Maternal exposure to amoxicillin and the risk of oral clefts

Epidemiology. 2012 Sep;23(5):699-705. doi: 10.1097/EDE.0b013e318258cb05.


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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Algorithms
  • Amoxicillin / adverse effects*
  • Anti-Bacterial Agents / adverse effects*
  • Case-Control Studies
  • Cleft Lip / chemically induced*
  • Cleft Palate / chemically induced*
  • Female
  • Humans
  • Infant, Newborn
  • Interviews as Topic
  • Logistic Models
  • Multivariate Analysis
  • Odds Ratio
  • Population Surveillance
  • Pregnancy
  • Pregnancy Trimester, First
  • Prenatal Exposure Delayed Effects / chemically induced*
  • Risk Factors
  • Self Report


  • Anti-Bacterial Agents
  • Amoxicillin