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

Abstract

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.