ABSTRACT: Preeclampsia recurs in individuals and clusters in families, but its heritable aspects are not thoroughly understood. Its heritability is estimated to be 30% to 55%; its etiology likely involves both maternal and paternal genetic factors along with environmental components. The current study was performed to investigate preeclampsia recurrence and associations between maternal and paternal family histories of preeclampsia and the risk for preeclampsia in the current pregnancy.
Using several Danish national registries, data on 1.4 million pregnancies were assessed. Early-, intermediate-, and late-onset preeclampsia were defined as occurring at less than 34 weeks, at 34 to 36 weeks, and at more than 36 weeks of gestation. All women who delivered 1 or more live singletons with a known gestational age at birth between 1978 and 2008 were included. The father and other family members were identified for each pregnancy, and maternal and paternal histories for preeclampsia were evaluated. Risk ratios for preeclampsia with onset in the specific risk periods were estimated. Analyses for the period of 34 to 36 weeks and more than 36 weeks of gestation considered only pregnancies that continued to and were free of preeclampsia until at least 34 weeks or 36 weeks. All risk ratios were adjusted for maternal age at birth and year of birth.
Of 1,377,479 pregnancies that resulted in live singleton births during the study period, 48,128 were complicated by preeclampsia, with 6639, 7570, and 33,919 instances of early-, intermediate-, and late-onset preeclampsia, respectively. Previous early-, intermediate-, or late-onset preeclampsia increased the risk for recurrent preeclampsia with the same timing of onset 25.2-fold (95% confidence interval [CI], 21.8–29.1), 19.7-fold (95% CI, 17.0–22.8), and 10.3-fold (95% CI, 9.85–10.9), respectively, compared with having no such history. A maternal family history of early-, intermediate-, or late-onset preeclampsia was associated with 2.15, 2.08, and 1.49 times the risk, respectively, of the corresponding form of preeclampsia compared with pregnancies in women with no family history of that type of preeclampsia. A history of early- or intermediate-onset preeclampsia in a female relative increased the risk for the corresponding form of preeclampsia by greater than 150% compared with the absence of such family histories. A history of late-onset preeclampsia in female relatives increased the risk for late-onset preeclampsia by 73%. Associations with preeclampsia in pregnancies fathered by male relatives had risks for early-, intermediate-, and late-onset preeclampsia increased by 78%, 45%, and 24%, respectively.
The risk for preeclampsia, especially early onset, was affected much less by a paternal family history of preeclampsia. Paternal family histories of intermediate- and late-onset preeclampsia were associated with 45% and 12% increases, respectively.
Previous preeclampsia was associated with a risk for preeclampsia in subsequent pregnancies that was substantially higher than the risk in women who had not had preeclampsia in prior pregnancies. This association was much stronger for early-onset preeclampsia than for preeclampsia with onset near term. A maternal family history of preeclampsia was associated with up to a 115% increase in preeclampsia risk, with the association strongest for early-onset preeclampsia. The timing of preeclampsia onset should be considered if preeclampsia heritability and etiology are to be thoroughly elucidated.
Department of Epidemiology Research, Statens Serum Institut, Copenhagen, Denmark