Molecular epidemiologic research on the effects of environmental pollutants on the fetus

Evidence shows that fetuses and infants are more affected than adults by a variety of environmental toxicants because of differential exposure, physio logic immaturity, and a longer lifetime over which disease initiated in ear ly life can develop. in this article we review data on the effects of in ut ero exposure to common environmental contaminants, including polycyclic aro matic hydrocarbons (PAH), particulate matter and environmental tobacco smok e (ETS). We then summarize results from our molecular epidemiologic study t o assess risks from in utero exposures to ambient air pollution and ETS. Th is research study, conducted in Poland, used biomarkers to measure the inte rnal and bioeffective dose of toxicants and individual susceptibility facto rs. The study included 160 mothers and 160 newborns. Ambient air pollution was significantly associated (p less than or equal to 0.05) with the amount of PAH bound to DNA (PAH-DNA adducts) in both maternal and infant cord whi te blood cells (WBC). Newborns with elevated PAH-DNA adducts (greater than the median) had significantly decreased birth weight (p = 0.05), birth leng th (p = 0.02), and head circumference (p = 0.0005) compared to the newborns with lower adducts (n = 135). Maternal and infant cotinine levels were inc reased by active and passive cigarette smoke exposure of the mother (p less than or equal to 0.01). An inverse correlation was seen between newborn pl asma cotinine (nanograms per milliliter) and birth weight (p = 0.0001) and length (p = 0.003). Adducts were elevated in placental tissue and WBC of ne wborns who were heterozygous or homozygous for the cytochrome P4501A1 Mspi restriction fragment length polymorphism (RFLP) compared to newborns withou t the RFLP. Levels of PAH-DNA and cotinine were higher in newborns than mot hers. These results document that there is significant transplacental trans fer of PAH and ETS constituents from mother to fetus, that PAH-DNA adduct l evels in maternal and newborn WBC were increased with environmental exposur e to PAH from ambient pollution, and that the fetus is more sensitive to ge netic damage than the mother. The study also provided the first molecular e vidence that transplacental PAH exposure to the fetus is compromising fetal development. ii confirmed, these findings could have significant public he alth implications since a number of studies have found that reduction of he ad circumference at birth correlates with lower intelligence quotient as we ll as poorer cognitive functioning and school performance in childhood. Key words: air pollution, cigarette smoking, CYP1A1 Mspi RFLP, GSTM1, newborns , PAH-DNA adducts, Poland.