Sei sulla pagina 1di 9

Short-Course Prophylactic Zinc Supplementation for

Diarrhea Morbidity in Infants of 6 to 11 Months


WHATS KNOWN ON THIS SUBJECT: Randomized controlled trials AUTHORS: Akash Malik, MBBS,a Davendra K. Taneja, MD,a
have shown that zinc supplementation during diarrhea Niveditha Devasenapathy, MBBS, MSc,b and K. Rajeshwari,
substantially reduces the incidence and severity. However, the MDc
effect of short-course prophylactic zinc supplementation has been Departments of aCommunity Medicine, and cPaediatrics, Maulana
observed only in children .12 months of age. Azad Medical College, New Delhi, India; and bIndian Institute of
Public Health-Delhi, Public Health Foundation of India, New Delhi,
India
WHAT THIS STUDY ADDS: The current study was able to show that
KEY WORDS
short-course prophylactic zinc supplementation signicantly
zinc, diarrhea, infants, randomized control trial
reduced diarrhea morbidity in apparently healthy infants of 6 to
ABBREVIATIONS
11 months even after 5 months of follow-up.
CIcondence interval
IRRincident rate ratio
RRrate ratio
Dr Malik formulated the research question and contributed to
designing the study, wrote the research grants, carried out the
abstract eld investigations, carried out the initial data analyses, and
drafted the initial manuscript; Dr Taneja contributed to
BACKGROUND: Zinc supplementation during diarrhea substantially designing the study, contributed to developing the standard
reduces the incidence and severity of diarrhea. However, the effect operating procedures, implemented randomization and blinding,
and reviewed and revised the manuscript; Dr Devasenapathy
of short-course zinc prophylaxis has been observed only in children supervised the data collection and managed the data, analyzed
.12 months of age. Because the incidence of diarrhea is comparatively the data, and interpreted the ndings; Dr Rajeshwari supervised
high in children aged 6 to 11 months, we assessed the prophylactic the clinical data collection and management, and contributed to
developing the standard operating procedures; and all authors
effect of zinc on incidence and duration of diarrhea in this age group.
approved the nal manuscript as submitted.
METHODS: In this randomized, double-blind, placebo-controlled trial, we This trial was registered with the Clinical Trial Registry-India, No.
enrolled infants aged 6 to 11 months from an urban resettlement colony in CTRI/2010/091/001417.
Delhi, India, between January 1, 2011, and January 15, 2012. We randomly The Indian Council of Medical Research, Department of Health
assigned 272 infants to receive either 20 mg of zinc or a placebo Research (Ministry of Health and Family Welfare), Government of
India, which funded the study, had no role in the study design,
suspension orally every day for 2 weeks. The primary outcome was
data collection, analysis, interpretation of results, or decision to
the incidence of diarrhea per child-year. All analyses were done by publish this research. AK, DKT, ND and KR had full access to all
intention-to-treat. the data in the study and had nal responsibility for the decision
to submit for publication.
RESULTS: A total of 134 infants in the zinc and 124 in the placebo groups
www.pediatrics.org/cgi/doi/10.1542/peds.2012-2980
were assessed for the incidence of diarrhea. There was a 39% reduction
doi:10.1542/peds.2012-2980
(crude incident rate ratio [IRR] 0.61, 95% condence interval [CI] 0.53
0.71) in episodes of diarrhea, 39% (adjusted IRR 0.61, 95% CI 0.540.69) Accepted for publication Mar 25, 2013

in the total number of days that a child suffered from diarrhea, and Address correspondence to Akash Malik, MBBS, Department of
Community Medicine, Maulana Azad Medical College and
reduction of 36% in duration per episode of diarrhea (IRR 0.64, 95% CI Associated Hospitals, Bahadur Shah Zafar Marg, New Delhi, India.
0.560.74) during the 5 months of follow-up. E-mail: drakashmalik28@gmail.com
CONCLUSIONS: Short-course prophylactic zinc supplementation for PEDIATRICS (ISSN Numbers: Print, 0031-4005; Online, 1098-4275).
2 weeks may reduce diarrhea morbidity in infants of 6 to 11 months Copyright 2013 by the American Academy of Pediatrics
for up to 5 months, in populations with high prevalence of wasting FINANCIAL DISCLOSURE: The authors have indicated they have
and stunting. Pediatrics 2013;132:e46e52 no nancial relationships relevant to this article to disclose.
FUNDING: Supported by the Indian Council of Medical Research,
Department of Health Research (Ministry of Health and Family
Welfare), Government of India. Reference No. 3/2/2011/PG-thesis-
MPD-10.

e46 MALIK et al
Downloaded from by guest on November 1, 2015
ARTICLE

Zinc is required for multiple cellular recruited from the similar adjacent area Each 5 mL of the preparation containing
tasks and the immune system depends of Gangavihar. The study was approved by placebo (syrup base) or zinc (20 mg
on the sufcient availability of this es- the Institutional Ethical Committee of elemental zinc as zinc sulfate) was
sential trace element.1 Zinc deciency Maulana Azad Medical College, New Delhi, packed in similar-looking bottles. The
is common in several developing coun- and Associated Lok Nayak Hospitals. The syrups were of similar color, taste, and
tries, including India. This is because the trial is registered with the Clinical Trial consistency. During the survey, after
commonly consumed staple foods have Registry-India, number CTRI/2010/091/ ascertaining the eligibility and obtaining
low zinc contents and are rich in phytates, 001417. informed consent, the infants were en-
which inhibit the absorption and utiliza- We hypothesized that zinc prophylaxis rolled sequentially. The mother received
tion of zinc.2 Randomized controlled trials for 2 weeks would reduce the incidence the bottles with prelabeled serial num-
have shown that zinc supplementation of diarrhea in subsequent months. bers. The eld investigator administered
during acute diarrhea reduces the du- Thus, we excluded any child receiving the rst dose of the intervention at the
ration and severity, as well as the zinc supplement at the time of study or time of enrollment and advised the
incidence of subsequent diarrheal epi- who had received it in the preceding mother to give 5 mL of syrup (using
sodes.37 However, recently published 3 months, those who were severely a standard 5-mL plastic spoon) daily to
meta-analyses conclude that pro- malnourished, immune-decient, cur- the infant for the remaining 13 days.
phylactic zinc supplementation signi- rently on steroid therapy, severely ill Subsequently, visits were made on the
cantly reduces the incidence of diarrhea requiring hospitalization, or of families 7th and the 14th days to ensure com-
only in children .12 months of age.810 likely to migrate from the study area. A pliance. If the syrup had not been given
Because the incidence of diarrhea is house-to-house survey was done at the regularly, a maximum of 1 week was
comparatively high in children 6 to 12 beginning of the study to identify and given to complete the dosages. We col-
months of age (4.8 episode per year),11 recruit the eligible infants. The study lected data for any possible side effects
coinciding with the starting of comple- purpose was explained to the family and as reported by the caregivers during
mentary feeding, the current study an informed consent was obtained from these visits. To ensure that the child did
aimed to evaluate whether zinc pro- parents of all infants before they were not receive additional doses of zinc, we
phylaxis for a short duration has any included in the trial. The recruitment provided mothers with identity cards
role in reducing the morbidity due to was done during the rst 2 weeks of indicating the study title and that the
diarrhea in this age group. Although the January and July, followed by subsequent infants had received zinc syrup. These
original trial included additional out- 5 months of follow-up, respectively. This cards were to be produced whenever
comes, such as acute respiratory tract ensured the assessment of outcomes for the child was taken to any medical
infections and growth, the results of a complete year from January 2011 to practitioner.
these will be reported separately. January 2012, to minimize the effect of
Outcomes and Follow-up
seasonality.
METHODS The primary outcome was the incidence
Randomization and Blinding of diarrhea per child-year. Diarrhea
Study Setting and Participants was dened as 3 or more loose, liquid,
Random sequence was generated by
This is a community-based, randomized, simple randomization method using or watery stools or any change in
double-blind, parallel-arm placebo- computer-generated random numbers consistency or frequency of stools or
controlled trial, conducted from Jan- (Excel 2010). The bottles were labeled at least 1 loose stool containing blood
uary 1, 2011, to January 15, 2012. We with serial numbers in the Department in a 24-hour period.12 Secondary out-
included all children 6 to 11 months of of Community Medicine, Maulana Azad comes included incidence density of
age residing in Gokulpuri, an urban Medical College, by DKT, without the acute diarrhea, dysentery, and persis-
resettlement colony in the northeast dis- knowledge of the eld investigator (AM). tent diarrhea; duration of diarrhea;
trict of Delhi, India, who were likely to stay The eld investigator and parents were and side effects. Acute diarrhea was
untilthecompletionofthestudy.Gokulpuri blinded to the treatment allocation and dened as an episode of diarrhea
has 2500 houses divided into 4 blocks, A, unblinding was done at the end of the lasting up to 14 days. If an episode
B, C, and D, with a predominantly migrant follow-up period for all 272 infants. lasted for .14 days, it was dened as
population of 23 000. Most of the pop- persistent diarrhea.12 The episode was
ulation belongs to the middle and lower Intervention classied as dysentery if the stool con-
socioeconomic strata. To achieve the - The zinc and placebo syrups were pre- tained blood.12 Duration was assessed
nal sample size, additional children were pared by Abyss Pharma (Delhi, India). as the number of days with diarrhea

PEDIATRICS Volume 132, Number 1, July 2013 e47


Downloaded from by guest on November 1, 2015
and as mean number of days a di- Sample Size episodes per child per year. The counts
arrheal episode lasted. A baseline as- The sample size was calculated taking were expressed by means and SD.
sessment (Table 1) was done at the time into account 4 primary outcomes: de- Difference between means was tested
of recruitment, which included weight crease in incidence of diarrhea, acute using t-test, for normally distributed
and length measurements using a respiratory tract infections, and in- data, or Mann-Whitney U test, for skewed
Salter weighing scale (up to 100 g crease in length and weight. For di- data.
[Model no. 235 6M; Salter India Ltd, arrhea, previous studies in similar Generalized estimating equations were
Daryaganj, New Delhi, India]) and an populations estimated an incidence of used to obtain an incident rate ratio
Infantometer (up to 1 mm [model no: AM 9.1 episodes (SD = 4.5) per child-year.7,9 (IRR) with 95% condence intervals
1744; ATICO Medical Pvt Ltd, Haryana, Thus, for a 20% reduction in the (CIs), to compare monthwise number
India]) respectively. All the outcomes incidence of diarrhea (a = 0.05 and of episodes and duration of diarrhea
were assessed by a trained eld power 80%), we required 90 infants in using Poisson log linear distribution,
investigator. each group. However, the largest by intention-to-treat analysis. The ex-
Follow-up for diarrhea began on the sample size required (for acute re- changeable working correlation matrix
15th day after intervention. Each child spiratory tract infection) was 258; thus, was selected for all the outcomes. We
was followed-up fortnightly 63 days we recruited the entire population of included all children who had taken at
and the follow-up continued for 5 216 infants from Gokulpuri and an least 2 doses of the intervention for the
months after the completion of zinc/ additional 56 infants from Gangavihar analyses. The follow-up visits for which
placebo supplementation. At each (total = 272). The outcomes for di- the infant outcomes were not available
follow-up, the mother/caregiver was arrhea were assessed for all recruited were imputed using the worst-case (2
asked about the occurrence of di- infants. episodes of diarrhea) and best-case
arrhea during the previous 15 days. scenarios (no episodes). However, this
Recovery from a diarrheal episode was Statistical Analysis did not change the study results; thus,
considered when the last day of di- The data were collected and checked for we present in this article results from
arrhea was followed by a 72-hour accuracy on a daily basis and entered complete data set analysis. We decided
diarrhea-free period.6 Subsequent epi- into SPSS version 16 (IBM SPSS Sta- to adjust the IRRs for covariates that
sodes were considered to be new di- tistics, IBM Corporation, Chicago, IL). appeared to be different at baseline in
arrheal episodes. The incidence density was expressed as the 2 groups. We also decided to com-
pare the monthwise mean episodes of
diarrhea in the 2 groups.
TABLE 1 Baseline Characteristics of the Study Subjects at the Time of Recruitment
Socioeconomic status was assessed by
Characteristic Zinc (n = 141) Placebo (n = 131)
using the Modied Kuppuswamy Scale
Gender, n (%)
(based on education and occupation of
Male 67 (47.5) 68 (51.9)
Female 74 (52.5) 63 (48.1) family head and total family income)
Age, mo, mean 6 SD 8.77 6 1.73 8.76 6 1.86 modied for Consumer Price Index for
Socioeconomic status, n (%) industrial workers of India for 2011.13
Upper 4 (2.8) 4 (3.1)
Upper Middle 39 (27.7) 30 (22.9) The z-scores for length and weight were
Lower Middle 65 (46.1) 58 (44.3) calculated by using World Health Orga-
Lower 33 (23.4) 39 (29.8) nization reference tables for length and
Average oor space per person, square meters 6 SD 7.75 6 4.13 8.26 6 5.21
Household water purication device, n (%)
weight.14,15
Yes 31 (22.0) 23 (17.6)
No 110 (78.0) 108 (82.4)
Observation and Results
Feeding type, n (%)
Exclusive breastfeeding 13 (9.2) 16 (12.2) From a total of 3155 households iden-
Complementary feeding 12 (8.5) 11 (8.4)
tied during the house to house survey,
Both 116 (82.3) 104 (79.4)
Length, cm, mean 6 SD 67.4 6 3.86 67.6 6 3.82 we assessed 272 infants for eligibility
Mean z score 21.76 6 1.46 21.69 6 1.48 (Fig 1). As there were no exclusions and
Stunted (,2Z WHO) , n (%) 51 (36.0) 54 (41.0) refusals, all the infants were recruited.
Weight, kg, mean 6 SD 7.26 6 1.1 7.21 6 1.2
Mean Z score 21.50 6 1.15 21.58 6 1.21 A total of 141 infants received zinc
Wasted (,2Z WHO) , n (%) 44 (31.2) 53 (41.0) and 131 received placebo. Both groups
WHO, World Health Organization. shared similar baseline characteristics

e48 MALIK et al
Downloaded from by guest on November 1, 2015
ARTICLE

(Table 1). Seven families (n = 4 in the (Table 2). Generalized estimating equa- Zinc signicantly reduced the mean
zinc group and n = 3 in the placebo tion regression model showed that there episodes of diarrhea for each of the
group, respectively) migrated during was a reduction of 39% (adjusted IRR 5 months (Table 4). However, the level of
the study period. The mean number of 0.61, 95% CI 0.530.71) in episodes of signicance decreased after the third
follow-ups was 10 in each group (zinc: diarrhea in the zinc group as compared month.
10.0 6 0.75, placebo: 10.0 6 0.76, P = with the placebo group after the model
.721). The nal analyses included 134 was adjusted for wasting. Side Effects
infants in the zinc group and 124 in the When types of diarrhea were analyzed Reported side effects were diarrhea,
placebo group, who had completed the separately (Table 2), we found a signif- vomiting, and constipation. The per-
study. A total of 19 infants (13.5%) in icant decrease of 31% in the episodes centage of children reporting these
the zinc group and 26 infants (20%) of acute diarrhea (adjusted IRR 0.69, were 9.0%, 10.4%, and 1.5%, respectively,
in the placebo group were given an 95% CI 0.590.81), 70% in the episodes in the zinc group and 7.3%, 4.8%, and 0%,
additional 1 week to complete the in- of persistent diarrhea (adjusted IRR respectively, in the placebo group, and
tervention, as they were found to be 0.30, 95% CI 0.170.51), and more than the difference was nonsignicant in the
initially noncompliant. 95% in the episodes of dysentery (ad- 2 groups.
justed IRR 0.03, 95% CI 0.010.24) in the Onedeathduetodiarrheawasreportedin
Effect on Diarrhea zinc group. thezincgroup3monthsafterrecruitment.
Zinc supplementation for 14 days caused Zinc supplementation led to a signicant Verbal autopsy revealed severe de-
a signicant reduction in the number of reduction of 39% (adjusted rate ratio [RR] hydrationduetononadministrationoforal
episodes of diarrhea. Of the total 829 0.61, 95% CI 0.540.69) in overall days rehydrationsolutionor theavailablehome
episodes observed, 329 episodes oc- with diarrhea. There was also a signi- uids were the cause of death. The fact
curred in the zinc group and 500 in the cant reduction of 36% in duration per that the death took place 3 months after
placebo group, accounting for an in- episode of diarrhea (adjusted RR 0.64, intervention, and the incorrect man-
cidence of 6.07 and 9.90 per child year 95% CI 0.560.74) observed in the zinc agement revealed in the verbal autopsy,
respectively, at the end of 5 months group (Table 3). rules out any possible role of zinc.

DISCUSSION
In the current trial, we report that
prophylactic zinc supplementation for
2 weeks signicantly reduced the in-
cidence and duration of diarrhea dur-
ing follow-up of 5 months. Although we
studied additional outcomes (ie, acute
respiratory tract infections and growth),
the results of these will be reported
separately.
Zinc depletion leads to upregulation of
neuropeptides, such as cyclic guanosine
monophosphate, and acute-phase reac-
tants, such as interleukin 1, which cre-
ates secretory conditions in the intestine
leading to diarrheal episodes.16 Thus,
zinc prophylaxis in zinc-decient pop-
ulations reduces diarrheal morbidity.
The major limitation of this study is that
serum zinc levels were not done to as-
sess the deciency and the subsequent
FIGURE 1 effect on serum zinc levels. Nevertheless,
Trial Prole. previous studies in similar populations

PEDIATRICS Volume 132, Number 1, July 2013 e49


Downloaded from by guest on November 1, 2015
TABLE 2 Effect of Zinc Supplementation on Incidence of Diarrhea on the Study Subjects Zinc prophylaxis was shown to reduce
Intervention Child Years Incidence Crude IRR Adjusted IRRa the incidence of diarrhea in both con-
Observed (Episodes Child1year21) (95% CI) (95% CI)
tinuous as well as short-course sup-
All forms of diarrhea
Zinc 54.08 6.07 0.61 (0.560.74) 0.61 (0.530.71)
plementation trials, in 2 meta-analyses.8,9
Placebo 50.25 9.90 1.00 1.00 However, the benecial effect was lim-
Acute diarrhea
ited to children .12 months of age.
Zinc 54.08 5.77 0.68 (0.570.83) 0.69 (0.590.81)
Placebo 50.25 8.33 1.00 1.00 In the current trial, a signicant re-
Persistent diarrhea duction of days with diarrhea per child
Zinc 54.08 0.28 0.29 (0.170.51) 0.30 (0.180.53)
Placebo 50.25 1.01 1.00 1.00 and duration per episode of diarrhea
Dysentery was observed. In contrast, results of 2
Zinc 54.08 0.02 0.032 (0.0040.24) 0.030 (0.010.24) previous trials have shown no effect of
Placebo 50.25 0.58 1.00 1.00
a
continuous zinc prophylaxis on the
Adjusted for wasting.
duration of diarrhea. Of these, 1 study
was done in the age group of 6 to
TABLE 3 Effect of Zinc Supplementation on Days with Diarrhea and Duration per Episode of 9 months and another in the age group
Diarrhea
of 18 to 36 months.19,26 Of the 2 meta-
Duration Intervention P Valueb Crude RR Adjusted RRc
(95% CI) (95% CI)
analyses, 1 with continuous zinc sup-
Zinc Placebo plementation trials showed fewer total
(n = 118)a (n = 116)a
days with diarrhea,27 whereas the other,
Mean 6 SD of days with diarrhea 10.10 6 7.06 23.19 6 13.8 ,.001 0.60 (0.530.76) 0.61 (0.540.69) which included studies with continuous
Mean 6 SD days per episode 3.60 6 2.23 5.34 6 2.16 ,.001 0.63 (0.550.77) 0.64 (0.560.74)
and short-course zinc supplementa-
RRrate ratio.
a The children with 0 episodes were excluded. tion, showed no effect on duration of
b Mann-Whitney U test, P , .05 considered signicant.
c Adjusted for wasting.
diarrhea.7
A signicant reduction in incidence
was seen when diarrhea was further
TABLE 4 Monthwise Episodes of Diarrhea in was used, only 1 study had shown sig-
the 2 Study Groups classied into acute diarrhea, persis-
nicant reduction in the incidence tent diarrhea, and dysentery in the
Month Zinc Placebo P Valuea
of diarrhea in a 12- to 35-month age current trial. In the past, only 1 study
Mean (SD) Mean (SD) group.18 Previous studies, which were concluded that the incidence of acute
First 0.44 (0.60) 0.85 (0.84) ,.0001 carried out in infants of 6 to 11 months, diarrhea was reduced signicantly by
Second 0.40 (0.56) 0.83 (0.87) ,.0001
Third 0.49 (0.65) 0.88 (0.77) ,.0001
have shown similar results to the zinc supplementation, but in a wider
Fourth 0.58 (0.65) 0.82 (0.78) .014 current trial but after continuous zinc age group (635 months).28 Three
Fifth 0.61 (0.80) 0.77 (0.73) .037 supplementation.1922 One of these tri- studies, which had a similar age group
a Mann-Whitney U test, P , .05 considered signicant.
als was carried out in a cohort of low or analyzed results for children ,12
birth weight infants.20 Trials have also months of age, showed no signicant
shown the effectiveness of continuous decrease in persistent diarrhea in
of Delhi have shown high prevalence of the zinc group.6,22,24 Although both
zinc deciency (normal: 11.522.2 mM) zinc prophylaxis among wider age groups
the meta-analyses show that risk of
to the extent of 73.3% for values (641 months and 635 months, re-
persistent diarrhea did decrease
,10.4 mM and 33.8% for values ,9.0 spectively), but subgroup analysis for
with zinc supplementation, subgroup
mM.3 Moreover, in our study, the pro- children ,12 months of age was not
analysis for the 6 to 11 months
portion of stunted infants was .20%, done.23,24 In a large study done in a sim-
age group is not available.9,27 Also
which suggests an elevated risk of zinc ilar population of Delhi as the current one of these meta-analyses included
deciency, because stunting is a proxy trial, zinc prophylaxis of 4 months was studies with continuous zinc supple-
indicator of zinc deciency in population found to be effective only in children .12 mentation only. Regarding dysentery,
studies.17 Also, baseline data on in- months of age.25 Thus, unlike the previous only 1 study showed signicant re-
cidence density of diarrhea in this age studies, the current trial showed that duction in incidence of dysentery fol-
group were not available. short-course zinc prophylaxis signi- lowing zinc supplementation, that too
Among the studies in which short- cantly reduced diarrheal incidence in an in a wide age group of 6 to 35 months
course zinc prophylaxis of 2 weeks age group of 6 to 11 months. with continuous supplementation.24

e50 MALIK et al
Downloaded from by guest on November 1, 2015
ARTICLE

A study with short-course zinc sup- arrhea is seen in the age group of 6 slum populations, and thus keep suf-
plementation showed a nonsignicant to 11 months,11 may have been re- fering from repeated episodes of di-
reduction in incidence of dysentery sponsible for such signicant results arrhea. The difculty of having to give
in the age group of 12 to 35 months.18 in the current study. zinc to apparently healthy children is
Of the 2 meta-analyses, 1 is in agree- that the delivery strategy has to be
ment with the current trial, although community based, thus requiring ad-
the age group is wide in this meta- CONCLUSIONS ditional time and work on the part
analysis and studies with only con- Previous trials and meta-analyses have of the health workers/community
tinuous zinc supplementation have shown the benecial effect of zinc volunteers.
been included.9,27 prophylaxis on diarrhea either by The results of this study have important
Among the previous studies in similar continuous supplementation for a long cost and operational implications, as
populations, we found that 1 study duration, ranging from 3 months to short-course prophylaxis of zinc in an
may have insufcient power to detect 1 year, or in age groups of .12 months. adequate dose might be more feasible
a signicant decrease in diarrhea The current study was able to show than continuous therapies.
morbidity in infants 6 to 11 months of signicant reduction in diarrhea mor- The results of this study may be
age.25 In other studies, zinc pro- bidity in infants of 6 to 11 months, extrapolated to similar zinc-decient
phylaxis was given to a subset of the even 5 months after short-course zinc populations only. Future trials on the
population that had already received prophylaxis. effect of zinc prophylaxis on diarrhea
therapeutic zinc for acute diarrhea, The advantage of zinc given as a should concentrate on zinc-decient
which might have led to reduced ef- community-based prophylactic interven- pockets in both developed and de-
fectiveness of the subsequent zinc tion is that all children in the target veloping countries. It is desirable that
prophylaxis.5,7,24,28 However, the cur- population will be covered. This in turn such trials follow a standardized pro-
rent study was done in a population will reduce the overall incidence of cedure regarding the duration and dose
that had not received zinc supple- diarrhea in the community compared of zinc prophylaxis. This would ensure
mentation for the preceding 3 months, with administration of zinc only to that policy makers have reliable and
was apparently healthy, and had children who seek treatment for di- valid evidence to implement zinc pro-
a high proportion of wasted and arrhea. This is because many children phylaxis programs for those child
stunted infants. This, coupled with the suffering from diarrhea may not come populations that will benet the most
fact that the maximum burden of di- to a health facility, as is common in the from them.

REFERENCES
1. Beisel WR. Single nutrients and immunity. duration and severity of the episode 9. Bhutta ZA, Black RE, Brown KH, et al. Pre-
Am J Clin Nutr. 1982;35(suppl 2):417468 a community based double-blind controlled vention of diarrhea and pneumonia by zinc
2. Black RE. Zinc deciency, immune function, trial. N Engl J Med. 1995;333:839844 supplementation in children in developing
and morbidity and mortality from in- 6. Sazawal S, Black RE, Bhan MK, et al. Zinc countries: pooled analysis of randomized
fectious disease among children in de- supplementation reduces the incidence of controlled trials. Zinc Investigators Col-
veloping countries. Food Nutr Bull. 2001;22: persistent diarrhea and dysentery among laborative Group. J Pediatr. 1999;135(6):
155162 low socioeconomic children in India. J Nutr. 689697
3. Baqui AH, Black RE, El Arifeen S, et al. Effect 1996;126(2):443450 10. Brown KH, Rivera JA, Bhutta Z, et al; In-
of zinc supplementation started during 7. Sazawal S, Black RE, Bhan MK, Jalla S, ternational Zinc Nutrition Consultative
diarrhea on morbidity and mortality in Sinha A, Bhandari N. Efcacy of zinc sup- Group (IZiNCG). Assessment of the risk of
Bangladeshi children: community random- plementation in reducing the incidence and zinc deciency in populations. Food Nutr
ized trial. BMJ. 2002;325(7372):1059 prevalence of acute diarrheaa community- Bull. 2004;25(1 suppl 2):S99S203
4. Walker CL, Black RE. Zinc for the treatment based, double-blind, controlled trial. Am J 11. Kosek M, Bern C, Guerrant RL. The global
of diarrhoea: effect on diarrhoea morbid- Clin Nutr. 1997;66(2):413418 burden of diarrhoeal disease, as estimated
ity, mortality and incidence of future epi- 8. Brown KH, Peerson JM, Baker SK, Hess SY. from studies published between 1992 and
sodes. Int J Epidemiol. 2010;39(suppl 1): Preventive zinc supplementation among 2000. Bull World Health Organ. 2003;81:
i63i69 infants, preschoolers, and older prepubertal 197204
5. Sazawal S, Black RE, Bhan MK. Effect of zinc children. Food Nutr Bull. 2009;30(suppl 1): 12. World Health Organization. Diarrhoeal dis-
supplementation during acute diarrhea on S12S40 ease. Available at: www.who.int/mediacentre/

PEDIATRICS Volume 132, Number 1, July 2013 e51


Downloaded from by guest on November 1, 2015
factsheets/fs330/en/index.html. Accessed on morbidity from diarrhea and respiratory 24. Penny ME, Marin RM, Duran A, et al. Ran-
October 7, 2010 infections among rural Guatemalan chil- domized controlled trial of the effect of
13. Kuppuswamy B. Manual of Socioeconomic dren. Pediatrics. 1997;99(6):808813 daily supplementation with zinc or multiple
Status (Urban). Delhi, India: Manasayan; 1981 20. Sur D, Gupta DN, Mondal SK, et al. Impact of micronutrients on the morbidity, growth,
14. World Health Organization. Child growth zinc supplementation on diarrheal mor- and micronutrient status of young Peruvian
standards. Weight-for-age. Available at: www. bidity and growth pattern of low birth children. Am J Clin Nutr. 2004;79(3):457
who.int/childgrowth/standards/weight_for_ weight infants in Kolkata, India: a ran- 465
age/en/index.html. Accessed July 23, 2011 domized, double-blind, placebo-controlled, 25. Bhandari N, Bahl R, Taneja S, et al. Sub-
15. World Health Organization. Child growth community-based study. Pediatrics. 2003; stantial reduction in severe diarrheal mor-
standards. Length/height-for-age. Available 112(6 pt 1):13271332 bidity by daily zinc supplementation in
at: www.who.int/childgrowth/standards/ 21. Brooks WA, Santosham M, Naheed A, et al. young north Indian children. Pediatrics.
height_for_age/en/index.html. Accessed Effect of weekly zinc supplements on in- 2002;109(6). Available at: www.pediatrics.
July 23, 2011 cidence of pneumonia and diarrhoea in org/cgi/content/full/109/6/e86
16. Wapnir RA. Zinc deciency, malnutrition children younger than 2 years in an urban, 26. Rosado JL, Lpez P, Muoz E, Martinez H,
and the gastrointestinal tract. J Nutr. 2000; low-income population in Bangladesh: Allen LH. Zinc supplementation reduced
130(suppl 5S):1388S1392S randomised controlled trial. Lancet. 2005; morbidity, but neither zinc nor iron sup-
17. de Benoist B, Darnton-Hill I, Davidsson L, 366(9490):9991004 plementation affected growth or body
Fontaine O, Hotz C. Conclusions of the joint 22. Long KZ, Montoya Y, Hertzmark E, Santos JI, composition of Mexican preschoolers. Am J
WHO/UNICEF/IAEA/IZiNCG interagency meet- Rosado JL. A double-blind, randomized, Clin Nutr. 1997;65:1319
ing on zinc status indicators. Food Nutr clinical trial of the effect of vitamin A and 27. Aggarwal R, Sentz J, Miller MA. Role of zinc
Bull. 2007;28(suppl 3):S480S484 zinc supplementation on diarrheal disease administration in prevention of childhood
18. Rahman MM, Vermund SH, Wahed MA, and respiratory tract infections in children diarrhea and respiratory illnesses: a meta-
Fuchs GJ, Baqui AH, Alvarez JO. Simulta- in Mexico City, Mexico. Am J Clin Nutr. 2006; analysis. Pediatrics. 2007;119(6):11201130
neous zinc and vitamin A supplementation 83(3):693700 28. Larson CP, Nasrin D, Saha A, Chowdhury MI,
in Bangladeshi children: randomised dou- 23. Gupta DN, Mondal SK, Ghosh S, Rajendran Qadri F. The added benet of zinc supple-
ble blind controlled trial. BMJ. 2001;323 K, Sur D, Manna B. Impact of zinc supple- mentation after zinc treatment of acute
(7308):314318 mentation on diarrhoeal morbidity in rural childhood diarrhoea: a randomized, double-
19. Ruel MT, Rivera JA, Santizo MC, Lnnerdal B, children of West Bengal, India. Acta Pae- blind eld trial. Trop Med Int Health. 2010;15
Brown KH. Impact of zinc supplementation diatr. 2003;92(5):531536 (6):754761

e52 MALIK et al
Downloaded from by guest on November 1, 2015
Short-Course Prophylactic Zinc Supplementation for Diarrhea Morbidity in
Infants of 6 to 11 Months
Akash Malik, Davendra K. Taneja, Niveditha Devasenapathy and K. Rajeshwari
Pediatrics 2013;132;e46; originally published online June 3, 2013;
DOI: 10.1542/peds.2012-2980
Updated Information & including high resolution figures, can be found at:
Services /content/132/1/e46.full.html
References This article cites 24 articles, 15 of which can be accessed free
at:
/content/132/1/e46.full.html#ref-list-1
Citations This article has been cited by 3 HighWire-hosted articles:
/content/132/1/e46.full.html#related-urls
Subspecialty Collections This article, along with others on similar topics, appears in
the following collection(s):
Gastroenterology
/cgi/collection/gastroenterology_sub
Pharmacology
/cgi/collection/pharmacology_sub
Therapeutics
/cgi/collection/therapeutics_sub
Permissions & Licensing Information about reproducing this article in parts (figures,
tables) or in its entirety can be found online at:
/site/misc/Permissions.xhtml
Reprints Information about ordering reprints can be found online:
/site/misc/reprints.xhtml

PEDIATRICS is the official journal of the American Academy of Pediatrics. A monthly


publication, it has been published continuously since 1948. PEDIATRICS is owned, published,
and trademarked by the American Academy of Pediatrics, 141 Northwest Point Boulevard, Elk
Grove Village, Illinois, 60007. Copyright 2013 by the American Academy of Pediatrics. All
rights reserved. Print ISSN: 0031-4005. Online ISSN: 1098-4275.

Downloaded from by guest on November 1, 2015


Short-Course Prophylactic Zinc Supplementation for Diarrhea Morbidity in
Infants of 6 to 11 Months
Akash Malik, Davendra K. Taneja, Niveditha Devasenapathy and K. Rajeshwari
Pediatrics 2013;132;e46; originally published online June 3, 2013;
DOI: 10.1542/peds.2012-2980

The online version of this article, along with updated information and services, is
located on the World Wide Web at:
/content/132/1/e46.full.html

PEDIATRICS is the official journal of the American Academy of Pediatrics. A monthly


publication, it has been published continuously since 1948. PEDIATRICS is owned,
published, and trademarked by the American Academy of Pediatrics, 141 Northwest Point
Boulevard, Elk Grove Village, Illinois, 60007. Copyright 2013 by the American Academy
of Pediatrics. All rights reserved. Print ISSN: 0031-4005. Online ISSN: 1098-4275.

Downloaded from by guest on November 1, 2015

Potrebbero piacerti anche