Fish Oil and Vitamin D Supplementations in Pregnancy Protect Against Childhood Croup

BACKGROUND: Croup is a prevalent respiratory disorder in early childhood most often caused by parainfluenza virus infections. There are no preventive strategies; therefore, we investigated the potential effects of prenatal micronutrient supplementations.OBJECTIVE: To investigate the supplementation effects of (1) 2.4-g n-3 long-chained polyunsaturated fatty acid (n-3 LCPUFA) (fish oil) versus olive oil and (2) high-dose (2800 IU/ d) versus standard-dose (400 IU/d) of vitamin D from pregnancy week 24 until 1 week after birth on the risk for offspring croup during the double-blinded first 3 years of life in a secondary analysis of a 2 3 2 factorial designed randomized controlled trial.METHODS: The study was completed in the Danish population-based single-center Copenhagen Prospective Studies on Asthma in Childhood 2010 motherechild cohort, which included 736 pregnant women. Croup was diagnosed by physi-cians' clinical examinations and medical record checks. Potential mediating mechanisms were investigated using blood metab-olomics, airway cytokines, and airway microbiome.RESULTS: Of 695 children, 97 had croup before age 3 years (14%). The risk of croup was reduced in the n-3 LCPUFA (ncases / ntotal = 38/346; 11%) versus olive oil group (59 of 349 children; 17%) (hazard ratio = 0.62; 95% CI, 0.41-0.93; P = .02) and in the high-dose vitamin D group (32 of 295 children; 11%) versus the standard-dose group (51 of 286 children; 18%) (hazard ratio = 0.60; 95% CI, 0.38-0.93; P = .02). There was no evidence of interaction or additive effects between the sup-plements (Pinteraction = .56). Furthermore, the results did not change when they were adjusted for each other, persistent wheeze, and lower respiratory tract infection.CONCLUSIONS: This analysis of the double-blinded period of the Copenhagen Prospective Studies on Asthma in Childhood 2010 randomized controlled trial of n-3 LCPUFA and high-dose vitamin D supplementation during pregnancy demonstrated a reduced risk of croup in early childhood. (c) 2022 American Academy of Allergy, Asthma & Immunology (J Allergy Clin Immunol Pract 2023;11:315-21)