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Endothelial dysfunction is a form of subclinical cardiovascular disease that may be involved in preterm birth and small-for-gestational-age deliveries. However, concentrations of biomarkers of endothelial dysfunction before pregnancy have rarely been measured. We hypothesized that higher levels of biomarkers of endothelial dysfunction (cellular adhesion molecules and selectins) would be associated with odds of preterm birth and/or small-for-gestational-age deliveries. We included 235 women from the Coronary Artery Risk Development in Young Adults (CARDIA) study who were nulliparous at Y7, reported ≥1 live birth through Y25, and had ≥1 biomarker measured at Y7. We tested for associations between individual biomarkers and an averaged z-score representing total endothelial dysfunction with preterm birth and/or small-for-gestational-age deliveries using Poisson regression, adjusted for demographic and clinical characteristics at the exam immediately preceding index birth. At Y7, total evidence of  endothelial dysfunction was similar in women who did (n = 59) and did not have (n = 176) preterm birth and/or small-for-gestational-age deliveries. There was no association between biomarkers of endothelial dysfunction (either individual biomarker or total score) with odds of preterm birth and/or small-for-gestational-age deliveries after adjustment: IRR = 1.01, 95% CI: 0.74, 1.39, p = 0.93 for total endothelial biomarker score. Associations were not modified by race. We conclude that biomarkers of endothelial dysfunction in nulliparous women, measured ~3 years before pregnancy, did not identify women at risk for preterm birth and/or small-for-gestational-age deliveries. This suggests that the maternal endothelial dysfunction that is believed to contribute to these birth outcomes may not be detectable before pregnancy.

The 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., (© The Author 2016. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

The objective of this study was to determine the association between maternal 25-hydroxyvitamin D (25(OH)D) and the risk of spontaneous preterm birth (sPTB) before 35 weeks' gestation. A random subcohort from the US Collaborative Perinatal Project (1959-1965) was sampled (n = 2,629) and augmented with all remaining cases of sPTB before 35 weeks' gestation for a total of 767 cases. Banked serum samples collected at 26 weeks' gestation or earlier were assayed for 25(OH)D. Constructs for vascular histology and inflammatory histology were developed from placental pathology examinations. There was no relationship between 25(OH)D and sPTB among white women. Among nonwhite mothers, serum 25(OH)D levels of 30-<50, 50-<75, and ≥75 nmol/L were associated with reductions of 1.0-1.6 cases of sPTB per 100 live births and 20%-30% reductions in risk of sPTB compared with 25(OH)D levels less than 30 nmol/L after adjustment for prepregnancy body mass index (weight (kg)/height (m)(2)), season, and other confounders. This association was driven by inflammation-mediated cases of sPTB and sPTB cases without placental lesions. A sensitivity analysis for unmeasured confounding by exercise, fish intake, and skin color suggested some bias away from the null in the conventional results, but conclusions were generally supported. The vitamin D-sPTB relationship should be examined in modern cohorts with detailed data on skin pigmentation and other covariates.

Background/aims: We sought to investigate the association between preconception serum lipids and their daily rate of change in relation to length of gestation., Methods: In a cohort of 70 women, 61 (87%) became pregnant, resulting in 48 (69%) live births. Serum lipid measurements (in milligrams per deciliter) included total cholesterol, free cholesterol, triglycerides and phospholipids at preconception, upon human chorionic gonadotropin-confirmed pregnancy and following pregnancy loss (<14 weeks) or post partum. Pregnancy outcome (loss, preterm and term delivery) and gestational length were modeled relative to daily rate of change in lipids using multinomial regression and Cox proportional hazards models, respectively, adjusting for body mass index and smoking., Results: A rate of triglyceride change below the median was associated with an increased risk for pregnancy loss compared with term birth (adjusted odds ratio: 9.02; 95% CI: 1.62-50.30). A rate of triglyceride change of ≤0.01 mg/dl per day versus above the median was associated with a trend for increased risk of pregnancy loss or preterm (<37 weeks) birth (adjusted hazard ratio: 1.77; 95% CI: 0.94-3.33)., Conclusion: A low rate of triglyceride change during early pregnancy may be a signal of risk of pregnancy loss or preterm birth. Lipids offer promise for identifying pregnancies at risk for adverse outcomes.

There is growing interest in the relationship between gestational weight gain (GWG) and long-term maternal and child outcomes, yet little is known about the accuracy of long-term maternal recall of GWG. Our objective was to assess the accuracy of maternal recall of GWG at 4-12 years postpartum (mean, 8 years) compared with medical-record documented GWG, and compare recalled GWG to documented GWG with respect to their associations with adverse pregnancy outcomes including small for gestational age (SGA) birth, preterm birth, cesarean delivery, and postpartum weight retention (PPWR) (n = 503). Adequacy of recalled and documented GWG was assessed according to the 2009 Institute of Medicine (IOM) guidelines. We observed moderate agreement between documented and maternal self-reported GWG as continuous variables (r = 0.63, P < 0.01). When recalled GWG was used to categorize women, 45, 53, and 20% of women with inadequate, adequate, and excessive documented GWG were misclassified, respectively. When comparing models fitted with documented or recalled GWG, there were no meaningful differences in associations between inadequate GWG and SGA birth (odds ratio 2.2 (95% confidence interval: 1.3, 3.7) vs. 2.1 (1.2, 3.8), respectively) or excessive GWG and PPWR (2.5 (1.6, 3.9) vs. 2.5 (1.5, 4.0), respectively). However, the use of recalled GWG attenuated associations between inadequate GWG and PPWR (documented: 0.5 (0.3, 0.9) vs. recalled GWG: 1.3 (0.7, 2.3)) and excessive GWG and preterm birth (documented: 2.5 (1.4, 4.5) vs. recalled GWG: 1.5 (0.9, 2.7)). Our data suggest a varying degree of bias when using recalled GWG to study selected adverse outcomes.

Objective: To evaluate whether early folic acid supplementation during pregnancy prevents diagnosis of autism spectrum disorders in offspring. Methods: Information on autism spectrum disorder diagnosis was obtained from the National Hospital Register and the Central Psychiatric Register. We estimated risk ratios for autism spectrum disorders for children whose mothers took folate or multivitamin supplements from 4 weeks prior from the last menstrual period through to 8 weeks after the last menstrual period (-4 to 8 weeks) by three 4-week periods. Results: We did not find an association between early folate or multivitamin intake for autism spectrum disorder (folic acid--adjusted risk ratio: 1.06, 95% confidence interval: 0.82-1.36; multivitamin--adjusted risk ratio: 1.00, 95% confidence interval: 0.82-1.22), autistic disorder (folic acid--adjusted risk ratio: 1.18, 95% confidence interval: 0.76-1.84; multivitamin--adjusted risk ratio: 1.22, 95% confidence interval: 0.87-1.69), Asperger's syndrome (folic acid--adjusted risk ratio: 0.85, 95% confidence interval: 0.46-1.53; multivitamin--adjusted risk ratio: 0.95, 95% confidence interval: 0.62-1.46), or pervasive developmental disorder--not otherwise specified (folic acid--adjusted risk ratio: 1.07, 95% confidence interval: 0.75-1.54; multivitamin--adjusted risk ratio: 0.87, 95% confidence interval: 0.65-1.17) compared with women reporting no supplement use in the same period. Conclusion: We did not find any evidence to corroborate previous reports of a reduced risk for autism spectrum disorders in offspring of women using folic acid supplements in early pregnancy.

BackgroundObesity is a well-established risk factor for both adverse pregnancy outcomes (APOs) and cardiovascular disease (CVD). However, it is not known whether APOs are mediators or markers of the obesity-CVD relationship. This study examined the association between body mass index, APOs, and postpartum CVD risk factors.MethodsThe sample included adults from the nuMoM2b (Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-To-Be) Heart Health Study who were enrolled in their first trimester (6 weeks-13 weeks 6 days gestation) from 8 United States sites. Participants had a follow-up visit at 3.7 years postpartum. APOs, which included hypertensive disorders of pregnancy, preterm birth, small-for-gestational-age birth, and gestational diabetes, were centrally adjudicated. Mediation analyses estimated the association between early pregnancy body mass index and postpartum CVD risk factors (hypertension, hyperlipidemia, and diabetes) and the proportion mediated by each APO adjusted for demographics and baseline health behaviors, psychosocial stressors, and CVD risk factor levels.ResultsAmong 4216 participants enrolled, mean±SD maternal age was 27±6 years. Early pregnancy prevalence of overweight was 25%, and obesity was 22%. Hypertensive disorders of pregnancy occurred in 15%, preterm birth in 8%, small-for-gestational-age birth in 11%, and gestational diabetes in 4%. Early pregnancy obesity, compared with normal body mass index, was associated with significantly higher incidence of postpartum hypertension (adjusted odds ratio, 1.14 [95% CI, 1.10-1.18]), hyperlipidemia (1.11 [95% CI, 1.08-1.14]), and diabetes (1.03 [95% CI, 1.01-1.04]) even after adjustment for baseline CVD risk factor levels. APOs were associated with higher incidence of postpartum hypertension (1.97 [95% CI, 1.61-2.40]) and hyperlipidemia (1.31 [95% CI, 1.03-1.67]). Hypertensive disorders of pregnancy mediated a small proportion of the association between obesity and incident hypertension (13% [11%-15%]) and did not mediate associations with incident hyperlipidemia or diabetes. There was no significant mediation by preterm birth or small-for-gestational-age birth.ConclusionsThere was heterogeneity across APO subtypes in their association with postpartum CVD risk factors and mediation of the association between early pregnancy obesity and postpartum CVD risk factors. However, only a small or nonsignificant proportion of the association between obesity and CVD risk factors was mediated by any of the APOs, suggesting APOs are a marker of prepregnancy CVD risk and not a predominant cause of postpartum CVD risk.

ObjectiveWe 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 designWe 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.ResultsOf 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.ConclusionWhether 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.Key points· Cotinine was detected in 5.7% of reported nonsmokers.. · Smoking and APOs were independently associated with CV health.. · Smoking was associated with MetS and dyslipidemia..

BackgroundOlder females show greater cognitive gains from physical activity (PA) than males, which may be related to long-term consequences of female-specific reproductive events (eg, pregnancy) on cognitive health.MethodsTo determine whether previous parity could moderate the relationship between PA and cognitive decline in older women, we conducted secondary analyses of data from the Health, Aging, and Body Composition Study. We tested whether the association between average PA over 10 years and cognition (Modified Mini-Mental State Examination [3MS]) and executive functioning (digit symbol substitution test [DSST]) over 10 years varied by previous parity (nulliparity, low parity, medium parity, and grand multiparity). An analysis of covariance was performed with cognition (average and change over 10 years) as the dependent variables, parity as a categorical predictor, average PA as a continuous predictor, and a set of relevant covariates.ResultsSignificant interactions were found between PA and parity group for all 4 comparisons: average 3MS (p = .014), average DSST (p = .032), change in 3MS (p = .016), and change in DSST (p = .017). Simple slope analyses indicated the positive relationship between PA and average 3MS and DSST was only significant in the nulliparity and grand multiparity groups, and the positive relationship between PA and change in 3MS and DSST was only significant in the grand multiparity group.ConclusionThe findings suggest the relationship between self-reported walking and cognitive performance was strongest in the groups at risk for cognitive decline and dementia, the nulliparous and grand multiparous groups.

Rationale: 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. Clinical trial registered with www.clinicaltrials.gov (NCT02231398).

Background 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

Maternal stress is a risk factor for adverse pregnancy outcomes (APOs). This study evaluates the associations of prenatal stress and APOs with maternal stress years after pregnancy. The 10-item Perceived Stress Scale (PSS) (0-40 range) was completed in the first and third trimesters, and 2-7 years after delivery among a subsample (n = 4161) of nulliparous women enrolled at eight US medical centers between 2010 and 2013 in a prospective, observational cohort study. Demographics, medical history, and presence of APOs (gestational diabetes (GDM), hypertensive disorders of pregnancy (HDP), preeclampsia (PE), and medically indicated or spontaneous preterm birth (miPTB, sPTB)) were obtained. The associations of prenatal PSS and the presence of APOs with PSS scores years after delivery were estimated using multivariable linear regression. Mean PSS scores were 12.5 (95% CI 12.3, 12.7) and 11.3 (95% CI 11.1, 11.5) in the first and third trimesters respectively and 14.9 (95% CI 14.7, 15.1) 2-7 years later, an average increase of 2.4 points (95% CI 2.2, 2.6) from the start of pregnancy. Regressing PSS scores after delivery on first-trimester PSS and PSS increase through pregnancy showed positive associations, with coefficients (95% CI) of 2.8 (2.7, 3.0) and 1.5 (1.3, 1.7) per 5-point change, respectively. Adding APO indicator variables separately showed higher PSS scores for women with HDP (0.7 [0.1, 1.3]), PE (1.3 [0.6, 2.1]), and miPTB (1.3 [0.2, 2.4]), but not those with GDM or sPTB. In this geographically and demographically diverse sample, prenatal stress and some APOs were positively associated with stress levels 2-7 years after pregnancy.ClinicalTrials.gov Registration number NCT02231398.

Background: Women with hypertensive disorders of pregnancy are at increased risk of cardiovascular disease in later life. We sought to determine the association between lactation and markers of maternal cardiovascular health among postpartum women with and without hypertensive disorders of pregnancy via measures of inflammation (high-sensitivity C-reactive protein [hsCRP]) and renal function (cystatin C). Materials and Methods: This prospective cohort study enrolled primarily overweight and obese women during early pregnancy. At a postpartum study visit occurring 6-24 months after delivery, we collected data on lactation duration and measured hsCRP and cystatin C. We assessed associations between lactation duration and levels of hsCRP and cystatin C among normotensive women and women with preeclampsia or gestational hypertension using analysis of variance and chi-squared tests. Linear regression models adjusted for age, race, education, prepregnancy body mass index, current smoking, and time since delivery. Results: Of 425 women, 37 (9%) had preeclampsia and 48 (11%) had gestational hypertension during enrollment pregnancy. The postpartum visit occurred at a mean of 8.6 ± 4.4 months after delivery. Women with a history of preeclampsia had significantly higher levels of cystatin C (mean 0.86 versus 0.78 mg/L; p = 0.03) compared with normotensive women, but nonsignificant elevation in hsCRP (mean 8.39 versus 6.04 mg/L; p = 0.08). Women with gestational hypertension had no differences in mean hsCRP or cystatin C compared with normotensive women. Among the 237 women with any lactation, 78 (18%) lactated for at least 6 months. Lactation duration both in the overall sample and among women with gestational hypertension or preeclampsia was not associated with levels of hsCRP or cystatin C. Conclusions: Preeclampsia history was associated with elevated postpartum levels of cystatin C; however, duration of lactation was not associated with postpartum hsCRP or cystatin C, regardless of history of gestational hypertension or preeclampsia. Further research is needed on mechanisms through which lactation may affect maternal risk of cardiovascular disease.

ObjectivesHypertension and obesity are common cardiometabolic risk factors in reproductive age women. The association of hypertensive disorders of pregnancy with later-life cardiovascular disease is well-established, however, it is unknown how obesity and hypertensive disorders of pregnancy converge to accelerate development of hypertension in the postpartum period. The aim of this study was to characterize rates of sustained hypertension at one year postpartum using the new American Heart Association/American College of Cardiology Guidelines among overweight and obese women with a normotensive pregnancy or hypertensive disorder of pregnancy.Study design315 early pregnant women were enrolled prospectively and followed up to 12 months after delivery (mean 7.0 ± 1.8 months). At a postpartum research visit, we measured blood pressure and collected blood samples to measure cystatin C and high sensitivity C-reactive protein.ResultsA total of 254 women had a normotensive pregnancy, 39 had gestational hypertension (12.4%) and 22 had preeclampsia (7.0%). 91 women had hypertension at the postpartum study visit (28.9%). After adjustment for maternal age, BMI, lactation and time postpartum, preeclampsia was associated with an aOR 2.35 (95%CI 1.63-3.41) of development of sustained hypertension and an aOR 3.23 (95%CI 1.56-6.68) of hypertension with abnormal biomarkers compared to women with normotensive pregnancies.ConclusionsWe demonstrate a high prevalence of hypertension and abnormal biomarkers associated with hypertensive disorders of pregnancy among overweight and obese women. Our findings support the need for structured follow up and risk reduction in overweight and obese women with hypertensive disorders of pregnancy as early as the first year postpartum.

BackgroundAlthough leisure-time physical activity (PA) contributes to overall health, including pregnancy health, patterns across pregnancy have not been related to birth outcomes. We hypothesized that women with sustained low leisure-time PA would have excess risk of adverse pregnancy outcomes, and that changing patterns across pregnancy (high to low and low to high) may also be related to risk of adverse pregnancy outcomes.MethodsNulliparous women (n = 10,038) were enrolled at 8 centers early in pregnancy (mean gestational age in weeks [SD] = 12.05 [1.51]. Frequency, duration, and intensity (metabolic equivalents) of up to three leisure activities reported in the first, second and third trimesters were analyzed. Growth mixture modeling was used to identify leisure-time PA patterns across pregnancy. Adverse pregnancy outcomes (preterm birth, [PTB, overall and spontaneous], hypertensive disorders of pregnancy [HDP], gestational diabetes [GDM] and small-for-gestational-age births [SGA]) were assessed via chart abstraction.ResultsFive patterns of leisure-time PA across pregnancy were identified: High (35%), low (18%), late decreasing (24%), early decreasing (10%), and early increasing (13%). Women with sustained low leisure-time PA were younger and more likely to be black or Hispanic, obese, or to have smoked prior to pregnancy. Women with low vs. high leisure-time PA patterns had higher rates of PTB (10.4 vs. 7.5), HDP (13.9 vs. 11.4), and GDM (5.7 vs. 3.1, all p

Women with gestational diabetes mellitus (GDM), hypertensive disorders of pregnancy (HDP), and preterm birth (PTB) have excess cardiovascular disease compared with those with uncomplicated births, perhaps related to prepregnancy inflammation, dysmetabolism, or endothelial dysfunction. We included 1238 women in the Coronary Artery Risk Development in Young Adults Study (1985-2011) with 2215 births classified according to outcomes (term, uncomplicated births were the referent). Using repeated measures analysis of variance, we estimated prepregnancy and postpregnancy biomarkers, as well as biomarker change according to pregnancy outcomes, adjusted for confounders. GDM and term HDP groups had higher prepregnancy high-sensitivity C-reactive protein (hsCRP) (+0.37 [95% CI, 0.08-0.65]; +0.29 [95% CI, 0.04-0.55] log mg/L), higher leptin (+0.29 [95% CI, 0.09-0.50]; +0.37 [95% CI, 0.17-0.56] log ng/ml), and lower adiponectin (−0.25 [95% CI, −0.36 to −0.13); −0.11 [95% CI, −0.22 to −0.01] log ng/ml) values than those with uncomplicated births, and these profiles persisted in magnitude postpregnancy. Controlling for body mass index attenuated most profiles, except that lower prepregnancy adiponectin remained associated with GDM. PTB without HDP or GDM was related to lower prepregnancy hsCRP and soluble intercellular adhesion molecule-1 (−0.31 [95% CI, −0.56 to −0.06] log mg/L; −0.05 [95% CI, −0.09 to −0.01] log ng/ml) and a larger leptin increase from before to after pregnancy (+0.20 [95% CI, 0.02-0.37] log ng/ml). Prepregnancy inflammation and metabolic dysfunction contributed to GDM and HDP, perhaps due to higher body mass index. PTB may be related to adverse metabolic changes postpregnancy, although the unexpected endothelial biomarker profile warrants further study. [ABSTRACT FROM AUTHOR]

BackgroundWomen with a history of hypertensive disorders of pregnancy are at an increased risk of hypertension and cardiovascular disease in later life. Lactation has been associated with a reduced risk of maternal hypertension, both in the postpartum period and later life. However, little is known about whether lactation is also cardioprotective in women with hypertensive disorders of pregnancy such as preeclampsia or gestational hypertension.ObjectiveThis study aimed to characterize the relationship between lactation and postpartum blood pressure among women with preeclampsia and gestational hypertension.Study designData were obtained from women who participated in the Prenatal Exposures and Preeclampsia Prevention study (n = 379; 66% African American; 85% overweight or obese). Women enrolled during pregnancy and attended a postpartum visit (on average, 9.1 months after delivery) during which data on lactation duration and blood pressure were collected. The significance of the associations between postpartum blood pressure and lactation among women who remained normotensive during pregnancy, developed gestational hypertension, or developed preeclampsia were assessed with an analysis of variance. Linear regression models were used to adjust for maternal age, race, education, prepregnancy weight, and time since delivery.ResultsGestational hypertension affected 42 subjects (11%) and preeclampsia affected 33 (9%). Lactation was reported by 217 (57%) with 78 (21%) reporting ≥ 6 months of lactation. Women who lactated were somewhat older, more educated, and had higher socioeconomic status. Among women who had gestational hypertension, lactation was associated with lower systolic blood pressure (P = .02) and diastolic blood pressure (P = .02). This association persisted after adjustment for age, race, education, prepregnancy weight, and time since delivery. However, for women who had preeclampsia and women who remained normotensive during pregnancy, lactation was not associated with postpartum blood pressure in either bivariate or multivariate analyses.ConclusionThis study found that lactation is associated with lower postpartum blood pressure among overweight women who develop gestational hypertension but not among women who develop preeclampsia. Future studies are needed to explore the association of lactation and blood pressure in later life for women with hypertensive disorders of pregnancy.

BACKGROUND Hypertensive disorders in pregnancy and other adverse pregnancy outcomes (APOs) increase the risk of developing chronic hypertension and cardiovascular disease. Perceptions of stress and neighborhood context also influence blood pressure (BP) fluctuations. We examined if APOs, higher perceived stress, and neighborhood deprivation were associated with hypertension phenotypes a decade after pregnancy in untreated individuals. METHODS Participants were 360 individuals who gave birth between 2008 and 2009 and participated in a research study 8–10 years following pregnancy. Standardized office and home BP readings were obtained, and we applied the AHA/ACC 2017 guidelines to identify sustained, white coat, and masked hypertension phenotypes. We measured personal stress with the perceived stress scale and neighborhood deprivation with the CDC Social Vulnerability Index. RESULTS Of the 38.3% (138/360) with any hypertension, 26.1% (36/138) reported a diagnosis of hypertension but were currently untreated. Sustained hypertension was the most common (17.8%), followed by masked and white coat hypertension, both 10.3%. Hypertensive disorders in pregnancy were associated with sustained (odds ratio [OR] 5.54 [95% confidence interval, CI 2.46, 12.46] and white coat phenotypes (OR 4.20 [1.66, 10.60], but not masked hypertension (OR 1.74 [0.62, 4.90]). Giving birth to a small for gestational age infant was also associated with sustained hypertension. In covariate adjusted models, perceived stress, but not neighborhood deprivation, was significantly associated with masked hypertension. CONCLUSIONS A decade after delivery, APOs were associated with sustained and white coat hypertension, but not masked hypertension. Exploration of the mechanisms underlying, and clinical implications of, these associations is warranted. [ABSTRACT FROM AUTHOR]

BACKGROUND: Hypertensive disorders of pregnancy are associated with cardiovascular disease; however, patterns of blood pressure (BP) recovery are understudied. We compared pregnancy and postpartum BP trajectories among individuals with hypertensive disorders of pregnancy who developed persistent hypertension at 1-year postpartum compared with individuals with normalization of BP. METHODS: We used data from a randomized clinical trial of individuals with overweight, obesity, and hypertensive disorders of pregnancy conducted in the first year after delivery. Pregnancy BPs were obtained during prenatal visits; postpartum BPs were prospectively obtained through home monitoring. Demographic characteristics and trajectories were compared by hypertensive status (systolic BP ≥130 mm Hg, diastolic BP ≥80 mm Hg, or use of antihypertensive medications) at 1 year. We used repeated BP measures to fit separate mixed-effects linear regression models for pregnancy and postpartum using restricted cubic splines. RESULTS: We included 129 individuals; 75 (58%) individuals progressed to hypertension by 1-year postpartum. Individuals with hypertension were older, delivered at earlier gestational ages, and had higher body mass index at 1-year postpartum compared with those with normalization. Individuals with hypertension had similar BP trajectories during pregnancy to those with BP normalization but a significantly different BP trajectory (P<0.01 for systolic and diastolic BPs) in the first year postpartum. These differences persisted in multivariable models after adjustment for early pregnancy body mass index, age, and severity of hypertensive disorder of pregnancy (P<0.01 for systolic and diastolic BPs). CONCLUSIONS: BP trajectories in the first year postpartum, but not during pregnancy, may provide important information for risk stratification after a hypertensive disorder of pregnancy. [ABSTRACT FROM AUTHOR]

This article discusses the importance of considering maternal health before, during, and after pregnancy in order to improve pregnancy outcomes. It highlights the need for a longitudinal approach to perinatal epidemiology, as well as the significance of mental health and chronic conditions in maternal health. The article presents two papers that provide evidence for the impact of pre-pregnancy health on pregnancy outcomes, emphasizing the importance of improving adolescent health for future pregnancies. The article also addresses the urgent need to address the increasing rates of cardiovascular disease and severe maternal morbidity and mortality in the United States. Overall, the article calls for a life course approach to understanding and improving maternal health. [Extracted from the article]

Women with adverse pregnancy outcomes later experience excess hypertension and cardiovascular disease, but how the events are linked is unknown. Examination of the placenta may provide clues to vascular impairments after delivery. Maternal vascular malperfusion lesions (MVMs) were abstracted from clinical reports, validated and characterized using clinical guidelines and severity score. A total of 492 women (170 with MVMs and 322 without MVMs) participated in a study visit 8 to 10 years after delivery to assess blood pressure, cardiometabolic factors, and sublingual microvascular features using sidestream dark field imaging. Covariates included age, race, adverse pregnancy outcomes (preeclampsia, small for gestational age, and preterm birth), and health behaviors. Women with versus without MVM had a distinct sublingual microvascular profile comprised of (1) lower microvascular density (-410 μm/mm2, P=0.015), (2) higher red blood cell filling as a marker of perfusion (2%, P=0.004), and (3) smaller perfused boundary region (-0.07 µm, P=0.025) as a measure of glycocalyx integrity, adjusted for covariates including adverse pregnancy outcomes. Women with MVM also had higher adjusted diastolic blood pressure (+2.6 mm Hg, P=0.021), total and LDL (low-density lipoprotein)-cholesterol (+11.2 mg/dL, P=0.016; +8.7 mg/dL, P=0.031). MVM associations with subsequent cardiovascular measures did not vary by type of adverse pregnancy outcome, except among women with preterm births where blood pressure was higher only among those with MVM. Results were similar when evaluated as MVM severity. A decade after delivery, women with placental vascular lesions had an adverse cardiovascular profile comprised of microvascular rarefaction, higher blood pressure and more atherogenic lipids. Placental histopathology may reveal a woman's early trajectory toward subsequent vascular disease. [ABSTRACT FROM AUTHOR]

Background: Evidence of placental maternal vascular malperfusion is associated with significant perinatal outcomes such as preeclampsia, intrauterine growth restriction and preterm birth. Elevations in pre-pregnancy blood pressure increase the risk for poor perinatal outcomes; however, the evidence linking pre-pregnancy blood pressure and placental malperfusion is sparse.Materials and Methods: We conducted a retrospective case-control study of women with singleton gestations with placental evaluations who delivered at Magee-Womens Hospital in 2012. Charts from 100 deliveries with placental malperfusion lesions (vasculopathy, advanced villous maturation, infarct, or fibrin deposition) and 102 deliveries without placental malperfusion were randomly selected for screening. Blood pressure, demographic, and clinical data were abstracted from pre-pregnancy electronic medical records and compared between women with and without subsequent placental malperfusion lesions.Results: Overall, 48% of women had pre-pregnancy records, and these were similarly available for women with and without placental malperfusion. Women with placental malperfusion demonstrated a reduction in their pre- to early pregnancy decrease in diastolic blood pressure (DBP). Adjusted for race, pre-pregnancy BMI, age, pre-conception interval, and gestational age at the first prenatal visit, the difference in pre- to early pregnancy DBP was significantly less in women with placental malperfusion compared to those without this pathologic finding (- 1.35 mmHg drop vs - 5.6mmg, p < 0.05).Conclusion: A blunted early gestation drop in DBP may be a risk factor for placental malperfusion, perhaps related to early pregnancy vascular maladaptation. The ability of the electronic medical record to provide pre-pregnancy data serves as an underutilized approach to study pre-pregnancy health. [ABSTRACT FROM AUTHOR]

Objective  We assessed if the initial response to medical nutritional therapy (MNT) can help predict the need for pharmacological therapy in women with gestational diabetes mellitus (GDM). Study Design  We identified 1,174 women with GDM who underwent standardized dietary counseling and reported glucose values from the first week of MNT. We compared women who required pharmacological therapy with those who did not use bivariate statistics, and used multivariable logistic regression modeling to assess for factors predicting the need for pharmacological therapy. Results  We identified 819 women (69.8%) who needed pharmacological therapy. They had higher prepregnancy body mass index, higher rates of GDM diagnosis before 24 weeks, and higher oral glucose tolerance test values. After adjustment for covariates, age (odds ratio [OR]: 1.04; 95% confidence interval [CI]: 1.01–1.08), obesity (OR: 2.49; 95% CI: 1.70–3.66), and ≥33% of abnormal glucose values from the first week of MNT (OR: 13.84; 95% CI: 9.4–20.20) were associated with the need for pharmacological therapy. Area under the curve of the regression model was 0.83, with a sensitivity of 72.2%, a specificity of 86.8%, and a positive predictive value of 92.5%. Conclusion  Glucose values from the first week of MNT were the strongest predictor of needing pharmacological therapy. Further studies are needed to define metabolic predictors of response to MNT in women with GDM. [ABSTRACT FROM AUTHOR]

Background: Women with preterm birth (PTB) have excess risk of cardiovascular disease (CVD) and metabolic dysregulation after delivery, but vascular mechanisms are poorly understood. We considered that women with PTB may have evidence of subclinical atherosclerosis after delivery, perhaps related to cardiometabolic risk factors. Materials and Methods: The Pregnancy Outcomes and Community Health Moms (POUCHmoms) study followed women from pregnancy through 7 to 15 years after delivery (n = 678). Women underwent B-mode ultrasound to measure the average intima-media thickness (IMT) across the common carotid, bulb, and internal carotid artery segments at follow-up (n = 605). Linear regression estimated the overall and segment-specific difference in IMT between women with preterm and term births. Results: Women were, on average, 38 years old (SD 5.7) at the follow-up visit. Those with a prior preterm versus term birth had thicker mean IMT (average of eight segments, 0.592 mm vs. 0.575, p = 0.04). Differences persisted after accounting for age, race, smoking, and body mass index (difference = +0.018 mm, p = 0.019) and were attenuated after adjustment for blood pressure, medication use, and total cholesterol (difference = +0.014, p = 0.052). Thicker mean bulb IMT in women with PTB was robust to cardiovascular risk factor adjustments (fully adjusted difference = +0.033, p = 0.029). Excluding cases of prepregnancy hypertension or preeclampsia did not change results. Conclusions: Mechanisms leading to subclinical atherosclerosis may link PTB with future CVD. PTB differences in maternal vessel remodeling in the carotid bulb, an arterial segment more prone to early development of atherosclerosis, were independent of traditional risk factors suggesting that novel processes may be involved. [ABSTRACT FROM AUTHOR]

Background: Abdominal obesity is an important indicator of cardiometabolic dysfunction in later life. Prior studies have observed an inverse association between breastfeeding and maternal waist circumference (WC) in the years after pregnancy, but this may be due to bias resulting from systematic differences in women who do and do not breastfeed. Materials and Methods: A total of 678 women enrolled in the Pregnancy Outcomes and Community Health (POUCH) cohort also participated in the POUCHmoms Study 7–15 years after delivery. Multivariable linear regression models and propensity scores were used to assess the relationship between WC measured at follow-up and self-reported history of breastfeeding duration of >6 months versus ≤6 months. Results: After a mean follow-up period of 11.0 (standard deviation = 1.4) years, breastfeeding was significantly associated with smaller WC. A threshold effect was detected for women who reported breastfeeding >6 months; their adjusted mean WC was 3.5 cm (95% confidence interval [CI]: −5.7 to −1.2) smaller compared with women who breastfed ≤6 months. The use of two propensity score approaches, weighted and matched, produced similar results; adjusted mean WC difference was −3.6 cm (95% CI: −5.6 to −1.6) and −3.1 cm (95% CI: −5.5 to −0.7), respectively. Conclusions: This study extends conventional observational study methods to incorporate propensity score approaches that make it possible to separate the study design from the study analysis to account for systematic differences in women who did and did not breastfeed. After reducing potential bias, breastfeeding for greater than 6 months was independently associated with smaller WC in the decade after delivery. [ABSTRACT FROM AUTHOR]

Objective: To assess brachial artery distensibility and associated factors in healthy primigravidas.Methods: We assessed brachial artery distensibility using the DynaPulse 5,000A in 37 women each trimester, and 6-8 weeks and 1-5 years postpartum. Associations with physical and cardiometabolic measures were considered.Results: Mean (SE) brachial artery distensibility (%Δ/mmHg) decreased (stiffened) from 7.50 (0.20) 12-14 weeks to 6.93 (0.22) 36-38 weeks (p < .01) and returned to baseline 7.52 (0.44) at 2.7 years postpartum. Weight gain and greater cardiac output were significantly related to greater stiffness.Conclusion: Increased weight and cardiac output of pregnancy were associated with brachial artery stiffening. [ABSTRACT FROM AUTHOR]

Recently, the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines revised the recommendations for diagnosis of chronic hypertension. The new classification system includes a diagnosis of stage 1 hypertension in adults with blood pressures 130 to 139/80 to 89 mm Hg. We sought to compare outcomes among women at high risk for preeclampsia with stage 1 hypertension and assessed whether women with stage 1 hypertension had benefit from aspirin treatment compared with high-risk normotensive women. We performed a secondary analysis of the high-risk aspirin trial and included women with prior preeclampsia or diabetes mellitus. Among these women, 827 (81%) were classified as normotensive, whereas 193 (19%) were classified as stage 1 hypertensive. Among women receiving placebo, preeclampsia occurred significantly more often in women with stage 1 hypertension compared with normotensive high-risk women after adjustment for maternal age and body mass index (39.1% versus 15.1%; risk ratio, 2.49; 95% confidence interval, 1.74-3.55). Further, women with stage 1 hypertension had a significant risk reduction related to aspirin prophylaxis (risk ratio, 0.61; 95% confidence interval, 0.39-0.94) that was not seen in normotensive high-risk women (risk ratio, 0.97; 95% confidence interval, 0.70-1.34). Application of the American College of Cardiology/American Heart Association guidelines in a high-risk population demonstrates that in the setting of other risk factors, the presence of stage 1 hypertension is associated with a significantly increased risk of preeclampsia when compared with high-risk normotensive women. These findings emphasize the importance of recognition of stage 1 hypertension as an additive risk factor in women at high risk for preeclampsia and the benefit of aspirin. [ABSTRACT FROM AUTHOR]

Women who delivered preterm infants have excess cardiovascular disease, but vascular pathways linking these conditions are not understood. We considered that higher blood pressure over 25 years among women with preterm delivery may be associated with coronary artery calcification (CAC). The CARDIA study (Coronary Artery Risk Development in Young Adults) enrolled 1049 black and white women with births between 1985 and 2010 (n=272 ever preterm [<37 weeks]; n=777 all term births [≥37 weeks]). Latent mixture modeling identified blood pressure trajectories across 20 years, and these were related to CAC at years 20 and 25. Three systolic blood pressure (SBP) patterns were identified: low stable (n=563; 53%), moderate (n=416; 40%), and moderate increasing (n=70; 7%). Women with moderate-increasing SBP were more likely to have delivered preterm compared with those in the low-stable group (40% versus 21%; P<0.0001), and they were more likely to have CAC (38.5% versus 12.2%). The SBP and CAC association varied by preterm birth (P interaction=0.04). Women with preterm delivery and a moderate-increasing SBP had a 2.17-fold higher hazards of CAC (95% confidence interval, 1.14-4.12) compared with women with term births and a lower SBP pattern, adjusted for cardiovascular disease risk factors and other pregnancy features. There was no excess CAC in women with moderate-increasing SBP and term births (adjusted hazard ratio, 1.02; 95% confidence interval, 0.49-2.14). Associations were stronger in women with hypertensive disorders of pregnancy but also detected in those with normotensive preterm deliveries. Women who deliver preterm infants are more likely to follow a high-risk blood pressure pattern throughout the childbearing years that is associated with CAC at midlife. [ABSTRACT FROM AUTHOR]

Background The concentration and size of lipoprotein particles are associated with race, inflammation, and disease. When triglycerides are high, as in pregnancy, lipoprotein particle size may have physiologic importance beyond conventional lipid measurements. We considered that lipoprotein particles may be related to preterm birth (PTB) and explored race differences. Materials and Methods Samples were collected at 9 weeks' gestation (22 PTB [< 37 weeks]; 42 term births [≥ 37 weeks]). Lipids were assayed using standard techniques. Concentrations of high-density lipoprotein, low-density lipoprotein, and very low- density lipoprotein particles (HDL-P, LDL-P, and VLDL-P, respectively) and markers of systemic inflammation were quantified using nuclear magnetic resonance spectroscopy and related to PTB. Results Women with PTB had lower VLDL-P (- 10.66 nmol/L, p = 0.03) and higher systemic inflammation (+ 19.2 µmol/L, p = 0.02) compared with women with term births, independent of race, pre-pregnancy body mass index, and smoking. Black versus white women had lower VLDL-P and higher HDL cholesterol (both p < 0.05). Race-specific results indicated that large HDL-P and inflammation (glycoprotein B) were higher with PTB versus term birth among black women only. Conclusion Women with PTB had lower VLDL-P early in pregnancy, which may represent impaired lipid response. Black-white differences in the lipoprotein profile are similar to nonpregnant adults, but race-specific lipoprotein and inflammation associations with PTB warrant further study. [ABSTRACT FROM AUTHOR]

Objective There is limited data regarding the use of oral hypoglycemic agents (OHAs) in pregnant women with type 2 diabetes mellitus (T2DM). Study Design This was a retrospective cohort study of women with T2DM who were treated with OHA or insulin from the first trimester onward. Bivariate and multivariate logistic regression analyses were used to compare pregnancy outcomes in women treated with OHA to those treated with insulin. Results One-third (67/198) of women were treated with OHA. Women treated with OHA had a shorter disease duration (4.4 vs. 6.8 years; p = 0.001), were more likely to have a normal prepregnancy body mass index, and had less gestational weight gain (GWG; 22.4 vs. 30.4 lbs; p = 0.005). A lower GWG was noted in obese women treated with OHA (19.9 ± 18.6 vs. 28.3 ± 17.7 pounds; p = 0.008). First-trimester hemoglobin A1c values were lower with OHAs, but second- and third-trimester values were similar. Among women who started pregnancy using OHA, 37/67 (55.2%) remained on OHA at delivery. Pregnancy outcomes did not differ between women who received OHA and those treated with insulin. Conclusion OHA treatment is more likely in women with T2DM who begin pregnancy with less severe disease, and use of OHA may be associated with decreased GWG. [ABSTRACT FROM AUTHOR]

Introduction: Maternal vascular malperfusion (MVM) lesions represent hypoxic-ischemic damage to the placenta, and they are associated with adverse pregnancy outcomes. Women with gestational diabetes (GDM) are at increased risk for pregnancy complications, so we set out to characterize the prevalence and clinical correlates of MVM lesions in this cohort.Methods: This was a retrospective cohort study of 1187/1374 (86.4%) women with GDM delivered between 2009 and 2012 who had placental pathology available. Placental lesions of all types were tabulated and grouped into constructs of related entities. MVM lesions specifically included villous infarcts, decidual vasculopathy, increased syncytial knots, perivillous fibrin, and fibrin deposition. We compared maternal characteristics between women with and without MVM lesions, and we also assessed the impact of these lesions on birth weight, preterm birth, and pre-eclampsia using multivariable logistic regression analysis.Results: MVM lesions were the most common placental lesion type in women with GDM (n = 362, 30.5%). Excess gestational weight gain was independently associated with MVM lesions (aOR 1.42, 95% CI 1.06-1.91, p = 0.02) after adjusting for maternal characteristics. MVM lesions were associated with lower birth weight (-90.3 g, 95% CI -148.0 to -32.7, p = 0.002), as well as a 2-fold increased risk for delivery of a small for gestational age infant (10.8 vs 5.9%, p = 0.01) in overweight and obese women. MVM lesions were also associated with increased risk for preterm birth <34 weeks (adjusted OR 2.36, 95% CI 1.31-4.23, p = 0.004) and hypertensive disorders of pregnancy (HDP; adjusted OR 1.58, 95% CI 1.13-2.22, p = 0.02).Discussion: Placental maternal vascular malperfusion lesions may be one pathway linking excess gestational weight gain to adverse pregnancy outcomes in women with GDM, and future studies are needed to identify metabolic factors that may explain this association. [ABSTRACT FROM AUTHOR]

Prominent syncytial knots (SK) in placentas signal advanced gestation or placental malperfusion, reflecting exposures that adversely affect placental development and pregnancy outcomes. Molecular-level interrogations of syncytiotrophoblast have altered perceptions of and raised questions about the function and disposition of SK. Quantifying SK and achieving acceptable levels of interrater reliability have been challenging. Our objective was to develop a simple, reproducible protocol for counting SK and demonstrate interrater reliability overall and within 3 parameters, ie, preterm vs term delivery, presence vs absence of diffuse prominent SK (DPSK), and SK relationship with a lesion, all of which could influence measurement reproducibility and interpretation. Criteria for defining SK and a grid system drawn on glass slides were developed for counting percentage of villi with SK. One disc section each from 151 placentas, sampled from 8 groups defined by the 3 parameters, was assessed by 2 pretrained pathologists. The resulting weighted kappa statistic for overall interrater agreement was 0.60 (very good) and Spearman correlation coefficient for ranking quartiles was >0.70. Agreement was best for preterm placentas, kappa = 0.61, and those only showing DPSK associated with a lesion, kappa = 0.67. Agreement was low in the absence of DPSK, kappa = 0.22, or when DPSK was present in a placenta not associated with a lesion, kappa = 0.32. The proposed method offers a potentially reliable approach for categorizing SK counts as normal vs abnormal or providing continuous measure counts. More extensive pretraining, focused on placentas with few SK and those without an associated lesion, is recommended to improve agreement. [ABSTRACT FROM AUTHOR]

Objective: To investigate whether women who deliver preterm have excess risk for metabolic dysregulation independent of prepregnancy factors.Methods: We conducted a multicenter, longitudinal, observational study of 1,205 women (50% black) in the Coronary Artery Risk Development in Young Adults study with at least one birth between baseline (1985-1986) and year 25 and no metabolic syndrome or diabetes before pregnancy. Cardiometabolic factors were measured prepregnancy and at up to five subsequent examinations. We estimated the relative hazards of incident metabolic syndrome in women with one or more preterm births (less than 37 weeks of gestation, n=295) compared with only term births (37 weeks of gestation or greater, n=910). Self-reported gestational diabetes mellitus, hypertension during pregnancy, and time-dependent weight gain were also considered as covariates.Results: Of 315 cases of metabolic syndrome in 17,717 person-years of follow-up, the incidence rate was higher among women with preterm compared with term births (22.0 compared with 16.4 per 1,000 person-years; relative hazard 2.91 [95% confidence interval (CI) 2.75-3.09]). After adjustment for prepregnancy cardiometabolic factors and covariates, the relative hazard (95% CI) for metabolic syndrome was 1.52 (1.22-1.88) for women with preterm compared with term births. Gestational diabetes mellitus, hypertension during pregnancy, and weight gain only modestly attenuated this association. Elevated blood pressure (36.3% compared with 26.7%, P=.002) and central adiposity (51.5% compared with 44.0%, P=.02) were the individual metabolic syndrome components that were different in women with preterm compared with term births.Conclusion: Women with a history of preterm birth have increased risk of incident metabolic syndrome compared with those with term births, independent of the prepregnancy metabolic status and pregnancy complications. [ABSTRACT FROM AUTHOR]

The mean infant birth weight in the United States increased for decades, but it might now be decreasing. Given race disparities in fetal growth, we explored race-specific trends in birth weight at Magee-Womens Hospital, Pittsburgh, Pennsylvania, from 1997 to 2011. Among singleton births delivered at 37-41 weeks (n = 70,607), we evaluated the proportions who were small for gestational age and large for gestational age and changes in mean birth weights over time. Results were stratified by maternal race/ethnicity. Since 1997, the number of infants born small for their gestational ages increased (8.7%-9.9%), whereas the number born large for their gestational ages decreased (8.9%-7.7%). After adjustment for gestational week at birth, maternal characteristics, and pregnancy conditions, birth weight decreased by 2.20 g per year (P< 0.0001). Decreases were greater for spontaneous births. Reductions were significantly greater in infants born to African-American women than in those born to white women (-3.78 vs. -1.88 per year; Pfor interaction = 0.010). Quantile regression models indicated that birth weight decreased across the entire distribution, but reductions among infants born to African-American women were limited to those in the upper quartile after accounting for maternal factors. Limiting the analysis to low-risk women eliminated birth weight reductions. Birth weight has decreased in recent years, and reductions were greater in infants born to African-American women. These trends might be explained by accumulation of risk factors such as hypertension and prepregnancy obesity that disproportionately affect African-American women. Our results raise the possibility of worsening race disparities in fetal growth. [ABSTRACT FROM AUTHOR]

Corresponding Author [ABSTRACT FROM AUTHOR]

We considered that accumulation of nonesterified (free) fatty acids (NEFAs) in the first trimester of pregnancy would mark women at excess risk of spontaneous preterm birth (sPTB) and examined the interplay between NEFAs, lipids, and other markers to explore pathways to sPTB. In a case-control study nested in the Pregnancy Exposures and Preeclampsia Prevention Study (Pittsburgh, Pennsylvania, 1997–2001), we assayed NEFA levels in nonfasting serum collected at a mean gestational week of 9.4 (range, 4–20 weeks) in 115 women with sPTB (<37 weeks) and 222 women with births occurring at ≥37 weeks. C-reactive protein, total cholesterol, low-density lipoprotein and high-density lipoprotein (HDL) cholesterol, triglycerides, and uric acid were also measured. Polytomous logistic regression models were used to evaluate tertiles of NEFA levels and sPTB at <34 weeks and 34–36 weeks; factor analysis was used to characterize patterns of biomarkers. Women with NEFA levels in the highest tertile versus the lowest were 2.02 (95% confidence interval: 1.13, 3.48) times more likely to have sPTB, after adjustment for covariates. Risk of sPTB before 34 weeks was particularly high among women with high NEFA levels (odds ratio = 3.73, 95% confidence interval: 1.33, 10.44). Six biomarker patterns were identified, and 2 were associated with sPTB: 1) increasing NEFA and HDL cholesterol levels and 2) family history of gestational hypertension. NEFA levels early in pregnancy were independently associated with sPTB, particularly before 34 weeks. We also detected a novel risk pattern suggesting that NEFAs together with HDL cholesterol may be related to sPTB. [ABSTRACT FROM PUBLISHER]