OBJECTIVE:To evaluate associations between maternal serum 25-hyroxyvitamin D [25(OH)D] measured at both preconception and 8 weeks gestation and the risk of preeclampsia. STUDY DESIGN:A secondary analysis of the EAGeR Trial (2006-2012), which was a multisite, prospective, double-blind, block-randomized, placebo-controlled clinical trial of women with regular menstrual cycles and 1-2 prior pregnancy losses. Analyses were restricted to participants who conceived and had a live birth (N = 552) and serum 25(OH)D measured at preconception and 8 weeks' gestation. MAIN OUTCOME MEASURES:Log-binomial regression with robust standard errors estimated risk ratios (RR) and 95% confidence intervals (CI) for preeclampsia across 25(OH)D categories. Inverse probability weighting accounted for selection bias from restricting analyses to live births. RESULTS:Overall, 55 (10.0%) women developed preeclampsia. In adjusted models excluding body mass index (BMI), deficient preconception 25(OH)D levels (≤20 ng/ml) were associated with an increased preeclampsia risk (RR: 2.32, 95% CI: 1.09, 4.95) compared with sufficient levels (≥30 ng/ml). These associations were attenuated after adjusting for BMI and other covariates (RR: 1.45, 95% CI: 0.64, 3.29). No significant associations were observed for insufficient 25(OH)D or for concentrations measured at 8 weeks' gestation. CONCLUSION:Deficient preconception 25(OH)D levels may be associated with an increased risk of preeclampsia, although this relationship appears partly mediated by BMI. These findings highlight the preconception period as a potentially critical window for optimizing maternal vitamin D status and reducing future preeclampsia risk. Addressing maternal nutritional status before conception may offer a novel prevention strategy warranting confirmation in larger and more diverse populations.

BACKGROUND:The American Heart Association introduced Life's Essential 8 (LE8) to promote cardiovascular health and longevity. However, its impact on brain ageing and interactions with genetic risk factors of dementia, such as APOE4, remains unclear. This study investigates the relationship between LE8 and white matter brain ageing and evaluates the moderating effects of the APOE4 allele. METHODS:This cross-sectional study utilized data from the UK Biobank, including genetic, neuroimaging, and health-related data from touchscreen questionnaires, physical examinations, and biological samples. Participants were non-pregnant whites with LE8 variables, diffusion tensor imaging (DTI) data, and APOE4 genetic information available, excluding those with extreme white matter hyperintensities. Regional fractional anisotropy measures from DTI data were used to predict white matter brain age via random forest regression. The white matter brain age gap (BAG) was calculated by subtracting chronological age from predicted brain age. FINDINGS:The analysis included 18,817 participants (9430 women and 9387 men; mean age 55.45 years [SD: 7.46]). Higher LE8 scores were associated with a lower white matter BAG, indicating delayed brain ageing. The effect was more pronounced in non-APOE4 carriers (124 days younger per 10-point increase, 95% CI: 102-146 days; p < 0.001) compared to APOE4 carriers (84 days younger per 10-point increase, 95% CI: 47-120 days; p < 0.001). Potential interaction between APOE4 and LE8 on brain ageing was observed for some age and sex groups but with only borderline significance, further investigation in larger and more targeted studies is needed to validate the finding. INTERPRETATION:Adherence to LE8 is associated with delayed brain ageing, with genetic factors such as APOE4 potentially moderating this effect in specific age and sex groups. The overall benefit from a healthier lifestyle in individuals' brain ageing across genetic, sex, and age groups underscore the importance and broad applicability of behavioural lifestyle interventions in promoting brain health. FUNDING:US National Institute of Health, University of Maryland, Montgomery County of Maryland.

White matter (WM) brain age, a neuroimaging-derived biomarker indicating WM microstructural changes, helps predict dementia and neurodegenerative disorder risks. The cumulative effect of chronic stress on WM brain aging remains unknown. In this study, we assessed cumulative stress using a multi-system composite allostatic load (AL) index based on inflammatory, anthropometric, respiratory, lipidemia, and glucose metabolism measures, and investigated its association with WM brain age gap (BAG), computed from diffusion tensor imaging data using a machine learning model, among 22 951 European ancestries aged 40 to 69 (51.40% women) from UK Biobank. Linear regression, Mendelian randomization, along with inverse probability weighting and doubly robust methods, were used to evaluate the impact of AL on WM BAG adjusting for age, sex, socioeconomic, and lifestyle behaviors. We found increasing one AL score unit significantly increased WM BAG by 0.29 years in association analysis and by 0.33 years in Mendelian analysis. The age- and sex-stratified analysis showed consistent results among participants 45-54 and 55-64 years old, with no significant sex difference. This study demonstrated that higher chronic stress was significantly associated with accelerated brain aging, highlighting the importance of stress management in reducing dementia and neurodegenerative disease risks.

Introduction: Despite known benefits of breastfeeding, including prevention against infections for infants, in the presence of numerous barriers, less than half of infants in high-income countries breastfeed for 6 months. One potential barrier to breastfeeding is birth by cesarean section (C-Section), which can invoke long-term difficulties. However, our structured literature review found that existing empirical research does not fully elucidate this relationship due to differences in operationalization of C-section and breastfeeding, omission of important confounders, and failure to exclude those who did not initiate breastfeeding (or use time-to-event analyses). In this article, we attempt to overcome these limitations.Methods: We analyzed data from 14,414 mother-infant dyads enrolled in the United Kingdom-based prospective Millennium Cohort Study, beginning in 2001. Using multivariable logistic regression, we examined the association between mode of birth (vaginal, emergency C-section, and elective C-section) and likelihood of breastfeeding initiation. We then applied adjusted Accelerated Failure Time survival models to examine the associations between mode of birth and duration of any and exclusive breastfeeding.Results: Those with planned (but not emergency) C-section were less likely to initiate breastfeeding (odds ratio: 0.84, 95% confidence interval [CI]: 0.71-0.99) relative to vaginal births. However, those with either planned or unplanned C-section discontinued both any and exclusive breastfeeding sooner than vaginal births. This effect was more pronounced for those with planned C-section (time ratio [TR]: 0.75, 95% CI: 0.64-0.89) than unplanned C-section (TR: 0.85, 95% CI: 0.74, 0.97) compared with vaginal births.Conclusions: Through application of rigorous methods, this study provides compelling evidence that breastfeeding duration may be impeded by C-section birth. The findings suggest that additional support for mothers who intend to breastfeed and have a C-section birth may be warranted.

Objective:To answer 3 questions: (1) Are infants breastfed by smokers at risk of rapid weight and length gain? (2) Is rapid growth during infancy partially attributable to ingestion of smokers' breastmilk? (3) If so, what are the implications for breastfeeding by smokers? Study design:Using data from the Norwegian Mother, Father and Child Cohort Study and Medical Birth Registry of Norway (n = 54 522), we examined changes in weight, length, weight-for-length z-score (WFLZ) during infancy in the context of maternal smoking (0, 1-10, or >10 cigarettes/day) and feeding method during the first 6 months (breastfed, formula fed, mixed fed). We fit generalized linear models, adding a smoking by feeding method interaction term to evaluate the effect of ingesting smokers' breastmilk. Results:Breastfed infants of both light and heavy smokers experienced WFLZ gains of 0.05 (95% CI, 0.01-0.09) and 0.13 (95% CI, 0.07-0.18), respectively. Among mixed-fed infants, only heavy maternal smoking predicted WFLZ gain (0.10; 95% CI, 0.05-0.16). Among exclusively formula-fed infants, maternal smoking did not predict rapid growth. Interaction models suggest that infants ever breastfed (ie, breastfed and mixed-fed groups combined) by heavy smokers gained weight (100 g; 95% CI, 30-231) and length (2.8 mm; 95% CI, 0.1-5.6), attributable to ingesting smoker's breastmilk. Conclusions:Infants breastfed by smokers experience rapid growth; some of these gains are attributable to ingesting smokers' breastmilk. Among infants breasted by light smokers, these gains are within the range of normative growth patterns for healthy, breastfed infants.

Background: Sibling studies of maternal smoking during pregnancy and subsequent risk of depression have produced mixed results. A recent study identified not considering the amount of maternal smoking and age of onset as potentially masking a true association. We examine these issues and also the amount of maternal smoking during pregnancy as a determinant of the severity of depressive symptoms. Methods: We analyzed data from the community-based National Longitudinal Survey of Youth (US, 1994–2016). Mothers reported smoking during pregnancy (none, <1 pack/day, ≥1 pack/day). We assessed offspring’s lifetime depression (i.e., ≥8 symptoms) and symptom counts with the Centers for Epidemiologic Studies Depression scale. We estimated the risk of these two outcomes in the full sample (n = 7172) and among siblings (n = 6145) using generalized linear mixed-effects models with random intercepts by family and family-averaged means for sibling analyses. Results: Among siblings, we observed dose-dependent elevations for both risk of depression (smoking during pregnancy <1 pack/day adjusted risk ratio [aRR] = 1.18; 95% confidence interval [CI] = 1.07, 1.30; smoking ≥1 aRR = 1.36; 95% CI = 1.19, 1.56) and severity of depressive symptoms (smoking <1 pack/day aRR = 1.12; 95% CI = 1.08, 1.16); smoking ≥1 pack/day aRR = 1.25; 95% CI = 1.18, 1.31). Among both samples, the P for trend was <0.01. In analysis limited to offspring diagnosed before age 18, results for severity were attenuated. Conclusions: This evidence supports the existence of an independent association between maternal smoking during pregnancy and both the risk of depression and the severity of depressive symptoms. The results highlight the utility of considering the amount of smoking, severity of symptoms, and age of onset.

Abstract Background Evidence of a biologically plausible association between maternal smoking during pregnancy (MSP) and the risk of depression is discounted by null findings from two sibling studies. However, valid causal inference from sibling studies is subject to challenges inherent to human studies of MSP and biases particular to this design. We addressed these challenges in the first sibling study of MSP and depression conducted among adults past the peak age for the onset of depression, utilizing a prospectively collected and biologically validated measure of MSP and accounting for non-shared as well as mediating factors. Methods We fit GEE binomial regression models to correct for dependence in the risk of depression across pregnancies of the same mother. We also fit marginal structural models (MSM) to estimate the controlled direct effect of MSP on depression that is not mediated by the offspring's smoking status. Both models allow the estimation of within- and between-sibling risk ratios. Results The adjusted within-sibling risk ratios (RRW) from both models (GEE: RRW = 1.97, CI 1.16–3.32; MSM: RRW = 2.08, CI 1.04–4.17) evinced an independent association between MSP and risk of depression. The overall effects from a standard model evinced lower associations (GEE: RRT = 1.12, CI 0.98–1.28; MSM: RRT = 1.18, CI 1.01–1.37). Conclusions Based on within-sibling information free of unmeasured shared confounders and accounting for a range of unshared factors, we found an effect of MSP on the offspring's risk of depression. Our findings, should they be replicated in future studies, highlight the importance of considering challenges inherent to human studies of MSP and affective disorders.

BACKGROUND:Despite the tenets of rights-based, person-centered maternity care, racialized groups, low-income people, and people who receive Medicaid insurance in the United States experience mistreatment, discrimination, and disrespectful care more often than people with higher income or who identify as white. This study aimed to explore the relationship between the presence of a doula (a person who provides continuous support during childbirth) and respectful care during birth, especially for groups made vulnerable by systemic inequality.METHODS:We used data from 1977 women interviewed in the Listening to Mothers in California survey (2018). Respondents who reported high levels of decision making, support, and communication during childbirth were classified as having "high" respectful care. To examine associations between respectful care and self-reported doula support, we conducted multivariable logistic regressions. Interactions by race/ethnicity and private or Medi-Cal (Medicaid) insurance status were assessed.RESULTS:Overall, we found higher odds of respectful care among women supported by a doula than those without such support (odds ratios [OR]: 1.4, 95% CI: 1.0-1.8). By race/ethnicity, the association was largest for non-Hispanic Black women (2.7 [1.1-6.7]) and Asian/Pacific Islander women (2.3 [0.9-5.6]). Doula support predicts higher odds of respectful care among women with Medi-Cal (1.8 [1.3-2.5]), but not private insurance.CONCLUSIONS:Doula support was associated with high respectful care, particularly for low-income and certain racial/ethnic groups in California. Policies supporting the expansion of doulas for low-income and marginalized groups are consistent with the right to respectful care and may address disparities in maternal experiences.

Background: Recent studies have suggested a link between reproductive health and later-life chronic conditions, yet the mechanism remains unclear. One proposed mechanism is through chronic inflammation. The objective of this study was to examine the association between endometriosis and uterine fibroids and biomarkers of inflammation and cellular aging. Materials and Methods: We used data from the National Health and Nutrition Examination Survey (N = 2342; 1999-2002). Adjusted logistic and linear regression were used to examine the association between these two reproductive conditions and elevated C-reactive protein (CRP; >3.0 mg/L) and leukocyte telomere length (T/S ratio), respectively. Given that a greater length of time spent with a condition may represent persistence of an inflammatory process, we further examined the association between time since disease diagnosis on telomere length among the subset of women with diagnosed endometriosis and fibroids. Results: Women with endometriosis had greater odds of having elevated CRP than those without endometriosis (OR = 1.60; 95% CI: 1.05 to 2.45). Women with endometriosis had a shorter telomere length than women without endometriosis (-3.4, 95% CI: -7.3 to -0.3 in age-adjusted models and -2.9, 95% CI: -8.8 to 3.5 in fully adjusted models). Telomeres were 1% (95% CI: -1.2 to -0.6) shorter for every elapsed year since endometriosis diagnosis. No substantive patterns emerged between uterine fibroids and CRP or telomere length. Conclusions: Women with endometriosis (or a longer duration of time spent with endometriosis) had higher inflammatory markers and shorter mean telomere length. These results provide further insights into potential mechanisms linking endometriosis to chronic disease and later-life health.

BACKGROUND:Asian/Pacific Islander (API) communities in the United States often reside in metropolitan areas with distinct social and environmental attributes. Residence in an ethnic enclave, a socially distinct area, is associated with lower gestational diabetes mellitus (GDM) risk, yet exposure to high levels of air pollution, including volatile organic compounds (VOCS), is associated with increased GDM risk. We examined the joint effects of ethnic enclaves and VOCs to better understand GDM risk among API women, the group with the highest prevalence of GDM.METHODS:We examined 9069 API births in the Consortium on Safe Labor (19 hospitals, 2002-2008). API ethnic enclaves were defined as areas ≥66th percentile for percent API residents, dissimilarity (geographic dispersal of API and White residents), and isolation (degree that API individuals interact with another API individual). High levels of 14 volatile organic compounds (VOC) were defined as ≥75th percentile. Four joint categories were created for each VOC: Low VOC/Enclave (reference group), Low VOC/No Enclave, High VOC/Enclave, High VOC/No Enclave. GDM was reported in medical records. Hierarchical logistic regression estimated odds ratios (OR) and 95% confidence intervals (95%CI) between joint exposures and GDM, adjusted for maternal factors and area-level poverty. Risk was estimated for 3-months preconception and first trimester exposures.RESULTS:Enclave residence was associated with lower GDM risk regardless of VOC exposure. Preconception benzene exposure was associated with increased risk when women resided outside enclaves [High VOC/No Enclave (OR:3.45, 95%CI:1.77,6.72)], and the effect was somewhat mitigated within enclaves, [High VOC/Enclave (OR:2.07, 95%:1.09,3.94)]. Risks were similar for 12 of 14 VOCs during preconception and 10 of 14 during the first trimester.CONCLUSIONS:API residence in non-enclave areas is associated with higher GDM risk, regardless of VOC level. Ethnic enclave residence may mitigate effects of VOC exposure, perhaps due to lower stress levels. The potential benefit of ethnic enclaves warrants further study.

BACKGROUND:Universal screening for postpartum depression (PPD) remains an unachieved national priority. A tacit screen that requires no additional resources for administration can help to achieve this priority. We examine the predictive utility of using smoking as a tacit screen for PDD. We first establish smoking is a valid proxy for more prominent psychosocial determinants of PPD and is a predictor for PPD.METHODS:We analyzed PRAMS data (2012-2015; N=134,435). Time of smoking was categorized as nonsmoker, during the prenatal period, the postpartum, or continuously; PPD was assessed using two PHQ-2 style questions.RESULTS:Compared to nonsmokers, women who smoked only during the prenatal period (OR: 1.41; 95% CI: 1.06 - 1.86), only during the postpartum (OR: 1.33; 95% CI: 1.18 - 1.49), and continuously throughout both periods (OR: 1.54; 95% CI: 1.41 - 1.69) were more likely to experience PPD. Smoking assessed at a prenatal visit (SN: 0.90, SP: 0.21), postpartum visit (SN: 0.86, SP: 0.25), or assessed at both visits (SN: 0.90, SP: 0.19) performed relatively well as a tacit screen for PPD, performing better among unmarried women (SN: 0.75 - 0.81; SP: 0.29 - 0.36).LIMITATIONS:In this study, the criterion of positivity used was PRAMS' adapted version of the PHQ-2. This tacit screen may perform differently relative to a clinical diagnosis.CONCLUSIONS:Time of smoking predicts risk of PPD and can be used to tacitly screen for PPD with reasonable accuracy without requiring any additional time in settings with limited resources for routine screening of PPD.

Although the association between stress and poor reproductive health is well established, this association has not been examined from a life course perspective. Using data from the National Longitudinal Survey of Youth 1997 cohort (N = 1652), we fit logistic regression models to test the association between stressful life events (SLEs) (e.g., death of a close relative, victim of a violent crime) during childhood, adolescence, and early adulthood and later experiences of infertility (inability to achieve pregnancy after 12 months of intercourse without contraception) reported by female respondents. Because reactions to SLEs may be moderated by different family life experiences, we stratified responses by maternal responsiveness (based on the Conger and Elder Parent-Youth Relationship scale) in adolescence. After adjusting for demographic and environmental factors, in comparison to respondents with one or zero SLEs, those with 3 SLEs and ≥ 4 SLEs had 1.68 (1.16, 2.42) and 1.88 (1.38, 2.57) times higher odds of infertility, respectively. Respondents with low maternal responsiveness had higher odds of infertility that increased in a dose-response manner. Among respondents with high maternal responsiveness, only those experiencing four or more SLEs had an elevated risk of infertility (aOR = 1.53; 1.05, 2.25). In this novel investigation, we demonstrate a temporal association between the experience of SLEs and self-reported infertility. This association varies by maternal responsiveness in adolescence, highlighting the importance of maternal behavior toward children in mitigating harms associated with stress over the life course.

Background: Asian/Pacific Islander (API) communities in the United States often reside in metropolitan areas with distinct social and environmental attributes. Residence in an ethnic enclave, a socially distinct area, is associated with lower gestational diabetes mellitus (GDM) risk, yet exposure to air pollution, which is often elevated in urban areas, is associated with increased GDM risk. We examined the joint effects of ethnic enclaves and air pollution to better understand GDM risk among API women, the group with the highest prevalence of GDM.Methods: We examined 9,069 API births in the Consortium on Safe Labor (19 hospitals, 2002-2008). API ethnic enclaves were defined as areas ≥66th percentile for percent API residents, dissimilarity (distribution of API and White residents), and isolation (degree that API individuals interact with another API individual). High levels of 14 volatile organic compounds (VOC) were defined as ≥75th percentile. Four joint categories were created for each VOC: Low VOC/Enclave (reference group), Low VOC/No Enclave, High VOC/Enclave, High VOC/No Enclave. GDM was reported in medical records. Hierarchical logistic regression estimated odds ratios (OR) and 95% confidence intervals (95%CI) between joint exposures and GDM, adjusted for maternal factors and area-level poverty. Risk was estimated for 3-months preconception and first trimester exposures.Results: Enclave residence was associated with lower GDM risk regardless of VOC exposure. Preconception benzene exposure was associated with increased risk when women resided outside enclaves [High VOC/No Enclave (OR:3.45, 95%CI:1.77,6.72)], and the effect was somewhat mitigated within enclaves, [High VOC/Enclave (OR:2.07, 95%:1.09,3.94)]. Risks were similar for 12 of 14 VOCs during preconception and 10 of 14 during the first trimester.Conclusions: API residence in non-enclave areas is associated with higher GDM risk, regardless of VOC level. Ethnic enclave residence may mitigate effects of VOC exposure, perhaps due to lower stress levels. The potential benefit of ethnic enclaves warrants further study.

Objective:Cardiometabolic disease is the leading cause of mortality in the United States. Cardiometabolic function during adolescence predicts future cardiometabolic disease, yet few studies have examined early determinants of cardiometabolic function. Informed by evidence of sex differences in the prevalence and severity of cardiometabolic disorders and evidence of sexual dimorphism in the stress response, we examined sex differences in the association between living in poverty and cardiometabolic function during adolescence, a precursor of later cardiometabolic disorders.Methods:We linked data from 10 415 adolescents aged 12-19 in the National Health and Nutrition Examination Survey (1999-2012) with US Census–tract data on area-level poverty (percentage of the population living in poverty, grouped into quartiles). We parameterized cardiometabolic dysfunction by summing the z scores of 6 cardiometabolic biomarkers, grouped into quintiles. Hierarchical ordinal models estimated associations.Results:Compared with residents in low-poverty areas, residents in high-poverty areas had elevated odds of cardiometabolic dysfunction (highest quartile of poverty odds ratio [OR] = 1.27; 95% confidence interval [CI], 1.08-1.50). This association was more pronounced among boys than girls (highest quartile of poverty for boys: OR = 1.36; 95% CI, 1.10-1.70; highest quartile of poverty for girls: OR = 1.17; 95% CI, 0.94-1.47).Conclusion:Our study supports the existence of sex-specific associations. These results highlight the potential for community-based programs, such as housing assistance, to improve population health.

Purpose: A key to better understanding the influence of the place of residence on cardiometabolic function is the effect of concomitant exposure to both air pollution and residence in economically marginalized areas. We hypothesized that, among adolescents, the association between air pollution and cardiometabolic function is exacerbated among residents of economically marginalized areas. Methods: In this cross-sectional study, individual-level data on cardiometabolic function collected from a representative sample of U.S. adolescents in the National Health and Nutrition Examination Survey (n = 10,415) were merged with data on area-level poverty (U.S. decennial survey and American Community Survey) and air pollution levels (National-Scale Air Toxics Assessment) using contemporary census-tract identifiers. We excluded respondents who were pregnant, had hypertension or diabetes or using medication for hypertension or diabetes, or with missing data on outcome variables. Results: We observed a significant interaction between area-level poverty and air pollution. Among residents of high-poverty areas, exposure to high levels of air pollution predicted a 30% elevated odds of cardiometabolic dysfunction (OR = 1.30; 95% CI: 1.04, 1.61), whereas in low-poverty areas, exposure to high levels of air pollution was not associated with elevated odds of cardiometabolic dysfunction (OR = 1.04; 95% CI: 0.85, 1.28). Conclusions: Our findings suggest that the cardiometabolic consequences of air pollution are more readily realized among residents of economically marginalized areas. Structural remedies are discussed. (C) 2020 Elsevier Inc. All rights reserved.

Introduction: Reducing racial/ethnic disparities in preterm birth is a priority for U.S. public health programs. The study objective was to quantify the relative contribution of geographic, sociodemographic, and health determinants to the black, non-Hispanic and white, non-Hispanic preterm birth disparity. Methods: Cross-sectional 2016 U.S. birth certificate data (analyzed in 2018-2019) were used. Black-white differences in covariate distributions and preterm birth and very preterm birth rates were examined. Decomposition methods for nonlinear outcomes based on logistic regression were used to quantify the extent to which black-white differences in covariates contributed to preterm birth and very preterm birth disparities. Results: Covariate differences between black and white women were found within each category of geographic, sociodemographic, and health characteristics. However, not all covariates contributed substantially to the disparity. Close to 38% of the preterm birth and 31% of the very preterm birth disparity could be explained by black-white covariate differences. The largest contributors to the disparity included maternal education (preterm birth, 11.3%; very preterm birth, 9.0%), marital status/paternity acknowledgment (preterm birth, 13.8%; very preterm birth, 14.7%), source of payment for delivery (preterm birth, 6.2%; very preterm birth, 3.2%), and hypertension in pregnancy (preterm birth, 9.9%; very preterm birth, 8.3%). Interpregnancy interval contributed a more sizable contribution to the disparity (preterm birth, 6.2%, very preterm birth, 6.0%) in sensitivity analyses restricted to all nonfirstborn births. Conclusions: These findings demonstrate that the known portion of the disparity in preterm birth is driven by sociodemographic and preconception/prenatal health factors. Public health programs to enhance social support and preconception care, specifically focused on hypertension, may provide an efficient approach for reducing the racial gap in preterm birth. (C) 2019 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.

Objective: To explore associations between infertility and metabolic syndrome, and cardiovascular events. Infertility is increasingly a public health issue, with emerging links to chronic disease. Existing literature on infertility focuses primarily on known causes, which likely excludes a substantial number of women for whom there is no known cause or formal diagnosis. Design/Setting: We conducted a cross-sectional analysis examining the association between self-reported infertility (i.e., ever experiencing inability to conceive after 12 months of trying to become pregnant) and metabolic syndrome and cardiovascular events (i.e., congestive heart failure, coronary heart disease, heart attack, or stroke). Data were analyzed using multivariate logistic regression. Patient(s): A total of 744 U.S. women, 20-59 years of age, from the National Health and Nutrition Examination Survey (2013-2014), participated in the study. Among them, 15.7% reported ever experiencing infertility, 27.6% met the definition of metabolic syndrome, and 2.84% reported ever having a cardiovascular event. Intervention(s): N/A. Main Outcome Measure(s): Metabolic syndrome and cardiovascular events. Results: Compared to women who had never experienced infertility, women who reported infertility had a 1.79 (95% confidence interval [CI] 1.04, 3.08) higher odds of reporting symptoms of metabolic syndrome and 1.83 (95% CI 1.15, 2.89) times higher odds of having experienced a cardiovascular event. Furthermore, women with self-reported infertility had a 71% higher odds of reporting a cardiovascular event after controlling for metabolic syndrome (95% CI 1.01, 3.00). Conclusions: Our results suggest that among U.S. women, the experience of infertility at any point in a woman's reproductive window may be associated with later-life cardiovascular health. (C) 2018 by American Society for Reproductive Medicine.