Intravenous iron isomaltoside versus oral iron supplementation for treatment of iron deficiency in pregnancy: protocol for a randomised, comparative, open-label trial

Abstract

Background: Iron deficiency is common in pregnancy. If left untreated, iron deficiency can lead to iron deficiency anaemia, which is a condition related to maternal and neonatal morbidity. The prevalence of iron deficiency increases through the trimesters, which means that women with iron deficiency in the beginning of pregnancy also have a great risk of developing iron deficiency anaemia during pregnancy. Standard treatment is oral iron in individualised intensified doses based on screening values in 1st trimester. Maternal symptoms of iron deficiency and iron deficiency anaemia include fatigue, reduced physical performance, and restless legs syndrome (RLS). Severe anaemia may cause dizziness, dyspnea, palpitation, orthostatism, and syncope, and it decreases the woman's ability to cope with blood loss during delivery. The anaemia may also compromise contractility in the uterine musculature increasing the risk for prolonged labour, caesarean section, and postpartum haemorrhage. Foetal iron deficiency may cause low birthweight and adversely affect foetal and early childhood brain development with long-term deficits. Methods: In this randomised comparative, open-label, single-centre, phase IV trial, 200 pregnant women between 14 and 21 weeks of gestation who have iron deficiency after 4 weeks of standard treatment will be randomised 1:1 to either a single 1000 mg dose of intravenously administered ferric derisomaltose/iron isomaltoside 1000 or a fixed dose of 100 mg oral ferrous fumarate containing 60 mg ascorbic acid. The primary endpoint is to prevent iron deficiency anaemia defined by a low level of haemoglobin throughout the trial. Other endpoints include other haematological indices of iron deficiency and anaemia, clinical outcomes by questionnaires, and collection of adverse events. Explorative endpoints by medical record follow-up include complications up to 7 days after delivery.

Clinical efficacy of polysaccharide iron complex plus vitamin C in the treatment of iron deficiency anemia in pregnancy and their effect on iron metabolism

“…Secondly, with continuous decrease of iron content, significant decline of erythropoiesis brings out more and more obvious signs and symptoms of anemia in pregnant women, with typical clinical symptoms such as pallor, weakness, easy fatigue, dizziness, shortness of breath, and abnormal nails (pale, thin and flat nails) [11]. Finally, following severe iron deficiency, hematopoietic functions of bone marrow of pregnant women is hampered, resulting in shrunken red blood cell volume and severely reduced hemoglobin amount, characterized by clinical concomitant symptoms such as abdominal pain and diarrhea [12]. Prolonged persistence of severe iron deficiency anemia in pregnancy is associated with postpartum complications (e.g., puerperal infections, postpartum hemorrhage, perineal pain, breast problems, and postpartum depression.)…”

Expert consensus guidelines: Intravenous iron uses, formulations, administration, and management of reactions

“…Administration of IV iron is generally avoided prior to the 13th week of gestation due to a lack of safety data. There is no difference in the administration of IV iron compared with the non‐pregnant person, and all IV iron formulations above have been shown to be safe and effective in pregnancy 21,45–47 . Fetal monitoring during or following IV iron administration is not required and the authors recommend against it.…”

Iron deficiency anemia in pregnancy

“…Blood transfusions are reserved for severely anemic pregnant patients with active bleeding, hemodynamically instability, and signs of cardiac decompensation [12 ▪▪ ,75]. Red cell alloimmunization, infection and allergic reactions, although minor, pose additional consequences for women of childbearing age.…”

“…Ferric derisomaltose, composed of iron hydroxide and derisomaltose, was approved by the FDA in 2020 [75,76]. In clinical trials conducted in nonpregnant adults, efficacy was comparable to iron sucrose.…”