Why is there a modifying effect of gestational age on risk factors for cerebral palsy?

Objective: To investigate risk factors for cerebral palsy in relation to gestational age. Design: Three case-control studies within a geographically defined cohort. Setting: The former Oxfordshire Health Authority. Participants: A total of 235 singleton children with cerebral palsy not of postnatal origin, born between 1984 and 1993, identified from the Oxford Register of Early Childhood Impairment; 646 controls matched for gestation in three bands: <= 32 weeks; 33-36 weeks; >= 37 weeks. Results: Markers of intrapartum hypoxia and infection were associated with an increased risk of cerebral palsy in term and preterm infants. The odds ratio (OR) for hypoxia was 12.2 (95% confidence interval 1.2 to 119) at <= 32 weeks and 146 (7.4 to 3651) at >= 37 weeks. Corresponding ORs for neonatal sepsis were 3.1 (1.8 to 5.4) and 10.6 (2.1 to 51.9). In contrast, pre-eclampsia carried an increased risk of cerebral palsy at >= 37 weeks (OR 5.1 (2.2 to 12.0)) but a decreased risk at <= 32 weeks (OR 0.4 (0.2 to 1.0)). However, all infants <= 32 weeks with maternal pre-eclampsia were delivered electively, and their risk of cerebral palsy was no lower than that of other electively delivered <= 32 week infants (OR 0.9 (0.3 to 2.7)). Nearly 60% of <= 32 week controls were delivered after spontaneous preterm labour, itself an abnormal event. Conclusion: Inflammatory processes, including pre-eclampsia, are important in the aetiology of cerebral palsy. The apparent reduced risk of cerebral palsy associated with pre-eclampsia in very preterm infants is driven by the characteristics of the gestation matched control group. Use of the term "protective" in this context should be abandoned.