Anemia in Pregnancy, Iron Deficiency Anemia
Conditions
Keywords
oral iron, ferrous sulfate, alternate-day dosing, hepcidin, second trimester, adherence
Brief summary
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.
Detailed description
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.
Interventions
DRUGFerrous Sulfate
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.
Sponsors
Pakistan Air Force (PAF) Hospital Islamabad
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Masking description
Participant and care-provider blinding is not feasible because the two arms follow visibly different dosing schedules. Outcome assessment is blinded: laboratory personnel analyzing hemoglobin and ferritin are masked to group allocation, with samples labeled by unique participant ID only.
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 40 Years
Healthy volunteers
No
Inclusion criteria
* Aged 18 to 40 years * Pregnant women in the second trimester (13 to 27 weeks gestation) * Hemoglobin below 11 g/dL with serum ferritin below 30 ng/mL * Singleton pregnancy
Exclusion criteria
* Known congenital or acquired hemoglobin disorders (e.g., thalassemia, hemoglobinopathies) * Chronic diseases affecting hemoglobin levels (e.g., chronic kidney disease, inflammatory disorders) * Bleeding disorders or a history of frequent blood loss * Gastrointestinal conditions impairing nutrient absorption (e.g., celiac disease or other malabsorption syndromes) * Currently receiving parenteral iron * Requiring blood transfusion
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in hemoglobin from baseline to Week 4 | Baseline and 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in serum ferritin from baseline to Week 4 | Baseline and Week 4 | Mean within-participant change in serum ferritin concentration (ng/mL) from baseline to Week 4, compared between groups. |
| Treatment adherence | Through Week 4 | Proportion of participants taking at least 80 percent of prescribed doses, determined by pill count cross-checked against patient dose diaries. |
| Frequency of gastrointestinal side effects | Through Week 4 | Proportion of participants reporting any gastrointestinal side effect (nausea, vomiting, constipation, metallic taste, or abdominal discomfort) recorded using a structured checklist. |
| Severity of gastrointestinal side effects | Through Week 4 | Severity of reported gastrointestinal side effects graded as mild, moderate, or severe on a structured checklist. |
Countries
Pakistan
Contacts
CONTACTAmmara Suleman
PRINCIPAL_INVESTIGATORAmmara Suleman, MBBS
Pakistan Air Force (PAF) Hospital Islamabad
Outcome results
None listed