Characterization of the exposure-disease continuum in neonates of mothers exposed to carcinogens during pregnancy.

The impact of maternal exposure to carcinogens during pregnancy on childhood cancer risk may be especially relevant for genetically susceptible infants. A molecular epidemiological approach, which has the potential to characterize processes between exposure and subsequent health effects in newborns by using biomarkers, is expected to provide valuable information for actually identifying such vulnerable neonates. Therefore, biomarkers of exposure (e.g. levels of cotinine and metals in cord blood), biomarkers of the biologically relevant dose (e.g. DNA and protein adducts) and biomarkers of early effects (e.g. the occurrence of somatic mutations in cord blood) have been studied in relation to birth outcomes. In this MiniReview, the most important data concerning these biomarker studies in relation to potential adverse health effects in neonates will be summarized and will be compared to the outcome of a small study population (59 mother-child pairs) in which all these biomarkers were assessed simultaneously. Overall, it can be concluded that plasma cotinine levels, macromolecule-carcinogen adduct levels and hypoxanthine phosphoribosyltransferase mutant frequencies are increased in cord blood of neonates of mothers who were exposed during pregnancy and their levels correlated with proxies of health effects, such as reduced birth weight. Moreover, DNA damage was found to be the highest in those neonates that carried risk alleles in genes that code for biotransformation enzymes. These results were confirmed in our study, which indicates that it is possible to identify a susceptible subgroup of newborns. In summary, there is a reason for profound concern of genotoxic effects in newborns of exposed mothers.