Early and late onset pre-eclampsia and small for gestational age risk in subsequent pregnancies

BACKGROUND: Pre-eclampsia shares pathophysiology with intrauterine growth restriction. OBJECTIVE: To investigate whether delivery of a small for gestational age (SGA) infant in the 1(st) pregnancy increases the risk of early and late onset pre-eclampsia in the 2(nd) pregnancy. Conversely, we investigated whether pre-eclampsia in the 1(st) pregnancy impacts SGA risk in the 2(nd) pregnancy. STUDY DESIGN: We studied a cohort from the Dutch Perinatal Registry of 265,031 women with 1(st) and 2(nd) singleton pregnancies who delivered between 2000 and 2007. We analyzed 2(nd) pregnancy risks of early and late onset pre-eclampsia—defined by delivery before or after 34 gestational weeks—as well as SGA below the 5(th) and between the 5(th) and 10(th) percentiles risks with multivariable logistic regressions. Interaction terms between 1(st) pregnancy hypertension, pre-eclampsia, SGA, and delivery before or after 34 gestational weeks were included in the regressions. RESULTS: First pregnancy early onset pre-eclampsia increased risk of SGA <5(th) percentile (OR 2.1, 95% CI 1.7–2.7) in the 2(nd) pregnancy. Late onset pre-eclampsia increased the SGA <5(th) percentile marginally (OR 1.1, 95% CI 1.0–1.3). In the absence of 1(st) pregnancy hypertensive disorder, women who delivered an SGA infant in their 1(st) pregnancy were at increased risk of 2(nd) pregnancy late onset pre-eclampsia (SGA <5(th): OR 2.05, 95% CI 1.58–2.66; SGA 5–10(th): OR 1.39, 95% CI 1.01–1.93). Early onset 2(nd) pregnancy pre-eclampsia risk was also increased, but this was only statistically significant for women who delivered an SGA infant below the 5(th) percentile in the 1(st) pregnancy (SGA <5(th): OR 2.44, 95% CI 1.19–5.00; SGA 5–10(th): OR 1.69, 95% CI 0.68–4.24;). CONCLUSION: Women with 1(st) pregnancy early onset pre-eclampsia have increased risk of SGA <5(th) percentile in the 2(nd) pregnancy. SGA in the 1(st) pregnancy increases pre-eclampsia risk in the 2(nd) pregnancy even in the absence of hypertensive disorders in the 1(st) pregnancy, although absolute risks remain low. These findings strengthen the evidence base associating intrauterine growth restriction with early onset pre-eclampsia.