Who Is at Risk for Preeclampsia? Risk Factors for Developing Initial Preeclampsia in a Subsequent Pregnancy

Background: The incidence of preeclampsia, which may cause significant maternal and perinatal morbidity, has risen in recent years, therefore it is critical to identify women at risk for preeclampsia. We aimed to identify risk factors in the first pregnancy (not complicated by preeclampsia) for preeclampsia in the subsequent pregnancy.

Methods: A retrospective population-based nested case-control study was conducted, including all women with first (P1) and second (P2) singleton consecutive deliveries. Women who had experienced preeclampsia in their first pregnancy were excluded. Cases were defined as women with preeclampsia in their second pregnancy, and were compared to the controls, defined as women without this diagnosis in second pregnancy. Characteristics and complications of the first pregnancy were compared between cases and controls, and multivariable regression models were used to study the association between pregnancy complications (in the first pregnancy) and preeclampsia (in the subsequent pregnancy), while adjusting for confounders.

Results: A total of 40,673 women were included in the study, 1.5% of second pregnancies were diagnosed with preeclampsia ( = 627, i.e., Cases). Cases, as compared to controls were older in their 1st pregnancy, with longer inter-pregnancy interval, and were more likely to have the following complications in their first pregnancy: preterm delivery (15.0% vs. 7.7%), low birthweight (17.9% vs. 10.3%), perinatal mortality (3.2% vs. 1.1%), and gestational diabetes (7.0% vs. 2.7%). In the multivariable model, adjusted for maternal age, obesity and inter-pregnancy interval, either one of these first pregnancy complications were independently associated with an increased risk for preeclampsia (adjusted OR for either of first pregnancy complication =1.73; 95% CI 1.37-2.14, <0.001), and the risk was greater for each additional complication (adjusted OR for ≥2 risk factors =3.54; 95% CI 2.28-5.52, < 0.001).

Conclusions: Complications in first pregnancy, including preterm delivery, perinatal mortality and gestational diabetes, are risk factors for primary preeclampsia in second pregnancy. First pregnancy may serve as a window of opportunity to identify women at risk for future preeclampsia and other morbidities later in life.