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Table 1 Characteristics of included RCTs

From: Relationship between vitamin D and asthma from gestational to adulthood period: a meta-analysis of randomized clinical trials

Studies

Type

Participants

Mean level of 25(OH)D at baseline [mean (SD)] or [median (IQR)]

Age

Mean age

Sex (girl/female)

Interventions

Treatment period

Observational period

Gestational period

Litonjua et al., 2016 [18]

randomized, double-blind, placebo-controlled study

876 women with asthma, eczema or allergic rhinitis history (or in the biological father)

806 children

I: 23.3 (10.1) ng/mL

C: 22.5 (10.1) ng/mL

18 – 39 years

I: 27.5

C: 27.3

I: 51%

C: 45%

I: 4000 IU/d of vitamin D plus a prenatal vitamin containing 400 IU vitamin D

C: placebo plus a prenatal vitamin containing 400 IU of vitamin D

pregnancy

asthma and wheezing were diagnosed in children up to 3 years of age

Chawes et al., 2016 [19]

randomized, double-blind, placebo-controlled study

581 healthy women

I: 31 (10) ng/mL

C: 31 (10) ng/mL

NA

I: 32.5

C: 32.0

NA

I: 2400 IU/d plus a prenatal vitamin containing 400 IU of vitamin D

C: placebo plus a prenatal vitamin containing 400 IU of vitamin D

pregnancy week 24 to 1 week postpartum

asthma and wheezing were diagnosed in children up to 3 years of age

Litonjua et al., 2020 [20]

a randomized, double-blind, placebo-controlled trial

876 women with asthma, eczema or allergic rhinitis history (or in the biological father)

806 children

I: 23.3 (10.3) ng/mL

C: 22.6 (10.2) ng/mL

18 – 39 years

I: 27.5

C: 27.2

I: 50.5%

C: 45.1%

I: 4000 IU/d of vitamin D plus a prenatal vitamin containing 400 IU of vitamin D

C: placebo plus a prenatal vitamin containing 400 IU of vitamin D

pregnancy

asthma and wheezing were diagnosed in children up to 6 years of age

Infantile period

Rosendahl et al., 2019 [15]

randomized, double

blinded controlled trial

975 infants

Cord blood

30 µg: 81.3 (24) nmol/L

10 µg: 81.7 (28) nmol/L

from the age of 2 weeks

-

I: 50%

C: 50%

30 µg: 1200 IU/d of vitamin D

10 µg: 400 IU/d of vitamin D

from 2 weeks to 24 months of age

asthma and wheezing were diagnosed up to 12 months of life

Rueter et al., 2020 [21]

randomized, double-blinded controlled trial

195 infants

Cord blood I: 67.8 (17.5) nmol/L

C: 61.1 (14.2) nmol/L

before 28 days of age

I: 13.2

C: 12.8

days at randomization

I: 47.4%

C: 45.9%

I: 400 IU/d of vitamin D3

C: placebo

for the first six months of life

asthma and wheezing were diagnosed up to 2.5 years of age

Hibbs et al., 2018 [22]

masked placebo-controlled randomized clinical trial

300 infants

I: 19.1 (15.7–28.0) ng/mL

C: 21.0 (17.0–25.0) ng/mL

NA

I: 11

C: 13

days at randomization

I: 49.7%

C: 39%

I: 400 IU/d of cholecalciferol

C: placebo

until 6 months of age

asthma and wheezing were diagnosed up to 12 months of life

Rueter et al., 2019 [23]

a double-blind, placebo-controlled RCT

195 inflants

NA

before 28 days of age

I: 13.2

C: 12.8

days at randomization

I: 47.4%

C: 45.9%

I: 400 IU/d of vitamin D3

C: placebo

for the first six months of life

wheezing was diagnosed up to 3 and 6 months of age

Childhood period

Thakur et al., 2021 [24]

placebo‐controlled, blinded, randomized controlled trial

60 children with moderate persistent asthma

I: 15.8 (8.2) ng/mL

C: 16.5 (9.9) ng/mL

6 – 11 years

I: 9

C: 8.7

I: 46.6%

C: 40%

I: 2000 IU/d of vitamin D

C: placebo

 + budesonide 400 μg and formoterol 24 μg daily

3 months

the C‐ACT score and FEV1 were measured at baseline and after 3 months

Jat et al., 2021 [14]

double-blind, randomized controlled trial

250 asthmatic children

I: 11.6 (4.6) ng/ml

C: 10.8 (4.4) ng/ml

4 – 12 years

I: 8.2

C: 7.8

I: 71.2%

C: 72.8%

I: 1000 IU/d of vitamin D

C: placebo

9 months

the C‐ACT score and FEV1 were measured at baseline and after 9 months

Kerley et al., 2016 [25]

a double-blind, randomized, PL-controlled trial

44 children with asthma

I: 58 (39–69) (nmol/l)

C: 51 (39–64) (nmol/l)

6–16 years

I: 10

C: 7

I: 35%

C: 41%

I: 2000 IU/d of vitamin D3

C: placebo

15 weeks

the C‐ACT score and FEV1 were measured at baseline and after 15 weeks

Adulthood period

Emami Ardestani et al., 2020 [26]

randomized, controlled clinical trial

132 mild-to-moderate asthma patients with vitamin D insufficiency and deficiency

Insufficient group

I: 23.42 (2.64) ng/ml

C: 23.64 (3.26) ng/ml

Deficient group

I: 11.29 (0.79) ng/ml

C: 11.36 (0.75) ng/ml

above 18 years old

I: 42.77

C: 41.00

Insufficient group

I: 33.3%

C: 57.6%

Deficient group

I: 51.5%

C: 39.4%

Insufficient group

I: 1000 U/d of vitamin D

C: placebo

Deficient group

I: 50,000 U/week of vitamin D to achieve serum 25(OH)D level > 20 ng/ml; followed by a maintenance dose of 1000 U/d

C: placebo

 + asthma controller (Symbicort)

3 months

the ACT score and FEV1 were measured at baseline and after 3 months

Andújar-Espinosa et al., 2021 [27]

randomized, triple-blind, placebo-controlled, parallel-group study

112 adult asthmatic patients

I: 16.71 (6.71) ng/mL

C: 17.48 (5.72) ng/mL

above 18 years old

I: 54.57

C: 56.61

I: 71.4%

C: 83.9%

I: 16,000 IU/week of calcifediol C: placebo

 + usual asthma treatment

6 months

the ACT score and FEV1 were measured at baseline and after 6 months

Ali et al., 2017 [28]

an open-label prospective randomized controlled trial

82 patients

with asthma

I: 18 (3.7–45) ng/mL

C: 18.5 (3.5–54.7) ng/mL

18 to 65 years old

I: 43

C: 48

I: 62.8%

C: 74.4%

I: 1 µg/d of alfacalcidol

C: standard asthma treatment

Vental inhaler as needed

 + Vental Compositum (mild asthma)

 + Foradil Aerolizer or Uniphyllin (moderate asthma)

Higher dose of Beclomethasone or Prednisolone added (severe asthma)

4 months

FEV1 was measured at baseline and after 4 months

Martineau et al., 2015 [29]

a prospective randomized, placebo controlled, triple-blind study

250 adults with asthma

I: 49.8 (25.2) nmol/L

C: 49.4 (24.2) nmol/L

16 to 80 years old

I: 49.4

C: 46.4

I: 56%

C: 57%

I: 120 000 IU/2 months of vitamin D3 (Vigantol oil)

C: placebo

12 months

the ACT score and FEV1 were measured at baseline and after 12 months

Nageswari et al., 2014 [30]

an open labeled, randomized comparative trial

68 patients with asthma

NA

35 to 65 years

I: 57.26

C: 56.23

I: 18%

C: 16%

I: 1000 IU/d of vitamin D3 + Budesonide 400 μg + formoterol 24 μg

C: Budesonide 400 μg + formoterol 24 μg

90 days

FEV1 was measured at baseline and after 90 days

  1. NA not applicable, IQR interquartile range, I intervention group, C control group, C‐ACT childhood asthma control test, ACT asthma control test, FEV1 forced expiratory volume in one second