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.
