Browsing by Author "Wapner, Ronald"
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Item A Comprehensive and Bias-Free Machine Learning Approach for Risk Prediction of Preeclampsia with Severe Features in a Nulliparous Study Cohort(Research Square, 2023-04-10) Lin, Yun; Mallia, Daniel; Clark-Sevilla, Andrea; Catto, Adam; Leshchenko, Alisa; Yan, Qi; Haas, David; Wapner, Ronald; Pe'er, Itsik; Raja, Anita; Salleb-Aouissi, Ansaf; Obstetrics and Gynecology, School of MedicineObjective: Preeclampsia is one of the leading causes of maternal morbidity, with consequences during and after pregnancy. Because of its diverse clinical presentation, preeclampsia is an adverse pregnancy outcome that is uniquely challenging to predict and manage. In this paper, we developed machine learning models that predict the onset of preeclampsia with severe features or eclampsia at discrete time points in a nulliparous pregnant study cohort. Materials and methods: The prospective study cohort to which we applied machine learning is the Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-to-be (nuMoM2b) study, which contains information from eight clinical sites across the US. Maternal serum samples were collected for 1,857 individuals between the first and second trimesters. These patients with serum samples collected are selected as the final cohort. Results: Our prediction models achieved an AUROC of 0.72 (95% CI, 0.69-0.76), 0.75 (95% CI, 0.71-0.79), and 0.77 (95% CI, 0.74-0.80), respectively, for the three visits. Our initial models were biased toward non-Hispanic black participants with a high predictive equality ratio of 1.31. We corrected this bias and reduced this ratio to 1.14. The top features stress the importance of using several tests, particularly for biomarkers and ultrasound measurements. Placental analytes were strong predictors for screening for the early onset of preeclampsia with severe features in the first two trimesters. Conclusion: Experiments suggest that it is possible to create racial bias-free early screening models to predict the patients at risk of developing preeclampsia with severe features or eclampsia nulliparous pregnant study cohort.Item Association between aspirin use during pregnancy and cardiovascular risk factors 2-7 years after delivery: The nuMoM2b Heart Health Study(Elsevier, 2022) Theilen, Lauren H.; Greenland, Philip; Varagic, Jasmina; Catov, Janet; Shanks, Anthony L.; Thorsten, Vanessa; Parker, Corette B.; McNeil, Rebecca; Mercer, Brian; Hoffman, Matthew; Wapner, Ronald; Haas, David; Simhan, Hyagriv; Grobman, William; Chung, Judith H.; Levine, Lisa D.; Barnes, Shannon; Merz, Noel Bairey; Saade, George; Silver, Robert M.; Obstetrics and Gynecology, School of MedicineObjectives: To evaluate the association between aspirin use during first pregnancy and later maternal cardiovascular risk. Study design: In this secondary analysis of a prospective cohort, we included participants who carried their first pregnancy to 20 + weeks, had data regarding aspirin use, and attended a study visit 2-7 years following delivery. The exposure was aspirin use during the first pregnancy. We calculated aspirin use propensity scores from logistic regression models including baseline variables associated with aspirin use in pregnancy and cardiovascular risk. Outcomes of interest were incident cardiovascular-related diagnoses 2-7 years following delivery. Robust Poisson regression calculated the risk of outcomes by aspirin exposure, adjusting for the aspirin use propensity score. Main outcome measures: The primary outcome was a composite of incident cardiovascular diagnoses at the time of the study visit: cardiovascular events, chronic hypertension, metabolic syndrome, prediabetes or type 2 diabetes, dyslipidemia, and chronic kidney disease. Results: Of 4,480 women included, 84 (1.9%) reported taking aspirin during their first pregnancy. 52.6% of participants in the aspirin-exposed group and 43.0% in the unexposed group had the primary outcome. After adjusting for the aspirin use propensity scores, aspirin use during the first pregnancy was not associated with any of the outcomes. Conclusion: We did not detect an association between aspirin use during the first pregnancy and cardiovascular-related diagnoses 2-7 years later. Our study was only powered to detect a large difference in relative risk, so we cannot rule out a smaller difference that may be clinically meaningful.Item Customized versus Population Growth Standards for Morbidity and Mortality Risk Stratification Using Ultrasonographic Fetal Growth Assessment at 22 to 29 Weeks' Gestation(Thieme, 2021) Blue, Nathan R.; Grobman, William A.; Larkin, Jacob C.; Scifres, Christina M.; Simhan, Hyagriv N.; Chung, Judith H.; Saade, George R.; Haas, David M.; Wapner, Ronald; Reddy, Uma M.; Mercer, Brian; Parry, Samuel I.; Silver, Robert M.; Obstetrics and Gynecology, School of MedicineObjective: The aim of study is to compare the performance of ultrasonographic customized and population fetal growth standards for prediction adverse perinatal outcomes. Study design: This was a secondary analysis of the Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-to-Be, in which l data were collected at visits throughout pregnancy and after delivery. Percentiles were assigned to estimated fetal weights (EFWs) measured at 22 to 29 weeks using the Hadlock population standard and a customized standard (www.gestation.net). Areas under the curve were compared for the prediction of composite and severe composite perinatal morbidity using EFW percentile. Results: Among 8,701 eligible study participants, the population standard diagnosed more fetuses with fetal growth restriction (FGR) than the customized standard (5.5 vs. 3.5%, p < 0.001). Neither standard performed better than chance to predict composite perinatal morbidity. Although the customized performed better than the population standard to predict severe perinatal morbidity (areas under the curve: 0.56 vs. 0.54, p = 0.003), both were poor. Fetuses considered FGR by the population standard but normal by the customized standard had morbidity rates similar to fetuses considered normally grown by both standards.The population standard diagnosed FGR among black women and Hispanic women at nearly double the rate it did among white women (p < 0.001 for both comparisons), even though morbidity was not different across racial/ethnic groups. The customized standard diagnosed FGR at similar rates across groups. Using the population standard, 77% of FGR cases were diagnosed among female fetuses even though morbidity among females was lower (p < 0.001). The customized model diagnosed FGR at similar rates in male and female fetuses. Conclusion: At 22 to 29 weeks' gestation, EFW percentile alone poorly predicts perinatal morbidity whether using customized or population fetal growth standards. The population standard diagnoses FGR at increased rates in subgroups not at increased risk of morbidity and at lower rates in subgroups at increased risk of morbidity, whereas the customized standard does not.Item Gestational Weight Gain and Pregnancy Outcomes among Nulliparous Women(Thieme, 2021) Dude, Annie M.; Grobman, William; Haas, David; Mercer, Brian M.; Parry, Samuel; Silver, Robert M.; Wapner, Ronald; Wing, Deborah; Saade, George; Reddy, Uma; Iams, Jay; Kominiarek, Michelle A.; Obstetrics and Gynecology, School of MedicineObjective: To determine the association between total gestational weight gain and perinatal outcomes. Study design: Data from the Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-To-Be (NuMoM2b) study were used. Total gestational weight gain was categorized as inadequate, adequate, or excessive based on the 2009 Institute of Medicine guidelines. Outcomes examined included hypertensive disorders of pregnancy, mode of delivery, shoulder dystocia, large for gestational age or small for-gestational age birth weight, and neonatal intensive care unit admission. Results: Among 8,628 women, 1,666 (19.3%) had inadequate, 2,945 (34.1%) had adequate, and 4,017 (46.6%) had excessive gestational weight gain. Excessive gestational weight gain was associated with higher odds of hypertensive disorders (adjusted odds ratio [aOR] = 2.05, 95% confidence interval [CI]: 1.78-2.36) Cesarean delivery (aOR = 1.24, 95% CI: 1.09-1.41), and large for gestational age birth weight (aOR = 1.49, 95% CI: 1.23-1.80), but lower odds of small for gestational age birth weight (aOR = 0.59, 95% CI: 0.50-0.71). Conversely, inadequate gestational weight gain was associated with lower odds of hypertensive disorders (aOR = 0.75, 95% CI: 0.62-0.92), Cesarean delivery (aOR = 0.77, 95% CI: 0.65-0.92), and a large for gestational age birth weight (aOR = 0.72, 95% CI: 0.55-0.94), but higher odds of having a small for gestational age birth weight (aOR = 1.64, 95% CI: 1.37-1.96). Conclusion: Both excessive and inadequate gestational weight gain are associated with adverse maternal and neonatal outcomes.Item Racial or Ethnic and Socioeconomic Inequalities in Adherence to National Dietary Guidance in a Large Cohort of US Pregnant Women(Elsevier, 2017-06) Bodnar, Lisa M.; Simhan, Hyagriv N.; Parker, Corette B.; Meier, Heather; Mercer, Brian M.; Grobman, William A.; Haas, David M.; Wing, Deborah A.; Hoffman, Matthew K.; Parry, Samuel; Silver, Robert M.; Saade, George R.; Wapner, Ronald; Iams, Jay D.; Wadhwa, Pathik D.; Elovitz, Michal; Peaceman, Alan M.; Esplin, Sean; Barnes, Shannon; Reddy, Uma M.; Obstetrics and Gynecology, School of MedicineBACKGROUND: The significance of periconceptional nutrition for optimizing offspring and maternal health and reducing social inequalities warrants greater understanding of diet quality among US women. OBJECTIVE: Our objective was to evaluate racial or ethnic and education inequalities in periconceptional diet quality and sources of energy and micronutrients. DESIGN: Cross-sectional analysis of data from the Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-to-Be cohort. PARTICIPANTS AND SETTING: Nulliparous women (N=7,511) were enrolled across eight US medical centers from 2010 to 2013. MAIN OUTCOME MEASURES: A semiquantitative food frequency questionnaire assessing usual dietary intake during the 3 months around conception was self-administered during the first trimester. Diet quality, measured using the Healthy Eating Index-2010 (HEI-2010), and sources of energy and micronutrients were the outcomes. STATISTICAL ANALYSES: Differences in diet quality were tested across maternal racial or ethnic and education groups using F tests associated with analysis of variance and χ2 tests. RESULTS: HEI-2010 score increased with higher education, but the increase among non-Hispanic black women was smaller than among non-Hispanic whites and Hispanics (interaction P value <0.0001). For all groups, average scores for HEI-2010 components were below recommendations. Top sources of energy were sugar-sweetened beverages, pasta dishes, and grain desserts, but sources varied by race or ethnicity and education. Approximately 34% of energy consumed was from empty calories (the sum of energy from added sugars, solid fats, and alcohol beyond moderate levels). The primary sources of iron, folate, and vitamin C were juices and enriched breads. CONCLUSIONS: Diet quality is suboptimal around conception, particularly among women who are non-Hispanic black, Hispanic, or who had less than a college degree. Diet quality could be improved by substituting intakes of refined grains and foods empty in calories with vegetables, peas and beans (legumes), seafood, and whole grains.Item Reliable detection of subchromosomal deletions and duplications using cell-based noninvasive prenatal testing(Wiley, 2018-10-25) Vossaert, Liesbeth; Wang, Qun; Salman, Roseen; Zhuo, Xinming; Qu, Chunjing; Henke, David; Seubert, Ron; Chow, Jennifer; U'ren, Lance; Enright, Brennan; Stilwell, Jackie; Kaldjian, Eric; Yang, Yaping; Shaw, Chad; Levy, Brynn; Wapner, Ronald; Breman, Amy; Veyver, Ignatia Van den; Beaudet, Arthur; Medical and Molecular Genetics, School of MedicineObjective To gather additional data on the ability to detect subchromosomal abnormalities of various sizes in single fetal cells isolated from maternal blood, using low-coverage shotgun next-generation sequencing for cell-based noninvasive prenatal testing (NIPT). Method Fetal trophoblasts were recovered from approximately 30 mL of maternal blood using maternal white blood cell depletion, density-based cell separation, immunofluorescence staining, and high-resolution scanning. These trophoblastic cells were picked as single cells and underwent whole genome amplification for subsequent genome-wide copy number analysis and genotyping to confirm the fetal origin of the cells. Results Applying our fetal cell isolation method to a series of 125 maternal blood samples, we detected on average 4.17 putative fetal cells/sample. The series included 15 cases with clinically diagnosed fetal aneuploidies and five cases with subchromosomal abnormalities. This method was capable of detecting findings that were 1 to 2 Mb in size, and all were concordant with the microarray or karyotype data obtained on a fetal sample. A minority of fetal cells showed evidence of genome degradation likely related to apoptosis. Conclusion We demonstrate that this cell-based NIPT method has the capacity to reliably diagnose fetal chromosomal abnormalities down to 1 to 2 Mb in size.Item The association between personal weight gain goals, provider recommendations, and appropriate gestational weight gain(Elsevier, 2020) Dude, Annie M.; Plunkett, Beth; Grobman, William; Scifres, Christina M.; Mercer, Brian M.; Parry, Samuel; Silver, Robert M.; Wapner, Ronald; Wing, Deborah A.; Saade, George; Reddy, Uma; Iams, Jay; Simhan, Hyagriv; Kominiarek, Michelle A.; Obstetrics and Gynecology, School of MedicineBackground: Nearly half of all women exceed the 2009 Institute of Medicine guidelines for gestational weight gain. Excess gestational weight gain is associated with adverse pregnancy outcomes. Objective: Our objective was to determine whether having a personal gestational weight gain goal consistent with the Institute of Medicine's recommendations for appropriate gestational weight gain and whether having a discussion with one's obstetrical provider regarding that goal were associated with appropriate gestational weight gain. Study design: This is a secondary analysis of the Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-To-Be study, a prospective cohort study of nulliparous women. We asked women at their first study visit (between 6 and 13 weeks' gestation) whether they had a gestational weight gain goal and what that goal was. Furthermore, we asked whether their provider discussed a gestational weight gain goal and what that goal was. We classified personal and provider-recommended gestational weight gain goals as consistent or inconsistent with the Institute of Medicine guidelines, taking into account a woman's initial body mass index category (underweight, normal weight, overweight, and obese). We included women with live singleton term deliveries (between 37 and 43 weeks' gestation) in this analysis. We classified the primary outcome, which was gestational weight gain (defined as the difference between first visit weight and final weight before delivery), as inadequate, appropriate, or excessive, based on the Institute of Medicine guidelines and initial body mass index category. We used Student t, Wilcoxon rank-sum, and chi-square tests for bivariable analyses, and multinomial logistic regression was performed to control for confounding variables. Results: Of 6727 eligible women, 3799 (56.5% of all eligible women) stated they had a gestational weight gain goal. Of the 3799 women with a stated goal, 2589 (38.5% of all women) had a goal consistent with the Institute of Medicine's recommendations. In addition, of the 6727 eligible women, 2188 (32.5%) reported that they discussed gestational weight gain with their provider, and 1548 of these (23.0% of all women) recalled that their provider gave a gestational weight gain goal in accordance with the Institute of Medicine guidelines. Although having any gestational weight gain goal was not associated with appropriate gestational weight gain, having a gestational weight gain goal that was consistent with the Institute of Medicine's recommendations was associated with a reduced risk of excessive (adjusted relative risk ratio, 0.77; 95% confidence interval, 0.64-0.92) and inadequate weight gain (adjusted relative risk ratio, 0.66; 95% confidence interval, 0.53-0.82). Conversely, discussing gestational weight gain goals with a provider was not associated with either inadequate or excessive gestational weight gain even if the provider's recommendations for gestational weight gain were consistent with the guidelines. Conclusion: Nulliparas who delivered singleton pregnancies at term who had a personal gestational weight gain goal consistent with the Institute of Medicine's recommendations were less likely to have excessive or inadequate gestational weight gain. Further study is required to evaluate the most effective way to communicate this information to patients.Item Weight gain in early, mid, and late pregnancy and hypertensive disorders of pregnancy(Elsevier, 2020-04) Dude, Annie M.; Kominiarek, Michelle A.; Haas, David M.; Iams, Jay; Mercer, Brian M.; Parry, Samuel; Reddy, Uma M.; Saade, George; Silver, Robert M.; Simhan, Hyagriv; Wapner, Ronald; Wing, Deborah; Grobman, William; Obstetrics and Gynecology, School of MedicineObjective: To examine the relationship of weight change during early, mid, and late pregnancy with the development of a hypertensive disorder of pregnancy (HDP). Study design: These data are from a prospective cohort study of nulliparous women with live singleton pregnancies. "Early" weight change was defined as the difference between self-reported pre-pregnancy weight and weight at the first visit (between 6 and 13 weeks' gestation); "mid" weight change was defined as the weight change between the first and second visits (between 16 and 21 weeks' gestation); "late" weight change was defined as the weight change between the second and third visits (between 22 and 29 weeks' gestation). Weight change in each time period was further characterized as inadequate, adequate, or excessive based on the Institute of Medicine's (IOM's) trimester-specific weekly weight gain goals based on pre-pregnancy body mass index. Multivariable Poisson regression was performed to adjust for potential confounders. Main outcome measure: Development of any hypertensive disorder of pregnancy. Results: Of 8296 women, 1564 (18.9%) developed a HDP. Weight gain in excess of the IOM recommendations during the latter two time periods was significantly associated with HDP. Specifically, trimester-specific excessive weight gain in the mid period (aIRR 1.16, 95% CI 1.01-1.35) as well as in the late period (aIRR = 1.19, 95% CI = 1.02-1.40) was associated with increased risk of developing HDP. The weight gain preceded the onset of clinically apparent disease. Conclusions: Excessive weight gain as early as the early second trimester was associated with increased risks of development of HDP.