PRENATAL AND CHILDHOOD EXPOSURES AND AGE AT MENARCHE

接触化学物质对发育中的胎儿和儿童造成的危害日益受到关注。发育终点检查主要是不良妊娠结局，以及一些神经行为发展的考虑。人们对正常的月经功能以及它是如何在青春期开始的知之甚少。在这项初步研究中，我们建议检查性发育的一项指标，即初潮年龄，以及它与产前接触化学物质（包括烟草、酒精和咖啡因）的关系。在怀孕期间，吸烟是一种已知的生殖危害，也与不孕和激素排泄水平的改变有关。产前酒精暴露与胎儿生长迟缓和后代神经功能障碍有关。大量研究表明酒精对成人内分泌系统的影响，并有暗示证据表明它可能影响性成熟。已知的咖啡因的作用为激素谱的改变提供了合理的机制，并与延迟受孕时间有关。因此，这三种暴露都可能通过对产前激素环境或发育中的神经系统的作用而影响性发育。拟议的试点研究将利用1960年代初确定的大量怀孕数据。本研究的对象将是1000个女儿，从童年到青春期，在此期间确定月经初潮的年龄。前瞻性地收集了大量产前暴露以及潜在混杂因素的数据。许多重要的儿童暴露和条件也被确定为前瞻性的，包括父母吸烟，儿童行为和成长。根据这些数据，我们建议检查子宫内暴露于TAC或童年暴露于父母吸烟是否与月经初潮年龄的扰动有关。月经初潮年龄早与乳腺癌风险增加有关，因此月经初潮年龄的改变可以作为对儿童和妇女健康的其他不利影响的哨兵。这些数据对于设计与早期生活接触有关的生殖过程和生长发育的进一步研究将是有价值的。

Hazards posed to the developing fetus and child by exposure to chemical substances are receiving increasing attention. The developmental endpoints examined primarily have been adverse pregnancy outcomes, as well as some consideration of neurobehavioral development. Little is known about normal menstrual function and how it is initiated during adolescence. In this pilot study we propose to examine a measure of sexual development, namely, age at menarche, and its relationship to prenatal exposure to chemical substances including, tobacco smoke, alcohol and caffeine (TAC). Active smoking is a known reproductive hazard during pregnancy and has also been associated with infertility and alterations in hormone excretion levels. Prenatal alcohol exposure is associated with fetal growth retardation and neurologic impairment in offspring. Numerous studies have shown effects of alcohol on the endocrine system of adults and there is suggestive evidence it may effect sexual maturation. Known actions of caffeine present plausible mechanisms for alteration of hormonal profiles and an association with delayed time to conception has been reported. Thus all three exposures may possibly affect sexual development via actions on the prenatal hormonal milieu or the developing nervous system. The proposed pilot study would make use of a large data base of pregnancies ascertained in the early 1960's. Subjects of this study will be the 1000 daughters followed through childhood and adolescence, at which time age at menarche was ascertained. Extensive data was collected prospectively on prenatal exposures, as well as on potential confounders. A number of important exposures and conditions of childhood were also ascertained prospectively, including parental cigarette smoking, childhood behaviors, and growth. With these data we propose to examine whether in utero exposure to TAC or childhood exposure to parental smoking are related to perturbations in age at menarche. Early age at menarche has been associated with an increased risk of breast cancer, thus alteration in menarcheal age may serve as a sentinel of other adverse effects on children's and women's health. Such data will be valuable in designing further studies of the reproductive process and growth and development in relation to early life exposures.