This randomized controlled trial compares daily versus alternate-day oral iron supplementation in pregnant women with iron deficiency anemia during the second trimester. The study evaluates changes in hemoglobin and serum ferritin, treatment adherence, and gastrointestinal side effects to inform more patient-centered, physiologically aligned dosing strategies.
Iron deficiency anemia is the leading cause of anemia in pregnancy. Although daily oral iron is standard first-line therapy, it is frequently associated with gastrointestinal side effects and poor adherence. Because hepcidin rises after an iron dose and remains elevated for 24 to 48 hours, daily dosing may reduce fractional absorption; alternate-day dosing allows hepcidin to fall between doses, potentially improving absorption and tolerance. This single-center, prospective, randomized, parallel-group trial will recruit pregnant women (13 to 27 weeks gestation) with hemoglobin below 11 g/dL and serum ferritin below 30 ng/mL from the antenatal clinic at PAF Teaching Hospital, Islamabad. Eligible, consenting participants will be randomized 1:1 to daily ferrous sulfate (one 325 mg tablet, approximately 65 mg elemental iron, once daily) or alternate-day ferrous sulfate (two 325 mg tablets, approximately 130 mg elemental iron, every other day) for four weeks. The primary outcome is change in hemoglobin from baseline to Week 4. Secondary outcomes are change in serum ferritin, treatment adherence (proportion taking at least 80 percent of doses, by pill count and diary), and the frequency and severity of gastrointestinal side effects. Outcome assessors (laboratory personnel) are blinded to allocation; participant blinding is not feasible given the differing dosing schedules. Planned enrollment is 184 participants (92 per group), giving 90 percent power to detect a 0.40 g/dL difference in hemoglobin change at a two-sided alpha of 0.05, assuming a standard deviation of 0.83 g/dL.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
SINGLE
Enrollment
184
Oral ferrous sulfate 325 mg tablets (approximately 65 mg elemental iron per tablet) administered for four weeks according to the assigned dosing schedule. All participants receive standardized counseling on administration, diet, side effects, and adherence, and are issued a dose diary.
Pakistan Air Force (PAF) Hospital Islamabad
Islamabad, Pakistan
Change in hemoglobin from baseline to Week 4
Mean within-participant change in hemoglobin concentration (g/dL), measured at baseline and at Week 4, compared between the daily and alternate-day arms.
Time frame: Baseline and Week 4
Change in serum ferritin from baseline to Week 4
Mean within-participant change in serum ferritin concentration (ng/mL) from baseline to Week 4, compared between groups.
Time frame: Baseline and Week 4
Treatment adherence
Proportion of participants taking at least 80 percent of prescribed doses, determined by pill count cross-checked against patient dose diaries.
Time frame: Through Week 4
Frequency of gastrointestinal side effects
Proportion of participants reporting any gastrointestinal side effect (nausea, vomiting, constipation, metallic taste, or abdominal discomfort) recorded using a structured checklist.
Time frame: Through Week 4
Severity of gastrointestinal side effects
Severity of reported gastrointestinal side effects graded as mild, moderate, or severe on a structured checklist.
Time frame: Through Week 4
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