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Background: Maternal obesity is associated with stillbirth, but uncertainty persists around the effects of higher obesity classes. We sought to compare the risk of stillbirth associated with maternal obesity alone versus maternal obesity and additional or undiagnosed factors contributing to high-risk pregnancy. Methods: We conducted a retrospective cohort study using the Better Outcomes Registry and Network (BORN) for singleton hospital births in Ontario between 2012 and 2018. We used multivariable Cox proportional hazard regression and logistic regression to evaluate the relationship between prepregnancy maternal body mass index (BMI) class and stillbirth (reference was normal BMI). We treated maternal characteristics and obstetrical complications as independent covariates. We performed mediator analyses to measure the direct and indirect effects of BMI on stillbirth through major common-pathway complications. We used fully adjusted and partially adjusted models, representing the impact of maternal obesity alone and maternal obesity with other risk factors on stillbirth, respectively. Results: We analyzed data on 681 178 births between 2012 and 2018, of which 1956 were stillbirths. Class I obesity was associated with an increased incidence of stillbirth (adjusted hazard ratio [HR] 1.55, 95% confidence interval [CI] 1.35–1.78). This association was stronger for class III obesity (adjusted HR 1.80, 95% CI 1.44–2.24), and strongest for class II obesity (adjusted HR 2.17, 95% CI 1.83–2.57). Plotting point estimates for odds ratios, stratified by gestational age, showed a marked increase in the relative odds for stillbirth beyond 37 weeks' gestation for those with obesity with and without other risk factors, compared with those with normal BMI. The impact of potential mediators was minimal. Interpretation: Maternal obesity alone and obesity with other risk factors are associated with an increased risk of stillbirth. This risk increases with gestational age, especially at term. [ABSTRACT FROM AUTHOR]

Low-dose aspirin is recommended for pregnant individuals at high-risk of developing preeclampsia, but less is known about those that develop preeclampsia even while using prophylactic aspirin for preeclampsia prevention as the best course of treatment. The objective of this study is to investigate the risk factors with the highest risk of developing preeclampsia among pregnant individuals already using aspirin from high-risk obstetrical centers across five countries. This is a secondary analysis of pregnant individuals from the Folic Acid Clinical Trial (FACT) who were using prophylactic aspirin before 16 weeks gestation. The FACT randomized control trial took place in 70 high risk obstetrical centers in Canada, United Kingdom, Australia, Jamaica, and Argentina between 2011–2015. Participants were included if they had any of the risk factors for preeclampsia: diabetes, chronic hypertension, twin pregnancy, history of preeclampsia, and/or obesity (Body Mass Index ≥35). The outcomes of interest were preeclampsia and preterm preeclampsia (<37 weeks). Log binomial regressions assessed factors significantly associated with any preeclampsia or preterm-preeclampsia (<37 weeks) using adjusted risk ratios (ARR) and 95% confidence intervals (CI). There were 2296 pregnant individuals with complete information on aspirin included in this study. At baseline, all patients were at high risk of preeclampsia and were eligible for aspirin prophylaxis, however, only 660 (28.7%) were taking aspirin. Among the 660 pregnant individuals taking aspirin, 132 (20%) developed preeclampsia and 60 (9.09%) preterm preeclampsia. Among pregnant individuals using aspirin, the risks of preeclampsia were highest for twins (ARR:2.62, 95% CI: 1.68–4.11), history of preeclampsia (ARR: 2.42, 95% CI: 1.74–3.38), and hypertension (ARR:1.92, 95% CI: 1.37–2.69). Similar trends were found for preterm-preeclampsia for twins (ARR:4.10, 95% CI:2.15–7.82), history of preeclampsia (ARR:2.75, 95% CI:1.62–4.67), and hypertension (ARR:2.18, 95% CI:1.28–3.72). No significant differences were found for obesity or diabetes. These findings suggest that individuals with twin pregnancies, a history of preeclampsia, or hypertension may not benefit from aspirin to the same extent as those with other complications such as obesity or diabetes. Careful clinical monitoring for these risks factors is recommended and future research into the effectiveness in these populations would increase our understanding of the current best practice of prophylactic aspirin use to prevent preeclampsia. TRIAL REGISTRATION: Current Controlled Trials ISRCTN23781770 and ClinicalTrials.gov NCT01355159 [ABSTRACT FROM AUTHOR]

To determine the efficacy of high-dose folic acid for the prevention of preeclampsia in twin pregnancies. Secondary analysis of a randomized controlled trial in 70 obstetrical sites in Argentina, Australia, Canada, Jamaica, and the UK between 2011 and 2015. Eligible women pregnant with twins who were aged 18 y or older and between 8 and 16 completed weeks' gestation were randomized between to receive daily high-dose folic acid (4.0–5.1 mg) or placebo. The primary outcome was preeclampsia, presenting as hypertension after 20 weeks' gestation with significant proteinuria. Secondary outcomes included severe preeclampsia, preterm birth, and adverse fetal and neonatal outcomes. Of 2464 participants randomized between 18 April 2011 and 14 December 2015, 462 (18.8%) had a confirmed twin pregnancy. Thirty-four of these participants withdrew consent or did not have primary outcome data available, and 428 women were analyzed. The rate of preeclampsia was significantly higher in the folic acid group compared to the placebo group in crude analyses (17.2 versus 9.9%; relative risk 1.75 [95% CI 1.06–2.88], p =.029). Multivariable analyses attenuated this effect, rendering it not statistically significant (RR 1.58 [95% CI 0.95–2.63], p =.079). High-dose folic acid supplementation was not significantly associated with preeclampsia in a subgroup of twin pregnancies. Although a suggested elevated risk cannot be confirmed, these results may help to gain novel insights in the etiology of preeclampsia, which continues to be poorly understood. ClinicalTrials.gov NCT01355159. [ABSTRACT FROM AUTHOR]

Summary: Multiple clinical practice guidelines (CPGs) have been established for pregnant women with obesity. The quality and consistency of recommendations remain unknown. The objective of this study is to conduct a systematic review to synthesize and appraise evidence from CPGs, available worldwide, for pregnant women affected by obesity. An experienced information specialist performed a rigorous search of the literature, searching MEDLINE, Embase, grey literature, and guideline registries to locate CPGs that reported on pregnancy care relating to obesity. CPGs related to antenatal care of pregnant women with obesity (pre‐pregnancy body mass index [BMI] ≥ 30 kg/m2) in low‐risk (eg, care provider = family physician or midwife) or high‐risk settings (eg, obstetrician or maternal fetal medicine) were included. CPGs were appraised for quality with independent data collection by two raters. Information was categorized into five domains: preconception care. care during pregnancy, diet and exercise during pregnancy, care immediately before, during, and after delivery, and postpartum care. The literature search yielded 2614 unique citations. Following screening of abstracts and full texts, 32 CPGs were included, with quality ranging between 0 and 100 on the AGREE II tool. The strongest evidence related to nutritional advice, exercise, and pregnancy risk counselling. Guidance was limited for timing of screening tests, antenatal visits and delivery, ideal postpartum care, and management of adverse pregnancy outcomes. Most guidelines in this population are not evidence based. Research is needed to bridge knowledge gaps pertaining to fetal antenatal surveillance, management of adverse outcomes and postpartum care, and enhance consistency across CPGs. [ABSTRACT FROM AUTHOR]