NYU School of Medicine, Erasmus University Medical Center and New York State Department of Health respond to PA-16-160, proposing to study preconception and prenatal phthalate and bisphenol exposures in relationship to time to pregnancy, embryonic and fetal growth, and infant growth. A substantial literature suggests that a diverse array of synthetic chemicals may influence developmental endocrine programming and provoke oxidant stress, a major pathophysiologic mechanism underlying adverse birth outcomes. These include: phthalates (which are used to soften plastics and as scents); and bisphenols (used in aluminum can linings and thermal paper receipts). Yet, longitudinal studies of early life exposure to phthalates and bisphenols and their effects on fetal and postnatal growth in humans have been limited, and the few studies to date have not yielded consistent findings. We propose to analyze samples from preconception, three timepoints in pregnancy (7, 13 and 30 weeks) in 1000 father-mother-infant triads in Generation R Next, a prospective, longitudinal multi-ethnic birth cohort study. Unique embryonic and placental assessments will have been performed through repeated ultrasounds at 7, 9 and 11 weeks. These analyses will also capture embryonic and placental growth as well as liver growth and cardiac size. The proposed study will also leverage echocardiography and abdominal sonography performed at 1 and 12 months of age, which will assess dimensions such as left ventricular end-diastolic volume, end-systolic volume, stroke volume, ejection fraction and mass, as well as abdominal fat and liver steatosis. The PI (Trasande) is an internationally renowned expert in children's environmental health and the proposed study also benefits from strong support from Generation R Next, including the Director (Jaddoe), an experienced pediatric and perinatal epidemiologist with a strong record in studying early determinants of cardiovascular disease. Analyses will be performed by K. Kannan at Wadsworth Laboratories of the New York State Department of Health, who has deep experience with precise measurement of phthalate and bisphenol biomarkers in urine. Given the long-term implications of the ?thrifty phenotype,? if preconceptional exposures are found to be important in shaping fetal growth and influencing birth outcomes, then guidance in anticipation of conception to limit environmental exposures before pregnancy may be indicated. Presently, such guidance is limited in the United States, save perhaps from couples seeking advanced reproductive technology.
Studies of phthalate and bisphenol exposure in pregnancy and their impact on growth have been limited by lack of data regarding exposures before conception and in early embryonic development. The proposed work leverages a large Dutch cohort begun before conception to examine exposures to these chemicals, especially those emerging as replacements for bisphenol A and di-2-ethyl-hexylphthalate. If preconceptional exposures are found to be important in shaping fetal growth and influencing birth outcomes, then guidance in anticipation of conception to limit environmental exposures before pregnancy may be indicated.