Effect of weekly vitamin D supplements on mortality, morbidity, and growth of low birthweight term infants in India up to age 6 months: randomised controlled trialBMJ 2011; 342 doi: https://doi.org/10.1136/bmj.d2975 (Published 31 May 2011) Cite this as: BMJ 2011;342:d2975
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Benefit of vitamin D supplementation on morbidity and mortality of term low birth weight infants- an under estimate?
Kumar et al have done a splendid job of conducting the trial by
enrolling most vulnerable population, and ensuring the highest quality. We
however propose that vitamin D supplementation would have a greater impact
on growth parameters and perhaps reduce morbidity and death in these
As the investigators admit, 28% and 38% of the enrolled infants were
lost to follow up for the primary and secondary outcomes respectively, who
were selectively from poorer and less well educated families in lowest
quintiles of socio-economic strata. Apparently these infants belonged to
migrant population of laborers, who come to bigger cities like Delhi for
Since infant mortality is inversely related to socioeconomic status
(54.6 per thousand live births among the urban poor compared to 35.5 among
the non-poor),1 and parental education2 especially of mother,3,4 it can be
safely concluded that the infants lost to follow up were at higher risk of
mortality compared to those who completed the study. Also, children born
to women with a low vitamin D level have been shown to have a 61% higher
risk of dying during follow-up.5 Since vitamin D deficiency is inversely
related to the socio-economic status6-8 and maternal education,7,8 mothers
of infants lost to follow up were likely to be more severely deficient and
hence their children at higher risk of mortality.
The above statements are consolidated by the fact that the mortality
among the study infants who were followed up was 2.5% and 2.6% in vitamin
D and placebo groups respectively, as against anticipated mortality of 6%.
These infants are also more likely to have suffered from more severe
vitamin D deficiency, and in corollary, more likely to be benefitted with
vitamin D supplementation compared to infants who completed the study.
This factor may be responsible for no difference in combined outcome of
death or severe morbidity, and small positive effect size of improved
weight, length and arm circumference. This is further substantiated by the
fact that in infants with z scores ?2 had much greater improvement on
vitamin D supplementation, though it was not statistically significant
because of smaller numbers.
Secondly, we would like to re-emphasize the point made by the authors
that the vitamin D dose might be insufficient. At the end of
supplementation of 200 IU/day for 6 months, nearly 43% of infants were yet
deficient in supplementation group. Current evidence suggests that 200
IU/day of vitamin D will not maintain 25OHD concentration >20 ng/mL (50
nmol/L) even in healthy infants,9 and a daily dose of minimum 400 IU/day
This is especially true in our context, as there is widespread
maternal vitamin D deficiency,11,12 which would not only result in lower
vitamin D levels of infants at birth, but also during the initial 6 months
of life, since most of the infants were exclusively breastfed.
In a recent randomized controlled trial of vitamin D supplementation
among Delhi schoolgirls, 93.7% of which were vitamin D deficient
(25OHD<20 nmol/L) at baseline, supplementation of 60,000 IU monthly or
two-monthly of vitamin D (approx 2000 and 1000 IU/day, respectively) was
done, which resulted in only 47% of them being vitamin D sufficient at the
end of one year.13
In a recently concluded study of ours from a similar setting and
population mix, we found universal severe vitamin D deficiency in
virtually all infants at birth and 3-6 months and in their mothers at
birth. Most of them (78.7% of term LBW and 90.9% of term NBW) were
exclusively/predominantly breastfed, with 19.7% and 27.3% having received
supplementation with vitamin D at a variable dose of 200-400 IU/day (Table
We would like to propose that supplementation of vitamin D deficiency
would have a greater impact in terms of growth parameter and perhaps
reducing death and morbidity, and further studies are required before we
can reach to a reasonable conclusion with regard to the supplementation of
this vulnerable population.
1. Agarwal S, Srivastava A. Social determinants of children's
health in urban areas in India. J Health Care Poor Underserved 2009;20(4
2. Badari S, Gopal YS, Devaramani SC. Infant mortality, its
components and correlates: findings from a longitudinal study in rural
Karnataka, India. Genus 1991 Jan-Jun;47(1-2):89-108.
3. Kravdal ?. Child mortality in India: the community-level
effect of education. Popul Stud (Camb) 2004;58(2):177-92.
4. Nath DC, Land KC, Singh KK . Birth spacing, breastfeeding,
and early child mortality in a traditional Indian society: a hazards model
analysis. Soc Biol 1994 Fall-Winter;41(3-4):168-80.
5. Mehta S, Hunter DJ, Mugusi FM, Spiegelman D, Manji KP,
Giovannucci EL, Hertzmark E, Msamanga GI, Fawzi WWPerinatal outcomes,
including mother-to-child transmission of HIV, and child mortality and
their association with maternal vitamin D status in Tanzania. J Infect Dis
2009 Oct 1;200(7):1022-30.
6. Marwaha RK, Tandon N, Reddy DR, Aggarwal R, Singh R, Sawhney
RC, Saluja B, Ganie MA, Singh S. Vitamin D and bone mineral density status
of healthy schoolchildren in northern India. Am J Clin Nutr. 2005
7. Olmez D, Bober E, Buyukgebiz A, Cimrin D. The frequency of
vitamin D insufficiency in healthy female adolescents. Acta Paediatr. 2006
8. Andiran N, Yordam N, Oz?n A. Risk factors for vitamin D
deficiency in breast-fed newborns and their mothers. Nutrition. 2002
9. Wagner CL, Greer FR; American Academy of Pediatrics Section
on Breastfeeding; American Academy of Pediatrics Committee on Nutrition.
Prevention of rickets and vitamin D deficiency in infants, children, and
adolescents. Pediatrics2008 Nov;122(5):1142-52.
10. Onal H, Adal E, Alpaslan S, Ersen A, Aydin A. Is daily 400 IU
of vitamin D supplementation appropriate for every country: a cross-
sectional study. Eur J Nutr 2010 Oct;49(7):395-400. Epub 2010 Feb 19
11. Sachan A, Gupta R, Das V, Agarwal A, Awasthi PK, Bhatia V.
High prevalence of vitamin D deficiency among pregnant women and their
newborns in northern India. Am J Clin Nutr 2005;81: 1060-4.
12. Sahu M. Vitamin D deficiency in rural girls and pregnant women
despite abundant sunsjhine in northern india. Clin Endocrinology 2009
13. Marwaha RK, Tandon N, Agarwal N, Puri S, Agarwal R, Singh S,
Mani K. Impact of two regimens of vitamin D supplementation on calcium -
vitamin D - PTH axis of schoolgirls of Delhi. Indian Pediatr 2010
Sep;47(9):761-9. Epub 2010 Jan 15
Table 1. Vitamin D levels of term low and normal birth weight infants and their mothers
Competing interests: No competing interests