14
days is therefore warranted in order to inform the policy-related
question of whether interventions of shorter intervals can achieve
comparable results to those achieved with routine supplementation [2].
In this issue of Indian Pediatrics, Malik,
et al. [4] report the findings of a double-blind RCT assessing the
effect of prophylactic oral zinc supplementation for 14 days on the
incidence and duration of ALRI among infants 6-11 months of age in an
urban area of Delhi, India. This is the first study designed to evaluate
the effect of preventive short-course zinc supplementation on the
occurrence and severity of subsequent upper and lower respiratory tract
infections among infants. Previously published estimates of the effects
of short-course zinc supplementation on ARI outcomes have originated
from one Bangladeshi study of children aged 12-35 months [5], and three
trials assessing ALRI outcomes in the months following zinc treatment
for diarrhea among children aged 2-59 months [6-8].
Malik, et al. randomized 272 infants to daily
supplementation with placebo or zinc (20 mg/5 mL elemental zinc as zinc
sulfate) syrup for 14 days, and subsequently conducted follow-up visits
every two weeks for 5 months to collect morbidity data. Short-course
zinc supplementation had no effect on the incidence of all ARI but
decreased the incidence of ALRI – defined as report of difficult and/or
rapid breathing – by 62% (95% CI: 44-74%). A previous review of ten
randomized trials concluded that preventive zinc supplementation reduced
the incidence of childhood ALRI as defined by relatively specific
clinical criteria but had no effect if less specific definitions were
used [3]. Malik, et al. found the large reduction in ALRI in
spite of using a non-specific definition without clinical confirmation.
The intervention also decreased the duration of ARI in terms of total
number of days of illness during the follow-up period (15%; 95% CI:
6-22%) and number of days per episode (12%; 95% CI: 6-22%).
An important strength of this study was the
availability of anthropometric data, which enabled a subgroup analysis
confirming similar effects of prophylactic zinc among wasted and stunted
infants compared to those of normal weight- and length-for-age. On the
other hand, the failure to assess serum zinc levels at baseline was a
study limitation indicated by the authors; a sub-analysis comparing
effect sizes by serum zinc status would have been a worthwhile addition
to existing scientific literature reporting intensified effects of
routine and therapeutic zinc supplementation among zinc-deficient
children [2]. This study was also limited by a relatively small sample
size and the use of caregiver report of signs and symptoms as opposed to
a more clinical case definition for diagnosis of ALRI [3]. A larger
trial with confirmed clinical outcomes would have been able to determine
whether zinc supplementation had an effect on severe lower respiratory
infections, including pneumonia, which cause a large proportion of child
deaths in India and worldwide [1].
Nonetheless, this study sheds light on the efficacy
of short-course prophylactic zinc supplementation in reducing the burden
of ALRI among infants during the subsequent months. Furthermore, the
magnitude and directionality of the effects estimated by this study
bolster the conclusions of a previous meta-analysis, which reported no
difference between the effects of short-course and routine zinc
supplementation trials [9]. Future studies should assess the
effectiveness of delivering prophylactic zinc supplementation at-scale,
comparing the feasibility and cost-benefit of short-course and
continuous regimens.
1. Fischer Walker CL, Rudan I, Liu L, Nair H,
Theodoratou E, Bhutta ZA, et al. Global burden of childhood
pneumonia and diarrhoea. Lancet. 2013;381:1405-16.
2. Fischer-Walker C, Lamberti L, Roth D, Black R.
Zinc and infectious diseases. In: Rink L (eds). Zinc in Human
Health. Amsterdam: IOS Press; 2011. P. 234-53.
3. Roth DE, Richard SA, Black RE. Zinc
supplementation for the prevention of acute lower respiratory
infection in children in developing countries: Meta-analysis and
meta-regression of randomized trials. Int J Epidemiol.
2010;39:795-808.
4. Malik A, Taneja DK, Devasenapathy N,
Rajeshwari K. Zinc supplementation for prevention of acute
respiratory infections in infants: A randomized controlled trial.
Indian Pediatr. 2014;51:780-4.
5. Rahman MM, Vermund SH, Wahed MA, Fuchs GJ,
Baqui AH, Alvarez JO. Simultaneous zinc and vitamin A
supplementation in Bangladeshi children: Randomised double blind
controlled trial. BMJ. 2001;323:314-8.
6. Fischer Walker CL, Black RE. Zinc for the
treatment of diarrhoea: Effect on diarrhoea morbidity, mortality and
incidence of future episodes. Int J Epidemiol. 2010;39 Suppl
1:i63-9.
7. Baqui AH, Black RE, El Arifeen S, Yunus M,
Chakraborty J, Ahmed S, et al. Effect of zinc supplementation
started during diarrhoea on morbidity and mortality in Bangladeshi
children: Community randomised trial. BMJ. 2002;325:1059.
8. Bhandari N, Mazumder S, Taneja S, Dube B,
Agarwal RC, Mahalanabis D, et al. Effectiveness of zinc
supplementation plus oral rehydration salts compared with oral
rehydration salts alone as a treatment for acute diarrhea in a
primary care setting: A cluster randomized trial. Pediatrics.
2008;121:e1279-85.
9. Bhutta ZA, Black RE, Brown KH, Gardner JM, Gore S, Hidayat A,
et al. Prevention of diarrhea and pneumonia by zinc supplementation
in children in developing countries: Pooled analysis of randomized
controlled trials. Zinc Investigators’ Collaborative Group. J Pediatr.
1999;135:689-97.