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Randomized Controlled Trial
. 2010 Mar 9:340:c1101.
doi: 10.1136/bmj.c1101.

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

Christine Stabell Benn  1 , Ane Baerent Fisker, Bitiguida Mutna Napirna, Adam Roth, Birgitte Rode Diness, Karen Rokkedal Lausch, Henrik Ravn, Maria Yazdanbakhsh, Amabelia Rodrigues, Hilton Whittle, Peter Aaby
Affiliations
Randomized Controlled Trial

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

Christine Stabell Benn et al. BMJ. .

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. Trial registration ClinicalTrials.gov NCT00168610.

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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 (1) No financial support for the submitted work from anyone other than their employer; (2) No financial relationships with commercial entities that might have an interest in the submitted work; (3) No spouses, partners, or children with relationships with commercial entities that might have an interest in the submitted work; (4) No non-financial interests that may be relevant to the submitted work.

Figures

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Fig 1 Trial profile
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Fig 2 Cumulative mortality during the first year of life for all children
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Fig 3 Cumulative mortality during the first year of life for boys
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Fig 4 Cumulative mortality during the first year of life for girls
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Fig 5 Causes of deaths by intervention group and sex. The “Other problems” category includes AIDS related deaths, sudden death, tumours, encephalitis, and hepatitis
See this image and copyright information in PMC

Comment in

References

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