Preeclampsia Is a Family Affair
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The risk for preeclampsia during pregnancy may have its roots in the preeclamptic pregnancies of the mother and father when they were born a generation earlier.
Genes inherited by an expectant mother and those that she and the father pass on to the fetus appear to increase the risk that she will have a pregnancy complicated by preeclampsia, reported epidemiologist Rolv Skjaerven of the University of Bergen here and colleagues at other institutions.
In a study of data on nearly 730,000 mother-child and father-child groups, they found that daughters of women who had preeclampsia were more than twice as likely as others to have preeclampsia themselves. Men born after a preeclamptic pregnancy were about 50% more likely to father a preeclamptic pregnancy as well. Preeclampsia occurs in about 3% to 5% of all pregnancies.
Results of the population-based cohort study were published today in an early online edition of the British Medical Journal.
“Both maternal and paternal factors contribute to the risk of preeclampsia,” the investigators wrote. “The risk through affected mothers is higher, presumably because these mothers carry susceptibility genes and also transmit independent genetic risk factors to their fetus. The risk through affected fathers is lower because fathers transmit only fetal risk factors.”
They also found that sisters who were not themselves born after a pregnancy complicated by preeclampsia had twice the risk of the complication compared with women who had no family history of it.
“Also, the differences that we observed between sisters and brothers suggest that genes that determine maternal susceptibility to preeclampsia differ from the paternal genes that may trigger preeclampsia through the fetus,” Dr. Skjaerven and colleagues wrote. “Finally, familial associations are stronger for the clinically more severe types of preeclampsia.”
The goal of the study was to evaluate the effect on risk of preeclampsia of genes that work through the mother, and as well as genes passed on to the fetus by the father.
To do this, the authors drew on linked generational data from the medical birth registry of Norway for births occurring between 1967 and 2003. They identified a total of 438,597 mother-offspring units and 286,945 father-offspring units. The primary outcome for the study was preeclampsia occurring among women in the second generation.
They found that for the daughters of women who had preeclampsia during pregnancy, the odds ratio that they would experience the complication in their own pregnancies was 2.2 (95% confidence interval, 2.0 to 2.4) compared with other women.
Men born after a pregnancy complicated by preeclampsia had a 50% greater risk that they would father a preeclamptic pregnancy (OR 1.5, 95% CI, 1.3 to 1.7).
Women who were not themselves born after a pregnancy in which preeclampsia occurred but had sisters or brothers who were had a two-fold risk of developing the complication in their own pregnancies (OR 2.0, 95% CI, 1.7 to 2.3).
“Women and men born after preeclamptic pregnancies were more likely to trigger severe preeclampsia 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,” the authors noted.
The authors hypothesized that women who are born after a preeclamptic pregnancy may carry genes for susceptibility to the condition from their mothers, and that their pregnancies may be affected by genes passed on to the fetus from either parent.
“For men who were born after an affected pregnancy, an increased risk of fathering a preeclamptic pregnancy can be attributed solely to paternal factors,” Dr. Skjaerven and colleagues wrote. “Brothers who were born after a pregnancy without preeclampsia would have a low probability of carrying fetal risk genes, which is confirmed by the near baseline risk of preeclampsia among pregnancies they father.”
Source: British Medical Journal
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