Uncovering the complex relationship between pre-eclampsia, preterm birth and cerebral palsy

Pre-eclampsia is a leading cause of preterm birth, which is strongly associated with cerebral palsy (CP). However, there is controversy about whether pre-eclampsia is associated with increased risk of CP. We evaluated the association between pre-eclampsia and CP in 122,476 mother-child pairs insured by the South Carolina Medicaid programme, with births between 1996 and 2002. Prenatal billing records were linked to the children's Medicaid billing records after birth until December 2008. The odds of CP were modelled using logistic regression with generalised estimating equations. There were 337 children (0.28%) diagnosed with CP by at least two different health care providers, and 4226 (3.5%) women were diagnosed with pre-eclampsia at least twice during pregnancy. Children whose mothers had pre-eclampsia were almost twice as likely to have CP compared with children of mothers without pre-eclampsia [odds ratio (OR)=1.94, 95% confidence interval (CI) 1.25, 2.97]. The association was only significant for pre-eclampsia diagnosed prior to 37 weeks' gestation. Full term (gestational age ≥ 37 weeks) infants whose mothers were diagnosed with pre-eclampsia prior to 37 weeks had increased odds of CP compared with full term children whose mothers did not have pre-eclampsia (OR=3.41, 95% CI 1.40, 8.31). Preterm infants whose mothers had pre-eclampsia were at significantly increased risk of CP compared with full term infants whose mothers did not have pre-eclampsia (OR=5.88, 95% CI 3.40, 10.17). The greatest risk for CP was in preterm infants whose mothers did not have pre-eclampsia (OR=8.12, 95% CI 6.49, 10.17 compared with full term infants without exposure to pre-eclampsia). We conclude that pre-eclampsia with onset before 37 weeks' gestation is a significant risk factor for CP. Some of the association is probably attributable to high risk of preterm birth because of early pre-eclampsia, while a 'direct' effect of pre-eclampsia on fetal brain development also seems likely.