Fetal, Neonatal And Childhood Effects Of In Utero Exposu

子宫内暴露于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%的人体内都能检测到，它们与儿童神经发育受损有关。此外，滴滴涕的主要代谢物p，p'-DDE是一种弱雌激素，在人体中观察到的浓度是雄激素受体阻滞剂。该项目的目的之一是确定妊娠期间获得的母体血清DDE浓度是否是男性后代隐睾、尿道下裂和多毛症的危险因素。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。其他目的是确定子宫内暴露于DDE是否随后与青春期女性月经初潮年龄的改变和青春期男性肥胖风险的增加有关，以及子宫内暴露于多氯联苯是否与儿童期肌肉张力、反射、智商和听力的次优相关。迄今为止的工作表明，这些化合物可以在相关浓度下从研究人群中恢复，并且这些化合物在妊娠早期和晚期血清中的浓度之间的相关性足够高，可以使用妊娠晚期血清作为妊娠早期暴露的替代品。2002财年完成的研究发现，母体血清DDE升高与胎儿流产史相关（60 mg/l的优势比=1.3,p <0.05）。由于许多发展中国家仍在使用滴滴涕控制疟疾，因此这些发现对国际卫生具有重要意义。研究还发现，母亲妊娠晚期血清多氯联苯水平与8月龄儿童的不良神经发育无关，尽管注意到大量的中心异质性。

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 impaired 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. Work completed in FY 2002 found that elevated maternal serum DDE was associated with a history of fetal loss (odds ratio for 60 mg/l=1.3, p for trend <0.05). Since DDT is still used for malaria control in many developing countries, these findings have important implications for international health. It was also found that maternal third-trimester serum PCB levels were not associated with adverse neurodevelopment in children at 8 months of age, although substantial center heterogeneity was noted.