(B-258) Association between cardiac congenital malformations and mothers’ drug use during pregnancy in Catalonia, Spain

Background: Cardiac congenital malformations (CCM) are among the most common birth defects. While drug use during pregnancy is known to entail risk of malformations, evidence of its prevalence and consequences is limited and inconclusive.

Objectives: To analyze the association between CCM in infants and the use of drugs by their mothers during pregnancy.

Methods:

Design: case-control study.
Participants: mother-child linked pairs, infants born in 2010-2022. Cases: infants with CCM. Controls: infants without CCM.
Exposure: drug exposure during pregnancy.
Main outcome measures: CCM.
Analysis: We described categorical variables by absolute frequency and percentage and numerical by mean and standard deviation. We calculated the prevalence of CCM in infants and drug exposure in mothers. To assess the association between pregnancy exposure and CCM, we balanced the case and control groups using inverse probability weights from propensity scores generated by logistic regression. We balanced the groups for sex and birth year of the child and maternal age. We calculated odds ratios (OR) and 95% confidence intervals (CI) of having CCM between exposed and unexposed mothers.

Results: We included 467,414 mother-child pairs. Mothers had a mean age of 32.5, 114,938 (24.6%) were multiparous, and 454,097 (97.2%) had a full-term baby. Their most frequent comorbidities were mental diagnoses (212,066, 45.4%), obesity (89,484, 19.1%), and neoplasms (61,826, 13.2%), and 345,268 (73.9%) had received at least one drug during pregnancy, being the drugs with highest prevalence of use supplements like folic acid (45.4%), iron (42.4%) or vitamin B12 and folic acid (38.1%), analgesics-anilides (23.6%), beta-lactam (14.5%) or other antibacterials (10.7%). We found 9,727 infants (2.1%) with CCM. Some medications were associated to CCM, with OR of: 1.47 (95%CI 1.3-1.66) for proton-pump inhibitors, 1.49 (1.39-1.59) for heparins, 1.37 (1.24-1.52) for antiplatelets, 1.33 (1.2-1.48) for progestogens, 1.53 (1.3-1.8) for glucocorticoids, 1.23 (1.05-1.43) for macrolides, 1.31 (1.12-1.53) for non-steroidal anti-inflammatory drugs (NSAID)-acid acetic derivatives, 1.24 (1.16-1.32) for NSAID-propionic acid derivatives, 1.33 (1.19-14.9) for analgesics-pyrazolones, 1.53 (1.35-1.72) for benzodiazepines, 1.44 (1.22-1.71) for antihistamines-aminoalkyl ethers, and 1.29 (1.1-1.51) for antihistamines-piperazines.

Conclusions: We conducted a preliminary analysis of all pharmacological drugs and selected CCM as one of the common birth defects, finding significant OR in some cases.
Our next steps include analyzing other malformations, focusing on specific pharmacological groups and specific substances and conducting separate analyses by pregnancy trimesters.