Fetal, Neonatal And Childhood Effects Of In Utero Exposu

宫内接触有机氯化合物的长期影响具有巨大的潜在重要性。这些化合物在全世界近100%的人类中都可以检测到，它们与儿童神经发育受损有关。此外，DDT的主要代谢产物p，p '-DDE是一种弱雌激素，在人体中观察到的浓度下是一种雄激素受体阻滞剂。该项目的一个目的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症、尿道下裂和多囊症的风险因素。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物。其他目的是确定宫内暴露于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，以及宫内暴露于PCB是否与儿童期次优肌张力、反射、智商和听力有关。迄今为止的工作已经证明，这些化合物可以在相关浓度下从研究人群中回收，并且这些化合物在妊娠早期和妊娠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物。2001财年完成的工作发现，母体血清DDE升高与早产（60 mg/l的比值比=3.1，趋势p <0.0001）和SGA（60 mg/l的比值比=2.6，趋势p =0.04）密切相关。由于许多发展中国家仍在使用滴滴涕控制疟疾，这些发现对国际卫生具有重要意义。还发现，即使在调整了与糖尿病相关的高脂血症后，糖尿病孕妇的血清PCB水平也高于非糖尿病妇女。最后，在妊娠期间母体血清DDE浓度与先天性异常之间观察到适度的正相关，提示男婴雄激素作用不足。

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 2001 found that elevated maternal serum DDE was strongly associated with both preterm (odds ratio for 60 mg/l=3.1, p for trend <0.0001) and SGA (odds ratio for 60 mg/l=2.6, p for trend=0.04) birth. 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 serum PCB levels are higher in pregnant diabetic women than in non-diabetic women, even after adjustment for the hyperlipidemia associated with diabetes. Finally, a modest positive association was observed between maternal serum DDE concentration during pregnancy and congenital anomalies suggestive of deficient androgen action in male infants.