Daily versus Alternate-Day Iron Supplementation for Pregnant Women with Iron Deficiency Anemia: A Randomized Controlled Trial

Abstract

This study aimed to evaluate the most effective regimen to raise hemoglobin (Hb) by comparing alternate-day dosing of iron to daily dosing in pregnant women with iron deficiency anemia. Women with Hb < 11.0 g/dL and ferritin ≤ 25 µg/L between 12^0/7 and 34^0/7 weeks' gestation were recruited. A total of 88 patients were randomized using block randomization with 1:1 allocation to receive either 1 tablet of 325 mg ferrous sulfate on consecutive days or 2 tablets every other day. The primary outcome, the change in Hb after 6 weeks of treatment was assessed using an analysis of covariance to adjust for baseline level. Secondary outcomes included change in ferritin, hepcidin, side effects, and compliance. Patients completed a questionnaire to assess for adverse symptoms and adherence was monitored by installing a pill reminder app on smartphones of patients. A total of 88 patients were consented. The daily iron group had a greater proportion of nulliparous women (40 vs. 7%). Most patients (98%) had mild anemia (Hb: 9-10.9 g/dL) at recruitment, with a median gestational age of 28.1 weeks (interquartile range [IQR]: 25.6, 30.9) and median duration of treatment of 42 days (IQR: 35, 45). At 6 weeks, the daily iron group had a mean increase in Hb of 0.8 ± 0.9 g/dL, whereas the alternate-day iron group had a mean increase of 0.5 ± 1.0 g/dL (baseline adjusted difference of means: -0.3 [95% confidence interval: -0.7, 0.1], p = 0.15). Frequency of adverse effects attributable to iron were similar between groups. Patient self-reported compliance to treatment was also similar between groups. Among those that used the app, compliance was higher among the daily group compared with the alternate daily group (median: 95.5% [IQR: 75, 100] vs. 85% [IQR: 40, 92]), although this difference was not statistically significant (p = 0.07). This trial suggests that there are no significant differences between alternate-day iron supplementation and daily iron supplementation for treating iron deficiency anemia. · Intermittent iron provides no additional benefit compared to daily iron in the treatment of anemia.. · Patient compliance to treatment was similar between the groups.. · The frequency of side effects was not significantly different between the groups..