Zinc Supplementation in Diarrhea,Zinc Deficiency

4th Pediatric Infectious Diseases Conference

ISSN 0973 - 0958

Gastrointestinal Disorders in Children

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ACUTE CHILDHOOD DIARRHEA: A REVIEW OF RECENT ADVANCES IN THE STANDARD MANAGEMENT

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Diarrhea Introduction

Causes Of Childhood Diarrhea

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SEEMA ALAM RAJEEV KHANNA UZMA FIRDAUS
Pediatric Gastroenterology Section, Department of Pediatrics, JNMC, AMU, Aligarh

Corresponding Author :

Dr Seema Alam, Reader, Department of Pediatrics, JN Medical College, AMU, Aligarh, UP. Email seema_alam@hotmail.com

Zinc Supplementation in Diarrhea:

Zinc deficiency is present in 30-50 % children living in developing countries 43 . The high prevalence of zinc deficiency in these countries can be explained by increased prevalence of malnutrition, low dietary intake of complementary animal source foods (rich in zinc & with higher bioavailability), insufficiency of the breast milk to fulfill the requirements after 6 months of age, higher consumption of cereals and legumes containing phytates which inhibit zinc absorption and low content of zinc in soil and crops 44-46 . Also, such children suffer from frequent diarrheal illnesses resulting in excessive fecal losses of zinc 47 . Zinc deficiency, on the other hand, predisposes to frequent diarrheal episodes, increasing their duration and severity, creating a vicious cycle. Zinc deficiency reduces brush border enzymes, d isrupts intestinal mucosa and increases mucosal permeability and intestinal secretion, thus making the diarrheal episode more severe and prolonged. Zinc supplementation has been known to cause early regeneration of intestinal mucosa thus improving intestinal permeability, restoration of intestinal brush border enzymatic function, overall causing reduction in intestinal secretion and regulation of water and electrolyte transport. Zinc by maintaining the integrity of the gut mucosa reduces and prevents the fluid losses. These responses begin to occur within 48 hours of starting zinc supplementation 48,49 . As is evident from the Table 7, zinc supplementation reduces the incidence (11-15%) 50-52 and prevalence (18-30%) 50,52 of diarrhea in children less than 5 years. Pooled analysis 53 ( Zinc Investigators' Collaborative Group taken 3 randomized controlled trials 54-56 on zinc in acute diarrhea from Indonesia, India and Bangladesh) revealed 15 % faster recovery, 24 % reduction in episodes lasting more than 7 days and 16% reduction in the mean duration of diarrhea. There was more variability (9-30%) in reduction of frequency of stools 50,54,57 or stool output 55,58,59 in the various studies. The pooled analysis 53 and the study by Bhatnagar et al 59 have found no differences in effects in the subgroups based on age, sex, zinc levels and nutrition, however more effect was seen in the pooled analysis in those with lower zinc levels. Bhandari et al 50 have found more significant effect in subjects more than 12 months of age, with serum zinc levels more than 60 µg/dL and without stunting or wasting. Sazawal et al 54 have found an increasingly significant effect of zinc in stunted and wasted children and those with serum zinc levels < 60 µg /dL, but without any association with gender. Overall, there doesn't seem to be ample evidence to suggest a specific target group whom zinc should be given during episodes of diarrhea. There were also slightly more chances of vomiting in the zinc supplemented group 50,57,59 . There was an attempt to add zinc in the ORS but the beneficial effect was not seen in the supplemented group 60 . This was possibly due to the variable amount of zinc received depending upon the ORS intake. The IAP National Task Force in 2003 26 and 2006 has recommended zinc supplementation for the duration of diarrhea and for 7 days after cessation of diarrhea in all children older than 3 months of age with diarrhea. The dosage is 10 mg/day for infants and 20/day mg for older children. Preferably only zinc preparation should be used. It is recently been reported that zinc supplementation may not be helpful in young infants with diarrhea 61 . We need more studies in children below 3 months to decide the issue. It was seen in recently published study that in the management of acute watery diarrhea, zinc plus ORS along with culturally appropriate messages in local language does not affect overall ORS use generally and decreases antibiotic/antidiarrheal use with children having good adherence without side effects 62 .

Table 7: Results of Randomized Controlled Trials in children with Acute Diarrhea comparing effect of Zinc with that of Placebo

Effect studied	Trial	No. of subjects (Zinc/Placebo treated)	Inference	Effect size (95% CI)
Effect on incidence	Bhandari et al ⁵⁰	1093 / 1133	12% reduction	0.88 (0.82-0.95)
	Baqui et al⁵¹	3974 / 4096	15% reduction	0.85 (0.76-0.96)
	Rahman et al ⁵²	345 / 161	11% reduction	0.89 (0.79-0.99)
Effect on prevalence	Bhandari et al ⁵⁰	1093 / 1133	30% reduction	-1.30 (-0.61 to -2.0)
Effect on prevalence	Rahman et al ⁵²	345 / 161	18% reduction	0.82 (0.78-0.87)
Effect on recovery	Pooled analysis ⁵³	1252 / 1194	15% faster recovery	0.85 (0.76 to 0.95)
	Strand et al ⁵⁷	442 / 449	26% faster recovery	1.26 (1.08-1.46)
	Bahl et al ⁶⁰	404 / 401	11% faster recovery	0.89 (0.80-0.99)
	Bhatnagar et al ⁵⁹	132 / 134	24% faster recovery	0.76 (0.59 to 0.97)
Effect on episodes lasting > 7 days	Pooled analysis⁵³	1252 / 1194	24% reduction	0.76 (0.63-0.91)
	Bhandari et al ⁵⁰	1093 / 1133	21% reduction	0.79 (0.65-0.95)
	Sazawal et al ⁵⁴	462 / 485	39% reduction	0.61 (0.30-0.94)*
	Strand et al ⁵⁷	442 / 449	43% reduction	0.57 (0.38-0.86)
	Bahl et al ⁶⁰	404 / 401	39% reduction	0.61 (0.33-1.12)
	Bhatnagar et al ⁵⁹	132 / 134	9% reduction	0.09 (0.01-0.73)
Effect on mean duration	Pooled analysis⁵³	1252 / 1194	16% reduction	0.16 (0.07-0.26)
	Baqui et al ⁵¹	3974 / 4096	24% reduction	0.76 (0.65-0.90)
	Bhatnagar et a ⁵⁰ l	132/134	9 hrs earlier (24% less)	0.76 (0.59- 0.97)
Effect on frequency	Strand et al⁵⁷	442 / 449	9% reduction	0.91 (0.85-0.97)
	Sazawal et al ⁵⁴	456 / 481	21% reduction	0.79 (0.30-0.94)
	Bhandari et al ⁵⁰	1093 / 1133	23% reduction	0.77 (0.63-0.94)
Effect on Stool output	Roy et al ⁵⁵	57/54	91 g less	-91 g
	Dutta et al ⁵⁸	44/36	900 g less	-900 g (-1200 to -590)
	Bhatnagar et al ⁵⁹	132/134	31% less	0.69 (0.48-0.99)
Adverse Effect vomiting / regurgitation	Bhandari et al ⁵⁰	1093 / 1133	1.7 days more	1.7 (1.3-2.1) days
	Strand et al ⁵⁷	442 / 449	14% more	1.7 (1.4-2.2)
	Bhatnagar et al ⁵⁹	132/134	3% more	1.1 (0.69-1.9)