Prior studies have shown significantly higher concentrations of maternal anti-angiogenic factors [17
] and androgens (A4 and T) [32
] in women with preeclampsia compared to those with uncomplicated pregnancies. Our results are consistent with prior studies that were primarily conducted in predominantly Caucasian populations [17
]. In addition, including maternal A4 and the anti-angiogenic factors simultaneously in the regression models did not alter the significance of the results, suggesting that both may be independently associated with preeclampsia.
In the cord samples, we found non-significantly lower levels of E3 and IGF-1 in samples from women with preeclampsia. Similar results have been reported in studies of Caucasian populations [36
]. When the cord analyses were restricted to only African-Americans, IGF1 was significantly lower in preeclamptic than in uncomplicated pregnancy.
This study has some limitations. The samples were collected at delivery and measurements may not represent analyte concentrations earlier in pregnancy. Accounting for mode of delivery, however, did not alter the associations suggesting that the stress of a vaginal delivery did not affect concentrations. The CV for maternal sEng measures was high (29%), yet there was such a large difference in the mean sEng levels between the two groups that a significantly higher concentration was detected in maternal samples from preeclamptic pregnancies. It is likely that the real mean differences are even greater than reported here.
The strengths of the study include a large sample of African-Americans, a population that despite its higher risk has been less characterized than Caucasians with regard to concentrations of biomarkers in preeclampsia. To our knowledge, this also is the most comprehensive set of angiogenic factors, steroid sex hormones, and components of the IGF axis measured in both maternal and cord samples in a single preeclampsia study. This provided us with greater opportunity to explore both the in utero environment and maternal circulation in this condition.
The altered angiogenic balance and increased androgen concentrations reported here may also have implications for later health outcomes in the mother. Mothers with a history of preeclampsia and the female offspring from these pregnancies are at reduced risk of developing breast cancer [6
] and mothers (and possibly offspring) are at higher risk of cardiovascular disease later in life [1
] when compared with mothers and offspring from normal pregnancies. Studies that have shown these associations of preeclampsia with later chronic disease risk have focused on either exclusively or predominantly Caucasian populations and did not stratify risk estimates by race/ethnicity [1
]. This is particularly surprising given the higher prevalence of risk factors for both preeclampsia and cardiovascular disease in African-American women [26
Currently there is debate as to whether preeclampsia initiates a long-lasting, altered vascular state that contributes to later health outcomes or alternatively, if women who are at higher risk of developing preeclampsia also have altered chronic disease susceptibility because of underlying risk factors in common across the conditions [2
]. A prior study evaluating the association of preeclampsia (or gestational hypertension) with reduced risk of breast cancer reported that the reduction in risk was even stronger among women who had male offspring (relative risk 0.62, 95% CI, 0.47–0.82 for son compared to relative risk 0.75, 95% CI, 0.62–0.91 for whole population) [41
]. This result was interpreted to “support the hypothesis that a protective effect of pre-eclampsia on breast cancer risk could originate from the particular pregnancy, rather than indicating an underlying biological trait that is protective against breast cancer in women who develop pre-eclampsia [41
].” Additional studies focusing on predominantly non-Caucasian populations and/or that are large enough to explore the analyses by race and/or offspring gender may provide more insight into the relationship of preeclampsia with chronic disease risk.