Recurrence of pre-eclampsia across generations: exploring fetal and maternal genetic components in a population based cohort.

OBJECTIVES To assess the impact on risk of pre-eclampsia of genes that work through the mother, and genes of paternal origin that work through the fetus. DESIGN Population based cohort study. SETTING Registry data from Norway. PARTICIPANTS Linked generational data from the medical birth registry of Norway (1967-2003): 438,597 mother-offspring units and 286,945 father-offspring units. MAIN OUTCOME MEASURES Pre-eclampsia in the second generation. RESULTS The daughters of women who had pre-eclampsia during pregnancy had more than twice the risk of pre-eclampsia themselves (odds ratio 2.2, 95% confidence interval 2.0 to 2.4) compared with other women. Men born after a pregnancy complicated by pre-eclampsia had a moderately increased risk of fathering a pre-eclamptic pregnancy (1.5, 1.3 to 1.7). Sisters of affected men or women, who were themselves born after pregnancies not complicated by pre-eclampsia, also had an increased risk (2.0, 1.7 to 2.3). Women and men born after pre-eclamptic pregnancies were more likely to trigger severe pre-eclampsia in their own (or their partner's) pregnancy (3.0, 2.4 to 3.7, for mothers and 1.9, 1.4 to 2.5, for fathers). CONCLUSIONS Maternal genes and fetal genes from either the mother or father may trigger pre-eclampsia. The maternal association is stronger than the fetal association. The familial association predicts more severe pre-eclampsia.