Pubertal study of offspring of preeclamptics and normote

子痫前期是一种以妊娠期蛋白尿和高血压为特征的疾病。怀孕期间被诊断为子痫前期的妇女和她们的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？子痫前期妊娠的激素环境的特点是雄激素、硫酸脱氢表雄酮（DHEAS）等激素水平升高，在动物研究中对乳腺癌有保护作用，而在人类研究中，雌激素和IGF-1水平较低与风险降低有关。事实上，与血压正常的孕妇相比，子痫前期新生儿的脐带血中出现了类似的激素模式（DHEAS水平较高，igf - 1水平较低）。此外，子痫前期的后代出现小胎龄（SGA）的风险是正常妊娠的四倍；SGA患相同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，这些母子对的荷尔蒙和其他数据几乎不存在。在整个生命周期中，儿童的生长速度、青春期和青春期的早期生长高峰以及月经初潮等生殖发育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 （CYP3A41B）的高活性遗传变异与青春期开始的年龄密切相关。本研究的目的是确定：坦纳期、激素谱、CYP3A41B基因变异和10-10.5岁和13-13.5岁子痫前期和正常妊娠的后代的人体测量状况是否存在差异；两组怀孕的女儿报告的月经初潮年龄是否不同；以及与血压正常的女性相比，未怀孕状态下被诊断为子痫前期的女性是否雌激素水平较低，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降低患乳腺癌和男性激素癌的风险有关的差距。这将是对1993年1月至1995年12月期间在挪威斯塔万格的罗加兰中心医院连续诊断为先兆子痫的307名妇女和两组血压正常的对照组（N = 619）进行的第一次研究。母亲及其后代的随访将在两个时间点进行，即指标儿童达到10-10.5岁时和13-13.5岁时。将从健康记录中提取1岁和4岁时的体重和身高间隔测量值，以检查儿童早期生长是否会改变子痫前期和胎儿大小对10岁和13岁男孩和女孩的人体测量状态和坦纳期的影响，以及对女孩报告的月经初潮年龄的影响。

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 (CYP3A41B), 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 CYP3A41B, 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.