Vitamin D supplementation for term breastfed infants to prevent vitamin D deficiency and improve bone health
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 vitami...
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| creator | Osborn, David A Tan, May Loong Abrams, Steven A Osborn, David A |
| description | 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 |
| doi_str_mv | 10.1002/14651858.CD013046.pub2 |
| format | Article |
| fullrecord | <record><control><sourceid>wiley_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_8812278</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>CD013046.pub2</sourcerecordid><originalsourceid>FETCH-LOGICAL-c4732-7cdafa1afa8560d11c9f4574a5902ede59a3539c3c266db916aea07d71511c853</originalsourceid><addsrcrecordid>eNqFkFtLAzEQhYMotl7-guQPtOay2cuLoK03KPiivoZpdtZGdpMlu63035tSW6ovPgwZOOd8Ew4hV5yNOWPimiep4rnKx5Mp45Il6bhdzsURGW6E0UY5PtgH5KzrPhmTaSGyUzKQUjKVCzEk9bvtobGOTmm3bNsaG3Q99NY7WvlAewwNnQeErq-wpNZV4PqO9p62AVfRSlf7fImVNRadWVNw0du0wa-Qzr1DukCo-8UFOamg7vDy5z0nbw_3r5On0ezl8XlyOxuZJJNilJkSKuBxcpWyknNTVInKElAFE1iiKkAqWRhpRJqW84KngMCyMuMqenMlz8nNlhs7abA08Z8Bat0G20BYaw9W_1acXegPv9J5zoXI8ghItwATfNcFrPZZzvSmf73rX-_63xBFDF4dXt7HdoVHw93W8GVrXGvjzSKAw3-4f658A2ngmQg</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype></control><display><type>article</type><title>Vitamin D supplementation for term breastfed infants to prevent vitamin D deficiency and improve bone health</title><source>MEDLINE</source><source>Cochrane Library</source><source>EZB-FREE-00999 freely available EZB journals</source><source>Alma/SFX Local Collection</source><creator>Osborn, David A ; Tan, May Loong ; Abrams, Steven A ; Osborn, David A</creator><creatorcontrib>Osborn, David A ; Tan, May Loong ; Abrams, Steven A ; Osborn, David A</creatorcontrib><description>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.</description><identifier>ISSN: 1465-1858</identifier><identifier>EISSN: 1465-1858</identifier><identifier>EISSN: 1469-493X</identifier><identifier>DOI: 10.1002/14651858.CD013046.pub2</identifier><identifier>PMID: 33305822</identifier><language>eng</language><publisher>Chichester, UK: John Wiley & Sons, Ltd</publisher><subject>25-Hydroxyvitamin D 2 ; 25-Hydroxyvitamin D 2 - blood ; Bone and Bones ; Bone and Bones - physiology ; Bone Density ; Breast Feeding ; Child health ; Feeding the term infant ; Female ; Humans ; Hypercalcemia ; Hypercalcemia - etiology ; Immediate care of the newborn ; Infant ; Lactation ; Medicine General & Introductory Medical Sciences ; Mothers ; Neonatal care ; Nutrition and Metabolism in the High-Risk Neonate ; Randomized Controlled Trials as Topic ; Rickets ; Rickets - blood ; Term Birth ; Vitamin & mineral supplementation ; Vitamin and Mineral Supplementation ; Vitamin D ; Vitamin D - administration & dosage ; Vitamin D - adverse effects ; Vitamin D Deficiency ; Vitamin D Deficiency - epidemiology ; Vitamin D Deficiency - prevention & control ; Vitamins ; Vitamins - administration & dosage ; Vitamins - adverse effects</subject><ispartof>Cochrane database of systematic reviews, 2020-12, Vol.2020 (12), p.CD013046</ispartof><rights>Copyright © 2020 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4732-7cdafa1afa8560d11c9f4574a5902ede59a3539c3c266db916aea07d71511c853</citedby><cites>FETCH-LOGICAL-c4732-7cdafa1afa8560d11c9f4574a5902ede59a3539c3c266db916aea07d71511c853</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,780,784,885,27915,27916</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/33305822$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Osborn, David A</creatorcontrib><creatorcontrib>Tan, May Loong</creatorcontrib><creatorcontrib>Abrams, Steven A</creatorcontrib><creatorcontrib>Osborn, David A</creatorcontrib><title>Vitamin D supplementation for term breastfed infants to prevent vitamin D deficiency and improve bone health</title><title>Cochrane database of systematic reviews</title><addtitle>Cochrane Database Syst Rev</addtitle><description>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.</description><subject>25-Hydroxyvitamin D 2</subject><subject>25-Hydroxyvitamin D 2 - blood</subject><subject>Bone and Bones</subject><subject>Bone and Bones - physiology</subject><subject>Bone Density</subject><subject>Breast Feeding</subject><subject>Child health</subject><subject>Feeding the term infant</subject><subject>Female</subject><subject>Humans</subject><subject>Hypercalcemia</subject><subject>Hypercalcemia - etiology</subject><subject>Immediate care of the newborn</subject><subject>Infant</subject><subject>Lactation</subject><subject>Medicine General & Introductory Medical Sciences</subject><subject>Mothers</subject><subject>Neonatal care</subject><subject>Nutrition and Metabolism in the High-Risk Neonate</subject><subject>Randomized Controlled Trials as Topic</subject><subject>Rickets</subject><subject>Rickets - blood</subject><subject>Term Birth</subject><subject>Vitamin & mineral supplementation</subject><subject>Vitamin and Mineral Supplementation</subject><subject>Vitamin D</subject><subject>Vitamin D - administration & dosage</subject><subject>Vitamin D - adverse effects</subject><subject>Vitamin D Deficiency</subject><subject>Vitamin D Deficiency - epidemiology</subject><subject>Vitamin D Deficiency - prevention & control</subject><subject>Vitamins</subject><subject>Vitamins - administration & dosage</subject><subject>Vitamins - adverse effects</subject><issn>1465-1858</issn><issn>1465-1858</issn><issn>1469-493X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>RWY</sourceid><sourceid>EIF</sourceid><recordid>eNqFkFtLAzEQhYMotl7-guQPtOay2cuLoK03KPiivoZpdtZGdpMlu63035tSW6ovPgwZOOd8Ew4hV5yNOWPimiep4rnKx5Mp45Il6bhdzsURGW6E0UY5PtgH5KzrPhmTaSGyUzKQUjKVCzEk9bvtobGOTmm3bNsaG3Q99NY7WvlAewwNnQeErq-wpNZV4PqO9p62AVfRSlf7fImVNRadWVNw0du0wa-Qzr1DukCo-8UFOamg7vDy5z0nbw_3r5On0ezl8XlyOxuZJJNilJkSKuBxcpWyknNTVInKElAFE1iiKkAqWRhpRJqW84KngMCyMuMqenMlz8nNlhs7abA08Z8Bat0G20BYaw9W_1acXegPv9J5zoXI8ghItwATfNcFrPZZzvSmf73rX-_63xBFDF4dXt7HdoVHw93W8GVrXGvjzSKAw3-4f658A2ngmQg</recordid><startdate>20201211</startdate><enddate>20201211</enddate><creator>Osborn, David A</creator><creator>Tan, May Loong</creator><creator>Abrams, Steven A</creator><creator>Osborn, David A</creator><general>John Wiley & Sons, Ltd</general><scope>7PX</scope><scope>RWY</scope><scope>ZYTZH</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>5PM</scope></search><sort><creationdate>20201211</creationdate><title>Vitamin D supplementation for term breastfed infants to prevent vitamin D deficiency and improve bone health</title><author>Osborn, David A ; Tan, May Loong ; Abrams, Steven A ; Osborn, David A</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4732-7cdafa1afa8560d11c9f4574a5902ede59a3539c3c266db916aea07d71511c853</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>25-Hydroxyvitamin D 2</topic><topic>25-Hydroxyvitamin D 2 - blood</topic><topic>Bone and Bones</topic><topic>Bone and Bones - physiology</topic><topic>Bone Density</topic><topic>Breast Feeding</topic><topic>Child health</topic><topic>Feeding the term infant</topic><topic>Female</topic><topic>Humans</topic><topic>Hypercalcemia</topic><topic>Hypercalcemia - etiology</topic><topic>Immediate care of the newborn</topic><topic>Infant</topic><topic>Lactation</topic><topic>Medicine General & Introductory Medical Sciences</topic><topic>Mothers</topic><topic>Neonatal care</topic><topic>Nutrition and Metabolism in the High-Risk Neonate</topic><topic>Randomized Controlled Trials as Topic</topic><topic>Rickets</topic><topic>Rickets - blood</topic><topic>Term Birth</topic><topic>Vitamin & mineral supplementation</topic><topic>Vitamin and Mineral Supplementation</topic><topic>Vitamin D</topic><topic>Vitamin D - administration & dosage</topic><topic>Vitamin D - adverse effects</topic><topic>Vitamin D Deficiency</topic><topic>Vitamin D Deficiency - epidemiology</topic><topic>Vitamin D Deficiency - prevention & control</topic><topic>Vitamins</topic><topic>Vitamins - administration & dosage</topic><topic>Vitamins - adverse effects</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Osborn, David A</creatorcontrib><creatorcontrib>Tan, May Loong</creatorcontrib><creatorcontrib>Abrams, Steven A</creatorcontrib><creatorcontrib>Osborn, David A</creatorcontrib><collection>Wiley-Blackwell Cochrane Library</collection><collection>Cochrane Library</collection><collection>Cochrane Library (Open Aceess)</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Cochrane database of systematic reviews</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Osborn, David A</au><au>Tan, May Loong</au><au>Abrams, Steven A</au><au>Osborn, David A</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Vitamin D supplementation for term breastfed infants to prevent vitamin D deficiency and improve bone health</atitle><jtitle>Cochrane database of systematic reviews</jtitle><addtitle>Cochrane Database Syst Rev</addtitle><date>2020-12-11</date><risdate>2020</risdate><volume>2020</volume><issue>12</issue><spage>CD013046</spage><pages>CD013046-</pages><issn>1465-1858</issn><eissn>1465-1858</eissn><eissn>1469-493X</eissn><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.</abstract><cop>Chichester, UK</cop><pub>John Wiley & Sons, Ltd</pub><pmid>33305822</pmid><doi>10.1002/14651858.CD013046.pub2</doi><oa>free_for_read</oa></addata></record> |
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| identifier | ISSN: 1465-1858 |
| ispartof | Cochrane database of systematic reviews, 2020-12, Vol.2020 (12), p.CD013046 |
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| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_8812278 |
| source | MEDLINE; Cochrane Library; EZB-FREE-00999 freely available EZB journals; Alma/SFX Local Collection |
| subjects | 25-Hydroxyvitamin D 2 25-Hydroxyvitamin D 2 - blood Bone and Bones Bone and Bones - physiology Bone Density Breast Feeding Child health Feeding the term infant Female Humans Hypercalcemia Hypercalcemia - etiology Immediate care of the newborn Infant Lactation Medicine General & Introductory Medical Sciences Mothers Neonatal care Nutrition and Metabolism in the High-Risk Neonate Randomized Controlled Trials as Topic Rickets Rickets - blood Term Birth Vitamin & mineral supplementation Vitamin and Mineral Supplementation Vitamin D Vitamin D - administration & dosage Vitamin D - adverse effects Vitamin D Deficiency Vitamin D Deficiency - epidemiology Vitamin D Deficiency - prevention & control Vitamins Vitamins - administration & dosage Vitamins - adverse effects |
| title | Vitamin D supplementation for term breastfed infants to prevent vitamin D deficiency and improve bone health |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-15T01%3A35%3A42IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-wiley_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Vitamin%20D%20supplementation%20for%20term%20breastfed%20infants%20to%20prevent%20vitamin%20D%20deficiency%20and%20improve%20bone%20health&rft.jtitle=Cochrane%20database%20of%20systematic%20reviews&rft.au=Osborn,%20David%20A&rft.date=2020-12-11&rft.volume=2020&rft.issue=12&rft.spage=CD013046&rft.pages=CD013046-&rft.issn=1465-1858&rft.eissn=1465-1858&rft_id=info:doi/10.1002/14651858.CD013046.pub2&rft_dat=%3Cwiley_pubme%3ECD013046.pub2%3C/wiley_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_id=info:pmid/33305822&rfr_iscdi=true |