Indian Pediatrics 2003; 40:296-301 

Anemia Prophylaxis in Adolescent School Girls by Weekly or Daily
Iron-Folate  Supplementation

 

K.N. Agarwal, S. Gomber, H. Bisht, M. Som

From the Department of Pediatrics, University College of Medical Sciences and GTB Hospital, Delhi 110 095, India.

Correspondence to: Prof. K.N. Agarwal, President, Health Care & Research Association for Adolescents, D-115/Sector 36, Noida 201 301, UP, India.
E-Mail: adolcare@hotmail.com

Manuscript received: December 4, 2001, Initial review completed: December 28, 2001,
Revision accepted: January 7, 2003.

Objective: To examine the benefits of anemia prophylaxis in adolescent school.girls by weekly or daily iron-folate supplementation. Design: Prospective study. Setting: Government girl schools of northeast Delhi. Subjects: 2088 subjects (with hemoglobin >7.9 g/dL), including 702 on daily and 695 on weekly iron-folate administration; 691 girls served as controls. Results: About 85% girls were iron deficient out of which 49.3% were anemic. Weekly administration took longer time to raise hemoglobin but was effective as well as practical. Plasma ferritin estimation in girls showed rise in level in both the treated groups. Conclusion: Weekly administration of iron-folate was a practical and effective strategy for anemia prophylaxis in adolescent school girls.

Key words: Adolescence, Ferritin, Iron deficiency anemia.

RECENT data from the District Nutrition Project (Indian Council Medical Research) in 16 districts of 11 states, on pre-valence of anemia in non-pregnant adolescent girls (total 4337; 11-18 years of age) showed rates as high as 90.1% with severe anemia (hemoglobin <7.0 g/dL) in 7.1%, suggesting prevalence of moderate-severe anemia during the second spurt of growth(1). Anemia is the late manifestation of deficiency of nutrient(s) needed for hemoglobin synthesis; such states are associated with health consequences(2). There is a general agreement that many adolescent girls in India need iron supplementation, which in turn will improve pre-pregnancy hemoglobin status and iron stores(3). Possibly, it may be easier to build their iron and folate reserves by supplementation/dietary diversification and education through schools. The question remains whether weekly supplementation will meet the need for growth, menstruation and future reproductive process demand or they will need regular daily supplementation. There are observations that weekly iron-supplementation may have similar or better response compared to the daily administration in controlling anemia. If true, weekly administration may be easier, cost effective and practical to administer.

Wright and Southern(4) and Viteri, et al.(5) demonstrated that biweekly/weekly iron administration in rats was equally or more effective than daily dose. This was possibly related to the time of mucosal turnover. Administration of iron with folate or other vitamins in pregnancy(6) and childhood(7) has shown rise in hemoglobin and iron stores. In a study on rural children, 6-72 months old, those Anganwadis receiving weekly/biweekly 20 mg iron showed better rise in hemoglobin than 10 mg daily(8). School teachers and balwadi set up have been successful in control of anemia by iron-folate administration (9,10). Studies in adolescents(11-17) showed that iron alone or in combination with folate and vitamin A and C was able to raise hemoglobin and plasma ferritin status. In the present study the efficacy of weekly and daily supplementation of iron and folate was investigated for control of anemia and building of iron stores among school girls.

Subjects and Methods

The study was carried out during August 1996 to February 1999 in four Government Senior Secondary Schools. All these schools cater to the middle socio-economic group population in North-East Delhi. The total number of girls in the age group 10-17 years in these four schools together was 2210. Girls with hemoglobin <7.0 g/dL (0.3%) were excluded from the analysis.

The expected rise of hemoglobin level by 0.75 g/dL after 100 days of treatment with 100 mg elemental iron and 500 µg of folic acid was considered significant. Taking significance at 95%, power 80% and with 5% dropouts, the calculated number of subjects was 118 for control and experimental groups. As school teachers did not agree to randomization at the individual girl level, the randomization was done at the class section level for the 60 class sections (all class sections taken). The study groups were I control; II daily and III weekly iron-folate tablets administered. Girls with all three measures of hemoglobin in each of the three groups were listed. The upper 118 girls from the selected subjects in each group were taken for the repeated measure MANOVA.

The girls, parents and the school officials (Delhi Government) gave their consent for the study. The study was approved by the Institutional Ethics Committee on a condition that the control group would also receive 100 tablets (one per day) though this may be given after completion of the study.

Group I. Control did not receive any tablets for the first 100 days and hemoglobin was estimated at 115 ± 5 days. They were thereafter given 100 iron folate tablets (iron 100 mg and folate 500 µg) with advice to take 1 tablet daily for 100 days; distributed weekly as in group II.

Group II. (Daily administered group) These girls received one tablet daily for 100 days. Compliance was monitored verbally on weekly visits when 7 tables in a blister pack were distributed. The used blisters were collected, each week.

Group III. (Weekly administered group) These girls were advised to take one tablet, which was distributed weekly in blister pack. They received the weekly tablet until group I completed the study (230 days).

As the control group received 100 tablets after 115 days, the study continued for another 115 days to estimate their hemoglobin. Thus, hemoglobin was estimated, initially, at 115 days and at 230±5 days in all the three study groups.

Seven girls in the daily administered group during the second week of intervention complained of gastric side effects and requested not to continue in the study and were excluded.

Anemia was defined as hemoglobin level <12.0 g/dL(18). Plasma ferittin and C-reactive proteins (CRP) were estimated in every tenth girl of the study groups.

Hemoglobin was estimated by the cyanmethemoglobin method(19). Briefly, 20 µl blood was added to tubes containing 5 ml of Drabkin’s solution (Ranbaxy, New Delhi). The variation in hemoglobin level on 2 consecutive determinations (separate, finger prick sample) on every fifth girl by two laboratory staff was 2.9%. The intra-indivi-dual variation was 1.7%. Plasma ferritin was estimated on samples stored at –20ºC. The ferritin was estimated on 10 µL plasma by an enzyme immunoassay method (Spectro Ferri-tin Kit, Ramco Lab, Houston). The variability on every fifth sample was 3.2 µg/L. C-reactive protein (CRP) was semi-quantitated using Reptiex CRP kit (Behring, USA).

Statistical analysis was done using repeated measures ANOVA and MANOVA, Z-test and Chi-square with SPSS/PC soft-ware. Tukey test was used for pairwise comparisons in order to control the type I error to 5% level.

Sexual maturity rating was done using Tanner’s criteria(20). The time of menarche and regularity of menstrual periods was noted.

Results

No girl in three study groups had hemoglobin level <7.0 g/dL at 115 and 230 days. Initially 0.3, 0.6 and 0.5% girls had hemoblobin level of 7-8 g/dL in-groups I, II and III respectively. After 115 days of intervention the corresponding values were 0.9, 0 and 0.3%. No girl had hemoglobin <8.0 g/dL at 230 days. More than 45% of these girls were anemic (level <12.0 g/dL) at the initial stage in each group. When no supple-mentation was given (control group) the prevalence of anemia increased by 3.2% at 115 days. In the intervention groups at 115 days anemia prevalence declined significantly by 12.5% and 7.7% in daily monitored and weekly monitored respectively. The difference between groups II and III was significant (P <0.001).

The mean hemoglobin prevalence of and plasma ferritin levels in different groups are given in Table I. The mean levels were not significantly different in the various groups at inclusion (P >0.05). Controls (group I) showed non-significant decline in the average hemoglobin level at 115 days, but mean hemoglobin at 230 days was significantly higher than the value at 115 days (P <0.05). Daily treatment (group II) showed the maximum rise (0.5 g/dL) at 115 days (P <0.01). These levels were sustained at the same level at 230 days. Weekly administered (group III) did not show a significant rise (P >0.05) at 115 days, but showed significant change similar to the daily group at 230 days (P <0.05). Girls with hemoglobin ³12 g/dL were also benefited by daily supplementation as 35% of them showed rise in hemoglobin, compared to 26.1% in the weekly supple-mented group at 115 days (Z = 2.62; P <0.05).

TABLE I

Mean±SD for Hemoglobin (Hb) g/dL, Plasma Ferritin  (PF) µg/L and Prevalence 
of Anemia (%)

Groups	Initial     Hb      PF     Anemia			115 days   Hb       Anemia		230 days     Hb        Anemia    PF
Control (n = 691)	11.8±1.3	8.7±4.9	47.1	11.6±1.2 (n = 691)	50.3	12.1±1.3* (n = 579)	35.6	17.2±8.9*
Daily treatment (n = 702)	11.7±1.3	9.4±2.4	48.5	12.3±1.1** (n = 699)	36.0	12.2±1.1** (n = 581)	37.2	16.7±10.5*
Weekly treatment	11.7±1.3	9.2±3.6	52.3	11.8±1.3 (n = 695)	44.6	12.1±1.3*** (n = 695)	38.1	14.2±9.7*

P* <0.01;  P** <0.005;  P*** <0.001.

Considering that the significant effects of iron-folate supplementation observed in this study could be due to larger sample size, repeated measure MANOVA was applied on 118 girls in each group for whom hemoglobin estimations were available at all three points. Data in Table II shows that there was a significant increase in hemoglobin level at 115 days by 0.9 and 0.4 g/dL in daily and weekly intervention groups respectively. However, the controls showed fall in hemo-globin by 0.1 g/dL. At 230 days, the weekly group showed hemoglobin increase by 0.9 g/dL (P <0.05).

Table II

Impact of Daily or Weekly Iron-Folate Administration on Hemoglobin in Adolescent 
School girls (N =118 girls in each group)

Time	Control	Daily Treatment	Weekly Treatment
Initial	11.5±1.33	11.2±1.40*	10.9±1.46+
115 days	11.4±1.21	12.1±0.97	11.3±1.30
230 days	11.9±1.07	11.9±0.67*	11.8±1.03+

+, *P <0.05.

Plasma ferritin levels were significantly increased in girls in all groups at 230 days compared to their initial values (Table I). All plasma samples subjected to ferritin estimation had serum CRP levels <0.8 mg/dL. The rise in hemoglobin was not related to ferritin levels.

Of 1187 girls who had attained menarche, 48.4% had baseline hemoglobin <12.0 g/dL. In 850 pre-menarcheal girls the prevalence was 46.6%. Further, the prevalence of anemia was 47.8%, 46.8%, 45.3%, 52.2% and 42.8% in breast development stages 1-5 respectively. Table III shows that pre-menarcheal girls had higher mean levels of hemoglobin on iron-folate therapy as compared to girls with regular menstrual periods. The hemoglobin rise in daily administered group was significantly (P <0.01) higher in menstruating and pre-menarcheal girls at 115 days as compared to the weekly intervention group.

Table III

Response to Daily/Weekly Iron-Folate Supplementation in Menstruating and
 Pre-menarcheal Adolescent girls (118 girls in each group)

	Menstruating hemoglobin (g/dL)			Premenarcheal hemoglobin (g/dL)
Groups	Initial	115 days	230 days	Initial	115 days	230 days
Control	11.9	11.8	12.0	12.0	11.6	12.0
	±1.2	±1.2	±1.2	±1.3	±1.2	±1.2
Daily treatment	11.8	12.3*	12.0	11.9	12.5*	12.3
	±1.3	±1.2	±1.1	±1.1	±1.0	±1.0
Weekly treatment	11.8	11.6	11.9	11.8	12.2	12.2
	±1.3	±1.4	±1.3	±1.2	±1.3	±1.2

Values represent mean ±SD, * P <0.05.

Discussion

The study conducted in schoolgirls with instructions to take iron-folate tablets was successful. The daily intake for 100 days raised hemoglobin level, which was main-tained until four months after withdrawal of intervention. Daily intake was able to raise hemoglobin even in 35% non-anemic girls. These observations suggest higher prevalence of iron deficiency in 50% with anemia and 35% with normal hemoglobin level(7,21). Inspite of adminis-tration of 100 iron folate tablets, a substantial proportion (30%) of adolescent girls were anemic and possibly required supplementation for a much longer period.

The weekly administration showed delayed response as prevalence of anemia was higher at 115 days compared to the daily group and at 230 days the response was comparable to the daily intervention group. The claimed superiority(4,5) of iron absorption on weekly administration is not supported by the observations of the present study.

Regular weekly administration was effective and seems suitable for populations with mild to moderate anemia. This can also be extended to non-school goers through panchayats/mahila mandals and possibly in the Integrated Child Development Services. Furthermore, anemia prevalence was similar in girls with different stages of sexual maturity. The pre-menarcheal girls main-tained better hemoglobin on iron-folate supplementation as compared to the menstru-ating group, thus suggesting a higher need for hematinics in menstruating girls. To improve iron absorption, enhancers such as vitamin A (in vitamin A deficiency areas) and vitamin B12 may be considered on the basis of prevalent deficiency in community(8,9) and availability of funds. As long-term measures, iron fortified foods and cooking in cast iron utensils may sustain iron stores(22).

Acknowledgement

The authors are indebted to UNICEF, Delhi for financial support. We thank Dr. (Ms) Sheila Vir, UNICEF, Lucknow, for valuable suggestions and Prof. M.M.A. Faridi, Head, Department of Pediatrics for providing the facilities.

Contributors: KNA, SG, HB and MS planned the study, collected data and wrote the manuscript. KNA will be the guarantor of the study.

Funding: UNICEF, New Delhi.

Competing interests: None stated.

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