Benzodiazepine exposure in pregnancy and risk of major malformations: a critical overview

Objective: Benzodiazepines (BDZs) safety profiles in pregnancy suggest that the risk of major malformations (MMs) cannot be considered simply as a "class effect". The aim of this paper was to review and update the available literature on the risks of MMs in women exposed to BDZs in the first trimester of pregnancy.

Methods: PubMed was searched for English-language articles, from January 2001 to November 2011, introducing as keywords "teratogens", " major malformation", "foetus", "infant", "newborn", "pregnancy", in conjunction with "benzodiazepines" as a keyword or BDZ generic name as text words.

Results: Twelve studies were selected for the review. BDZ exposure during the first trimester of pregnancy seems not to be associated with an increasing risk of congenital MMs. Diazepam and chlordiazepoxide should be considered drugs of first choice.

Conclusions: Data published in the last 10 years did not indicate an absolute contraindication in prescribing BDZs during the first gestational trimester. In any case, studies analyzed suffer from a number of methodological limitations such as lack of careful report of BDZ patterns of use in pregnancy, possible influences of recall bias, lack of controlling for confounding factors and lack of data concerning possible MMs in aborted fetuses.