START UP, PREPARATION, AND TEST ENROLLMENT FOR THE STUDY OF PREGNANCY AND NEONATAL HEALTH (SPAN)

Duke University, Durham NC

Investigators

Abstract

Introduction The Division of Intramural Population Health Research (DIPHR) at the Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD) designs and conducts original epidemiological, behavioral, and biostatistical research encompassing several research domains such as human reproduction and development, pregnancy and related complications, pediatric and adolescent health and behaviors, and methodologic research relevant for our mission. The Division comprises three intramural research branches, Epidemiology, Biostatistics & Bioinformatics, and Social and Behavioral Sciences, and its mission is to design and implement original research with the potential for high impact findings that impact public health. Under the Developmental Origins of Health and Disease (DOHaD) hypothesis, early life exposures can ?program? an individual for health and chronic disease risk through cellular adaptations to biological processes. Prenatal exposures and genetic factors impact fetal growth and development and neonatal health, important determinants of life-long health and disease. We propose an approach to examine a) the father?s role, b) placental determinants, and c) timing of delivery in relation to fetal and neonatal health and development. A cohort study will be performed to collect common data elements from approximately 7700 pregnant women and their neonates and approximately 3825 male partners with a randomized control trial conducted in women with gestational diabetes (approximately 720 women). African American women will be oversampled (~4250). It is anticipated that multiple study sites will be established. Objective This study will establish a prospective pregnancy cohort with a nested randomized control trial, recruiting women in early pregnancy and retaining them throughout pregnancy for assessment of neonatal outcomes to address the specific aims below. 1) Paternal Contribution to DOHaD (DAD aim): To determine whether paternal cardiovascular disease (CVD) risk factors (i.e., BMI, waist circumference, % body fat, HbA1c, blood pressure, arterial stiffness) are associated with fetal growth, neonatal anthropometry, and placental function (as measured by ultrasound and placental characteristics at delivery); and whether semen epigenetic differences explain associations. 2) Genetics of fetal Growth And Placental aging (gGAP aim): To identify genetic mechanisms associated with variations in fetal growth and birth anthropometry, and to determine genetic loci associated with placental age acceleration and the functional link between associated genetic loci, placental gene expression and fetal growth in African Americans. 3) Timing of delivery for GDM (Gestational Diabetes Mellitus) (TIME aim): To determine the optimal time for GDM complicated deliveries between 38-39 weeks where neonatal morbidity and mortality is the lowest without increasing fetal mortality. (n= approximately 720 women) Newborn developmental and behavior outcomes, and anthropometric measures will also be explored, as well as an exploratory analysis to investigate whether there are clinical, non-clinical or biochemical factors such as glucose measures that will further assist in refining the interval for optimizing time of GDM complicated deliveries relative to neonatal morbidity and mortality. SCOPE The study site (Contractor) shall complete all activities pertaining to the preparation of the study materials, regulatory procedures, and training of site study staff relevant to the described cohort and trial. The preparatory activities will ready the study team, including the site, DCC, and NICHD members for successful Study initiation. Multiple sites will establish a cohort consisting of approximately 7,700 pregnant women, of whom around 4250 (55%) are self-reported to be Black or African American. It is anticipated that about 50% of their male partners (n= approximately 3825) will also participate in data collection. Women who enroll in the cohort early in pregnancy and are diagnosed with GDM (about 10%) will be approached for randomization to timing of delivery. All other women diagnosed with GDM, regardless of having entered the cohort in the first trimester will also be invited into the TIME trial to reach a randomization goal of a total of approximately 720 women with GDM. Refer to the Technical Notes section, Attachment 1, for additional details.