Browsing by Author "Levine, Lisa D."
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Item Allostatic Load and Adverse Pregnancy Outcomes(Wolters Kluwer, 2022-01-12) Lueth, Amir J.; Allshouse, Amanda A.; Blue, Nathan M.; Grobman, William A.; Levine, Lisa D.; Simhan, Hyagriv N.; Kim, Jin Kyung; Johnson, Jasmine; Wilson, Fernando A.; Murtaugh, Maureen; Silver, Robert M.; National Institutes of Health (NIH); National Institute of Child Health and Human Development (NICHD); Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-to-Be (nuMoM2b); National Heart, Lung, and Blood Institute (NHLBI) nuMoM2b Heart Health Study; Obstetrics and Gynecology, School of MedicineObjective: To assess the association between allostatic load, as an estimate of chronic stress, and adverse pregnancy outcomes. Methods: This was a secondary analysis of the Nulliparous Pregnancy Outcomes Study Monitoring-to-be (nuMoM2b) study, a prospective observational cohort study. Our primary exposure was dichotomous high allostatic load in the first trimester, defined as four or more out of 12 biomarkers in the “worst” quartile. The primary outcome was a composite adverse pregnancy outcome: hypertensive disorders of pregnancy (HDP), preterm birth, small for gestational age (SGA) neonate, and stillbirth. Secondary outcomes included components of the composite. Multivariable logistic regression was used to test the association between high allostatic load and adverse pregnancy outcomes, adjusted for potential confounders. Mediation and moderation analyses were conducted to assess the role of allostatic load along the causal pathway between racial disparities and adverse pregnancy outcomes. Results: Among 4,266 individuals, 34.7% had a high allostatic load. Composite adverse pregnancy outcome occurred in 1,171 (27.5%): 14.0% HDP, 8.6% preterm birth (48.0% spontaneous and 52.2% indicated), 11.0% SGA, and 0.3% stillbirth. After adjustment for maternal age, gravidity, smoking, bleeding in the first trimester, and health insurance, high allostatic load was significantly associated with composite adverse pregnancy outcome (aOR 1.5, 95% CI: 1.3, 1.7) and HDP (2.5, 2.0–2.9), but not preterm birth and SGA. High allostatic load partially mediated the association between self-reported race and adverse pregnancy outcomes. The association between allostatic load and HDP differed by self-reported race, but not for composite adverse pregnancy outcome, preterm birth, and SGA. Conclusion: High allostatic load in the first trimester is associated with adverse pregnancy outcomes, particularly HDP. Allostatic load was a partial mediator between race and adverse pregnancy outcomes. The association between allostatic load and HDP differed by self-reported race.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 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 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 Association of second trimester uterine artery Doppler parameters with maternal hypertension 2-7 years after delivery(Elsevier, 2021-08-12) Miller, Eliza C.; Carper, Benjamin; Bello, Natalie A.; Merz, C. Noel Bairey; Greenland, Philip; Levine, Lisa D.; Haas, David M.; Grobman, William A.; McNeil, Rebecca B.; Chung, Judith H.; Jolley, Jennifer; Saade, George R.; Silver, Robert M.; Simhan, Hyagriv N.; Wapner, Ronald J.; Parker, Corette B.; NIH NICHD nuMoM2b and NHLBI nuMoM2b Heart Health Study Networks; Obstetrics and Gynecology, School of MedicineBackground: Reduced uterine artery compliance is associated with adverse pregnancy outcomes (APOs) and may indicate underlying maternal cardiovascular pathology. We investigated associations between second trimester uterine artery Doppler (UAD) parameters and incident maternal hypertension 2-7 years after delivery. Methods: A cohort of 10,038 nulliparous US participants was recruited early in pregnancy. A subgroup of 3739, without baseline hypertension and with complete follow-up visits 2-7 years after delivery, were included in this analysis. We investigated UAD indicators of compliance including: 1) early diastolic notch; 2) resistance index (RI); and 3) pulsatility index (PI). We defined hypertension as systolic blood pressure ≥130 mmHg, diastolic ≥80 mmHg, or antihypertensive medication use. We calculated odds ratios (OR) and 95 % confidence intervals (95%CI) for associations between UAD parameters and hypertension, adjusting for age, obesity, race/ethnicity, insurance, smoking, and APOs. Results: A total of 187 (5 %) participants developed hypertension after the index pregnancy. Presence of early diastolic notch on UAD was not associated with incident hypertension. Increased RI and PI correlated with higher odds of hypertension (RI: adjusted OR 1.15 [95 % CI 1.03-1.30]; PI: adjusted OR 1.03 [95%CI 1.01-1.05] for each 0.1 unit increase). Maximum RI above 0.84 or maximum PI above 2.3 more than doubled the odds of incident hypertension (RI: adjusted OR 2.49, 95%CI 1.45-4.26; PI: adjusted OR 2.36, 95%CI 1.45-3.86). Conclusion: Higher resistance and pulsatility indices measured on second trimester UAD were associated with increased odds of incident hypertension 2-7 years later, and may be biomarkers of higher maternal cardiovascular risk.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 Sleep-disordered Breathing in Pregnancy and after Delivery: Associations with Cardiometabolic Health(American Thoracic Society, 2022) Facco, Francesca L.; Redline, Susan; Hunter, Shannon M.; Zee, Phyllis C.; Grobman, William A.; Silver, Robert M.; Louis, Judette M.; Pien, Grace W.; Mercer, Brian; Chung, Judith H.; Merz, C. Noel Bairey; Haas, David M.; Nhan-Chang, Chia-Ling; Simhan, Hyagriv N.; Schubert, Frank P.; Parry, Samuel; Reddy, Uma; Saade, George R.; Hoffman, Matthew K.; Levine, Lisa D.; Wapner, Ronald J.; Catov, Janet M.; Parker, Corette B.; Obstetrics and Gynecology, School of MedicineRationale: Knowledge gaps exist regarding health implications of sleep-disordered breathing (SDB) identified in pregnancy and/or after delivery. Objectives: To determine whether SDB in pregnancy and/or after delivery is associated with hypertension (HTN) and metabolic syndrome (MS). Methods: nuMoM2b-HHS (Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-to-be Heart Health Study) (N = 4,508) followed participants initially recruited during their first pregnancy. Participants returned for a visit 2-7 years after pregnancy. This study examined a subgroup who underwent SDB assessments during their first pregnancy (n = 1,964) and a repeat SDB assessment after delivery (n = 1,222). Two SDB definitions were considered: 1) apnea-hypopnea index (AHI) ⩾ 5 and 2) oxygen desaturation index (ODI) ⩾ 5. Associations between SDB and incident HTN and MS were evaluated with adjusted risk ratios (aRRs). Measurements and Main Results: The aRR for MS given an AHI ⩾ 5 during pregnancy was 1.44 (95% confidence interval [CI], 1.08-1.93), but no association with HTN was found. ODI ⩾ 5 in pregnancy was associated with both an increased risk for HTN (aRR, 2.02; 95% CI, 1.30-3.14) and MS (aRR, 1.53; 95% CI, 1.19-1.97). Participants with an AHI ⩾ 5 in pregnancy that persisted after delivery were at higher risk for both HTN (aRR, 3.77; 95% CI, 1.84-7.73) and MS (aRR, 2.46; 95% CI, 1.59-3.76). Similar associations were observed for persistent ODI ⩾ 5 after delivery. Conclusions: An AHI ⩾ 5 in pregnancy was associated with an increased risk of MS. An ODI ⩾ 5 in pregnancy was significantly associated with both HTN and MS. Participants with persistent elevations in AHI and ODI during pregnancy and at 2-7 years after delivery were at the highest risk for HTN and MS.