Pubertal study of offspring of preeclamptics and normote

先兆子痫和正常子代的青春期研究

• 批准号: 7064517
• 负责人: Michele Robin Forman
• 金额: --
• 依托单位: DIVISION OF BASIC SCIENCES - NCI
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/7064517
• 关键词: Scandinavian country; adolescence (12-20); adult human (21+); androgens; blood pressure; body physical characteristic; breast neoplasms; cancer risk; child physical development; early experience; epidemiology; estrogens; female; genetic polymorphism; hormone regulation /control mechanism; hormone related neoplasm /cancer; human population study; human puberty; human subject; male; menstrual cycle; middle childhood (6-11); preeclampsia; pregnancy; prostate neoplasms

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.

先兆子痫是一种以妊娠期蛋白尿和高血压为特征的疾病。与血压正常的母亲和后代相比，在怀孕期间被诊断患有先兆子痫的妇女及其女儿患乳腺癌的风险较低，而他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征是激素水平升高，如雄激素、硫酸脱氢表雄酮（DHEAS），在动物研究中对乳腺癌具有保护作用，而在人类研究中雌激素和IGF-1水平较低与风险降低相关。事实上，类似的激素模式（较高的DHEAS水平和较低的IGF-I水平）出现在先兆子痫（比正常血压）妊娠的新生儿脐带血。此外，先兆子痫的后代中小于胎龄儿（SGA）的风险是血压正常妊娠的四倍; SGA可能会降低患相同癌症的风险。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，儿童期的生长速度、青春期和青春期的早期生长高峰以及生殖发育的早期指标（如月经初潮）与乳腺癌风险增加有关。此外，细胞色素P450 3A 4（CYP 3A 41 B）的高活性遗传变异，主要在睾酮catastrophic，强烈相关的青春期开始时的年龄。本研究的目的是确定：坦纳期，激素谱，CYP 3A 41 B的遗传变异，以及10-10.5岁和13-13.5岁时的人体测量状态在先兆子痫和血压正常妊娠的后代中是否不同;两组妊娠的女儿报告的初潮年龄是否不同;以及与血压正常的妇女相比，先前诊断为先兆子痫的非妊娠状态的妇女是否具有较低的雌激素水平和较高的雄激素水平。这样的研究有可能弥合差距，了解为什么这种情况与乳腺癌和男性激素癌症的风险降低有关。这将是第一项研究，以遵循307名妇女谁是连续诊断为先兆子痫和两套血压正常的控制（N = 619）谁生了一个单胞胎从1993年1月至1995年12月在罗加兰中心医院在斯塔万格，挪威。对母亲及其子女的跟踪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岁时的体重和身高的间隔测量值，以检查儿童早期生长是否会改变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坦纳分期以及女孩月经初潮年龄的影响。