The risk that a woman who had pre-eclampsia would deliver a child with cerebral palsy (CP) was higher if the baby was born prematurely, was small at birth, or both, a population based cohort study found.
Overall, children whose mothers had pre-eclampsia while pregnant had a higher risk of CP (unadjusted OR 2.5, 95% CI 2.0-3.2) than children whose mothers did not have the condition, researchers reported online in BMJ.
Babies of pre-eclamptic mothers born at term (≥37 weeks) but small for gestational age -- defined as the 10th centile -- were at an even higher risk for CP (OR 3.2, 95% CI 1.5-6.7). And those born moderately pre-term -- between 32 and 36 weeks -- had a nearly five-fold excess risk of CP compared with children born at term following normal pregnancies (OR 4.64, 95% CI 2.98-7.23), said study author Kristin Melheim Strand, of the Norwegian University of Science and Technology in Trondheim.
Babies exposed to pre-eclampsia and born at less than 32 weeks but at normal size for their gestational age were at reduced risk of CP compared with unexposed babies born at the same gestational age (OR 0.5, 95% CI 0.3-0.8). But the reduction lost statistical significance if the babies were small for their gestational age (0.7 OR, 95% CI 0.4-1.3).
Exposed babies born at term and at appropriate size for their gestational age were not associated with higher risk for CP (OR 1.2, 95% CI 0.7-2.0).
The study was based on data on all babies born in Norway between 1996 and 2006, and included 849 children with cerebral palsy and 616,658 control children. Data came from the Norwegian Cerebral Palsy Registry and the Medical Birth Registry of Norway.
Pre-eclampsia is a pregnancy complication that affects 3% to 5% of pregnant women. It typically causes hypertension and proteinuria after 20 weeks of gestation. It contributes "substantially to prematurity, perinatal morbidity and mortality," Strand and her co-authors wrote.
The cause of cerebral palsy is still unknown, "although several factors, including preterm birth and low birth weight for gestation, are associated with excess risk," they wrote.
Placental dysfunction is common in pre-eclampsia before 34 weeks and can compromise blood supply, restrict fetal growth, cause chronic hypoxemia and possibly brain damage, the authors wrote. "Hence it is possible that pre-eclampsia could be a risk factor for cerebral palsy."
In the study, "excess risk was mainly mediated through preterm birth, but also through being born small for gestational age," they said.
"Our study might indicate that early signs of a smaller than average fetus should be taken into account when delivery of pre-eclamptic pregnancies are considered," said Strand. "However, further studies would have to confirm these findings before they can have any direct clinical implications. Hopefully our study will stimulate further research."
There were potential limitations to the study. For example, 381 children born with cerebral palsy during the study period were not included in the cerebral palsy register. However "comparing the children with cerebral palsy who were excluded and included in our final study group revealed no differences in cerebral palsy subtypes or severity," wrote the authors.
Pre-eclampsia could have been misdiagnosed in the medical birth registry, although the authors considered it unlikely that misclassification would explain their results. Milder cases of pre-eclampsia might also have been missed, which could have led to an underestimation of the risk of CP associated with pre-eclampsia in children born at term.
Finally, the researchers used small-for-gestational-age as a proxy for fetal growth restriction. Their definition of "small" was based on the 10th centile, which "even when adjusted for parity and sex, is liable to include constitutionally small children in addition to those who are growth restricted," said the authors.
Using a lower cutoff, they wrote, might have reduced misclassification.
The authors received no financial support from any organization for this study, and declared no financial relationships relevant to this work.
- Reviewed by Zalman S. Agus, MD Emeritus Professor, Perelman School of Medicine at the University of Pennsylvania and Dorothy Caputo, MA, BSN, RN, Nurse Planner