Major malformations following exposure to nonsteroidal antiinflammatory drugs during the first trimester of pregnancy

Sharon Daniel, Ilan Matok, Rafael Gorodischer, Gideon Koren, Elia Uziel, Arnon Wiznitzer, Amalia Levy*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

42 Scopus citations


Objective. Nonsteroidal antiinflammatory drugs (NSAID) are among the most common medicines used by pregnant women. Published data are controversial regarding fetal safety following intra - uterine exposure to NSAID. We investigated exposure to NSAID in the first trimester in a large cohort of infants and fetuses. Methods. A computerized database of medications dispensed from 1998 to 2009 to all women registered in the "Clalit" health maintenance organization in Southern Israel was linked with 2 computerized databases containing maternal and infant hospitalization records. Pregnancy terminations for medical reasons were analyzed. The following confounders were controlled for: parity, maternal age, ethnicity, maternal pregestational diabetes, maternal inflammatory disease, and year of birth or pregnancy termination. First trimester exposure to nonselective cyclooxygenase (COX) inhibitors and to selective COX-2 inhibitors as groups and to individual drugs was analyzed. Results. There were 110,783 pregnancies during the study period: 109,544 singleton births and 1239 pregnancy terminations for medical reasons. In total, 5267 mothers were exposed to NSAID during the first trimester of pregnancy: 5153 to nonselective COX inhibitors and 114 to COX-2 selective inhibitors. Exposure to NSAID in the first trimester, as groups (nonselective COX and selective COX-2 inhibitors) and as individual drugs, was not associated with an increased risk of major congenital malformations in general (adjusted OR 1.07, 95% CI 0.96-1.21 for nonselective; and adjusted OR 1.40, 95% CI 0.70-2.78, for selective COX-2 inhibitors), although an increased risk for musculoskeletal malformations was found following exposure to COX-2 selective inhibitors (adjusted OR 3.39, 95% CI 1.37-8.34). Conclusion. Intrauterine exposure to NSAID was not associated with increased risk for major congenital malformations. Further studies are needed to assess the risk for malformations after exposure to COX-2 selective inhibitors. The Journal of Rheumatology

Original languageAmerican English
Pages (from-to)2163-2169
Number of pages7
JournalJournal of Rheumatology
Issue number11
StatePublished - Nov 2012
Externally publishedYes


  • Congenital malformations
  • Drug exposure
  • Nonsteroidal antiinflammatory drugs
  • Pregnancy


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