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.