(BSPOT18) Concomitant Use of Antidepressants and Benzodiazepines During Pregnancy and Associated Risk of Congenital Malformations in Offspring: Population Based Cohort study

Background: Despite the frequent co-administration of antidepressants and benzodiazepines (BZD), the association between such concomitant use during pregnancy and the risk of congenital malformations remains inadequately explored.

Objectives: To examine the association between concomitant use of antidepressants and BZDs during the first trimester and organ-specific congenital malformations.

Methods:

Design: Population-based cohort study with a propensity score fine-stratification weighting approach (PS-FSW), confounding by indication control and sibling comparison analyses.

Setting: Taiwan’s National Birth Certificate Application (BCA) database, the Maternal and Child Health Database (MCHD), and Taiwan’s National Health Insurance (NHI) database.

Participants: A total of 2,634,021 pregnant women aged 15 and 50 with singleton births and their infants between 2004 and 2018 were included.

Exposures: Antidepressants and BZDs use was defined as at least one prescription during the first trimester, and concomitant use was defined as the simultaneous prescription of both drugs with overlapping prescription period.

Main outcome measures: Overall congenital malformations and eight organ-specific malformations, including nervous system, heart, respiratory system, oral cleft, digestive system, urinary system, genital organs, and limb malformations.

Results: The cohort included 2,634,021 singleton pregnancies, and 8,599 (0.33%) were concomitant users for antidepressants and BZDs during the first trimester. Absolute risk of overall malformations was 3.81 per 100 pregnancies exposed to antidepressants and BZDs, as compared with 2.87 per 100 unexposed pregnancies. The propensity score-weighted odds ratios (wORs) did not suggest an increased risk for overall malformations (wOR 1.10, 95% CI 0.94 to 1.28), heart defects (1.01, 0.83 to 1.23), and most of the other organ-specific malformations. The absence of a significant risk for congenital malformations associated with concomitant use of antidepressants and BZDs was further supported by the analyses controlling for confounding by indication and sibling-matched comparisons.

Conclusions: Our findings suggest that the concomitant use of antidepressants and BZDs during the first trimester is not associated with a substantial increase in risk of most malformation subtypes. However, considering the potential adverse effects and the limited efficacy of using both medications concomitantly, a thorough assessment of the risks and benefits is crucial in clinical decision-making.