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Maternal Exposure to Amoxicillin and the Risk of Oral Clefts

Lin, Kueiyu Joshuaa; Mitchell, Allen A.b; Yau, Wai-Pinga,c; Louik, Carolb; Hernández-Díaz, Soniaa

doi: 10.1097/EDE.0b013e318258cb05
In-Utero Exposures

Background: Prior studies have suggested an increased risk of oral clefts after exposure to amoxicillin in early pregnancy, but findings have been inconsistent.

Methods: Among participants in the Slone Epidemiology Center Birth Defects Study from 1994 to 2008, we identified 877 infants with cleft lip with/without cleft palate and 471 with cleft palate alone. Controls included 6952 nonmalformed infants. Mothers were interviewed about demographic, reproductive and medical factors, and details of medication use. We estimated odds ratios (ORs) and 95% confidence intervals (CIs) associated with use of amoxicillin in the first trimester using conditional logistic regression and adjusting for known risk factors for oral clefts, as well as for infections, fever, and concomitant treatments.

Results: In the control group, 2.1% of women had used amoxicillin in the first trimester. Maternal use of amoxicillin was associated with an increased risk of cleft lip with/without cleft palate (adjusted OR = 2.0 [95% confidence interval = 1.0–4.1]), with an OR of 4.3 (1.4–13.0) for third-gestational-month use. Risks were not elevated for use of other penicillins or cephalosporins. For cleft palate, the OR for first-trimester amoxicillin was 1.0 (0.4–2.3) with an OR of 7.1 (1.4–36) for third-gestational month use.

Conclusions: Amoxicillin use in early pregnancy may be associated with an increased risk of oral clefts.

From the aDepartment of Epidemiology, Harvard School of Public Health, Boston, MA; bSlone Epidemiology Center at Boston University, Boston, MA; cDepartment of Pharmacy, National University of Singapore, Singapore.

Submitted 21 July 2011; accepted 28 February 2012; posted 3 July 2012.

Supported by grant R01 HD046595-04 from the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD). The authors reported no other financial interests related to this research.

Correspondence: Allen A. Mitchell, Slone Epidemiology Center, 1010 Commonwealth Ave. Boston, MA 02215. E-mail:

© 2012 Lippincott Williams & Wilkins, Inc.