Fetal/Neonatal/Childhood Effects Of In Utero PCB 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受损有关。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。2005财年完成的研究发现，孕妇血清多氯联苯的升高与儿童神经发育、胎儿发育或妊娠持续时间、怀孕时间或感觉神经性听力丧失无关，但与月经周期异常有关，孕妇血清DDE与胎儿丧失的病史有关，怀孕时间延长，儿童发育减慢的程度最高。在青春期男性中，母体血清DDE和多氯联苯都与青春期发育或大小无关。

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 2005 found that elevated maternal serum PCBs were not associated with childhood neurodevelopment, fetal growth or duration of pregnancy, time to pregnancy or sensorineural hearing loss, but are associated with abnormalities of the menstrual cycle, that maternal serum DDE is associated with history of fetal loss increased time to pregnancy, and reduced childhood growth at the highest levels. Neither maternal serum DDE nor PCBs were associated with pubertal development nor size in adolescent males.