Table 2.
Randomized controlled trials on vitamin D or omega-3 fatty acid supplementation during infancy for the primary prevention of pediatric wheeze/asthma.
| Authors, Years | Population (N), Characteristics | Time of Exposure |
Interventions | Outcomes | Findings on Wheeze/Asthma |
|---|---|---|---|---|---|
| Rueter 2020 [17] |
195 infants, high risk for atopy, sufficient vitamin D levels at birth |
Postnatal | 400 IU VD3 vs. placebo, daily for the first 6 months of life | Allergic disease at 1 and 2.5 years of age | No differences in incidence for wheeze or recurrent wheeze/asthma at either 1 year (relative risk 1.66, 95% CI 0.92, 3.01; p = 0.13) or at 2.5 years of age (relative risk 1.32, 95% CI 0.79, 2.23; p = 0.38) |
| Hibbs 2018 [18] |
300, black premature infants (born at 28–36 weeks’ gestation) |
Postnatal | 400 IU VD3/d vs. placebo (diet-limited supplementation), daily from birth to 6 months of life | Recurrent wheezing by 12 months’ adjusted age | Reduced risk of recurrent wheezing (31.1% vs. 41.8%; risk difference, -10.7%, 95% CI, -27.4%, -2.9%; relative risk 0.66, 95% CI, 0.47, 0.94; p =0.02) |
| Grant 2016 [19] |
260, pregnant women and their infants |
Pre and postnatal |
Woman–Infant pair assigned to: placebo-placebo vs. 1.000 IU—400 IU VD3/daily vs. 2.000 IU—800 IU VD3 daily, from 27 weeks gestation to birth, and then to infants for the first 6 months of life |
Aeroallergen sensitization and healthcare visit for acute respiratory illness (i.e., cold, otitis media, an upper respiratory infection, croup, asthma, bronchitis, bronchiolitis, a wheezy lower respiratory infection or fever and cough) at 18 months old | Differences in the proportion of children with primary care visits described by the doctor as being for asthma (11%, 0%, 4%, p = 0.02), but not for the other respiratory diagnoses |
| Mihrshahi 2004 [20] | 376 infants, high risk for atopy |
Postnatal | Tuna fish oil and omega-3-rich margarine and cooking oils vs. placebo (polyunsaturated margarine and cooking oils), from 6 months of life (or at the start of formula feeding) | Allergic sensitization and asthma/wheezing at 18 months old | Wheeze ever, doctor visits for wheeze, bronchodilator use and nocturnal coughing were significantly reduced in children in the higher quintiles of omega-3 fatty acid concentration in plasma (p < 0.05). No difference in diagnosed asthma or atopy between the exposure quintiles. |
| Marks 2006 [21] |
516 children, high-risk for atopy |
Postnatal | House dust mite avoidance (mattress cover) vs. placebo; dietary fatty acid modification (see reference 95) vs. placebo | Asthma, allergic sensitization, and eczema at 5 years of age | The prevalence of asthma, wheezing, eczema, or allergic sensitization did not differ between the diet groups (p > 0.1). |
| Foiles 2016 [22] |
91 children | Postnatal | As infants, they were fed either a control formula without LCPUFA or one of three formulas that contained 0.64% of total fatty acids as arachidonic acid and either 0.32, 0.64, or 0.96% of total fatty acids as DHA | Allergic skin and respiratory illnesses through 4 years of age | If the mother reported allergy, the LCPUFA group had a 74% reduction (hazard ratio = 0.26; 95% CI 0.07, 0.9; p =0.02) in wheezing/asthma in the first 4 years of life compared to the control group, whereas LCPUFA and control groups did not differ if the mother reported no history of allergy (hazard ratio = 0.78; 95% CI 0.2, 2.9; p = 0.71) |
| Birch 2010 [23] |
89 infants | Postnatal | DHA/arachidonic acid-supplemented milk formula (0.32%–0.36%/0.64%–0.72% of total fatty acids, respectively) vs. non-supplemented formula (control), fed during the first year of life | Upper respiratory infection (URI), wheezing, asthma, bronchiolitis, bronchitis, allergic rhinitis, allergic conjunctivitis, otitis media, sinusitis, atopic dermatitis (AD), and urticaria up to 3 years of age | Lower odds for developing URI (odds ratio 0.22, 95% CI 0.08, 0.58), wheezing/asthma (odds ratio 0.32, 95% CI 0.11,0.97) in the intervention group compared to controls. |
| D’Vaz 2012 [24] |
420 infants, high-risk for atopy |
Postnatal | Fish oil (280 mg DHA and 110 mg EPA) vs. placebo (olive oil), from birth to age 6 months | Eczema, food allergy, and asthma at 1 year of age | No significant differences in recurrent wheeze or persistent coughing between 6 or 12 months, but plasma DHA levels at 6 months significantly associated with less recurrent wheezing in the first year of life (p = 0.029) |
Cfu, colony-forming units; DHA, (omega-3 fatty acid) docosahexaenoic acid; EPA, (omega-3 fatty acid) eicosapentaenoic acid; IU, International Units; lcFOS, long-chain fructo-oligosaccharides; LC, long-chain; PUFA, polyunsaturated fatty acids; pAOS, pectin-derived acidic oligosaccharides; scGOS, short-chain galacto-oligosaccharides; VD, vitamin D.