Abstract

Objective To test the hypothesis that pre-eclampsia is a risk factor for cerebral palsy mediated through preterm birth and being born small for gestational age.

Design Population based cohort study.

Setting Clinical data from the Norwegian Cerebral Palsy Registry were linked with perinatal data prospectively recorded by the Medical Birth Registry of Norway.

Participants All singleton babies who survived the neonatal period during 1996-2006 (849 children with cerebral palsy and 616 658 control children).

Main outcome measures Cerebral palsy and cerebral palsy subtypes.

Results Children exposed to pre-eclampsia had an excess risk of cerebral palsy (unadjusted odds ratio 2.5, 95% confidence interval 2.0 to 3.2) compared with unexposed children. Among children born at term (≥37 weeks), exposure to pre-eclampsia was not associated with an excess risk of cerebral palsy in babies not born small for gestational age (1.2, 0.7 to 2.0), whereas children exposed to pre-eclampsia and born small for gestational age had a significantly increased risk of cerebral palsy (3.2, 1.5 to 6.7). Non-small for gestational age babies born very preterm (<32 weeks) and exposed to pre-eclampsia had a reduced risk of cerebral palsy compared with unexposed children born at the same gestational age (0.5, 0.3 to 0.8), although the risk was not statistically significantly reduced among children exposed to pre-eclampsia and born small for gestational age (0.7, 0.4 to 1.3). Exposure to pre-eclampsia was not associated with a specific cerebral palsy subtype.

Conclusions Exposure to pre-eclampsia was associated with an increased risk of cerebral palsy, and this association was mediated through the children being born preterm or small for gestational age, or both. Among children born at term, pre-eclampsia was a risk factor for cerebral palsy only when the children were small for gestational age.

Discussion

In this study we found that pre-eclampsia was associated with an increased risk of cerebral palsy and that the excess risk was mainly mediated through preterm birth, but also through being born small for gestational age. Exposed children born at term as non-small for gestational age did not have an excess risk of cerebral palsy and we did not find that a specific cerebral palsy subtype was more common in children exposed to pre-eclampsia than not exposed. Thus we were not able to find evidence for a direct effect of pre-eclampsia on the risk of cerebral palsy.

What is already known on this topic

• Pre-eclampsia is a frequent cause of preterm birth and being born small for gestational age, both of which are known risk factors for cerebral palsy
• Observational studies have shown conflicting results with respect to whether pre-eclampsia is a risk factor for cerebral palsy
• Pre-eclampsia is a risk factor for cerebral palsy mainly mediated through preterm birth and being small for gestational age
• Among term born children exposed to pre-eclampsia only those born small for gestational age had an excess risk of cerebral palsy
• Pre-eclampsia was not associated with specific subtypes of cerebral palsy

What this study adds

Source: BMJ