Oral zinc for treating diarrhoea in children

The Cochrane Database of Systematic Reviews

Dec 2016

DOI: 10.1002/14651858.CD005436.pub5

Citations:65

Influential Citations:2

Systematic Reviews / Meta-Analyses

Enhanced Details

Methods

Randomized controlled trials in children aged 1 month to 5 years with acute or persistent diarrhoea (including dysentery); settings included hospital and community; many trials double-blind; total 33 trials with 10,841 children.

Intervention

Oral zinc supplementation (zinc sulfate, zinc acetate, or zinc gluconate) taken by mouth; typical daily dose around 20 mg (range from 5 mg/day to >20 mg/day in some trials); duration commonly about 14 days (half of trials), with some shorter (4 days) or longer (up to 14 days); dosing mostly once daily (some trials used twice or thrice daily).

Results

Zinc supplementation reduces diarrhoea duration and persistence in several subgroups. In acute diarrhoea, zinc reduces mean duration by about 13.4 hours overall (MD −13.42 hours; 95% CI −20.52 to −6.31; 5096 children, 20 trials), with substantial heterogeneity (I2 = 84%). In older than six months, duration shortened by around half a day; in malnourished children, duration reduced by about a day; in infants under six months, little or no effect on duration and possible increased persistence to day seven. Vomiting was more common with zinc in both age groups (moderate certainty). In persistent diarrhoea, zinc probably shortens duration by about 16 hours (MD −15.84 hours; 95% CI −25.43 to −6.24; 529 children, 5 trials). There is no clear evidence that zinc reduces death or hospitalization. Conclusion: In areas with high zinc deficiency or malnutrition, zinc may benefit children aged six months or older; in well-nourished or low-deficiency settings, benefits are unclear. More research is needed to clarify mortality/hospitalization effects and to explain heterogeneity.

Limitations

High heterogeneity across trials with varying populations, settings, dosing regimens, and co-supplementation; risk-of-bias concerns in some trials; most trials conducted in hospital settings and in populations with higher zinc deficiency; limited data on mortality/hospitalization; potential publication bias suggested by funnel plots; results not fully generalizable to low-deficiency populations.

Abstract

Abstract Background In developing countries, diarrhoea causes around 500,000 child deaths annually. Zinc supplementation during acute diarrhoea is currently recommended by the World Health Organization (WHO) and the United Nations Children's Fund (UNICEF). Objectives To evaluate oral zinc supplementation for treating children with acute or persistent diarrhoea. Search methods We searched the Cochrane Infectious Diseases Group Specialized Register, CENTRAL (the Cochrane Library 2016, Issue 5), MEDLINE, Embase, LILACS, CINAHL, mRCT, and reference lists up to 30 September 2016. We also contacted researchers. Selection criteria Randomized controlled trials (RCTs) that compared oral zinc supplementation with placebo in children aged one month to five years with acute or persistent diarrhoea, including dysentery. Data collection and analysis Both review authors assessed trial eligibility and risk of bias, extracted and analysed data, and drafted the review. The primary outcomes were diarrhoea duration and severity. We summarized dichotomous outcomes using risk ratios (RR) and continuous outcomes using mean differences (MD) with 95% confidence intervals (CI). Where appropriate, we combined data in meta‐analyses (using either a fixed‐effect or random‐effects model) and assessed heterogeneity. We assessed the certainty of the evidence using the GRADE approach. Main results Thirty‐three trials that included 10,841 children met our inclusion criteria. Most included trials were conducted in Asian countries that were at high risk of zinc deficiency. Acute diarrhoea There is currently not enough evidence from well‐conducted RCTs to be able to say whether zinc supplementation during acute diarrhoea reduces death or number of children hospitalized (very low certainty evidence). In children older than six months of age, zinc supplementation may shorten the average duration of diarrhoea by around half a day (MD −11.46 hours, 95% CI −19.72 to −3.19; 2581 children, 9 trials, low certainty evidence), and probably reduces the number of children whose diarrhoea persists until day seven (RR 0.73, 95% CI 0.61 to 0.88; 3865 children, 6 trials, moderate certainty evidence). In children with signs of malnutrition the effect appears greater, reducing the duration of diarrhoea by around a day (MD −26.39 hours, 95% CI −36.54 to −16.23; 419 children, 5 trials, high certainty evidence). Conversely, in children younger than six months of age, the available evidence suggests zinc supplementation may have no effect on the mean duration of diarrhoea (MD 5.23 hours, 95% CI −4.00 to 14.45; 1334 children, 2 trials, low certainty evidence), or the number of children who still have diarrhoea on day seven (RR 1.24, 95% CI 0.99 to 1.54; 1074 children, 1 trial, low certainty evidence). None of the included trials reported serious adverse events. However, zinc supplementation increased the risk of vomiting in both age groups (children greater than six months of age: RR 1.57, 95% CI 1.32 to 1.86; 2605 children, 6 trials, moderate certainty evidence; children less than six months of age: RR 1.54, 95% CI 1.05 to 2.24; 1334 children, 2 trials, moderate certainty evidence). Persistent diarrhoea In children with persistent diarrhoea, zinc supplementation probably shortens the average duration of diarrhoea by around 16 hours (MD −15.84 hours, 95% CI −25.43 to −6.24; 529 children, 5 trials, moderate certainty evidence). Authors' conclusions In areas where the prevalence of zinc deficiency or the prevalence of malnutrition is high, zinc may be of benefit in children aged six months or more. The current evidence does not support the use of zinc supplementation in children less six months of age, in well‐nourished children, and in settings where children are at low risk of zinc deficiency. 12 April 2019 Up to date All studies incorporated from most recent search All eligible published studies found in the last search (30 Sep, 2016) were included and two ongoing studies have been identified (see 'Characteristics of ongoing studies' section) show less