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

Phase 4

Completed

Conditions: Iron Malabsorption
Iron Deficiency Anemia of Pregnancy

Interventions: Drug: Ferrous sulfate 325mg
Drug: Iron dextran

Registration Number: NCT03438227

Lead Sponsor: Indiana University

Brief Summary: 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 United Kingdom 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: 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 United States, 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 United Kingdom. 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 United States 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.

Recruitment & Eligibility

Status: COMPLETED

Sex: Female

Target Recruitment: 38

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Oral ferrous sulfate supplementation	Ferrous sulfate 325mg	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.
Intravenous iron dextran infusion	Iron dextran	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

Primary Outcome Measures

Name	Time	Method
Maternal Anemia at Delivery	At delivery	Number of participants with maternal hemoglobin \<11g/dl at delivery

Secondary Outcome Measures

Name	Time	Method
Number of Participants With Medication Adverse Events	2 - 3 days after single intravenous iron infusion or initiation of oral iron	Participants reporting symptoms when contacted by via telephone 2 - 3 days after their infusion of intravenous iron or initiation of oral iron
Maternal Hemoglobin at Delivery	On admission to inpatient obstetrics unit for delivery	Maternal hemoglobin on admission to inpatient obstetrics unit for delivery
Maternal Ferritin at Delivery	At delivery	Maternal serum ferritin level in μg/L at delivery
Number of Participants Who Received Blood Transfusion	During inpatient admission for delivery of neonate	Participant receiving transfusion of packed red blood cells during admission for delivery of infant obtained via medical chart review.
Birth Weight	Obtained once, at infant delivery	Neonatal weight at delivery
Maternal Hemoglobin Below 10g/dl at Delivery	At delivery	Number of participants with hemoglobin below 10g/dl at delivery
Mode of Delivery	Once, at infant delivery	Whether infant was delivered vaginally or via cesarean section
Gestational Age at Delivery	Once, at infant delivery	Gestational age in weeks at delivery
Umbilical Cord Arterial pH	Drawn once from umbilical cord segment at delivery	Umbilical cord arterial pH obtained at delivery
Neonatal Hemoglobin	Drawn once from umbilical cord segment at birth	Neonatal hemoglobin in g/dl at delivery
Composite Neonatal Morbidity (Defined by the Occurrence of One or More of 10 Neonatal Morbidities.	At birth	Neonatal morbidity composite, defined by the occurrence of one or more of the following neonatal morbidities: neonatal seizures (diagnosed by clinician), intraventricular hemorrhage (diagnosed by clinician on brain MRI or Ultrasound), hypoxic-ischemic encephalopathy (diagnosed by clinician), neonatal hypothermic therapy (brain cooling as documented on inpatient record, sepsis (diagnosed by blood culture), respiratory distress syndrome (diagnosed by clinician), hyperbilirubinemia requiring photo therapy (diagnosed by clinician), birth injury (diagnosed by clinician), or meconium aspiration syndrome (diagnosed by clinician), neonatal intensive care unit admission (documented in the inpatient record).
Neonatal Ferritin	Drawn once from umbilical cord segment at birth	Neonatal ferritin in ug/L at delivery
APGAR Scores at 1 Minutes of Life	Obtained at 1 minute of life	The APGAR score, named after the Virginia Apgar, pediatrician who came up with it, measures the physical condition of a newborn infant on a scale ranging from a minimum of 0 (worsts) to a maximum of 10 (best).

Trial Locations

Locations (2): Indiana University School of Medicine
🇺🇸
Indianapolis, Indiana, United States
Center for Outpatient Health, Washington University in St. Louis
🇺🇸
Saint Louis, Missouri, United States