TY - JOUR
T1 - Major malformations following exposure to nonsteroidal antiinflammatory drugs during the first trimester of pregnancy
AU - Daniel, Sharon
AU - Matok, Ilan
AU - Gorodischer, Rafael
AU - Koren, Gideon
AU - Uziel, Elia
AU - Wiznitzer, Arnon
AU - Levy, Amalia
PY - 2012/11/1
Y1 - 2012/11/1
N2 - 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
AB - 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
KW - Congenital malformations
KW - Drug exposure
KW - Nonsteroidal antiinflammatory drugs
KW - Pregnancy
UR - http://www.scopus.com/inward/record.url?scp=84868376574&partnerID=8YFLogxK
U2 - 10.3899/jrheum.120453
DO - 10.3899/jrheum.120453
M3 - Article
C2 - 22984274
AN - SCOPUS:84868376574
SN - 0315-162X
VL - 39
SP - 2163
EP - 2169
JO - Journal of Rheumatology
JF - Journal of Rheumatology
IS - 11
ER -