The effect of neonatal vitamin A supplementation on growth in the first year of life among low-birth-weight infants in Guinea-Bissau: two by two factorial randomised controlled trial

BMC Pediatrics

Christine Stabell Benn¹  Peter Aaby³  Ivan Monteiro³  Luis Camala²  Henrik Ravn¹  Ane Bærent Fisker³  Sofie Biering-Sørensen³ 

[1] Research Center for Vitamins and Vaccines (CVIVA), Bandim Health Project, Statens Serum Institut, Artillerivej 5, Copenhagen S 2300, Denmark;Maternidade, Hospital Nacional Simão Mendes, Bissau, Guinea-Bissau;Bandim Health Project, Indepth Network, Apartado 861, Bissau, Guinea-Bissau

关键词: BCG;    DTP;    Non-specific effects;    Growth;    Low-birth-weight;    Neonatal vitamin A supplementation;   

Others  :  1144770
DOI  :  10.1186/1471-2431-13-87

 received in 2012-11-30, accepted in 2013-05-15,  发布年份 2013

【 摘 要 】

Background

Vitamin A supplementation (VAS) may amplify the effect of vaccines. We therefore investigated if neonatal VAS given with and without Bacille Calmette-Guérin (BCG) vaccine to low-birth-weight (LBW) neonates had an effect on growth in the first year of life. We hypothesised that VAS would be particularly beneficial when provided with BCG.

Methods

We conducted a randomised two-by-two factorial trial in Guinea-Bissau; 1,717 LBW neonates were randomly allocated to VAS or placebo at birth as well as early or the usual postponed BCG vaccination. Anthropometric measurements were obtained at 2, 6, and 12 months after inclusion.

Results

Overall there was no effect of neonatal VAS on growth in the first year of life. By 2 months, VAS tended to have a beneficial effect on weight and head circumference when given with BCG but not when given without BCG (interaction: weight-for-age p = 0.07 and head circumference-for-age: p = 0.06). By 6 months, there was a beneficial effect of VAS on head circumference and weight among children who had not received DTP vaccine 2 months after inclusion (weight: 0.18 (0.00; 0.36) and head circumference 0.27 (0.06; 0.48)), but no beneficial effect among those who had received DTP.

Conclusion

The results support other trials indicating that neonatal VAS does not have consistent effects on childhood growth and if anything the effects seem to be temporary. They also show that the effect may differ by vaccination status, being beneficial when given with BCG at birth and when DTP is delayed.

Trial registration

http://www.ClinicalTrials.gov webcite (NCT00168610) (nct00168610)

【 授权许可】

   
2013 Biering-Sørensen et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

【 参考文献 】

• [1]Brink EW, Perera WD, Broske SP, Cash RA, Smith JL, Sauberlich HE, Bashor MM: Vitamin A status of children in Sri Lanka. Am J Clin Nutr 1979, 32(1):84-91.
• [2]Fawzi WW, Herrera MG, Willett WC, Nestel P, el Amin A, Mohamed KA: Dietary vitamin A intake in relation to child growth. Epidemiology 1997, 8(4):402-407.
• [3]Tarwotjo I, Katz J, West KP Jr, Tielsch JM, Sommer A: Xerophthalmia and growth in preschool Indonesian children. Am J Clin Nutr 1992, 55(6):1142-1146.
• [4]Ramakrishnan U, Nguyen P, Martorell R: Effects of micronutrients on growth of children under 5 y of age: meta-analyses of single and multiple nutrient interventions. Am J Clin Nutr 2009, 89(1):191-203.
• [5]Hadi H, Stoltzfus RJ, Dibley MJ, Moulton LH, West KP Jr, Kjolhede CL, Sadjimin T: Vitamin A supplementation selectively improves the linear growth of indonesian preschool children: results from a randomized controlled trial. Am J Clin Nutr 2000, 71(2):507-513.
• [6]Humphrey JH, Agoestina T, Juliana A, Septiana S, Widjaja H, Cerreto MC, Wu LS, Ichord RN, Katz J, West KP Jr: Neonatal vitamin A supplementation: effect on development and growth at 3 y of age. Am J Clin Nutr 1998, 68(1):109-117.
• [7]Fisker AB, Benn CS, Diness BR, Martins C, Rodrigues A, Aaby P, Bibby BM: The Effect of 50 000 IU Vitamin A with BCG Vaccine at Birth on Growth in the First Year of Life. J Trop Med 2011, 2011:570170.
• [8]Shah RS, Rajalakshmi R: Vitamin A status of the newborn in relation to gestational age, body weight, and maternal nutritional status. Am J Clin Nutr 1984, 40(4):794-800.
• [9]Adelekan DA, Northrop-Clewes CA, Owa JA, Oyedeji AO, Owoeye AA, Thurnham DI: Use of biomarkers of sub-clinical infection, nutrition and neonatal maturity to interpret plasma retinol in Nigerian neonates. Br J Nutr 2007, 90(02):353.
• [10]Benn CS, Martins C, Rodrigues A, Ravn H, Fisker AB, Christoffersen D, Aaby P: The effect of vitamin A supplementation administered with missing vaccines during national immunization days in Guinea-Bissau. Int J Epidemiol 2009, 38(1):304-311.
• [11]Benn CS, Bale C, Sommerfelt H, Friis H, Aaby P: Hypothesis: Vitamin A supplementation and childhood mortality: amplification of the non-specific effects of vaccines? Int J Epidemiol 2003, 32(5):822-828.
• [12]Benn CS, Fisker AB, Napirna BM, Roth A, Diness BR, Lausch KR, Ravn H, Yazdanbakhsh M, Rodrigues A, Whittle H, et al.: Vitamin A supplementation and BCG vaccination at birth in low birthweight neonates: two by two factorial randomised controlled trial. BMJ 2010, 340(mar09):c1101. c1101
• [13]Aaby P, Roth A, Ravn H, Napirna BM, Rodrigues A, Lisse IM, Stensballe L, Diness BR, Lausch KR, Lund N, et al.: Randomized trial of BCG vaccination at birth to low-birth-weight children: beneficial nonspecific effects in the neonatal period? J Infect Dis 2011, 204(2):245-252.
• [14]Jakobsen MS, Sodemann M, Molbak K, Aaby P: Reason for termination of breastfeeding and the length of breastfeeding. Int J Epidemiol 1996, 25(1):115-121.
• [15]Aaby P, Ravn H, Roth A, Rodrigues A, Lisse IM, Diness BR, Lausch KR, Lund N, Rasmussen J, Biering-Sorensen S, et al.: Early diphtheria-tetanus-pertussis vaccination associated with higher female mortality and no difference in male mortality in a cohort of low birthweight children: an observational study within a randomised trial. Arch Dis Child 2012, 97(8):685-691.
• [16]World Health Organization: WHO Multicentre Growth Reference Study Group. WHO Child Growth Standards: Growth velocity based on weight, length and head circumference. Geneva: Methods and development; 2009.
• [17]Rasmussen J, Andersen A, Fisker AB, Ravn H, Sodemann M, Rodrigues A, Benn CS, Aaby P: Mid-upper-arm-circumference and mid-upper-arm circumference z-score: the best predictor of mortality? Eur J Clin Nutr 2012, 66(9):998-1003.
• [18]Barros AJ, Hirakata VN: Alternatives for logistic regression in cross-sectional studies: an empirical comparison of models that directly estimate the prevalence ratio. BMC Med Res Methodol 2003, 3:21. BioMed Central Full Text
• [19]Benn CS, Fisker AB, Diness BR, Aaby P: Neonatal vitamin a supplementation: sex-differential effects on mortality? J Infect Dis 2006, 194(5):719.
• [20]Benn CS, Rodrigues A, Yazdanbakhsh M, Fisker AB, Ravn H, Whittle H, Aaby P: The effect of high-dose vitamin A supplementation administered with BCG vaccine at birth may be modified by subsequent DTP vaccination. Vaccine 2009, 27(21):2891-2898.
• [21]Benn CS, Whittle H, Fisker AB, Aaby P: Neonatal vitamin A supplementation in South Asia: Rapid implementation or understanding the variation? BMJ 2008. http://www.bmj.com/rapid-response/2011/11/02/neonatal-vitamin-supplementation-south-asia-rapid-implementation-or-unders webcite