Prevention of Iron Deficiency Anemia Post-delivery

PRIORITY is a 2-arm, randomized-controlled trial (RCT) that will be implemented at 8 sites in 7 countries: Bangladesh, Democratic Republic of the Congo, Guatemala, India (Nagpur and Belagavi), Kenya, Pakistan, and Zambia. The research team for each site will enroll approximately 600 women who deliver at a hospital or other facility such as a health center with delivery services. Following informed consent, women with moderate anemia, defined as Hb concentration 7-9.9 g/dL at enrollment, will be randomized to one of two study arms and subsequently receive a single-dose infusion of IV iron within 6-48 hours of delivery and prior to discharge or be given standard care consisting of the provision of tablets containing 60 mg of elemental iron to be taken twice daily for 6 weeks postpartum. Folic acid (400 mcg) will be given daily for 6 weeks postpartum to all participants as per WHO guidelines. The trial's primary endpoint is maternal non-anemic state (Hb ≥11 g/dL) at 6 weeks postpartum. Oral iron treatment with folic acid to 6 months postpartum will be dependent on maternal anemic state at 6 weeks postpartum.

Secondary endpoints include maternal functional outcomes and hematological/biochemical measures of iron status, and maternal and neonatal/infant clinical outcomes. Hb, as well as markers of iron status and inflammatory markers, will be measured at 6 weeks and 6 months postpartum. Other secondary endpoints of interest include intrapartum complications, post-discharge blood transfusions, maternal and neonatal/infant hospitalizations, and maternal and neonatal/infant mortality through 6 months postpartum, as well as rates of exclusive breastfeeding at 6 weeks, 3 months, and 6 months postpartum.

Validated instruments will be used to explore the possible impact of IV iron versus oral iron treatment for IDA on maternal functional outcomes at 6 weeks and 6 months postpartum. Maternal depression, based on the score on the Edinburgh Postnatal Depression Scale (EPDS), will be assessed at 6 weeks and 6 months postpartum. Fatigue is one of the most common symptoms of anemia and will be assessed at 6 weeks and 6 months postpartum using the modified 5-item version of the Maternal Fatigue Severity Scale (FSS-5R). Maternal quality of life will be measured at 6 weeks and 6 months postpartum with the World Health Organization Quality of Life (WHOQOL) score, an assessment tool developed to be applicable cross culturally. Maternal-infant bonding will be measured at 6 weeks postpartum using the Mother-to-Infant Bonding Scale (MIBS).

The PRIORITY RCT will include an implementation research (IR) sub-study to complement the findings of the RCT trial and provide evidence about facilitators, barriers, and costs of implementation to inform global guidelines on the use of IV iron in postpartum women in Low-Middle Income Countries (LMIC). This Implementation Research (IR) sub-study will build upon the PRIORITY trial as well as other research projects to assess IV iron that are being conducted by the Jawaharlal Nehru Medical College research team in Belagavi, India, Thomas Jefferson University (TJU) and by the Aga Khan University team in Pakistan. The IR will utilize a mixed methods approach, employing both quantitative and qualitative data collection to better understand the potential barriers and facilitators to IV iron use in India and Pakistan. The implementation research will be harmonized with the timeline of the main PRIORITY trial, enabling the investigators to collect the IR data in parallel with the trial. The mixed methods IR study for the PRIORITY trial in India and Pakistan will be guided by the Consolidated Framework for Implementation Research (CFIR) and by Proctor's implementation outcomes framework. CFIR and Proctor's framework are complementary and provide a structure for guiding the types of questions and target groups for the implementation research data collection during the trial.

Inclusion criteria

• Established pregnancy ≥28 weeks gestational age by last menstrual period and/or clinical assessment and/or ultrasonography
• Age: 18 years (or lower limit age eligible*) to 49 years
• Confirmed moderate anemia (Hb 7.0 to 9.9 g/dL, 6-48 hour after delivery based on a venous blood sample on Hemocue®)
• Deliver in participating study hospital or health facility
• Able to provide informed consent
• Plans to remain in study area for at least 6 months postpartum

Exclusion criteria

• IV Iron infusion received in past 3 weeks
• Prior reaction to IV iron or oral iron or folic acid
• Contraindication to iron supplementation (some examples may include severe allergic states including asthma, hemolytic anemia, allergy, or severe infection)
• Blood transfusion already received or scheduled during the current hospital admission
• Known diagnosis of pre-existing depression or other psychiatric illness
• Major congenital anomaly prior to randomization
• Stillbirth or neonatal loss prior to randomization
• Presenting with symptomatic anemia with dyspnea or fatigue and need for immediate correction
• Known hemoglobinopathy (sickle cell disease or thalassemia)
• Positive malaria RDT prior to randomization (sub-Saharan African sites only)
• Any illness/condition requiring immediate medical care per physician's assessment