Will iron supplementation given during menstruation improve iron status better than weekly supplementation? Daily iron supplementation is more efficacious than twice weekly iron supplementation for the treatment of childhood anemia in western Kenya. Efficacy and acceptability of two iron supplementation schedules in adolescent school girls in Lima, Peru. Daily iron supplementation is more effective than twice weekly iron supplementation in pregnant women in Pakistan in a randomized double-blind clinical trial. Intermittent oral iron supplementation during pregnancy. Intermittent administration of iron and sulfadoxine-pyrimethamine to control anaemia in Kenyan children: a randomised controlled trial. The effect of weekly iron and vitamin A supplementation on hemoglobin levels and iron status in adolescent schoolgirls in western Kenya. Weekly vs daily iron and folic acid supplementation in adolescent Nepalese girls. Does iron therapy benefit children with severe malaria-associated anaemia? A clinical trial with 12 weeks supplementation of oral iron in young children from the Turiani Division, Tanzania.
To investigate the efficacy of two different iron supplements administered either on a weekly basis or during menstruation, a 16-week community experimental study was carried out among postmenarcheal female adolescent students in Kupang, East Nusa Tenggara, Indonesia. Forty eight students received a placebo tablet weekly, 48 other students got an iron tablet weekly and 41 students took an iron tablet for four consecutive days during their menstruation cycle. All subjects were given deworming tablets before supplementation. Haemoglobin, serum ferritin, height, weight, mid-upper arm circumference and dietary intake were assessed before and after intervention. The supplementation contributed to a significant improvement in the iron status of the intervention groups compared to the placebo group (P < 0.05). In the menstruation group, the haemoglobin concentrations of the anaemic subjects improved significantly (P < 0.05) while for the non-anaemic subjects, serum ferritin concentrations also increased significantly (P < 0.05). In the weekly group for anaemic and nonanaemic subjects, there was a significant increase in both haemoglobin and serum ferritin concentrations (P < 0.05). This study revealed that weekly supplementation of iron tablets continued for 16 weeks contributed a higher improvement to haemoglobin concentration, compared with supplementing iron tablets for four consecutive days during menstruation for four menstrual cycles. This suggests that weekly iron supplementation is preferable. A recent meta-analysis of 14 clinical trials indicated that daily compared with intermittent iron supplementation resulted in significantly greater hematological improvement in pregnant women. No such definitive beneficial effect was demonstrated in preschool children. We compared the efficacy of daily and twice weekly iron supplementation for 6 wk under supervised and unsupervised conditions in the treatment of mild and moderate anemia [hemoglobin (Hb) 50-109 g/L] in children aged 2-59 mo living in a malaria-endemic area of western Kenya. The study was a cluster-randomized trial using a factorial design; participants were aware of the treatment assigned. All children (n = 1049) were administered a single dose of sulfadoxine-pyrimethamine at enrollment followed by 6 wk of daily supervised iron supplementation [3-6 mg/(kg.d)], twice weekly supervised iron supplementation [6-12 mg/(kg.wk)], daily unsupervised iron supplementation, or twice weekly unsupervised iron supplementation. In the supervised groups, Hb concentrations at 6 and 12 wk (6 wk postsupplementation) were significantly higher in children given iron daily rather than twice weekly [mean (95% CI) difference at 6-wk: 4.2 g/L (2.1, 6.4); 12-wk: 4.4 g/L (1.8, 7.0)]. Among the unsupervised groups, Hb concentrations were not different at 6 wk [mean (95% CI) difference: 0.86 g/L (-1.4, 3.1)], but significantly higher at 12 wk for those assigned daily iron [mean (95% CI) difference: 3.4 g/L (0.79, 6.0), P = 0.02]. In this malarious area and after initial antimalarial treatment, 6 wk of daily iron supplementation results in better hematological responses than twice weekly iron supplementation in the treatment of anemia in preschool children, regardless of whether adherence can be ensured. To assess the efficacy and acceptability of a daily and intermittent iron supplementation, a double-blind, placebo-controlled trial was conducted in a public school located in periurban Lima, Peru. Adolescent girls (n = 312), 12-18 y old, were randomly assigned to one of the following three groups: 1) 60 mg iron as ferrous sulfate daily from Monday to Friday; 2) 60 mg iron as ferrous sulfate 2 d/wk and 3 d placebo (intermittent); 3) placebo, from Monday to Friday. Field workers gave the girls supplements during school hours for 17 wk; 296 girls completed the trial. Girls took 94% of the expected dose of 85 pills. Few side effects were reported. Postintervention, hemoglobin (Hb), serum ferritin (SF) and free erythrocyte protoporphyrin (FEP) were improved significantly in the iron-supplemented groups compared with placebo (P<0.05). Daily supplements led to higher Hb increases than intermittent supplements (P<0.05), but SF and FEP were similar between the two groups. Thus, both iron supplementation schedules were efficacious in preventing iron deficiency in adolescent girls through the school system, and the daily schedule was better than the intermittent schedule at increasing Hb values and reducing anemia. 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 x 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 microgram/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. It has been suggested that in pregnant women weekly iron supplements are as effective as daily supplements in preventing iron deficiency anaemia (IDA).
                To compare the effectiveness of prophylactic antenatal oral iron supplements given weekly, thrice weekly and daily in preventing IDA in pregnancy.
                A randomised control trial.
                University antenatal clinic, (UANC) Galle.
                An oral iron supplement containing 100 mg of elemental iron was randomly given weekly (n = 26) thrice weekly (n = 35) and daily (n = 31) to 92 women who were 14 to 24 weeks pregnant. Haemoglobin (Hb), serum ferritin (SF) and haematocrit (Hct) were assessed before and after 12 to 20 weeks of supplementation and a logistic regression analysis carried out.
                The risk of developing anaemia was significantly higher in the weekly (odds ratio 15, 95% CI 1.4-165.6, p < 0.03) and possibly higher in the thrice weekly (odds ratio 3, 95% CI 0.3-30.3, p = 0.3) groups. The risk of developing iron deficiency (SF < 12 micrograms/l) was also significantly higher in the weekly (odds ratio 18, 95% CI 2.8-115.5, p < 0.003) and thrice weekly (odds ratio 10, 95% CI 1.6-64.8, p < 0.02) groups.
                Prophylactic oral iron supplements when given intermittently were not effective in preventing iron deficiency anaemia in pregnancy. Iron supplementation is recommended for children at high risk of anaemia, but its benefits may not outweigh the associated risk of malaria in areas of seasonal transmission. We investigated the effect on haemoglobin concentrations of intermittent administration of iron supplements and sulfadoxine-pyrimethamine in symptom-free children under intense health surveillance.
                In a trial of two by two factorial design, 328 anaemic Kenyan children were randomly assigned either iron or placebo and sulfadoxine-pyrimethamine or placebo (82 to each group). Primary outcomes were haemological indicators of iron status and inflammation at the end of the follow-up, and occurrence of malaria attacks. Morbidity surveillance consisted of medical examinations every 4 weeks, continuous passive case detection, and visits twice a week to community health-workers. Analyses were by intention to treat.
                After 12 weeks, the groups assigned iron plus sulfadoxine-pyrimethamine, iron alone, or sulfadoxine-pyrimethamine alone had higher haemoglobin concentrations than the group assigned placebo (treatment effect adjusted for prognostic factors at baseline: 11.1 g/L [95% CI 7.5 to 14.7]; 10.7 g/L [7.1 to 14.3]; and 3.1 g/L [-0.5 to 6.7]). Administration of iron plus sulfadoxine-pyrimethamine also lowered the proportion with anaemia from 100% at baseline to 36% at 12 weeks, and of iron deficiency from 66% at baseline to 8% at 12 weeks. Survival analysis showed no evidence of substantially increased risk of malaria after iron supplementation.
                Iron supplementation gives substantial health benefits, which may outweigh possible inherent risks caused by malaria. A larger study than ours is needed to assess benefits and risks of intermittent administration of sulfadoxine-pyrimethamine in reducing the incidence of malaria attacks in areas of seasonal malaria transmission. Iron deficiency anemia is a major public health problem in developing countries and may affect school performance and physical work capacity in nonpregnant adolescents, and may increase the risk of anemia during subsequent teenage pregnancies. We assessed the effect of weekly iron (120 mg elemental iron) and vitamin A (25 000 IU) supplementation on hemoglobin, iron status and malaria and nonmalaria morbidity in adolescent schoolgirls.
                A total of 279 schoolgirls aged 12-18 years from public primary schools in Kisumu, western Kenya. Double-blind randomized placebo-controlled trial using a factorial design.
                Five months of iron supplementation was associated with a 0.52 g dl(-1) (0.21, 0.82) greater increase in hemoglobin relative to iron placebo. The effect was only observed in girls with iron deficiency on enrollment (1.34 g dl(-1) (0.79, 1.88)), but not in iron-replete girls (-0.20 g dl(-1) (-0.59, 0.18)). Similar differences in treatment effect were seen between menstruating and nonmenstruating girls. The effect of iron was independent of vitamin A. The baseline prevalence of vitamin A deficiency was low (6.7%) and no sustained increase in hemoglobin was seen with weekly vitamin A (-0.07 g dl(-1) (-0.38, 0.25)). Incidence of malaria parasitemia was higher in the iron than iron-placebo groups (Rate ratio 1.33 (0.94, 1.88)).
                Weekly iron supplementation results in substantial increases in hemoglobin concentration in adolescent schoolgirls in western Kenya, which may outweigh possible risks caused by malaria, but only in iron-deficient or menstruating girls and not in iron-replete and nonmenstruating girls. To compare the effectiveness of weekly vs daily iron and folic acid supplementation for control of anemia in adolescent Nepalese girls.
                Randomized controlled trial.
                A Government Girl School in Dharan, Nepal, an urban foothill town that is 305 m above sea level.
                Consecutive healthy adolescent girls (n = 209, median age 15 years) randomized to 3 groups matched for age, anthropometry, and personal and sociodemographic characteristics. Of 209 subjects, 181 completed the trial. Two girls had adverse reactions to treatment and were excluded.
                Group A (n = 70) received a 350-mg ferrous sulfate and 1.5-mg folic acid combination once daily for 90 to 100 days. Group B (n = 67) received the tablet under supervision once a week for 14 weeks. Group C (n = 72) did not receive any drugs.
                Presupplementation and postsupplementation differences in prevalence of anemia and change in hematocrit.
                Prevalence of anemia (defined as hematocrit <36%) declined from 68.6% and 70.1% in groups A and B to 20% and 13.4%, respectively, postsupplementation (P<.001), whereas the prevalence in group C changed little (68.1% to 65.3%, P =.81). There was a significant rise in the mean hematocrit of both supplemented groups (group A, 32.9% +/- 3.5% to 41.0% +/- 5.6%, P<.001; group B, 33.2% +/- 3.6% to 40.4% +/- 4.9%, P<.001) but no appreciable change in controls (34.2% +/- 2.9% to 34.1% +/- 3.3%, P =.91). Net change in mean hematocrit in both the supplementation groups was comparable (P =.57).
                The prevalence of anemia in adolescent Nepalese girls is high. Supervised iron and folic acid therapy once a week is an effective alternative to daily administration and helps lower the prevalence of anemia in adolescent girls. Oral iron supplementation is often routinely given to children with malaria-associated anaemia, but its contribution to recovery is controversial. A randomized clinical trial, evaluating such routine, was carried out among 100 children, who had a haemoglobin of < or = 5 g/dl and a positive blood smear for malaria parasites. All children received malaria therapy (chloroquin + fansidar) and were randomly allocated to two groups, one receiving additional oral iron treatment, the other being the control. In the 12-week follow-up period the haemoglobin level and malaria indices were measured at 2, 4, 8, and 12 weeks. There was a 100 per cent compliance during the follow-up period. In each group 20 children (40 per cent) required a blood transfusion. In the remaining 60 children, after 2 weeks the haemoglobin had risen 3.7 g/dl in the ferrous-supplemented group compared to 3.5 g/dl in the non-ferrous group. Thereafter, the increase in haemoglobin in both groups was steady. At follow-up measurements, the groups did not differ for haemoglobin levels. The mean haemoglobin at 12 weeks was 9.2 and 9.0 g/dl, respectively. It was concluded that iron supplementation did not have any effect on the rate of parasitaemia and on parasite density during the 12 weeks. However, the iron-supplemented group had a significantly increased morbidity from other causes than malaria. It appears that iron does not have an effect on the recovery of haemoglobin level in children with malaria-associated anaemia. This study provides no evidence supporting routine iron supplementation to these children.
Intermittent iron supplementation in menstruating women is a feasible intervention in settings where daily supplementation is likely to be unsuccessful or not possible. In comparison with daily supplementation, the provision of iron supplements intermittently is less effective in preventing or controlling anaemia. More information is needed on morbidity (including malaria outcomes), side effects, work performance, economic productivity, depression and adherence to the intervention.