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Birth defects after maternal exposure to corticosteroids: Prospective cohort study and meta-analysis of epidemiological studies

Authors

  • Laura Park-Wyllie,

    1. Faculty of Pharmacy, University of Toronto, Toronto, Canada
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  • Paolo Mazzotta,

    1. Motherisk Program, Division of Clinical Pharmacology and Toxicology, Research Institute, Hospital for Sick Children, CIBC World Market Children's Miracle Chair in Child Health Research and University of Toronto, Toronto, Canada M5G 1X8
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  • Anne Pastuszak,

    1. Fetal Diagnosis and Treatment Centre, University of Toronto, Toronto, Canada
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  • Myla E. Moretti,

    1. Motherisk Program, Division of Clinical Pharmacology and Toxicology, Research Institute, Hospital for Sick Children, CIBC World Market Children's Miracle Chair in Child Health Research and University of Toronto, Toronto, Canada M5G 1X8
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  • Lizanne Beique,

    1. Faculty of Pharmacy, University of Toronto, Toronto, Canada
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  • Laura Hunnisett,

    1. Motherisk Program, Division of Clinical Pharmacology and Toxicology, Research Institute, Hospital for Sick Children, CIBC World Market Children's Miracle Chair in Child Health Research and University of Toronto, Toronto, Canada M5G 1X8
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  • Mark H. Friesen,

    1. Faculty of Pharmacy, University of Toronto, Toronto, Canada
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  • Sheila Jacobson,

    1. Motherisk Program, Division of Clinical Pharmacology and Toxicology, Research Institute, Hospital for Sick Children, CIBC World Market Children's Miracle Chair in Child Health Research and University of Toronto, Toronto, Canada M5G 1X8
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  • S. Kasapinovic,

    1. Motherisk Program, Division of Clinical Pharmacology and Toxicology, Research Institute, Hospital for Sick Children, CIBC World Market Children's Miracle Chair in Child Health Research and University of Toronto, Toronto, Canada M5G 1X8
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  • Debra Chang,

    1. Motherisk Program, Division of Clinical Pharmacology and Toxicology, Research Institute, Hospital for Sick Children, CIBC World Market Children's Miracle Chair in Child Health Research and University of Toronto, Toronto, Canada M5G 1X8
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  • Orna Diav-Citrin,

    1. Motherisk Program, Division of Clinical Pharmacology and Toxicology, Research Institute, Hospital for Sick Children, CIBC World Market Children's Miracle Chair in Child Health Research and University of Toronto, Toronto, Canada M5G 1X8
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  • David Chitayat,

    1. Department of Genetics, Toronto General Hospital, Toronto, Canada
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  • Irena Nulman,

    1. Motherisk Program, Division of Clinical Pharmacology and Toxicology, Research Institute, Hospital for Sick Children, CIBC World Market Children's Miracle Chair in Child Health Research and University of Toronto, Toronto, Canada M5G 1X8
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  • Thomas R. Einarson,

    1. Faculty of Pharmacy, University of Toronto, Toronto, Canada
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  • Gideon Koren

    Corresponding author
    1. Motherisk Program, Division of Clinical Pharmacology and Toxicology, Research Institute, Hospital for Sick Children, CIBC World Market Children's Miracle Chair in Child Health Research and University of Toronto, Toronto, Canada M5G 1X8
    • Division of Clinical Pharmacology and Toxicology, Hospital for Sick Children, 555 University Avenue, Toronto, Canada M5G 1X8
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Abstract

Background

Corticosteroids are first-line drugs for the treatment of a variety of conditions in women of childbearing age. Information regarding human pregnancy outcome with corticosteroids is limited.

Methods

We collected prospectively and followed up 184 women exposed to prednisone in pregnancy and 188 pregnant women who were counseled by Motherisk for nonteratogenic exposure. The primary outcome was the rate of major birth defects. A meta-analysis of all epidemiological studies was conducted. The Mantel-Haenszel summary odds ratio was calculated for the pooled studies with 95% confidence intervals. A cumulative summary odds ratio was also calculated by combining studies in chronological order. Chi-squared for homogeneity was determined to establish the comparability of the studies.

Results

In our prospective study, there was no statistical difference in the rate of major anomalies between the corticosteroid-exposed and control groups. In the meta-analysis, the Mantel-Haenszel summary odds ratio for major malformations with all cohort studies was 1.45 [95% CI 0.80, 2.60] and 3.03 [95% CI 1.08, 8.54] when Heinonen et al. ('77) was removed. This suggests a marginally increased risk of major malformations after first-trimester exposure to corticosteroids. In addition, summary odds ratio for case-control studies examining oral clefts was significant (3.35 [95% CI 1.97, 5.69]).

Conclusions

Although prednisone does not represent a major teratogenic risk in humans at therapeutic doses, it does increase by an order of 3.4-fold the risk of oral cleft, which is consistent with the existing animal studies. Teratology 62:385–392, 2000. © 2000 Wiley-Liss, Inc.

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