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Marzia Lazzerini, Luca Ronfani

This review should be cited as:

Lazzerini Marzia, Ronfani Luca. Oral zinc for treating diarrhoea in children. Cochrane

Database of Systematic Reviews. In: The Cochrane Library, Issue 10, Art. No.

CD005436. DOI: 10.1002/14651858.CD005436.pub3. The independent commentary is written by Mauro Batista de Morais.

ABSTRACT

BACKGROUND: Diarrhoea causes around two million childdeaths annually. Zinc supplementation could help reduce the durationand severity o diarrhoea, and is recommended by the World HealthOrganization and UNICEF.

OBJECTIVE: o evaluate oral zinc supplementation or treatingchildren with acute or persistent diarrhoea.

CRITERIA FOR CONSIDERING STUDIES FOR THIS RE- VIEW: In November 2007, we searched the Cochrane In ectious Dis-

eases Group Specialized Register, CEN RAL (Te Cochrane Library 2007, Issue 4), MEDLINE, EMBASE, LILACS, CINAHL, mRC ,and re erence lists. We also contacted researchers.

SELECTION CRITERIA: Randomized controlled trials com-paring oral zinc supplementation ( 5 mg/day or any duration) withplacebo in children aged one month to ve years with acute or persistentdiarrhoea, including dysentery.

DATA COLLECTION AND ANALYSIS: Both authors assessedtrial eligibility and methodological quality, extracted and analyseddata, and dra ted the review. Diarrhoea duration and severity were theprimary outcomes. We summarized dichotomous outcomes using risk ratios (RR) and continuous outcomes using mean di erences (MD)

with 95% con dence intervals (CI). Where appropriate, we combineddata in meta-analyses (using the xed- or random-e ects model) andassessed heterogeneity.

MAIN RESULTS: Eighteen trials enrolling 6165 participants metour inclusion criteria. In acute diarrhoea, zinc resulted in a shorterdiarrhoea duration (MD -12.27 h, 95% CI -23.02 to -1.52 h; 2741children, 9 trials), and less diarrhoea at day three (RR 0.69, 95% CI0.59 to 0.81; 1073 children, 2 trials), day ve (RR 0.55, 95% CI 0.32to 0.95; 346 children, 2 trials), and day seven (RR 0.71, 95% CI 0.52to 0.98; 4087 children, 7 trials). Te our trials (1458 children) thatreported on diarrhoea severity used di erent units and time points,and the e ect o zinc was less clear. Subgroup analyses by age (trials with only children aged less than six months) showed no bene t withzinc. Subgroup analyses by nutritional status, geographical region,background zinc de ciency, zinc type, and study setting did not a ectthe results signi cance. Zinc also reduced the duration o persistentdiarrhoea (MD -15.84 h, 95% CI -25.43 to -6.24 h; 529 children, 5trials). Few trials reported on severity, and results were inconsistent. Notrial reported serious adverse events, but vomiting was more commonin zinc-treated children with acute diarrhoea (RR 1.71, 95% 1.27 to2.30; 4727 children, 8 trials).

AUTHORS CONCLUSIONS: In areas where diarrhoea is animportant cause o child mortality, research evidence shows zinc isclearly o bene t in children aged six months or more.

PLAIN LANGUAGE SUMMARY: In developing countries, mil-lions o children su er rom severe diarrhoea every year. Tis is due toin ection and malnutrition, and many die rom dehydration due to thediarrhoea. Giving uids by mouth (using an oral rehydration solution)has been shown to save childrens lives, but it seems to have no e ecton the length o time the children su er with diarrhoea. Children indeveloping countries are o ten zinc de cient. Zinc supplementation isa possible treatment or diarrhoea though it can have adverse e ects i given in high doses. Te review o trials identi ed 18 trials involving6165 children o all ages. Zinc reduced the time that children overthe age o six months su ered rom symptoms o acute or persistentdiarrhoea. However, there were insufcient data to see any impact onthe number o children who died. More children vomited when givenzinc, but it was considered that the bene ts outweighed these adversee ects. Zinc seemed to have no impact on children aged less than sixmonths. In areas where diarrhoea is an important cause o child mortal-ity, research evidence shows zinc is clearly o bene t in children agedsix months or more with diarrhoeal diseases.

FURTHER INFORMATION

Brazilian Cochrane Center Rua Pedro de Toledo, 598

Vila Clementino So Paulo (SP) Brasil

CEP 04039-001

Tel. (+55 11) 5575-2970

Email:cochrane.dmed@unifesp.br http: www.centrocochranedobrasil.org.br

This section was edited under the responsibility of the Brazilian Cochrane Center

COMMENTS

During the 20 th century, oral rehydration therapy or children su -

ering rom diarrhea was developed and applied in an e ective manner.Tis has been considered to be the therapeutic method that singly savedthe largest number o lives during that century. Tus, the two pillarso treatment or acute diarrhea and persistent diarrhea (i.e. the ormthat begins with an episode o acute diarrhea, o presumably in ectiousorigin, and extends or longer than 14 days, in children less than veyears o age, and brings about negative repercussions on nutritionalstatus) became solidi ed: 1. oral rehydration therapy; and 2. preventionand combating o malnutrition through adequate eeding.

Starting rom this point, space was created such that the maintherapeutics or acute diarrhea were broadened towards additional ob-

jectives, especially reduction o the duration o diarrhea and reduction o abnormal ecal losses. o this end, clinical research ocused on the thera-peutic role o zinc, probiotics and intestinal secretion reducers such asracecadotril, bismuth subsalicylate and vitamin A, among others. Tesetherapeutic measures, used in conjunction with nutritional care and oralrehydration, were recently analyzed in detail in the Guidelines o theEuropean Society or Pediatric Gastroenterology, Hepatology and Nu-trition1 and in the Iberian-Latin American Clinical Practice Guide.2

Te systematic review and meta-analysis by Lazzerini and Ron ani3

demonstrated that zinc administration is associated with mean reduc-tions in the duration o acute diarrhea and persistent diarrhea o 12.3hours and 15.8 hours, respectively, or children between the ages o sixmonths and ve years. Considering that the clinical trials were carried

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out in underdeveloped countries, the authors concluded that in areas in which diarrhea is an important cause o mortality among in ants andyoung children, the scienti c evidence indicates that zinc therapy is e -

cient. Furthermore, the World Health Organization (WHO) considersthat zinc reduces the uture risk o a new diarrhea outbreak during thesubsequent two to three months. Te addition o such measures withinthe Brazilian public health scenario requires a cost-e ectiveness analysisthat takes into consideration the need or preparation and distributiono zinc-containing products, in the same way in which oral rehydrationsalts were investigated in the past.

REFERENCES

1. Guarino A, Albano F, Ashkenazi S, et al. European Society for Paediatric Gastroenterology,Hepatology, and Nutrition/European Society for Paediatric Infectious Diseases evidence-based guidelines for the management of acute gastroenteritis in children in Europe. J Pedia-tr Gastroenterol Nut. 2008;46 Suppl 2:S81-122.

2. Gutirrez Castrelln P; Polanco Allu I; Salazar Lindo E. Manejo de la gastroenteritis agu-da en menores de 5 aos: un enfoque basado en la evidencia Gua de prctica clnicaIbero-Latinoamericana. An Pediatr (Barc) 2010;72:1-19. Available from: http://xa.yimg.com/kq/groups/23509852/1431031162/name/Gu%C3%ADa Ibero Latinoamericana de gastroenteritis en ni%C3%B1os menores de 5a%C3%B1os.pdf. Accessed in

2010 (Dec 21).3. Lazzerini M, Ronfani L. Oral zinc for treating diarrhoea in children. Cochrane Data base

Syst Rev. 2008;(3):CD005436. Available from: http://www.cochranejournalclub.com/probiotics-acute-infectious-diarrhoea-clinical/pdf/CD005436_standard.pdf. accessed in2011 (Apr 18).

Mauro Batista de Morais. President of the Department of Gastroenterology, Sociedade

de Pediatria de So Paulo, and Associate Full Professor of the Discipline of Pediatric

Gastroenterology and Head of the Department of Pediatrics, Universidade Federal de

So Paulo Escola Paulista de Medicina (Unifesp-EPM), So Paulo, Brazil.