Environmental exposures and fetal growth: The Haifa pregnancy cohort study David Stieb, Cecile Boot, Michelle Turner, Osmar Zaiane

Background: The developing fetus is susceptible to environmental insults. Studying the effects of environmental exposures on fetal growth is essential for understanding the causal pathway between prenatal exposures and pregnancy outcomes. Here we describe the Haifa Pregnancy Cohort Study (HPCS) and discuss challenges and opportunities in applying "big data" paradigm. Methods: Maccabi Healthcare Services (MHS), is the second largest Israeli health maintenance organization (HMO) providing care services to two million beneficiaries. The HPCS cohort potentially includes ~750,000 newborns born between 1998 and 2017. We will estimate daily exposures to air pollutants, temperature and greenness, using satellite-based data and models. We hypothesize that residents of Haifa have higher exposures to environmental pollutants and that in pregnant women this higher exposure is associated with poorer fetal growth. We will evaluate outcomes such as birth-weight, head-circumference and gestational age at birth. We will adjust for pregnancy complications such as pre-eclampsia and gestational diabetes and parental variables, such as maternal weight, age and smoking habits as potential confounders. In addition, we will conduct a multi-tiered field study, nested within this population, among 150 pregnant women residing in two geographical regions-one in the polluted Haifa area, and one in a relatively unpolluted area in central Israel. Blood and urinary samples will be collected, as well as personal and indoor exposure to air pollution. Discussion: Evaluating environmental exposures of pregnant women and assessing in utero growth over the course of the pregnancy during different exposure windows, is of great scientific and public health interest. Recent advances in data collection and analysis pose great promise to provide insights into contribution of environment to the health of the developing fetus, but also pose major challenges and pitfalls, such as data management, proper statistical framework and integration of data in the population-based study and selectiveness in the nested field study. Yet the continuing follow-up of the study cohort, integrating data from different services, health-promotion, and eventually, application later in real life of our main promises. Our study aims to meet these challenges and to provide evidence of the environmental exposures associated with fetal growth.