RevPaulPediatr.2016;34(1):3---4
www.rpped.com.br
REVISTA
PAULISTA
DE
PEDIATRIA
EDITORIAL
In
time:
vitamin
D
deficiency:
who
needs
supplementation?
Em
tempo:
deficiência
da
Vitamina
D:
quem
precisa
de
suplementac
¸ão?
Tania
Winzenberg
a,b,∗,
Graeme
Jones
aaMenziesInstituteforMedicalResearch,UniversityofTasmania,Hobart,Tasmania,Australia bFacultyofHealth,UniversityofTasmania,Hobart,Tasmania,Australia
Received25August2015
Vitamin D has a critical role in calcium metabolism and bone healthin childrenandis postulatedtocontributeto non-bone conditions, such as respiratory illnesses, atopy andschizophrenia.1 Thereareclearlinksbetweenvitamin
D deficiencyandricketsand neonatalhypocalcaemia,but vitaminDalsohasapotentialroleinoptimisingbone acquisi-tioninchildhood.2ThustheneedforvitaminDsupplements
requiresconsiderationfromarangeofperspectives.
Rickets
Rickets can be caused by low serum vitamin D levels and/or low dietary calcium intakes, and, less commonly, by disorders of phosphate metabolism. It is important to differentiatethesecausesasvitaminDsupplementsalone will notcorrect ricketsunless vitamin D deficiency is the only or majorcause.This isseen in a randomisedcontrol trial (RCT)in Nigerian childrenwith ricketsin whichonly 19% ofthosetreated withvitamin Dalone hadnear com-pleteresolution,comparedto61%and58%ofthosetreated withcalciumandcalciumwithvitaminD,respectively.3 In
developingcountriescalciopenicricketsappearsmore com-mon.VitaminD givenwithcalciumfor calciopenicrickets canresultinbetteroutcomesthatcalciumalone.4
∗Correspondingauthor.
E-mail:tania.winzenberg@utas.edu.au(T.Winzenberg).
When low calcium intake contributes to rickets, cau-sation may be incorrectly attributed to vitamin D levels whichcan resultin overestimation of athreshold of vita-min D above which vitamin D deficiency rickets does not occur.However,inaRCTofvitaminDsupplementationfor ricketspreventioninChineseinfants,evenwithlowserum 25-hydroxy vitamin D (25(OH)D) concentrations (around 30nmol/L) rickets did not occur.5 Thus vitamin D-related
ricketsmaybemostcommonbelowthislevel.Thisis con-sistentwith datafrom developed countries where rickets predominantlyoccursinpopulationsat knownhighrisk of moderate to severe vitamin D deficiency such as African American populations in the US6 and dark-skinned
immi-grantpopulationsinAustralia.7,8Inthelatterstudies,serum
25(OH)Dwas<20mmol/Lin73%ofcasesandin88%ofcases agedlessthan6months,7thoughricketsoccurredatupto
50nmol/L.8 Therefore, indeveloped countries,these high
riskgroupsrequireintervention,eitherbyscreeningforand correctingsignificantvitaminDdeficiencyorbyroutine vita-minDsupplementationofbreastfeedinginfantsathighrisk.
Vitamin
D
supplementation
to
optimise
peak
bone
mass
Observationalevidencelinksvitamindeficiencyinuteroand childhoodtoreducedbonemineraldensity,2butRCTdata
arelimited.TherearenoRCTsofvitaminDsupplementation in pregnancy with bone density outcomes in children. In
http://dx.doi.org/10.1016/j.rppede.2015.10.003
4 WinzenbergT,JonesG.
generalhumanmilk-fed infantshavelowerbone accretion comparedtoformulafedinfants.9Whilethisdeficitappears
temporary, ascatch upgrowth occurs, it is possible that bone developmentin breastfeedinginfants couldbe aug-mentedthroughvitaminDsupplements.Thisandconcerns abouttheriskofricketsinchildrenatriskofvitaminD defi-ciencyhasledtowidespreadrecommendationofvitaminD supplementation of breastfeeding infants.2 Unfortunately,
RCT data are sparse and unconvincing. Of three small trialsof400IUdaily ofvitamin D,none demonstratedany benefitsof vitamin D supplementation onbone density in thefirstyearoflife.2However,morethanhalftheinfants
were likely to have vitamin D levels >50nmol/L, so RCTs indeficientinfantsareurgentlyneededbeforebenefitsin suchinfantscanberuled out.Thisisimportantasvitamin D supplements may only benefit bone mass in deficient children. In a meta-analysis10,11 of six RCTs, vitamin D
supplementationhadnostatisticallysignificantorclinically importanteffectsontotalbodybone mineralcontent(TB BMC), hip bone mineral density (BMD) or forearm BMD, witha trend to a small effect on lumbar spine (LS) BMD (standardisedmeandifference(SMD)+0.15,(95%CI−0.01to +0.31),p=0.07),whenstudieswereanalysed regardlessof meanstudy baseline25(OH)D.However,when groupedby meanbaseline25(OH)D,therewerestatisticallysignificant effectsonTBBMCandLSBMDinstudieswithmeanbaseline 25(OH)D <35nmol/L, and the magnitude of effects at all siteswereatleast0.2SMDhigherthaninstudieswithmean baseline 25(OH)D ≥35nmol/L. Even in studies with mean serum25(OH)D<35nmol/L,around20%ofchildrenwouldbe vitaminDreplete,sotoproperlyestimatethemagnitudeof anybenefits,RCTstargetingdeficientchildrenareneeded.
Vitamin
D
and
other
chronic
diseases
ThesuggestionthatvitaminDlevelsinchildhoodarerelated totheoccurrenceofotherchronicdiseasesisbasedon lim-itedobservationaldata,1withonlysparseconfirmatoryRCT
evidence.Theexceptionisforbirthweight,where observa-tionalandRCTdataarecongruentwithapooledeffectsize in RCTsof 130g.12 Despite observational associations with
respiratoryillnesses,RCTsdemonstratenobenefitofvitamin Dsupplementsforpreventionofpneumoniaininfants,orof maternalsupplementationinpregnancyforrisk ofwheeze inoffspringat3yearsofage.1,13 Ininfantswithpneumonia
fromapopulationathighriskofdeficiency,vitaminDdidnot reduceillnessdurationbutreducedthelikelihoodofrepeat pneumoniawithin90days(RR0.78,95%CI0.64---0.94).14
Conclusion
Insummary,vitaminDsupplementationofpregnantwomen orchildren athighrisk ofverylow serum25(OH)levelsis clearlyrequired to preventrickets andneonatal hypocal-caemia.Supplementation is alsoneeded totreat children withvitamin D deficiencyricketsandpotentially augment calciumsupplementsin calciopenicrickets.The ability to
improve peak bone mass by correcting vitamin D defi-ciency in children or in pregnancy remains unproven, so routinevitaminDsupplementationcannotberecommended forthispurpose.EvidencethatvitaminDsupplementation improvesotherhealth-outcomesisalsoinsufficientto sup-portwidespreadsupplementation.
Funding
Thestudyreceivednofunding.
Conflicts
of
interest
Theauthorshavenoconflictsofinteresttodeclare.
References
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