Effect of Vitamin D₃Supplementation During Pregnancy on Risk of Persistent Wheeze in the Offspring

Abstract

IMPORTANCE Observational studies have suggested that increased dietary vitamin D intake during pregnancy may protect against wheezing in the offspring, but the preventive effect of vitamin D supplementation to pregnant women is unknown. OBJECTIVE To determine whether supplementation of vitamin D 3 during the third trimester of pregnancy reduces the risk of persistent wheeze in the offspring. DESIGN, SETTING, AND PARTICIPANTS A double-blind, single-center, randomized clinical trial conducted within the Copenhagen Prospective Studies on Asthma in Childhood 2010 cohort. Enrollment began March 2009 with a goal of 708 participants, but due to delayed ethical approval, only 623 women were recruited at 24 weeks of pregnancy. Follow-up of the children (N = 581) was completed when the youngest child reached age 3 years in March 2014. INTERVENTIONS Vitamin D 3 (2400 IU/d; n = 315) or matching placebo tablets (n = 308) from pregnancy week 24 to 1 week postpartum. All women received 400 IU/d of vitamin D 3 as part of usual pregnancy care. MAIN OUTCOMES AND MEASURES Age at onset of persistent wheeze in the first 3 years of life. Secondary outcomes included number of episodes of troublesome lung symptoms, asthma, respiratory tract infections, and neonatal airway immunology. Adverse events were assessed. RESULTS Of the 581 children, persistent wheeze was diagnosed during the first 3 years of life in 47 children (16%) in the vitamin D 3 group and 57 children (20%) in the control group. Vitamin D 3 supplementation was not associated with the risk of persistent wheeze, but the number of episodes of troublesome lung symptoms was reduced, and the airway immune profile was up-regulated (principal component analysis, P = .04). There was no effect on additional end points. Intrauterine death was observed in 1 fetus (<1%) in the vitamin D 3 group vs 3 fetuses (1%) in the control group and congenital malformations in 17 neonates (5%) in the vitamin D 3 group vs 23 neonates (8%) in the control group. End Point Vitamin D 3 Control Estimate (95% CI) P Value Persistent wheeze, No. (%) 47 (16) 57 (20) Hazard ratio (HR), 0.76 (0.52-1.12) .16 Episodes of troublesome lung symptoms, mean (95% CI) 5.9 (5.2-6.6) 7.2 (6.4-8.1) Incidence risk ratio (IRR), 0.83 (0.71-0.97) .02 Asthma at 3 y, No. (%) 32 (12) 47 (14) Odds ratio, 0.82 (0.50-1.36) .45 Respiratory tract infections Upper, annual mean (95% CI) 5.2 (4.8-5.5) 5.3 (4.9-5.6) IRR, 0.99 (0.90-1.09) .84 Lower, No. (%) 94 (32) 95 (33) HR, 0.96 (0.72-1.27) .76 CONCLUSIONS AND RELEVANCE The use of 2800 IU/d of vitamin D 3 during the third trimester of pregnancy compared with 400 IU/d did not result in a statistically significant reduced risk of persistent wheeze in the offspring through age 3 years. However, interpretation of the study is limited by a wide CI that includes a clinically important protective effect.

Maternal vitamin D levels during pregnancy and neonatal health: evidence to date and clinical implications

“…A total of 31 of them developed bronchopulmonary dysplasia (BPD) [Onwuneme et al 2015]. A recent RCT from Denmark studied 623 pregnant women [Chawes et al 2016]. Focusing mainly on offspring respiratory health, the group reported that daily supplementation with 2400 IU vitamin D 3 from week 24 until week 1 postpartum had a positive impact.…”

In utero exposure to 25-hydroxyvitamin D and risk of childhood asthma, wheeze, and respiratory tract infections: A meta-analysis of birth cohort studies

“…[9][10][11] Also, epidemiologic studies have suggested that maternal vitamin D intake 12, 13 as well 82 as vitamin D levels in blood [14][15][16] were inversely associated with respiratory tract infections and 83 other wheezing illnesses, presumably because of its multiple immune effects including induction 84 of antibacterial responses and modulation of T-lymphocytes to suppress inflammation. 17,18 Data 85 from randomized clinical trials are sparse, but two recently-published trials reported a non-86 significant more than 20% reduced risk of persistent wheeze/asthma at age 0-3 years from 87 prenatal vitamin D supplementation 19,20 In addition to the relatively short follow-up period, the 88 investigators acknowledged that the studies might be underpowered. Another systematic review of 23 published articles including 9 cross-sectional, 2 case-control, 93 and 12 cohort studies in both children and adults suggested that higher serum levels of 25- effect on development of asthma in childhood.…”

Vitamin D and Allergy

“…After maternal vitamin D supplementation, rate of wheezing development was found to be low at 3-5 years of age (but no relation with asthma incident at 5 years of age) [28,29]. Between maternal vitamin D 2.800 IU/ day and 400 IU/day supplementation, there was no significant difference for allergy development at 3 years of age [30]. Another study performed in UK study demonstrated that high maternal plasma [25(OH) D3] level during late pregnancy was found to be associated higher risk of eczema in children at 9 months of age [31].…”