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 trial

Geeta Trilok Kumar, Harshpal Singh Sachdev, Harish Chellani, Andrea M Rehman, Vini Singh, Harsh Arora, Suzanne Filteau, Geeta Trilok Kumar, Harshpal Singh Sachdev, Harish Chellani, Andrea M Rehman, Vini Singh, Harsh Arora, Suzanne Filteau

Abstract

Objective: To investigate whether vitamin D supplementation can decrease the mortality and morbidity of low birthweight infants in low income countries.

Design: Randomised controlled trial.

Setting: Large government hospital in New Delhi, India.

Participants: 2079 low birthweight infants born at term (>37 weeks' gestation).

Main outcome measures: Primary outcome was admission to hospital or death during the first six months of life. Main secondary outcome was growth.

Interventions: Weekly vitamin D supplements for six months at a dose of one recommended nutrient intake per day (35 µg/week). Infants were visited weekly at home for observed supplementation and were brought to the clinic monthly for clinical examination and anthropometric measurements.

Results: Between group differences were not significant for death or hospital admissions (92 among 1039 infants in the vitamin D group v 99 among 1040 infants in the placebo group; adjusted rate ratio 0.93, 95% confidence interval 0.68 to 1.29; P = 0.68), or referral to the outpatient clinic for moderate morbidity. Vitamin D supplementation resulted in better vitamin D status as assessed by plasma calcidiol levels at six months. In adjusted analyses, vitamin D treatment significantly increased standard deviation (z) scores at six months for weight, length, and arm circumference and decreased the proportion of children with stunted growth (length for age z score ≤ 2) or with arm circumference z scores of 2 or less.

Conclusion: A weekly dose of vitamin D resulted in better vitamin D status and benefited the classic vitamin D function of bone growth but did not decrease the incidence of severe morbidity or death among young low birthweight infants. Trial registration ClinicalTrials.gov NCT00415402.

Conflict of interest statement

Competing interests: All authors have completed the Unified Competing Interest form at www.icmje.org/coi_disclosure.pdf (available on request from the corresponding author) and declare: no support from any organisation for the submitted work; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years, no other relationships or activities that could appear to have influenced the submitted work.

Figures

https://www.ncbi.nlm.nih.gov/pmc/articles/instance/4788083/bin/kumg841403.f1_default.jpg
Fig 1 Flow of participants through study
https://www.ncbi.nlm.nih.gov/pmc/articles/instance/4788083/bin/kumg841403.f2_default.jpg
Fig 2 Kaplan-Meier plot of time to admission to hospital or death of infants receiving vitamin D supplementation or placebo

References

    1. Holick MF. Vitamin D deficiency. N Engl J Med 2007;357:266-81.
    1. Van Etten E, Stoffels K, Gysemans C, Mathieu C, Overbergh L. Regulation of vitamin D homeostasis: implications for the immune system. Nutr Rev 2008;66(10 suppl 2):S125-34.
    1. Roth DE, Shah R, Black RE, Baqui AH. Vitamin D status and acute lower respiratory infection in early childhood in Sylhet, Bangladesh. Acta Paediatr 2010;99:389-93.
    1. Laaksi I, Ruohola JP, Tuohimaa P, Auvinen A, Haataja R, Pihlajamaki H, et al. An association of serum vitamin D concentrations < 40 nmol/L with acute respiratory tract infection in young Finnish men. Am J Clin Nutr 2007;86:714-7.
    1. Gibney KB, MacGregor L, Leder K, Torresi J, Marshall C, Ebeling PR, et al. Vitamin D deficiency is associated with tuberculosis and latent tuberculosis infection in immigrants from sub-Saharan Africa. Clin Infect Dis 2008;46:443-6.
    1. Wayse V, Yousafzai A, Mogale K, Filteau S. Association of subclinical vitamin D deficiency with severe acute lower respiratory infection in Indian children under 5 y. Eur J Clin Nutr 2004;58:563-7.
    1. Wejse C, Gomes VF, Rabna P, Gustafson P, Aaby P, Lisse IM, et al. Vitamin D as supplementary treatment for tuberculosis: a double-blind, randomized, placebo-controlled trial. Am J Respir Crit Care Med 2009;179:843-50.
    1. Li-Ng M, Aloia JF, Pollack S, Cunha BA, Mikhail M, Yeh J, et al. A randomized controlled trial of vitamin D3 supplementation for the prevention of symptomatic upper respiratory tract infections. Epidemiol Infect 2009;137:1396-404.
    1. Avenell A, Cook JA, Maclennan GS, Macpherson GC. Vitamin D supplementation to prevent infections: a sub-study of a randomised placebo-controlled trial in older people (RECORD trial, ISRCTN 51647438). Age Ageing 2007;36:574-7.
    1. Urashima M, Segawa T, Okazaki M, Kurihara M, Wada Y, Ida H. Randomized trial of vitamin D supplementation to prevent seasonal influenza A in schoolchildren. Am J Clin Nutr 2010;91:1255-60.
    1. Goswami R, Gupta N, Goswami D, Marwaha RK, Tandon N, Kochupillai N. Prevalence and significance of low 25-hydroxyvitamin D concentrations in healthy subjects in Delhi. Am J Clin Nutr 2000;72:472-5.
    1. Agarwal KS, Mughal MZ, Upadhyay P, Berry JL, Mawer EB, Puliyel JM. The impact of atmospheric pollution on vitamin D status of infants and toddlers in Delhi, India. Arch Dis Child 2002;87:111-3.
    1. Neonatal Mortality Formative Research Working Group. Developing community-based intervention strategies to save newborn lives: lessons learned from formative research in five countries. J Perinatol 2008;28(suppl 2):S2-8.
    1. Food and Agriculture Organization, World Health Organization. Expert consultation on human vitamin and mineral requirements. FAO/WHO, 2002.
    1. World Health Organization. Child growth standards. 2006. .
    1. Ulijaszek S, Kerr D. Anthropometric measurement error and the assessment of nutritional status. Br J Nutr 1999;82:165-77.
    1. Lucas RM, Ponsonby AL, Pasco JA, Morley R. Future health implications of prenatal and early-life vitamin D status. Nutr Rev 2008;66:710-20.
    1. Filmer D, Pritchett L. Estimating wealth effects without expenditure data—or tears: an application to educational enrolments in states of India. Demography 2001;38:115-32.
    1. Sarna MS, Saili A, Dutta AK, Kumari S. Neonatal mortality patterns in an urban hospital. Indian Pediatr 1991;28:719-24.
    1. Sazawal S, Black RE, Menon VP, Dinghra P, Caulfield LE, Dhingra U, et al. Zinc supplementation in infants born small for gestational age reduces mortality: a prospective, randomized, controlled trial. Pediatrics 2001;108:1280-6.
    1. Lira PI, Ashworth A, Morris SS. Effect of zinc supplementation on the morbidity, immune function, and growth of low-birth-weight, full-term infants in northeast Brazil. Am J Clin Nutr 1998;68(suppl 2):418-24S.
    1. Victora CG, de Onis M, Hallal PC, Blossner M, Shrimpton R. Worldwide timing of growth faltering: revisiting implications for interventions. Pediatrics 2010;125:e473-80.
    1. Gale CR, Robinson SM, Harvey NC, Javaid MK, Jiang B, Martyn CN, et al. Maternal vitamin D status during pregnancy and child outcomes. Eur J Clin Nutr 2008;62:68-77.
    1. McCann JC, Ames BN. Is there convincing biological or behavioral evidence linking vitamin D deficiency to brain dysfunction? FASEB J 2008;22:982-1001.
    1. Autier P, Gandini S. Vitamin D supplementation and total mortality: a meta-analysis of randomized controlled trials. Arch Intern Med 2007;167:1730-7.
    1. Manaseki-Holland S, Qader G, Isaq Masher M, Bruce J, Zulf Mughal M, Chandramohan D, et al. Effects of vitamin D supplementation to children diagnosed with pneumonia in Kabul: a randomised controlled trial. Trop Med Int Health 2010;15:1148-55.
    1. Martineau AR, Timms PM, Bothamley GH, Hanifa Y, Islam K, Claxton AP, et al. High-dose vitamin D(3) during intensive-phase antimicrobial treatment of pulmonary tuberculosis: a double-blind randomised controlled trial. Lancet 2011;377:242-50.
    1. Kovacs CS. Vitamin D in pregnancy and lactation: maternal, fetal, and neonatal outcomes from human and animal studies. Am J Clin Nutr 2008;88:520-8S.
    1. Sahu M, Das V, Aggarwal A, Rawat V, Saxena P, Bhatia V. Vitamin D replacement in pregnant women in rural north India: a pilot study. Eur J Clin Nutr 2009;63:1157-9.

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