cohort study., Setting: This study population included 104 059 fetal records who participated in The Japan Environment and Children's Study from 2011 to 2014., Participants: Pregnant women whose children had undergone developmental testing were included in this analysis., Primary and Secondary Outcome Measures: Neurodevelopment of offspring was assessed using the Japanese version of the Ages and Stages Questionnaire, third edition, comprising five developmental domains. The number of comorbidities among the pregnant women was categorised as zero, single disease or multimorbidity (two or more diseases). Maternal chronic conditions included in multimorbidity were defined as conditions with high prevalence among women of reproductive age. A multivariate logistic regression analysis was conducted to examine the association between multimorbidity in pregnant women and offspring development., Results: Pregnant women with multimorbidity, single disease and no disease accounted for 3.6%, 30.6% and 65.8%, respectively. The ORs for neurodevelopmental impairment during the follow-up period were similar for infants of mothers with no disease comorbidity and those with a single disease comorbidity. However, the ORs for neurodevelopmental impairment were significantly higher for children born to mothers with multimorbidity compared with those born to healthy mothers., Conclusion: An association was observed between the number of comorbidities in pregnant women and developmental delay in offspring. Multimorbidity in pregnant women may be associated with neurodevelopmental delay in their offspring. Further research is required in this regard in many other regions of the world., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Near miss occurs in far greater numbers than maternal deaths and allows a more robust quantification on risk factors and determinants of life-threatening complications. A 'Three delay model' has been proposed in identification of causes of near miss and maternal deaths. There may be delay in seeking and obtaining health care: delay in recognising danger signs and deciding to reach source of care, delay in reaching appropriate source of care and delay in obtaining appropriate and adequate treatments. We compared various delays between near miss cases (n = 100) and controls (n = 200). Women who fulfilled criteria of near miss were taken as cases. Women who had obstetrical complications like near miss but were managed successfully and did not reach near miss state were labelled as controls. Near miss were then compared with maternal death. For normally distributed measurable data, outcome was compared using Student's t-test, for non-normally distributed/ordinal data, outcome was compared using Mann–Whitney's test. For categorical/classified data, association with outcome was analysed using Chi-Square test/Fisher's exact test. Delay in all three levels was seen among the groups. Lack of knowledge, non-availability of decision maker, and concern of cost of transport were main contributors of these delays. What is already known on this subject? Nonavailability of healthcare and low socio-economic status strongly correlate with maternal morbidity and mortality. What do the results of this study add? Lack of knowledge, non-availability of the decision maker, and concern of cost of transport were the main contributors of delay in seeking medical care. Majority of the cases of near miss were attributed to poor utilisation of health resources, ignorance and lack of emergency obstetric care at the primary level. What are the implications of these findings for clinical practice and/or further research? Patient and attendant education to ensure follow-up visits, recognise danger signs and report without undue delay, compliance to dietary modifications, medications given needs to be addressed at every visit to reduce the impact of socio-behavioural determinants on maternal near miss and mortality which are preventable in majority of cases. [ABSTRACT FROM AUTHOR]

In the present study, we investigated the effect of maternal iron deficiency anaemia (IDA) on expression of the newly discovered iron transporter, Zyklopen in term placenta, in 200 pregnant women. Placental expression of Zyklopen was studied by mRNA analysis and immunohistochemistry for the protein. In addition neonatal anthropometric parameters were also analysed. 58.8% of 200 subjects were anaemic. Both Zyklopen mRNA as well as protein expression in the placenta showed a statistically significant increase with increasing severity of anaemia. Although all the neonatal anthropometric parameters were lower in newborns of anaemic mothers, none showed any statistical significance. Zp mRNA levels did not show any significant correlation with newborn and placental parameters (except newborn skinfold thickness and head circumference). Similar to mRNA expression, Zp IHC expression correlated positively, albiet non-significantly, with newborn length and Hb levels, the correlation was however negative with birth weight, head circumference, mid-arm circumference unlike the mRNA expression, where it positively correlated with the above parameters. Our study for the first time demonstrated a definite increase in expression of Zyklopen at both mRNA and protein levels in term placenta, in maternal IDA. What is already known on this subject? Iron deficiency anaemia (IDA) in a pregnant mother can lead to anaemia in the developing foetus; which is frequently observed to be of lesser severity than that in the mother. Recently a copper-containing oxidase called Zyklopen was discovered which was involved in iron efflux in BeWo cells. The gene encoding Zyklopen has been identified with a putative C-terminal membrane-spanning sequence and high sequence identitical to hephaestin (Heph) and ceruloplasmin (Cp), the other known vertebrate multicopper ferroxidase (MCF). Protein expression of this new MCF was observed in multiple diverse mouse tissues, including placenta and mammary gland. What do the results of this study add? Zyklopen protein immunohistochemical expression showed a statistically significant increase with increasing severity of anaemia. Similarly, placental mRNA expression of the Zyklopen gene was observed to be higher in anaemic mothers when compared to non-anaemic mothers. Our study for the first time demonstrated a definite increase in expression of Zyklopen at both protein and mRNA levels in term placenta, in maternal IDA. What are the implications of these findings for clinical practice and/or further research? This study will help us to understand better, the increased potential for influx of iron from mother to foetus in the condition of maternal iron deficiency. This study will help to determine how placental iron transport proteins can be regulated in response to maternal and neonatal iron status and will further our existing knowledge on relationships between maternal and neonatal iron status and mechanisms by which placental iron transport is modified in relation to these parameters. [ABSTRACT FROM AUTHOR]

(1) Background: Pregnant women are at risk of vitamin D deficiency. Data on pregnancy outcomes in women with vitamin D deficiency during pregnancy are controversial, and prospective longitudinal data on vitamin D deficiency with consistent definitions in pregnant women are scarce. (2) Methods: The aim of this prospective longitudinal cohort study was to investigate 25-hydroxyvitamin D levels over the course of pregnancy and postpartum in singleton and twin pregnancies with regard to dietary and supplemental vitamin D intake and environmental factors influencing vitamin D levels, evaluated by a standardized food frequency questionnaire. (3) Results: We included 198 healthy singleton and 51 twin pregnancies for analysis. A total of 967 study visits were performed over a 3-year period. Overall, 59.5% of pregnant women were classified as vitamin D deficient in the first trimester, 54.8% in the second trimester, 58.5% in the third trimester, 66.9% at birth, and 60% 12 weeks postpartum, even though 66.4% of the study population reported daily pregnancy vitamin intake containing vitamin D. Dietary vitamin D intake did not affect vitamin D levels significantly. (4) Conclusions: The majority of pregnant women evaluated in this study were vitamin D deficient, despite administration of pregnancy vitamins containing vitamin D. Individualized vitamin D assessment during pregnancy should be considered to ensure adequate supplementation and prevention of hypovitaminosis D.

Introduction: Peripheral vasodilation causes a redistribution of body temperature from the core to the periphery, resulting in shivering and hypothermia. These are normal pathological and physiological processes during spinal anaesthesia. Two drugs, norepinephrine and phenylephrine, have peripheral vasoconstrictive effects. It is unclear the effects of norepinephrine and phenylephrine on shivering and hypothermia in patients undergoing caesarean section under spinal anaesthesia., Methods Analysis: 240 eligible parturients will be recruited for this randomised, double-blind, controlled trial and randomly assigned to either the norepinephrine or phenylephrine groups. The primary outcome will be the incidence of shivering while secondary outcomes will include the severity of shivering, rectal temperature, incidence of hypothermia and umbilical artery blood pH value., Ethics and Dissemination: The Institutional Ethics Committee of The Second People's Hospital of Hefei approved the trial protocol (ID: 2023-093). The results will be published in a compliant journal. The original data will be released in December 2029 on the ResMan original data-sharing platform of the China Clinical Trial Registry (http://www.medresman.org.cn)., Trial Registration Number: ChiCTR2300077164., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Pregnancies resulting from in vitro fertilisation are associated with an increased risk of developing hypertensive disorders of pregnancy, such as preeclampsia, when compared with naturally conceived pregnancies., Objective: The efficacy of aspirin prophylaxis to reduce the incidence of preeclampsia is well established in naturally conceived pregnancies identified as high risk for developing preeclampsia. However, the efficacy of aspirin to reduce the rate of preeclampsia for all pregnancies resulting from in vitro fertilisation remains uncertain, although in vitro fertilisation conception is a well-known risk factor for preeclampsia. Therefore, the purpose of this scoping review is to provide a comprehensive overview of the current literature regarding the use of low-dose aspirin to prevent hypertensive disorders of pregnancy after in vitro fertilisation., Inclusion Criteria: This review will identify all peer-reviewed published articles including pregnant women who underwent embryo transfer after in vitro fertilisation and were prescribed low-dose aspirin to reduce the risk of hypertensive disorders of pregnancy., Methods: We have devised a comprehensive search strategy to systematically identify pertinent studies published from January 2000 until May 2024, within the Medline (PubMed interface), Embase and Scopus databases. The search strategy is based on the keywords 'aspirin,' 'pregnancy-induced hypertension,' and ('in vitro fertilization' OR 'oocyte donation' OR 'embryo transfer' OR 'donor conception'). Two reviewers will independently screen the titles, abstracts and full-text articles to select the relevant articles, using the Covidence software., Ethics and Dissemination: No patients are involved in this study. This study aims to be published in a peer-reviewed journal and could be presented at a conference., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: This study compares rectal administration with vaginal administration of progesterone as luteal phase support in hormone replacement therapy frozen embryo transfer (HRT-FET) cycles. The reason for comparing the two routes of administration is that rectal administration has been suggested to be more patient friendly., Methods and Analysis: This study is a randomised controlled trial comparing the ongoing pregnancy rate (OPR) at week 12 in HRT-FET cycles after rectal administered progesterone as the only administered progesterone compared with a vaginal luteal phase support regimen. All patients are enrolled from a Danish public fertility clinic and randomised to one of two groups, with 305 patients receiving embryo transfer assigned to each group. Endometrial preparation includes 6 mg oestradiol daily. The intervention group receives rectally administered progesterone (400 mg/12 hours) and the control group receives vaginally administered progesterone (400 mg/12 hours). If P4 is <35 nmol/L on blastocyst transfer day an additional rectal luteal phase rescue regimen is started (control group). Thawing and transferring of a single autologous vitrified blastocyst is scheduled on the sixth day of progesterone administration in both groups. The power calculation is based on a non-inferiority analysis with an expected OPR in both groups of 44% and the upper limit of a one-sided 95% CI will exclude a difference in favour of the control group of more than 10.0%. An interim analysis will be conducted once half of the study population has been enrolled., Ethics and Dissemination: The trial was approved on 21 November 2023 by the Danish National Ethical Committee and the Danish Medicines Agency and is authorised by the Clinical Trials Information System (EUCT number 2023-504616-15-02). All patients will provide informed consent before being enrolled in the study. The results will be published in an international journal., Trial Registration Number: EUCT number: 2023-504616-15-02., Competing Interests: Competing interests: The study group has no personal economic interest in the project. Furthermore, Gedeon Richter Nordic was not involved in planning or designing the study and will not be involved in study flow, analysis or reporting. BA has received unrestricted grants from Gedeon Richter Nordic and Merck and honoraria for lectures from Gedeon Richter, Merck, IBSA and Marckyrl Pharma. PH has received honoraria for lectures from Gedeon Richter, Merck and IBSA., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Oocyte donation (OD) pregnancy is accompanied by a high incidence of hypertensive complications, with serious consequences for mother and child. Optimal care management, involving early recognition, optimisation of suitable treatment options and possibly eventually also prevention, is in high demand. Prediction of patient-specific risk factors for hypertensive complications in OD can provide the basis for this. The current project aims to establish the first prediction model on the risk of hypertensive complications in OD pregnancy., Methods and Analysis: The present study is conducted within the DONation of Oocytes in Reproduction project. For this multicentre cohort study, at least 541 OD pregnancies will be recruited. Baseline characteristics and obstetric data will be collected. Additionally, one sample of maternal peripheral blood and umbilical cord blood after delivery or a saliva sample from the child will be obtained, in order to determine the number of fetal-maternal human leucocyte antigen mismatches. Following data collection, a multivariate logistic regression model will be developed for the binary outcome hypertensive complication 'yes' and 'no'. The Prediction model Risk Of Bias ASsessment Tool will be used as guide to minimise the risk of bias. The study will be reported in line with the 'Transparent Reporting of a multivariable prediction model for Individual Prognosis Or Diagnosis' guideline. Discrimination and calibration will be determined to assess model performance. Internal validation will be performed using the bootstrapping method. External validation will be performed with the 'DONation of Oocytes in Reproduction individual participant data' dataset., Ethics and Dissemination: This study is approved by the Medical Ethics Committee LDD (Leiden, Den Haag, Delft), with protocol number P16.048 and general assessment registration (ABR) number NL56308.058.16. Further results will be shared through peer-reviewed journals and international conferences., Competing Interests: Competing interests: EELOL has received the ZonMw Clinical Fellows 2021 Grant, with project code 09032212110062. YL has received honoraria for lectures and presentations by Merck and Ferring. Moreover, YL is supported by Gideon Richter to attend the ORBIS program (a 3-year expert-led program). GCML, VHWVdE, SlC and M-LPvdH have no competing interests., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

Objectives: To investigate the associations of traffic-related air pollution exposures in early pregnancy with birth outcomes and infant neurocognitive development., Design: Cohort study., Setting: Eligible women attended six visits in the maternity clinics of two centres, the First Affiliated Hospital of Chongqing Medical University and Chongqing Health Centre for Women and Children., Participants: Women who were between 20 and 40 years of age and were at 11-14 weeks gestation with a singleton pregnancy were eligible for participation. Women were excluded if they had a history of premature delivery before 32 weeks of gestation, maternal milk allergy or aversion or severe lactose intolerance. 1273 pregnant women enrolled in 2015-2016 and 1174 live births were included in this analysis., Exposures: Air pollution concentrations at their home addresses, including particulate matter with diameter ≤2.5 µm (PM 2.5 ) and nitrogen dioxide (NO 2 ), during pre-conception and each trimester period were estimated using land-use regression models., Outcome Measures: Birth outcomes (ie, birth weight, birth length, preterm birth, low birth weight, large for gestational age and small for gestational age (SGA) status) and neurodevelopment outcomes measured by the Chinese version of Bayley Scales of Infant Development., Results: An association between SGA and per-IQR increases in NO 2 was found in the first trimester (OR: 1.57, 95% CI: 1.06 to 2.32) and during the whole pregnancy (OR: 1.33, 99% CI: 1.01 to 1.75). Both PM 2.5 and NO 2 exposure in the 90 days prior to conception were associated with lower Psychomotor Development Index scores (β: -6.15, 95% CI: -8.84 to -3.46; β: -2.83, 95% CI: -4.27 to -1.39, respectively). Increased NO 2 exposure was associated with an increased risk of psychomotor development delay during different trimesters of pregnancy., Conclusions: Increased exposures to NO 2 during pregnancy were associated with increased risks of SGA and psychomotor development delay, while increased exposures to both PM 2.5 and NO 2 pre-conception were associated with adverse psychomotor development outcomes at 12 months of age., Trial Registration Number: ChiCTR-IOR-16007700., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

Introduction: Preterm pre-eclampsia is a leading cause of maternal morbidity and mortality. The Pre-eclampsia Intervention 2 (PI 2) trial suggested that metformin sustained release (XR) may prolong gestation by a week in pregnant women undergoing expectant management (7.6 days, geometric mean ratio 1.39, 95% CI 0.99 to 1.95; p=0.057). These findings should be confirmed with a larger sample size, and we need to know if such a prolongation improves neonatal outcome. Here, we describe the protocol for such a follow-up trial., Methods: The PI 3 trial is a phase III, intention-to-treat, double-blind, placebo-controlled randomised clinical trial to assess if metformin XR can prolong gestation and improve neonatal outcomes in women undergoing expectant management for preterm pre-eclampsia. We will recruit women who are between 26+0 and 31+6 weeks pregnant. Women will be randomised to receive either 3 g metformin XR or an identical placebo in divided daily doses. The primary outcome is prolongation of pregnancy. Secondary outcomes are neonatal birth weight and length of neonatal care admission (an indicator of neonatal health at birth). All other outcomes will be exploratory. We will record tolerability and adverse events. We plan a sample size of 500 participants to be powered for the primary and secondary outcomes., Ethics and Dissemination: PI 3 has ethical approval (Health Research Ethics Committee 2, Stellenbosch University, Protocol number M21/03/007, Project ID 21639, Federal Wide Assurance Number 00001372, Institutional Review Board Number IRB0005239), and is registered with the Pan African Clinical Trial Registry (PACTR202104532026017) and the South African Medicine Control Council (20211211). Data will be presented at international conferences and published in peer-reviewed journals., Trial Registration Number: PACTR202104532026017)., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: National-level coverage estimates of maternal and child health (MCH) services mask district-level and community-level geographical inequities. The purpose of this study is to estimate grid-level coverage of essential MCH services in Nigeria using machine learning techniques., Methods: Essential MCH services in this study included antenatal care, facility-based delivery, childhood vaccinations and treatments of childhood illnesses. We estimated generalised additive models (GAMs) and gradient boosting regressions (GB) for each essential MCH service using data from five national representative cross-sectional surveys in Nigeria from 2003 to 2018 and geospatial socioeconomic, environmental and physical characteristics. Using the best-performed model for each service, we map predicted coverage at 1 km 2 and 5 km 2 spatial resolutions in urban and rural areas, respectively., Results: GAMs consistently outperformed GB models across a range of essential MCH services, demonstrating low systematic prediction errors. High-resolution maps revealed stark geographic disparities in MCH service coverage, especially between rural and urban areas and among different states and service types. Temporal trends indicated an overall increase in MCH service coverage from 2003 to 2018, although with variations by service type and location. Priority areas with lower coverage of both maternal and vaccination services were identified, mostly located in the northern parts of Nigeria., Conclusion: High-resolution spatial estimates can guide geographic prioritisation and help develop better strategies for implementation plans, allowing limited resources to be targeted to areas with lower coverage of essential MCH services., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)