This trial is being conducted across 20 health facilities across the board, 5 health facilities from each of the 4 selected state comprising of one primary health care, three secondary facilities and one tertiary facility.

Postpartum women with moderate to severe iron deficiency anemia.

Inclusion criteria:

1.     Women aged between 15 and 49 years.

2.     Between six and 48 hours after delivery. A minimum of six hours has been chosen because we expect the initial post-birth blood loss to have subsided and the hemoglobin concentration to be sufficiently representative of the true hemoglobin concentration at that time; 48 hours has been chosen as the upper limit for pragmatic reasons because women are usually discharged from hospital after 48 hours.

3.     Baseline (enrolment) moderate or severe anemia (Hb≤9.9g/dl), confirmed by Hemocue haemoglobinometer.

4.     Able and willing to give written informed consent.

Exclusion criteria:

1.     Having received a blood transfusion, for any indication, within the last three months.

2.     Symptomatic anemia and a need for urgent correction.

3.     Known haemoglobinopathy such as sickle cell disease, HbCC disease.

4.     Clinically confirmed malabsorption syndrome.

5.     Known hypersensitivity or contraindication to any form of iron treatment, study drug or any of its excipients.

6.     Self-reported pre-existing maternal depression or other psychiatric illness and as evidenced by a YES response to Any Past history of Psychiatry ward hospitalization, Psychiatry medications, behavioural changes, or past consultation with Psychiatry services.

7.     Severe allergic conditions such as severe asthma, eczema, or other atopic condition.

8.     Known autoimmune conditions e.g., systemic lupus erythematosus, rheumatoid arthritis or known severe drug allergies.

9.     Planning to move or reside outside the research area.

10.  Women who have had intravenous iron administered in the last two years.

We will enrol 1400 women into the trial. Power calculations assume a 1:1 randomization ratio to each of the two treatment groups.

a)     Administration of ferric carboxymaltose (FCM): Eligible women randomized to the intervention arm (FCM) will be observed at the dedicated ward or day-care room for treatment initiation and will be given intravenous ferric carboxymaltose (FCM) in a single dose of 20mg/kg up to a maximum of 1000mg. This dose will be administered as an infusion diluted in 200 ml 0.9% sodium chloride and infused over a minimum of 15 - 20 minutes. Thereafter, they will be observed closely for a minimum of 30 minutes after infusion.

b)    Administration of Ferrous Sulphate (FS): The women randomized to the control arm (FS) will be given for take home, one 200mg tablet of study drug, ferrous sulphate which contains 65mg of elemental iron, to be taken two times daily and 1 hour before meals or 2 hours after meals with a full glass of water till 6 weeks postpartum. The study drug for the control arm (FS) will be prepared in sachets, dispensed, and packaged in 2-week, 4-week and 6-week doses for the appropriate visit schedule. The women will be sent daily reminders by text messages and asked to bring in their empty sachets for sighting and for a pill count and evaluation of compliance at each study visit.

1.     Clinical outcomes

Primary outcome:

Proportion of participants who are non-anemic at six weeks postpartum. Non-anemic state is defined as hemoglobin level ≥ 11.0g/dl.

Secondary outcomes:

·      Proportion of women with postpartum depression, measured using the Edinburgh Postnatal Depression Scale at six weeks and six months postpartum.

·      Change in mean postpartum hemoglobin levels at two weeks and six weeks postpartum.

·      Achievement of a non-anemic state (Hb≥11.0g/dl) at six months postpartum.

·      Prevalence of moderate/severe anemia at six weeks and six months postpartum. Moderate anemia is defined as hemoglobin level 7.0-9.9g/dl and severe anemia as hemoglobin level <7.0g/dl.

·      Change in mean serum ferritin, serum transferrin, serum iron and % transferrin saturation at two weeks and six weeks postpartum.

·      Need for blood transfusion after iron treatment during the first 6 weeks postpartum.

·      Prevalence of fatigue at six weeks and six months postpartum, measured using the Fatigue Severity Scale (revised FSS-5R version) (22).

·      Proportion of women with secondary postpartum hemorrhage after treatment. This will be defined as excessive bleeding requiring surgical intervention or blood transfusion from 24 hours after delivery till 12 weeks postpartum (23).

·      Proportion of infants being breastfed (exclusive and any) at six weeks and six months postpartum.

·      Prevalence of impaired maternal-infant bonding at six weeks and six months postpartum measured using the mother-to-Infant Bonding Scale (MIBS) (20).

·      Incidence confirmed or suspected maternal infection within 6 weeks of birth, as defined by a new prescription of antibiotics for presumed perineal wound-related infection, endometritis or uterine infection, urinary tract infection or other systemic infection (clinical sepsis).

·      Incidence of hypophosphatemia at two weeks and six weeks postpartum. We will measure vitamin D, alkaline phosphatase, P1NP, FGF23, Ca, PO4, which are biomarkers of phosphorus homeostasis and bone turnover. Hypophosphatemia is defined as serum phosphate level <2.5mg/dL (0.81mmol/L). Mild hypophosphatemia as 2-2.5 mg/dL (0.65-0.81 mmol/L), moderate as 1-2 mg/dL (0.32-0.65 mmol/L), and severe as <1 mg/dL (0.32 mmol/L).

·      Incidence of early neonatal death, defined as death of new-born from enrolment of the mother to before seven completed days.

·      Incidence of late neonatal death, defined as death of the new-born from enrolment of the mother to before 28 completed days.

·      Incidence of infant death, defined as death from enrolment before the age of six months.

·      Incidence of post-natal maternal death from enrolment up to six weeks and at six months postpartum.

·      Incidence of adverse drug events.

·      Quality of life measured using the WHOQOL BREF at enrolment, six weeks, and six months post-partum.

2.     Implementation outcomes:

·      Acceptability of the intervention to women and health care professionals

·      Feasibility of implementing the intervention