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Chorioamnionitis as a Risk Factor for Cerebral Palsy:  A Meta-analysis

Yvonne W. Wu, MD, MPH; John M. Colford, Jr, MD, PhD
JAMA. 2000;284(11):1417-1424. doi:10.1001/jama.284.11.1417.
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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.

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Figure. Chorioamnionitis and Cerebral Palsy (CP) or Cystic Periventricular Leukomalacia (cPVL) in Premature Infants
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Asterisks indicate that P values refer to the test of homogeneity. This test evaluates the likelihood that differences between studies are due to random variation alone. If P>.10, the studies are considered homogeneous, and variability in study results is more likely to be due to chance alone.

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