Abstract
BackgroundFor over a decade, the importance of zinc in the treatment of acute and persistent diarrhea has been recognized. In spite of recently published reviews, there remain several unanswered questions about the role of zinc supplementation in childhood diarrhea in the developing countries. Our study aimed to assess the therapeutic benefits of zinc supplementation in the treatment of acute or persistent diarrhea in children, and to examine the causes of any heterogeneity of response to zinc supplementation.Methods and FindingsEMBASE®, MEDLINE ® and CINAHL® databases were searched for published reviews and meta-analyses on the use of zinc supplementation for the prevention and treatment of childhood diarrhea. Additional RCTs published following the meta-analyses were also sought. The reviews and published RCTs were qualitatively mapped followed by updated random-effects meta-analyses, subgroup meta-analyses and meta-regression to quantify and characterize the role of zinc supplementation with diarrhea-related outcomes. We found that although there was evidence to support the use of zinc to treat diarrhea in children, there was significant unexplained heterogeneity across the studies for the effect of zinc supplementation in reducing important diarrhea outcomes. Zinc supplementation reduced the mean duration of diarrhea by 19.7% but had no effect on stool frequency or stool output, and increased the risk of vomiting. Our subgroup meta-analyses and meta-regression showed that age, stunting, breast-feeding and baseline zinc levels could not explain the heterogeneity associated with differential reduction in the mean diarrheal duration. However, the baseline zinc levels may not be representative of the existing zinc deficiency state.ConclusionsUnderstanding the predictors of zinc efficacy including the role of diarrheal disease etiology on the response to zinc would help to identify the populations most likely to benefit from supplementation. To improve the programmatic use of zinc, further evaluations of the zinc salts used, the dose, the frequency and duration of supplementation, and its acceptability are required. The significant heterogeneity of responses to zinc suggests the need to revisit the strategy of universal zinc supplementation in the treatment children with acute diarrhea in developing countries.
Highlights
Despite significant improvements in the interventions to treat diarrhea in children, it continues to pose a daunting public health challenge, especially in children from developing countries
Understanding the predictors of zinc efficacy including the role of diarrheal disease etiology on the response to zinc would help to identify the populations most likely to benefit from supplementation
Asia and Africa have an alarmingly high incidence of childhood diarrhea. [1,2,3] the burden of the diarrhea-related mortality has significantly decreased since the introduction of oral rehydration therapy in 1980, diarrheal diseases in children remain a substantial global health problem. [4,5,6] In 2004, the World Health Organization (WHO) and the United Nations Children’s Fund (UNICEF) took two significant steps to reduce this burden by recommending the use of low-osmolarity oral rehydration solution (ORS), and supplementation with zinc for up to two weeks as part of the case management of acute diarrhea. [7,8]
Summary
Despite significant improvements in the interventions to treat diarrhea in children, it continues to pose a daunting public health challenge, especially in children from developing countries. Five meta-analyses have been published far [9,16,17,18,20,21]that have all observed a protective effect of zinc on some diarrhea outcomes, but all of these meta-analyses have reported a significant degree of heterogeneity in effect sizes across studies. Such heterogeneity raises concerns regarding the reliability of the synthetic estimates of the use of zinc supplementation. Our study aimed to assess the therapeutic benefits of zinc supplementation in the treatment of acute or persistent diarrhea in children, and to examine the causes of any heterogeneity of response to zinc supplementation
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