NUTRITION RESEARCH, Vol. 7, pp. 1117-1126, 1987 0271-5317/87 $3.00 + .00 Printed in the USA. Copyright (c) 1987 Pergamon Journals Ltd. All rights reserved. IMPACT OF HEMATINIC SUPPLEMENTATION ON COGNITIVE FUNCTION IN UNDERPRIVILEGED SCHOOL GIRLS (8-15 YRS OF AGE)* PURNIMA KASHYAP, Ph.D. and TARA GOPALDAS, Ph.D. Department of Foods and Nutrition M.S. University, Baroda 390 002, Gujarat, INDIA. ABSTRACT The effect of prophylactic hematinic dosing with 60 mg elemental iron (FeSO 4) for 60 days at a stretch, twice in a school year on selected tests of Cognitive Function (CF), namely, Clerical Task, Visual Recall, Digit Span and Mazes in underprivileged school girls(8-15 yrs) with an initial mean Hb of 10.42 • 0.09 g/dl was investigated. Sixtyfive pairs of subjects initially matched for age, Hb, individual and total CF test scores were randomly assigned to either the treatment or placebo group. Hb levels and CF tests were assessed every four months ie. baseline at the initiation of the study(0 month); at the end of the first school term ( 4th month); at the end of the second school term(8th month); and ~ollowing a withdrawal of inputs ( 12th month). Results of the study indicated that (a) Hb levels in the hematinic treated group were 12.33 • 0.09 g/dl as against 10.68 g/dl in the placebo group (b) CF test scores rose in both the hematinic treated and placebo groups with successive testing. Hematinic treated group demontrated significantly higher scores versus the placebo group in Clerical Task (5.83 vs 4.93), Digit Span (4.75 vs 4.33), Mazes ( 7.54 vs 6.20) at 8th month evaluation, but not at 4th month evaluation. At 12th month, a significant drop in Mazes score and Total Score was noted. The beneficial effect of a twice-a- year hematinic dosing for subjects under study in tests of CF mainly, concentration, discrimination, perception and visual motor coordination was indicated. Key words: Hematinic supplementation, anemia, cognitive function, underprivileged school girls. Presented at the 13th International Congress of Nutrition at Brighton, UK, held in August, 1985; supported by grants from the University Grants Commission, New Delhi, India; and forms a part of the doctoral work of Purnima Kashyap. 1117
Transcript
NUTRITION RESEARCH, Vol. 7, pp. 1117-1126, 1987 0271-5317/87 $3.00 + .00 Printed in the USA. Copyright (c) 1987 Pergamon Journals Ltd. All rights reserved.
IMPACT OF HEMATINIC SUPPLEMENTATION ON COGNITIVE FUNCTION IN UNDERPRIVILEGED SCHOOL GIRLS (8-15 YRS OF AGE)*
PURNIMA KASHYAP, Ph.D. and TARA GOPALDAS, Ph.D.
Department of Foods and Nutrition M.S. University, Baroda 390 002,
Gujarat, INDIA.
ABSTRACT
The effect of prophylactic hematinic dosing with 60 mg elemental iron (FeSO 4) for 60 days at a stretch, twice in a school year on selected tests of Cognitive Function (CF), namely, Clerical Task, Visual Recall, Digit Span and Mazes in underprivileged school girls(8-15 yrs) with an initial mean Hb of 10.42 • 0.09 g/dl was investigated. Sixtyfive pairs of subjects initially matched for age, Hb, individual and total CF test scores were randomly assigned to either the treatment or placebo group. Hb levels and CF tests were assessed every four months ie. baseline at the initiation of the study(0 month); at the end of the first school term ( 4th month); at the end of the second school term(8th month); and ~ollowing a withdrawal of inputs ( 12th month). Results of the study indicated that (a) Hb levels in the hematinic treated group were 12.33 • 0.09 g/dl as against 10.68 g/dl in the placebo group (b) CF test scores rose in both the hematinic treated and placebo groups with successive testing. Hematinic treated group demontrated significantly higher scores versus the placebo group in Clerical Task (5.83 vs 4.93), Digit Span (4.75 vs 4.33), Mazes ( 7.54 vs 6.20) at 8th month evaluation, but not at 4th month evaluation. At 12th month, a significant drop in Mazes score and Total Score was noted. The beneficial effect of a twice-a- year hematinic dosing for subjects under study in tests of CF mainly, concentration, discrimination, perception and visual motor coordination was indicated.
Key words: Hematinic supplementation, anemia, cognitive function, underprivileged school girls.
Presented at the 13th International Congress of Nutrition at Brighton, UK, held in August, 1985; supported by grants from the University Grants Commission, New Delhi, India; and forms a part of the doctoral work of Purnima Kashyap.
1117
1118 P. KASHYAP and T. GOPALDAS
INTRODUCTION
There is clinical evidence to demonstrate that patients with iron deficiency have altered behavior, characterised by apathy, irritability, inability to concentrate and impaired visual motor coordination. Most of the studies conducted on behavioral changes associated with nutritional anemia have either been on animals, infants or preschoolers(l). There is a great paucity of data on school children, especially girls. In an earlier study from this department (2) a beneficial effect of a prophylactic hematinic dosing at 40 mg elemental Fe for 60 days at a stretch on selected tests of Cognitive Function(CF), namely, Visual Recall, Digit Span, Clerical Task and Mazes was observed in underprivileged school boys (8-15 yrs of age). However, no study to our knowledge has been conducted on the changes in CF test scores on hematinic dosing in underprivileged school girls. In light of the higher iron requirements for girls compared to boys in the preadoles- cent/adolescent stage (3) the present study was designed to investigate the impact of a prophylactic dose of 60 mg elemental Fe/day for 60 days at a stretch, twice in a school year on selected tests of CF known to be affected in anemia, in underprivileged school girls, 8-15 yrs of age.
METHODS
Sample selection
Four schools, out of 45 primary schools catering exclusively to underprivileged school girls in Baroda city, Gujarat, were purposively selected(for logistical ease) for the study on the basis of the willingness of the school authorities to cooperate in the year long study. Only subjects with recorded birth dates between 8-15 years, with family incomes not exceeding Rs. 500/= (US 42.00) per month and those whose parents gave informed consent for participation in the study were enrolled.
Based on the above, 207 subjects were initially enrolled for the study~ but the sample was reduced to 130 subjects due attrition over time and inability to collect complete data on all subjects (See Experimental Design).
Dosage level of hematinic compound
The red cell morphology examination established iron deficiency as the primary cause of anemia(4). Thus, the cheapest and the most effective form of iron supplement, FeSO 4 (5), was selected. The dosage was calculated on the basis of the World Health Organisation recommendation(6) of 3 mg elemental iron per kg body weight per day as 60 mg elemental iron per day( Mean weight of the study group was 21 kg).
HEMATINICS AND COGNIIIVE FUNCTION 1119
Experimental Design
Eightythree pairs of subjects were initially matched for age, Hb, individual and total CF test scores. However, by the end of the year long study, data on only 65 pairs could be retained for analysis as the rest could not attempt the Clerical Task test at the baseline evaluation due to their inability to read the text. Also, some of these subjects performed the test on subsequent testing as they had learned to read and this could not be attributed to the treatment. As such it would have vitiated the results. The baseline (0 month) data on Hb and CF test scores (Table I) on 65 pairs of subjects indicated no significant difference between the two groups. This ensured that these groups were comparable and whatever differences emerged during the course of the study could be attributed to the treatment effect.
TABLE 1
Matching criteria for Hb and Cognitive Function test scores for hematinic tre -ated and placebo group underprivileged school girls(8-15yrs) at baseline evaluation.
Hb Group g/dl
Cognitive Function test scores
Clerical Task
Digit Span Visual ~gzes ~otal Memory Score
Iron 10.28• 4.00• treated (N= 65)
Placebo i0.39!O.14 4.11•
(N=65)
3.88_+0.16 7.89_+0.19 4.36_+0.22 20.11_+0.54
4.04_+0.13 7.77_+O.13 4.71• 20.55•
't' 0.5308 NS 0.483~ S 0.8083 NS 0.490~ S 0.3355 NS 0.6139 NS values
All values are mean • SE. NS - Difference between the means of the various criteria between the two
groups was non significant, thereby indicating that the two groups were well matched priorto the hematinic supplementation trial.
One subject from each pair was randomly assigned to either the iron treated (60 mg elemental Fe/day) or the placebo ( sugar tablets) group. The experimental design of the study was such that data was collected every four months ie. baseline (0 month), at the initiation of the study; mid evaluation (4th month), at the end of the lirst school term; final evaluat- ion (8th month), at the end of the second school term; and post final evaluation (12th month), following a withdrawal of supplements.
Dosing procedure
Distribution of the tablets was done from the commencement
1120 P. KASHYAP and T. GOPALDAS
of each school term of roughly 4 months duration, at the level of one tablet/day for 60 days at a stretch, for one full school year.
Estimation of Hemoglobin (Hb)
Hb data was obtained using the filter paper technique (7) of the cyanmethemoglobin method (8) at all four points of time.
Cognitive Function (CF) tests
A battery of four tests was selected, which included two tests from the Gujarati adaptation of Weschler's Intelligence Scale for Children (G-WISC)(9). These tests were standardised on a similar population of school girls, before final use on the study population. These tests were carried out individually, in privacy to prevent any consultation between subjects and distraction to the study subjects. The total testing time was approximately half an hour per subject.
Detalis about the tests
i. Clerical Task (CT) test. Each subject was given a printed text in Gujarati and was instructed to encircle all 'matras' ( vowels 'a' and 'o' of Gujarati) in the entire text as quickly as possible over a 5 minutes period. The score was calculated as a ratio of the number of matras encircled to the total number of matras in the text. This was then multiplied by i0, which was the maximum obtainable score. The CT test was used to test attention, concentration and discrimination.
2. Visual Memory (VM) test. Ten items of everyday use were displayed to the subject for a period of one minute. The subject was required to recall as many items as possible in the next one minute, testing the ability to remember non-verbal (visual) material.
3. Digit Span (DS) test. Series of digits gradually increasing in length were presented to the subjects, who were to repeat the series in the correct order, vocally. Different series were presented for the forward and backward recall. The series for the forward recall started from 3 upto 9 digits and for backward recall 2 to 8 digits. The longest group of digits the subject recalled in correct order, determined the memory span for digits.
4. Mazes test. A series of line mazes in the increasing order of difficulty were presented to the subject who was to mark the way out within a stipulated time and within a set number of errors permitted (9) for each Maze. A test intended to measure foresight~ ~lanning capacity (perception) and visual motor coordination.
The scoring for DS and Mazes tests were as per the WISC manual (9)9 but for simplicity of final scoring, a ratio of the
* Tests selected were in consultation with Dr. S. Anandlakshmi, a noted Child Psychologist, and presently Director~ Lady Irwin College, New Delhi, India.
HEMATINICS AND COGNITIVE FUNCTION 1121
score obtained, to the maximum score, was obtained. This was then multiplied by i0, which now became the maximum obtainable score ( just the way percentage is calculated).
Statistical Analysis
Means and standard errors were calculated for both groups for all parameters. The independent 't' test was used to compare the hematinic treated and placebo groups at each evaluation. The paired 't' test was used to study the changes over time in each group.
RESULTS
Impact of hematinic supplementation over one year on Hb and CF test scores is presented in Table 2, and the same type of data is presented for the placebo group in Table 3.
TABLE 2
Impact of hematinic supplementation (60 mg/day for 60 days) twice in a school year on Cognitive Function test scores in underprivileged school
*** *** NS 1.04~S *** *** B Vs M 12.25.** 4.88*** 1.96.** 6.45*** 7.51.** B Vs F 16.95.. 6.74*** 5.38*** 2.43, 13.18.** 12.08.** B Vs PF 3.96*** 8.13,** 4.80*** 2.04. 9.54*** 10.84.** M Vs F 7.78*** 4.92*** 4.79** 2.37NS 7.66** 10.42.** M Vs PF -8.65*** 6.32~ 3.56~ ~ 1.48~8 3.51.** 7.57*** F Vs PF -15.32 0.4 S -1.29 ~ -1.19 5.92 -3.60
NS - Non significant difference between the means of the two groups. Difference between the means of the two groups significant at p < 0.05 Difference between the means of the two groups significa~it at p 4 0.01 Difference bet~en the means of the two groups significant at p40.001
Results indicated significant increase (p<0.001) in the initial Hb values from 10.28 g/dl to 11.61 g/dl at 4th month and 12.33 g/dl at the 8th month evaluation of the hematinic supplementation ( Table 2). In the 4th month after withdrawal of hematinic supplements ie. 12th month evaluation, the Hb values dropped significantly, approaching the baseline values. However, the Hb values of the placebo group (Table 3) indicated only marginal changes throughout the same intervention period.
1122 P. KASHYAP and T. GOPALDAS
TABLE 3
Impact of placebo on Cognitive Function test scores over one year period, in underprivileged school girls, 8-15 years of age.
Values are mean _+ SE. NS - Difference between means non significant. * - Difference between means significant at p ~ 0.05. ** - Difference between ~ans significant at p < 0.01. *** - Difference between means significant at p < 0.001.
Changes in the CF test scores in the hematinic supplemen- ted group ( Table 2) indicated a significant (p < 0.001) improvement from baseline in the CT test ( 4.0 to 4.65 to 5.83), Mazes test (4.36 to 5.72 to 7.54) and Total Score (20.11 to 22.60 to 26.54) at 4th month, which increased further at 8th month evaluation �9 The enhancement in DS and VM were significant only at 8th month evaluation.
On withdrawal of the hematinic compound (12th month evalu- ation), a significant (p < 0.001) drop in the Mazes and Total Score were observed.
A similar analysis for the placebo group ( Table 3), indicated significant improvement in CT, VM, Mazes and Total Score at the 4th and 8th month evaluations. Increments in the placebo group could be attributed to their familiarisation with the task on subsequent testing, which could also be expected in the Fe treated group. This made a comparison between the two groups necessary, in order to establish the true effect of hematinic supplementation on CF test scores. This could only be established if the increments in scores in the hematinic supplemented group were substantially and significantly larger than that in the placebo group.
The results of the comparison (Fig.l) indicated no significant difference between the subjects of the hematinic treated and placebo group at 0 month or at 4th month evaluation.
HEMATINICS AND COGNITIVE FUNCTION 1123
However, at the 8th month evaluation significantly higher scores than placebo group were observed in the hematinic treated group for CT (5.83 vs 4.93), DS (4.75 vs 4.33), Mazes (7.53 vs 6.20) and Total Score (26.54 vs 23.78). At the 12th month evaluation, no difference between the two groups was observed except for Mazes(p~ 0.05) which continued to remain higher in the hematinic treated group. The inference, therefore, was that the prophylac- tic hematinic dosing at 60 mg elemental Fe/day for 60 days at a stretch, twice in a school year was effective in improving attention, concentration, discrimination (CT test), memory (DS test) and visual motor coordination (Mazes test) in a free living population group of subjects. However, the benefit of hematinic supplementation was sustained for all CF tests except the Mazes test at the 12th month evaluation, following a withdrawal of of therapy for four months.
F I G . 1 CHANGES IN CF TEST SCORES IN THE Fe
TREATED Vs PLACEBO GROUP AT O,4TH, 8TH ~,ND 12TH MONTH OF THE STUDY
% 28}- BASELINE (0 MONTH)
'~ 24 m
22 ~
20
18
12
10 mo~ 8 r---~
q"-:mq ~:. 4 2
CTIDSIVMI M ITS
MID (4TH MONTH)
ICTIDStVM! M ITS1
FINAL ~o ~5TH MONTH/ j I ICTIDSIVMI MITS
POST FINAL(12TH MONTH)
i
c6Ca~c ~ , ~
I CTIDSIVMIM ITSI ~jFe TREATED CT--CLERICALTASK VM--VISUAL MEMORY TS--TOTALSCORE
GROUP [-]PLACEBO DS--DIGIT SPAN M-MAZES
GROUP
The inference of this study appears to be that there is a beneficial effect of a twice-a-year hematinic supplementa- tion at the level used on CF test scores of the underprivileged 8-15 year old school girls. Further, this effect was sustained, till about 4 months after withdrawal of inputs in most of the CF tests.
DISCUSSION
The effect of iron on affective derangements has been studied and the results have been extremely variable ranging from a dramatic improvement (i0), to the entire lack of one (11,12).
The behavioral abnormalities in the iron deficient
1124 P. KASHYAP and T. GOPALDAS
children have been related to changes in the concentration of chemical mediators in the brain. An enzyme apparently sensitive to the state of body iron stores is the mitochondrial mono amine oxidase (MAC). Behavioral abberations commonly attributed to Fe deficiency may be caused by impaired MAC function and associated excesses of the Central Nervous System (CNS) catechols and ~concomitant rise in the urinary nor epine- phrine concentration which is thought to influence behavior in man (13,14,15).
Most studies on the beneficial effects of hematinic supplementation on CF have been conducted on unfants and preschoolers (1). Infants appear to be more alert and responsive and display improved gross and fine motor coordinations on treatment with iron and similar findings have been reported in preschoolers. Harris and Kellermeyer (16) reported resolution of symptoms such as lassitude, decreased attention span and irritability on iron therapy, substantially before any significant improvement in the hemoglobin concentration was observed. However, the results of the present study were contradictory to this observation, wherein a delayed response to hematinic therapy in CF was observed and the response was sustained even after a drop in hemoglobin values.
The only study to our knowledge on the effects of hematinic dosing on CF scores in the school children has been conducted by Gopaldas et al (2). The effect of hematinic supplementation at 40 mg and 30 mg Fe/day as FeSO 4 for 60 days at a stretch on selected tests of CF was compared to the placebo group receiving a sugar tablet for the same period, after 4 months, in underprivileged school boys (8-15 yrs) matching the three groups initially for age, Hb levels, individual and overall CF test scores. The battery of tests used was the same as that used in the present study. Results indicated a greater benefit of the 40 mg Fe dose in all tests of CF studied.
However, the results of the present study indicated that an oral dose of 60 mg elemental iron/day as FeSO 4 for 60 consecutive days alone could not improve the CF test scores in the hematinic treated group of girl subjects (8-15 yrs) to a level greater than that observed in the placebo group. It may be noted that in the present study, in the hematinic treated group the mean Hb value at 4 months was 11.62 g/dl as against 12.11 g/dl in the earlier study (2). On continued therapy for another 60 days, the mean Hb value was 12.33 g/dl (ie. at the 8th month evaluation). At this stage, a significant improvement in test score for attention, discrimi- nation, memory, perception and visual mtor coordination was observed in the hematinic group as against the placebo group.
Youdim et al (17) studied the effect of oral iron (200mg FeSO4, thrice a day for 38 days) treatment on hematolo- gical responseand platelet MAC activity in a group of 7 iron deficient adult patients (5 females and 2 males). Four days after cessation of therapy the serum iron concentration did not
return to normal and the platelet activity remained low. This could also, perhaps, explain the delay in response in CF
HEMATINICS AND COGNITIVE FUNCTION 1125
scores of the hematinic group in the present study. As already indicated the mean Hb value at 4th month evaluation was lower than the WHO norm (18) of 12 g/dl, which had been crossed at the 8th month evaluation, indicating that the continued therapy further improved the hematological status of the study population.
The CF scores of anemic subjects are reportedly(l) lower than those of the non anemics in tests for attention, memory, perception and visual motor coordination. It was for this reason that we considered appropriate, to select those tests that would measure these specific functions.
To sum up, the findings of this study have shown that a prophylactic supplementation of 60 mg elemental iron for 60 days at a stretch, twice in a school year can bring about a benefit in attention, memory and concentration. This in turn could be expected to improve the scholastic performance of these subjects in the schools. Further, the demonstration of a concrete benefit such as improved scholastic performance may help to convince the planners and policy makers to implement large scale nutrition anemia prophylaxis programs for school children of the low socio economic segments.
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1126 P. KASHYAP and T. GOPALDAS
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