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Vitamin A supplementation and BCG vaccination at birth in low birthweight neonates: two by two factorial randomised controlled trial

Benn, Christine Stabell; Fisker, Ane Baerent; Napirna, Bitiguida Mutna; Roth, Adam LU ; Diness, Birgitte Rode; Lausch, Karen Rokkedal; Ravn, Henrik; Yazdanbakhsh, Maria; Rodrigues, Amabelia and Whittle, Hilton, et al. (2010) In B M J: British Medical Journal1995-01-01+01:00 340.
Abstract
Objective To investigate the effect of vitamin A supplementation and BCG vaccination at birth in low birthweight neonates. Design Randomised, placebo controlled, two by two factorial trial. Setting Bissau, Guinea-Bissau. Participants 1717 low birthweight neonates born at the national hospital. Intervention Neonates who weighed less than 2.5 kg were randomly assigned to 25 000 IU vitamin A or placebo, as well as to early BCG vaccine or the usual late BCG vaccine, and were followed until age 12 months. Main outcome measure Mortality, calculated as mortality rate ratios (MRRs), after follow-up to 12 months of age for infants who received vitamin A supplementation compared with those who received placebo. Results No interaction was observed... (More)
Objective To investigate the effect of vitamin A supplementation and BCG vaccination at birth in low birthweight neonates. Design Randomised, placebo controlled, two by two factorial trial. Setting Bissau, Guinea-Bissau. Participants 1717 low birthweight neonates born at the national hospital. Intervention Neonates who weighed less than 2.5 kg were randomly assigned to 25 000 IU vitamin A or placebo, as well as to early BCG vaccine or the usual late BCG vaccine, and were followed until age 12 months. Main outcome measure Mortality, calculated as mortality rate ratios (MRRs), after follow-up to 12 months of age for infants who received vitamin A supplementation compared with those who received placebo. Results No interaction was observed between vitamin A supplementation and BCG vaccine allocation (P=0.73). Vitamin A supplementation at birth was not significantly associated with mortality: the MRR of vitamin A supplementation compared with placebo, controlled for randomisation to "early BCG" versus "no early BCG" was 1.08 (95% CI 0.79 to 1.47). Stratification by sex revealed a significant interaction between vitamin A supplementation and sex (P=0.046), the MRR of vitamin A supplementation being 0.74 ( 95% CI 0.45 to 1.22) in boys and 1.42 (95% CI 0.94 to 2.15) in girls. When these data were combined with data from a complementary trial among normal birthweight neonates in Guinea-Bissau, the combined estimate of the effect of neonatal vitamin A supplementation on mortality was 1.08 ( 95% CI 0.87 to 1.33); 0.80 ( 95% CI 0.58 to 1.10) in boys and 1.41 ( 95% CI 1.04 to 1.90) in girls (P=0.01 for interaction between neonatal vitamin A and sex). Conclusions The combined results of this trial and the complementary trial among normal birthweight neonates have now shown that, overall, it would not be beneficial to implement a neonatal vitamin A supplementation policy in Guinea-Bissau. Worryingly, the trials show that vitamin A supplementation at birth can be harmful in girls. Previous studies and future trials should investigate the possibility that vitamin A supplementation has sex differential effects. (Less)
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B M J: British Medical Journal1995-01-01+01:00
volume
340
publisher
BMJ Publishing Group
external identifiers
  • wos:000275656700001
  • scopus:77949731128
ISSN
1756-1833
DOI
10.1136/bmj.c1101
language
English
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yes
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4753be4d-e39e-4c9d-950d-115291cf19ae (old id 1589140)
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2010-04-20 14:02:31
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2018-06-17 03:21:00
@article{4753be4d-e39e-4c9d-950d-115291cf19ae,
  abstract     = {Objective To investigate the effect of vitamin A supplementation and BCG vaccination at birth in low birthweight neonates. Design Randomised, placebo controlled, two by two factorial trial. Setting Bissau, Guinea-Bissau. Participants 1717 low birthweight neonates born at the national hospital. Intervention Neonates who weighed less than 2.5 kg were randomly assigned to 25 000 IU vitamin A or placebo, as well as to early BCG vaccine or the usual late BCG vaccine, and were followed until age 12 months. Main outcome measure Mortality, calculated as mortality rate ratios (MRRs), after follow-up to 12 months of age for infants who received vitamin A supplementation compared with those who received placebo. Results No interaction was observed between vitamin A supplementation and BCG vaccine allocation (P=0.73). Vitamin A supplementation at birth was not significantly associated with mortality: the MRR of vitamin A supplementation compared with placebo, controlled for randomisation to "early BCG" versus "no early BCG" was 1.08 (95% CI 0.79 to 1.47). Stratification by sex revealed a significant interaction between vitamin A supplementation and sex (P=0.046), the MRR of vitamin A supplementation being 0.74 ( 95% CI 0.45 to 1.22) in boys and 1.42 (95% CI 0.94 to 2.15) in girls. When these data were combined with data from a complementary trial among normal birthweight neonates in Guinea-Bissau, the combined estimate of the effect of neonatal vitamin A supplementation on mortality was 1.08 ( 95% CI 0.87 to 1.33); 0.80 ( 95% CI 0.58 to 1.10) in boys and 1.41 ( 95% CI 1.04 to 1.90) in girls (P=0.01 for interaction between neonatal vitamin A and sex). Conclusions The combined results of this trial and the complementary trial among normal birthweight neonates have now shown that, overall, it would not be beneficial to implement a neonatal vitamin A supplementation policy in Guinea-Bissau. Worryingly, the trials show that vitamin A supplementation at birth can be harmful in girls. Previous studies and future trials should investigate the possibility that vitamin A supplementation has sex differential effects.},
  author       = {Benn, Christine Stabell and Fisker, Ane Baerent and Napirna, Bitiguida Mutna and Roth, Adam and Diness, Birgitte Rode and Lausch, Karen Rokkedal and Ravn, Henrik and Yazdanbakhsh, Maria and Rodrigues, Amabelia and Whittle, Hilton and Aaby, Peter},
  issn         = {1756-1833},
  language     = {eng},
  publisher    = {BMJ Publishing Group},
  series       = {B M J: British Medical Journal1995-01-01+01:00},
  title        = {Vitamin A supplementation and BCG vaccination at birth in low birthweight neonates: two by two factorial randomised controlled trial},
  url          = {http://dx.doi.org/10.1136/bmj.c1101},
  volume       = {340},
  year         = {2010},
}