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BACKGROUND:Despite a call to study the effect of weight gain pattern on development of gestational diabetes mellitus, few studies have correctly adjusted for independent effects of gain after the first trimester. We used a conditional percentile approach to model the independent association between first and second trimester weight-gain trajectories and development of gestational diabetes. METHODS:We sampled women delivering singleton infants from 1998-2010 at Magee-Womens Hospital in Pittsburgh, PA (n=124,590) using a case–cohort design. We modeled weight-gain trajectories in the first and second trimesters of pregnancy using conditional weight-gain percentiles, and used multivariable logistic regression to assess independent associations of the trajectory with gestational diabetes. We studied associations separately by pre-pregnancy body mass index category. RESULTS:The final cohort included 806 women with gestational diabetes and 4,819 randomly sampled women who delivered without gestational diabetes. In normal-weight women, every standard deviation increase in weight gain in the first trimester above her predicted gain was associated with a 23% increased odds of gestational diabetes [95% CI0.2%, 51%]. Second trimester gain trajectory was not associated with gestational diabetes (OR1.1, [95% CI0.9, 1.3]) although the direction of effect was positive. This pattern was similar in obese class I and II but not in overweight and obese class III women. CONCLUSIONS:An upward weight gain trajectory in the first trimester was positively associated with gestational diabetes for women of most pre-pregnancy BMI categories. Second trimester weight gain trajectory was not associated with gestational diabetes for any group.

Background: We sought to determine the association between maternal vitamin D status at ≤26 weeks' gestation and the risk of preeclampsia by clinical subtype. Methods: We conducted a case–cohort study among women enrolled at 12 US sites from 1959 to 1966 in the Collaborative Perinatal Project. In serum collected at ≤26 weeks' gestation (median 20.9 weeks) from 717 women who later developed preeclampsia (560 mild and 157 severe cases) and from 2986 mothers without preeclampsia, we measured serum 25-hydroxyvitamin D, over 40 years later, using liquid chromatography–tandem mass spectrometry. Results: Half of women in the subcohort had 25-hydroxyvitamin D (25(OH)D) >50 nmol/L. Maternal 25(OH)D 50 to 74.9 nmol/L was associated with a reduction in the absolute and relative risk of preeclampsia and mild preeclampsia compared with 25(OH)D <30 nmol/L in the crude analysis but not after adjustment for confounders, including race, prepregnancy body mass index, and parity. For severe preeclampsia, 25(OH)D ≥50 nmol/L was associated with a reduction in three cases per 1000 pregnancies (adjusted risk difference = −0.003 [95% confidence interval = −0.005 to 0.0002]) and a 40% reduction in risk (0.65 [0.43 to 0.98]) compared with 25(OH) D <50 nmol/L. Conclusions were unchanged (1) after restricting to women with 25(OH)D measured before 22 weeks' gestation or (2) with formal sensitivity analyses for unmeasured confounding. Conclusions: Maternal vitamin D deficiency may be a risk factor for severe preeclampsia but not for its mild subtypes. Contemporary cohorts with large numbers of severe preeclampsia cases would be needed to confirm or refute these findings.

Life course factors may be associated with pre-pregnancy body mass index and gestational weight gain; however, collecting information on pre-pregnancy exposures and pregnancy health in the same cohort is challenging. The Life-course Experiences And Pregnancy (LEAP) study aims to identify adolescent and young adult risk factors for pre-pregnancy weight and gestational weight gain (GWG). We built upon an existing cohort study to overcome challenges inherent to studying life course determinants of pregnancy health. Participants in an ongoing prospective cohort study of weight-related health who identified as women. Retrospective cohort study. In 2019-2020, 1,252 women participating since adolescence in a cohort study of weight-related health were invited to complete an online reproductive history survey. Participants who reported a live birth were invited to release their prenatal, delivery, and postpartum medical records for validation of survey reports. Descriptive analyses were conducted to assess the characteristics of the overall cohort and the medical record validation subsample, and to describe adolescent and young adult characteristics of those with high (>80th percentile), moderate (20th-80th percentile), and low (<20th percentile) GWG z-score for gestational age and pre-pregnancy weight status. Nine hundred seventy-seven women (78%) completed the LEAP survey and 656 reported a live birth. Of these, 379 (58%) agreed to release medical records, and 250 records were abstracted (66% of the 379). Of the 977 survey respondents 769 (79%) reported attempting a pregnancy, and 656 (67%) reported at least one live birth. The validation subsample was similar to the overall cohort. Women with a high GWG had a higher adolescent BMI percentile and prevalence of unhealthy weight control behaviors than those with moderate or low GWG. LEAP offers a valuable resource for identifying life course factors that may influence the health of pregnant people and their offspring.

Background: Prepregnancy overweight is a risk factor for mild preeclampsia and mild transient hypertension of pregnancy. Its association with severe subtypes of these disorders has received less attention. Methods: To assess the association of prepregnancy body mass index (BMI) with severe and mild preeclampsia and transient hypertension of pregnancy, we used data from a 1958-1964 prospective cohort study of 38,188 pregnant women receiving care at 12 U.S. hospitals. Results: There was a monotonic, dose-response relation between prepregnancy BMI and risk of both severe and mild preeclampsia, as well as the risk of severe and mild transient hypertension of pregnancy. Compared with white women with a BMI of 20, the odds ratios for severe preeclampsia at BMI values of 25 and 30 in white women were 1.7 (95% confidence interval = 1.1-2.5) and 3.4 (2.1-5.6), respectively, and 2.1 (1.4-3.2) and 3.2 (2.1-5.0) in black women. The effect of BMI on risk of severe preeclampsia was similar to its effect on mild disease. Compared with the same referent, odds ratios for severe transient hypertension of pregnancy at BMI values of 25 and 30 in white women were 3.6 (2.0-6.5) and 8.8 (4.4-18), respectively, and 3.0 (1.6-5.8) and 4.9 (2.5-9.6) in black women. Overweight was a stronger risk factor for severe than for mild transient hypertension. Conclusions: Incidence of both mild and severe hypertensive disorders of pregnancy rises with increasing BMI. Escalating obesity rates may increase pregnancy hypertensive disorders and ensuing perinatal morbidity.

Introduction Multistakeholder engagement is crucial for conducting health services research. Delphi‐based methodologies combining iterative rounds of questions with feedback on and discussion of group results are a well‐documented approach to multistakeholder engagement. This study develops hypotheses about the impact of panel composition and topic on the propensity and meaningfulness of response changes in multistakeholder modified‐Delphi panels. Methods We conducted three online modified‐Delphi (OMD) multistakeholder panels using the same protocol. We assigned 60 maternal and child health professionals to a homogeneous (professionals only) panel, 60 pregnant or postpartum women (patients) to a homogeneous panel, and 30 professionals and 30 patients to a mixed panel. In Round 1, participants rated the seriousness of 11 maternal and child health outcomes using a 0–100 scale and explained their ratings. In Round 2, participants saw their own and their panel's Round 1 results and discussed them using asynchronous, anonymous discussion boards moderated by the study investigators. In Round 3, participants revised their original ratings. Our outcome measures included binary indicators of response changes to ratings of the low, medium and high severity maternal and child health outcomes and their meaningfulness, measured by a change of 10 or more points. Results Participants changed 818 of 1491 (55%) of responses; the majority of response changes were meaningful. Patterns of response changes were different for patients and professionals and for different levels of outcome seriousness. Using study results and the literature, we developed three hypotheses. First, OMD participants, regardless of their stakeholder group, are more likely to change their responses on preference‐sensitive topics where there is a range of viable alternatives or perspectives. Second, patients are more likely to change their responses and to do so meaningfully in mixed panels, whereas professionals are more likely to do so in homogeneous panels. Third, the association between panel composition and response change varies according to the topic (e.g., the level of outcome seriousness). Conclusions Results of our work not only helped generate empirically derived hypotheses to be tested in future research but also offer practical recommendations for designing multistakeholder OMD panels. Patient or Public Contribution Pregnant or postpartum women were involved in this study.

Background Birthing people with pre-pregnancy body mass indices (BMIs) ≥ 25 kg/m 2 , particularly those without prior breastfeeding experience, are at increased risk for suboptimal lactation outcomes. Antenatal milk expression (AME) may be one way to counteract the negative effects of early infant formula supplementation common in this population. Methods This ongoing, randomized controlled trial in the United States evaluates the efficacy of a telelactation-delivered AME education intervention versus an attention control condition on lactation outcomes to 1 year postpartum among 280 nulliparous-to-primiparous, non-diabetic birthing people with pre-pregnancy BMI ≥ 25 kg/m 2 . The assigned study treatment is delivered via four weekly online video consultations between gestational weeks 37–40. Participants assigned to AME meet with study personnel and a lactation consultant to learn and practice AME. Instructions are provided for home practice of AME between study visits. Control group participants view videos on infant care/development at study visits. Participants complete emailed surveys at enrollment (34 0/7 –36 6/7 gestational weeks) and 2 weeks, 6 weeks, 12 weeks, 6 months, and 12 months postpartum. Surveys assess lactation and infant feeding practices; breastfeeding self-efficacy, attitudes, and satisfaction; perception of insufficient milk; onset of lactogenesis-II; lactation support and problems; and reasons for breastfeeding cessation. Surveys also assess factors associated with lactation outcomes, including demographic characteristics, health problems, birth trauma, racial discrimination, and weight stigma. Health information and infant feeding data are abstracted from the pregnancy and birth center electronic health record. Milk samples are collected from the intervention group at each study visit and from both groups at each postpartum follow-up for future analyses. Qualitative interviews are conducted at 6 weeks postpartum to understand AME experiences. Primary outcomes of interest are breastfeeding exclusivity and breastfeeding self-efficacy scores at 2 weeks postpartum. Outcomes will be examined longitudinally with generalized linear mixed-effects modeling. Discussion This is the first adequately powered trial evaluating the effectiveness of AME among U.S. birthing people and within a non-diabetic population with pre-pregnancy BMI ≥ 25 kg/m 2 . This study will also provide the first evidence of acceptability and effectiveness of telelactation-delivered AME. Trial registration ClinicalTrials.gov: NCT04258709.

Background Compelled by the intuitive appeal of predicting each individual patient’s risk of an outcome, there is a growing interest in risk prediction models. While the statistical methods used to build prediction models are increasingly well understood, the literature offers little insight to researchers seeking to gauge a priori whether a prediction model is likely to perform well for their particular research question. The objective of this study was to inform the development of new risk prediction models by evaluating model performance under a wide range of predictor characteristics. Methods Data from all births to overweight or obese women in British Columbia, Canada from 2004 to 2012 ( n  = 75,225) were used to build a risk prediction model for preeclampsia. The data were then augmented with simulated predictors of the outcome with pre-set prevalence values and univariable odds ratios. We built 120 risk prediction models that included known demographic and clinical predictors, and one, three, or five of the simulated variables. Finally, we evaluated standard model performance criteria (discrimination, risk stratification capacity, calibration, and Nagelkerke’s r 2 ) for each model. Results Findings from our models built with simulated predictors demonstrated the predictor characteristics required for a risk prediction model to adequately discriminate cases from non-cases and to adequately classify patients into clinically distinct risk groups. Several predictor characteristics can yield well performing risk prediction models; however, these characteristics are not typical of predictor-outcome relationships in many population-based or clinical data sets. Novel predictors must be both strongly associated with the outcome and prevalent in the population to be useful for clinical prediction modeling (e.g., one predictor with prevalence ≥20 % and odds ratio ≥8, or 3 predictors with prevalence ≥10 % and odds ratios ≥4). Area under the receiver operating characteristic curve values of >0.8 were necessary to achieve reasonable risk stratification capacity. Conclusions Our findings provide a guide for researchers to estimate the expected performance of a prediction model before a model has been built based on the characteristics of available predictors.

There are concerns that current gestational weight gain recommendations for women with obesity are too high and that guidelines should differ on the basis of severity of obesity. In this study we investigated the safety of gestational weight gain below current recommendations or weight loss in pregnancies with obesity, and evaluated whether separate guidelines are needed for different obesity classes. In this population-based cohort study, we used electronic medical records from the Stockholm–Gotland Perinatal Cohort study to identify pregnancies with obesity (early pregnancy BMI before 14 weeks' gestation ≥30 kg/m2) among singleton pregnancies that delivered between Jan 1, 2008, and Dec 31, 2015. The pregnancy records were linked with Swedish national health-care register data up to Dec 31, 2019. Gestational weight gain was calculated as the last measured weight before or at delivery minus early pregnancy weight (at <14 weeks' gestation), and standardised for gestational age into z-scores. We used Poisson regression to assess the association of gestational weight gain z-score with a composite outcome of: stillbirth, infant death, large for gestational age and small for gestational age at birth, preterm birth, unplanned caesarean delivery, gestational diabetes, pre-eclampsia, excess postpartum weight retention, and new-onset longer-term maternal cardiometabolic disease after pregnancy, weighted to account for event severity. We calculated rate ratios (RRs) for our composite adverse outcome along the weight gain z-score continuum, compared with a reference of the current lower limit for gestational weight gain recommended by the US Institute of Medicine (IOM; 5 kg at term). RRs were adjusted for confounding factors (maternal age, height, parity, early pregnancy BMI, early pregnancy smoking status, prepregnancy cardiovascular disease or diabetes, education, cohabitation status, and Nordic country of birth). Our cohort comprised 15 760 pregnancies with obesity, followed up for a median of 7·9 years (IQR 5·8–9·4). 11 667 (74·0%) pregnancies had class 1 obesity, 3160 (20·1%) had class 2 obesity, and 933 (5·9%) had class 3 obesity. Among these pregnancies, 1623 (13·9%), 786 (24·9%), and 310 (33·2%), respectively, had weight gain during pregnancy below the lower limit of the IOM recommendation (5 kg). In pregnancies with class 1 or 2 obesity, gestational weight gain values below the lower limit of the IOM recommendation or weight loss did not increase risk of the adverse composite outcome (eg, at weight gain z-score –2·4, corresponding to 0 kg at 40 weeks: adjusted RR 0·97 [95% CI 0·89–1·06] in obesity class 1 and 0·96 [0·86–1·08] in obesity class 2). In pregnancies with class 3 obesity, weight gain values below the IOM limit or weight loss were associated with reduced risk of the adverse composite outcome (eg, adjusted RR 0·81 [0·71–0·89] at weight gain z-score –2·4, or 0 kg). Our findings support calls to lower or remove the lower limit of current IOM recommendations for pregnant women with obesity, and suggest that separate guidelines for class 3 obesity might be warranted. Karolinska Institutet and the Eunice Kennedy Shriver National Institute of Child Health and Human Development.

Life course factors may be associated with pre-pregnancy body mass index and gestational weight gain; however, collecting information on pre-pregnancy exposures and pregnancy health in the same cohort is challenging. The Life-course Experiences And Pregnancy (LEAP) study aims to identify adolescent and young adult risk factors for pre-pregnancy weight and gestational weight gain (GWG). We built upon an existing cohort study to overcome challenges inherent to studying life course determinants of pregnancy health. Retrospective cohort study. In 2019-2020, 1,252 women participating since adolescence in a cohort study of weight-related health were invited to complete an online reproductive history survey. Participants who reported a live birth were invited to release their prenatal, delivery, and postpartum medical records for validation of survey reports. Descriptive analyses were conducted to assess the characteristics of the overall cohort and the medical record validation subsample, and to describe adolescent and young adult characteristics of those with high (>80.sup.th percentile), moderate (20.sup.th -80.sup.th percentile), and low (<20.sup.th percentile) GWG z-score for gestational age and pre-pregnancy weight status. LEAP offers a valuable resource for identifying life course factors that may influence the health of pregnant people and their offspring.