Table 1.
Randomized controlled trials on vitamin D or omega-3 fatty acid supplementation during pregnancy/lactation for the primary prevention of pediatric wheeze/asthma.
| Authors, Years | Population (N), Characteristics | Time of Exposure | Interventions | Outcomes | Findings on Wheeze/Asthma |
|---|---|---|---|---|---|
| Litonjua 2016 [6] | 876 pregnant women, high-risk cohort for asthma | Pregnancy | High dose (4400 IU VD3/day) vs. standard dose (400 IU VD3/day) VD supplementation, starting at 10–18 weeks of gestation until delivery | Asthma or recurrent wheezing in offspring at 3 years of age | No statistically significant reduced risk of persistent wheeze; however, a clinically important protective effect could not be excluded (hazard ratio, 0.8; 95% CI, 0.6–1.0; p = 0.051) |
| Litonjua 2020 [7] | Asthma or recurrent wheezing in offspring at 6 years of age | No effect on the incidence of asthma and recurrent wheeze at age 6 years | |||
| Chawes 2016 [8] | 623 pregnant women, unselected cohort | Pregnancy | High dose (2400 IU VD3/day) vs. standard dose (400 IU VD3/day) VD supplementation, starting at 24 weeks of gestation until delivery | Persistent wheeze and asthma in offspring at 3 years of age | No statistically significant reduced risk of persistent wheeze; however, a clinically important protective effect could not be excluded (hazard ratio, 0.76 [95% CI, 0.52–1.12]; p = 0.16) |
| Brustad 2020 [9] | Asthma in offspring at 6 years of age | No effect on child’s risk of asthma by the age of 6 years | |||
| Goldring 2013 [10] |
180 pregnant women | Pregnancy | No VD vs. 800 IU VD2 daily from 27 weeks gestation until delivery vs. single oral bolus of 200,000 IU VD3 at week 27 of gestation |
Wheezing illnesses (assessed by validated questionnaire) in offspring at 3 years of age |
No effect on the risk of wheezing (risk ratio 0.86; 95% CI 0.49, 1.50; p = 0.69) |
| Norizoe 2014 [11] |
164 mothers of infants with facial eczema at 1 month of age | Lactation | 800 IU VD3 vs. placebo daily, for 6 weeks | Infantile eczema at the 3-month check-up (primary outcome). Atopic dermatitis, food allergy, and wheeze diagnosed by doctors up to 2 years of age, assessed by questionnaire (secondary outcomes). | No effect on child’s risk of wheeze (risk difference 0.11; 95% CI −0.05, 0.26; p = 0.19) |
| Olsen 2008 [12] |
533 pregnant women, unselected cohort |
Pregnancy | Capsule with fish oil (2.7 g n-3 PUFAs) vs. capsules with olive oil vs. no oil capsules, daily from 30 weeks of gestation until delivery | Asthma at 16 years of age | The hazard rate of asthma was reduced by 63% (95% CI: 8%, 85%; p = 0.03), whereas the hazard rate of allergic asthma was reduced by 87% (95% CI: 40%, 97%; p = 0.01) in the fish oil compared with the olive oil group. |
| Bisgaard 2011 [13] |
736 pregnant women, unselected cohort |
Pregnancy | Fish oil (2.4 g LCPUFA) vs. olive oil (placebo), daily from 24 weeks of gestation until 1 week after delivery | Persistent wheeze or asthma from birth to 3–5 years of age (primary outcome). Lower respiratory tract infections, asthma exacerbations, eczema, and allergic sensitization (secondary outcome). | Reduced risk of persistent wheeze or asthma (16.9% vs. 23.7%; hazard ratio, 0.69; 95% CI, 0.49, 0.97; p = 0.035). Reduced risk of lower respiratory tract infections (31.7% vs. 39.1%; hazard ratio, 0.75; 95% CI, 0.58 to 0.98; p = 0.033), but no effect on asthma exacerbations, eczema or allergic sensitization. |
| Noakes 2012 [14] |
123 pregnant women, high-risk cohort for atopy |
Pregnancy | Diet with 2 portions of salmon per week (providing 3.45 g EPA plus DHA) vs. habitual diet (which was low in oily fish), from 20 wk gestation until delivery | Clinical outcomes at 6 months (secondary outcomes) | No difference in the incidence of wheeze, eczema, lower respiratory tract infections, and allergic sensitization |
| Best 2018 [15] |
701 pregnant women, high-risk cohort for atopy |
Pregnancy | Fish oil capsules (900 mg of LCPUFA ~800 mg DHA and 100 mg EPA) vs. vegetable oil capsules without LCPUFA, daily from <21 weeks’ gestation until birth | Allergic disease symptoms (eczema, wheeze, rhinitis) at 1, 3, and 6 years of age reported by parents using a standardized questionnaire. Allergic sensitization assessed by skin prick testing. | No difference in wheeze symptoms with sensitization across the 1-, 3-, and 6-year assessments (adjusted relative risk 0.81, 95% CI 0.55, 1.21, p = 0.31) |
| Furuhjelm 2011 [16] | 145 pregnant women, high-risk cohort for atopy | Pregnancy and Lactation | LCPUFA (1.6 g EPA and 1.1 g DHA) vs. placebo, daily from 25 weeks of gestation continuing through 3.5 months of breastfeeding. | Allergic disease in infants up to 2 years of age | No difference in cumulative and point prevalence at 2 years of age of asthma and allergic asthma, despite lower cumulative incidence of allergic sensitization and IgE-related disease up to 24 months of age (adjusted odds ratio 0.29, 95% CI 0.1–0.86. p = 0.03). |
DHA, (omega-3 fatty acid) docosahexaenoic acid; EPA, (omega-3 fatty acid) eicosapentaenoic acid; IU, International Units; LC, long-chain; PUFA, polyunsaturated fatty acids; VD, vitamin D.