Nutritional status of infants at six months of age following maternal influenza immunization: A randomized placebo-controlled trial in rural Nepal

Joanne Katz, Janet A Englund, Mark C Steinhoff, Subarna K Khatry, Laxman Shrestha, Jane Kuypers, Luke C Mullany, Helen Y Chu, Steven C LeClerq, Naoko Kozuki, James M Tielsch, Joanne Katz, Janet A Englund, Mark C Steinhoff, Subarna K Khatry, Laxman Shrestha, Jane Kuypers, Luke C Mullany, Helen Y Chu, Steven C LeClerq, Naoko Kozuki, James M Tielsch

Abstract

Background: Maternal influenza vaccination has increased birth weight in two randomized trials in South Asia but the impact on infant growth is unknown.

Methods: A randomized placebo-controlled trial of year round maternal influenza immunization was conducted in two annual cohorts in Sarlahi District, southern plains of Nepal, from April 2011 through April 2014. Infants born to women enrolled in the trial had weight, length, and head circumference measured at birth and 6 months of age. The study was powered for the 3 primary trial outcomes but not for stunting and wasting at 6 months of age.

Results: 3693 women received placebo or influenza vaccine between 17 and 34 weeks gestation, resulting in 3646 live births. About 72% of infants who survived had weight and length measurements between 150 and 210 days of age. Prevalence of stunting (<-2 Z scores length-for-age) was 14.8% in the placebo and 13.6% in the vaccine groups, respectively. Stunting < -3 Z scores was 3.2% versus 2.0% in placebo versus vaccine groups (RR: 0.64 (95% CI: 0.39, 1.04)). Wasting (< -2 Z scores weight for length) was 10.3% versus 11.0% for placebo versus vaccine groups. Severe wasting (< -3 Z scores weight for length) was 3.8% for placebo versus 2.6% for vaccine (RR: 0.69 (95% CI: 0.44, 1.07)). The impact of flu vaccine on wasting was greater in cohort 2 than in cohort 1, (RR: 0.66 (0.44, 0.99) for any wasting), and RR: 0.45 (0.19, 1.09) for severe wasting. This corresponded to a larger impact on birth weight and a better vaccine match with circulating viruses in cohort 2.

Conclusions: Although maternal immunization reduced low birth weight by 15%, only wasting at 6 months in the 2nd cohort was statistically significantly difference. However, the study was underpowered to detect reductions of public health importance.

Trial registration: Clinicaltrials.gov (NCT01034254).

Keywords: Birthweight; Early infancy; Maternal influenza vaccination; Small for gestational age; Stunting; Wasting.

Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Figures

Fig. 1
Fig. 1
Flow diagram of participation and follow up of infant growth in the randomized controlled trial of maternal influenza vaccination in rural Nepal.
Fig. 2a
Fig. 2a
Mean weight at 6 months of age in grams (left Y axis) for infants born to mothers who received vaccine or placebo in pregnancy by calendar time (X axis) overlaid on incidence of circulating influenza strains (right Y axis).
Fig. 2b
Fig. 2b
Mean length at 6 months of age in centimeters (left Y axis) for infants born to mothers who received vaccine or placebo in pregnancy by calendar time (X axis) overlaid on incidence of circulating influenza strains (right Y axis).

References

    1. Murray C.J., Vos T., Lozano R. Disability-adjusted life years (DALYs) for 291 diseases and injuries in 21 regions, 1990–2010: a systematic analysis for the Global Burden of Disease Study 2010. Lancet. 2012;380(9859):2197–2223.
    1. Rasmussen S.A., Jamieson D.J., Uyeki T.M. Effects of influenza on pregnant women and infants. Am J Obstet Gynecol. 2012 Sep;207(3 Suppl):S3–S8.
    1. Fell D.B., Savitz D.A., Kramer M.S. Maternal influenza and birth outcomes: systematic review of comparative studies. BJOG. 2017 Jan;124(1):48–59. Epub 2016 Jun 6.
    1. Vaccines against influenza WHO position paper – Weekly Epidemiological Record. 2012;87:461–476.
    1. Vazquez-Benitez G., Kharbanda E.O., Naleway A.L. Risk of preterm or small-for-gestational-age birth after influenza vaccination during pregnancy: caveats when conducting retrospective observational studies. Am J Epidemiol. 2016 Aug 1;184(3):176–186. Epub 2016 Jul 22.
    1. Savitz D.A., Fell D.B., Ortiz J.R., Bhat N. Does influenza vaccination improve pregnancy outcome? Methodological issues and research needs. Vaccine. 2015 Nov 25;33(47):6430–6435. Epub 2015 Aug 28.
    1. Omer S.B., Richards J.L., Madhi S.A. Three randomized trials of maternal influenza immunization in Mali, Nepal, and South Africa: Methods and expectations. Vaccine. 2015;33(32):3801–3812. doi: 10.1016/j.vaccine.2015.05.07. Epub 2015 Jun 19. Review.
    1. Steinhoff M.C., Omer S.B., Roy E. Neonatal outcomes after influenza immunization during pregnancy: a randomized controlled trial. CMAJ. 2012;184(6):645–653.
    1. Tapia M.D., Sow S.O., Tamboura B. Maternal immunisation with trivalent inactivated influenza vaccine for prevention of influenza in infants in Mali: a prospective, active-controlled, observer-blind, randomised phase 4 trial. Lancet Infect Dis. 2016
    1. Madhi S.A., Cutland C.L., Kuwanda L. Influenza vaccination of pregnant women and protection of their infants. N Engl J Med. 2014 Sep 4;371(10):918–931.
    1. Tielsch J.M., Steinhoff M., Katz J. Designs of two randomized, community-based trials to assess the impact of influenza immunization during pregnancy on respiratory illness among pregnant women and their infants and reproductive outcomes in rural Nepal. BMC Pregnancy Childbirth. 2015;15:40.
    1. Steinhoff MC, Katz J, Englund JA, et al. Year-round influenza immunization in pregnancy: a randomized placebo-controlled trial in Nepal. Lancet Inf Dis 2017;May 15. doi:10.1016/S1473-3099(17)30252-9 [EPub ahead of print].
    1. Kozuki N., Katz J., Englund J.A. Impact of maternal vaccination timing and influenza virus circulation on birth outcomes in rural Nepal. Int J Gynaecol Obstet. 2017
    1. Kuypers J., Wright N., Ferrenberg J. Comparison of real-time PCR assays with fluorescent-antibody assays for diagnosis of respiratory virus infections in children. J Clin Microbiol. 2006;44:2382–2388.
    1. Villar J., Cheikh Ismail L., Victora C.G. International standards for newborn weight, length, and head circumference by gestational age and sex: the Newborn Cross-Sectional Study of the INTERGROWTH-21st Project. Lancet. 2014 Sep 6;384(9946):857–868.
    1. World Health Organization. WHO child growth standards: height-for-age, weight-for-age, weight-for-length, weight-for-height and body mass index-for-age: methods and development Geneva: WHO; 2006. Available: .
    1. Rubin D.B. Multiple imputation after 18+ years. J Am Stat Assoc. 1996;91:473–489.
    1. Christian P. Fetal growth restriction and preterm as determinants of child growth in the first two years and potential interventions. Nestle Nutr Inst Workshop Ser. 2014;78:81–91.

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