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Chorioamnionitis and Cerebral Palsy: A Meta-Analysis

Shatrov, Jobe G. BSc; Birch, Samuel C. M. BSc; Lam, Lawrence T. PhD; Quinlivan, Julie A. MB, BS, PhD; McIntyre, Sarah MPS; Mendz, George L. PhD

doi: 10.1097/AOG.0b013e3181e90046

OBJECTIVE: To examine the relationships between clinical or histological chorioamnionitis and cerebral palsy using a meta-analysis approach.

DATA SOURCES: A systematic review of the literature appeared in PubMed between 2000 and 2009 was conducted using the search terms “cerebral palsy” and “infection,” with broad-scope variations in terminology of “white matter damage,” “periventricular leukomalacia,” “cystic periventricular leukomalacia,” “chorioamnionitis,” “intrauterine infection,” “intraventricular hemorrhage,” “funisitis,” “fetal inflammatory response,” “early neonatal sepsis,” “neurological impairment,” “virus,” “bacteria,” “fungi,” and “protozoa,” with variations of suffixes (eg, “viral,” “bacterial,” “fungal,” “protozoan,” etc), and “urinary tract infection,” “bacterial vaginosis,” “bacteriuria,” and “cytokines.” The related key words “gestational age,” “small for gestational age,” “preterm,” and “low birth weight” also were added to the search terms. Only studies published in English were included.

METHODS: Three hundred eight articles were retrieved and systematically reviewed independently by two authors. Application of four inclusion criteria led to 15 studies being considered for data abstraction. An exposure was considered relevant if it met the established criteria for clinical or histological chorioamnionitis. The outcome was a diagnosis of cerebral palsy in accordance with established criteria.

RESULTS: The data were abstracted onto standard forms, correlated according to eight characteristics, and tabulated. Twelve of the 15 studies contained information on the association between clinical chorioamnionitis and cerebral palsy, and eight studies included information on the association between histological chorioamnionitis and cerebral palsy. The results indicated that there were significant associations between clinical chorioamnionitis or histological chorioamnionitis and cerebral palsy, for clinical chorioamnionitis (χ12=13.91; P<.001) with a pooled odds ratio of 2.42 (95% confidence interval 1.52–3.84), and for histological chorioamnionitis (χ12=6.86; P=.009) with a pooled odds ratio of 1.83 (95% confidence interval, 1.17–2.89). The data suggested increased risks of 140% and 80% for neonates exposed to clinical chorioamnionitis or histological chorioamnionitis, respectively.

CONCLUSION: The significant association of clinical or histological chorioamnionitis with cerebral palsy suggested that clinical strategies to prevent or reduce chorioamnionitis would lead to a reduction in cerebral palsy. The culture techniques currently used to diagnose the presence of pathogenic microorganisms during pregnancy need to improve, both in their methodology and in the length of time they require.

A review of publications from 2000 to 2009 demonstrates strong correlation between clinical and histological chorioamnionitis and the development of cerebral palsy.

From School of Medicine, Sydney, The University of Notre Dame Australia; and Cerebral Palsy Institute, Darlinghurst, New South Wales, Australia.

Supported by a Cerebral Palsy Institute grant to Drs. Mendz and Quinlivan, and by RUSC research scholarships to Jobe G. Shatrov and Samuel C. M. Birch.

Corresponding author: Professor George L. Mendz, School of Medicine, Sydney, The University of Notre Dame Australia, 160 Oxford Street, Darlinghurst, NSW 2010, Australia; e-mail:

Financial Disclosure The authors did not report any potential conflicts of interest.

© 2010 by The American College of Obstetricians and Gynecologists. Published by Wolters Kluwer Health, Inc. All rights reserved.