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