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Item Association of Adverse Pregnancy Outcomes With Hypertension 2 to 7 Years Postpartum(Wiley Open Access, 2019-10-01) Haas, David M.; Parker, Corette B.; Marsh, Derek J.; Grobman, William A.; Ehrenthal, Deborah B.; Greenland, Philip; Merz, C. Noel Bairey; Pemberton, Victoria L.; Silver, Robert M.; Barnes, Shannon; McNeil, Rebecca B.; Cleary, Kirsten; Reddy, Uma M.; Chung, Judith H.; Parry, Samuel; Theilen, Lauren H.; Blumenthal, Elizabeth A.; Levine, Lisa D.; Mercer, Brian M.; Simhan, Hyagriv; Polito, LuAnn; Wapner, Ronald J.; Catov, Janet; Chen, Ida; Saade, George R. Saade; NHLBI nuMoM2b Heart Health Study; Medicine, School of MedicineBackground Identifying pregnancy-associated risk factors before the development of major cardiovascular disease events could provide opportunities for prevention. The objective of this study was to determine the association between outcomes in first pregnancies and subsequent cardiovascular health. Methods and Results The Nulliparous Pregnancy Outcomes Study Monitoring Mothers-to-be Heart Health Study is a prospective observational cohort that followed 4484 women 2 to 7 years (mean 3.2 years) after their first pregnancy. Adverse pregnancy outcomes (defined as hypertensive disorders of pregnancy, small-for-gestational-age birth, preterm birth, and stillbirth) were identified prospectively in 1017 of the women (22.7%) during this pregnancy. The primary outcome was incident hypertension (HTN). Women without adverse pregnancy outcomes served as controls. Risk ratios (RR) and 95% CIs were adjusted for age, smoking, body mass index, insurance type, and race/ethnicity at enrollment during pregnancy. The overall incidence of HTN was 5.4% (95% CI 4.7% to 6.1%). Women with adverse pregnancy outcomes had higher adjusted risk of HTN at follow-up compared with controls (RR 2.4, 95% CI 1.8-3.1). The association held for individual adverse pregnancy outcomes: any hypertensive disorders of pregnancy (RR 2.7, 95% CI 2.0-3.6), preeclampsia (RR 2.8, 95% CI 2.0-4.0), and preterm birth (RR 2.7, 95% CI 1.9-3.8). Women who had an indicated preterm birth and hypertensive disorders of pregnancy had the highest risk of HTN (RR 4.3, 95% CI 2.7-6.7). Conclusions Several pregnancy complications in the first pregnancy are associated with development of HTN 2 to 7 years later. Preventive care for women should include a detailed pregnancy history to aid in counseling about HTN risk.Item Association of N-Terminal Pro-Brain Natriuretic Peptide Concentration in Early Pregnancy With Development of Hypertensive Disorders of Pregnancy and Future Hypertension(American Medical Association, 2022) Hauspurg, Alisse; Marsh, Derek J.; McNeil, Rebecca B.; Bairey Merz, C. Noel; Greenland, Philip; Straub, Adam C.; Rouse, Caroline E.; Grobman, William A.; Pemberton, Victoria L.; Silver, Robert M.; Chen, Yii-Der Ida; Mercer, Brian M.; Levine, Lisa D.; Hameed, Afshan; Hoffman, Matthew K.; Simhan, Hyagriv N.; Catov, Janet M.; NICHD nuMoM2b and NHLBI nuMoM2b Heart Health Study Networks; Obstetrics and Gynecology, School of MedicineImportance: Hypertensive disorders of pregnancy are associated with future cardiovascular disease, perhaps because of subclinical cardiac dysfunction before pregnancy leading to impaired adaptation to pregnancy. Natriuretic peptides are promising biomarkers for detecting subclinical cardiac dysfunction outside of pregnancy. Objective: To investigate whether higher concentrations of N-terminal pro-brain natriuretic peptide (NT-proBNP) in early pregnancy would be associated with hypertensive disorders of pregnancy and hypertension 2 to 7 years post partum. Design, setting, and participants: This cohort study used data from the The Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-to-Be Heart Health Study, a prospective multicenter observational study. A total of 4103 nulliparous women with complete data and no prepregnancy hypertension or diabetes who were treated at 8 clinical sites were included. Women were followed up with for 2 to 7 years after pregnancy. Data were collected from October 2010 to October 2017, and data were analyzed from August 2020 to November 2021. Exposures: NT-proBNP concentration, measured using an electrochemiluminescence immunoassay from a first-trimester blood sample. Main outcomes and measures: Hypertensive disorders of pregnancy and incident hypertension (systolic blood pressure of 130 mm Hg or diastolic blood pressure of 80 mm Hg or use of antihypertensive agents) at follow-up visit. Results: A total of 4103 women met inclusion criteria; the mean (SD) age was 27.0 (5.6) years. Among these women, 909 (22.2%) had an adverse pregnancy outcome, and 817 (19.9%) had hypertension at the follow-up visit. Higher NT-proBNP concentrations were associated with a lower risk of hypertensive disorders of pregnancy (adjusted odds ratio per doubling, 0.81; 95% CI, 0.73-0.91), which persisted after adjustment for age, self-reported race and ethnicity, early-pregnancy body mass index, smoking, and aspirin use. Similarly, higher NT-proBNP concentration in early pregnancy was also associated with a lower risk of incident hypertension 2 to 7 years after delivery (adjusted odds ratio per doubling, 0.84; 95% CI, 0.77-0.93), an association that persisted after controlling for confounders, including hypertensive disorders of pregnancy. Conclusions and relevance: In this cohort study, higher NT-proBNP concentrations in early pregnancy were associated with a lower risk of hypertensive disorders of pregnancy and hypertension 2 to 7 years post partum. These findings suggest that normal early-pregnancy cardiovascular physiology, as assessed by NT-proBNP concentration, may provide biologic insights into both pregnancy outcome and cardiovascular disease risk.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 Design and Rationale of the Fontan Udenafil Exercise Longitudinal (FUEL) Trial(Elsevier, 2018) Goldberg, David J.; Zak, Victor; Goldstein, Bryan H.; McCrindle, Brian W.; Menon, Shaji C.; Schumacher, Kurt R.; Payne, R. Mark; Rhodes, Jonathan; McHugh, Kimberly E.; Penny, Daniel J.; Trachtenberg, Felicia; Hamstra, Michelle S.; Richmond, Marc E.; Frommelt, Peter C.; Files, Matthew D.; Yeager, James L.; Pemberton, Victoria L.; Stylianou, Mario P.; Pearson, Gail D.; Paridon, Stephen M.; Pediatrics, School of MedicineThe Fontan operation creates a circulation characterized by elevated central venous pressure and low cardiac output. Over time, these characteristics result in a predictable and persistent decline in exercise performance that is associated with an increase in morbidity and mortality. A medical therapy that targets the abnormalities of the Fontan circulation might, therefore, be associated with improved outcomes. Udenafil, a phosphodiesterase type 5 inhibitor, has undergone phase I/II testing in adolescents who have had the Fontan operation and has been shown to be safe and well tolerated in the short-term. However, there are no data regarding the long-term efficacy of udenafil in this population. The Fontan Udenafil Exercise Longitudinal (FUEL) Trial is a randomized, double blind, placebo controlled phase III clinical trial being conducted by the Pediatric Heart Network in collaboration with Mezzion Pharma Co., Ltd. This trial is designed to test the hypothesis that treatment with udenafil will lead to an improvement in exercise capacity in adolescents who have undergone the Fontan operation. A safety extension trial, the FUEL Open-Label Extension Trial (FUEL OLE), offers the opportunity for all FUEL subjects to obtain open-label udenafil for an additional 12 months following completion of FUEL, and evaluates the long-term safety and tolerability of this medication. This manuscript describes the rationale and study design for FUEL and FUEL OLE. Together, these trials provide an opportunity to better understand the role of medical management in the care of those who have undergone the Fontan operation.Item Early Pregnancy Atherogenic Profile in a First Pregnancy and Hypertension Risk 2 to 7 Years After Delivery(American Heart Association, 2021-02) Catov, Janet M.; McNeil, Rebecca B.; Marsh, Derek J.; Mercer, Brian M.; Merz, C. Noel Bairey; Parker, Corette B.; Pemberton, Victoria L.; Saade, George R.; Chen, Yii-Der (Ida); Chung, Judith H.; Ehrenthal, Deborah B.; Grobman, William A.; Haas, David M.; Parry, Samuel; Polito, LuAnn; Reddy, Uma M.; Silver, Robert M.; Simhan, Hyagriv N.; Wapner, Ronald J.; Kominiarek, Michelle; Kreutz, Rolf; Levine, Lisa D.; Greenland, Philip; Obstetrics and Gynecology, School of MedicineBackground: Cardiovascular risk in young adulthood is an important determinant of lifetime cardiovascular disease risk. Women with adverse pregnancy outcomes (APOs) have increased cardiovascular risk, but the relationship of other factors is unknown. Methods and Results: Among 4471 primiparous women, we related first-trimester atherogenic markers to risk of APO (hypertensive disorders of pregnancy, preterm birth, small for gestational age), gestational diabetes mellitus (GDM) and hypertension (130/80 mm Hg or antihypertensive use) 2 to 7 years after delivery. Women with an APO/GDM (n=1102) had more atherogenic characteristics (obesity [34.2 versus 19.5%], higher blood pressure [systolic blood pressure 112.2 versus 108.4, diastolic blood pressure 69.2 versus 66.6 mm Hg], glucose [5.0 versus 4.8 mmol/L], insulin [77.6 versus 60.1 pmol/L], triglycerides [1.4 versus 1.3 mmol/L], and high-sensitivity C-reactive protein [5.6 versus 4.0 nmol/L], and lower high-density lipoprotein cholesterol [1.8 versus 1.9 mmol/L]; P<0.05) than women without an APO/GDM. They were also more likely to develop hypertension after delivery (32.8% versus 18.1%, P<0.05). Accounting for confounders and factors routinely assessed antepartum, higher glucose (relative risk [RR] 1.03 [95% CI, 1.00-1.06] per 0.6 mmol/L), high-sensitivity C-reactive protein (RR, 1.06 [95% CI, 1.02-1.11] per 2-fold higher), and triglycerides (RR, 1.27 [95% CI, 1.14-1.41] per 2-fold higher) were associated with later hypertension. Higher physical activity was protective (RR, 0.93 [95% CI, 0.87-0.99] per 3 h/week). When evaluated as latent profiles, the nonobese group with higher lipids, high-sensitivity C-reactive protein, and insulin values (6.9% of the cohort) had increased risk of an APO/GDM and later hypertension. Among these factors, 7% to 15% of excess RR was related to APO/GDM. Conclusions: Individual and combined first-trimester atherogenic characteristics are associated with APO/GDM occurrence and hypertension 2 to 7 years later.Item Factors associated with duration of breastfeeding in women giving birth for the first time(BMC, 2022-09-22) Haas, David M.; Yang, Ziyi; Parker, Corette B.; Chung, Judith; Parry, Samuel; Grobman, William A.; Mercer, Brian M.; Simhan, Hyagriv N.; Silver, Robert M.; Wapner, Ronald J.; Saade, George R.; Greenland, Philip; Merz, Noel Bairey; Reddy, Uma M.; Pemberton, Victoria L.; nuMoM2b study; nuMoM2b Heart Health Study; Obstetrics and Gynecology, School of MedicineObjective: To examine maternal, psychosocial, and pregnancy factors associated with breastfeeding for at least 6 months in those giving birth for the first time. Methods: We performed a planned secondary analysis of an observational cohort study of 5249 women giving birth for the first time. Women were contacted at least 6 months after delivery and provided information regarding breastfeeding initiation, duration, and exclusivity. Maternal demographics, psychosocial measures, and delivery methods were compared by breastfeeding groups. Results: 4712 (89.8%) of the women breastfed at some point, with 2739 (58.2%) breastfeeding for at least 6 months. Of those who breastfed, 1161 (24.7% of the entire cohort), breastfed exclusively for at least 6 months. In the multivariable model among those who ever breastfed, not smoking in the month prior to delivery (adjusted odds ratio [aOR] 2.04, 95%CI 1.19-3.45), having a Master's degree of higher (aOR 1.89, 95%CI 1.51-2.36), having a planned pregnancy (aOR 1.48, 95%CI 1.27-1.73), older age (aOR 1.02, 95% CI, 1.01-1.04), lower BMI (aOR 0.96 95% CI 0.95-0.97), and having less anxiety measured during pregnancy (aOR 0.990, 95%CI 0.983-0.998) were associated with breastfeeding for at least 6 months. Compared to non-Hispanic White women, Hispanic women, while being more likely to breastfeed initially (aOR 1.40, 95%CI 1.02-1.92), were less likely to breastfeed for 6 months (aOR 0.72, 95%CI 0.59-0.88). While non-Hispanic Black women were less likely than non-Hispanic White women to initiate breastfeeding (aOR 0.68, 95%CI 0.51-0.90), the odds of non-Hispanic Black women of continuing to breastfeed for at least 6 months was similar to non-Hispanic White women (aOR 0.92, 95%CI 0.71-1.19). Conclusions: In this cohort of women giving birth for the first time, duration of breastfeeding was associated with several characteristics which highlight groups at greater risk of not breastfeeding as long as currently recommended.Item Pregnancy as a Window to Future Cardiovascular Health: Design and Implementation of the nuMoM2b Heart Health Study(Oxford University Press, 2016-03-15) Haas, David M.; Ehrenthal, Deborah B.; Koch, Matthew A.; Catov, Janet M.; Barnes, Shannon E.; Facco, Francesca; Parker, Corette B.; Mercer, Brian M.; Bairey-Merz, C. Noel; Silver, Robert M.; Wapner, Ronald J.; Simhan, Hyagriv N.; Hoffman, Matthew K.; Grobman, William A.; Greenland, Philip; Wing, Deborah A.; Saade, George R.; Parry, Samuel; Zee, Phyllis C.; Reddy, Uma M.; Pemberton, Victoria L.; Burwen, Dale R.; Department of Obstetrics and Gynecology, IU School of MedicineThe National Institute of Child Health and Human Development's Nulliparous Pregnancy Outcomes Study-Monitoring Mothers-to-Be (nuMoM2b) Heart Health Study (HHS) was designed to investigate the relationships between adverse pregnancy outcomes and modifiable risk factors for cardiovascular disease. The ongoing nuMoM2b-HHS, which started in 2013, is a prospective follow-up of the nuMoM2b cohort, which included 10,038 women recruited between 2010 and 2013 from 8 centers across the United States who were initially observed over the course of their first pregnancies. In this report, we detail the design and study procedures of the nuMoM2b-HHS. Women in the pregnancy cohort who consented to be contacted for participation in future studies were approached at 6-month intervals to ascertain health information and to maintain ongoing contact. Two to 5 years after completion of the pregnancy documented in the nuMoM2b, women in the nuMoM2b-HHS were invited to an in-person study visit. During this visit, they completed psychosocial and medical history questionnaires and had clinical measurements and biological specimens obtained. A subcohort of participants who had objective assessments of sleep-disordered breathing during pregnancy were asked to repeat this investigation. This unique prospective observational study includes a large, geographically and ethnically diverse cohort, rich depth of phenotypic information about adverse pregnancy outcomes, and clinical data and biospecimens from early in the index pregnancy onward. Data obtained from this cohort will provide mechanistic and clinical insights into how data on a first pregnancy can provide information about the potential development of subsequent risk factors for cardiovascular disease.Item Results of the Fontan Udenafil Exercise Longitudinal (FUEL) Trial(American Heart Association, 2020-02-25) Goldberg, David J.; Zak, Victor; Goldstein, Bryan H.; Schumacher, Kurt R.; Rhodes, Jonathan; Penny, Daniel J.; Petit, Christopher J.; Ginde, Salil; Menon, Shaji C.; Kim, Seong-Ho; Kim, Gi Beom; Nowlen, Todd T.; DiMaria, Michael V.; Frischhertz, Benjamin P.; Wagner, Jonathan B.; McHugh, Kimberly E.; McCrindle, Brian W.; Shillingford, Amanda J.; Sabati, Arash A.; Yetman, Anji T.; John, Anitha S.; Richmond, Marc E.; Files, Matthew D.; Payne, R. Mark; Mackie, Andrew S.; Davis, Christopher K.; Shahanavaz, Shabana; Hill, Kevin D.; Garg, Ruchira; Jacobs, Jeffrey P.; Hamstra, Michelle S.; Woyciechowski, Stacy; Rathge, Kathleen A.; McBride, Michael G.; Frommelt, Peter C.; Russell, Mark W.; Urbina, Elaine M.; Yeager, James L.; Pemberton, Victoria L.; Stylianou, Mario P.; Pearson, Gail D.; Paridon, Stephen M.; Pediatrics, School of MedicineBackground: The Fontan operation creates a total cavopulmonary connection, a circulation in which the importance of pulmonary vascular resistance is magnified. Over time, this circulation leads to deterioration of cardiovascular efficiency associated with a decline in exercise performance. Rigorous clinical trials aimed at improving physiology and guiding pharmacotherapy are lacking. Methods: The FUEL trial (Fontan Udenafil Exercise Longitudinal) was a phase III clinical trial conducted at 30 centers. Participants were randomly assigned udenafil, 87.5 mg twice daily, or placebo in a 1:1 ratio. The primary outcome was the between-group difference in change in oxygen consumption at peak exercise. Secondary outcomes included between-group differences in changes in submaximal exercise at the ventilatory anaerobic threshold, the myocardial performance index, the natural log of the reactive hyperemia index, and serum brain-type natriuretic peptide. Results: Between 2017 and 2019, 30 clinical sites in North America and the Republic of Korea randomly assigned 400 participants with Fontan physiology. The mean age at randomization was 15.5±2 years; 60% of participants were male, and 81% were white. All 400 participants were included in the primary analysis with imputation of the 26-week end point for 21 participants with missing data (11 randomly assigned to udenafil and 10 to placebo). Among randomly assigned participants, peak oxygen consumption increased by 44±245 mL/min (2.8%) in the udenafil group and declined by 3.7±228 mL/min (-0.2%) in the placebo group (P=0.071). Analysis at ventilatory anaerobic threshold demonstrated improvements in the udenafil group versus the placebo group in oxygen consumption (+33±185 [3.2%] versus -9±193 [-0.9%] mL/min, P=0.012), ventilatory equivalents of carbon dioxide (-0.8 versus -0.06, P=0.014), and work rate (+3.8 versus +0.34 W, P=0.021). There was no difference in change of myocardial performance index, the natural log of the reactive hyperemia index, or serum brain-type natriuretic peptide level. Conclusions: In the FUEL trial, treatment with udenafil (87.5 mg twice daily) was not associated with an improvement in oxygen consumption at peak exercise but was associated with improvements in multiple measures of exercise performance at the ventilatory anaerobic threshold.Item Serum Cotinine and Adverse Cardiovascular Outcomes: A Cross-sectional Secondary Analysis of the nuMoM2b Heart Health Study(Thieme, 2023) Theilen, Lauren H.; McNeil, Rebecca B.; Hunter, Shannon; Grobman, William A.; Parker, Corette B.; Catov, Janet M.; Pemberton, Victoria L.; Ehrenthal, Deborah B.; Haas, David M.; Hoffman, Matthew K.; Chung, Judith H.; Mukhtar, Farhana; Arzumanyan, Zorayr; Mercer, Brian; Parry, Samuel; Saade, George R.; Simhan, Hyagriv N.; Wapner, Ronald J.; Silver, Robert M.; NHLBI nuMoM2b Heart Health Study Network; Obstetrics and Gynecology, School of MedicineObjective: We aimed to (1) compare serum cotinine with self-report for ascertaining smoking status among reproductive-aged women; (2) estimate the relative odds of adverse cardiovascular (CV) outcomes among women by smoking status; (3) assess whether the association between adverse pregnancy outcomes (APOs) and CV outcomes varies by smoking status. Study design: We conducted a cross-sectional study of the nuMoM2b Heart Health Study. Women attended a study visit 2 to 7 years after their first pregnancy. The exposure was smoking status, determined by self-report and by serum cotinine. Outcomes included incident chronic hypertension (HTN), metabolic syndrome (MetS), and dyslipidemia. Multivariable logistic regression estimated odds ratios (ORs) for each outcome by smoking status. Results: Of 4,392 women with serum cotinine measured, 3,610 were categorized as nonsmokers, 62 as secondhand smoke exposure, and 720 as smokers. Of 3,144 women who denied tobacco smoke exposure, serum cotinine was consistent with secondhand smoke exposure in 48 (1.5%) and current smoking in 131 (4.2%) After adjustment for APOs, smoking defined by serum cotinine was associated with MetS (adjusted OR [aOR] = 1.52, 95% confidence interval [CI]: 1.21, 1.91) and dyslipidemia (aOR = 1.28, 95% CI: 1.01, 1.62). When stratified by nicotine exposure, nonsmokers with an APO in their index pregnancy had higher odds of stage 1 (aOR = 1.64, 95% CI: 1.32, 2.03) and stage 2 HTN (aOR = 2.92, 95% CI: 2.17, 3.93), MetS (aOR = 1.76, 95% CI: 1.42, 2.18), and dyslipidemia (aOR = 1.55, 95% CI: 1.25, 1.91) relative to women with no APO. Results were similar when smoking exposure was defined by self-report. Conclusion: Whether determined by serum cotinine or self-report, smoking is associated with subsequent CV outcomes in reproductive-aged women. APOs are also independently associated with CV outcomes in women.