FETAL, NEONATAL AND CHILDHOOD EFFECTS OF IN UTERO EXPOSURE TO PCBS AND DDE

宫内接触有机氯化合物的长期影响具有重要的潜在意义。这些化合物在全世界几乎100%的人类中都能检测到，它们与儿童神经发育迟缓有关。此外，DDT的主要代谢物p，p‘-DDE是一种弱雌激素，在人体内观察到的浓度是雄激素受体阻滞剂。该项目的一个目标是确定怀孕期间获得的母体血清DDE浓度是否是男性后代隐睾症、尿道下裂和多发性硬化症的危险因素。之所以选择这些畸形，是因为它们是子宫内雄激素活性不足的标志。其他目标是确定宫内接触DDE是否随后与青春期女性月经初潮年龄改变和青春期男性肥胖风险增加有关，以及宫内接触多氯联苯是否与儿童期肌肉张力、反射、智商和听力不佳有关。到目前为止的工作已经证明，这些化合物可以在适当浓度下从研究人群中恢复，并且这些化合物在第一和第三孕期血清中浓度之间的相关性足够高，可以使用第三孕期血清作为第一孕期暴露的替代物。主要研究的血清中DDE和多氯联苯浓度的分析从2000财年开始。对青少年结局的血清分析将于01财年开始。

The long-term effects of in utero exposure to organochlorine compounds is of great potential importance. These compounds, which are detectable in nearly 100% of humans worldwide, have been linked to reduced neurodevelopment in children. In addition, p,p'-DDE, the primary metabolite of DDT, is a weak estrogen, and an androgen receptor blocker at concentrations observed in humans. One objective of this project is to determine whether maternal serum concentration of DDE, obtained during pregnancy, is a risk factor for cryptorchidism, hypospadias and polythelia in male offspring. These malformations were chosen because they are markers of deficient androgen activity in utero. Other objectives are to determine whether in utero exposure to DDE is subsequently associated with an altered age at menarche in adolescent females and an increased risk of obesity in adolescent males, and whether in utero exposure to PCBs is associated with suboptimal muscle tone, reflexes, IQ and hearing during childhood. Work to date has demonstrated that these compounds can be recovered from the study population at relevant concentrations, and that the correlation between concentrations of these compounds in first and third trimester serum is sufficiently high to employ third-trimester serum as a surrogate for first-trimester exposure. Analysis of the concentrations of DDE and PCBs in serum for the main study began in FY 00. Serum analysis for the adolescent outcomes will begin in FY 01.