EXPOSOME BIOCHEMICAL ANALYSIS FOR BIRTH WEIGHT/OBESITY

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The Division of Intramural Population Health Research, NICHD, is uniquely positioned to be on the forefront of exposome research, in that its intramural designation is consistent with the conduct of high risk research, many prospective pregnancy cohorts that have generated rich databases with longitudinally collected (in varying degrees) biospecimens during sensitive windows of human development are available, and the Division has biostatisticians with the level of expertise needed to develop appropriate analytical methods. These resources afford Division investigators an opportunity to design research initiatives within the exposome paradigm. Perhaps one of the earliest and most critical sensitive windows occurs during human reproduction and development. Currently the Division has a proof-of-concept study underway to characterize and quantify the pregnancy exposome using an existing pregnancy cohort study with normal outcomes. The goal of the present study is to build upon our previous work that focuses on the characterization of the normal pregnancy exposome by extending the same methodology to 'normal' pregnant women whose infants were born at the extremes of birth weight, as women with offspring small for gestational age (SGA) defined as birth weight < 10th percentile and large for gestational age (LGA) defined as birth weight > 90th percentile (Brenner, 1976) were excluded from the prior analysis. [20] Both low and high birth weight are associated with increased short term morbidity and mortality,and also have been repeatedly related to Increased risk of chronic diseases in later life, such as cardiovascular disease and type 2 diabetes. [21] Comprehensive Investigation of the exposome related to birth weight would potentially improve our understanding or early life determinants of the chronic diseases and help develop early preventive strategies of life long chronic diseases. Evidence has also linked the long-term impact of exposure to maternal obesity to increase risk of obesity and cardiometabolic risk. [22] Of added note is our effort to ensure comparable sampling frameworks for both groups in that all eligible women have their Initial biospecimens collected <13 weeks gestation and during each trimester. Restricting to women with a first trimester biospecimen collection is critical for assessing longitudinal changes during pregnancy, as pregnancy induces many physiologic changes following conception and implantation. Thus, having two randomly selected groups of 'normal’ pregnant women who differ only in terms of infants' birth weight will allow us to characterize and quantify the exposome during pregnancy for each of these two samples of pregnant women. This strategy was a part of our initial work presented to the Division for FY13, but later restricted to only the former group in light of concerns about the integrity of the biospecimens for research purposes. We now demonstrate that the sample integrity is there, and variation can be quantified. Our second objective is to sample a third group of 'normal' pregnant women who are obese and who are most relevant given the increasing prevalence of obesity in contemporary obstetric populations.