Prevention of Anemia Post-delivery
- Conditions
- Anemia complicating pregnancy, childbirth and the puerperium,
- Registration Number
- CTRI/2022/10/046632
- Lead Sponsor
- Eunice Kennedy Shriver National Institute of Child Health and Human Development
- Brief Summary
**Background**
The most common cause of anemia worldwide is iron deficiency. And while it is increasingly being reported that iron deficiency anemia (IDA) during pregnancy increases the risk of adverse maternal, fetal, and neonatal outcomes, it is important to address other critical time points during a woman’s life, particularly immediately after delivery when hemoglobin (Hb) concentrations often drop precipitously.
This study, **Prevention of Iron Deficiency Anemia Post-delivery (PRIORITY)**is designed as a 2-arm, randomized-controlled trial focused on postpartum women. If successful, its application can contribute to a reduction in anemia prevalence rates among women of reproductive age consistent with the resolution of the World Health Assembly. The trial will recruit women who are diagnosed with moderate anemia based on a blood sample taken 6-48 hours after childbirth. A total of 4,800 eligible women, or 600 women per research site, will be consented and enrolled in the trial by the research teams of eight international sites that, together with their US partners, participate in the *Eunice Kennedy Shriver* National Institute of Child Health and Human Development’s (NICHD’s) Global Network for Women’s and Children’s Health Research.
Women with Hb concentration 7-9.9 g/dL at enrollment, following informed consent, will be randomized to one of two study arms and subsequently receive a single-dose intravenous (IV) iron infusion (± folate tablets as per local guidelines) 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 post-delivery (± folate as per local guidelines). The trial’s primary outcome is maternal non-anemic state (Hb >11 g/dL) at 6 weeks post-delivery. It is expected that there will be a 30% relative difference in the prevalence of anemia between the two arms when hemoglobin is assessed at 6 weeks post-delivery (based on anemia defined as Hb <11 g/dL).
Validated instruments will be used to explore the possible impact of IV iron versus oral iron treatment for IDA on functional outcomes at 6 weeks and 6 months post-delivery. Maternal-infant bonding will be measured using the Mother-to-Infant Bonding Scale (MIBS). Fatigue is one of the most common symptoms of anemia, and will be assessed using the Maternal Fatigue Severity Scale (FSS-5R), a 5-item survey for assessing fatigue (REF. Quality of life will be measured with the World Health Organization Quality of Life (WHOQOL) Scale, an assessment tool developed to be applicable cross culturally by its developers.
**Primary Outcome and Hypothesis**
**Primary Outcome:**
Maternal non-anemic state at 6 weeks post-delivery
*Explanation Relevant to Study Arms:*
Eligible and consenting anemic women with Hb 7-9.9 g/dL based upon a venous blood sample obtained after childbirth but before discharge from a hospital or other facility with delivery services (such as a health center) will be randomized between 6 and 48 hours post-delivery equally to one of two study arms. Women randomized to **Arm 1** will receive a single-dose infusion (maximum of 1 gram or less depending on participant weight) of intravenous (IV) iron; and those in **Arm 2** will receive standard of care defined for this study as 60 mg elemental iron to be taken at a treatment dose of twice daily for 6 weeks. Both arms will also receive folate supplements as per local guidelines.
**Primary Hypothesis to be Tested:**
At 6 weeks post-delivery, prevalence of the non-anemic state in women in study Arm 1 will be greater than that of women in study Arm 2.
**Secondary Outcomes:**
***Maternal***
a. Maternal mortality (from delivery to 6 mo post-delivery)
b. Post-discharge blood transfusion through 6 mo post-delivery
c. Postpartum hemorrhage (from intervention through 6 wk post-delivery) requiring transfusion or major surgery
d. Hospitalization (as an indicator to capture infection through 6 mo post-delivery)
e. Documentation of major antenatal or intrapartum complications (diabetes, preeclampsia, fetal demise)
f. Rate of screening for postpartum depression (6 wk, 6 mo)
g. Maternal fatigue severity scores (6 wk, 6 mo)
h. Infant-mother bonding scale scores (6 wk
i. Quality of life assessment scores (6 wk, 6 mo)
j. Prevalence of severe/moderate/mild anemia (also at time of recruitment and at 6 mo)
k. Change resulting in severe/moderate/mild anemia by treatment arm (6 mo)
l. Hemoglobin concentration by mode of delivery (6 mo)
m. Differences in ferritin and inflammatory markers on all randomized patients (delivery, 6 wk, 6 mo)
n. Hb concentration and ferritin measured in first trimester of an intercurrent pregnancy
***Infant***
a. Neonatal/infant mortality (birth to 6 mo)
b. Infant hospitalization (birth to 6 mo)
c. Exclusive breastfeeding rate (6 wk, 6 mo) and intent to continue breastfeeding through 12 mo post-delivery (6 mo)
**Study Aims**
a. To compare the effects of two approaches for early treatment of postpartum anemia
b. To explore findings related to secondary outcomes to better understand scope and duration of anemia in the postpartum period as well as health-related consequences
c. To compare the effects of two approaches in screening test results of maternal depression
d. To assess if differences between the two arms continue for as long as 6 mo post-delivery
e. To assess specific clinical outcomes in the infant due to differences in a mother’s postpartum anemia status
f. To define whether ferritin values and/or inflammatory markers are associated with study outcomes
**Available Study Population**
All recently delivered women confirmed to have moderate anemia, who have no contraindication to iron supplementation, have not already received or are scheduled to receive a transfusion, and meet other eligibility criteria (such as planning to remain in the research area for at least 6 months post-delivery) may participate in the study if they provide informed consent.
*Inclusion Criteria:*
*a.*Established pregnancy >20 wk gestation by LMP and/or clinical assessment
b. Age eligible\*
c. Confirmed moderate anemia (Hb 7.0 to 9.9 g/dL, 6-48 hr after delivery based on a venous blood sample)
d. Deliver in participating study hospital or health facility
e. Able to provide informed consent
f. Plans to remain in study area for duration of the study
*Exclusion Criteria:*
a. Contraindication to iron supplementation
b. Blood transfusion already received or scheduled
c. Known diagnosis of pre-existing depression or other psychiatric illness
d. Stillbirth, major congenital anomaly, or neonatal loss prior to facility discharge
e. Women testing positive and previously untreated for malaria
f. Presenting with symptomatic anemia with dyspnea or fatigue and need for immediate correction
g. Women with known hemoglobinopathy (sickle cell disease or thalassemia)
h. Presence of severe allergic conditions such as severe asthma or known drug allergies
i. Women presenting with any illness/condition requiring immediate medical care per physician’s assessment
[\*Note: Some sites will be able to include a woman giving birth regardless of age if she is considered an adult or an emancipated minor. However, other sites will require a woman to be at least 18 years of age. We will adhere to local regulations.]
**Treatment Arms:**
***Intervention:*** Single dose IV iron ± folate as per local guidelines (Arm 1)
***Comparison:***Standard care (oral iron ± folate as per local guidelines) (Arm 2)
**Randomization Procedures**
Postpartum women found eligible who provide consent to study participation will be individually randomized and allocated 1:1 to one of two arms stratified by site:
1) An IV iron arm which will result in receipt of a single-dose IV iron infusion between 6 and 48 hours after delivery and prior to discharge from the facility; folate tablets will be given as per local guidelines.
2) An oral iron comparator arm which will result in a participant being given a supply of oral iron tablets (containing 60 mg of elemental iron (± folate as per local guidelines)) to be taken at a treatment dose of twice daily for 6 weeks.
A computer algorithm generated by the data coordinating center (DCC) will create the random assignment to one of the treatment arms based on randomly permuted block design with randomly varied block sizes. Randomization will be stratified based on delivery mode (Cesarean section vs. vaginal birth) and site. The block sizes will be known only by the DCC personnel.
**Study Duration:**The length of the study being proposed is approximately 30 months.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Closed to Recruitment of Participants
- Sex
- Female
- Target Recruitment
- 4800
- Established pregnancy >20 wk gestation by LMP and/or clinical assessment 2.
- Confirmed moderate anemia (Hb 7.0 to 9.9 g/dL, 6-48 hr after delivery based on a venous blood sample) 3.
- Deliver in participating study hospital or health facility 4.
- Able to provide informed consent 5.
- Plans to remain in study area for duration of the study.
- Contraindication to iron supplementation 2.
- Blood transfusion already received or scheduled 3.
- Known diagnosis of pre-existing depression or other psychiatric illness 4.
- Stillbirth, major congenital anomaly, or neonatal loss prior to facility discharge 5.
- Women testing positive and previously untreated for malaria 6.
- Presenting with symptomatic anemia with dyspnea or fatigue and need for immediate correction 7.
- Women with known hemoglobinopathy (sickle cell disease or thalassemia) 8.
- Presence of severe allergic conditions such as severe asthma or known drug allergies 9.
- Women presenting with any illness/condition requiring immediate medical care per physician’s assessment.
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Maternal non-anemic state At 6 weeks post-delivery
- Secondary Outcome Measures
Name Time Method Postpartum hemorrhage requiring transfusion or major surgery From intervention through 6 weeks post-delivery Hospitalization From delivery to 6 months post-delivery Documentation of major antenatal or intrapartum complications (diabetes, preeclampsia, fetal demise) From delivery to 6 months post-delivery Rate of screening for postpartum depression At 6 weeks and 6 months Prevalence of severe/moderate/mild anemia At time of recruitment and at 6 months Hemoglobin concentration by mode of delivery At 6 months Differences in ferritin and inflammatory markers on all randomized patients At delivery, 6 weeks and 6 months Hb concentration and ferritin During first trimester of an intercurrent pregnancy Neonatal/infant mortality Birth to 6 months Maternal fatigue severity scores At 6 weeks and 6 months Infant-mother bonding scale scores 6 weeks Maternal mortality From delivery to 6 months post-delivery Post-discharge blood transfusion From delivery to 6 months post-delivery Quality of life assessment scores At 6 weeks and 6 months Change resulting in severe/moderate/mild anemia by treatment arm At 6 months Infant hospitalization Birth to 6 months Exclusive breastfeeding rate At 6 weeks and 6 months Intent to continue breastfeeding through 12 months post-delivery At 6 months
Trial Locations
- Locations (4)
Government Medical College and Hospital, Nagpur
🇮🇳Nagpur, MAHARASHTRA, India
Jawaharlal Nehru Medical College Belgaum
🇮🇳Belgaum, KARNATAKA, India
Lata Medical Research Foundation Nagpur
🇮🇳Nagpur, MAHARASHTRA, India
Mahatma Gandhi Institute of Medical Sciences and Kasturba Health Society, Wardha
🇮🇳Wardha, MAHARASHTRA, India
Government Medical College and Hospital, Nagpur🇮🇳Nagpur, MAHARASHTRA, IndiaDr Manjushree WaikarPrincipal investigator9823099031manjuw123@gmail.com