Daily Iron Supplementation Is More Effective than Twice Weekly Iron Supplementation in Pregnant Women in Pakistan in a Randomized Double-Blind Clinical Trial

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 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.

Impact of twice weekly versus daily iron supplementation during pregnancy on maternal and fetal haematological indices: a randomized clinical trial

“…Both groups had similar rates of anaemia at delivery, providing evidence that low doses of iron during pregnancy could be beneficial in preventing anaemia. A number of studies showed that reducing the iron dose or intermittent prescriptions are less effective in improving Hb and iron status than a daily standard dose (30-60 mg elemental iron) [1,8,12]. However, this difference was small, with no reported significant effect on pregnancy outcomes and might be related to factors other than type of iron regimen, such as pre-pregnancy haematological status, nutritional behaviour, diet during pregnancy and the prevalence of iron deficiency or other micronutrient deficiencies [16].…”

“…Despite widespread preventive programmes, iron-deficiency anaemia during pregnancy is still prevalent and is associated with adverse pregnancy outcomes for both mother and newborn [1][2][3][4]. Poor client compliance with national iron supplementation protocols because of side-effects, especially gastrointestinal (GI) complications such as nausea, vomiting and constipation, is suggested as one of the main reasons for the inefficiency of these programmes [5].…”

“…Poor client compliance with national iron supplementation protocols because of side-effects, especially gastrointestinal (GI) complications such as nausea, vomiting and constipation, is suggested as one of the main reasons for the inefficiency of these programmes [5]. Several studies indicate that iron absorption could improve if iron supplements were administered intermittently, matched with mucosal regeneration time of the intestine, which in turn diminishes sideeffects and enhances compliance rates [1,6]. Interaction of iron with other micronutrients especially zinc, and also the postulated relationship between high-dose iron supplementation and pregnancy complications such as gestational diabetes, preterm labour and low birth weight, suggest that the amount of iron recommended in the current protocol is too high [3,[7][8][9][10].…”

“…The controversy regarding maintaining the effectiveness of iron supplementation when reducing the dose has not been solved yet [1,12]. Although routine daily iron supplementation from the 4th month of pregnancy is a standard part of prenatal care, iron deficiency anaemia is still a commonly reported complication of pregnancy in the Islamic Republic of Iran [13].…”

Iron Deficiency Anemia: A Public Health Problem of Global Proportions

“…Prevention and control is typically achieved through iron fortification of food staples like flour, rice, and pasta, and/or through administration of iron supplements most often in iron pill or, more recently sprinkle form (Baltussen et al, 2004;Faqih et al, 2006;Mumtaz et al 2000;. Although iron supplements are widely available and fortified foods constitute a major component of the diet in the developed world, access is limited in the developing world and cost if often prohibitive.…”