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Vitamin D supplementation for term breastfed infants to prevent vitamin D deficiency and improve bone health.

The Cochrane database of systematic reviews
January 1, 1970
May Loong Tan et al. (3 authors)
Journal ArticleMeta-AnalysisResearch Support, Non-U.S. Gov'tSystematic ReviewHuman Study
Study Details

Study Goal

The researchers aimed to determine the effect of vitamin D supplementation given to infants or lactating mothers on vitamin D deficiency, bone density, and growth in healthy term breastfed infants.

Results Summary

Vitamin D supplementation (400 IU/day) in infants increased 25-OH vitamin D levels and reduced insufficiency, while maternal supplementation reduced insufficiency and deficiency in high-risk populations. However, evidence on bone health and deficiency was insufficient.

Population

Healthy term breastfed infants and lactating mothers, with some studies focusing on high-risk populations for vitamin D deficiency.

Effective Dosage

Infant supplementation: 400 IU/day; maternal supplementation: varied from 400 IU/day to >4000 IU/day, with some studies using 60,000 IU/day for short periods.

Duration

Up to six months for infant supplementation; maternal supplementation durations varied.

Interactions

None mentioned

Extracted Claims (14)
InterventionDirectionEndpointPopulationDosageImpactClaim #
Vitamin D supplementation given to infants at 400 IU/day
increase
25-OH vitamin D levels
healthy term breastfed infants
MD 22.63 nmol/L, 95% CI 17.05 to 28.21
may increase
#1
Vitamin D supplementation given to infants at 400 IU/day
decrease
incidence of vitamin D insufficiency (25-OH vitamin D < 50 nmol/L)
healthy term breastfed infants
RR 0.57, 95% CI 0.41 to 0.80
may reduce
#2
Vitamin D supplementation given to infants
decrease
risk of vitamin D deficiency (25-OH vitamin D < 30 nmol/L) up till six months of age
healthy term breastfed infants
RR 0.41, 95% CI 0.16 to 1.05
insufficient evidence to determine if it reduces
#3
Vitamin D supplementation given to infants
no change
bone mineral content (BMC)
healthy term breastfed infants
-
insufficient evidence to determine if it affects
#4
Vitamin D supplementation given to infants
no change
incidence of biochemical or radiological rickets
healthy term breastfed infants
-
insufficient evidence to determine if it affects
#5
Vitamin D supplementation given to lactating mothers
increase
infant 25-OH vitamin D levels
infants of lactating mothers
MD 24.60 nmol/L, 95% CI 21.59 to 27.60
may increase
#6
Vitamin D supplementation given to lactating mothers
decrease
incidences of vitamin D insufficiency
infants of lactating mothers
RR 0.47, 95% CI 0.39 to 0.57
may reduce
#7
Vitamin D supplementation given to lactating mothers
decrease
incidences of vitamin D deficiency
infants of lactating mothers
RR 0.15, 95% CI 0.09 to 0.24
may reduce
#8
Vitamin D supplementation given to lactating mothers
decrease
incidences of biochemical rickets
infants of lactating mothers
RR 0.06, 95% CI 0.01 to 0.44
may reduce
#9
Vitamin D supplementation given to lactating mothers
no change
radiological rickets
infants of lactating mothers
RR 0.76, 95% CI 0.18 to 3.31
insufficient evidence to determine if it has an effect on
#10
Infant vitamin D supplementation (400 IU/day)
increase
infant 25-OH vitamin D levels
infants at high risk of vitamin D deficiency
MD 14.35 nmol/L, 95% CI 9.64 to 19.06
compared to lactating mother supplementation may increase
#11
Infant vitamin D supplementation (400 IU/day)
decrease
incidence of vitamin D insufficiency
infants at high risk of vitamin D deficiency
RR 0.61, 95% CI 0.40 to 0.94
compared to lactating mother supplementation may reduce
#12
Infant vitamin D supplementation (400 IU/day)
decrease
incidence of vitamin D deficiency
infants at high risk of vitamin D deficiency
RR 0.35, 95% CI 0.17 to 0.72
compared to lactating mother supplementation may reduce
#13
Maternal higher dose supplementation (≥ 4000 IU/day)
no change
infant 25-OH vitamin D levels
infants at high risk of vitamin D deficiency
similar to infant supplementation of 400 IU/day
produced similar
#14
Abstract

BACKGROUND: Vitamin D deficiency is common worldwide, contributing to nutritional rickets and osteomalacia which have a major impact on health, growth, and development of infants, children and adolescents. Vitamin D levels are low in breast milk and exclusively breastfed infants are at risk of vitamin D insufficiency or deficiency. OBJECTIVES: To determine the effect of vitamin D supplementation given to infants, or lactating mothers, on vitamin D deficiency, bone density and growth in healthy term breastfed infants. SEARCH METHODS: We used the standard search strategy of Cochrane Neonatal to 29 May 2020 supplemented by searches of clinical trials databases, conference proceedings, and citations. SELECTION CRITERIA: Randomised controlled trials (RCTs) and quasi-RCTs in breastfeeding mother-infant pairs comparing vitamin D supplementation given to infants or lactating mothers compared to placebo or no intervention, or sunlight, or that compare vitamin D supplementation of infants to supplementation of mothers. DATA COLLECTION AND ANALYSIS: Two review authors assessed trial eligibility and risk of bias and independently extracted data. We used the GRADE approach to assess the certainty of evidence. MAIN RESULTS: We included 19 studies with 2837 mother-infant pairs assessing vitamin D given to infants (nine studies), to lactating mothers (eight studies), and to infants versus lactating mothers (six studies). No studies compared vitamin D given to infants versus periods of infant sun exposure. Vitamin D supplementation given to infants: vitamin D at 400 IU/day may increase 25-OH vitamin D levels (MD 22.63 nmol/L, 95% CI 17.05 to 28.21; participants = 334; studies = 6; low-certainty) and may reduce the incidence of vitamin D insufficiency (25-OH vitamin D < 50 nmol/L) (RR 0.57, 95% CI 0.41 to 0.80; participants = 274; studies = 4; low-certainty). However, there was insufficient evidence to determine if vitamin D given to the infant reduces the risk of vitamin D deficiency (25-OH vitamin D < 30 nmol/L) up till six months of age (RR 0.41, 95% CI 0.16 to 1.05; participants = 122; studies = 2), affects bone mineral content (BMC), or the incidence of biochemical or radiological rickets (all very-low certainty). We are uncertain about adverse effects including hypercalcaemia. There were no studies of higher doses of infant vitamin D (> 400 IU/day) compared to placebo. Vitamin D supplementation given to lactating mothers: vitamin D supplementation given to lactating mothers may increase infant 25-OH vitamin D levels (MD 24.60 nmol/L, 95% CI 21.59 to 27.60; participants = 597; studies = 7; low-certainty), may reduce the incidences of vitamin D insufficiency (RR 0.47, 95% CI 0.39 to 0.57; participants = 512; studies = 5; low-certainty), vitamin D deficiency (RR 0.15, 95% CI 0.09 to 0.24; participants = 512; studies = 5; low-certainty) and biochemical rickets (RR 0.06, 95% CI 0.01 to 0.44; participants = 229; studies = 2; low-certainty). The two studies that reported biochemical rickets used maternal dosages of oral D3 60,000 IU/day for 10 days and oral D3 60,000 IU postpartum and at 6, 10, and 14 weeks. However, infant BMC was not reported and there was insufficient evidence to determine if maternal supplementation has an effect on radiological rickets (RR 0.76, 95% CI 0.18 to 3.31; participants = 536; studies = 3; very low-certainty). All studies of maternal supplementation enrolled populations at high risk of vitamin D deficiency. We are uncertain of the effects of maternal supplementation on infant growth and adverse effects including hypercalcaemia. Vitamin D supplementation given to infants compared with supplementation given to lactating mothers: infant vitamin D supplementation compared to lactating mother supplementation may increase infant 25-OH vitamin D levels (MD 14.35 nmol/L, 95% CI 9.64 to 19.06; participants = 269; studies = 4; low-certainty). Infant vitamin D supplementation may reduce the incidence of vitamin D insufficiency (RR 0.61, 95% CI 0.40 to 0.94; participants = 334; studies = 4) and may reduce vitamin D deficiency (RR 0.35, 95% CI 0.17 to 0.72; participants = 334; studies = 4) but the evidence is very uncertain. Infant BMC and radiological rickets were not reported and there was insufficient evidence to determine if maternal supplementation has an effect on infant biochemical rickets. All studies enrolled patient populations at high risk of vitamin D deficiency. Studies compared an infant dose of vitamin D 400 IU/day with varying maternal vitamin D doses from 400 IU/day to > 4000 IU/day. We are uncertain about adverse effects including hypercalcaemia. AUTHORS' CONCLUSIONS: For breastfed infants, vitamin D supplementation 400 IU/day for up to six months increases 25-OH vitamin D levels and reduces vitamin D insufficiency, but there was insufficient evidence to assess its effect on vitamin D deficiency and bone health. For higher-risk infants who are breastfeeding, maternal vitamin D supplementation reduces vitamin D insufficiency and vitamin D deficiency, but there was insufficient evidence to determine an effect on bone health. In populations at higher risk of vitamin D deficiency, vitamin D supplementation of infants led to greater increases in infant 25-OH vitamin D levels, reductions in vitamin D insufficiency and vitamin D deficiency compared to supplementation of lactating mothers. However, the evidence is very uncertain for markers of bone health. Maternal higher dose supplementation (≥ 4000 IU/day) produced similar infant 25-OH vitamin D levels as infant supplementation of 400 IU/day. The certainty of evidence was graded as low to very low for all outcomes.

Medical Subject Headings (MeSH)
25-Hydroxyvitamin D 2Bone DensityBone and BonesBreast FeedingFemaleHumansHypercalcemiaInfantLactationMothersRandomized Controlled Trials as TopicRicketsTerm BirthVitamin DVitamin D DeficiencyVitamins
Study Links
Quality Scores
Safety75
Efficacy70/10
Quality80/10
Citation Metrics
Total Citations46
Citations/Year9.2
Relative Citation Ratio4.22
NIH Percentile90.9%
Research Impact Scores
APT Score0.95
Weight Score1.85
Normalized Score0.74
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