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

• Published in: BMJ Vol. 340; no. 7747; p. 636
• Main Authors: Benn, Christine Stabell, Fisker, Ane Bærent, Napirna, Bitiguida Mutna, Roth, Adam, Diness, Birgitte Rode, Lausch, Karen Rokkedal, Ravn, Henrik, Yazdanbakhsh, Maria, Rodrigues, Amabelia, Whittle, Hilton, Aaby, Peter
• Format: Journal Article
• Language: English
• Published: England British Medical Journal Publishing Group 09.03.2010; British Medical Association; BMJ Publishing Group LTD; BMJ Publishing Group Ltd
• Subjects: Adjuvants, Immunologic - administration & dosage; Age; Babies; Basic Medicine; BCG Vaccine - administration & dosage; Birth weight; Children & youth; Clinical Trials (Epidemiology); Epidemiologic Studies; Experimentation; Factorials; Female; Girls; Guinea-Bissau - epidemiology; Hospitals; Humans; Immunization; Immunology (Including Allergy); Infant; Infant Mortality; Infant, Low Birth Weight; Infant, Newborn; Injections, Intradermal; Intervention; Low birth weight; Male; Medical and Health Sciences; Medical research; Medicin och hälsovetenskap; Medicinska och farmaceutiska grundvetenskaper; Microbiology in the medical area; Mikrobiologi inom det medicinska området; Mortality; Newborn babies; Newborns; Placebos; Prognosis; Seasons; Studies; Survival Rate; Teaching aids & devices; Vaccination; Vitamin A; Vitamin A - administration & dosage; Vitamin A Deficiency - diet therapy; Vitamin A Deficiency - mortality; Vitamins - administration & dosage; Zinc; Guinea-Bissau; Asia; Africa; South Asia
• ISSN: 0959-8138; 1756-1833; 1468-5833; 1756-1833
• DOI: 10.1136/bmj.c1101

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.