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American Journal of Clinical Nutrition, Vol. 84, No. 3, 667, September 2006
© 2006 American Society for Nutrition


LETTER TO THE EDITOR

Zinc, infectious diseases, and low birth weight

W Abdullah Brooks, Mathuram Santosham and Robert E Black

Head of Infectious Diseases Unit
Division of Health Systems & Infectious Diseases
ICDDR, B: Centre for Health and Population Research
GPO Box 128 Mohakhali 1000
Dhaka
Bangladesh
E-mail: abrooks{at}icddrb.org

Dear Sir:

In his editorial on zinc and pneumonia, Hambidge (1) draws attention to an important area of active interest in zinc research, namely the role of zinc in young infants aged <6 mo, specifically those with diarrhea. Despite substantial progress in reducing diarrhea-related child mortality in recent years, largely because of the success of oral rehydration solutions, diarrhea remains the second leading cause of death in children worldwide, accounting for 1.9 million deaths/y (2). In their 2004 joint statement on the clinical management of diarrhea (3), WHO and UNICEF embrace the use of zinc at a dose of 20 mg/d for 10–14 d for preschool-aged children, except for those aged <6 mo, for whom they recommend 10 mg/d. This regimen was based on a systematic review of research findings and recommendations by leading experts at a WHO-sponsored symposium in Delhi in 2000 (4).

Hambidge points out that our 2005 publication on the effects of zinc in acute watery diarrhea management in infants aged <6 mo (5) found no acute treatment benefit. This negative finding, he argues, could result in the discouragement of the use of zinc in that age group, specifically for diarrhea but perhaps for pneumonia. He correctly points out that one thing our study did not report was the birth weight status of our patients, specifically whether any of the patients were of low birth weight (LBW). This was indeed 1 of 2 principal weaknesses of our study, the other being an absence of follow-up to document the effects of acute treatment with zinc on subsequent illness. Indeed, postdiarrhea treatment effects of zinc on both morbidity (6) and mortality (7) have been reported in a broader age group but never in young infants.

The efficacy of zinc in LBW is well documented in terms of morbidity, but more importantly in terms of mortality reduction, whether given to treat acute diarrheal disease (7) or for prophylaxis (8). Concerns that this vulnerable population might therefore be denied a proven intervention against infant mortality are thus well founded.

Although our study in young infants did not collect data on birth weight, because of concerns about reporting accuracy in the absence of hospital records, we did collect data on gestational age and anthropometric measures. Although gestational age does not address LBW per se, it does identify those who may have been at increased risk of prematurity, some of whom may have been of LBW. We found that only 43 (15.6%) of the study children were born in the hospital; the remainder had been born at home under the care of traditional birth attendants. Furthermore, only 26 (9.4%) of the children claimed to have been born preterm, with a median gestational age of 38.5 wk (95% CI: 38, 39; range: 32–39 wk).

Moreover, we excluded infants who were malnourished according to ICDDR, B's standard criteria, ie, <60% of weight-for-age, which is based on National Center for Health Statistics data (9). Given that malnourished infants were excluded and that the median discharge weight-for-age was 81.5% (95% CI: 80.0, 83.3), it is unlikely that any of the subjects in the present study were truly of LBW.

Thus, our findings should be interpreted accordingly, ie, our negative result should be seen as representative of a "normative" population in this setting and not applied to the case of LBW. Furthermore, diarrhea is a zinc-losing enteropathy, and we cannot exclude the possibility of subsequent benefit even to those young infants who do not derive an immediate benefit of zinc treatment for acute diarrhea. Finally, zinc is well tolerated and has not been associated with any harmful effects in the management of acute diarrhea in the age groups studied or at the current recommended doses. We therefore endorse the continued use of zinc for the treatment of acute diarrhea in patients aged <6 mo, unless further information indicates a contraindication in this population generally or in those who are of LBW particularly.

ACKNOWLEDGMENTS

The authors had no conflicts of interest to declare.

REFERENCES

  1. Hambidge KM. Zinc and pneumonia. Am J Clin Nutr 2006;83:991–2.[Free Full Text]
  2. Bryce J, Boschi-Pinto C, Shibuya K, Black RE. WHO estimates of the causes of death in children. Lancet 2005;365:1147–52.[Medline]
  3. WHO/UNICEF. WHO/UNICEF joint statement: clinical management of acute diarrhoea. New York, NY: World Health Organization/The United Nations Childrens Fund, 2004:1–8.
  4. Fontaine O. Effect of zinc supplementation on clinical course of acute diarrhoea. J Health Popul Nutr 2001;19:339–46.[Medline]
  5. Brooks WA, Santosham M, Roy SK, et al., Efficacy of zinc in young infants with acute watery diarrhea. Am J Clin Nutr 2005;82:605–10.[Abstract/Free Full Text]
  6. Roy SK, Tomkins AM, Haider R, et al. Impact of zinc supplementation on subsequent growth and morbidity in Bangladeshi children with acute diarrhoea. Eur J Clin Nutr 1999;53:529–34.[Medline]
  7. Baqui AH, Black RE, El Arifeen S, et al. Effect of zinc supplementation started during diarrhoea on morbidity and mortality in Bangladeshi children: community randomised trial. BMJ 2002;325:1059.[Abstract/Free Full Text]
  8. Sazawal S, Black RE, Menon VP, et al. Zinc supplementation in infants born small for gestational age reduces mortality: a prospective, randomized, controlled trial. Pediatrics 2001;108:1280–6.[Abstract/Free Full Text]
  9. Hamil PV, Drizd TA, Johnson CL. Physical growth: National Center for Health Statistic percentages. Am J Clin Nutr 1979;32:607–29.[Abstract/Free Full Text]




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