Community and International Nutrition

Daily Iron Supplementation Is More Effective than Twice Weekly Iron Supplementation in Pregnant Women in Pakistan in a Randomized Double-Blind Clinical Trial1
Zubia Mumtaz,2 Saqib Shahab, Naila Butt, M. Abdur Rab and Aime DeMuynck
Health Services Academy, West Blue Area, Islamabad, Pakistan.
ABSTRACT In the context of limited effectiveness of iron supplementation programs, intermittent iron supplementation is currently under debate as a possible alternative strategy that may enhance the effectiveness of operational programs. This field-based trial assessed the outcome of twice weekly iron supplementation compared to daily in Pakistan. A double-blind, randomized, clinical trial was conducted in Northern Pakistan. Anemic pregnant women (n 191) were assigned to receive daily (200 mg ferrous sulfate) or twice weekly (2 200 mg ferrous sulfate) iron supplementation. Hemoglobin was measured at baseline and at 4-wk intervals for up to 12 wk. Serum ferritin was measured at baseline and 8 or 12 wk. Analysis was by intention to treat. The two groups did not differ in age, parity, sociodemographic characteristics, hemoglobin or serum ferritin concentrations at baseline. Women who received iron daily had a greater rise in hemoglobin compared with women who received iron twice weekly (17.8 1.8 vs. 3.8 1.2 g/L, P 0.001). The serum ferritin concentrations increased by 17.7 3.9 g/L (P 0.001) in the daily supplemented group and did not change in the twice weekly group. Daily iron supplementation remained superior to twice weekly supplementation after controlling initial hemoglobin Z-scores and duration of treatment. The body mass index (BMI) modified the effect of daily versus twice weekly iron supplementation. For every unit increase in BMI, the difference between the two treatment groups was reduced by 0.0014 (final hemoglobin Z-score; P 0.027). We recommend continuation of daily iron supplementation as opposed to intermittent iron supplementation in pregnant women in developing countries. J. Nutr. 130: 2697–2702, 2000. KEY WORDS:

Downloaded from jn.nutrition.org by guest on November 28, 2010

anemia

iron supplementation

pregnant women

intervention trial

Pakistan

Iron deficiency anemia is still a major nutritional and public health problem in developing countries including Pakistan (UNICEF 1994). Pregnant women and preschool children are most commonly affected (Galloway and MCGuire 1994). It is estimated that 50% of pregnant women in developing countries and up to 80% in South Asia have iron deficiency anemia (WHO 1998). The consequences of maternal anemia may be serious, with reported associations ranging from preeclampsia to low birth weight and increased risk of maternal deaths (Quillan et al. 1983, Sapre and Joshi 1996, Spinillo et al. 1994). The maternal and child health services of Pakistan distribute oral therapeutic iron supplements through the existing primary health care system. The aim of this program is to reduce the prevalence of anemia in this vulnerable group of women. The effectiveness of this intervention is often poor. Factors include low utilization of services (Pakistan Medical Research Council 1998), lack of compliance (Galloway and MCGuire 1994, Schultink et al. 1993, Simmons and Cook 1993) and varying bioavailability of iron in the iron prepara-

1 The Pakistan Medical Research Council funded this study (Project No. P/61). 2 To whom correspondence should be addressed: Center for Population Studies, London School of Hygiene and Tropical Medicine, 49-51 Bedford Square, London WCIB 3DP.

tions dispensed (Dawson et al. 1998). In the context of ineffective iron supplementation programs, intermittent iron supplementation appeared as a possible alternate strategy. There is concern that compliance is reduced by the undesirable side effects of the iron supplements. These side effects are related to the dosage and formulation of the therapy (Rani et al. 1995). These concerns have led to studies looking at intermittent versus daily iron dosing in an attempt to identify the optimum therapeutic protocol. A study in rats demonstrated that iron supplementation timed to match mucosal renewal is more efficient (Viteri et al. 1995). Iron absorption is suppressed for at least 24 h after consumption of a high iron meal or iron supplement, principally by controlled suppression of intestinal mucosal cell uptake (Fairweather-Tait et al. 1985 and 1986, O’Neill-Cutting and Crosby 1987, Solomans et al. 1983). It has been suggested that less frequent supplementation may reduce the transient iron overload and may be as beneficial to the subject as routine daily supplementation (Liu et al. 1995). This might also reduce the unpleasant side effects such as nausea and epigastric pain by reducing the iron content in the gut on a day-to-day basis. It has been demonstrated in anemic rats that iron supplements every 3rd d had a similar effect as in those receiving a daily supplement (Wright and Southon 1990). This phenomenon also was true in preschool children in whom the treat-

0022-3166/00 $3.00 © 2000 American Society for Nutritional Sciences. Manuscript received 14 December 1999. Initial review completed 10 April 2000. Revision accepted 21 July 2000.. 2697

Long Grove. Capsules containing 200 mg of ferrous sulfate (60 mg elemental iron) and 1 mg of folic acid had been especially manufactured and packed in blister packs (Hakimsons Chemical Industries. The randomization code was opened only after the follow-up for all patients had been completed. 2010 . an ultrasound confirmation was done. This variable thus served as a proxy indicator of compliance with the study protocol and in turn with drug ingestion. subject by subject. 191 of whom were eligible and enrolled in the study.2698 MUMTAZ ET AL. The former is a tertiary care hospital in the capital. the debate on the relative merits of daily versus intermittent iron supplementation revolves around the balance between the less-than-optimum benefit of intermittent iron supplementation and the efficiency of a large-scale program through the primary health care system. Germany). After a 20 –22 wk gestation. In case of a discrepancy. Gestational age was determined by the date of the last menstruation and fundal height. A complex variable reflecting socioeconomic status. to a Z-score relative to an external reference curve adjusted for gestational age (Beaton and MCCabe 1999). number of rooms and ownership of transport. North Bend. Data included age. Ministry of Health. the fundal height in centimeters ( 2 cm) was taken as equal to the number of weeks of gestation. Assuming a dropout rate of 20%. number of days for which drugs were dispensed and the total dosage of iron given. The women were randomly distributed into two groups. Blood samples from every 20th woman were distributed in two microvials and analyzed in the same batch. Between March and November 1998. Ridwan et al. 1994. 3rd and 4th visits. Complete blood count was done using a Sysmex SF 3000 autoanalyzer (Sysmex Corporation of America. duration of follow-up in weeks. approved the study protocol.nutrition. but the methods can be applied to situations in which the outcome is positive such as cure (Collett 1994). power 90%). controlling for the time from the start of treatment to the time to attain a hemoglobin concentration of 110 g/L. Webb City. A predesigned. Taxila. Venous blood samples were taken for complete blood count at each visit and for serum ferritin at the 1st. whereas the latter is a mission hospital serving a peri-urban and rural population. survival analysis was developed to measure survival time. Women who were late for their follow-up visit were paid a home visit. Blood for serum ferritin was drawn at the 3rd visit in case the women delivered before their final visit. Each woman was given a 4-wk treatment pack and health education regarding the importance of diet in pregnancy. with a reference range of 8 –140 g/L (women aged 20 –25 y). with a possible range of 0 – 42. with each component variable assigned a weight (Patil 1995). Pakistan). no history of previous cesarean section. 191 pregnant women were selected from the maternity wing of the Federal Government Services Hospital. we planned to recruit 200 women. and the Maternal & Child Health Clinic of the Christian Mission Hospital. of varying quality. A scoring system was developed. education levels of the women and their husbands. adjusting for covariates such as initial hemoglobin Z-score. Socioeconomic status was measured as a complex variable consisting of component variables that included education of the subject. The purpose of the study was explained and informed consent was obtained. Currently. and each subject was assigned a unique identifier. The appearance of the capsules and the blister packs of the two groups was identical. The serum ferritin assay was validated using the ES 300 testing procedure according to the manufacturer’s instructions. The subjects and the investigator were blinded to the allocation of treatment group (daily versus twice weekly) at initial recruitment and the three follow-up visits. was developed by the addition of all component values. Originally. and underutilized (Pakistan Medical Research Council 1998). A peripheral film was made to rule out congenital disorders such as thalassemia minor. and often the patients were keen to show the used blister packs. type of construction of the house. one receiving daily. Our study was designed to test whether twice-weekly iron supplements would be as effective as daily iron supplements in treating anemia in pregnant women in the Pakistani primary health care system. socioeconomic status. pretested questionnaire was filled out at the initial visit. body mass index (BMI). WHO and UNICEF are considering the option of intermittent iron supplementation as a therapeutic protocol that may enhance the effectiveness of large-scale direct supplementation programs (Stoltzfus and Dreyfuss 1998). parity of not 5 and a fixed address at which the subject could be followed up at home. MATERIALS AND METHODS A randomized. Roche Diagnostics GmbH. Women were weighed on a digital scale accurate to 100 g (Measurement Concepts. The ethics committee of the Health Services Academy. particularly in developing countries like Pakistan where women are poorly nourished and eat a high phytate diet and where antenatal and obstetric services are mal-distributed. with an initial hemoglobin of 110 g/L. The International Nutritional Anemia Consultative Group. Studies in pregnant and nonpregnant women suggested that supplementation on a weekly basis was as effective as daily supplementation in improving the iron status of those with moderate anemia (Gross et al. which contained ferrous sulfate and folic acid for all 7 d. Randomization was performed using a random number generator. Sample size estimations indicated that 164 women were required to be able to distinguish a difference between groups in hemoglobin of 5 g/L (5% significance level. The final hemoglobin Z-score was taken as the outcome measure. MO). The CDC reference hemoglobin values (developed from reported mean concentrations in iron supplemented healthy pregnant women in Europe) were used as the standard (data courtesy of Ray Yip cited in Beaton 1999). A validation protocol was followed to confirm the validity and reliability of the laboratory measurements. double-blind. time since previous pregnancy. IL). Islamabad. The selection criteria were as follows: between the age of 17–35 y. monthly income. total parity. 1996). This stringent criterion was to ensure that women with high-risk pregnancies would not be enrolled. We argue that this could result in underdosing of unidentified vulnerable iron-deficient and anemic subgroups. Kaplan-Meier analysis was performed to determine whether there was a significant difference in the probability of improvement relative to time in the two groups. their occupations. Karachi. Height was measured to the nearest centimeter using a height rod (Cardinal. One set contained two capsules of 200-mg ferrous sulfate for days 1 and 4 and placebo for the rest of the days. family size and past obstetric history. One mg of folic acid was present in all the capsules. with death as the outcome.org by guest on November 28. The lower limit of measuring the concentration of ferritin range was set at 10 g/L. To address the complex issue of physiological anemia of pregnancy (which produces a U-shaped distribution of mean hemoglobin with gestational age) and changes in the magnitude of iron demand related to gestational age. The number of days for which the drugs were dispensed was recorded once a woman returned for her next batch of drugs. education of husband. Serum ferritin was determined using a commercial kit (Enzymun-Test Ferritin. and the other twice-weekly iron supplementation. ment effect of the two dosage schedules was the same after controlling for initial hemoglobin (Schultink and Gross 1995). The other set consisted of identical-appearing strips. Mannheim. The fundal height was taken with a tape measure from the top of the pubic bone to the fundus of the uterus. placebo-controlled trial was conducted. A multiple linear regression model was fitted to assess the effect of the two treatment types. hemoglobin Z-scores were calculated. Downloaded from jn. An attempt was made to verbally verify compliance. an uneventful obstetrical history with no history of placenta previa or abruptio placenta. Two hundred forty-one women were screened. The objective of this exercise is to explore difference in treatment effect. household income. WA). Two-way interaction terms of treatment and significant covariates were generated. This was done by converting the observed hemoglobin values. The results were analyzed according to the intention to treat principle. Log-rank test was done to assess the equality of success across the two groups (STATA. thinking that this would ensure dispensation of another packet.

03).001).9 (0–5) 19.89 0.0 12. Women with a lower BMI had a significantly greater increase in final hemoglobin Z-score in the daily group than in the twice-weekly group. there was no difference between the women who dropped out in the two treatment groups (41 versus 45). The remaining 30% did not complete the entire 12 wk of planned follow-up due to a variety of reasons including delivery at home.55 0. parity and duration of pregnancy (Table 2). In pregnant anemic women daily iron therapy caused a significantly greater rise in hemoglobin and serum ferritin than twice-weekly therapy (P 0. the comparative increase in the twice-weekly group was 3.7 (1–103) 56. g/L Initial ferritin.38 0.6 (2–30) 21.001). 2 P-values are calculated using Student’s t test. Similarly. The model predicted that at a BMI of approximately 30 kg/m2. initial hemoglobin. whereas in the twiceweekly group it did not change (P 0. Only differences at 0.2 1. Thus.9 1.0.05 are reported. there would be no significant difference between the two treatment protocols.076).0037). the difference between the two treatment groups narrowed.3 (1–66) 56. kg/m2 Initial hemoglobin. 160 were successfully followed for at least 4 wk and supplemented for an average of 10. Of these.6 (10–30) 10. the serum ferritin concentrations in the daily group increased by 17. Fifteen percent of the women recruited did not return for even one visit and were excluded from the analysis. m Initial hemoglobin. Similarly.1 P 0.0014 (final hemoglobin Z-score. In the daily group there was a 17. For every unit increase in BMI. mo Body mass index.16). 2010 TABLE 2 Comparison of subjects lost to follow-up with those who completed the trial Population characteristics1 n Age. Fig.DAILY IRON SUPPLEMENT MORE EFFECTIVE IN PREGNANT WOMEN 2699 TABLE 1 Selected characteristics of the women at the beginning of the study1 Population characteristics n Age. to support an average family size of seven).6 24.9 wk of iron supplementation. Texas).3 1. 2 SES scale was a continuous 0 – 42 point scale.1 4. mo Weight.4 1. the difference between the two treatment groups was reduced by 0.01. wk Completed 105 24. As BMI increased. College Station.5 9. then the Kaplan-Meier analysis showed that women in the daily supplementation group attained normal hemoglobin concentrations in a shorter period of time than the women in the twice-weekly group (P 0.4 7. n Duration of follow-up.4 (1–103) 23.nutrition. moving to their parental house towards the end of term.55 0.6 (0–5) 16.9 (10–32) 10. y Women with 5 y of school attendance. n Gestational age at beginning of study.e. % Socioeconomic status (SES)2 Parity Time since last pregnancy. expense involved in attending routine antenatal visits. although some were as late as 2–3 wk for their appointments. If. Women in the daily supplemented group achieved normal hematological status in 44 d on average. Fifty-five percent completed the entire duration of follow-up (i. RESULTS A total of 191 women were prospectively recruited. initial hemoglobin Z-score (P 0.70 0. Fortythree percent had received no formal education. kg Height. STATA. The final multiple linear regression model (Table 4) showed a significant association of final hemoglobin Z-score with daily versus twice-weekly treatment (P 0. BMI (P 0. serum ferritin concentrations of the two groups did not differ (P 0. we take hemoglobin 110 g/L as normal.16 0. Socioeconomic status.7 4. The two groups did not differ in socioeconomic status.9 wk without supervision (Table 1). time since last pregnancy and age were not significantly associated with final hemoglobin Z-score.027)..8 3. and 92% belonged to the low income group (earning less than $130 per month.0 19. y Socioeconomic status score Parity.2 10.4 63 19 6. total parity. although mean hemoglobin concentration of the daily group was marginally lower (Table 3). Most of the husbands were skilled or unskilled workers or office clerical staff. After an average 10.0 51 20 5.9 23.7 (4–18) Twiceweekly dose 76 4.45 Lost 86 24. although 19% had no formal education.0 5.8 g/L (P 0.8 18.4 29.7 3. There was no difference between the women who dropped out compared with those who continued in the trial in terms of age.0 22. g/L Dependants/family. inability of patients and hospital staff to appreciate the importance of regular follow-up.8 (0–5) 20.8 10.00 1 All values are mean (range) or SD. compared with 73 d in the twiceweekly group.07 95.org by guest on November 28. Ninety-five percent of the women were housewives.001).9 7.90). At the start of the study. g/L Dependants/family. n Time since last pregnancy.7 94. wk Duration of iron supplementation.2 12. Their husbands were better educated. This difference in the rise of hemoglobin in the two groups persisted after controlling for significant covariates that include initial hemoglobin Z-score and the duration for which the drugs were dispensed. Similarly. both hemoglobin and serum ferritin increased significantly more in the daily group than in the twice-weekly group.34 0.5 (2–22) 7.2 7. DISCUSSION Intermittent iron dosing to conform to the cycle of intestinal mucosa turnover has been suggested as a method to Downloaded from jn.5 33.44 0.001). there was a significant improvement in the hemoglobin con- centrations in both groups.90 0. four follow-up visits).7 94.5 1. P 0. .8 g/L increase in hemoglobin (P 0. using WHO criteria.02) and the number of weeks that the drug was dispensed (P 0. there was no significant difference between initial hemoglobin concentrations of the two groups (P 0. 1).4 1.3 (2–30) 12.2 13.1 3.7 g/L (P 0. version 5.001).2 4. and difficulty of identifying correct addresses for home visits if the patient did not keep an appointment.6 (2–22) 21.7 (0–5) 19.0 (1–72) 23.4 7.0 6. The initial hemoglobin Z-score and the duration of supplementation did not interact significantly with the treatment type (Table 4).2 1. The BMI modified the effect of daily and twice-weekly iron supplementation.05 93. wk Daily dose 84 24.9 (4–16) 1 Values are mean SD or range.

05).83) 0.0014 ( 0. FIGURE 1 Kaplan-Meier estimate of time to attain hemoglobin concentration 11 g/L in pregnant women given daily and twiceweekly iron supplements.019. 0.9 10.2700 MUMTAZ ET AL.65 (0. it appears that the regimens were equally TABLE 4 Multiple regression model comparing the effect of daily vs.4b 12.8 g/L and was of negligible clinical importance. Despite large variations in absolute serum ferritin concentrations. Previous studies have shown no significant difference between daily and twice-weekly regimens in children.10)2 0. Schultink and Gross 1995). wk Treatment BMI Treatment initial hemoglobin Treatment duration of ingestion 1 2 3 4 ineffective (Hallberg 1998).9 SD. Values in parentheses are the 95% confidence intervals. Not significant.002 0. The only study published to date that compares weekly and daily administration of iron to pregnant women included both anemic and nonanemic women (Ridwan et al.001 0.org by guest on November 28. These studies have become the basis of promoting twice-weekly iron therapy (Baynes and Cook 1996). are consistent with a meta-analysis of 21 published and unpublished studies. body mass index. Ridwan et al.8 41.05.2 97. Z-score BMI.6 14.6 g/L 95.002) 0.3* 11. However.8 14.001 0. with higher final hemoglobin concentration associated with daily administration of iron. that there was a significant difference between the two treatment groups. Values are small because the outcome is a Z-score. kg/m2 Duration of ingestion of iron supplements.0015 (0.nutrition. 1995 and 1995.0008 (0. 1996.6 29.3a g/L 33. Our study subjects consisted of poor illiterate anemic women who were self-selected to attend an antenatal clinic. Beaton and MCCabe (1999) found.2a 17.015 ( 0. 0. the final hemoglobin concentrations were lower than any value reported in the many well-controlled studies in developing and developed countries.6 108. a critical review of these five published studies showed that the subjects had low-grade anemia initially and that very small doses of iron were needed for them to reach their optimal hemoglobin concentrations (Hallberg 1998). 0.8 g/L in the daily group was both statistically significant and clinically important.5. 0. Gross et al.8 96.6b 10. The gain of 17.027 NS4 NS Adjusted for gestational age. with an initial hemoglobin of 110 g/L.05 (Student’s t test). These results offer strong evidence that the daily administration of iron has a greater impact on body iron than twice-weekly supplementation. All the women in this motivated self-selected group were anemic. Although this study found the regimens equally effective.0006. 1996). This was especially notable in pregnant women. Liu et al.7 31. upon pooling the data.0 100. 0. P 0. TABLE 3 Hematological values at baseline and follow-up contact points in women supplemented with iron daily or twice weekly1 Daily Hemoglobin Baseline First assessment Second assessment Final assessment Serum Ferritin Baseline Last assessment point 1 Values are mean Twice weekly g/L n 91 76 61 50 n 61 61 23. BMI. although it was true across all groups. Hg.7 113. Although the increase in hemoglobin in the twice-weekly group was significant.03 0. * Significantly different.7* 12. twice-weekly iron supplementation regimens in women with final hemoglobin Z-score1 as the outcome measure Covariates Treatment type Daily therapy Twice-weekly therapy Initial hemoglobin.2 5. 2010 -coefficient P-Value 0. nonpregnant women and women in early pregnancy (Berger et al.002)3 0. The results of our study.6* wk 0 4 8 12 n 100 84 68 55 n 92. improve the efficiency of uptake of therapeutic doses of iron (Solomons 1995).0 27.6 101.0006.0* Hg. hemoglobin. p 0.2a 18. women in the daily supplementation group achieved Downloaded from jn. Significant differences were not seen in all of the studies.3a g/L 0 8 or 12 68 68 23. possibly because of limitations of statistical power. These may be the reasons that no significant differences were observed between the two treatment regimens. in which the daily iron supplemented group had a higher final hemoglobin Z-score than the twice-weekly group.003. it was only 3. . they closely followed the hemoglobin concentrations in the two groups. g/L 3. Equally important.b Values marked “a” are significantly greater than values marked “b” (Student’s t test. The hemoglobin response was clearly superior in those who received iron therapy daily. 1997.5b 11. 1994. a.5 0.0002) 0. P 0.1b 15.7 34.

W. Fairweather-Tait. D. P. Berger. randomized. ACKNOWLEDGMENTS The authors thank the women who participated in this project for their compliance and patience. R. W. others were mostly social or financial reasons. 1988). economical and political facets. Hameed made it possible for us to collect the data.nutrition.. field-based trial that closely resembled real-life conditions in Pakistan. 51: 381–386. Delivery traditionally takes place in the maternal home and some patients moved at the end of term to geographically distant locations. Collett. effort and expense of traveling to the MCH center were perceived to be higher than the potential health benefit of the free pills provided.. J. & Wright. Arrangements had been made for blood to be taken when presented in labor while enrolled in the trial. There may be several reasons for the loss to follow-up. Hallberg 1998). Although the causal pathway of these is fairly well established. Med. (1998) Comparison of oral and intraperitoneal iron supplementation in anaemic rats: a re-evaluation of the mucosal block theory of iron absorption. a high phytate diet (Fox et al. P. Med. an aspect that is not sustainable or cost-effective in large-scale programs. This is important.. A. Further research is recommended to assess the effectiveness and efficiency of the two treatment types in different groups at risk under field conditions. The interaction between BMI and type of treatment protocol underscores the importance of nutrition status. based on the present study and as long as the current situation prevails. Moreover. (1997) Weekly iron supplementation is as effective as 5 day per week iron supplementation in Bolivian school children living at high altitude. frequent and closely spaced pregnancies (Pakistan Fertility and Family Planning Survey 1998). Eur. J. 1998) and concurrent calcium administration (Whiting 1995).. Tablet ingestion was not supervised. Tonglet. House. V. we assume that the groups remained comparable throughout the study. The critical issue of efficiency of iron supplementation programs was not addressed in the present study. predominantly illiterate. at one of the MCH centers. The number of women followed kept decreasing with time. B. FAO (1994) Body mass index. Beaton. (1985) Further studies . It is important to look at the effectiveness of otherwise efficacious regimens in field conditions and not make decisions based on perceived efficiencies alone. Final Report to the Micronutrient Initiative. Until then.Chaudhry and R. Some investigators accept that. Benito. poverty (Mahbub ul Haq 1997) and misconceptions about the nature and extent of the women’s health problems by the policy-makers including professionals and failure to mobilize resources to adequately address the need (De Brouwere et al. Br.000 live births and a life expectancy of 63 y (UNDP 1996). Hematol. A. D. a norm in Pakistan. Clin. intermittent supplementation is more efficient and cost-effective in large-scale programs (Schultink and Gross 1999). A measure of chronic energy deficiency in adults. The results of this analysis should therefore more closely match the actual impact of an iron supplementation program in poor. V. many women chose to deliver at either their own or their parents’ home. D. G. but we were not always successful in contacting the patient. thus ending effective follow-up. (1998) Iron in prenatal multivitamin/multimineral supplements. J. Some patients were fictitiously registered under the name and address of a government employee. M. C. The patients often would not come on the exact day and date specified. Women with a low BMI had a significantly greater increase in final hemoglobin when taking an iron supplementation pill daily than those supplemented twice weekly. E. large parts of the Asian populations have low BMI (1994). Lall. although daily supplementation may be more efficacious. Rome: FAO. the staff of the Christian Mission Hospital. J. J. We are grateful to Shifa International Hospital Laboratory for their contribution in ensuring quality control of all laboratory measurements and accepting blood samples at all hours of the day or night.. 43: 133–140. & Lerberghe. indicating that they had difficulty adhering to the treatment protocol.. & San Miguel.A. J. Chapman & Hall. Dawson. and according to FAO. Opin. S. Lall. Islamabad.DAILY IRON SUPPLEMENT MORE EFFECTIVE IN PREGNANT WOMEN 2701 hemoglobin concentrations 110 mg/L in a shorter time than women in the twice-weekly group. our position is that the current policy of daily iron supplementation in pregnancy should continue and that efforts be made to find other ways to improve the effectiveness of iron supplementation programs. Curr. V. thus including patients who dropped out after the 1st or 2nd visit and did not complete the full 12 wk. GHB Consulting.5 kg/m2. 2010 LITERATURE CITED Baynes. and the Maternity Wing of the Federal Government Services Hospital. The poorest group. Nutr. Because randomization was successful. had unreliable addresses. & MCGanity. E. because time is a limiting factor in our attempts to normalize the hematological status of pregnant women. W. there is a complex set of distal determinants. G.. An inadequate diet is still the most common reason for the high prevalence of anemia in women in Pakistan (Karim et al.. 79: 533–540. E. low rate of iron supplementation before and during pregnancy (Tinker and Koblinsky 1993). This study was a double-blind. Traissac. Behrens. Pregnant women are routinely anemic due to iron deficiency in developing countries such as Pakistan (National Nutrition Survey 1987). 1998). R. Intern. D. high-risk populations to gain some physiological advantage in iron absorption might be premature. & MCCabe. including a low status of women leading to low self-esteem and a lack of empowerment in decision making regarding their health and reproductive choice (Sattar and Kazi 1997). 3: 145–149. Reprod. Their actual impact on women’s health is low. Swindell. J. Nutr. There is an extensive network of basic health units and community health workers in Pakistan with the purported aim of providing primary health care. (1998) Strategies for reducing maternal mortality in developing countries: what can we learn from the history of the industrialized West? Trop. The analysis of the results was done on the intention-totreat basis. Food and Nutrition paper 56. which included displaced Afghan refugee women. worm infestations. J. Taxila. and because there was no difference in the characteristics of dropouts in the two groups. (1999) Efficacy of intermittent iron supplementation in the control of iron deficiency anemia in developing countries: an analysis of experience. London. Siddiqui for his constant guidance at all stages of the project.20 that was not waived for the study. Downloaded from jn.. To suggest an across-the-board change in treatment protocol to reduce possible side effects in poorly nourished. which has an impact on women’s health. L. R. there was a nominal user fee of $0. (1994) Modelling survival data in medical research. T. Only one patient mentioned side effects of the tablets as the reason for dropping out of the study. & Miller. W. although some samples were obtained. DeVora. as can be gauged by statistics such as a maternal mortality rate of 340/100. The existence of mucosal block with the administration of oral iron supplements has been challenged (Benito et al. The mean BMI of our study sample was 23. Lujan. Tellez. One MCH center attended government employees free of cost. Opportunity costs of taking the time. Health 13: 771–782. Iron supplementation works in a complex multidimensional context that includes sociocultural. A home visit was then made. anemic pregnant women with a reasonable access to free or subsidized antenatal services.. The proximate determinants include poor nutrition (Pakistan Integrated Household Survey 1991). J. Aguayo. for their cooperation. M. Toronto. A special thanks to S. Dawson. 1998. & Cook.J. De Brouwere. J. (1996) Current issues in iron deficiency.org by guest on November 28.

H. Matulessi. J. N. Clin. Mahbub ul Haq. Federal Bureau of Statistics. World Health Organization. N. & Juliawati. Pakistan. & MCGuire. R. (1993) Making motherhood safe.. J. Am. Singh. X. H. A. Obstet. Government of Pakistan. O’ Neill-Cutting. Viteri. 38: 293–297. 38: 271–272. J. 125: 82–91. R. Microbiol. Pakistan. S. J.nutrition. Nutr. (1998) Pakistan fertility and family planning survey. J. side effects. (1987) Nutritional Division. A. Pathol. J.. R. D. J. Schultink. Dillon. Pandey. Pineda. Wel. Clin. & Bagati. & Cook. Z. R. Rani. (1998) The World Health Report 1997: conquering suffering. Sci. Capuzzo. W. L.. Am. Nutr. 52. W. Das. & Gross. Br. E. Liu. M. S. J. 86: 185–191. & Gross.. T. Van Der Ree.. (1997) Human Development Report in South Asia. Indian J. Dev. Thailand. 52: 135–139. 2: 7–11. (1991) Pakistan integrated household survey. (1995) Annual Report 1994. 2010 . J. Bull. Pakistan. L. & Joshi. A. Islamabad. Schultink. S. Am. Schultink. (1990) The effectiveness of various iron-supplementation regimens in improving the Fe status of anemic rats. & Southon.. Pakistan. & Gross. J. S. H. W. & Iasci. & Passmore. Wright. & Minski. Solomons. (1983) An epidemiological investigation of pre-eclampsia and elevated blood pressure among Kampuchean refugee women at Sakaeo Holding Center. Fox. on rats on the influence of previous intake on the estimation of bio-availability of Fe.. or psychology? Soc. Med. Nutr. Piazzi. (1995) Effect of daily vs. F. J. (1986) Studies on iron-availability in man using stable isotope techniques. W. 24: 259 –268. H.. Gross. P. Clin. p. Karachi.org by guest on November 28. 63: 579 —585. S.. enriching humanity. Nicola. A.-N. V. (1996) 3 E’s for safe motherhood. 68: 213–217. V. 58: 622– 626. J. (1999) Use of daily compared with weekly iron supplementation: apples and pears. 67: 664 – 668. W.. Downloaded from jn. A. X.C. J.. Kwong. 53: 326 –327. & Viteri. Nutr. Primary Health Care Cell. (1998) Bioavailability of iron glycine as a fortificant in infant foods. (1998) National Health Survey of Pakistan: Health Profile of the People of Pakistan. E. (1994) Treatment of anemia with weekly iron supplementation. Khurshid. (1995) Weekly versus daily oral iron administration: are we asking the right questions? Nutr. Nutr. Islamabad. (1993) Evaluation of a gastric delivery system for iron supplementation in pregnancy. Tolomei. W. Indonesia. K. F. J. WHO. Clin. Nutr. J. M. (1995) The inhibitory effect of dietary calcium on iron bioavailability: a cause for concern? Nutr. J. Geneva. R. A. & Fairweather-Tait. J. Schultink. W. Government of Pakistan. Sapre.. D. (1998) Guidelines for the use of iron supplements to prevent and treat iron deficiency anemia. & Martin.2702 MUMTAZ ET AL. Demo. Clin. Pakistan Medical Research Council. Y. United Nations Children’s Fund. (1997) Human Development Report 1996. Islamabad. A. (1998) Combating iron deficiency: daily administration of iron is far superior to weekly administration. Government of Pakistan. Solomons. & Crosby. Am. (1997) Women’s autonomy. H. World Bank Discussion Papers 202. R.. (1988) Anaemia in pregnancy: occurrence in two economically different clinic populations of Karachi. L. Ridwan. & Song. twice weekly iron supplementation in Indonesian pre-school children with low iron status. Ind. (1994) Maternal high-risk factors and severity of growth deficit in small for gestational age infants. Fairweather-Tait.. (1994) Determinants of compliance with iron supplementation: supplies. Liu. Yang. Shruti Talib. 113: 337–349. J. (1995) Measurement of household socio-economic status. E. livelihood and fertility. J. Lancet 344: 821. & Sandstead. Nutr. Tinker. G. Karim. Pakistan. Switzerland. J. Zhao. 155. Islamabad. S. Simmons. Trop. E. Br. Intern. P. Eagles. Early Hum. M. J. K. Whiting. 147: 489 – 491. National Institute of Population Sciences and the London School of Hygiene and Tropical Medicine. Ministry of Population Welfare. Am. S. Br. Nutr. 39: 381–390. Colonna. Nutr. Stoltzfus.. United Nations Development Program. J. p. Spinillo. A. Kang. & Gross. W. Chung Hua Yu Fang Hsueh Tsa Chih 29: 34 –37. Rev. A. Pakistan. 61: 111–115. N. UNICEF.. Quillan. Washington. Patil. JPMA. Nutr. & Dreyfuss. 55: 279 –285. Oxford University Press. Viteri. National Institute of Health. Federal Ministry of Health. 16: 139 –146. Schultink. J. 38: 35– 43. W. & Kazi... New York. V. Arch. Nutr. The World Bank. Pakistan. M. & Rizvi. (1987) Blocking of iron absorption by a preliminary oral dose of iron. M. Hyg. (1995) True absorption and retention of supplemental iron is more efficient when iron is administered every three days rather than daily to iron-normal and iron-deficient rats. Oxford University Press. F. (1996) Second quarterly HMIS Feedback Reports of the Health Management Information System of Pakistan. (1983) Studies on the bio-availability of zinc in human: mechanism of the intestinal interaction on non-heme Fe and Zinc. Nutr. International Nutritional Anemia Consultative Group. J. (1995) Intermittent iron supplementation in Chinese pre-school children is efficient and safe. New York. Fam.. Rev. Med. R. & Koblinsky. Clin. Hallberg. 69: 739 –742. R. Med. O. R. X. W. 63: 884 – 890. S. 51: 185–191.. P. 53: 77– 80. Liu. (1995) Pregnancy associated anemia and iron: a pilot study. M. J. Gyn. D. Pakistan Institute of Development Economics. Islamabad. Government of Pakistan.C.. J. (1995) Evaluation of the effects of intermittent iron supplements on iron-deficiency anemia in children. B. National Nutrition Survey. Sattar.. Islamabad. Food Nutr. Clin. Am. (1993) Low compliance with an iron-supplementation program: a study among pregnant women in Jakarta. L. (1996) Effects of weekly iron supplementation on pregnant Indonesian women are similar to those of daily supplementation.. Am. Washington. Galloway.

Sign up to vote on this title
UsefulNot useful