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Background: Postpartum haemorrhage (PPH) is the leading cause of maternal mortality worldwide. Accurate diagnosis of PPH can prevent adverse outcomes by enabling early treatment., Objectives: What is the accuracy of methods (index tests) for diagnosing primary PPH (blood loss ≥ 500 mL in the first 24 hours after birth) and severe primary PPH (blood loss ≥ 1000 mL in the first 24 hours after birth) (target conditions) in women giving birth vaginally (participants) compared to weighed blood loss measurement or other objective measurements of blood loss (reference standards)?, Search Methods: We searched CENTRAL, MEDLINE, Embase, Web of Science Core Collection, ClinicalTrials.gov, and the World Health Organization International Clinical Trials Registry Platform to 24 May 2024., Selection Criteria: We included women who gave birth vaginally in any setting. Study types included diagnostic cohort studies and cross-sectional studies that reported 2 x 2 data (number of true positive, false positive, false negative, and true negative results) or where the 2 x 2 data could be derived from test accuracy estimates. Eligible index tests included: visual estimation; calibrated blood collection devices; approach with calibrated drape and observations; blood loss estimation using the SAPHE (Signalling a Postpartum Hemorrhage Emergency) Mat; blood loss field image analysis and other technologies; uterine atony assessment; clinical variables (e.g. heart rate, blood pressure, shock index); early warning charts; haemoglobin levels; and predelivery fibrinogen levels. Eligible reference standards included objective methods such as: gravimetric blood loss measurement, which involves weighing collected blood, as well as weighing blood-soaked pads, gauze and sheets, and subtracting their dry weight; calibrated devices to measure blood volume (volumetric blood loss measurement); the alkaline-haematin method of blood loss estimation; and blood extracted using machine-extraction and measured spectrometrically as oxyhaemoglobin., Data Collection and Analysis: At least two review authors, working independently, undertook study screening, selection, data extraction, assessment of risk of bias, and assessment of the certainty of the evidence. We resolved any differences through consensus or with input from another author. We generated 2 x 2 tables of the true positives, true negatives, false positives, and false negatives to calculate the sensitivity, specificity, and 95% confidence intervals for each index test. We presented sensitivity and specificity estimates from studies in forest plots. Where possible, we conducted meta-analyses for each index test and reference standard combination for each target condition. We examined heterogeneity by visual inspection of the forest plots., Main Results: Our review included 18 studies with a total of 291,040 participants. Fourteen studies evaluated PPH and seven studies evaluated severe PPH. Most studies were conducted in a hospital setting (16 of 18). There were four studies at high risk of bias for the patient selection domain and 14 studies at low risk. For the index test domain, 10 studies were at low risk of bias, seven studies at high risk, and one study at uncertain risk. For the reference standard domain, one study was at high risk of bias and 17 studies at low risk. For the flow and timing domain, three studies were at high risk of bias and 15 studies at low risk. The applicability concerns were low for all studies across the domains. In the abstract, we have prioritised reporting results for common, important thresholds for index tests or where the certainty of the evidence for the sensitivity estimate was at least moderate. Full results are in the main body of the review. PPH (blood loss ≥ 500 mL) For PPH, visual estimation with gravimetric blood loss measurement as the reference standard had 48% sensitivity (95% confidence interval (CI) 44% to 53%; moderate certainty) and 97% specificity (95% CI 95% to 99%; high certainty) (4 studies, 196,305 participants). Visual estimation with volumetric blood loss measurement as the reference standard showed 22% sensitivity (95% CI 12% to 37%; moderate certainty) and 99% specificity (95% CI 97% to 100%; moderate certainty) (2 studies, 514 participants). The diagnostic approach with calibrated drape plus observations, with gravimetric blood loss measurement as the reference standard for PPH, showed 93% sensitivity (95% CI 92% to 94%; high certainty) and 95% specificity (95% CI 95% to 96%; high certainty) (2 studies, 53,762 participants). A haemoglobin level of less than 10 g/dL with gravimetric blood loss measurement as the reference standard showed 37% sensitivity (95% CI 30% to 44%; high certainty) and 79% specificity (95% CI 76% to 82%; high certainty) (1 study, 1058 participants). Severe PPH (blood loss ≥ 1000 mL) For severe PPH, visual estimation, with volumetric plus gravimetric blood loss measurement as the reference standard, showed 9% sensitivity (95% CI 0% to 41%; low certainty) and 100% specificity (95% CI 99% to 100%; moderate certainty) (1 study, 274 participants). A shock index level of 1.0 or higher (commonly used as a threshold for severe PPH) up to two hours after birth, with gravimetric blood loss measurement as the reference standard, showed 30% sensitivity (95% CI 27% to 33%; moderate certainty) and 93% specificity (95% CI 92% to 93%; moderate certainty) (1 study, 30,820 participants). A haemoglobin level of less than 10 g/dL, with gravimetric blood loss measurement as the reference standard, showed 71% sensitivity (95% CI 51% to 87%; moderate certainty) and 77% specificity (95% CI 75% to 80%; high certainty) (1 study, 1058 participants)., Authors' Conclusions: Visual estimation of blood loss to diagnose PPH showed low sensitivity and is likely to miss the diagnosis in half of women giving birth vaginally. A diagnostic approach using a calibrated drape to objectively measure blood loss plus clinical observations showed high sensitivity and specificity for diagnosing PPH. Other index tests showed low to moderate sensitivities in diagnosing PPH and severe PPH. Future research should determine the accuracy of diagnostic tests in non-hospital settings and consider combining index tests to increase the sensitivity of PPH diagnosis., Funding: Bill and Melinda Gates Foundation REGISTRATION: PROSPERO (CRD42024541874)., (Copyright © 2025 The Authors. Cochrane Database of Systematic Reviews published by John Wiley & Sons, Ltd. on behalf of The Cochrane Collaboration.)

Cervical cancer continues to disproportionately burden women in sub-Saharan Africa, and is the commonest gynecological cancer in Ghana. The Cervical Cancer Prevention and Training Centre (CCPTC), Battor, Ghana spearheaded the Ghana arm of the mPharma 10,000 Women Initiative (mTTWI) between September 2021 and October 2022. The aim of this study was to examine the outcomes of nationwide concurrent screening using high-risk human papillomavirus (hr-HPV) DNA testing and visual inspection methods, as well as factors associated with the screening outcomes. We conducted a descriptive retrospective cross-sectional study to estimate the prevalence of hr-HPV infection (nationally and regionally) and cervical lesions among women screened by graduates of our training center in their own settings (spokes) with remote supervision and mentoring by CCPTC trainers (hub). We modeled factors associated with hr-HPV infection using nominal logistic regression. Among 5217 women screened (mean age, 40.1 years), the overall prevalence of hr-HPV infection and cervical lesions were 29.1% (95% confidence interval [CI] 27.9-30.3) and 3.7% (95% CI 3.2-4.2), respectively. The prevalence distribution varied widely among regions, with the highest recorded in the Oti Region (32.8%) and the lowest recorded in the Upper West (20.7%) and North-East (20.7%) regions. The most frequently detected HPV genotype was other hr-HPV type(s) only (non-HPV16, non-HPV18) (23.5%; 95% CI 22.3-24.7), followed by HPV16 only (1.5%; 95% CI 1.2-1.8), and mixed infection with HPV18 + other hr-HPV type(s) (1.2%; 95% CI 0.9-1.5). Factors found to be significantly associated with hr-HPV infection among women screened included age < 35 years, having a relationship status apart from married/cohabitation, nulliparity, and HIV positivity. Drawing from our implementation of this model within the mTTWI, we posit that while Ghana prepares for organized screening, coordinating opportunistic screening could enable a phased expansion of cervical precancer screening with the help of international and local partners. This approach, combined with concurrent testing (hr-HPV DNA testing and visual inspection), holds promise for mitigating loss to follow-up among women requiring additional evaluation and lesion management., Competing Interests: Declarations. Competing interests: The authors declare that the research was conducted in the absence of any financial and non-financial relationships that could be construed as a potential conflict of interest. Ethical approval: This study complied with the Declaration of Helsinki (1964) and its later amendments. Verbal informed consent was sought from the women before administering the questionnaire, collecting cervical samples, and additional screening procedures. The consent procedure was approved by the Ethical Review Committee of the Catholic Hospital, Battor (approval no. CHB-ERC 0120/06/22), which also permitted the researchers to publish the study findings retrospectively., (© 2025. The Author(s).)

Residual microcalcifications on mammograms after neoadjuvant chemotherapy (NACT) pose a challenge in surgical decision-making. This single-centre retrospective review of all patients who had NACT for breast cancer over five years, evaluated the relationship between pathological complete response and residual microcalcifications, controlling for tumour size, nodal stage, grade, and receptor status, as well as the impact of residual microcalcifications on recurrence and survival. There was no significant association between pathological complete response (pCR) and residual microcalcifications (p = 0.763). We computed hazard ratios (HR) for Time to recurrence (TTR) and overall survival (OS) which were both not significant, with HR = 2.599, [0.290, 23.264], p = 0.393 and HR = 1.362 [0.123, 15.062], p = 0.801 respectively. The predictive and prognostic significance of residual microcalcifications remains to be proven. The surgical excision of these lesions should be considered based on individual patient risk., Competing Interests: Declaration of competing interest No relevant competing interests., (Copyright © 2024 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Background: The World Health Organization has set ambitious goals to eliminate cervical cancer, necessitating evidence on increasing coverage and access to screening and treatment in high-burden areas. We implemented a pilot program to assess the feasibility of obtaining self-collected specimens for high-risk human papillomavirus (hr-HPV) testing in Nzulezo stilt village, a hard-to-reach community in Ghana, and inviting only hr-HPV-positive women to a central location for colposcopy and possible treatment. Subsequently, this study aimed to investigate the prevalence of hr-HPV infection and cervical lesions among the women and to explore factors potentially associated with hr-HPV infection among them., Methods: This pilot community-based cross-sectional study utilized data from screening sessions held from 2 to 20 November 2021 with specimens collected by participants using Evalyn brushes. HPV DNA testing was performed using the Sansure MA-6000 platform, while visual inspection utilized the Enhanced Visual Assessment (EVA) mobile colposcope. Univariate and multivariable nominal logistic regression was employed to explore factors associated with hr-HPV positivity., Results: Among 100 women screened (mean age, 43.6 ± 14.5 years), the overall hr-HPV prevalence rate was 39.0% (95% CI, 29.4-49.3). The prevalence rates of hr-HPV genotypes were stratified as follows: HPV16-8.0% (95% CI, 3.5-15.2), HPV18-5.0% (95% CI, 1.6-11.2), and other genotype(s) - 31.0% (95% CI, 22.1-41.0). Single-genotype infections with HPV16 and HPV18 were found in 4.0% (95% CI, 1.1-9.9) and 3.0% (95% CI, 0.6-8.5) of women, respectively. Mixed infections were observed in 1.0% (95% CI, 0.0-5.4) for HPV16 + 18, 3.0% (95% CI, 0.6-8.5) for HPV16 + other type(s), and 1.0% (95% CI, 0.0-5.4) for HPV18 + other type(s). The prevalence of cervical lesions among hr-HPV-positive women screened via colposcopy was 11.4% (95% CI, 3.2-26.7). In the multivariable model, reliance on other sources for medical bill payment was associated with hr-HPV infection (aOR, 0.20; 95% CI, 0.04-0.93), whereas age was not (aOR, 1.02; 95% CI, 0.99-1.05)., Conclusions: A high hr-HPV infection prevalence was recorded among the women. Utilizing technologies such as self-sampling, HPV DNA testing, and mobile colposcopy enables screening and treatment in remote and hard-to-reach communities where access to cervical cancer screening and treatment would otherwise be limited. Further research is warranted to assess the value and scalability of this approach in similar remote areas and its potential implementation in future programs., (© 2024. The Author(s).)

Objective: To identify and prioritise early pregnancy risk factors for stillbirth to inform prognostic factor and model research., Study Design: We used a modified e-Delphi method and consultation meeting to achieve consensus. Risk factors for early, late and stillbirth at any gestation identified from an umbrella review of risk factors for stillbirth were entered into a two-stage online Delphi survey with an international group of stakeholders made up of healthcare professionals and researchers. The RAND/ University of California at Los Angeles appropriateness method was used to evaluate consensus. Responders voted on a scale of 1-9 for each risk factor in terms of importance for early, late, and stillbirth at any gestation. Consensus for inclusion was reached if the median score was in the top tertile and at least two thirds of panellists had scored the risk factor within the top tertile., Results: Twenty-six risk factors were identified from an umbrella review and presented to stakeholders in round 1 of our e-Delphi survey. Round 1 was completed by 68 stakeholders, 79% (54/68) of whom went on to complete the second round. Seventeen risk factors were discussed at the consensus meeting. From the twenty-six risk factors identified, fifteen of these were prioritised for stillbirth at any gestation, eleven for early stillbirth, and sixteen for late stillbirth, across three domains of maternal characteristics, ultrasound markers and biochemical markers. The prioritised maternal characteristics common to early, late, and stillbirth at any gestation were: maternal age, smoking, drug misuse, history of heritable thrombophilia, hypertension, renal disease, diabetes, previous stillbirth and multiple pregnancy. Maternal BMI, access to healthcare, and socioeconomic status were prioritised for late stillbirth and stillbirth at any gestation. Previous pre-eclampsia and previous small for gestational age baby were prioritised for late stillbirth. Of the ultrasound markers, uterine artery Doppler pulsatility index and congenital fetal anomaly were prioritised for all. One biochemical marker, placental growth factor, was prioritised for stillbirth at any gestation., Conclusions: Our prioritised risk factors for stillbirth can inform formal factor-outcome evaluation of early pregnancy risk factors to influence public health strategies on prevention of such risk factors to prevent stillbirth., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Crown Copyright © 2024. Published by Elsevier B.V. All rights reserved.)

Objective : Ensuring the sustainability of the migrant workforce requires a comprehensive understanding of the psychological challenges faced by this sub-population due to concerns about the wellbeing and financial situation of family members in their home countries. Therefore, this study investigates the factors associated with psychological distress among sub-Saharan Africa (SSA) migrant workers across Australia and Canada during the COVID-19 pandemic. Method : Data were collected from 378 first-generation migrant workers with SSA ancestry residing in Australia and Canada using the Depression Anxiety and Stress Scale 21 (DASS-21). Multivariate logistic regression analysis was used to determine socio-demographic factors associated with depression, anxiety, and stress among SSA migrants' populations. Results : Across both countries, migrants with lower levels of education were more prone to reporting feelings of depression, anxiety, and stress during the pandemic. Female participants in Australia were more likely to report feeling of depression. Participants in Australia and Canada who were separated/divorced/widowed were less likely to report stress and depression, respectively. Participants in Australia who had lived in Australia between 11 and 20 years and those between 36 and 50 years old were more likely to report feelings of depression. Participants residing in Australia whose SSA ancestry was Southern Africa/Central Africa were more likely to report anxiety. Participants in Australia who worked as part-time permanent workers and those who worked as fixed-term workers/short-term/casual workers were less likely to report anxiety. Finally, participants in Canada who reported two or more people living with them had higher odds of reporting anxiety. Conclusions : The findings from this study highlight key factors associated with SSA migrant workers' psychological distress during the pandemic. The results can inform policies and provide insight to the development of mental health intervention strategies for migrant workers to minimize similar distress during pandemics.

Objective: To predict birth weight at various potential gestational ages of delivery based on data routinely available at the first antenatal visit., Design: Individual participant data meta-analysis., Data Sources: Individual participant data of four cohorts (237 228 pregnancies) from the International Prediction of Pregnancy Complications (IPPIC) network dataset., Eligibility Criteria for Selecting Studies: Studies in the IPPIC network were identified by searching major databases for studies reporting risk factors for adverse pregnancy outcomes, such as pre-eclampsia, fetal growth restriction, and stillbirth, from database inception to August 2019. Data of four IPPIC cohorts (237 228 pregnancies) from the US (National Institute of Child Health and Human Development, 2018; 233 483 pregnancies), UK (Allen et al, 2017; 1045 pregnancies), Norway (STORK Groruddalen research programme, 2010; 823 pregnancies), and Australia (Rumbold et al, 2006; 1877 pregnancies) were included in the development of the model., Results: The IPPIC birth weight model was developed with random intercept regression models with backward elimination for variable selection. Internal-external cross validation was performed to assess the study specific and pooled performance of the model, reported as calibration slope, calibration-in-the-large, and observed versus expected average birth weight ratio. Meta-analysis showed that the apparent performance of the model had good calibration (calibration slope 0.99, 95% confidence interval (CI) 0.88 to 1.10; calibration-in-the-large 44.5 g, -18.4 to 107.3) with an observed versus expected average birth weight ratio of 1.02 (95% CI 0.97 to 1.07). The proportion of variation in birth weight explained by the model (R 2 ) was 46.9% (range 32.7-56.1% in each cohort). On internal-external cross validation, the model showed good calibration and predictive performance when validated in three cohorts with a calibration slope of 0.90 (Allen cohort), 1.04 (STORK Groruddalen cohort), and 1.07 (Rumbold cohort), calibration-in-the-large of -22.3 g (Allen cohort), -33.42 (Rumbold cohort), and 86.4 g (STORK Groruddalen cohort), and observed versus expected ratio of 0.99 (Rumbold cohort), 1.00 (Allen cohort), and 1.03 (STORK Groruddalen cohort); respective pooled estimates were 1.00 (95% CI 0.78 to 1.23; calibration slope), 9.7 g (-154.3 to 173.8; calibration-in-the-large), and 1.00 (0.94 to 1.07; observed v expected ratio). The model predictions were more accurate (smaller mean square error) in the lower end of predicted birth weight, which is important in informing clinical decision making., Conclusions: The IPPIC birth weight model allowed birth weight predictions for a range of possible gestational ages. The model explained about 50% of individual variation in birth weights, was well calibrated (especially in babies at high risk of fetal growth restriction and its complications), and showed promising performance in four different populations included in the individual participant data meta-analysis. Further research to examine the generalisability of performance in other countries, settings, and subgroups is required., Trial Registration: PROSPERO CRD42019135045., Competing Interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/disclosure-of-interest/ and declare: support from the National Institute for Health and Care Research Health Technology Assessment UK programme for the submitted work; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 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: Fetal growth restriction is associated with perinatal morbidity and mortality. Early identification of women having at-risk fetuses can reduce perinatal adverse outcomes., Objectives: To assess the predictive performance of existing models predicting fetal growth restriction and birthweight, and if needed, to develop and validate new multivariable models using individual participant data., Design: Individual participant data meta-analyses of cohorts in International Prediction of Pregnancy Complications network, decision curve analysis and health economics analysis., Participants: Pregnant women at booking. External validation of existing models (9 cohorts, 441,415 pregnancies); International Prediction of Pregnancy Complications model development and validation (4 cohorts, 237,228 pregnancies)., Predictors: Maternal clinical characteristics, biochemical and ultrasound markers., Primary Outcomes: fetal growth restriction defined as birthweight <10th centile adjusted for gestational age and with stillbirth, neonatal death or delivery before 32 weeks' gestation birthweight., Analysis: First, we externally validated existing models using individual participant data meta-analysis. If needed, we developed and validated new International Prediction of Pregnancy Complications models using random-intercept regression models with backward elimination for variable selection and undertook internal-external cross-validation. We estimated the study-specific performance ( c -statistic, calibration slope, calibration-in-the-large) for each model and pooled using random-effects meta-analysis. Heterogeneity was quantified using τ 2 and 95% prediction intervals. We assessed the clinical utility of the fetal growth restriction model using decision curve analysis, and health economics analysis based on National Institute for Health and Care Excellence 2008 model., Results: Of the 119 published models, one birthweight model (Poon) could be validated. None reported fetal growth restriction using our definition. Across all cohorts, the Poon model had good summary calibration slope of 0.93 (95% confidence interval 0.90 to 0.96) with slight overfitting, and underpredicted birthweight by 90.4 g on average (95% confidence interval 37.9 g to 142.9 g). The newly developed International Prediction of Pregnancy Complications-fetal growth restriction model included maternal age, height, parity, smoking status, ethnicity, and any history of hypertension, pre-eclampsia, previous stillbirth or small for gestational age baby and gestational age at delivery. This allowed predictions conditional on a range of assumed gestational ages at delivery. The pooled apparent c -statistic and calibration were 0.96 (95% confidence interval 0.51 to 1.0), and 0.95 (95% confidence interval 0.67 to 1.23), respectively. The model showed positive net benefit for predicted probability thresholds between 1% and 90%. In addition to the predictors in the International Prediction of Pregnancy Complications-fetal growth restriction model, the International Prediction of Pregnancy Complications-birthweight model included maternal weight, history of diabetes and mode of conception. Average calibration slope across cohorts in the internal-external cross-validation was 1.00 (95% confidence interval 0.78 to 1.23) with no evidence of overfitting. Birthweight was underestimated by 9.7 g on average (95% confidence interval -154.3 g to 173.8 g)., Limitations: We could not externally validate most of the published models due to variations in the definitions of outcomes. Internal-external cross-validation of our International Prediction of Pregnancy Complications-fetal growth restriction model was limited by the paucity of events in the included cohorts. The economic evaluation using the published National Institute for Health and Care Excellence 2008 model may not reflect current practice, and full economic evaluation was not possible due to paucity of data., Future Work: International Prediction of Pregnancy Complications models' performance needs to be assessed in routine practice, and their impact on decision-making and clinical outcomes needs evaluation., Conclusion: The International Prediction of Pregnancy Complications-fetal growth restriction and International Prediction of Pregnancy Complications-birthweight models accurately predict fetal growth restriction and birthweight for various assumed gestational ages at delivery. These can be used to stratify the risk status at booking, plan monitoring and management., Study Registration: This study is registered as PROSPERO CRD42019135045., Funding: This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 17/148/07) and is published in full in Health Technology Assessment ; Vol. 28, No. 14. See the NIHR Funding and Awards website for further award information.

Objective: Central diabetes insipidus or vasopressin deficiency (AVP-D) is the most frequent water balance disorder after transsphenoidal surgery (TSS) with variable prevalence amongst studies. We aimed to determine rates of newly developed transient or permanent AVP-D in patients with pituitary tumours treated with TSS., Design and Methods: We performed systematic review of Medline, Embase, and Cochrane Library between January 1, 2000 and January 31, 2021 for studies reporting on outcomes for pituitary adenoma, craniopharyngioma, and Rathke's cleft cyst (RCC) after TSS and providing definition of post-operative AVP-D. We pooled the results as proportions with 95% confidence intervals (CIs) using Freeman-Tukey transformation random effects meta-analysis., Results: From 11 694 studies, 51 were included. Rates of transient or permanent AVP-D were: 17% (95% CI, 13-21) and 3% (95% CI, 2-5) in total group, 16% (95% CI, 12-21) and 2% (95% CI, 2-3) in pituitary adenomas, 31% (95% CI, 24-39) and 30% (95% CI, 22-39) in craniopharyngiomas, and 35% (95% CI, 16-57) and 14% (95% CI, 6-23) in RCCs, respectively. Based on diagnostic criteria, rates of transient or permanent AVP-D were: For hypotonic polyuria, 14% (95% CI, 8-22) and 3% (95% CI, 1-4), for hypotonic polyuria and hypernatraemia, 21% (95% CI, 13-29) and 5% (95% CI, 2-11), and for desmopressin administration, 22% (95% CI, 15-29) and 9% (95% CI, 0-30), respectively., Conclusions: Following TSS, a small proportion of patients with pituitary adenoma have permanent AVP-D (2%), but prevalence reaches 30% in ones with craniopharyngioma and 14% in those with RCC. Diagnostic criteria for post-operative AVP-D remain variable affecting reported rates of this condition., (© The Author(s) 2024. Published by Oxford University Press on behalf of European Society of Endocrinology.)

Background: ART is associated with higher rates of twin pregnancies than singleton pregnancies. Whether twin pregnancies conceived following ART have additional maternal and neonatal complications compared with non-ART twin pregnancies is not known., Objective and Rationale: The objective was to quantify the risk of adverse maternal and perinatal outcomes among twin pregnancies conceived following ART compared with non-ART and natural conception. Existing reviews vary in the reported outcomes, with many studies including triplet pregnancies in the study population. Therefore, we aimed to perform an up-to-date review with an in-depth analysis of maternal and perinatal outcomes limited to twin pregnancies., Search Methods: We searched electronic databases MEDLINE and EMBASE from January 1990 to May 2023 without language restrictions. All cohort studies reporting maternal and perinatal outcomes following ART compared with non-ART twin pregnancies and natural conception were included. Case-control studies, case reports, case series, animal studies, and in vitro studies were excluded. The Newcastle-Ottawa Scale was used to assess the methodological quality of the studies. Using random-effects meta-analysis, the estimates were pooled and the findings were reported as odds ratios (OR) with 95% CI., Outcomes: We included 111 studies (802 462 pregnancies). Twin pregnancies conceived following ART were at higher risk of preterm birth at <34 weeks (OR 1.33, 95% CI 1.14-1.56, 29 studies, I2 = 73%), <37 weeks (OR 1.26, 95% CI 1.19-1.33, 70 studies, I2 = 76%), hypertensive disorders in pregnancy (OR 1.29, 95% CI 1.14-1.46, 59 studies, I2 = 87%), gestational diabetes mellitus (OR 1.61, 95% CI 1.48-1.75, 51 studies, I2 = 65%), and caesarean delivery (OR 1.80, 95% CI 1.65-1.97, 70 studies, I2 = 89%) compared with non-ART twins. The risks for the above maternal outcomes were also increased in the ART group compared with natural conception. Of the perinatal outcomes, ART twins were at significantly increased risk of congenital malformations (OR 1.17, 95% CI 1.05-1.30, 39 studies, I2 = 59%), birthweight discordance (>25% (OR 1.31, 95% CI 1.05-1.63, 7 studies, I2 = 0%)), respiratory distress syndrome (OR 1.32, 95% CI 1.09-1.60, 16 studies, I2 = 61%), and neonatal intensive care unit admission (OR 1.24, 95% CI 1.14-1.35, 32 studies, I2 = 87%) compared with non-ART twins. When comparing ART with natural conception, the risk of respiratory distress syndrome, intensive care admissions, and birthweight discordance >25% was higher among the ART group. Perinatal complications, such as stillbirth (OR 0.83, 95% CI 0.70-0.99, 33 studies, I2 = 49%), small for gestational age <10th centile (OR 0.90, 95% CI 0.85-0.95, 26 studies, I2 = 36%), and twin-twin transfusion syndrome (OR 0.45, 95% CI 0.25-0.82, 9 studies, I2 = 25%), were reduced in twin pregnancies conceived with ART versus those without ART. The above perinatal complications were also fewer amongst the ART group than natural conception., Wider Implications: ART twin pregnancies are associated with higher maternal complications than non-ART pregnancies and natural conception, with varied perinatal outcomes. Women seeking ART should be counselled about the increased risks of ART twin pregnancies and should be closely monitored in pregnancy for complications. We recommend exercising caution when interpreting the study findings owing to the study's limitations., (© The Author(s) 2024. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology.)

Objective: To assess the effects of COVID-19 vaccines in women before or during pregnancy on SARS-CoV-2 infection-related, pregnancy, offspring and reactogenicity outcomes., Design: Systematic review and meta-analysis., Data Sources: Major databases between December 2019 and January 2023., Study Selection: Nine pairs of reviewers contributed to study selection. We included test-negative designs, comparative cohorts and randomised trials on effects of COVID-19 vaccines on infection-related and pregnancy outcomes. Non-comparative cohort studies reporting reactogenicity outcomes were also included., Quality Assessment, Data Extraction and Analysis: Two reviewers independently assessed study quality and extracted data. We undertook random-effects meta-analysis and reported findings as HRs, risk ratios (RRs), ORs or rates with 95% CIs., Results: Sixty-seven studies (1 813 947 women) were included. Overall, in test-negative design studies, pregnant women fully vaccinated with any COVID-19 vaccine had 61% reduced odds of SARS-CoV-2 infection during pregnancy (OR 0.39, 95% CI 0.21 to 0.75; 4 studies, 23 927 women; I 2 =87.2%) and 94% reduced odds of hospital admission (OR 0.06, 95% CI 0.01 to 0.71; 2 studies, 868 women; I 2 =92%). In adjusted cohort studies, the risk of hypertensive disorders in pregnancy was reduced by 12% (RR 0.88, 95% CI 0.82 to 0.92; 2 studies; 115 085 women), while caesarean section was reduced by 9% (OR 0.91, 95% CI 0.85 to 0.98; 6 studies; 30 192 women). We observed an 8% reduction in the risk of neonatal intensive care unit admission (RR 0.92, 95% CI 0.87 to 0.97; 2 studies; 54 569 women) in babies born to vaccinated versus not vaccinated women. In general, vaccination during pregnancy was not associated with increased risk of adverse pregnancy or perinatal outcomes. Pain at the injection site was the most common side effect reported (77%, 95% CI 52% to 94%; 11 studies; 27 195 women)., Conclusion: COVID-19 vaccines are effective in preventing SARS-CoV-2 infection and related complications in pregnant women., Prospero Registration Number: CRD42020178076., Competing Interests: Competing interests: None declared., (© World Health Organization 2024. Licensee BMJ.)

Background: Pregnant women infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are more likely to experience preterm birth and their neonates are more likely to be stillborn or admitted to a neonatal unit. The World Health Organization declared in May 2023 an end to the coronavirus disease 2019 (COVID-19) pandemic as a global health emergency. However, pregnant women are still becoming infected with SARS-CoV-2 and there is limited information available regarding the effect of SARS-CoV-2 infection in early pregnancy on pregnancy outcomes., Objective and Rationale: We conducted this systematic review to determine the prevalence of early pregnancy loss in women with SARS-Cov-2 infection and compare the risk to pregnant women without SARS-CoV-2 infection., Search Methods: Our systematic review is based on a prospectively registered protocol. The search of PregCov19 consortium was supplemented with an extra electronic search specifically on pregnancy loss in pregnant women infected with SARS-CoV-2 up to 10 March 2023 in PubMed, Google Scholar, and LitCovid. We included retrospective and prospective studies of pregnant women with SARS-CoV-2 infection, provided that they contained information on pregnancy losses in the first and/or second trimester. Primary outcome was miscarriage defined as a pregnancy loss before 20 weeks of gestation, however, studies that reported loss up to 22 or 24 weeks were also included. Additionally, we report on studies that defined the pregnancy loss to occur at the first and/or second trimester of pregnancy without specifying gestational age, and for second trimester miscarriage only when the study presented stillbirths and/or foetal losses separately from miscarriages. Data were stratified into first and second trimester. Secondary outcomes were ectopic pregnancy (any extra-uterine pregnancy), and termination of pregnancy. At least three researchers independently extracted the data and assessed study quality. We calculated odds ratios (OR) and risk differences (RDs) with corresponding 95% CI and pooled the data using random effects meta-analysis. To estimate risk prevalence, we performed meta-analysis on proportions. Heterogeneity was assessed by I2., Outcomes: We included 120 studies comprising a total of 168 444 pregnant women with SARS-CoV-2 infection; of which 18 233 women were in their first or second trimester of pregnancy. Evidence level was considered to be of low to moderate certainty, mostly owing to selection bias. We did not find evidence of an association between SARS-CoV-2 infection and miscarriage (OR 1.10, 95% CI 0.81-1.48; I2 = 0.0%; RD 0.0012, 95% CI -0.0103 to 0.0127; I2 = 0%; 9 studies, 4439 women). Miscarriage occurred in 9.9% (95% CI 6.2-14.0%; I2 = 68%; 46 studies, 1797 women) of the women with SARS CoV-2 infection in their first trimester and in 1.2% (95% CI 0.3-2.4%; I2 = 34%; 33 studies; 3159 women) in the second trimester. The proportion of ectopic pregnancies in women with SARS-CoV-2 infection was 1.4% (95% CI 0.02-4.2%; I2 = 66%; 14 studies, 950 women). Termination of pregnancy occurred in 0.6% of the women (95% CI 0.01-1.6%; I2 = 79%; 39 studies; 1166 women)., Wider Implications: Our study found no indication that SARS-CoV-2 infection in the first or second trimester increases the risk of miscarriages. To provide better risk estimates, well-designed studies are needed that include pregnant women with and without SARS-CoV-2 infection at conception and early pregnancy and consider the association of clinical manifestation and severity of SARS-CoV-2 infection with pregnancy loss, as well as potential confounding factors such as previous pregnancy loss. For clinical practice, pregnant women should still be advised to take precautions to avoid risk of SARS-CoV-2 exposure and receive SARS-CoV-2 vaccination., (© The Author(s) 2023. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology.)

Objectives: Daily calcium supplements are recommended for pregnant women from 20 weeks' gestation to prevent pre-eclampsia in populations with low dietary calcium intake. We aimed to improve understanding of barriers and facilitators for calcium supplement intake during pregnancy to prevent pre-eclampsia., Design: Mixed-method systematic review, with confidence assessed using the Grading of Recommendations, Assessment, Development and Evaluations-Confidence in the Evidence from Reviews of Qualitative research approach., Data Sources: MEDLINE and EMBASE (via Ovid), CINAHL and Global Health (via EBSCO) and grey literature databases were searched up to 17 September 2022., Eligibility Criteria: We included primary qualitative, quantitative and mixed-methods studies reporting implementation or use of calcium supplements during pregnancy, excluding calcium fortification and non-primary studies. No restrictions were imposed on settings, language or publication date., Data Extraction and Synthesis: Two independent reviewers extracted data and assessed risk of bias. We analysed the qualitative data using thematic synthesis, and quantitative findings were thematically mapped to qualitative findings. We then mapped the results to behavioural change frameworks to identify barriers and facilitators., Results: Eighteen reports from nine studies were included in this review. Women reported barriers to consuming calcium supplements included limited knowledge about calcium supplements and pre-eclampsia, fears and experiences of side effects, varying preferences for tablets, dosing, working schedules, being away from home and taking other supplements. Receiving information regarding pre-eclampsia and safety of calcium supplement use from reliable sources, alternative dosing options, supplement reminders, early antenatal care, free supplements and support from families and communities were reported as facilitators. Healthcare providers felt that consistent messaging about benefits and risks of calcium, training, and ensuring adequate staffing and calcium supply is available would be able to help them in promoting calcium., Conclusion: Relevant stakeholders should consider the identified barriers and facilitators when formulating interventions and policies on calcium supplement use. These review findings can inform implementation to ensure effective and equitable provision and scale-up of calcium interventions., Prospero Registration Number: CRD42021239143., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY. Published by BMJ.)

Background: There is an ongoing debate on how to best identify patients with gastroesophageal reflux disease (GERD) before bariatric surgery. The value of routine preoperative esophagogastroduodenoscopy (EGD) is questioned, and patient reported symptoms are commonly used for screening. The goal of this study is to determine if patient reported symptoms using a validated questionnaire correlate with preoperative EGD findings., Methodology: A prospective cohort study at a single institution was performed. Patients undergoing bariatric surgery between December 2020 and March 2023 were required to report symptoms of reflux by completing a preoperative GERD. Health-Related Quality of Life (GERD-HRQL) questionnaire and undergo a mandatory preoperative screening EGD. Patients were stratified into two cohorts: (group A) asymptomatic (score = 0) and (group B) symptomatic (score > 0). Statistical analysis was conducted using Pearson's chi-squared test and Wilcoxon rank-sum test in RStudio version 4.2.2. The predictive value of the GERD-HRQL score was analyzed using Areas Under the Curve (AUC; AUC = 0.5 not predictive, 0.5 < AUC ≥ 6 poor prediction & AUC > 0.9 excellent prediction) calculated from Receiver Operating Characteristic (ROC) curves., Results: 200 patients were included; median age was 42.0 years (IQR 36.0 to 49.2). There were 79 patients (39.5%) in Group A and 121 patients (60.5%) in Group B. There was no difference in the frequency esophagitis (27.8% vs 32.2%, p = 0.61) or hiatal hernias (49.4% vs 47.1%, p = 0. 867) between group A and group B, respectively. ROC analysis revealed that the total GERD HRQL scores, heartburn only scores and regurgitation only scores, were poor predictors of esophagitis found on EGD (AUC 0.52, 0.53, 0.52), respectively. In asymptomatic patients, higher BMI was significantly associated with esophagitis (OR 1.15, 95% CI 1.06-1.27, p = 0.002)., Conclusion: Symptoms, identified through the GERD-HRQL questionnaire, are a poor indicator of esophagitis or its severity in patients undergoing workup for bariatric surgery. Therefore, liberal screening upper endoscopy is recommended for pre-bariatric surgery patients to guide appropriate procedure selection., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Introduction: Maternal obesity increases the risk of multiple maternal and infant pregnancy complications, such as gestational diabetes and pre-eclampsia. Current UK guidelines use body mass index (BMI) to identify which women require additional care due to increased risk of complications. However, BMI may not accurately predict which women will develop complications during pregnancy as it does not determine amount and distribution of adipose tissue. Some adiposity measures (eg, waist circumference, ultrasound measures of abdominal visceral fat) can better identify where body fat is stored, which may be useful in predicting those women who need additional care., Methods and Analysis: This prospective cohort study (SHAPES, Study of How Adiposity in Pregnancy has an Effect on outcomeS) aims to evaluate the prognostic performance of adiposity measures (either alone or in combination with other adiposity, sociodemographic or clinical measures) to estimate risk of adverse pregnancy outcomes. Pregnant women (n=1400) will be recruited at their first trimester ultrasound scan (11 +2 -14 +1 weeks') at Newcastle upon Tyne National Health Service Foundation Trust, UK. Early pregnancy adiposity measures and clinical and sociodemographic data will be collected. Routine data on maternal and infant pregnancy outcomes will be collected from routine hospital records. Regression methods will be used to compare the different adiposity measures with BMI in terms of their ability to predict pregnancy complications. If no individual measure performs better than BMI, multivariable models will be developed and evaluated to identify the most parsimonious model. The apparent performance of the developed model will be summarised using calibration, discrimination and internal validation analyses., Ethics and Dissemination: Ethical favourable opinion has been obtained from the North East: Newcastle & North Tyneside 1 Research Ethics Committee (REC reference: 22/NE/0035). All participants provide informed consent to take part in SHAPES. Planned dissemination includes peer-reviewed publications and additional dissemination appropriate to target audiences, including policy briefs for policymakers, media/social-media coverage for public and conferences for research TRIAL REGISTRATION NUMBER: ISRCTN82185177., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

The risk of adverse perinatal and maternal outcomes increases with gestational age, and although induction of labour may reduce these risks, the optimal timing of induction remains unknown. We carried out a systematic review and meta-analysis, to determine the gestational age at which induction should be offered. We searched Cochrane Central Register of Controlled Trials, Medline, and Embase databases from inception to July 2022, to identify randomised trials comparing induction of labour at or beyond 37' weeks gestation with expectant management or delayed induction, and according to the gestational age at planned induction. We undertook random effects meta-analysis and pooled estimates as odds ratios with 95% confidence intervals. We assessed risk of bias of studies using the Cochrane Risk of Bias tool 2.0. We included 44 trials (23,960 women and 22,191 offspring) from 1,839 citations in our meta-analysis. The odds of perinatal death (odds ratio 0.42, 95% confidence interval 0.22 to 0.81; 26 studies, 20,154 offspring), stillbirth (0.40, 0.16 to 0.98; 25 studies, 19,412 offspring), admission to neonatal intensive care unit (0.86, 0.78 to 0.96; 23 studies, 18,846 offspring), and caesarean section (0.90, 0.83 to 0.98; 40 studies, 23,616 women) were reduced in the induction of labour group compared to expectant management or delayed induction. The odds of admission to neonatal intensive care unit (0.82, 0.70 to 0.96; 6 studies, 9,316 offspring) were lower with induction of labour at 41 weeks compared to induction at or after 42 weeks' gestation, and the odds of caesarean section were reduced with labour induction at 39 weeks' compared to induction at or after 40 weeks' (0.83, 0.74 to 0.93; 8 studies, 7,677 women). There were no significant differences in pregnancy outcomes by method of induction of labour. Induction of labour compared to expectant management or delayed induction reduces the risk of adverse pregnancy outcomes, and the optimal timing may depend on the specific outcome of interest., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Introduction: Low dietary calcium intake is a risk factor for pre-eclampsia, a major contributor to maternal and perinatal mortality and morbidity worldwide. Calcium supplementation can prevent pre-eclampsia in women with low dietary calcium. However, the optimal dose and timing of calcium supplementation are not known. We plan to undertake an individual participant data (IPD) meta-analysis of randomised trials to determine the effects of various calcium supplementation regimens in preventing pre-eclampsia and its complications and rank these by effectiveness. We also aim to evaluate the cost-effectiveness of calcium supplementation to prevent pre-eclampsia., Methods and Analysis: We will identify randomised trials on calcium supplementation before and during pregnancy by searching major electronic databases including Embase, CINAHL, MEDLINE, CENTRAL, PubMed, Scopus, AMED, LILACS, POPLINE, AIM, IMSEAR, ClinicalTrials.gov and the WHO International Clinical Trials Registry Platform, without language restrictions, from inception to February 2022. Primary researchers of the identified trials will be invited to join the International Calcium in Pregnancy Collaborative Network and share their IPD. We will check each study's IPD for consistency with the original authors before standardising and harmonising the data. We will perform a series of one-stage and two-stage IPD random-effect meta-analyses to obtain the summary intervention effects on pre-eclampsia with 95% CIs and summary treatment-covariate interactions (maternal risk status, dietary intake, timing of intervention, daily dose of calcium prescribed and total intake of calcium). Heterogeneity will be summarised using tau 2 , I 2 and 95% prediction intervals for effect in a new study. Sensitivity analysis to explore robustness of statistical and clinical assumptions will be carried out. Minor study effects (potential publication bias) will be investigated using funnel plots. A decision analytical model for use in low-income and middle-income countries will assess the cost-effectiveness of calcium supplementation to prevent pre-eclampsia., Ethics and Dissemination: No ethical approvals are required. We will store the data in a secure repository in an anonymised format. The results will be published in peer-reviewed journals., Prospero Registration Number: CRD42021231276., Competing Interests: Competing interests: None declared., (© World Health Organization 2023. Licensee BMJ.)

Introduction: Women and their infants are at increased risk of complications if gestational diabetes mellitus (GDM) or excessive gestational weight gain (GWG) occurs in pregnancy. Weight management interventions in pregnancy, consisting of diet and physical activity components are targeted based on maternal body mass index (BMI). However, the relative effectiveness of interventions targeted based on alternative measures of adiposity to BMI is unclear. This individual patient data (IPD) meta-analysis aims to explore whether interventions are more effective at preventing GDM and reducing GWG in women according to their level of adiposity., Methods: The International Weight Management in Pregnancy Collaborative Network has a living database of IPD from randomised trials of diet and/or physical activity interventions in pregnancy. This IPD meta-analysis will use IPD from trials identified from systematic literature searches up until March 2021, where maternal adiposity measures (eg, waist circumference) were collected prior to 20 weeks' gestation. A two-stage random effects IPD meta-analysis approach will be taken for each outcome (GDM and GWG) to understand the effect of early pregnancy adiposity measures on the effect of weight management interventions for GDM prevention and GWG reduction. Summary intervention effects with 95% CIs) will be derived along with treatment covariate interactions. Between-study heterogeneity will be summarised by I 2 and tau 2 statistics. Potential sources of bias will be evaluated, and the nature of any missing data will be explored and appropriate imputation methods adopted., Ethics and Dissemination: Ethics approval is not required. The study is registered on the International Prospective Register of Systematic Reviews (CRD42021282036). Results will be submitted to peer-reviewed journals., Prospero Registration Number: CRD42021282036., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Existing evidence on the effects of race and ethnicity on pregnancy outcomes is restricted to individual studies done within specific countries and health systems. We aimed to assess the impact of race and ethnicity on perinatal outcomes in high-income and upper-middle-income countries, and to ascertain whether the magnitude of disparities, if any, varied across geographical regions., Methods: For this individual participant data (IPD) meta-analysis we used data from the International Prediction of Pregnancy Complications (IPPIC) Network of studies on pregnancy complications; the full dataset comprised 94 studies, 53 countries, and 4 539 640 pregnancies. We included studies that reported perinatal outcomes (neonatal death, stillbirth, preterm birth, and small-for-gestational-age babies) in at least two racial or ethnic groups (White, Black, south Asian, Hispanic, or other). For our two-step random-effects IPD meta-analysis, we did multiple imputations for confounder variables (maternal age, BMI, parity, and level of maternal education) selected with a directed acyclic graph. The primary outcomes were neonatal mortality and stillbirth. Secondary outcomes were preterm birth and a small-for-gestational-age baby. We estimated the association of race and ethnicity with perinatal outcomes using a multivariate logistic regression model and reported this association with odds ratios (ORs) and 95% CIs. We also did a subgroup analysis of studies by geographical region., Findings: 51 studies from 20 high-income and upper-middle-income countries, comprising 2 198 655 pregnancies, were eligible for inclusion in this IPD meta-analysis. Neonatal death was twice as likely in babies born to Black women than in babies born to White women (OR 2·00, 95% CI 1·44-2·78), as was stillbirth (2·16, 1·46-3·19), and babies born to Black women were at increased risk of preterm birth (1·65, 1·46-1·88) and being small for gestational age (1·39, 1·13-1·72). Babies of women categorised as Hispanic had a three-times increased risk of neonatal death (OR 3·34, 95% CI 2·77-4·02) than did those born to White women, and those born to south Asian women were at increased risk of preterm birth (OR 1·26, 95% CI 1·07-1·48) and being small for gestational age (1·61, 1·32-1·95). The effects of race and ethnicity on preterm birth and small-for-gestational-age babies did not vary across regions., Interpretation: Globally, among underserved groups, babies born to Black women had consistently poorer perinatal outcomes than White women after adjusting for maternal characteristics, although the risks varied for other groups. The effects of race and ethnicity on adverse perinatal outcomes did not vary by region., Funding: National Institute for Health and Care Research, Wellbeing of Women., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Introduction: The prevalence of COVID-19 and its impact varied between countries and regions. Pregnant women are at high risk of COVID-19 complications compared with non-pregnant women. The magnitude of variations, if any, in SARS-CoV-2 infection rates and its health outcomes among pregnant women by geographical regions and country's income level is not known., Methods: We performed a random-effects meta-analysis as part of the ongoing PregCOV-19 living systematic review (December 2019 to April 2021). We included cohort studies on pregnant women with COVID-19 reporting maternal (mortality, intensive care admission and preterm birth) and offspring (mortality, stillbirth, neonatal intensive care admission) outcomes and grouped them by World Bank geographical region and income level. We reported results as proportions with 95% confidence intervals (CI)., Results: We included 311 studies (2 003 724 pregnant women, 57 countries). The rates of SARS-CoV-2 infection in pregnant women varied significantly by region (p&lt;0.001) and income level (p&lt;0.001), with the highest rates observed in Latin America and the Caribbean (19%, 95% CI 12% to 27%; 13 studies, 38 748 women) and lower-middle-income countries (13%, 95% CI 6% to 23%; 25 studies, 100 080 women). We found significant differences in maternal and offspring outcomes by region and income level. Lower-middle-income countries reported significantly higher rates of maternal mortality (0.68%, 95% CI 0.24% to 1.27%; 3 studies, 31 136 women), intensive care admission (4.53%, 95% CI 2.57% to 6.91%; 54 studies, 23 420 women) and stillbirths (1.09%, 95% CI 0.48% to 1.88%; 41 studies, 4724 women) than high-income countries. COVID-19 complications disproportionately affected South Asia, which had the highest maternal mortality rate (0.88%, 95% CI 0.16% to 1.95%; 17 studies, 2023 women); Latin America and the Caribbean had the highest stillbirth rates (1.97%, 95% CI 0.9% to 3.33%; 10 studies, 1750 women)., Conclusion: The rates of SARS-CoV-2 infection in pregnant women vary globally, and its health outcomes mirror the COVID-19 burden and global maternal and offspring inequalities., Prospero Registration Number: CRD42020178076., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: The ability to calculate the absolute risk of adverse pregnancy outcomes for an individual woman with gestational diabetes mellitus (GDM) would allow preventative and therapeutic interventions to be delivered to women at high-risk, sparing women at low-risk from unnecessary care. We aimed to develop, validate and evaluate the clinical utility of a prediction model for adverse pregnancy outcomes in women with GDM., Methods: A prediction model development and validation study was conducted on data from a observational cohort. Participants included all women with GDM from three metropolitan tertiary teaching hospitals in Melbourne, Australia. The development cohort comprised those who delivered between 1 July 2017 to 30 June 2018 and the validation cohort those who delivered between 1 July 2018 to 31 December 2018. The main outcome was a composite of critically important maternal and perinatal complications (hypertensive disorders of pregnancy, large-for-gestational age neonate, neonatal hypoglycaemia requiring intravenous therapy, shoulder dystocia, perinatal death, neonatal bone fracture and nerve palsy). Model performance was measured in terms of discrimination and calibration and clinical utility evaluated using decision curve analysis., Findings: The final PeRSonal (Prediction for Risk Stratified care for women with GDM) model included body mass index, maternal age, fasting and 1-hour glucose values (75-g oral glucose tolerance test), gestational age at GDM diagnosis, Southern and Central Asian ethnicity, East Asian ethnicity, nulliparity, past delivery of an large-for-gestational age neonate, past pre-eclampsia, GWG until GDM diagnosis, and family history of diabetes. The composite adverse pregnancy outcome occurred in 27% (476/1747) of women in the development (1747 women) and in 26% (244/955) in the validation (955 women) cohorts. The model showed excellent calibration with slope of 0.99 (95% CI 0.75 to 1.23) and acceptable discrimination ( c- statistic 0.68; 95% CI 0.64 to 0.72) when temporally validated. Decision curve analysis demonstrated that the model was useful across a range of predicted probability thresholds between 0.15 and 0.85 for adverse pregnancy outcomes compared to the alternatives of managing all women with GDM as if they will or will not have an adverse pregnancy outcome., Interpretation: The PeRSonal GDM model comprising of routinely available clinical data shows compelling performance, is transportable across time, and has clinical utility across a range of predicted probabilities. Further external validation of the model to a more disparate population is now needed to assess the generalisability to different centres, community based care and low resource settings, other healthcare systems and to different GDM diagnostic criteria., Funding: This work is supported by the Mothers and Gestational Diabetes in Australia 2 NHMRC funded project #1170847., Competing Interests: SDC reports grants from the National Health and Medical Research Council (NHMRC), Diabetes Australia, the Australian Academy of Science and the Australian Government Department of Education and Training during the conduct of the study; JAB reports grants from the NHMRC during the conduct of the study; BMFF reports grants from CIBER (Biomedical Research Network in Epidemiology and Public Health, Madrid, Spain) during the conduct of the study and HJT reports grants from the NHMRC and the Medical Research Future Fund during the conduct of the study; no other relationships or activities that could appear to have influenced the submitted work. All the other authors report no conflict of interests., (© 2022 The Author(s).)

Objectives: To map the care provided to pregnant women with epilepsy in UK maternity units and identify future research priorities by conducting a nationwide survey of healthcare professionals., Study Design: A prospective cross-sectional electronic survey was conducted between 29 April and 30 October 2021. The survey included 23 questions developed and refined with relevant stakeholders, including a woman with lived experience of epilepsy and pregnancy. We used descriptive analyses to summarise responses and estimated proportions with medians and interquartile ranges., Results: 144 individual healthcare professionals from 94 hospitals, representing 77 NHS Trusts, participated in the survey. Obstetricians were the most common responders (45%, 65/144) and almost half (47%, 7/15) of regions had a survey response rate per NHS Trust greater than 50%. Six pregnant women with epilepsy, on average, were booked into antenatal care per hospital per month, and 49% (46/94) of hospitals saw women for specialist antenatal care in the first trimester. The care provided across healthcare systems varied, with multiple pathways for referral to specialist care within regions. Midwife referral was the most used care pathway (80%, 75/94). Less than a third of hospitals (31%, 29/94) ran joint obstetric/neurology clinics for pregnant women with epilepsy. Most survey respondents (81%, 117/144) were confident talking to pregnant women about their risk of seizures but only a minority (20%, 29/144) used validated calculators to assess this risk. There was broad agreement across healthcare professionals that the priorities for research should focus on how to improve communication and address pregnant women's concerns regarding epilepsy and pregnancy, and to develop further understanding on the optimal use and long-term effects of anti-seizure medication., Conclusion: Our UK nationwide survey of hospital-based maternity services for pregnant women with epilepsy identified wide variation in when, how and by whom these women are seen, with differences between and within the UK regions. This survey highlights areas for improvement in the care of pregnant women with epilepsy., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Objective: Stillbirth is a potentially preventable complication of pregnancy. Identifying women at high risk of stillbirth can guide decisions on the need for closer surveillance and timing of delivery in order to prevent fetal death. Prognostic models have been developed to predict the risk of stillbirth, but none has yet been validated externally. In this study, we externally validated published prediction models for stillbirth using individual participant data (IPD) meta-analysis to assess their predictive performance., Methods: MEDLINE, EMBASE, DH-DATA and AMED databases were searched from inception to December 2020 to identify studies reporting stillbirth prediction models. Studies that developed or updated prediction models for stillbirth for use at any time during pregnancy were included. IPD from cohorts within the International Prediction of Pregnancy Complications (IPPIC) Network were used to validate externally the identified prediction models whose individual variables were available in the IPD. The risk of bias of the models and cohorts was assessed using the Prediction study Risk Of Bias ASsessment Tool (PROBAST). The discriminative performance of the models was evaluated using the C-statistic, and calibration was assessed using calibration plots, calibration slope and calibration-in-the-large. Performance measures were estimated separately in each cohort, as well as summarized across cohorts using random-effects meta-analysis. Clinical utility was assessed using net benefit., Results: Seventeen studies reporting the development of 40 prognostic models for stillbirth were identified. None of the models had been previously validated externally, and the full model equation was reported for only one-fifth (20%, 8/40) of the models. External validation was possible for three of these models, using IPD from 19 cohorts (491 201 pregnant women) within the IPPIC Network database. Based on evaluation of the model development studies, all three models had an overall high risk of bias, according to PROBAST. In the IPD meta-analysis, the models had summary C-statistics ranging from 0.53 to 0.65 and summary calibration slopes ranging from 0.40 to 0.88, with risk predictions that were generally too extreme compared with the observed risks. The models had little to no clinical utility, as assessed by net benefit. However, there remained uncertainty in the performance of some models due to small available sample sizes., Conclusions: The three validated stillbirth prediction models showed generally poor and uncertain predictive performance in new data, with limited evidence to support their clinical application. The findings suggest methodological shortcomings in their development, including overfitting. Further research is needed to further validate these and other models, identify stronger prognostic factors and develop more robust prediction models. © 2021 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology., (© 2021 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.)

ALK-positive histiocytosis is a rare subtype of histiocytic neoplasm first described in 2008 in 3 infants with multisystemic disease involving the liver and hematopoietic system. This entity has subsequently been documented in case reports and series to occupy a wider clinicopathologic spectrum with recurrent KIF5B-ALK fusions. The full clinicopathologic and molecular spectra of ALK-positive histiocytosis remain, however, poorly characterized. Here, we describe the largest study of ALK-positive histiocytosis to date, with detailed clinicopathologic data of 39 cases, including 37 cases with confirmed ALK rearrangements. The clinical spectrum comprised distinct clinical phenotypic groups: infants with multisystemic disease with liver and hematopoietic involvement, as originally described (Group 1A: 6/39), other patients with multisystemic disease (Group 1B: 10/39), and patients with single-system disease (Group 2: 23/39). Nineteen patients of the entire cohort (49%) had neurologic involvement (7 and 12 from Groups 1B and 2, respectively). Histology included classic xanthogranuloma features in almost one-third of cases, whereas the majority displayed a more densely cellular, monomorphic appearance without lipidized histiocytes but sometimes more spindled or epithelioid morphology. Neoplastic histiocytes were positive for macrophage markers and often conferred strong expression of phosphorylated extracellular signal-regulated kinase, confirming MAPK pathway activation. KIF5B-ALK fusions were detected in 27 patients, whereas CLTC-ALK, TPM3-ALK, TFG-ALK, EML4-ALK, and DCTN1-ALK fusions were identified in single cases. Robust and durable responses were observed in 11/11 patients treated with ALK inhibition, 10 with neurologic involvement. This study presents the existing clinicopathologic and molecular landscape of ALK-positive histiocytosis and provides guidance for the clinical management of this emerging histiocytic entity., (© 2022 by The American Society of Hematology.)

Objective: Clinical trials evaluating pharmacological and non-pharmacological treatment of COVID-19, either excluded pregnant women or included very few women. Unlike the numerous systematic reviews on prevalence, symptoms and adverse outcomes of COVID-19 in pregnancy, there are very few on the effects of treatment on maternal and neonatal outcomes in pregnancy. We undertook a systematic review of all published and unpublished studies on the effects of pharmacological and non-pharmacological interventions for COVID-19 on maternal and neonatal pregnancy outcomes., Data Sources: We performed a systematic literature search of the following databases: Medline, Embase, Cochrane database, WHO (World Health Organization) COVID-19 database, China National Knowledge Infrastructure (CNKI), and Wanfang databases from 1 December 2019 to 1 December 2020., Study Eligibility Criteria: Studies were only included if they involved pregnant or postnatal women who were exposed to pregnancy specific interventions like the mode of delivery and type of anaesthesia, pharmacological or non-pharmacological interventions., Study Appraisal and Synthesis Methods: We first screened the titles and abstracts of studies and then assessed the full text of the selected studies in detail for eligibility. Data on study design, population, type of screening for COVID-19, country, hospital, country status (high or low and middle income), treatment given (mode of delivery, type of anaesthesia, type of pharmacological and non-pharmacological treatment was extracted. The pre-defined maternal outcomes we collected were mode of delivery (vaginal or by caesarean section), severe or critical COVID-19 (as defined by the authors), symptomatic COVID-19, maternal death, maternal hospital admission, ICU admission, mechanical ventilation, ECMO and maternal pneumonia. The pre-defined neonatal outcomes we extracted were preterm birth (<37 weeks), stillbirth, neonatal death, NICU admission, neonatal COVID-19 positive, neonatal acidosis (pH < 7.0) and Apgar scores (<8 after 5 min). Study quality assessment was performed., Results: From a total of 342 potential eligible studies, we included 27 studies in our systematic review, including 4943 pregnant women (appendix 3). Sixteen studies had a retrospective cohort design and 11 a prospective cohort design. There were no randomised controlled trials. There was a significant association between caesarean section and admission to ICU (OR 4.99, 95% CI 1.24 to 20.12; 4 studies, 153 women, I 2  = 0%), and diagnosis of maternal COVID-19 pneumonia as defined by study authors (OR 3.09, 95% CI 1.52 to 6.28; 2 studies, 228 women, I 2  = 0%). Women who had a preterm birth were more likely to have the baby via caesarean section (OR 3.03, 95% CI 1.71 to 5.36, 12 studies; 314 women, I 2  = 0%). For pharmacological and non-pharmacological we provided estimates of the expected rates of outcomes in women exposed to various treatment of COVID-19. Comparative data for pregnant women, in particular for treatments proven to be effective in the general population, however, is lacking to provide clinically meaningful interpretation., Conclusions: We found associations for pregnancy specific interventions, like mode of delivery and outcomes of the disease, but there were too few data on pharmacological and non-pharmacological treatments in pregnant women with COVID-19. We report the rates of complications found in the literature. We encourage researchers to include pregnant women in their trials and report the data on pregnant women separately., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Graph neural networks trained on experimental or calculated data are becoming an increasingly important tool in computational materials science. Networks once trained are able to make highly accurate predictions at a fraction of the cost of experiments or first-principles calculations of comparable accuracy. However, these networks typically rely on large databases of labeled experiments to train the model. In scenarios where data are scarce or expensive to obtain, this can be prohibitive. By building a neural network that provides confidence on the predicted properties, we are able to develop an active learning scheme that can reduce the amount of labeled data required by identifying the areas of chemical space where the model is most uncertain. We present a scheme for coupling a graph neural network with a Gaussian process to featurize solid-state materials and predict properties including a measure of confidence in the prediction. We then demonstrate that this scheme can be used in an active learning context to speed up the training of the model by selecting the optimal next experiment for obtaining a data label. Our active learning scheme can double the rate at which the performance of the model on a test dataset improves with additional data compared to choosing the next sample at random. This type of uncertainty quantification and active learning has the potential to open up new areas of materials science, where data are scarce and expensive to obtain, to the transformative power of graph neural networks.

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

Introduction: Mothers with gestational diabetes mellitus (GDM) are at increased risk of pregnancy-related complications and developing type 2 diabetes after delivery. Diet and physical activity-based interventions may prevent GDM, but variations in populations, interventions and outcomes in primary trials have limited the translation of available evidence into practice. We plan to undertake an individual participant data (IPD) meta-analysis of randomised trials to assess the differential effects and cost-effectiveness of diet and physical activity-based interventions in preventing GDM and its complications., Methods: The International Weight Management in Pregnancy Collaborative Network database is a living repository of IPD from randomised trials on diet and physical activity in pregnancy identified through a systematic literature search. We shall update our existing search on MEDLINE, Embase, BIOSIS, LILACS, Pascal, Science Citation Index, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, Database of Abstracts of Reviews of Effects and Health Technology Assessment Database without language restriction to identify relevant trials until March 2021. Primary researchers will be invited to join the Network and share their IPD. Trials including women with GDM at baseline will be excluded. We shall perform a one and two stage random-effect meta-analysis for each intervention type (all interventions, diet-based, physical activity-based and mixed approach) to obtain summary intervention effects on GDM with 95% CIs and summary treatment-covariate interactions. Heterogeneity will be summarised using I 2 and tau 2 statistics with 95% prediction intervals. Publication and availability bias will be assessed by examining small study effects. Study quality of included trials will be assessed by the Cochrane Risk of Bias tool, and the Grading of Recommendations, Assessment, Development and Evaluations approach will be used to grade the evidence in the results. A model-based economic analysis will be carried out to assess the cost-effectiveness of interventions to prevent GDM and its complications compared with usual care., Ethics and Dissemination: Ethics approval is not required. The study is registered on the International Prospective Register of Systematic Reviews (CRD42020212884). Results will be submitted for publication in peer-reviewed journals., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Endometriosis is a chronic inflammatory condition affecting 6%-10% of women of reproductive age and is defined by the presence of endometrial-like tissue outside the uterus (lesions), commonly affecting the pelvis and ovaries. It is associated with debilitating pelvic pain, infertility, and fatigue and often has devastating effects on the quality of life (QoL). Although it is as common as back pain, it is poorly understood, and treatment and diagnosis are often delayed, leading to unnecessary suffering. Endometriosis has no cure. Surgery is one of several management options. Quantifying the probability of successful surgery is important for guiding clinical decisions and treatment strategies. Factors predicting success through pain reduction after endometriosis surgery have not yet been adequately identified., Objective: This study aims to determine which women with confirmed endometriosis benefit from surgical improvement in pain and QoL and whether these women could be identified from clinical symptoms measured before laparoscopy., Methods: First, we will carry out a systematic search and review and, if appropriate, meta-analysis of observational cohort and case-control studies reporting one or more risk factors for endometriosis and postsurgical treatment success. We will search PubMed, Embase, and Cochrane databases from inception without language restrictions and supplement the reference lists by manual searches. Second, we will develop separate clinical prediction models for women with confirmed and suspected diagnoses of endometriosis. A total of three suitable databases have been identified for development and external validation (the MEDAL [ISRCTN13028601] and LUNA [ISRCTN41196151] studies, and the BSGE database), and access has been guaranteed. The models will be developed using a linear regression approach that links candidate factors to outcomes. Third, we will hold 2 stakeholder co-design workshops involving eight clinicians and eight women with endometriosis separately and then bring all 16 participants together. Participants will discuss the implementation, delivery, usefulness, and sustainability of the prediction models. Clinicians will also focus on the ease of use and access to clinical prediction tools., Results: This project was funded in March 2018 and approved by the Institutional Research Ethics Board in December 2019. At the time of writing, this study was in the data analysis phase, and the results are expected to be available in April 2021., Conclusions: This study is the first to aim to predict who will benefit most from laparoscopic surgery through the reduction of pain or increased QoL. The models will provide clinicians with robustly developed and externally validated support tools, improving decision making in the diagnosis and treatment of women., International Registered Report Identifier (irrid): DERR1-10.2196/20986., (©Nadine Marlin, Carol Rivas, John Allotey, Julie Dodds, Andrew Horne, Elizabeth Ball. Originally published in JMIR Research Protocols (http://www.researchprotocols.org), 05.04.2021.)