Browsing by Author "Saade, George"
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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 Association between asthma and hypertensive disorders of pregnancy: a secondary analysis of the Nulliparous Pregnancy Outcomes Study: monitoring mothers-to-be (nuMoM2b) prospective cohort study(Elsevier, 2023) Meislin, Rachel; Bose, Sonali; Huang, Xiaoning; Wharton, Robert; Ponce, Jana; Simhan, Hyagriv; Haas, David; Saade, George; Silver, Robert; Chung, Judith; Mercer, Brian M.; Grobman, William A.; Khan, Sadiya S.; Bianco, Angela; Obstetrics and Gynecology, School of MedicineObjective:: Asthma is one of the most common comorbid conditions in pregnancy. While asthma has been identified as an independent risk factor for cardiovascular disease in the general population, the influence of active asthma during pregnancy on future cardiac risk is unclear. Growing evidence has linked maternal active asthma to adverse pregnancy outcomes (APOs), such as hypertensive disorders of pregnancy (HDP), including preeclampsia which is a well-defined risk factor for future cardiovascular disease including altered cardiac structure and diastolic dysfunction. A thorough understanding of the relationship between pre-existing asthma and APOs may be instrumental in identifying upstream factors contributing to lifetime maternal cardiovascular risk. However, current knowledge of these relationships has been largely derived from retrospective clinical studies, which limit the precision of capturing APOs. Therefore, we investigated associations between pre-existing asthma and individual subtypes of APOs in a secondary analysis of a prospective multi-center cohort of nulliparous individuals with rigorously adjudicated pregnancy outcomes. Study design:: We included participants from the multisite Nulliparous Outcomes in Pregnancy: Monitoring Mothers to be (nuMom2b) cohort, which recruited nulliparous individuals with a viable, singleton gestation between 60/7 and 136/7 weeks. Details of the study design have been previously described, which included medical histories in standardized interviews. This secondary analysis included individuals aged 18 years or older with a live birth and excluded those with a history of pre-pregnancy hypertension or diabetes. For the purposes of this analysis, we defined active asthma as a self-reported history of asthma and on current asthma treatment, including use of bronchodilator, inhaled steroid, or immune modulator, captured at the first trimester visit. The primary outcome was HDP and secondary outcomes included other APOs. Characteristics between participants who did and did not have asthma were compared. Univariate and multivariate logistic regression, described using odds ratios (ORs) and adjusted ORs (aORs) and 95% confidence intervals (95% CI), was used to determine risk of APOs. Models were adjusted for maternal age, study site, insurance type (marker of socioeconomic status), and smoking status at the first trimester visit. Race/ethnicity and body mass index (BMI) were excluded from fully adjusted models as race/ethnicity was considered as a factor reflective of the social determinants of health and BMI was conceptualized as within the casual pathway for developing HDP. The study was approved by all local institutional review boards, and participants gave written informed consent. Analyses were conducted using STATA (MP 17, College Station, TX). Results: Of 8,741 individuals included, 1,521 (17.4%) reported a diagnosis of asthma at the first trimester visit, of whom 588 (38.7%) reported the use of any asthma medication. When comparing participants with and without asthma, a higher proportion of those with asthma reported smoking tobacco in the three months prior to pregnancy (20.7% vs 16.5%) (Table 1). Univariate logistic regression revealed that a diagnosis of asthma was associated with a significantly higher risk of HDP (OR: 1.21 [1.04, 1.42]). Following adjustment, risk of HDP remained significantly higher (aOR: 1.23 [1.06, 1.42]), specifically preeclampsia (aOR: 1.21, [1.02, 1.45]). Secondary analyses in participants with active asthma (ie additional reported use of asthma medication during or before the first trimester) demonstrated a significantly higher risk of HDP (aOR 1.32 [1.06–1.65]) including preeclampsia (aOR 1.27 [1.07–1.51]; in addition to spontaneous preterm birth (aOR 1.60 [1.30–1.96]). Conclusions: In a diverse, nationally representative sample of nulliparous individuals,, a diagnosis of asthma was associated with a significantly higher risk of HDP. Active asthma increased the risk of both spontaneous preterm birth and HDP. This analysis supports the importance of identifying active asthma as a risk factor for APOs associated with a higher risk of future cardiovascular disease.Item Associations of the Neighborhood Built Environment with Gestational Weight Gain(Thieme, 2023) Grobman, William A.; Crenshaw, Emma G.; Marsh, Derek J.; McNeil, Rebecca B.; Pemberton, Victoria L.; Haas, David M.; Debbink, Michelle; Mercer, Brian M.; Parry, Samuel; Reddy, Uma; Saade, George; Simhan, Hyagriv; Mukhtar, Farhana; Wing, Deborah A.; Kershaw, Kiarri N.; NICHD nuMoM2b NHLBI nuMoM2b Heart Health Study Networks; Obstetrics and Gynecology, School of MedicineObjective: This study aimed to determine whether specific factors of the built environment related to physical activity and diet are associated with inadequate and excessive gestational weight gain (GWG). Study design: This analysis is based on data from the Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-To-Be, a prospective cohort of nulliparous women who were followed from the beginning of their pregnancies through delivery. At each study visit, home addresses were recorded and geocoded. Locations were linked to several built-environment characteristics such as the census tract National Walkability Score (the 2010 Walkability Index) and the number of gyms, parks, and grocery stores within a 3-km radius of residential address. The primary outcome of GWG (calculated as the difference between prepregnancy weight and weight at delivery) was categorized as inadequate, appropriate, or excessive based on weight gained per week of gestation. Multinomial regression (generalized logit) models evaluated the relationship between each factor in the built environment and excessive or inadequate GWG. Results: Of the 8,182 women in the analytic sample, 5,819 (71.1%) had excessive GWG, 1,426 (17.4%) had appropriate GWG, and 937 (11.5%) had inadequate GWG. For the majority of variables examined, built environments more conducive to physical activity and healthful food availability were associated with a lower odds of excessive or inadequate GWG category. For example, a higher number of gyms or parks within 3 km of a participant's residential address was associated with lower odds of having excessive (gyms: adjusted odds ratio [aOR] = 0.93 [0.89-0.96], parks: 0.94 [0.90-0.98]) or inadequate GWG (gyms: 0.91 [0.86-0.96]; parks: 0.91 [0.86-0.97]). Similarly, a higher number of grocery stores was associated with lower odds of having excessive GWG (0.94 [0.91-0.97]). Conclusion: Among a diverse population of nulliparous women, multiple aspects of the built environment are associated with excessive and inadequate GWG.Item Associations of the Neighborhood Built Environment With Physical Activity Across Pregnancy(Human Kinetics, 2021-04-15) Kershaw, Kiarri N.; Marsh, Derek J.; Crenshaw, Emma G.; McNeil, Rebecca B.; Pemberton, Victoria L.; Cordon, Sabrina A.; Haas, David M.; Debbink, Michelle P.; Mercer, Brian M.; Parry, Samuel; Reddy, Uma; Saade, George; Simhan, Hyagriv; Wapner, Ronald J.; Wing, Deborah A.; Grobman, William A.; NICHD nuMoM2b Heart Health Study Network; NHLBI nuMoM2b Heart Health Study Network; Obstetrics and Gynecology, School of MedicineBackground: Several features of the neighborhood built environment have been shown to promote leisure-time physical activity (PA) in the general population, but few studies have examined its impact on PA during pregnancy. Methods: Data were extracted from 8362 Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-to-Be cohort participants (2010-2013). Residential address information was linked to 3 built environment characteristics: number of gyms and recreation areas within a 3-km radius of residence and census block level walkability. Self-reported leisure-time PA was measured in each trimester and dichotomized as meeting PA guidelines or not. Relative risks for cross-sectional associations between neighborhood characteristics and meeting PA guidelines were estimated using Poisson regression. Results: More gyms and recreation areas were each associated with a greater chance of meeting PA guidelines in models adjusted for sociodemographic characteristics and preexisting conditions. Associations were strongest in the third trimester where each doubling in counts of gyms and recreation areas was associated with 10% (95% confidence interval, 1.07-1.13) and 8% (95% confidence interval, 1.03-1.12), respectively, greater likelihood of meeting PA guidelines. Associations were similar though weaker for walkability. Conclusions: Results from a large, multisite cohort suggest that these built environment characteristics have similar PA-promoting benefits in pregnant women as seen in more general populations.Item Development of a Generic Physiologically-Based Pharmacokinetic Model for Lactation and Prediction of Maternal and Infant Exposure to Ondansetron via Breast Milk(Wiley, 2022) Job, Kathleen M.; Dallmann, André; Parry, Samuel; Saade, George; Haas, David M.; Hughes, Brenna; Berens, Pamela; Chen, Jia-Yu; Fu, Christina; Humphrey, Kelsey; Hornik, Christoph; Balevic, Stephen; Zimmerman, Kanecia; Watt, Kevin; Obstetrics and Gynecology, School of MedicineOndansetron is commonly used in breastfeeding mothers to treat nausea and vomiting. There is limited information in humans regarding safety of ondansetron exposure to nursing infants and no adequate study looking at ondansetron pharmacokinetics during lactation. We developed a generic physiologically based pharmacokinetic lactation model for small molecule drugs and applied this model to predict ondansetron transfer into breast milk and characterize infant exposure. Drug-specific model inputs were parameterized using data from the literature. Population-specific inputs were derived from a previously conducted systematic literature review of anatomic and physiologic changes in postpartum women. Model predictions were evaluated using ondansetron plasma and breast milk concentration data collected prospectively from 78 women in the Commonly Used Drugs During Lactation and infant Exposure (CUDDLE) study. The final model predicted breast milk and plasma exposures following a single 4 mg dose of intravenous ondansetron in 1000 simulated women who were two days postpartum. Model predictions showed good agreement with observed data. Breast milk median prediction error (MPE) was 18.4% and median absolute prediction error (MAPE) was 53.0%. Plasma MPE was 32.5% and MAPE was 43.2%. The model-predicted daily and relative infant doses were 0.005 mg/kg/day and 3.0%, respectively. This model adequately predicted ondansetron passage into breast milk. The calculated low relative infant dose indicates that mothers receiving ondansetron can safely breastfeed. The model building blocks and population database are open-source and can be adapted to other drugs.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 Maternal Preconception Omega-6, Omega-3, and Omega-6:Omega-3 Intake and Uterine Artery Indices in Mid-Gestation(Thieme, 2025) Finch, Amara; Joss-Moore, Lisa; Allshouse, Amanda A.; Blue, Nathan; Haas, David M.; Grobman, William; Parry, Samuel; Saade, George; Silver, Robert M.; Obstetrics and Gynecology, School of MedicineObjective: Maternal preconception diet influences pregnancy health and fetal outcomes. We examined the relationship between preconception fatty acid (FA) intake and uterine artery indices in mid-gestation in a large, heterogeneous cohort of nulliparous individuals. Study design: This is a secondary analysis of the nuMom2b (Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-to-be) study. Dietary ω-6 and ω-3 FA intake was assessed with food frequency questionnaires and uterine artery indices were obtained via Doppler studies in the second trimester. For our primary outcome of pulsatility index (PI) > 1.6, we compared proportions by each dichotomous FA exposure and tested differences with chi-square test. Results: For PI > 1.6, odds ratio for the unfavorable FA quartile compared with remaining quartiles for the exposures were 0.96 to 1.25, p = 0.157 (ω-6 FA); 0.97 to 1.26, p = 0.124 (ω-3 FA); 0.87 to 1.14, p = 1.00 (ω-6:ω-3 FA ratio). Conclusion: No significant associations between self-reported maternal preconception ω-6 and ω-3 FA intake and uterine artery Doppler indices measured during the second trimester were observed.Item Neighborhood Socioeconomic Disadvantage and Abnormal Birth Weight(Wolters Kluwer, 2023) Venkatesh, Kartik K.; Yee, Lynn M.; Johnson, Jasmine; Wu, Jiqiang; McNeil, Becky; Mercer, Brian; Simhan, Hyagriv; Reddy, Uma M.; Silver, Robert M.; Parry, Samuel; Saade, George; Chung, Judith; Wapner, Ronald; Lynch, Courtney D.; Grobman, William A.; Obstetrics and Gynecology, School of MedicineObjective: To examine whether exposure to community or neighborhood socioeconomic disadvantage as measured by the ADI (Area Deprivation Index) is associated with risk of abnormal birth weight among nulliparous individuals with singleton gestations. Methods: This was a secondary analysis from the prospective cohort NuMoM2b study (Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-To-Be). Participant addresses at cohort enrollment between 6 and 13 weeks of gestation were geocoded at the Census tract level and linked to the 2015 ADI. The ADI, which incorporates the domains of income, education, employment, and housing quality into a composite national ranking of neighborhood socioeconomic disadvantage, was categorized by quartiles (quartile 1, least disadvantaged, reference; quartile 4, most disadvantaged). Outcomes were large for gestational age (LGA; birth weight at or above the 90th percentile) and small for gestational age (SGA; birth weight below the 10th percentile) compared with appropriate for gestational age (AGA; birth weight 10th-90th percentile) as determined with the 2017 U.S. natality reference data, standardized for fetal sex. Multinomial logistic regression models were adjusted for potential confounding variables. Results: Of 8,983 assessed deliveries in the analytic population, 12.7% (n=1,143) were SGA, 8.2% (n=738) were LGA, and 79.1% (n=7,102) were AGA. Pregnant individuals living in the highest ADI quartile (quartile 4, 17.8%) had an increased odds of delivering an SGA neonate compared with those in the lowest referent quartile (quartile 1, 12.4%) (adjusted odds ratio [aOR] 1.32, 95% CI 1.09-1.55). Pregnant individuals living in higher ADI quartiles (quartile 2, 10.3%; quartile 3, 10.7%; quartile 4, 9.2%) had an increased odds of delivering an LGA neonate compared with those in the lowest referent quartile (quartile 1, 8.2%) (aOR: quartile 2, 1.40, 95% CI 1.19-1.61; quartile 3, 1.35, 95% CI 1.09-1.61; quartile 4, 1.47, 95% CI 1.20-1.74). Conclusion: Neonates of nulliparous pregnant individuals living in U.S. neighborhoods with higher area deprivation were more likely to have abnormal birth weights at both extremes.Item Outcomes of shared institutional review board compared with multiple individual site institutional review board models in a multisite clinical trial(Elsevier, 2023) Martin, Samantha L.; Allman, Phillip H.; Dugoff, Lorraine; Sibai, Baha; Lynch, Stephanie; Ferrara, Jennifer; Aagaard, Kjersti; Zornes, Christina; Wilson, Jennifer L.; Gibson, Marie; Adams, Molly; Longo, Sherri A.; Staples, Amy; Saade, George; Beche, Imene; Carter, Ebony B.; Owens, Michelle Y.; Simhan, Hyagriv; Frey, Heather A.; Khan, Shama; Palatnik, Anna; August, Phyllis; Irby, Les'Shon; Lee, Tiffany; Lee, Christine; Schum, Paula; Chan-Akeley, Rosalyn; Duhon, Catera; Rincon, Monica; Gibson, Kelly; Wiegand, Samantha; Eastham, Donna; Oparil, Suzanne; Szychowski, Jeff M.; Tita, Alan; Chronic Hypertension and Pregnancy Consortium; Obstetrics and Gynecology, School of MedicineBackground: Institutional review boards play a crucial role in initiating clinical trials. Although many multicenter clinical trials use an individual institutional review board model, where each institution uses their local institutional review board, it is unknown if a shared (single institutional review board) model would reduce the time required to approve a standard institutional review board protocol. Objective: This study aimed to compare processing times and other processing characteristics between sites using a single institutional review board model and those using their individual site institutional review board model in a multicenter clinical trial. Study design: This was a retrospective study of sites in an open-label, multicenter randomized control trial from 2014 to 2021. Participating sites in the multicenter Chronic Hypertension and Pregnancy trial were asked to complete a survey collecting data describing their institutional review board approval process. Results: A total of 45 sites participated in the survey (7 used a shared institutional review board model and 38 used their individual institutional review board model). Most sites (86%) using the shared institutional review board model did not require a full-board institutional review board meeting before protocol approval, compared with 1 site (3%) using the individual institutional review board model (P<.001). Median total approval times (41 vs 56 days; P=.42), numbers of submission rounds (1 vs 2; P=.09), and numbers of institutional review board stipulations (1 vs 4; P=.12) were lower for the group using the shared institutional review board model than those using the individual site institutional review board model; however, these differences were not statistically significant. Conclusion: The findings supported the hypothesis that the shared institutional review board model for multicenter studies may be more efficient in terms of cumulative time and effort required to obtain approval of an institutional review board protocol than the individual institutional review board model. Given that these data have important implications for multicenter clinical trials, future research should evaluate these findings using larger or multiple multicenter trials.Item Performance of a Multianalyte 'Rule-Out' Assay in Pregnant Individuals With Suspected Preeclampsia(Wolters Kluwer, 2022) Costantine, Maged M.; Sibai, Baha; Bombard, Allan T.; Sarno, Mark; West, Holly; Haas, David M.; Tita, Alan T.; Paidas, Michael J.; Clark, Erin A. S.; Boggess, Kim; Grotegut, Chad; Grobman, William; Su, Emily J.; Burd, Irina; Saade, George; Chavez, Martin R.; Paglia, Michael J.; Merriam, Audrey; Torres, Carlos; Habli, Mounira; Macones, Georges; Wen, Tony; Bofill, James; Palatnik, Anna; Edwards, Rodney K.; Haeri, Sina; Oberoi, Pankaj; Mazloom, Amin; Cooper, Matthew; Lockton, Steven; Hankins, Gary D.; Obstetrics and Gynecology, School of MedicineBackground: The ability to diagnose preeclampsia clinically is suboptimal. Our objective was to validate a novel multianalyte assay and characterize its performance, when intended for use as an aid to rule-out preeclampsia. Methods: Prospective, multicenter cohort study of pregnant individuals presenting between 280/7 and 366/7 weeks' with preeclampsia-associated signs and symptoms. Individuals not diagnosed with preeclampsia after baseline evaluation were enrolled in the study cohort, with those who later developed preeclampsia, classified as cases and compared with a negative control group who did not develop preeclampsia. Individuals with assay values at time of enrollment ≥0.0325, determined using a previously developed algorithm, considered at risk. The primary analysis was the time to develop preeclampsia assessed using a multivariate Cox regression model. Results: One thousand thirty-six pregnant individuals were enrolled in the study cohort with an incidence of preeclampsia of 30.3% (27.6%-33.2%). The time to develop preeclampsia was shorter for those with an at-risk compared with negative assay result (log-rank P<0.0001; adjusted hazard ratio of 4.81 [3.69-6.27, P<0.0001]). The performance metrics for the assay to rule-out preeclampsia within 7 days of enrollment showed a sensitivity 76.4% (67.5%-83.5%), negative predictive value 95.0% (92.8%-96.6%), and negative likelihood ratio 0.46 (0.32-0.65). Assay performance improved if delivery occurred <37 weeks and for individuals enrolled between 28 and 35 weeks. Conclusions: We confirmed that a novel multianalyte assay was associated with the time to develop preeclampsia and has a moderate sensitivity and negative likelihood ratio but high negative predictive value when assessed as an aid to rule out preeclampsia within 7 days of enrollment.