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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.

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