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

¹ National Perinatal Epidemiology Unit, Old Road, Headington, Oxford OX3 7LF, UK and John Radcliffe Hospital, Headley Way, Oxford OX3 9DU, UK
² Department of Primary Health Care, Old Road, Headington, Oxford OX3 7LF, UK
³ United Bristol Hospital Trust, formerly John Radcliffe Hospital, Headley Way, Oxford OX3 9DU, UK
⁴ John Radcliffe Hospital, Headley Way, Oxford OX3 9DU, UK
⁵ London School of Hygiene and Tropical Diseases, Keppel St, London WC1, UK

Correspondence to:
Correspondence to:
Dr Greenwood
Level 4, The Women’s Centre, John Radcliffe Hospital, Headley Way, Headington, Oxford OX3 9DU, UK; Catherine.Greenwood{at}orh.nhs.uk

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.

Abbreviations: CP, cerebral palsy; SGA, small for gestational age

Keywords: cerebral palsy; epidemiology; inflammation; pre-eclampsia

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