Safety and Efficacy of Ferric Carboxymaltose in Anemic Pregnant Women: A Retrospective Case Control Study

Safety and Efficacy of Ferric Carboxymaltose in Anemic Pregnant Women: A Retrospective Case Control Study Anouk Pels and Wessel Ganzevoort Department of Obstetrics and Gynecology, Academisch Medisch Centrum, Meibergdreef 9, 1105 AZ Amsterdam, Netherlands Received 6 August 2015; Revised 8 November 2015; Accepted 10 November 2015 Academic Editor: Enrique Hernandez Copyright © 2015 Anouk Pels and Wessel Ganzevoort. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Abstract Background. Anemia during pregnancy is commonly caused by iron deficiency and can have severe consequences for both the mother and the developing fetus. The aim of this retrospective study was to assess the safety and efficacy of intravenous ferric carboxymaltose (FCM) in pregnant women. Methods. All women treated with FCM for anemia during pregnancy between 2010 and 2012 at our institution were included. A matched control group was selected, including women who either were nonanemic or had anemia but were not considered for intravenous iron. Main outcome measures were maternal safety and pregnancy outcomes. Results. The study included 128 patients (FCM: 64; control: 64). Median FCM dose was 1000 mg and median gestational age at the time of first treatment was 34 weeks and 6 days. Median Hb increased from 8.4 g/dL (interquartile range 7.7; 8.9 g/dL) at the first FCM administration to 10.7 g/dL (9.8; 11.5 g/dL; <glyph.data ascent="3443" descent="-2856" horiz-adv-x="512" vert-adv-y="512"></glyph.data><glyph.data ascent="3443" descent="-2856" horiz-adv-x="611" vert-adv-y="611"></glyph.data><glyph.data ascent="3443" descent="-2856" horiz-adv-x="487" vert-adv-y="487"></glyph.data><glyph.data ascent="3443" descent="-2856" horiz-adv-x="487" vert-adv-y="487"></glyph.data> with available Hb at delivery) at the time of delivery, achieving levels similar to those in the control group (10.8 g/dL [9.8; 11.8 g/dL; <glyph.data ascent="3443" descent="-2856" horiz-adv-x="512" vert-adv-y="512"></glyph.data><glyph.data ascent="3443" descent="-2856" horiz-adv-x="611" vert-adv-y="611"></glyph.data><glyph.data ascent="3443" descent="-2856" horiz-adv-x="487" vert-adv-y="487"></glyph.data><glyph.data ascent="3443" descent="-2856" horiz-adv-x="487" vert-adv-y="487"></glyph.data>]). No treatment-related adverse events were reported and no statistically significant differences in pregnancy outcomes were observed between groups. Conclusions. Within the limitations of this case control study, FCM was a safe and efficient treatment of anemia during pregnancy. 1. Introduction Iron deficiency anemia is a prevalent condition during pregnancy and may result from different factors [1]. Many women have low or empty iron stores already at the start of pregnancy. A large French study, which included a total of 6648 women, showed depleted iron stores (serum ferritin <15 μg/L) in one out of five women (22.7%) of childbearing age [2]. During pregnancy, the physiological need for absorbed iron increases from 0.8 mg/day in the first trimester to 7.5 mg/day in the third trimester [3]. Dietary iron intake does not compensate for this strongly increased iron demand. Consequently, the risk of iron deficiency and, ultimately, iron deficient anemia increases during pregnancy. General symptoms of anemia are fatigue, dizziness, and impaired immune response predisposing to infections [4]. Anemia during pregnancy is associated with increased morbidity and mortality of pregnant women and their developing fetuses [5]. Iron deficiency anemia has been shown to be associated with an increased risk of premature birth and low birth weight [6], preeclampsia [7], placental abruption, and increased peripartum blood loss [8] as well as cardiac failure and related death [9–11]. In pregnant women, oral iron is often used for prophylaxis of iron deficiency and is recommended as first-line treatment for pregnant women with iron deficiency anemia [12]. However, oral iron substitution has shown to be insufficient for the treatment of severe iron deficiency anemia and is often associated with gastrointestinal side effects [13]. Therefore, guidelines recommend that physicians consider intravenous (i.v.) iron administration in pregnant women with severe iron deficiency anemia (Hb < 9.0 g/dL), and in case of intolerability to oral iron as well, insufficient Hb increase after oral iron treatment or if there is a need for rapid Hb reconstitution [12–14]. Intravenous (i.v.) iron preparations provide greater and more rapid repletion of iron stores than oral iron therapy without the gastrointestinal side effects associated with oral substitution [13]. Ferric carboxymaltose (FCM) is an i.v. iron formulation which can be used at high doses and allows rapid administration (up to 1000 mg in a single dose infused in 15 min). Because it is free of dextran and its derivatives, FCM does not cross-react with dextran antibodies [15, 16] and never needed the administration of a test dose. More recently, the European Medicines Agency (EMA) concluded that no test dose should apply to i.v. iron products authorized in the European Union; yet staff and facilities to evaluate and manage anaphylactic or anaphylactoid reactions should be immediately available [17]. The FCM molecules consist of an iron-hydroxide core chelated in a carbohydrate shell and this complex is taken up as a whole by macrophages, leading to very low levels of non-transferrin bound iron, avoiding iron toxicity and oxidative stress [16]. FCM’s clinical efficacy and safety have been proven in several large clinical studies across different indications with up to one-year follow-up in severe disease types such as chronic kidney disease and chronic heart failure [18–28]. At least four postpartum studies compared the safety and efficacy of FCM versus oral iron [26–29]. Faster and greater Hb-responses were achieved in FCM-treated patients compared to those receiving oral iron and FCM replenished iron stores efficiently. Rather few studies or cases with limited numbers of FCM-treated pregnant women have been reported [30–33]. A recently completed study comparing FCM and oral iron in pregnant women with iron deficiency anemia (ClinicalTrials.gov NCT01131624) has not been reported yet. The aim of this retrospective case control study was to assess the efficacy of i.v. FCM in pregnant women. 2. Materials and Methods2.1. Study Design and Patients Data for this retrospective case control study were obtained from the electronic patient charts of the Department of Obstetrics and Gynecology of the Academisch Medisch Centrum in Amsterdam, Netherlands. The study design has been reviewed by the Medical Ethical Committee of the Academisch Medisch Centrum and it was confirmed that an official approval of this study by the committee is not required, since the Medical Rese (...truncated)