Preterm delivery and maternal cardiovascular disease risk Abstract The objective of this applications is to identify: 1) mechanisms that link preterm birth to later life maternal cardiovascular risk;and 2) subgroups of women who deliver preterm and might benefit from early tracking and interventions to reduce future cardiovascular disease (CVD). Preterm delivery (PTD) occurs in 12.5 percent of pregnancies in the U.S., and rates are increasing. Women who have delivered a preterm infant have excess risk of developing CVD compared to those with term deliveries, but mechanisms relating these conditions are not understood. PTD is a heterogenous outcome, and it is likely that subsets of women who deliver preterm may have different later life sequelae. We hypothesize that pregnancy unmasks a predisposition to CVD and that inflammation, dyslipidemia and thrombogenesis converge in pregnancy to compromise placentation and/or maternal vascular integrity among a subset of women who deliver preterm. Therefore women with PTD, particularly those with placental vascular lesions, will have an atherogenic profile post partum and early evidence of atherosclerosis. We propose a follow-up study of women enrolled in the Pregnancy Outcomes and Community Health (POUCH) Study, a prospective cohort enrolled from 1998-2004 designed to examine pathways to PTD. Blood samples were collected at enrollment, 15-27 weeks'gestation. Prenatal, labor and delivery records were abstracted and placentas were examined in a blinded fashion by a single placental pathologist. We plan to build on this framework by studying the cardiovascular profile among women with and without PTD and by identifying subtypes of PTD associated with evidence of cardiovascular risk at 6-11 years after POUCH Study participation. We will enroll approximately 896 women (513 white/other and 383 African Americans);217 who delivered preterm and 679 who delivered at term during the POUCH Study. We will collect questionnaire data and measures of an atherogenic profile such as anthropometrics (height, weight, waist circumference), blood pressure, and blood levels of inflammatory markers, lipids, and thrombogenic factors. In addition we will assess early evidence of atherosclerosis via carotid ultrasound scans (carotid intimal- medial thickness).
Our aims will be to compare the outcome measures at follow-up. i.e. atherogenic profile and early atherosclerosis among women with term births and: 1) women with a prior PTD;2) women with PTD subtypes grouped by clinical circumstance and placental pathology;and 3) women with PTD subtypes grouped by levels of dyslipidemia and inflammation biomarkers in mid-pregnancy. In addition we will examine whether associations in Aim 1 might be modified by factors such as socioeconomic status, race, or maternal depression/distress. Studies that uncover pathways linking PTD to maternal CVD risk can lead to new intervention strategies for both of these medical problems, and help to identify women very early in the disease process when intervention may delay or prevent onset of disease.
Recent evidence indicates that women who deliver preterm may be at increased risk of CVD later in life, but the nature of this connection is poorly understood and remains a 'black box.'In this study we have a unique opportunity to assess the atherogenic profile and early evidence of atherosclerosis in a cohort of women for whom we have detailed pregnancy data (biomarkers, placental pathology) as part of an earlier study on preterm delivery. This proposed follow-up study will lead to a more in-depth understanding of the pathways that connect preterm delivery and later CVD risk, and will aid in targeting women at high risk for CVD and selecting appropriate early interventions.
