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

Croup is a common respiratory disorder in young children, frequently caused by parainfluenza virus infections. n-3 polyunsaturated fatty acids and vitamin D possess immunoregulatory effects. The current study investigated the effects of supplementation with (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 per day) versus standard-dose (400 IU per day) vitamin D from pregnancy week 24 until 1 week after birth on the risk of croup for offspring.

The Copenhagen Prospective Studies on Asthma in Childhood 2010 mother-child cohort included 736 pregnant women. Data from the current study were obtained from secondary analysis of a double-blinded randomized-control trial (DB-RCT) that demonstrated the protective effects of n-3 LCPUFA and high dose vitamin D in pregnancy on the development of persistent wheeze, asthma, and lower respiratory tract infections.

Pregnant women participated in a 2 × 2 factorial designed trial and were randomized (1:1) to receive either daily fish oil capsules of 2.4 g (55% eicosapentaenoic acid and 37% docosahexaenoic) of n-3 LCPUFA or matching olive oil capsules. A subgroup of 623 women were randomized (1:1) to receive either 2800 IU/d of vitamin D 3 or matching capsules containing the Danish Health Authority recommended intake of 400 IU/d. Adherence to interventions was assessed by counting returned capsules complemented by pre and postinterventional measurements of blood eicosapentaenoic acid, docosahexaenoic, and 25 hydroxyvitamin D. Investigators and participants were blinded to the protocol until the youngest child turned 3.

A total of 695 and 581 children were included in the n-3 LCPUFA and vitamin D trials, respectively. In the n-3 LCPUFA DB-RCT, 38 of the 346 children in the n-3 LCPUFA group (11%) and 59 of the 349 children in the olive oil group (17%) had a diagnosis of croup, demonstrating a reduction in the risk of croup (hazard ratio = 0.62; 95% confidence interval, 0.41–0.93, P = .02). In the high-dose vitamin D DB-RCT, 32 of the 295 children in the high-dose group (11%) and 51 of the 286 children in the standard-dose group (18%) were diagnosed with croup, demonstrating a protective effect of the high-dose vitamin D (hazard ratio = 0.60; 95% confidence interval, 0.38–0.93, P = .02). There was no evidence of interaction or additive effects between the 2 interventions on the risk of croup (P interaction = 0.56). Results were unchanged in mutually adjusted analyses independent of the effects on wheezing and lower respiratory tract infections.

The risk of croup during the first 3 years of life was reduced by 38% and 40% by prenatal supplementation with n-3 LCPUFA and high-dose vitamin D, respectively.

The authors propose that the beneficial effects of the supplements on croup might be explained by immune system upregulation with improved clearance of airway infections, modulations in anti-inflammatory and antioxidant systems, or improved lung maturation. The authors additionally suggest that prenatal immune system programming may modify susceptibility to infection in later life. Micronutrient interventions during pregnancy may reduce the risk of acute respiratory diseases in childhood. Additional study is needed given the promising results detailed in the current analysis.