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Maternal Infections during Pregnancy and Cerebral Palsy: A Population-based Cohort Study

Authors

  • Jessica E. Miller,

    Corresponding author
    1. Department of Epidemiology, Fielding School of Public Health, University of California, Los Angeles, CA
    • Correspondence:

      Jessica E. Miller, Department of Epidemiology, UCLA Fielding School of Public Health, 650 Charles E Young Drive South, Los Angeles, CA 90095-1772, USA.

      E-mail: jemille@ucla.edu

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  • Lars Henning Pedersen,

    1. Department of Obstetrics and Gynecology, Institute of Clinical Medicine, Aarhus University, Aarhus, Denmark
    2. Department of Public Health, Section for Epidemiology, Aarhus University, Aarhus, Denmark
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  • Elani Streja,

    1. Department of Epidemiology, Fielding School of Public Health, University of California, Los Angeles, CA
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  • Bodil H. Bech,

    1. Department of Public Health, Section for Epidemiology, Aarhus University, Aarhus, Denmark
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  • Marshalyn Yeargin-Allsopp,

    1. National Center on Birth Defects and Developmental Disabilities, Centers for Disease Control and Prevention, Atlanta, GA
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  • Kim Van Naarden Braun,

    1. National Center on Birth Defects and Developmental Disabilities, Centers for Disease Control and Prevention, Atlanta, GA
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  • Diana E. Schendel,

    1. National Center on Birth Defects and Developmental Disabilities, Centers for Disease Control and Prevention, Atlanta, GA
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  • Deborah Christensen,

    1. National Center on Birth Defects and Developmental Disabilities, Centers for Disease Control and Prevention, Atlanta, GA
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  • Peter Uldall,

    1. The Danish Cerebral Palsy Registry, National Institute of Public Health, University of Southern Denmark, Copenhagen, Denmark
    2. Pediatric Department, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
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  • Jørn Olsen

    1. Department of Epidemiology, Fielding School of Public Health, University of California, Los Angeles, CA
    2. Department of Public Health, Section for Epidemiology, Aarhus University, Aarhus, Denmark
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Abstract

Background

Cerebral palsy (CP) is a common motor disability in childhood. We examined the association between maternal infections during pregnancy and the risk of congenital CP in the child.

Methods

Liveborn singletons in Denmark between 1997 and 2003 were identified from the Danish National Birth Registry and followed from 1 year of life until 2008. Redemption of antibiotics from the National Register of Medicinal Product Statistics and maternal infections reported by the National Hospital Register were used as markers of maternal infection during pregnancy. CP diagnoses were obtained from the Danish Cerebral Palsy Registry. Adjusted hazard ratio (HR) and 95% confidence interval (CI) were estimated by Cox proportional hazard models.

Results

Of the 440 564 singletons with follow-up data, 840 were diagnosed with congenital CP. Maternal genito-urinary tract infections (HR 2.1, 95% CI 1.4, 3.2) were associated with CP in all births, in term births (HR 1.9, 95% CI 1.1, 3.2), in children with spastic CP (HR 2.1, 95% CI 1.4, 3.3), and among first-born children (HR 1.9, 95% CI 1.4, 3.3). Overall, we found associations between redeemed nitrofurantoin (HR 1.7, 95% CI 1.1, 2.8) and CP. Among trimester-specific exposures, CP risk was associated with prescriptions redeemed in the first trimester for any antibacterials, beta-lactam antibacterials, and nitrofurantoin, an antibiotic commonly used to treat lower urinary tract infection, and genito-urinary tract infections in the third trimester.

Conclusion

Genito-urinary tract infections and antibiotic use during pregnancy were associated with increased risks of CP, indicating that some maternal infections or causes of maternal infections present in prenatal life may be part of a causal pathway leading to CP.

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