Key messages
• The children of women given high doses of vitamin D during pregnancy are less likely to develop wheeze (a whistling sound heard on exhalation, due to lower airway swelling, inflammation, or constriction) than children whose mothers did not take vitamin D in pregnancy.
• Vitamin D treatment in early childhood may have little effect on preventing asthma or wheeze, though we are uncertain of these results.
• We are very uncertain about the evidence for any unwanted effects of vitamin D treatment in pregnant or breastfeeding women or young children.
Background
Asthma is a common childhood condition that affects the lungs. Children with asthma experience recurrent attacks of breathlessness, wheezing, and coughing due to inflammation, mucous production, and narrowing of the airways. Atopic dermatitis (a chronic inflammatory skin disease), sensitisation to allergens, and recurrent respiratory tract infections may contribute to the development of asthma. Vitamin D is an essential nutrient that affects the immune system. Previous studies have connected low vitamin D status to an increased risk of allergic disease.
What did we want to find out?
We wanted to find out if vitamin D treatment in early life helps prevent: (a) childhood asthma, wheeze, or both; and (b) risk factors for childhood asthma, including atopic dermatitis, airway infections, sensitisation to allergens, and airway inflammation.
We also wanted to find out if vitamin D treatment was associated with any unwanted effects.
What did we do?
We searched for studies exploring any of the following comparisons:
• any vitamin D versus placebo (an inactive 'dummy' medicine) or no treatment in pregnant or breastfeeding women;
• any vitamin D versus placebo/no treatment in young children;
• higher-dose vitamin D with lower/standard dose (400 international units/day or less) vitamin D in pregnant or breastfeeding women,
• higher-dose vitamin D with lower/standard dose (400 international units/day or less) vitamin D in young children.
Our outcomes of interest were childhood asthma, wheeze, atopic dermatitis, airway infections, allergic sensitisation, and airway inflammation.
We compared and summarised the results of the studies and rated our confidence in the evidence, based on factors such as study methods and the number of people in the study.
What did we find?
We found 18 studies involving a total of 10,611 pregnant women, infants, mother/infant pairs, and children up to age five. Four studies compared any vitamin D with placebo/no treatment in pregnant women, five studies compared any vitamin D with placebo/no treatment in young children, four studies compared higher versus lower doses of vitamin D in pregnant women, and seven studies compared higher versus lower doses of vitamin D in young children. Studies were conducted around the world; most were done in higher-income countries. The largest study included 3046 participants; the smallest included 50. The duration of vitamin D treatment ranged from 28 days to two years, with most studies treating for six months or less.
Main results
Any vitamin D treatment in pregnancy may help prevent childhood asthma (1 study, 236 participants), and higher-dose vitamin D treatment in pregnancy likely helps prevent childhood wheeze (3 studies, 1439 participants).
Vitamin D treatment in early childhood, regardless of dose and comparison, may have little effect on asthma or wheeze, though we are uncertain of these results. High-dose vitamin D treatment in early childhood may help prevent airway infections (6 studies, 2385 participants).
Vitamin D treatment in pregnancy or early childhood, regardless of dose and comparison, may have little to no effect on atopic dermatitis, sensitisation to allergens, and markers of airway inflammation.
We are uncertain whether vitamin D treatment in pregnancy or early childhood has any unwanted effects because the studies reported limited information about unwanted effects.
What are the limitations of the evidence?
For interventions in pregnancy, we are moderately confident in the effects of high-dose vitamin D on wheeze and asthma. We are less confident in the effects of any vitamin D on asthma because the evidence is based on results from one small study. However, these findings are limited to prenatal vitamin D treatment in the second and third trimesters; the effects of vitamin D treatment starting around the time a woman becomes pregnant or in the first trimester are unclear.
For interventions in young children, we have low confidence in our findings for the effects of vitamin D, regardless of dose, on any outcome evaluated.
We have little confidence in the findings for unwanted effects because the evidence is based on a few cases and there were not enough studies evaluating most unwanted effects.
How current is this evidence?
The evidence is current to October 2023.
Pročitajte cijeli sažetak
Randomised controlled studies evaluating vitamin D supplementation in pregnancy or early childhood for preventing childhood asthma have yielded inconclusive results. Previous systematic reviews of vitamin D for asthma prevention focused on studies comparing vitamin D to placebo or studies intervening in pregnancy, limiting the body of evidence.
Ciljevi
Primary: to evaluate the efficacy of any vitamin D supplementation and high-dose vitamin D supplementation in early life, including the prenatal period, for preventing asthma in children.
Secondary: to assess the efficacy of vitamin D supplementation:
• for preventing asthma in children at risk of vitamin D deficiency at the start of the trial or whose mothers were at risk;
• by intervention timing and the cumulative dose administered;
• in preventing factors associated with early childhood asthma, including atopic dermatitis, respiratory tract infections, sensitisation to allergens, and airway inflammation.
Metode pretraživanja
We searched CENTRAL, MEDLINE, Embase, ClinicalTrials.gov, the International Clinical Trials Registry Platform, and the Cochrane Airways and Skin Trial Registers. We checked the reference lists of relevant systematic reviews and meta-analyses. We contacted authors to obtain additional study information as needed. Date of last search: October 2023.
Kriteriji odabira
We included randomised controlled studies comparing higher versus lower/standard dose vitamin D (≤ 400 international units (IU)/day) or any vitamin D versus placebo/no treatment in generally healthy pregnant or lactating women or children up to five years of age that evaluated childhood asthma, wheeze, atopic dermatitis, airway infections, allergic sensitisation, and airway inflammation. We excluded trials recruiting populations with pre-existing conditions.
Prikupljanje podataka i obrada
We followed standard Cochrane methodological procedures, including using Cochrane's Screen4Me workflow. We considered participants rather than events as the unit of analysis, performed fixed-effect meta-analysis, and reported risk ratios (RRs) or mean differences (MDs) with 95% confidence intervals (CIs) for four comparisons: (1) any vitamin D versus placebo/no supplementation in pregnant or breastfeeding women; (2) any vitamin D versus placebo/no supplementation in infants or children; (3) high versus low/standard dose vitamin D in pregnant or breastfeeding women; (4) high versus low/standard dose vitamin D in infants or children. Our outcomes were: asthma, wheeze, atopic dermatitis, airway infections, allergic sensitisation, airway inflammation, and adverse events. We narratively described results that could not be meta-analysed. We used the Cochrane risk of bias tool (RoB) to assess bias in the studies. We used GRADE to assess the certainty of the evidence.
Glavni rezultati
We included 18 studies involving a total of 10,611 participants, of which 16 contributed data to meta-analyses. Studies were conducted around the world, with most taking place in higher-income countries. The dose and frequency of vitamin D ranged from 200 IU/day to 100,000 IU bolus quarterly, and the duration of supplementation ranged from 28 days to two years.
Comparison 1. Any vitamin D versus placebo/no supplementation in pregnant or breastfeeding women (4 studies)
Compared to placebo or no supplementation, any vitamin D given to pregnant or breastfeeding women may reduce the risk of early childhood asthma (RR 0.17, 95% CI 0.05 to 0.61; 1 study, 236 participants; low-certainty evidence) and likely has little to no effect on childhood airway infections (RR 1.00, 95% CI 0.97 to 1.04; 3 studies, 1564 participants; moderate-certainty evidence). The evidence is very uncertain for wheeze, atopic dermatitis, allergic sensitisation, airway inflammation, or adverse events.
Comparison 2. Any vitamin D versus placebo/no supplementation in infants or children (5 studies)
Compared to placebo or no supplementation, any vitamin D given to infants or children may have little to no effect on childhood wheeze (RR 0.89, 95% CI 0.68 to 1.16; 2 studies, 431 participants; low-certainty evidence), atopic dermatitis (RR 1.01, 95% CI 0.80 to 1.28; 2 studies, 448 participants; low-certainty evidence), airway infections (RR 0.92, 95% CI 0.83 to 1.01; 2 studies, 500 participants; low-certainty evidence), allergic sensitisation (RR 2.25, 95% CI 0.60 to 8.50; 1 study, 228 participants; low-certainty evidence), or airway inflammation measured by eosinophil counts (RR 1.06, 95% CI 0.65 to 1.74; 1 study, 226 participants; low-certainty evidence). The evidence is very uncertain for asthma and adverse events.
Comparison 3. High versus low/standard dose vitamin D in pregnant or breastfeeding women (4 studies)
Compared to low/standard dose, high-dose vitamin D given to pregnant or breastfeeding women likely reduces the risk of childhood wheeze (RR 0.79, 95% CI 0.64 to 0.98; 3 studies, 1439 participants; moderate-certainty evidence), but likely results in little to no difference in childhood asthma, although the direction and magnitude of effect is similar to that for wheeze (RR 0.81, 95% CI 0.63 to 1.04; 2 studies, 1355 participants; moderate-certainty evidence). Compared to low/standard dose, high-dose vitamin D in pregnancy likely has little to no effect on childhood atopic dermatitis (RR 0.91, 95% CI 0.75 to 1.11; 3 studies, 1439 participants; moderate-certainty evidence), airway infections (RR 0.95, 95% CI 0.82 to 1.11; 3 studies, 1441 participants; moderate-certainty evidence), or allergic sensitisation (RR 1.01, 95% CI 0.87 to 1.18; 2 studies, 1110 participants; moderate-certainty evidence). The evidence is very uncertain for adverse events. No studies evaluated airway inflammation.
Comparison 4. High versus low/standard dose vitamin D in infants or children (7 studies)
Compared to low/standard dose, high-dose vitamin D given to infants or children may slightly reduce airway infections (RR 0.94, 95% CI 0.90 to 0.98; 6 studies, 2385 participants; low-certainty evidence) but may have little to no effect on atopic dermatitis (RR 0.76, 95% CI 0.55 to 1.05; 1 study, 769 participants; low-certainty evidence). The evidence is very uncertain for asthma, wheeze, allergic sensitisation, and adverse events. No studies evaluated airway inflammation.
Zaključak autora
Evidence supporting a protective effect of vitamin D supplementation in early life, including the prenatal period, on childhood asthma is limited. Moderate-certainty evidence suggests that high-dose vitamin D in pregnancy likely helps prevent childhood wheeze. Evidence for the effects of vitamin D in early childhood on asthma or wheeze is less certain. Additional high-quality studies, especially in infants and children, are needed to establish with any certainty the effects of vitamin D supplementation on childhood asthma and associated factors.
