Exposure to pseudoephedrine during pregnancy and major congenital malformations: Findings from a large population‐based cohort of pregnancies

AIMS: The aim of this study was to assess the risk of major congenital malformations following first-trimester pseudoephedrine (PSE) exposure. METHODS: A population-based observational cohort study was conducted on pregnancies of women aged 15-49 years, insured by Clalit Health Services in southern Israel, who gave birth or had elective pregnancy terminations due to suspected fetal malformation at Soroka Medical Center (1999-2017). The study focused on Clarinase, a drug that contains a high dose of PSE (120 mg) and 5 mg of loratadine. Multivariable negative binomial regression models were used to evaluate the risk for major congenital malformations, adjusting for potential confounders. RESULTS: Of 251 543 pregnancies, 313 (0.12%) were exposed to high-dose PSE in the first trimester. PSE exposure was not associated with major congenital malformations overall (adjusted relative risk [aRR] = 0.90, 95% confidence interval [CI] 0.558-1.45; P = 0.66) or by organ system (cardiovascular: aRR = 0.938, 95% CI 0.499-1.762; central nervous system: aRR = 0.618, 95% CI 0.086-4.451; musculoskeletal: aRR = 1.800, 95% CI 0.801-4.042; gastrointestinal: aRR = 1.013, 95% CI 0.142-7.241; genitourinary: aRR = 0.704, 95% CI 0.225-2.204). CONCLUSIONS: First-trimester PSE exposure was not an independent risk factor for major congenital malformations, either overall or by organ system.