Efficacy and Demonstration of IntraVenous Iron for Anaemia in pregnancy (EDIVA)

INTERVENTION: This will be a two‐arm (1:1) Phase III open‐label superiority individual‐randomised controlled trial assessing the effectiveness of the intravenous iron ferric carboxymaltose in reducing maternal anaemia, compared to the standard of care of oral iron supplementation. Women in their second or third trimester of pregnancy will be screened for anaemia and those found to be moderately‐severely anaemic (haemoglobin <10g/dL) will be randomized to receive the intervention or the control. Intervention: intravenous iron treatment course administered once during pregnancy. Intravenous ferric carboxymaltose (FCM) 1000 mg total dose for body weight of 50 kg or more, or 20 mg/kg for body weight less than 50 kg, will be given over 15 minutes by a skilled study physician/ medical technologist. For participants receiving the intravenous iron treatment course: the skin will be cleaned with ethanol following standard aseptic procedure, and a sterile cannula will be inserted into the forearm or hand by a skilled study physician/medical technologist, and the cannula will be fixed in place with a sterile Tegaderm or clinical tape. The participant will be monitored over the 15 minutes of the infusion for any adverse events and at 10 minutes into the infusion, she will be asked if she experiences any problems and everything will be recorded. If the participant develops any complications, these will be attended to promptly and treated according to standard clinical management guidelines. The participant will be observed for a further 45 minutes and similarly, any problems experienced will be recorded. CONDITION: Anaemia;Iron deficiency;Maternal depression;Low birthweight;Prematurity;small for gestational age; ; Anaemia ; Iron deficiency ; Maternal depression ; Low birthweight ; Prematurity ; small for gestational age Blood ‐ Anaemia Diet and Nutrition ‐ Other diet and nutrition disorders Mental Health ‐ Depression Reproductive Health and Childbirth ‐ Fetal medicine and complications of pregnancy PRIMARY OUTCOME: Maternal anaemia (haemoglobin <11g/dL), assessed by a finger prick test using a HemoCue301 portable haemolgobin analyzer[36 weeks gestation (this timepoint is after delivery of the intervention)] SECONDARY OUTCOME: Abortion (pregnancy loss before 28 weeks of gestation) as reported by participant, study staff or based on clinical records[<28 weeks gestation] Adverse perinatal events including postpartum haemorrhage, need for blood transfusion, intensive care admission or mortality, as reported by patient or based on clinical records, or as observed by study staff.[From recruitment to 28 days postpartum] Birthweight (as a continuous variable measured in grams) using infant scales[At delivery visit] Child neurodevelopment, assessed by neonatal behavioral assessment scale[At delivery and 42 days postnatal] Child neurodevelopment, assessed by the auditory brainstem response tool[42 days postnatal and 6 months postnatal] Child neurodevelopment, assessed by the Bayleys scales of infant development[6 months postnatal] Child physical growth (length and weight) as a composite outcome, measured using infant scales and measuring tape[42 days postnatal, 3 months postnatal and 6 months postnatal] Child physical growth (length, cm) measured with measuring tape[42 days postnatal, 3 months postnatal and 6 months postnatal] Gestational age at birth (weeks), based on calculated duration of gestation, using dating at baseline ultrasound examination to date of actual delivery.[At delivery visit] Infant adverse events including hospitalisation and clinic visits as reported by mother, study staff or based on clinical records[Throughout study from delivery through to 6 months old] Infant ferritin levels (continuous), assessed by enzyme‐linked immunosorbent assays (ELISAs) for serum ferritin.[42 days postnatal, 3 months postnatal and 6 months postnatal] Infant haemoglobin levels (as a continuous variable) assessed by a finger prick test using a HemoCue301 portable haemolgobin analyzer[42 days postnatal, 3 months postnatal and 6 months postnatal] Infusion related adverse events including allergic reactions as reported by study staff or based on clinical records[Time of administration of intervention, and any severe adverse events reported by study staff or based on clinical records up to two weeks post intervention] Low birth weight (as a categorical variable, birth weight <2500g) using infant scales[At delivery visit] Maternal anaemia (haemoglobin <11g/dL), assessed by a finger prick test using a HemoCue301 portable haemolgobin analyzer[4 weeks post intervention, 42 days postpartum, 3 months postpartum and 6 months postpartum] Maternal depression measured by the Edinburgh postnatal depression scale[4 weeks post intervention, 36 weeks gestation, and 3 months postpartum ] Maternal ferritin levels (as a continuous variable), assessed by enzyme‐linked immunosorbent assays (ELISAs) for serum ferritin.[4 weeks post intervention, 36 weeks gestation, 42 days postpartum, 3 months postpartum and 6 months postpartum] Maternal haemoglobin levels (as a continuous variable), assessed by a finger prick test using a HemoCue301 portable haemolgobin analyzer[4 weeks post intervention, 36 weeks gestation, 42 days postpartum, 3 months and 6 months postpartum] Maternal hypophosphatemia based on biochemical measurement of serum phosphate[4 weeks post intervention, 36 weeks gestation] Maternal inflammation, measured by enzyme‐linked immunosorbent assays (ELISAs) for C‐reactive protein[4 weeks post intervention, 36 weeks gestation, 42 days postpartum, 3 months postpartum and 6 months postpartum] Maternal iron deficiency (ferritin <15 mg/L), assessed by enzyme‐linked immunosorbent assays (ELISAs) for serum ferritin.[4 weeks post intervention, 36 weeks gestation, 42 days postpartum, 3 months postpartum, 6 months postpartum] Mother to infant bonding measured by the mother to infant bonding scale [3 months postpartum] Neonatal mortality as reported by participant, study staff or based on clinical records[Death of child within the first month of life] Premature birth (<37 weeks) Gestational age at birth (weeks), based on calculated duration of gestation, using dating at baseline ultrasound examination to date of actual delivery.[At delivery visit] Small for gestation age as a dichotomous variable (<10th centile), based on baseline ultrasound dating of pregnancy adjusted birth weight[At delivery visit] Stillbirth (birth of a baby showing no signs of life after 28 weeks gestation) as reported by participant, study staff or based on clinical records[> 28 weeks gestation] INCLUSION CRITERIA: ‐ In their second (13‐25 completed weeks) or third trimester (26‐32 completed weeks of gestation), dated by Last Menstrual Period. ‐ Moderate to severe anaemia (capillary Hb <10g/dL). ‐ Not known to have a multiple pregnancy. ‐ Expected to deliver the baby inside or within 30 minutes of road transport of the study catchment area. ‐ Have drinking water groundwater iron <1mg/L. ‐ Willing to provide written informed consent (if the pregnant woman is <18 years of age, consent will be collected from her guardian, while she will sign an assent form).