Table 2.

Main features and results of studies investigating active supplementation of Vitamin D.

References	Study design	Population	Conclusion
Vitamin D and wheezing
(32)	Randomized double-blind controlled trial	195 infants, supplemented with Vitamin D (400 IU/d) or placebo from birth until 6 months of age. Some infants wore personal UV dosimeters to measure direct UV light exposure	The frequency of wheezing did not differ significantly between the vitamin D and placebo group No significant difference in UV exposure between infants who did or did not have doctor-diagnosed wheeze in the first 6 months of life
(33)	Prospective cohort study	5161 children (0-5 years) supplemented with single product vitamin D, multivitamin or multivitamin with iron, containing usually a vitamin D dose of 400 IU	Vitamin D supplementation during pregnancy was associated with reduced wheezing, but child vitamin D supplementation was not associated with reduced wheezing
(34)	Randomized controlled trial	975 infants supplemented with 400 IU/day or 1,200 IU/day from the age of 2 weeks. At 12 months of age, wheezing was evaluated	The number of children with wheezing was similar in both groups. High-dose vitamin D supplementation did not prevent wheezing during the first year of life
(35)	Randomized double-blind controlled trial	195 infants at “high-risk” for allergic disease (positive family history) and born from mothers with a sufficient 25(OH)D serum concentration between 36 and 40 GW. Oral vitamin D supplementation (400 IU/day) or a placebo for the first 6 months of life	No statistically significant differences in the incidence of allergic diseases (including wheezing) over the first 2.5 years of life between the vitamin D and placebo group
(36)	Prospective cohort study	300 premature infants (28-34 gw), supplemented with multivitamin, containing 400 IU/dose of cholecalciferol, in first year of age	Black infants supplemented with multivitamins early in life experienced increased wheezing, whereas non-black supplemented infants experienced decreased wheezing
(37)	Randomized double-blind controlled trial	300 black preterm infants, supplemented for the first 6 months of age with 400 IU of cholecalciferol or placebo	Among black infants born preterm, sustained supplementation with vitamin D, compared with diet-limited supplementation, resulted in a reduced risk of recurrent wheezing by 12 month of age
Vitamin D and asthma
(35)	Randomized double-blind controlled trial	195 infants at “high-risk” for allergic disease (positive family history) and born from mothers with a sufficient 25(OH)D serum concentration between 36 and 40 GW. Oral vitamin D supplementation (400 IU/day) or a placebo for the first 6 months of life	No statistically significant differences in the incidence of allergic diseases (including asthma) over the first 2.5 years of life between the vitamin D and placebo group
(38)	Population-based cohort	61,676 infants, supplemented in the first 6 months of life with vitamin D only, cod liver oil, multivitamins, and any vitamin D supplement	No protective effect of vitamin D only, or cod liver oil, on asthma at school age
(39)	Population-based cohort	8,690 infants, supplemented in the first year of life (with the contemporary recommended dose of 2,000 UI/day)	Vitamin D supplementation in the first year of life is associated with an increased risk of asthma later in life (at 31 years of age)
(40)	Randomized double-blind controlled trial	260 mother-infant pairs, supplemented from birth to 6 months in one of the following groups: placebo/placebo, 1,000 IU/ 400 IU or 2,000 IU/800 IU	The number of primary care asthma visits per child and the number of visits per child for which salbutamol or prednisone was prescribed were smaller in the vitamin D supplemented groups
(41)	Prospective birth cohort	4,089 newborn infants, supplemented in the first year of life with vitamins based in peanut oil, in water-soluble form, in both the 2 preparations, and no vitamins	Children supplemented with vitamins A and D in water-soluble form during the first year of life had an almost 2-fold increased risk of asthma at age 4 years compared with those receiving vitamins in peanut oil
Vitamin D and RTI
(42)	Randomized double-blind controlled trial	239 infants, supplemented from birth and for 9 months with 10 μg vitamin D preparation orally daily or placebo syrup	Daily infant supplementation with vitamin D along with sun exposure is superior to sun exposure alone in maintaining normal infant 25(OH)D at 3.5 months, and provide protection from infectious morbidity
(43)	Prospective birth cohort study	2,244 infants, supplemented with Vitamin D (daily dose 400-600 IU) from birth to 6 months of age	Infants supplemented with Vitamin D had a longer period without experiencing the first RTI and a decreased risk of RTI
(44)	Randomized double-blind controlled trial	3,460 infants aged 1–11 months, supplemented with oral 100,000 IU (2.5 mg) vitamin D3 or placebo, once every 3 months for 18 months	No significant difference between the incidence of pneumonia between the vitamin D and the placebo group