Intravenous Iron for Iron-deficiency Anemia in Pregnancy: a Randomized Controlled Trial

Study Overview
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Brief Summary
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Iron deficiency is the most common cause of anemia in pregnancy worldwide, and, when severe, can have serious consequences for mothers and babies. While treatment of iron-deficiency anemia with iron supplementation is recommended, treatment strategies remain controversial: the American College of Obstetrics and Gynecology recommends oral iron supplementation with parental iron reserved for the rare patient who cannot tolerate or will not take oral iron, while UK professional organizations recommend a more liberal use of parenteral iron. The reason for these disparate recommendations is that few high-quality studies comparing oral to parenteral iron have been conducted in developed countries, and the potential impact of parental iron treatment on obstetric and perinatal outcomes remains unclear. We propose the first randomized-controlled trial in the United States describing the effectiveness and safety of treating pregnant women with iron-deficiency anemia with a protocol including parenteral iron compared with a protocol based on oral iron.

Detailed Description
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Iron deficiency is the most common cause of anemia in pregnancy worldwide, and, when severe, can have serious consequences for mothers and babies. In the U.S., anemia affects nearly 20% of pregnancies and the majority is iron-deficiency anemia. Therefore, treatment of iron-deficiency anemia with iron supplementation is recommended.1 However, there is controversy about the treatment strategies. The American College of Obstetrics and Gynecology recommends oral iron supplementation for iron-deficiency anemia in pregnancy, with parental iron reserved only for the rare patient who cannot tolerate or will not take oral iron (1) Conversely, guidelines from the U.K. are more liberal on the use of parental iron for the treatment of iron-deficiency anemia in pregnancy (2). Both treatment guidelines are based on limited data regarding the risks and benefits of parental iron for treatment of iron-deficiency anemia in pregnancy. The majority of randomized trials were conducted in developing country settings. In fact, few high-quality studies have been conducted in developed countries, and none has been conducted in the U.S. Moreover, there is limited data from prior studies on the impact of parental iron treatment on perinatal outcomes. The most recent Cochrane review including mostly from trials conducted in low-income countries found that, although parenteral iron improved hemoglobin levels and iron stores than the oral route, no clinical outcomes were assessed and there were insufficient data on adverse effects (3). The authors concluded that large, good quality trials, assessing clinical outcomes including adverse effects … are required (3). This randomized controlled trial aims to assess the effectiveness and safety of treating pregnant women with iron-deficiency anemia with a protocol including parenteral iron compared with a protocol based on oral iron. We hypothesize that treating iron-deficiency anemia with parental iron is associated with improved maternal and neonatal outcomes compared with a protocol based on oral iron. To increase generalizability of the findings, we will use broad inclusion criteria and analyze data using the intention-to-treat principle.

Official Title
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Intravenous Iron for Iron-deficiency Anemia in Pregnancy: a Randomized Controlled Trial

Conditions
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Iron Deficiency Anemia of Pregnancy, Iron Malabsorption

Intervention / Treatment
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* Drug: Iron dextran
* Drug: Ferrous sulfate 325mg


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Iron-deficiency anemia (serum ferritin <30 micrograms, normal hemoglobin electrophoresis, and hemoglobin <10 mg/dL), planned delivery at Barnes-Jewish Hospital Exclusion Criteria: Non-iron-deficiency anemia, multiple gestation, prenatally diagnosed major fetal anomalies, known aneuploidy, planned delivery at other hospital, inability to obtain consent
Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: All participants at less than 28 weeks gestation will have an anemia evaluation and work up per standard prenatal care. Those who meet a clinical diagnosis of iron-deficiency anemia will initiate oral iron and have their CBC rechecked between 24 and 28 weeks gestation. If their hemoglobin is less than 10 mg/dL, they will be randomized to either continue their oral iron supplementation or receive a single intravenous dextran iron transfusion. If the patient is enrolled after 28 weeks and receives a diagnosis of iron deficiency anemia, she will be randomized at that time.
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intravenous iron dextran infusion<br>Women randomized to receive intravenous iron infusion will receive a single infusion of dextran 1000mg IV as an inpatient on the antepartum or Labor & Delivery Unit. They will receive continuous fetal monitoring for 30 minutes before and after the infusion as well for the duration of the infusion | Drug: Iron dextran<br>* Single intravenous infusion of iron dextran 1000mg.<br>* Other names: Experimental;|
| Active Comparator: Oral ferrous sulfate supplementation<br>Women randomized to continue oral iron will continue to take ferrous sulfate 325mg one to three tablets daily, with the final dose at the discretion of the patient's obstetric provider. | Drug: Ferrous sulfate 325mg<br>* Oral iron supplementation with ferrous sulfate 325mg one to three times daily<br>* Other names: Active comparator;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maternal outcome: hemoglobin on admission to inpatient obstetrics unit for delivery of infant | Hemoglobin | On admission to inpatient obstetrics unit for delivery of infant | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Medication Adverse events [Safety and Tolerability] | Research assistants will contact all patients receiving iron infusions 2 days after their infusion to assess for symptoms via a telephone questionnaire. | 2 days after after iron infusion | 
| Maternal outcome: hemoglobin on postpartum day #1 | Hemoglobin | On day after participant delivered her infant (i.e. postpartum day #1) | 
| Maternal outcome: incidence of blood transfusion | Participant receiving transfusion of packed red blood cells during admission for delivery of infant obtained via medical chart review. | During inpatient admission for delivery of neonate | 
| Maternal outcome: mode of delivery | Whether infant was delivered vaginally or via cesarean section | Once, at infant delivery | 
| Neonatal outcomes: gestational age at delivery | Gestational age at delivery | Once, at infant delivery | 
| Neonatal outcomes: birth weight | Infant birth weight | Obtained once, at infant delivery | 
| Neonatal outcomes: umblical cord gases | Umbilical cord gases | Drawn once from umbilical cord segment at birth | 
| Neonatal outcomes: APGAR scores | APGAR scores. The APGAR score measures the physical condition of a newborn infant on a scale from 0 to 10 by adding points (2, 1, or 0) for heart rate, respiratory effort, muscle tone, response to stimulation, and skin color. | Obtained at 1 minute and 5 minutes of life | 
| Neonatal outcomes: neonatal hemoglobin | Neonatal hemoglobin | Drawn once from umbilical cord segment at birth | 
| Neonatal outcomes: neonatal morbidity composite | Neonatal morbidity composite, defined by the occurrence of one or more of the following neonatal morbidities: neonatal seizures, intraventricular hemorrhage, hypoxic-ischemic encephalopathy, neonatal hypothermic therapy, sepsis, respiratory distress syndrome, hyperbilirubinemia requiring photo therapy, birth injury, or meconium aspiration syndrome, NICU admission | At birth | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Iron Deficiency Anemia of Pregnancy, oral iron supplementation, parenteral iron supplementation, maternal anemia