Preeclampsia and other circulatory diseases during pregnancy : etiological aspects and impact on female offspring

Abstract: The aims of this thesis were to investigate and compare environmental effects on the liability of developing preeclampsia and gestational hypertension; to estimate the relative importance of genetic and environmental effects on the liability of developing preeclampsia and gestational hypertension; to assess the effect of childbearing on the risk of circulatory diseases; and to explore the effect of preeclampsia on the female offspring anthropometry in early adulthood. We used the Swedish Birth Register to compare the effect of maternal diabetes, multiple birth, smoking, place of birth and obesity, on the liability of developing preeclampsia and gestational hypertension among 10,666 primiparous women. Maternal diabetes, multiple birth and obesity were all associated with increased risk of preeclampsia and gestational hypertension. Maternal smoking and non-Nordic maternal place of birth were associated with decreased risk of preeclampsia and gestational hypertension. The similarities in risk factor patterns may indicate similarities in the biological mechanisms underlying the two conditions. To estimate the relative importance of genetic and environmental effects on the liability of developing preeclampsia and gestational hypertension, we used the Swedish Twin Register linked to the Medical Birth Register and used quantitative genetic analyses of pregnancies of 917 monozygotic and 1,199 dizygotic twin pairs. For preeclampsia, we found that genetic and environmental effects are of about equal importance. For gestational hypertension, the estimates of heritability and non-shared environmental effect were 0.24 and 0.76, respectively. When we considered both diseases together as pregnancy-induced hypertension with different degrees of severity, the estimates of heritability and non-shared environmental effect were 0.47 and 0.53, respectively. We assessed the effect of childbearing on the risk of circulatory diseases by a cross-linkage of the Swedish Medical Birth Register and the Inpatient Register and analyzed 1,003,489 deliveries among 654,957 women. Compared with non-pregnant and early pregnant period, the risks of venous thromboembolic diseases were increased in third trimester, peaked during three days around delivery (relative risk 80) and declined during the puerperium. For arterial diseases (subarachnoid hemorrhage, intracerebral hemorrhage and cerebral infarction), there was, compared with non-pregnant and early pregnant period, a more than 30-fold increased risk during three days around delivery, which declined during the puerperium. We also studied the effects of maternal characteristics on the risk of stroke and pulmonary embolism during the third trimester of pregnancy, around, and after delivery. Although preeclampsia, multiple birth and Cesarean section were all associated with highly increased risk of both pulmonary embolism and stroke, these complications did not explain the increased risks related to pregnancy. We explored the effect of intrauterine exposure to preeclampsia on the anthropometry in early adulthood among females. In all 230 young women exposed to preeclampsia in utero and 359 non-exposed women were included. In young adulthood there were no differences in height, body-mass index (BMI), waist to hip ratio or age at menarche between preeclampsia exposed female offspring as compared to non-exposed.