title: Birth defects after maternal exposure to corticosteroids: prospective cohort study and meta-analysis of epidemiological studies.
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.
authors.affiliation: Faculty of Pharmacy, University of Toronto, Toronto, Canada.
authors.forename: L
authors.initials: L
authors.lastname: Park-Wyllie
authors.forename: P
authors.initials: P
authors.lastname: Mazzotta
authors.forename: A
authors.initials: A
authors.lastname: Pastuszak
authors.forename: M E
authors.initials: ME
authors.lastname: Moretti
authors.forename: L
authors.initials: L
authors.lastname: Beique
authors.forename: L
authors.initials: L
authors.lastname: Hunnisett
authors.forename: M H
authors.initials: MH
authors.lastname: Friesen
authors.forename: S
authors.initials: S
authors.lastname: Jacobson
authors.forename: S
authors.initials: S
authors.lastname: Kasapinovic
authors.forename: D
authors.initials: D
authors.lastname: Chang
authors.forename: O
authors.initials: O
authors.lastname: Diav-Citrin
authors.forename: D
authors.initials: D
authors.lastname: Chitayat
authors.forename: I
authors.initials: I
authors.lastname: Nulman
authors.forename: T R
authors.initials: TR
authors.lastname: Einarson
authors.forename: G
authors.initials: G
authors.lastname: Koren
mesh_terms: D000014:Abnormalities, Drug-Induced / Q000453:epidemiology* / Q000209:etiology; D000305:Adrenal Cortex Hormones / Q000009:adverse effects*; D000328:Adult; D016009:Chi-Square Distribution; D002972:Cleft Palate / Q000139:chemically induced / Q000453:epidemiology; D015331:Cohort Studies; D003376:Counseling; D005260:Female; D006801:Humans; D007231:Infant, Newborn; D008427:Maternal Health Services; D016017:Odds Ratio; D009864:Ontario / Q000453:epidemiology; D011241:Prednisone / Q000009:adverse effects; D011247:Pregnancy; D011256:Pregnancy Outcome; D011261:Pregnancy Trimester, First; D011446:Prospective Studies
chemical_list: D000305:Adrenal Cortex Hormones; D011241:Prednisone