Influence of Zinc Supplementation in Acute Diarrhea Differs by the Isolated Organism

Zinc supplementation is recommended in all acute diarrheas in children from developing countries. We aimed to assess whether zinc supplementation would be equally effective against all the common organisms associated with acute diarrheas. We used data on 801 children with acute diarrhea recruited in a randomized, double blind controlled trial (ISRCTN85071383) of zinc and copper supplementation. Using prespecified subgroup analyses, multidimensionality reduction analyses, tests of heterogeneity, and stepwise logistic regression for tests of interactions, we found that the influence of zinc on the risk of diarrhea for more than 3 days depended on the isolated organism—beneficial in Klebsiella, neutral in Esherichia coli and parasitic infections, and detrimental in rotavirus coinfections. Although we found similar results for the outcome of high stool volume, the results did not reach statistical significance. Our findings suggest that the current strategy of zinc supplementation in all cases of acute diarrheas in children may need appropriate fine tuning to optimize the therapeutic benefit based on the causative organism, but further studies need to confirm and extend our findings

Therapeutic Value of Zinc Supplementation in Acute and Persistent Diarrhea: A Systematic Review

BACKGROUND: For 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 FINDINGS: EMBASE, 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. CONCLUSIONS: 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. 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

Clinical Study Influence of Zinc Supplementation in Acute Diarrhea Differs by the Isolated Organism

Zinc supplementation is recommended in all acute diarrheas in children from developing countries. We aimed to assess whether zinc supplementation would be equally effective against all the common organisms associated with acute diarrheas. We used data on 801 children with acute diarrhea recruited in a randomized, double blind controlled trial (ISRCTN85071383) of zinc and copper supplementation. Using prespecified subgroup analyses, multidimensionality reduction analyses, tests of heterogeneity, and stepwise logistic regression for tests of interactions, we found that the influence of zinc on the risk of diarrhea for more than 3 days depended on the isolated organism-beneficial in Klebsiella, neutral in Esherichia coli and parasitic infections, and detrimental in rotavirus coinfections. Although we found similar results for the outcome of high stool volume, the results did not reach statistical significance. Our findings suggest that the current strategy of zinc supplementation in all cases of acute diarrheas in children may need appropriate fine tuning to optimize the therapeutic benefit based on the causative organism, but further studies need to confirm and extend our findings

What zinc supplementation does and does not achieve in diarrhea prevention: a systematic review and meta-analysis

<p>Abstract</p> <p>Background</p> <p>Prevention of diarrhea has presented indomitable challenges. A preventive strategy that has received significant interest is zinc supplementation. Existing literature including quantitative meta-analyses and systematic reviews tend to show that zinc supplementation is beneficial however evidence to the contrary is augmenting. We therefore conducted an updated and comprehensive meta-analytical synthesis of the existing literature on the effect of zinc supplementation in prevention of diarrhea.</p> <p>Methods</p> <p>EMBASE^®, MEDLINE ^®and CINAHL^®databases were searched for published reviews and meta-analyses on the use of zinc supplementation for the prevention childhood diarrhea. Additional RCTs published following the meta-analyses were also sought. Effect of zinc supplementation on the following five outcomes was studied: incidence of diarrhea, prevalence of diarrhea, incidence of persistent diarrhea, incidence of dysentery and incidence of mortality. The published RCTs were combined using random-effects meta-analyses, subgroup meta-analyses, meta-regression, cumulative meta-analyses and restricted meta-analyses to quantify and characterize the role of zinc supplementation with the afore stated outcomes.</p> <p>Results</p> <p>We found that zinc supplementation has a modest beneficial association (9% reduction) with incidence of diarrhea, a stronger beneficial association (19% reduction) with prevalence of diarrhea and occurrence of multiple diarrheal episodes (28% reduction) but there was significant unexplained heterogeneity across the studies for these associations. Age, continent of study origin, zinc salt and risk of bias contributed significantly to between studies heterogeneity. Zinc supplementation did not show statistically significant benefit in reducing the incidence of persistent diarrhea, dysentery or mortality. In most instances, the 95% prediction intervals for summary relative risk estimates straddled unity.</p> <p>Conclusions</p> <p>Demonstrable benefit of preventive zinc supplementation was observed against two of the five diarrhea-related outcomes but the prediction intervals straddled unity. Thus the evidence for a preventive benefit of zinc against diarrhea is inconclusive. Continued efforts are needed to better understand the sources of heterogeneity. The outcomes of zinc supplementation may be improved by identifying subgroups that need zinc supplementation.</p

Determinants of inappropriate complementary feeding practices in young children in India : secondary analysis of National Family Health Survey 2005-2006

In India, poor feeding practices in early childhood contribute to the burden of malnutrition as well as infant and child mortality. This paper aims to use the newly developed World Health Organization (WHO) infant feeding indicators to determine the prevalence of complementary feeding indicators among children of 6–23 months of age and to identify the determinants of inappropriate complementary feeding practices in India. The study data on 15 028 last-born children aged 6–23 months was obtained from the National Family Health Survey 2005–2006. Inappropriate complementary feeding indicators were examined against a set of child, parental, household, health service and community level characteristics. The prevalence of timely introduction of complementary feeding among infants aged 6–8 months was 55%. Among children aged 6–23 months, minimum dietary diversity rate was 15.2%, minimum meal frequency 41.5% and minimum acceptable diet 9.2%. Children in northern and western geographical regions of India had higher odds for inappropriate complementary feeding indicators than in other geographical regions. Richest households were less likely to delay introduction of complementary foods than other households. Other determinants of not meeting minimum dietary diversity and minimum acceptable diet were: no maternal education, lower maternal Body Mass Index (BMI) (<18.5 kg/m2), lower wealth index, less frequent (<7) antenatal clinic visits, lack of post-natal visits and poor exposure to media. A very low proportion of children aged 6–23 months in India received adequate complementary foods as measured by the WHO indicators

Infant and young child feeding indicators and determinants of poor feeding practices in India : secondary data analysis of National Family Health Survey 2005-06

In India, poor feeding practices in early childhood contribute to the burden of malnutrition and infant and child mortality. The objective of this study was to estimate infant and young child feeding indicators and determinants of selected feeding practices in India. The sample consisted of 20,108 children aged 0 to 23 months from the National Family Health Survey India 2005–06. Selected indicators were examined against a set of variables using univariate and multivariate analyses. Only 23.5% of mothers initiated breastfeeding within the first hour after birth, 99.2% had ever breastfed their infant, 89.8% were currently breastfeeding, and 14.8% were currently bottle-feeding. Among infants under 6 months of age, 46.4% were exclusively breastfed, and 56.7% of those aged 6 to 9 months received complementary foods. The risk factors for not exclusively breastfeeding were higher household wealth index quintiles (OR for richest = 2.03), delivery in a health facility (OR = 1.35), and living in the Northern region. Higher numbers of antenatal care visits were associated with increased rates of exclusive breastfeeding (OR for ≥ 7 antenatal visits = 0.58). The rates of timely initiation of breastfeeding were higher among women who were better educated (OR for secondary education or above = 0.79), were working (OR = 0.79), made more antenatal clinic visits (OR for ≥ 7 antenatal visits = 0.48), and were exposed to the radio (OR = 0.76). The rates were lower in women who were delivered by cesarean section (OR = 2.52). The risk factors for bottle-feeding included cesarean delivery (OR = 1.44), higher household wealth index quintiles (OR = 3.06), working by the mother (OR=1.29), higher maternal education level (OR=1.32), urban residence (OR=1.46), and absence of postnatal examination (OR=1.24). The rates of timely complementary feeding were higher for mothers who had more antenatal visits (OR=0.57), and for those who watched television (OR=0.75). Revitalization of the Baby Friendly Hospital Initiative in health facilities is recommended. Targeted interventions may be necessary to improve infant feeding practices in mothers who reside in urban areas, are more educated, and are from wealthier households

Outcomes and summary effects related to acute diarrhea observed in published meta-analyses.

<p>M1, Bhutta et al 2000 <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0010386#pone.0010386-Bhutta1" target="_blank">[9]</a>; M2, Lukacik et al 2008 <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0010386#pone.0010386-Lukacik1" target="_blank">[17]</a>; M3, Patro et al 2008 <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0010386#pone.0010386-Patro1" target="_blank">[18]</a>; M4, Lazzerini et al 2008 <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0010386#pone.0010386-Lazzerini1" target="_blank">[16]</a>; M5, Haider and Bhutta <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0010386#pone.0010386-Haider1" target="_blank">[15]</a>.</p><p>OR, odds ratio; RR, relative risk; RH, relative hazards; WMD, weighted mean difference; RCT, Lumber of randomized control trials used; N, Number of subjects included in meta-analysis; ES, summary effect size, CI, confidence interval; d, days; h, hours; % ↓, percentage reduction.</p><p>M1 reported Q statistic and degrees of freedom and the I² statstic was derived using the formula I² = (Q-df)/Q. *, statistically significant; ---, not mentioned and not estimable.</p