Risk of major congenital malformations and heart defects in pregnancies exposed to first-trimester drugs for depression and co-medications

Abstract

Introduction:

Managing depression during pregnancy requires balancing maternal health and fetal safety. As drugs for depression are often used alongside other medications, understanding if these combinations relate to teratogenic risks is important. This study explored patterns of major congenital malformations (MCMs), including congenital heart defects (CHDs), following first-trimester drugs for depression, alone, or with co-medications.

Methods:

Using Danish national registry data, we analyzed 674,154 pregnancies, of which 2.2% were exposed to first-trimester drugs for depression. We compared MCMs and CHD occurrences in pregnancies exposed to these drugs, alone or with co-medications, to nonexposed pregnancies and generated estimates to explore potential associations and interactions.

Results:

Exploratory assessments suggested that overall MCM risk among pregnancies exposed to drugs for depression was similar to nonexposed pregnancies (adjusted odds ratio (95% confidence interval): 1.05 (0.96–1.15)), while CHD risk appeared higher (1.26 (1.08–1.47). Certain co-medications showed signals warranting further study, including possible increases in MCM risk with antihistamines (1.64 (1.14–2.28)) and levothyroxine (1.72 (1.12–2.53)) and a potential decrease with opioids (0.51 (0.27–0.86). For CHDs, drugs for psychosis (1.67 (1.01–2.60)), nonsteroidal anti-inflammatory/antirheumatic medications (2.07 (1.23–3.25)), topical corticosteroid (2.07 (1.02–3.71)), and progesterone (2.01 (1.06–3.45)) showed patterns potentially indicating elevated risk.

Conclusion:

This study provides exploratory insights into how first-trimester use of drugs for depression, alone or with selected co-medications, may relate to MCM and CHD patterns. These findings suggest potential interactions but could also result from confounding or chance. Further research is needed to support clinical decision-making.