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Maternal Exposure to Caffeine and Risk of Congenital Anomalies: A Systematic Review

Browne, Marilyn L.

doi: 10.1097/01.ede.0000208476.36988.44
Review Article

Background: Caffeine is teratogenic in animal studies when administered at high concentrations. Previous review articles have concluded that maternal caffeine consumption does not influence the risk of congenital anomalies. These reviews were narrative rather than systematic. The objective of the current systematic review is to provide a critical appraisal of epidemiologic evidence.

Methods: A search of the MEDLINE/PUBMED database (1966–October 2004) was conducted for all published epidemiologic studies with maternal intake of caffeine as an exposure and major malformations as an outcome. Study characteristics were abstracted, internal validity evaluated, and study findings summarized.

Results: Twenty-five papers met the initial criteria for inclusion, of which 18 were subsequently excluded as a result of other limitations. Effect estimates for the remaining 7 studies were generally close to null. Specific subgroup analyses were summarized across studies (associations between coffee and cardiovascular malformations, coffee and oral clefts, and tea and cardiovascular malformations). Summary point estimates ranged from 1.0 to 1.2; the upper limits of all confidence intervals were less than 1.7.

Conclusions: There is no evidence to support a teratogenic effect of caffeine in humans. Current epidemiologic evidence is not adequate to assess the possibility of a small change in risk of congenital anomalies resulting from maternal caffeine consumption.

Supplemental Digital Content is Available in the Text.

From the Bureau of Environmental and Occupational Epidemiology, New York State Department of Health, Troy, NY.

Submitted 23 May 2005; accepted 19 December 2005.

This study was supported by a cooperative agreement from the Centers for Disease Control and Prevention (U50/CCU223184).

Supplemental material for this article is available with the online version of the journal at; click on “Article Plus.”

Correspondence: Marilyn L. Browne, Flanigan Square, 547 River Street, Room 200, Troy, NY 12180. E-mail:

© 2006 Lippincott Williams & Wilkins, Inc.