Risk of major birth defects after first‐trimester exposure to carbocisteine and ambroxol: A multicenter prospective cohort study using counseling data for drug safety during pregnancy

<jats:title>Abstract</jats:title><jats:p>To assess the risk of major birth defects after first‐trimester exposure to carbocisteine and ambroxol during pregnancy, we conducted a prospective cohort study using counseling data for drug use during pregnancy provided by the Japan Drug Information Institute in Pregnancy and Toranomon Hospital. Counseling information, including drug usage and participants' demographic information, was collected between April 1988 and December 2017. Pregnancy outcome data, including major birth defects, were obtained using a questionnaire administered 1 month after delivery. The risks of major birth defects after first‐trimester exposure to carbocisteine (<jats:italic>n</jats:italic> = 588) and ambroxol (<jats:italic>n</jats:italic> = 341) were compared with those of nonteratogenic drug use during the first trimester (<jats:italic>n</jats:italic> = 1525). The adjusted odds ratio (aORs) for major birth defects was calculated using a multiple logistic regression analysis adjusted for confounders. The incidence of major birth defects was 1.2% (7/588) and 2.1% (7/341) in the carbocisteine and ambroxol groups, respectively, which was comparable to the control group (26/1525, 1.7%). Results of multiple logistic regression demonstrated similar nonsignificant risks for both carbocisteine (aOR: 0.66, 95% confidence interval [CI]: 0.40–1.1, <jats:italic>p</jats:italic> = 0.11) and ambroxol (aOR: 1.1, 95% CI: 0.18–7.2, <jats:italic>p</jats:italic> = 0.88). No specific major birth defects were reported in the carbocisteine or ambroxol groups. This study demonstrated that carbocisteine and ambroxol exposure during the first trimester was not associated with an increased risk of major birth defects. These results could help in counseling for the use of these drugs during pregnancy and further alleviate anxiety in patients.</jats:p>