Pubertal study of offspring of preeclamptics and normote

先兆子痫是一种以妊娠期间蛋白尿和高血压为特征的疾病。与正常妊娠的母亲和子女相比，怀孕期间被诊断为先兆子痫的妇女及其女儿患乳腺癌的风险较低，而她们的儿子患前列腺癌和睾丸癌的风险较低。为什么会这样呢？先兆子痫妊娠的激素环境的特点是激素水平升高，如雄激素，脱氢表雄酮硫酸盐(DHEAS)，在动物研究中对乳腺癌有保护作用，而在人类研究中，较低的雌激素和IGF-1水平与降低风险有关。事实上，在先兆子痫(比正常血压)妊娠的新生儿脐带血中也出现了类似的激素模式(DHEAS水平较高，IGF-I水平较低)。此外，先兆子痫的后代小于胎龄(SGA)的风险是正常妊娠的四倍；SGA患同样癌症的风险可能会降低。令人惊讶的是，除了怀孕和分娩之外，这些母子对中的荷尔蒙和其他数据实际上是不存在的。在整个生命周期中，儿童生长速度、青春期和青春期生长迅速的早期年龄以及月经初潮等生殖发展的早期指标与乳腺癌风险增加有关。此外，在睾酮分解代谢中占主导地位的细胞色素P450 3A4(CYP3A4*1B)的高活性遗传变异与青春期开始时的年龄密切相关。本研究的目的是确定：先兆子痫和正常血压孕妇的后代是否有不同的Tanner分期、激素谱、CYP3A4*1B基因变异和10-10.5岁和13-13.5岁的人体测量状态；两组孕妇的女儿报告的月经初潮年龄是否有差异；以及先前诊断为先兆子痫的非妊娠状态的妇女是否与正常血压妇女相比，雌激素水平较低，雄激素水平较高。这样的研究有可能弥合理解为什么这种情况与乳腺癌和男性荷尔蒙癌症风险降低相关的差距。这将是对307名连续被诊断为先兆子痫的妇女和两组血压正常的对照组(N=619)进行的第一次研究，这些妇女从1993年1月到1995年12月在挪威斯塔万格的罗加兰中心医院生下了一个独生子女。对母亲及其子女的跟踪将在两个时间点进行，即指数儿童达到10-10.5岁和13-13.5岁。将从健康记录中提取一岁和四岁时体重和身高的间隔测量，以检查儿童早期发育是否改变了先兆子痫和胎儿大小对10岁和13岁男孩和女孩的人体测量状态和Tanner阶段以及女孩报告的初潮年龄的影响。

Preeclampsia is a condition characterized by proteinuria and hypertension in pregnancy. Women diagnosed with preeclampsia in pregnancy and their daughters have a lower risk of breast cancer while their sons have a lower risk of prostate and testicular cancers compared to mothers and offspring of normotensive pregnancies. Why is this so? The hormonal milieu of the preeclamptic pregnancy is characterized by elevated levels of hormones such as the androgen, dehydroepiandosterone sulfate (DHEAS), that, in animal research has a protective effect on breast cancer, and lower levels of estrogens and IGF-1 that in human research are associated with a reduced risk. Indeed a similar hormonal pattern (of higher DHEAS levels and lower IGF-I levels) appears in cord blood of neonates of preeclamptic (than of normotensive) pregnancies. Also the risk of being small-for-gestational age (SGA) is four times higher in offspring of preeclampsia than in normotensive pregnancies; the SGA may be at reduced risk of the same cancers. Surprisingly, hormonal and other data beyond the pregnancy and delivery in these mother-offspring pairs are virtually non-existent. Over the life cycle, childhood growth velocity, early ages at growth spurts in puberty and adolescence, and early indicators of reproductive development such as menarche are associated with increased risk for breast cancer. Also a high activity genetic variant of cytochrome P450 3A4 (CYP3A4*1B), which predominates in testosterone catabolism, was strongly associated with age at onset of puberty. The objectives of this study are to determine whether: Tanner Stage, hormonal profiles, a genetic variant of CYP3A4*1B, and anthropometric status at 10-10.5 and at 13-13.5 years differ in offspring of preeclamptic and normotensive pregnancies; whether reported age at menarche differs in daughters of the two groups of pregnancies; and whether women in the non-pregnant state previously diagnosed with preeclampsia have lower estrogen levels and higher androgen levels compared to normotensive women. Such a study has the potential to bridge the gap in understanding why this condition is associated with a reduced risk for breast and male-hormone cancers. This will be the first study to follow 307 women who were consecutively diagnosed with preeclampsia and two sets of normotensive controls (N = 619) who gave birth to a singleton from January 1993-December 1995 in The Rogaland Central Hospital in Stavanger, Norway. The follow-up of mothers and their offspring will occur at two points in time, i.e. when the index child reaches 10-10.5 years, and at 13-13.5 years. Interval measures of weight and height at one and four years will be abstracted from health records to examine whether early childhood growth modifies the effects of preeclampsia and fetal size on anthropometric status and Tanner Stage in boys and girls of 10 and 13 years, and on reported age at menarche in girls.