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Effect of micronutrient supplementation on health and nutritional statusof schoolchildren: growth and morbidity

K. V. Rameshwar Sarma, M.D., M.Sc.*, P. Udaykumar, M.D., N. Balakrishna, Ph.D.,K. Vijayaraghavan, M.B.B.S, M.Sc., and B. Sivakumar, Ph.D.

National Institute of Nutrition (Indian Council of Medical Research), Hyderabad, India

Manuscript received April 6, 2004; accepted July 23, 2005.

bstract Objective: We evaluated the effect of a micronutrient-fortified beverage on growth and morbidityin apparently healthy schoolchildren.Methods: This was a double-blind, placebo-controlled, matched-pair, cluster, randomized study insemi-urban middle-income residential schoolchildren aged 6 to 16 y. Anthropometrics (height andweight), clinical symptoms of deficiency, and morbidity data were collected at baseline in thesupplemented group (n � 446 in 10 grades) and the placebo group (n � 423 in 10 grades) and after14 mo of supplementation (n � 355 in the supplement group and n � 340 in the placebo group fromnine pairs).Results: After 14 mo of supplementation, there was a significant increase in mean increments ofheight and weight z scores of �0.04 and 0.02, respectively, in the supplemented group comparedwith �0.14 and �0.09 in the placebo group. Velocity of weight (3.56 versus 3.00) was significantly(P � 0.01) higher with supplementation. Although there were no differences in the incidence ofcommon childhood diseases such as fever, cough and cold, diarrhea, and ear infections elicited fora reference period of 1 mo at every quarterly follow-up examination, the mean duration of illness(calculated per person per year) was significantly shorter (5.0 d) in the supplemented group than inthe placebo group (7.4 d).Conclusions: The micronutrient-fortified beverage was beneficial in promoting growth and de-creasing duration of common illnesses among middle-class residential schoolchildren who hadadequate energy and protein intakes. © 2006 Elsevier Inc. All rights reserved.

Nutrition 22 (2006) S8–S14www.elsevier.com/locate/nut

eywords: Micronutrients; Growth; Anthropometry; Morbidity; Nutritional supplementation; India

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ntroduction

With gradual and progressive decreases in severe formsf protein-energy malnutrition, micronutrient deficiencyisorders are emerging as major impediments to growth andell-being in India [1]. The Mid-day Meal program forrimary schoolchildren in India was shown to exert onlyimited beneficial effect on nutrition, enrollment, atten-ance, and scholastic performance [2–4]. Micronutrient

This study was supported by M/S GlaxoSmithKline Consumer Health-are, Ltd., India.

* Corresponding author. Tel.: �91-40-2701-8234; fax: �91-40-2701-234/-9074.

mE-mail address: rameshwar_kv@yahoo.co.in (R. Sarma).

899-9007/06/$ – see front matter © 2006 Elsevier Inc. All rights reserved.oi:10.1016/j.nut.2005.07.011

alnutrition (in particular vitamin A, iron, and iodine) is aajor public health problem in India [5,6]. It has been

eported that deficiencies in zinc, B-complex vitamins, andalcium are also prevalent [7,8]. In general, micronutrientalnutrition affects growth and mental development in

ounger children more severely than older children [8,9].Adverse effects of micronutrient deficiencies on growth

nd development, particularly on mental health, physicaltatus, and immune status, warrant immediate attention7–11]. Many studies have shown that micronutrients havepositive influence on growth [8,12,13], psychomotor co-

rdination [14,15], mental function [12,16], and skeletalealth in children [14,17,18]. Some study populations with

ultiple micronutrient deficiencies have been shown to ex-

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S9R. Sarma et al. / Nutrition 22 (2006) S8–S14

ibit improvement only when more than one nutrient wasupplemented [12,14,18,19]. The beneficial response, inhysical and mental development, to multiple micronutri-nts was observed only when energy intakes were adequate14,17,20]. Conditional improvements in the growth andemoglobin status in anemic children, growth in stuntedhildren, and work capacity in micronutrient-deficient chil-ren have been shown, suggesting that the effects of sup-lementation are more marked in those with poorer nutri-ional status at baseline [9,21–23].

In the past, a positive relation among micronutrient supple-entation, physical, biochemical, visual, and psychomotor de-

elopment, and academic performance has been demonstratedn children in low-income groups [24–26].

This study tested the hypothesis that supplementationith a micronutrient-fortified beverage can improve growth,evelopment, nutrition, and health in apparently normalchoolchildren with no obvious evidence of dietary inade-uacy of energy and protein.

aterials and methods

Details of deriving sample size, randomization, distribu-ion of the beverage, and statistical analysis are providedlsewhere [27]. Briefly, a double-blind, placebo-controlled,atched-pair, cluster randomized study was undertaken in

hildren 6 to 16 y of age in grades 1 to 10 from twoesidential schools that catered to middle-income, semi-rban children. Data on outcome measurements were col-ected at baseline from 446 subjects in the supplementedroup and 423 in the placebo group from 10 grades or pairs.fter 14 mo of supplementation, there were 355 subjects in

he supplemented group and 340 in the placebo group fromine pairs.

Data on anthropometric measurements (height andeight) and presence of clinical deficiencies and morbidityere collected at baseline (March and July 1999) and aftermo (November to December 1999), 8 mo (February toarch 2000), and 14 mo (September to October 2000) of

upplementation. However, for the present study, only thenitial and final values were considered for analysis.

ssessment of outcome variables

Trained investigators using standard procedures and equip-ent [30] measured and recorded anthropometric measure-ents (height and weight). In addition, any signs of clinical

eficiencies in vitamin A (Bitot’s spots), B vitamins (angulartomatitis, glossitis, and cheilosis), vitamin C (bleeding gums),nd iodine (goiter) and conditions such as fluorosis (mottlednamel) and tooth caries were assessed by medical doctors andecorded. Assessment of age was made by using birth certifi-ates, Janma kundali/Jatakam (local calendars that use astro-ogic calculations) or any other available records. A history of

cute illness during the previous month was recorded during p

ach round of clinical examination and that of any chronicllness during the previous year was recorded at the time ofaseline examination. In the case of young children, assistancey an auxiliary nurse and the children in the school was soughto record any history of illness.

ietary intake

Dietary intake of children participating in the study wasssessed by an institutional diet survey at baseline and in theiddle of the supplementation period. Individually weighed

ietary intake was recorded on 3 consecutive days in a sub-roup of 90 children (10% of total sample selected at random)ho represented the subjects (supplemented group, n � 46;lacebo group, n � 44, from eight pairs). Care was taken tonclude one holiday during the 3 consecutive days becausepecial food items are often prepared on holidays. All raw andooked foods that were prepared and consumed by the childrenn the schools were weighed on a digital weighing scale.ortions consumed by selected children for the dietary surveyere weighed on a digital weighing scale (1-kg capacity with

ensitivity of 1 g; Mignon, Wedo, Germany) and record theeight of each food item served to calculate the raw foods in

hose portions. Any plate wastage was also weighed and re-orded. Plate wastage, which was minimal, was subtractedrom total dietary intake on the day of the dietary survey.utrient intake for each child was calculated by using theutrient values of Indian foods [29]. Reported nutrient intakeas calculated on the basis of nutritive value of the dietary

ngredients and therefore did not allow for the losses that mightave occurred during cooking.

nthropometry

Standing height and weight were recorded for all childrenho participated in the study by using standard equipment and

dopting standard procedures [30]. Body weight was measuredn a weighing scale (SECA, Germany) with an accuracy of00 g and height was measured with an anthropometric rodGPM, Switzerland) with an accuracy of 0.1 cm.

esults

overage

The number of children available for supplementationnd placebo distribution in all grades at the start of the studyere 446 and 423, respectively, from 10 pairs. More than0% of subjects consumed the beverage for more than 80%f the days in the study period and coverage of cohorts in allollow-ups for anthropometry and morbidity was 80% [27].

ietary intake

Mean dietary intakes by treatment groups, expressed as

ercentages of the Indian recommended dietary allowance,

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s presented in Table 1. Intake included milk used in thereparation of the nutritional beverage in the treatmentroup but did not include the fortified nutrients because theode was broken after locking in of the data at the comple-ion of the study. Nutrient intake was essentially similar inhe supplemented and placebo groups. On average, the dietet 80% of the children’s calorie requirement. Intakes of

rotein, fat, calcium, folate, and vitamin C were above thendian recommended dietary allowance. The limiting nutri-nts in the diet were observed to be iron, thiamin, niacin,nd vitamin A.

nthropometric status

Mean ages (10.1 � 2.46 y in the supplemented group and0.2 � 2.36 y in the placebo group) and key anthropometriceasurements, namely height (135.0 � 13.44 versus 134.911.75 cm) and weight (28.3 � 7.64 versus 28.6 � 7.12

able 1utrient intake of subjects at baseline

Supplement (n � 8)

Mean(%RDA)

SD

rotein (g) 53.2 (132.7) 6.92otal fat (g) 30.6 (134.5) 2.41nergy (kcal) 1857.8 (86.5) 278.09alcium (mg) 743.1 (148.6) 50.21hosphorus (mg) 1191.2 (NA) 143.48ron (mg) 9.8 (31.7) 1.06itamin A (�g) 354.2 (58.7) 52.84hiamin (mg) 0.75 (69.6) 0.10iboflavin (mg) 1.3 (97.7) 0.11iacin (mg) 9.9 (68.6) 1.51itamin C (mg) 42.7 (105.0) 6.17olic acid (�g) 155.7 (215.4) 23.04inc (mg) 6.9 (NA) 1.07

NA, not available; %RDA, percentage of recommended dietary allowan

able 2ge and anthropometric measurements by grade and groups at baseline*

rade Age (y) Height (cm) W

S P S P S

6.74 6.87 116.7 116.9 197.23 7.61 120.4 122.8 208.07 8.55 123.8 127.0 229.31 9.19 129.8 131.8 25

10.15 10.10 134.6 134.2 2710.97 11.21 140.2 137.2 3012.17 11.87 144.5 143.9 3212.83 12.59 149.0 147.6 3613.52 13.88 155.7 152.5 42

ean 10.1 10.2 135.0 134.9 28D 2.46 2.36 13.44 11.75 7

NS NS

HAZ, height-for-age z score; NS, not significant; P, placebo group; S,

*Values are means of each classroom (cluster); weighted paired t test was perf

g), in the two cohorts were not significantly different ataseline. The z scores of heights and weights of the twoohorts were also not different at baseline (Table 2).

At the end of the study, the mean height of children in theupplemented group was 142.7 � 13.3 cm compared with41.5 � 12.51 cm in children in the placebo group, and thisas statistically significantly different (P � 0.036). No suchifference was observed with regard to measurement ofeight. No differences were observed in the z scores of finaleasurements of height and weight (Table 3).Results for velocities, i.e., rates of change (standardized

or 12 mo), in height and weight z scores for increments ofeight and weight are presented in Table 4 and Figs. 1 and. The rate of change of growth in weight, i.e., velocity ineight, was significantly (P � 0.05) better in the supple-ented group than in the placebo group, whereas the ve-

ocity of height showed a trend (P � 0.057) in the supple-ented group. However, mean velocities of height between

Placebo (n � 8) P

Mean(%RDA)

SD

53.4 (135.6) 8.07 0.8730.5 (132.8) 1.92 0.91

1830.1 (87.3) 316.55 0.67750.3 (150.1) 53.85 0.49

1174.8 (NA) 165.06 0.669.5 (32.1) 1.45 0.46

355.9 (60.4) 66.21 0.890.74 (70.1) 0.13 0.52

1.3 (98.7) 0.12 0.819.8 (70.3) 1.78 0.77

41.7 (104.7) 7.41 0.54155.6 (216.5) 26.65 0.98

7.0 (NA) 1.24 0.85

, standard deviation

g) HAZ WAZ

P S P S P

19.8 �0.60 �0.65 �1.02 �0.9422.2 �0.39 �0.29 �0.91 �0.6823.8 �0.58 �0.45 �1.05 �0.8325.3 �0.63 �0.23 �0.94 �0.8726.5 �0.59 �0.65 �1.04 �1.1628.2 �0.45 �1.06 �0.97 �1.4033.9 �0.82 �0.72 �1.24 �0.9837.0 �0.78 �0.75 �1.09 �0.9240.8 �0.46 �1.15 �0.78 �1.2228.6 �0.58 �0.66 �1.01 �1.007.12 0.145 0.314 0.128 0.220

S NS NS

ented group; SD, standard deviation; WAZ, weight-for-age z score

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S11R. Sarma et al. / Nutrition 22 (2006) S8–S14

roups remained significantly different after adjusting forhe initial values. The z scores for the increments in heightnd weight were also significantly higher in the supple-ented group than in the placebo group.Mean body mass index values were comparable at base-

ine and final follow-up, whereas increments of body massndex were significantly (P � 0.05) higher in the micronu-rient-supplemented group (Table 5).

eficiency signs

The prevalence of signs of clinical deficiency at baselinend final follow-up in the supplemented and placebo groupss presented in Table 6. Prevalence of signs of vitamineficiency was minimal and almost similar between groups.revalence of goiter was relatively high in both groups,

ndicating a prevalence of iodine deficiency in the area.

able 3nthropometric measurements by grade and groups at end of study*

rade Height (cm) Weight (kg)

S P S P

125.1 123.3 22.1 21128.4 129.4 23.7 25131.5 132.0 25.8 27136.9 136.6 29.0 28141.1 140.1 31.8 29148.5 145.2 36.1 33152.9 150.6 39.9 39157.5 155.9 43.7 43162.2 160.4 49.6 46

ean 142.7 141.5 33.5 32D 13.30 12.51 9.47 8

0.036 0.153 (NS)

HAZ, height-for-age z score; NS, not significant; P, placebo group; S,* Values are means of each classroom (cluster); weighted paired t test

able 4elocities of height and weight and z scores of increments in height and

rade Height (cm) Weight (kg)

S P S P

5.96 5.31 1.91 1.75.58 4.95 2.17 2.15.20 4.15 2.59 2.64.77 3.95 2.65 2.54.64 4.50 3.40 2.55.62 5.52 4.12 3.85.71 4.91 5.00 3.85.94 5.81 5.23 4.24.37 5.36 4.98 3.5

ean 5.31 4.94 3.56 3.0D 0.590 0.632 1.305 0.8

0.057† 0.017

HAZ, height-for-age z score; P, placebo group; S, supplemented group;* Values are means of each classroom (cluster); weighted paired t test

† Mean velocities of height between groups were significantly different after a

orbidity

Episodes of morbidity per child per year are presented inable 7. There were no differences in the incidence ofpisodes between groups. However, the mean duration ofickness was significantly longer in the placebo group (Ta-le 8).

iscussion

Although genetic factors are important in linear growth,nvironmental factors experienced during fetal developmentnd childhood cannot be discounted. In developing coun-ries, environmental factors are more likely causes of stunt-ng. As a result, the importance of micronutrient deficiencyas been increasingly debated, resulting in the paradigm

HAZ WAZ

S P S P

�0.43 �0.66 �1.05 �1.08�0.32 �0.42 �0.95 �0.84�0.76 �0.67 �0.98 �0.85�0.77 �0.51 �1.02 �0.94�0.54 �0.88 �1.00 �1.28�0.92 �1.13 �0.94 �1.37�0.79 �0.93 �1.16 �1.07�0.53 �0.82 �1.06 �1.00�0.66 �1.18 �0.74 �1.39�0.63 �0.80 �0.99 �1.09

0.194 0.260 0.113 0.2100.108 (NS) 0.312 (NS)

ented group; SD, standard deviation; WAZ, weight-for-age z scoreformed for comparison of mean differences between S and P groups.

by grade and groups*

HAZ WAZ

S P S P

0.18 �0.01 �0.03 �0.130.06 �0.13 �0.03 �0.160.00 �0.22 0.07 �0.02

�0.13 �0.28 �0.07 �0.07�0.18 �0.23 0.04 �0.12�0.19 �0.06 0.03 0.03�0.10 �0.21 0.08 �0.08�0.01 �0.07 0.03 �0.07�0.07 �0.02 0.04 �0.17�0.04 �0.14 0.02 �0.08

0.110 0.102 0.052 0.0660.016 0.002

andard deviation; WAZ, weight-for-age z scoreformed for comparison of mean differences between S and P groups.

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hift from “child survival” to “child health and develop-ent.” Apart from severe to chronic protein-energy malnu-

rition, which has been proved conclusively to be an impor-ant causative factor in stunting, subclinical micronutrienteficiencies among those who have adequate macronutrientntake may be an important contributing factor for stuntedrowth. In recent years, research and policy interests havehifted to iron, iodine, and vitamin A deficiencies. Thistudy investigated whether long-term (14 mo) supplemen-ation with a micronutrient-fortified beverage in otherwiseealthy children with adequate energy and protein intakeseads to greater body weight and height.

nthropometry

Anthropometric indicators showed that the present sub-ects were better nourished than those in previous reports ofural children [1]. The proportion of children who showedody height and weight less than �2 standard deviations ofhe National Center Health Statistics standards, considered autoff for undernutrition, ranged from 10% to 13% andhere were no significant differences between groups.

The rate of change in measurements of subjects’ heightnd weight was much higher than the national averageheight 5.0 versus 4.7 cm, weight 3.5 versus 2.6 kg) as

ig. 1. Height velocities by groups and grades. Mean velocities betweenroups were significantly different (P � 0.05) after adjusting for initialalues.

b

eported in survey data reported by National Nutrition Mon-toring Bureau (NNMB) [28] (an organization that has mon-tored nutrition in India in the past three decades, covering0 populous states in the country). In addition, the propor-ion of children who registered during the year increasedate of change in height and weight, which was significantlyigher in the supplemented group (weight 62%, height6%) than in the placebo group (weight and height 51%)nd higher than that reported by the NNMB [28]. Even theroportion of children who showed improvements in heightnd weight was significantly higher in the supplementedroup than in the placebo group. These results are in generalccord with the increased functional status such as entireone area [31] and attention and concentration [32] in chil-ren who received micronutrient supplements comparedith those who received placebo.

able 6revalence (percentage) of signs of deficiency (per child per year)*

linical sign Initial Final

Supplement Placebo Supplement Placebo

itot’s spots 0.0 0.3 0.0 0.0ngular stomatitis 2.5 2.4 0.3 0.0heliosis 3.4 6.2 1.4 0.9lossitis 2.0 1.8 0.3 0.3leeding gums 2.0 2.9 1.1 2.1ooth caries 10.1 13.8 5.9 6.8ottled enamel 8.5 2.9 0.0 1.2oiter 1 15.8 13.8 9.6 7.1oiter 2 5.4 2.9 4.2 2.6

* All clinical signs were comparable (P � 0.05) between groups at

able 5ody mass index by grade and groups at start and end of the study*

rade Initial Final Final � initial

S P S P S P

14.2 14.5 14.1 14.4 �0.16 �0.1114.2 14.6 14.3 14.9 0.16 0.2214.3 14.7 14.9 15.4 0.55 0.7214.8 14.5 15.4 15.2 0.59 0.6414.9 14.7 15.9 15.1 1.02 0.4915.2 14.9 16.3 15.9 1.09 0.9815.5 16.2 17.0 17.1 1.45 0.8716.2 16.9 17.5 17.7 1.30 0.7917.3 17.4 18.7 17.9 1.46 0.50

ean 15.2 15.4 16.0 16.0 0.83 0.57D 1.03 1.16 1.54 1.31 0.58 0.341

NS NS 0.049

NS, not significant; P, placebo group; S, supplemented group; SD,tandard deviation

* Values are means of each classroom (cluster); weighted paired t testas performed for comparison of mean differences between S and Proups.

aseline and at the end of the study (n � 9 pairs).

ig. 2. Weight velocities by groups and grades. *P � 0.05.

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icronutrient intake

The dietary intake of nutrients serving as biochemicalndicators [33] of nutritional status clearly demonstratedhat, even though the children belonged to a middle-incomeroup with body weights (87%) and heights (90%) withreater than mean �2 standard deviations of the Nationalenter Health Statistics standards had on adequate protein-nergy intake. Inadequate micronutrient intake and, hence,iochemical deficiencies were a prominent feature of thetudy group. The biochemical status of many micronutri-nts, namely iron (hemoglobin � 120 g/L, 55%), vitamin A33% to 55%), vitamin B2 (66%), folic acid (almost all),itamin B12 (4.5% to 9%), vitamin B6 (67%), and vitamin

(60%), was inadequate. This confirms several previousndings and is probably due to poor dietary intake, cookingr processing losses, and poor bioavailability. The extent ofeficiencies varied across micronutrients, with the mostimiting being iron, folate, riboflavin, pyridoxine, and vita-in A. Although many previous studies have shown thaticronutrient deficiency is widely prevalent in India [28],

his is the first Indian study to demonstrate that biochemicaleficiency in apparently healthy children [33] may also berevalent, indicating a definite need for food-based supple-ents.Several workers have observed growth changes on mi-

ronutrient repletion singly or in combination [19], withhanges being pronounced in young children. A meta-nalysis of 33 studies carried out by Brown et al. [34] toetermine the effect of supplemental zinc on growth anderum zinc concentrations in prepubertal children indicatedhat zinc supplementation produced highly significant, pos-tive responses in height and weight increments and con-luded that interventions to improve children’s zinc nutrit-re should be considered in populations at risk of zinceficiency, especially when there are increased rates ofnderweight or stunting.

The present results are on similar lines and the fortifiedeverage significantly affected growth, reflecting growth-timulating effect of micronutrients in general. Other inves-igators have studied the effect of zinc supplements onrowth [12], with initial improvement but no final beneficialffect; however, the present study showed an increase inncrements of height and weight. It is also worth mentioning

able 7pisodes of morbidity in the cohort of children (per child per year)*

isease Supplement Placebo

ever 3.3 3.5ough and cold 5.3 5.4iarrhea 1.0 1.2ar infection 0.6 0.6

* Different episodes of morbidity were comparable (P � 0.05) betweenroups (n � 9 pairs).

hat the present results would have been more amplified if

he placebo were not based on milk, with its inherent mi-ronutrients, which would have contributed beneficial ef-ects to the placebo recipients, thereby decreasing the actualifference between the supplemented and placebo groups. Its also possible that these effects would have been larger ifhe beverage had been administered to very young children2 to 5 y of age) and in children with more clinical defi-iencies, the prevalence of which is much smaller in thisroup even compared with other Indian data (NNMB) [28].

This micronutrient-fortified beverage given as a supple-ent showed a positive effect on the nutritional status of

hildren as reflected by increments in weight and height (zcores were standardized and reflected) and the proportionf children who registered greater velocity of height andeight compared with the NNMB survey data [28].The supplement affected the duration of common mor-

idity and not the incidence, probably due to a uniformnvironment where external exposures are minimal. Vantuijvenberg et al [16] studied the effect of fortified biscuitsn the micronutrient status of children in primary school.heir study showed that supplementation had no significantffect on growth and morbidity, although absenteeism wasuch lower in supplemented group.The study supports the idea that the prevalence of stunt-

ng to a great extent may be decreased if a food basket isnlarged or special micronutrient-fortification programs arenstituted to reach the masses and that, simultaneously,dequate care is taken to bridge the energy gap. The presenttudy has shown that food-based approaches are practical,ulturally acceptable, and simple by methodology to im-rove the dietary intake of micronutrients and macronutri-nts.

cknowledgments

The authors thank the three school authorities and stu-ents for participation and kind cooperation extendedhroughout the study. They also thank K. Narasimha Reddy,. P. V. Prasad, P. Kalyani, Y. Sudha, S. Anitha, Jyothihandrika, Y. Rajendra Prasad, T. T. Swamy, S. Sudhakarao, and R. Sambasiva Rao for valuable technical help inrganizing and conducting the study. They also thank A.

able 8ean duration (days) of illness in affected children*

isease Treatment

Supplement Placebo

ll diseases 5.0 � 0.87† 7.4 � 0.84pecific diseaseRespiratory 12.1 � 12.47 5.0 � 7.89Fever 3.3 � 1.56 5.3 � 1.96Gastroenteritis 5.0 � 7.89 2.2 � 5.09

* Comparisons of mean duration between groups (n � 9 pairs).

† P � 0.05.

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S14 R. Sarma et al. / Nutrition 22 (2006) S8–S14

adamuni Naidu of the National Institute of Nutrition,yderabad for expert statistical advice.

eferences

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[3] Rameshwar Sarma KV, Hanumantha Rao D, Mallikharjuna Rao K,GalReddy C, Sharad K, Vardhan Rao V, Pralhad Rao N. Impact ofmid-day meal program on educational and nutritional status of schoolgoing children in Andhra Pradesh, India. Asia Pac J Publ Health1995;8:48–52.

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