Flame Retardant and Adverse Perinatal Outcome (FRAPO)

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DESCRIPTION (provided by applicant): Polybromated Diphenyl Ethers (PBDEs) are one of the most prevalent organic pollutants due to their wide- spread use during the past 40 years as flame retardants, especially in the United States and Canada. As a result, North Americans have the highest blood and breast milk concentrations of PBDEs anywhere in the world. PBDEs are present in the plasma of almost all pregnant women. They have also been isolated from the placenta, umbilical chord, amniotic fluid and fetal membranes but their effects on pregnancy outcome are unclear. PBDEs have been widely investigated as endocrine disruptors of the thyroid system due to their structural similarity with thyroxine (T4) and tri-iodothyronine (T3). Women with hypothyroidism are at increased risk for preterm birth, the foremost problem in modern obstetrics, through an unknown mechanism. Many preterm births are associated with inflammation in the placenta and fetal membranes. There is emerging evidence that thyroid hormones have anti-inflammatory properties, improving survival and reducing the production of proin- flammatory cytokines in animal models of sepsis. It is possible that inhibition of T3 and T4 bioactivity, by PBDEs increases the risk of pretem birth by favoring a pro-inflammatory environment. Our preliminary studies suggest that treatment of placental cultures with PBDE enhances the production of cytokines and prostaglandins associated with preterm birth. To determine if PBDE exposure may enhance the risk for preterm birth in women, we propose to collect blood samples from a women receiving prenatal care in southern California at each trimester of pregnancy. Samples from women who deliver preterm and 1000 randomly selected controls will be assayed for PBDE-47, the most prevalent conger detected in maternal plasma and thyroid-stimulating hormone (TSH). We hypothesize that women who deliver preterm will have increased concentrations of PBDE-47 throughout their pregnancy, especially when evidence of infection (histological chorioamnionitis) is present. Plasma PBDE-47 levels are expected to be positively correlated with plasma concentrations of TSH, suggesting reduced bioactivity of the thyroid hormones. This study will help fulfill the critical need to better understand the potential role of PBDEs, which were detectable in >90% of all pregnant women, on risk for adverse pregnancy outcomes.