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

Review question: do vitamin D supplements for breastfed infants or their mothers prevent vitamin D deficiency and improve bone health?

Background: vitamin D deficiency is common worldwide with infants at higher risk due to pigmentation, covering, avoidance of sun exposure or the latitude of where they live. Vitamin D is important for bone health, helping prevent nutritional rickets and fractures. Vitamin D levels are low in breast milk and exclusively breastfed infants are at risk of low vitamin D levels.

Study characteristics: evidence is up‐to‐date as of May 2020. We identified 19 studies with 2837 mother-infant pairs assessing vitamin D given to infants (nine studies), to breastfeeding mothers (eight studies), and to infants versus breastfeeding mothers (six studies). No studies compared vitamin D given to infants versus periods of infant sun exposure.

Key results: for breastfed infants, vitamin D supplements may increase vitamin D levels and reduce the incidence of mildly low vitamin D levels, but there was insufficient information to determine if there was a reduction in vitamin D deficiency or in signs of poor bone health (low bone mineral content, nutritional rickets or fractures). For breastfed infants at higher risk of vitamin D deficiency, vitamin D supplementation for the mother may increase infant vitamin D levels and may prevent vitamin D deficiency. There was not enough information to determine if there are benefits for bone health. In populations at higher risk of vitamin D deficiency, vitamin D supplementation of infants may be better than vitamin D supplementation of the mother whilst breastfeeding for preventing vitamin D deficiency. However, the evidence is very uncertain for markers of bone health. High-dose maternal supplementation (≥ 4000 IU per day) achieved similar infant vitamin D levels as infant supplementation with 400 IU per day.

Certainty of evidence: the evidence is currently very uncertain for supplementation of vitamin D for breastfeeding mothers or supplementation of their infants in populations at low risk of vitamin D deficiency. In populations at high risk of vitamin D deficiency, there is low-certainty evidence that vitamin D 400 IU per day given to the infant or higher doses given to the breastfeeding mother may prevent vitamin D deficiency, although effects on bone health are unclear.

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.

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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 strategy: 

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.

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