title: Neonatal vitamin A supplementation for the prevention of mortality and morbidity in term neonates in low and middle income countries.
abstract: Vitamin A deficiency is a major public health problem in low and middle income countries. Vitamin A supplementation in children six months of age and older has been found to be beneficial, but no effect of supplementation has been noted for children between one and five months of age. Supplementation during the neonatal period has been suggested to have an impact by increasing body stores in early infancy.
  
  
  
  To evaluate the role of vitamin A supplementation for term neonates in low and middle income countries with respect to prevention of mortality and morbidity.
  
  
  
  We used the standard search strategy of the Cochrane Neonatal Review Group to search the Cochrane Central Register of Controlled Trials (CENTRAL; 2016, Issue 2), MEDLINE via PubMed (1966 to 13 March 2016), Embase (1980 to 13 March 2016) and the Cumulative Index to Nursing and Allied Health Literature (CINAHL; 1982 to 13 March 2016). We also searched clinical trials databases, conference proceedings and reference lists of retrieved articles for randomised controlled trials and quasi-randomised trials.
  
  
  
  Randomised and quasi-randomised controlled trials. Also trials with a factorial design.
  
  
  
  Two review authors independently assessed trial quality and extracted study data. We used the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach to assess the quality of evidence.
  
  
  
  We included 12 trials (168,460 neonates) in this review, with only a few trials reporting disaggregated data for term infants. Therefore, we analysed data and presented estimates for term infants (when specified) and for all infants.Data for term neonates from three studies did not show a statistically significant effect on the risk of infant mortality at six months in the vitamin A group compared with the control group (typical risk ratio (RR) 0.80; 95% confidence interval (CI) 0.54 to 1.18; I2= 63%). Analysis of data for all infants from 11 studies revealed no evidence of a significant reduction in the risk of infant mortality at six months among neonates supplemented with vitamin A compared with control neonates (typical RR 0.98, 95% CI 0.89 to 1.07; I2= 47%). We observed similar results for infant mortality at 12 months of age with no significant effect of vitamin A compared with control (typical RR 1.04, 95% CI 0.94 to 1.15; I2= 47%). Limited data were available for the outcomes of cause-specific mortality and morbidity, vitamin A deficiency, anaemia and adverse events.
  
  
  
  Given the high burden of death among children younger than five years of age in low and middle income countries, and the fact that mortality in infancy is a major contributory cause, it is critical to obtain sound scientific evidence of the effect of vitamin A supplementation during the neonatal period on infant mortality and morbidity. Evidence provided in this review does not indicate a potential beneficial effect of vitamin A supplementation among neonates at birth in reducing mortality during the first six months or 12 months of life. Given this finding and the absence of a clear indication of the biological mechanism through which vitamin A could affect mortality, along with substantial conflicting findings from individual studies conducted in settings with potentially varying levels of maternal vitamin A deficiency and infant mortality, absence of follow-up studies assessing any long-term impact of a bulging fontanelle after supplementation and the finding of a potentially harmful effect among female infants, additional research is warranted before a decision can be reached regarding policy recommendations for this intervention.
authors.affiliation: Department of Global Health and Population, Harvard School of Public Health, 677 Huntington Avenue, Boston, MA, USA, 02115.
authors.forename: Batool A
authors.initials: BA
authors.lastname: Haider
authors.affiliation: Centre for Global Child Health, Hospital for Sick Children, Toronto, Canada.
authors.forename: Renee
authors.initials: R
authors.lastname: Sharma
authors.affiliation: Centre for Global Child Health, Hospital for Sick Children, Toronto, Canada.
authors.forename: Zulfiqar A
authors.initials: ZA
authors.lastname: Bhutta
mesh_terms: D003906:Developing Countries; D006801:Humans; D007223:Infant; D007226:Infant Mortality; D007231:Infant, Newborn; D009017:Morbidity; D016032:Randomized Controlled Trials as Topic; D014801:Vitamin A / Q000008:administration & dosage* / Q000009:adverse effects; D014802:Vitamin A Deficiency / Q000517:prevention & control; D014815:Vitamins / Q000008:administration & dosage* / Q000009:adverse effects
chemical_list: D014815:Vitamins; D014801:Vitamin A