Browsing by Subject "Gestational diabetes"
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Item Association of a Mediterranean Diet Pattern With Adverse Pregnancy Outcomes Among US Women(American Medical Association, 2022-12-01) Makarem, Nour; Chau, Kristi; Miller, Eliza C.; Gyamfi-Bannerman, Cynthia; Tous, Isabella; Booker, Whitney; Catov, Janet M.; Haas, David M.; Grobman, Wiliam A.; Levine, Lisa D.; McNeil, Rebecca; Merz, C. Noel Bairey; Reddy, Uma; Wapner, Ronald J.; Wong, Melissa S.; Bello, Natalie A.; Obstetrics and Gynecology, School of MedicineImportance: The Mediterranean diet pattern is inversely associated with the leading causes of morbidity and mortality, including metabolic diseases and cardiovascular disease, but there are limited data on its association with adverse pregnancy outcomes (APOs) among US women. Objective: To evaluate whether concordance to a Mediterranean diet pattern around the time of conception is associated with lower risk of developing any APO and individual APOs. Design, setting, and participants: This prospective, multicenter, cohort study, the Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-to-Be, enrolled 10 038 women between October 1, 2010, and September 30, 2013, with a final analytic sample of 7798 racially, ethnically, and geographically diverse women with singleton pregnancies who had complete diet data. Data analyses were completed between June 3, 2021, and April 7, 2022. Exposures: An Alternate Mediterranean Diet (aMed) score (range, 0-9; low, 0-3; moderate, 4-5; and high, 6-9) was computed from data on habitual diet in the 3 months around conception, assessed using a semiquantitative food frequency questionnaire. Main outcomes and measures: Adverse pregnancy outcomes were prospectively ascertained and defined as developing 1 or more of the following: preeclampsia or eclampsia, gestational hypertension, gestational diabetes, preterm birth, delivery of a small-for-gestational-age infant, or stillbirth. Results: Of 7798 participants (mean [SD] age, 27.4 [5.5] years), 754 (9.7%) were aged 35 years or older, 816 (10.5%) were non-Hispanic Black, 1294 (16.6%) were Hispanic, and 1522 (19.5%) had obesity at baseline. The mean (SD) aMed score was 4.3 (2.1), and the prevalence of high, moderate, and low concordance to a Mediterranean diet pattern around the time of conception was 30.6% (n=2388), 31.2% (n=2430), and 38.2% (n=2980), respectively. In multivariable models, a high vs low aMed score was associated with 21% lower odds of any APO (adjusted odds ratio [aOR], 0.79 [95% CI, 0.68-0.92]), 28% lower odds of preeclampsia or eclampsia (aOR, 0.72 [95% CI, 0.55-0.93]), and 37% lower odds of gestational diabetes (aOR, 0.63 [95% CI, 0.44-0.90]). There were no differences by race, ethnicity, and prepregnancy body mass index, but associations were stronger among women aged 35 years or older (aOR, 0.54 [95% CI, 0.34-0.84]; P = .02 for interaction). When aMed score quintiles were evaluated, similar associations were observed, with higher scores being inversely associated with the incidence of any APO. Conclusions and relevance: This cohort study suggests that greater adherence to a Mediterranean diet pattern is associated with lower risk of APOs, with evidence of a dose-response association. Intervention studies are needed to assess whether dietary modification around the time of conception can reduce risk of APOs and their downstream associations with future development of cardiovascular disease risk factors and overt disease.Item Association of Genetic Predisposition and Physical Activity With Risk of Gestational Diabetes in Nulliparous Women(American Medical Association, 2022-08-01) Pagel, Kymberleigh A.; Chu, Hoyin; Ramola, Rashika; Guerrero, Rafael F.; Chung, Judith H.; Parry, Samuel; Reddy, Uma M.; Silver, Robert M.; Steller, Jonathan G.; Yee, Lynn M.; Wapner, Ronald J.; Hahn, Matthew W.; Natarajan, Sriraam; Haas, David M.; Radivojac, Predrag; Obstetrics and Gynecology, School of MedicineImportance: Polygenic risk scores (PRS) for type 2 diabetes (T2D) can improve risk prediction for gestational diabetes (GD), yet the strength of the association between genetic and lifestyle risk factors has not been quantified. Objective: To assess the association of PRS and physical activity in existing GD risk models and identify patient subgroups who may receive the most benefits from a PRS or physical activity intervention. Design, settings, and participants: The Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-to-Be cohort was established to study individuals without previous pregnancy lasting at least 20 weeks (nulliparous) and to elucidate factors associated with adverse pregnancy outcomes. A subcohort of 3533 participants with European ancestry was used for risk assessment and performance evaluation. Participants were enrolled from October 5, 2010, to December 3, 2013, and underwent genotyping between February 19, 2019, and February 28, 2020. Data were analyzed from September 15, 2020, to November 10, 2021. Exposures: Self-reported total physical activity in early pregnancy was quantified as metabolic equivalents of task (METs). Polygenic risk scores were calculated for T2D using contributions of 84 single nucleotide variants, weighted by their association in the Diabetes Genetics Replication and Meta-analysis Consortium data. Main outcomes and measures: Estimation of the development of GD from clinical, genetic, and environmental variables collected in early pregnancy, assessed using measures of model discrimination. Odds ratios and positive likelihood ratios were used to evaluate the association of PRS and physical activity with GD risk. Results: A total of 3533 women were included in this analysis (mean [SD] age, 28.6 [4.9] years). In high-risk population subgroups (body mass index ≥25 or aged ≥35 years), individuals with high PRS (top 25th percentile) or low activity levels (METs <450) had increased odds of a GD diagnosis of 25% to 75%. Compared with the general population, participants with both high PRS and low activity levels had higher odds of a GD diagnosis (odds ratio, 3.4 [95% CI, 2.3-5.3]), whereas participants with low PRS and high METs had significantly reduced risk of a GD diagnosis (odds ratio, 0.5 [95% CI, 0.3-0.9]; P = .01). Conclusions and relevance: In this cohort study, the addition of PRS was associated with the stratified risk of GD diagnosis among high-risk patient subgroups, suggesting the benefits of targeted PRS ascertainment to encourage early intervention.Item Exploiting Domain Knowledge as Causal Independencies in Modeling Gestational Diabetes(World Scientific, 2023) Mathur, Saurabh; Karanam, Athresh; Radivojac, Predrag; Haas, David M.; Kersting, Kristian; Natarajan, Sriraam; Obstetrics and Gynecology, School of MedicineWe consider the problem of modeling gestational diabetes in a clinical study and develop a domain expert-guided probabilistic model that is both interpretable and explainable. Specifically, we construct a probabilistic model based on causal independence (Noisy-Or) from a carefully chosen set of features. We validate the efficacy of the model on the clinical study and demonstrate the importance of the features and the causal independence model.Item Genetic polymorphisms associated with adverse pregnancy outcomes in nulliparas(Springer Nature, 2024-05-07) Khan, Raiyan R.; Guerrero, Rafael F.; Wapner, Ronald J.; Hahn, Matthew W.; Raja, Anita; Salleb‑Aouissi, Ansaf; Grobman, William A.; Simhan, Hyagriv; Silver, Robert M.; Chung, Judith H.; Reddy, Uma M.; Radivojac, Predrag; Pe’er, Itsik; Haas, David M.; Obstetrics and Gynecology, School of MedicineAdverse pregnancy outcomes (APOs) affect a large proportion of pregnancies and represent an important cause of morbidity and mortality worldwide. Yet the pathophysiology of APOs is poorly understood, limiting our ability to prevent and treat these conditions. To search for genetic markers of maternal risk for four APOs, we performed multi-ancestry genome-wide association studies (GWAS) for pregnancy loss, gestational length, gestational diabetes, and preeclampsia. We clustered participants by their genetic ancestry and focused our analyses on three sub-cohorts with the largest sample sizes: European, African, and Admixed American. Association tests were carried out separately for each sub-cohort and then meta-analyzed together. Two novel loci were significantly associated with an increased risk of pregnancy loss: a cluster of SNPs located downstream of the TRMU gene (top SNP: rs142795512), and the SNP rs62021480 near RGMA. In the GWAS of gestational length we identified two new variants, rs2550487 and rs58548906 near WFDC1 and AC005052.1, respectively. Lastly, three new loci were significantly associated with gestational diabetes (top SNPs: rs72956265, rs10890563, rs79596863), located on or near ZBTB20, GUCY1A2, and RPL7P20, respectively. Fourteen loci previously correlated with preterm birth, gestational diabetes, and preeclampsia were found to be associated with these outcomes as well.Item Kinetic Analysis of Vasculogenesis Quantifies Dynamics of Vasculogenesis and Angiogenesis In Vitro(JoVE, 2018-01-31) Varberg, Kaela M.; Winfree, Seth; Dunn, Kenneth W.; Haneline, Laura S.; Cellular and Integrative Physiology, School of MedicineVasculogenesis is a complex process by which endothelial stem and progenitor cells undergo de novo vessel formation. Quantitative assessment of vasculogenesis has become a central readout of endothelial progenitor cell functionality, and therefore, several attempts have been made to improve both in vitro and in vivo vasculogenesis models. However, standard methods are limited in scope, with static measurements failing to capture many aspects of this highly dynamic process. Therefore, the goal of developing this novel protocol was to assess the kinetics of in vitro vasculogenesis in order to quantitate rates of network formation and stabilization, as well as provide insight into potential mechanisms underlying vascular dysfunction. Application of this protocol is demonstrated using fetal endothelial colony forming cells (ECFCs) exposed to maternal diabetes mellitus. Fetal ECFCs were derived from umbilical cord blood following birth, cultured, and plated in slides containing basement membrane matrix, where they underwent vasculogenesis. Images of the entire slide wells were acquired using time-lapse phase contrast microscopy over 15 hours. Images were analyzed for derivation of quantitative data using an analysis software called Kinetic Analysis of Vasculogenesis (KAV). KAV uses image segmentation followed by skeletonization to analyze network components from stacks of multi-time point phase contrast images to derive ten parameters (9 measured, 1 calculated) of network structure including: closed networks, network areas, nodes, branches, total branch length, average branch length, triple-branched nodes, quad-branched nodes, network structures, and the branch to node ratio. Application of this protocol identified altered rates of vasculogenesis in ECFCs obtained from pregnancies complicated by diabetes mellitus. However, this technique has broad implications beyond the scope reported here. Implementation of this approach will enhance mechanistic assessment and improve functional readouts of vasculogenesis and other biologically important branching processes in numerous cell types or disease states.Item Objectively measured short sleep duration and later sleep midpoint in pregnancy are associated with a higher risk of gestational diabetes(Elsevier, 2017-10) Facco, Francesca L.; Grobman, William A.; Reid, Kathryn J.; Parker, Corette B.; Hunter, Shannon M.; Silver, Robert M.; Basner, Robert C.; Saade, George R.; Pien, Grace W.; Manchanda, Shalini; Louis, Judette M.; Nhan-Chang, Chia-Ling; Chung, Judith H.; Wing, Deborah A.; Simhan, Hyagriv N.; Haas, David M.; Iams, Jay; Parry, Samuel; Zee, Phyllis C.; Medicine, School of MedicineBACKGROUND: Experimental and epidemiologic data suggest that among nonpregnant adults, sleep duration may be an important risk factor for chronic disease. Although pregnant women commonly report poor sleep, few studies objectively evaluated the quality of sleep in pregnancy or explored the relationship between sleep disturbances and maternal and perinatal outcomes. OBJECTIVE: Our objective was to examine the relationship between objectively assessed sleep duration, timing, and continuity (measured via wrist actigraphy) and maternal cardiovascular and metabolic morbidity specific to pregnancy. STUDY DESIGN: This was a prospective cohort study of nulliparous women. Women were recruited between 16 0/7 and 21 6/7 weeks' gestation. They were asked to wear a wrist actigraphy monitor and complete a daily sleep log for a period of 7 consecutive days. The primary sleep exposure variables were the averages of the following over the total valid nights (minimum 5, maximum 7 nights): short sleep duration during the primary sleep period (<7 h/night), late sleep midpoint (midpoint between sleep onset and sleep offset >5 am), and top quartile of minutes of wake time after sleep onset and sleep fragmentation index. The primary outcomes of interest were a composite of hypertensive disorders of pregnancy (mild, severe, or superimposed preeclampsia; eclampsia; or antepartum gestational hypertension) and gestational diabetes mellitus. We used χ2 tests to assess associations between sleep variables and categorical baseline characteristics. Crude odds ratios and 95% confidence intervals were estimated from univariate logistic regression models to characterize the magnitude of the relationship between sleep characteristics and hypertensive disorders of pregnancy and gestational diabetes. For associations significant in univariate analysis, multiple logistic regression was used to explore further the association of sleep characteristics with pregnancy outcomes. RESULTS: In all, 901 eligible women consented to participate; 782 submitted valid actigraphy studies. Short sleep duration and a later sleep midpoint were associated with an increased risk of gestational diabetes (odds ratio, 2.24; 95% confidence interval, 1.11-4.53; and odds ratio, 2.58; 95% confidence interval, 1.24-5.36, respectively) but not of hypertensive disorders. A model with both sleep duration and sleep midpoint as well as their interaction term revealed that while there was no significant interaction between these exposures, the main effects of both short sleep duration and later sleep midpoint with gestational diabetes remained significant (adjusted odds ratio, 2.06; 95% confidence interval, 1.01-4.19; and adjusted odds ratio, 2.37; 95% confidence interval, 1.13-4.97, respectively). Additionally, after adjusting separately for age, body mass index, and race/ethnicity, both short sleep duration and later sleep midpoint remained associated with gestational diabetes. No associations were demonstrated between the sleep quality measures (wake after sleep onset, sleep fragmentation) and hypertensive disorders or gestational diabetes. CONCLUSION: Our results demonstrate a relationship between short sleep duration and later sleep midpoint with gestational diabetes. Our data suggest independent contributions of these 2 sleep characteristics to the risk for gestational diabetes in nulliparous women.Item Perinatal Outcomes of Two Screening Strategies for Gestational Diabetes Mellitus: A Randomized Controlled Trial(Wolters Kluwer, 2021) Davis, Esa M.; Abebe, Kaleab Z.; Simhan, Hyagriv N.; Catalano, Patrick; Costacou, Tina; Comer, Diane; Orris, Steven; Ly, Kathleen; Decker, Alison; Mendez, Dara; Day, Nancy; Scifres, Christina M.; Obstetrics and Gynecology, School of MedicineObjective: To evaluate differences in short-term perinatal outcomes between the two prominent screening strategies for gestational diabetes mellitus, the International Association of Diabetes and Pregnancy Study Groups (IADPSG) and Carpenter-Coustan. Methods: In this single-site, blinded, randomized, comparative effectiveness trial, participants received a nonfasting 50-g oral glucose tolerance test and, if less than 200 mg/dL (less than 11.1 mmol/L), were randomized to further screening with either IADPSG or Carpenter-Coustan criteria. Gestational diabetes treatment occurred per routine clinical care. The primary outcome was incidence of large-for-gestational-age (LGA) neonates. Prespecified secondary outcomes included small-for-gestational-age (SGA) neonates, cesarean birth, and neonatal and maternal composites of adverse perinatal outcomes. Assuming a 15% incidence of LGA neonates in the Carpenter-Coustan group, 782 participants provided more than 80% power to detect a 7% absolute risk reduction with the use of IADPSG; planned recruitment was 920 for anticipated attrition. Results: From June 2015 to February 2019, 1,016 participants were enrolled and 921 were randomized to IADPSG (n=461) or Carpenter-Coustan (n=460) groups. Gestational diabetes incidence (14.4% vs 4.5%, P<.001) and diabetes medication use (9.3% vs 2.4%; P<.001) were more common in the IADPSG group; there were no differences in LGA neonates, either overall (risk reduction 0.90, 97.5% CI 0.53-1.52) or among women without gestational diabetes (risk reduction 0.85, 97.5% CI 0.49-1.48). Those screened with IADPSG had higher rates of neonatal morbidity but fewer study-related adverse events. Rates of SGA neonates, cesarean birth, and maternal morbidity composite did not differ significantly between study groups. Conclusions: The IADPSG screening criteria resulted in more women diagnosed and treated for gestational diabetes than Carpenter-Coustan without reducing the incidence of LGA birth weight or maternal or neonatal morbidity.Item Pilot Randomized Controlled Trial of Diabetes Group Prenatal Care(Thieme, 2022) Carter, Ebony B.; Barbier, Kate; Hill, Pamela K.; Cahill, Alison G.; Colditz, Graham A.; Macones, George A.; Tuuli, Methodius G.; Mazzoni, Sara E.; Obstetrics and Gynecology, School of MedicineObjective: This study aimed to determine the feasibility and effectiveness of Diabetes Group Prenatal Care to increase patient engagement in diabetes self-care activities. Study design: A pilot randomized controlled trial was conducted at two sites. Inclusion criteria were English or Spanish speaking, type 2 or gestational diabetes, 22 to 34 weeks of gestational age at first study visit, ability to attend group care at specified times, and willingness to be randomized. Exclusion criteria included type 1 diabetes, multiple gestation, major fetal anomaly, serious medical comorbidity, and serious psychiatric illness. Women were randomized to Diabetes Group Prenatal Care or individual prenatal care. The primary outcome was completion of diabetes self-care activities, including diet, exercise, blood sugar testing, and medication adherence. Secondary outcomes included antenatal care characteristics, and maternal, neonatal, and diabetes management outcomes. Analysis followed the intention-to-treat principle. Results: Of 159 eligible women, 84 (53%) consented to participate in the study and were randomized to group (n = 42) or individual (n = 42) prenatal care. Demographic characteristics were similar between study arms. Completion of diabetes self-care activities was similar overall, but women in group care ate the recommended amount of fruits and vegetables on more days per week (5.1 days/week ± 2.0 standard deviation [SD] in group care vs. 3.4 days ± 2.6 SD in individual care; p < 0.01) and gained less weight per week during the study period (0.2 lbs/week [interquartile range: 0-0.7] vs. 0.5 lbs/week [interquartile range: 0.2-0.9]; p = 0.03) than women in individual care. Women with gestational diabetes randomized to group care were 3.5 times more likely to have postpartum glucose tolerance testing than those in individual care (70 vs. 21%; relative risk: 3.5; 95% confidence interval: 1.4-8.8). Other maternal, neonatal, and pregnancy outcomes were similar between study arms. Conclusion: Diabetes group care is feasible and shows promise for decreasing gestational weight gain, improving diet, and increasing postpartum diabetes testing among women with pregnancies complicated by diabetes.Item Radon Exposure and Gestational Diabetes(American Medical Association, 2025-01-02) Zhang, Yijia; Angley, Meghan; Lu, Liping; Smith, Brian J.; Grobman, William; Wylie, Blair J.; Zork, Noelia M.; D'Alton, Mary E.; McNeil, Becky; Mercer, Brian M.; Silver, Robert M.; Simhan, Hyagriv N.; Haas, David M.; Saade, George R.; Parry, Samuel; Reddy, Uma; Kahe, Ka; Obstetrics and Gynecology, School of MedicineImportance: Understanding environmental risk factors for gestational diabetes (GD) is crucial for developing preventive strategies and improving pregnancy outcomes. Objective: To examine the association of county-level radon exposure with GD risk in pregnant individuals. Design, setting, and participants: This multicenter, population-based cohort study used data from the Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-to-Be (nuMoM2b) cohort, which recruited nulliparous pregnant participants from 8 US clinical centers between October 2010 and September 2013. Participants who had pregestational diabetes or were missing data on GD or county-level radon measurements were excluded from the current study. Data were analyzed from September 2023 to January 2024. Exposures: County-level radon data were created by the Lawrence Berkeley National Laboratory based on the Environmental Protection Agency's short- and long-term indoor home radon assessments. Radon exposure was categorized into 3 groups: less than 1, 1 to less than 2, and 2 or more picocuries (pCi)/L (to convert to becquerels per cubic meter, multiply by 37). Because radon, smoking, and fine particulate matter air pollutants (PM2.5) may share similar biological pathways, participants were categorized by joint classifications of radon level (<2 and ≥2 pCi/L) with smoking status (never smokers and ever smokers) and radon level with PM2.5 level (above or below the median). Main outcomes and measures: The main outcome was GD, identified based on glucose tolerance testing and information from medical record abstraction. Multiple logistic regression models were used to assess the association between radon exposure and GD. Results: Among the 9107 participants, mean (SD) age was 27.0 (5.6) years; 3782 of 9101 (41.6%) had ever used tobacco. The mean (SD) county-level radon concentration was 1.6 (0.9) pCi/L, and 382 participants (4.2%) had GD recorded. After adjusting for potential confounders, individuals living in counties with the highest radon level (≥2 pCi/L) had higher odds of developing GD compared with those living in counties with the lowest radon level (<1 pCi/L) (odds ratio [OR], 1.37; 95% CI, 1.02-1.84); after additional adjustment for PM2.5, the OR was 1.36 (95% CI, 1.00-1.86). Elevated odds of GD were also observed in ever smokers living in counties with a higher (≥2 pCi/L) radon level (OR, 2.09; 95% CI, 1.41-3.11) and participants living in counties with higher radon and PM2.5 levels (OR, 1.93; 95% CI, 1.31-2.83), though no statistically significant interactions were observed. Conclusions and relevance: This cohort study suggests that higher radon exposure is associated with greater odds of GD in nulliparous pregnant individuals. Further studies are needed to confirm the results and elucidate the underlying mechanisms, especially with individual-level residential radon exposure assessment.Item Treatment of Gestational Diabetes Mellitus and Offspring Early Childhood Growth(Endocrine Society, 2021-04) Feghali, Maisa; Atlass, Jacqueline; Abebe, Kaleab Z.; Comer, Diane; Catov, Janet; Caritis, Steve; Arslanian, Silva; Scifres, Christina; Obstetrics and Gynecology, School of MedicineBackground: Gestational diabetes mellitus (GDM) is associated with fetal overgrowth, and certain treatments are associated with an increased risk of macrosomia. However, there are limited data about the long-term effect of GDM treatment on childhood growth. Methods: Cohort study of 816 women with GDM and their offspring delivered between 2009 and 2012. Childhood height and weight through age 3 were collected from the medical record and z-scores and body mass index (BMI) were calculated. We assessed the association between GDM treatment and childhood growth using linear mixed modeling. Results: Treatment was divided into medical nutritional therapy (MNT) (n = 293), glyburide (n = 421), and insulin (n = 102). At delivery, birthweight, z-score, and BMI were higher in the offspring of women treated with either glyburide or insulin compared to MNT. However, weight, z-score, and BMI were similar among all offspring at 6 months and 1, 2, and 3 years of age. After controlling for covariates, there were differences in the weight z-score (P = 0.01) over the 3-year period by treatment group, but no differences in weight (P = 0.06) or change in BMI (P = 0.28). Pairwise comparisons indicated that insulin was associated with more weight gain compared with MNT (0.69 kg; 95% CI, 0.10-1.28; P = 0.02) and glyburide was associated with a trend toward lower weight z-score compared with MNT (-0.24; 95% CI, -0.47 to 0.003; P = 0.05). Conclusion: Despite growth differences detected at birth, we observed no meaningful differences in childhood growth from 6 months to 3 years among treatment groups, including in the offspring of women with GDM treated with glyburide.