TY - JOUR
T1 - Early neonatal Vitamin A supplementation and infant mortality
T2 - An individual participant data meta-analysis of randomised controlled trials
AU - West, Keith P.
AU - Wu, Lee S.F.
AU - Ali, Hasmot
AU - Klemm, Rolf D.W.
AU - Edmond, Karen Margaret
AU - Hurt, Lisa
AU - Kirkwood, Betty
AU - Newton, Sam
AU - Shannon, Caitlin
AU - Taneja, Sunita
AU - Mazumder, Sarmila
AU - Bhatia, Kiran
AU - Bhandari, Nita
AU - Katz, Joanne
AU - Tielsch, James M.
AU - Humphrey, Jean
AU - Agoestina, Tina
AU - Soofi, Sajid Bashir
AU - Ariff, Shabina
AU - Bhatti, Zaid
AU - Cousens, Simon
AU - Bhutta, Zulfiqar A.
AU - Ntozini, Robert
AU - Masanja, Honorati
AU - Smith, Emily R.
AU - Muhihi, Alfa
AU - Fawzi, Wafaie
AU - Bahl, Rajiv
AU - Martines, Jose
AU - Yoshida, Sachiyo
N1 - Publisher Copyright:
© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.
PY - 2019/3/1
Y1 - 2019/3/1
N2 - Biannual vitamin A supplementation is a well-established survival tool for preschool children 6 months and older in vitamin A deficient populations but this schedule misses the opportunity to intervene on most young infant deaths. Randomised trials of neonatal vitamin A supplementation (NVAS) in the first few days of life to assess its impact on under 6-month mortality in low/middle-income countries have had varying results. Methods Investigators of 11 published randomised placebo-controlled NVAS trials (n=163 567 children) reanalysed their data according to an agreed plan and pooled the primary outcomes of mortality from supplementation through 6 and 12 months of age using random effects models and meta-regression. One investigator withdrew but allowed use of the data. Findings Overall there was no effect of NVAS on infant survival through 6 (risk ratio (RR) 0.97; 95% CI 0.89 to 1.06) or 12 months of age (RR 1.00; 95% CI 0.93 to 1.08) but results varied by study population characteristics. NVAS significantly reduced 6-month mortality among the trials conducted in Southern Asia (RR 0.87; 95% CI 0.77 to 0.98), in contexts with moderate or severe vitamin A deficiency (defined as 10% or higher proportion of women with serum retinol <0.7 μmol/L or 5% or more women with night blindness) (RR 0.87; 95% CI 0.80 to 0.94), early infant mortality was 30 or more per 1000 live births (RR 0.91; 95% CI 0.85 to 0.98), 75% or more of infant mortality occurred in the first 6 months of life (RR 0.92; 95% CI 0.84 to 1.01), or where >32% mothers had no schooling (RR 0.88; 95% CI 0.80 to 0.96). NVAS did not reduce mortality in the first 6 months of life in trials conducted in Africa, in contexts characterised by a low prevalence of vitamin A deficiency, lower rates of infant mortality and where maternal education was more prevalent. There was a suggestion of increased infant mortality in trials conducted in Africa (RR 1.07; 95% CI 1.00 to 1.15). Individual-level characteristics such as sex, birth weight, gestational age and size, age at dosing, parity, time of breast feeding initiation, maternal education and maternal vitamin A supplementation did not modify the impact of NVAS. Conclusion NVAS reduced infant mortality in South Asia, in contexts where the prevalence of maternal vitamin A deficiency is moderate to severe and early infant mortality is high; but it had no beneficial effect on infant survival in Africa, in contexts where the prevalence of maternal vitamin A deficiency is lower, early infant mortality is low.
AB - Biannual vitamin A supplementation is a well-established survival tool for preschool children 6 months and older in vitamin A deficient populations but this schedule misses the opportunity to intervene on most young infant deaths. Randomised trials of neonatal vitamin A supplementation (NVAS) in the first few days of life to assess its impact on under 6-month mortality in low/middle-income countries have had varying results. Methods Investigators of 11 published randomised placebo-controlled NVAS trials (n=163 567 children) reanalysed their data according to an agreed plan and pooled the primary outcomes of mortality from supplementation through 6 and 12 months of age using random effects models and meta-regression. One investigator withdrew but allowed use of the data. Findings Overall there was no effect of NVAS on infant survival through 6 (risk ratio (RR) 0.97; 95% CI 0.89 to 1.06) or 12 months of age (RR 1.00; 95% CI 0.93 to 1.08) but results varied by study population characteristics. NVAS significantly reduced 6-month mortality among the trials conducted in Southern Asia (RR 0.87; 95% CI 0.77 to 0.98), in contexts with moderate or severe vitamin A deficiency (defined as 10% or higher proportion of women with serum retinol <0.7 μmol/L or 5% or more women with night blindness) (RR 0.87; 95% CI 0.80 to 0.94), early infant mortality was 30 or more per 1000 live births (RR 0.91; 95% CI 0.85 to 0.98), 75% or more of infant mortality occurred in the first 6 months of life (RR 0.92; 95% CI 0.84 to 1.01), or where >32% mothers had no schooling (RR 0.88; 95% CI 0.80 to 0.96). NVAS did not reduce mortality in the first 6 months of life in trials conducted in Africa, in contexts characterised by a low prevalence of vitamin A deficiency, lower rates of infant mortality and where maternal education was more prevalent. There was a suggestion of increased infant mortality in trials conducted in Africa (RR 1.07; 95% CI 1.00 to 1.15). Individual-level characteristics such as sex, birth weight, gestational age and size, age at dosing, parity, time of breast feeding initiation, maternal education and maternal vitamin A supplementation did not modify the impact of NVAS. Conclusion NVAS reduced infant mortality in South Asia, in contexts where the prevalence of maternal vitamin A deficiency is moderate to severe and early infant mortality is high; but it had no beneficial effect on infant survival in Africa, in contexts where the prevalence of maternal vitamin A deficiency is lower, early infant mortality is low.
KW - infant mortality
KW - neonatal Vitamin A supplementation
UR - http://www.scopus.com/inward/record.url?scp=85056585731&partnerID=8YFLogxK
U2 - 10.1136/archdischild-2018-315242
DO - 10.1136/archdischild-2018-315242
M3 - Article
C2 - 30425075
AN - SCOPUS:85056585731
SN - 0003-9888
VL - 104
SP - 217
EP - 226
JO - Archives of Disease in Childhood
JF - Archives of Disease in Childhood
IS - 3
ER -