Author Affiliations: Departments of Neurology and Pediatrics, University of California, San Francisco (Dr Wu); and the Division of Epidemiology, School of Public Health, University of California, Berkeley (Dr Colford).
Context Chorioamnionitis has been implicated in the pathogenesis of cerebral
palsy, but most studies have not reported a significant association. Cystic
periventricular leukomalacia (cPVL) is believed to be a precursor of cerebral
palsy in preterm infants.
Objectives To determine whether chorioamnionitis is associated with cerebral palsy
or cPVL and to examine factors that may explain differences in study results.
Data Sources Searches of MEDLINE (1966-1999), Index Medicus (1960-1965), Doctoral
Dissertation Abstracts On-Line (1861-1999), bibliographies, and online conference
proceedings (1999) were performed for English-language studies with titles
or abstracts that discussed prenatal risk factors for cerebral palsy or cPVL.
Study Selection Of 229 initially identified publications, meta-analyses were performed
on studies that addressed the association between clinical (n = 19) or histologic
(n = 7) chorioamnionitis and cerebral palsy or cPVL in both preterm and full-term
infants. Inclusion criteria were: presence of appropriate exposure and outcome
measures, case-control or cohort study design, and provision of sufficient
data to calculate relative risks (RRs) or odds ratios with 95% confidence
intervals (CIs). Studies evaluating risk of cerebral palsy following maternal
fever, urinary tract infection, or other maternal infection were collected,
but not included in the meta-analysis.
Data Extraction Information from individual studies was abstracted using standardized
forms by 2 independent observers blinded to authors' names, journal titles,
and funding sources.
Data Synthesis Using a random effects model, clinical chorioamnionitis was significantly
associated with both cerebral palsy (RR, 1.9; 95% CI, 1.4-2.5) and cPVL (RR,
3.0; 95% CI, 2.2-4.0) in preterm infants. The RR of histologic chorioamnionitis
and cerebral palsy was 1.6 (95% CI, 0.9-2.7) in preterm infants, and histologic
chorioamnionitis was significantly associated with cPVL (RR, 2.1; 95% CI,
1.5-2.9). Among full-term infants, a positive association was found between
clinical chorioamnionitis and cerebral palsy (RR, 4.7; 95% CI, 1.3-16.2).
Factors explaining differences in study results included varying definitions
of clinical chorioamnionitis, extent of blinding in determining exposure status,
and whether individual studies adjusted for potential confounders.
Conclusion Our meta-analysis indicates that chorioamnionitis is a risk factor for
both cerebral palsy and cPVL.
Wu YW, Colford, Jr JM. Chorioamnionitis as a Risk Factor for Cerebral Palsy: A Meta-analysis. JAMA. 2000;284(11):1417–1424. doi:10.1001/jama.284.11.1417
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