Daily versus intermittent iron supplementation in pregnant women: hematological and pregnancy outcome. Intermittent oral iron supplementation during pregnancy. Comparison of effect of daily versus weekly iron supplementation during pregnancy on lipid peroxidation. Daily iron supplementation is more effective than twice weekly iron supplementation in pregnant women in Pakistan in a randomized double-blind clinical trial. Efficacy and trial effectiveness of weekly and daily iron supplementation among pregnant women in rural Bangladesh: disentangling the issues. Daily versus intermittent iron supplementation in pregnant women. [Effect of iron supplementation and its frequency during pregnancy]. Weekly iron as a safe alternative to daily supplementation for nonanemic pregnant women. The effectiveness of weekly iron supplementation in pregnant women of rural northern Malawi. Once a week (200 mg) elemental iron: an effective option for prophylaxis in non-anaemic pregnant women. Role of iron supplementation in promoting maternal and fetal outcome. Effects of weekly iron supplementation on pregnant Indonesian women are similar to those of daily supplementation.
To compare the hematological parameters and pregnancy outcome in women receiving daily versus weekly iron supplements during pregnancy.
                A prospective randomized controlled study was carried out at the Department of Obstetrics and Gynaecology of the All India Institute of Medical Sciences, New Delhi, India, during which 111 women were randomized to receive either 100 mg elemental iron daily (n=55) or 200 mg elemental iron weekly (n=56). Hemogram and serum ferritin level estimation were carried out at the beginning of pregnancy and within the 32-34-week period of gestation. Side-effects, compliance and the number of tablets consumed were noted for each group. The mean birth weight, period of gestation at delivery and mode of delivery were also compared between the two intervention groups.
                There was no significant difference in the mean hemoglobin levels between the two intervention groups at the end of an average 17 weeks of iron supplementation. However, among anemic women who received daily supplementation, there was a greater rise in hemoglobin compared with those receiving supplementation weekly. The serum ferritin level was lower in the weekly supplemented group compared with that in the daily. There was no difference in the mean birth weight, period of gestation and mode of delivery between the two groups. Side-effects and non-compliance were significantly higher (P<0.001) in the daily supplemented group.
                Weekly iron supplementation is an effective option for prophylaxis in non-anemic pregnant women, but has less than optimal benefit in anemic women. 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. To compare the effect of daily versus weekly iron supplementation on lipid peroxidation, hemoglobin levels and maternal and perinatal outcome in non-anemic pregnant women.
                Of 109 women randomly allocated into three groups, 90 completed the study. Group I (n = 30) received daily iron folic acid; Group II (n = 30) received weekly iron folic acid; Group III (n = 30) received daily iron (III)-hydroxide polymaltose complex. Hemoglobin levels, hematological indices, thiobarbituric acid reactive substances (TBARS) and glutathione levels were measured at baseline (14-16 weeks) and at 30-34 weeks. Statistical analysis was done using the anova test.
                Group I had a highly significant increase in TBARS level (0.61 +/- 0.26 micromol/L, P = 0.000) compared to groups II and III in which the change in TBARS was not significant (0.02 +/- 0.06 and 0.007 +/- 0.06 micromol/L, respectively). There was an insignificant fall in glutathione levels in all groups. There was no significant difference in the mean period of gestation, pregnancy complications and neonatal outcome between the three groups. Among 22.2% of women who were non-compliant, Group I had significantly higher incidence of non-compliance (P = 0.016) and side-effects (P = 0.001). Final hemoglobin was higher in Group I than II (11.9 +/- 1.2, 11.3 +/- 0.9, respectively, P = 0.041). The TBARS level was not statistically different between preterm and term deliveries. Nine out of 11 patients who developed hypertension during pregnancy had preeclampsia. The final TBARS level was significantly higher in these women (P = 0.000).
                Daily supplementation with ferrous sulphate results in greater lipid peroxidation than weekly supplementation, the latter is comparable with daily iron (III)-hydroxide polymaltose complex. Lipid peroxidation levels are significantly higher in preeclampsia. 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. According to our current understanding, iron absorption with weekly iron supplements is not higher than that with daily supplements (ie, there is no mucosal block). However, community-based trials have repeatedly shown that a weekly regimen is as effective as a daily one. Furthermore, when differences in absorption are found, they are commonly smaller than would be expected on the basis of differences in the amount of iron provided. The possibility of differential compliance between the regimens needs to be evaluated to explain these findings.
                Taking compliance into account, we compared the efficacy and trial effectiveness of weekly and daily iron supplementation during pregnancy.
                In Bangladesh, 50 antenatal centers were randomly assigned to prescribe either 2 doses of 60 mg Fe once weekly or 1 dose of 60 mg Fe/d. Compliance was monitored by using a pill bottle equipped with an electronic counting device. Hemoglobin concentrations were measured at baseline and after 4, 8, and 12 wk of supplementation.
                There was no differential effect per iron tablet between weekly and daily regimens. A 12-wk daily regimen (68% compliance) produced a small but significantly greater hemoglobin response than did the weekly regimen (104% compliance). The first 20 tablets consumed produced most of the effect; after 40 tablets, there was no further response.
                There was no evidence of a mucosal block in the daily regimen. Over 12 wk, 50% of the amount of iron in a daily regimen was sufficient for maximum hemoglobin effect. The weekly regimen provided a large part of this amount, explaining the limited difference in effect. It appears that the current international recommendation for iron supplementation in pregnancy is higher than necessary. The purpose of this study was compare of daily iron supplementation in three time frames- daily, weekly and three time weekly supplementation in preventing anemia in healthy pregnant women.
                The present study was a prospective simply randomized clinical trial. During January 2006- January 2008, 150 healthy pregnant women without anemia, in their 16th week of pregnancy were randomly allocated into three equal groups. The first group (n = 50) received a 50 mg-ferrous sulfate tablet daily, second group (n = 50) received a 50 mg-ferrous sulfate tablet three times a week, and the third group (n = 50) received two 50 mg-ferrous sulfate tablets (100 mg) weekly, respectively for 12 consecutive weeks. Serum hemoglobin, ferritin, and iron were measured before and after the supplementation. Paired t and ANOVA tests were used as appropriated.
                There were no significant differences between the pre- and post-treatment hemoglobin levels with iron supplementation in the three group (P = 0.518, P = 0.276, respectively). The mean serum iron level before and after treatment with iron supplementation in the three groups was not statistically significant (P = 0.962, P = 0.970, respectively). Although the mean serum ferritin level before and after treatment with iron supplementation was statistically significant in the three groups, no significant differences were found comparing the three groups (P = 0.827, P = 0.635 respectively).
                This results suggested, three times a week or weekly iron supplementation is as effective as daily supplementation for healthy pregnant women without anemia.
                ISRCTN: IRCT201101093820N1. The iron (Fe) nutritional status of 203 healthy pregnant women was assessed at the first prenatal visit (To) (gestational age: 16.9 weeks +/- 3.81. Women were randomly assigned to one of three groups: G1 and G2 were supplemented with ferrous fumarate (60 mg elemental Fe) daily or intermittently (three times a week), respectively; and GC was the control group, without supplementation. The follow up was carried out until 34-37 weeks of gestational age (Tf), but only 43% of pregnant women completed the trial. At To and Tf fasting blood samples were collected and Hematocrit (Hct), Hemoglobin (Hb), Erythrocyte Protoporphyrin (EP) and Serum Ferritin (FERR) were determined. The percentage of women with abnormal biochemical values at To (n = 203) was: Hb (g/dl) < 10.5: 2.6%; PE (microgram/dl of red blood cells) > 70: 4.8%; FERR (ng/ml) < 10: 4.4%. Results (X +/- DE) of women that completed the follow up were at To and Tf, respectively: Hct (%): GC: 37.7 +/- 3.4 and 36.0 +/- 3.2 (p < 0.05); G1: 38.8 +/- 2.2 and 38.0 +/- 2.6; G2: 39.0 +/- 2.7 and 37.7 +/- 3.7; Hb (g/dl): GC: 12.5 +/- 1.2 and 11.9 +/- 1.3 (p < 0.05); G1: 12.6 +/- 1.1 and 12.8 +/- 1.1; G2: 12.9 +/- 0.9 and 12.2 +/- 1.5; PE (microgram/dl red blood cells): GC: 30 +/- 17 and 43 +/- 22 (p < 0.01); G1: 26 +/- 13 and 38 +/- 21 (p < 0.01); G2: 26 +/- 16 and 31 +/- 26; FERR (ng/ml): GC: 75 +/- 67 and 31 +/- 49 (p < 0.01); G1: 46 +/- 34 and 19 +/- 10 (p < 0.01); G2: 43 +/- 11 and 11 +/- 7 (p < 0.01). These results show: a) Fe administration was efficient to mitigate Hb decrease; b) Fe stores decreased during pregnancy regardless of Fe supplementation and frequency; c) EP values indicate that intermittent Fe administration was more efficient to maintain normal erythropoiesis. We undertook this study to compare the effectiveness and safety of antenatal daily and weekly supplementation with iron, folic acid, and vitamin B(12) in healthy, pregnant women who were not anemic at gestational week 20.
                Women with singleton pregnancies and blood hemoglobin (Hb) >115 g/L at gestational week 20 (equivalent to 105 g/L at sea level) were randomly assigned to two groups, one consuming one tablet containing 60 mg iron, 200 mug folic acid and 1 mug vitamin B(12) daily (DS, n = 56); the other consuming two tablets once weekly (WS, n = 60). Blood Hb and serum ferritin concentrations were measured every 4 weeks from weeks 20 to 36, and pregnancy outcomes were evaluated.
                Mild anemia and hypoferritinemia throughout pregnancy occurred less frequently in DS than WS. None of the 116 women had Hb concentrations <103 g/L at any evaluation point. In contrast, hemoconcentration (Hb >145 g/L) from gestational week 28 onwards occurred in 11% in DS and 2% in WS. We observed ex post facto that hemoconcentration at gestational week 28 was associated with a significantly higher relative risk of low birth weight (RR 6.23, 95% CI 1.46-26.57) and premature delivery (RR 7.78, 95% CI 1.45-24.74).
                In women who were nonanemic at gestational week 20, both schemes (DS and WS) prevented the occurrence of Hb levels <100 g/L. DS women had a higher incidence of hemoconcentration. Hemoconcentration was associated with increased risk of low birth weight and premature delivery. A weekly iron/folate supplement was compared with a standard daily iron/folate supplement in pregnant women living in rural Malawi. Women were enrolled as they attended the local antenatal clinic, stratified by grade of anaemia and then randomized to receive either 60 mg iron/0.25 mg folate per day (n = 211) or 120 mg iron/0.50 mg folate once a week (n = 202). Supplementation was continued for a minimum of 8 weeks (10 weeks on average) and was self administered by the women at home. Initial haemoglobin values for the daily (mu = 105.7 g/l) and weekly (mu = 104.4 g/l) groups as well as final haemoglobin values (107.5 g/l and 105.6 g/l, respectively) did not differ significantly between the two groups. Haemoglobin values increased by similar levels in both groups with the subset of anaemic women increasing by an average of 6.3 g/l in the daily group (n = 70) and 5.9 g/l in the weekly group (n = 66) for all women. For compliant, anaemic women, the increases were 7.4 g/l and 6.6 g/l for the daily and weekly groups, respectively. Compliance, as indicated by self reporting and by regular counts of remaining tablets, was significantly higher in the weekly group (76% compared with 60%, P < 0.05), however compliance was identical in both groups when assessed by a stool test for elemental iron. Reported side effects were significantly reduced in the weekly group (6% compared with 17%, P < 0.05). We conclude that a weekly iron supplement given to pregnant women in rural Malawi has similar haematologic effects, and an improved side effect profile, in comparison with a standard daily supplement when administered through an existing primary healthcare programme, although both regimens are relatively unsuccessful in the reduction of anaemia prevalence during pregnancy. To evaluate effectiveness of 200 mg elemental iron once per week for prophylaxis in non-anaemic pregnant women, a prospective longitudinal study with observational design was carried out at a tertiary care teaching hospital. Fifty pregnant women received daily (group 1) and 50 pregnant women received weekly (group II) oral therapy (100 mg elemental iron, 1.5 mg folic acid and 15 microg of vitamin B12). Haemoglobin, PCV estimation were carried out during follow-up periods at 4, 8 and 14 weeks. Iron profile (serum iron, TIBC, serum ferritin) estimation was done before and after 14 weeks of iron supplementation. Haemoglobin, PCV and serum iron increased significantly in both the groups (p < 0.001) but on intergroup comparison it was significantly higher in group I than group II (p < 0.001). Serum ferritin improved in both the groups but improvement was not significant in weekly supplemented group. Compliance was better and side-effects were less in group II as compared to group I (11.36% versus 39.9%) The supplementation of pregnant women once per week with 200 mg of elemental iron is an effective option for prophylaxis in mild anaemic or non-anaemic pregnant women. The data comparing daily versus intermittent iron supplementation during pregnancy remain controversial. This study was undertaken to compare the efficacy of daily versus two different intermittent iron supplementation regimes on hematologic markers and birth outcomes in nonanemic pregnant women.
                Two hundred and ten women with singleton pregnancies, no known disease, and hemoglobin levels >11.0 g/dL were randomly assigned to one of three groups, ie, Group A consuming two iron supplementation tablets once weekly (100 mg iron per week, n = 70), Group B consuming one tablet twice weekly (100 mg iron per week, n = 70) and Group C, consuming one tablet daily (50 mg iron per day, n = 70). No additional micronutrients were supplied. Hemoglobin and serum ferritin levels were measured at 20, 28, and 38 weeks. Pregnancy and birth outcomes (pregnancy termination, method of delivery, birth weight, stillbirth) were analyzed.
                In total, 201 women completed the protocol. There was a significant difference in mean hemoglobin and ferritin levels in Group B at 38 weeks (P = 0.018 and P = 0.035, respectively) but this difference was not clinically significant (hemoglobin >12 g/dL, ferritin >19 μg/L). There was a significant increase in ferritin in Group C (P = 0.03) at 28 weeks. No significant difference was observed with respect to pregnancy or birth outcome across the groups. All regimens prevented the occurrence of hemoglobin <10.5 g/dL, but weekly supplementation was associated with development of a hemoglobin level <11.0 g/dL (risk ratio 0.044).
                Twice-weekly supplementation is as effective as daily supplementation, and may represent an acceptable compromise in iron supplementation regimens for nonanemic pregnant women. The effect of daily rather than weekly iron supplementation was compared in women who were 8-24 wk pregnant. One group (n = 68) received 60 mg Fe/d, the second group (n = 71) received 120 mg Fe/wk, given at once. Supplementation lasted 11.3 wk on average, depending on gestational date at entry, and was not supervised. Hemoglobin increased in both groups (P < 0.001); serum ferritin did not change significantly. There was no significant difference between groups for changes in hemoglobin and serum ferritin. In a subgroup of women with a hemoglobin concentration < 110 g/L at baseline (n = 45 daily; n = 54 weekly) no significant within-group changes occurred in serum ferritin, but the change in the daily group was 4.1 micrograms/L higher than in the weekly group (P = 0.049). Compliance, as indicated by two positive stool tests, was approximately equal to 54.3% in the daily group and 62.2% in the weekly group. We conclude that for the complete sample of subjects, the treatment effect of daily compared with weekly supplementation was similar under conditions resembling a normal antenatal care program.
The present systematic review is the most comprehensive summary of the evidence assessing the benefits and harms of intermittent iron supplementation regimens in pregnant women on haematological and pregnancy outcomes. The findings suggest that intermittent iron+folic acid regimens produce similar maternal and infant outcomes at birth as daily supplementation but are associated with fewer side effects. Women receiving daily supplements had increased risk of developing high levels of Hb in mid and late pregnancy but were less likely to present mild anaemia near term. Although the evidence is limited and the quality of the trials was low or very low, intermittent may be a feasible alternative to daily iron supplementation among those pregnant women who are not anaemic and have adequate antenatal care.