Safety and Efficacy of High-Dose Intravenous Ferric Carboxymaltose for the Management of Iron Deficiency Anemia in Pregnancy: A Retrospective Study at a Tertiary Care Center in Japan

Safety and Efficacy of High-Dose Intravenous Ferric Carboxymaltose for the Management of Iron Deficiency Anemia in Pregnancy: A Retrospective Study at a Tertiary Care Center in Japan | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Safety and Efficacy of High-Dose Intravenous Ferric Carboxymaltose for the Management of Iron Deficiency Anemia in Pregnancy: A Retrospective Study at a Tertiary Care Center in Japan Hiroto Yamamoto, Kaoru Yamawaki, Mizusa Nishikiori, Kosuke Yoshihara, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8611806/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background Ferric carboxymaltose (FCM) is a novel intravenous iron formulation that allows high-dose administration in a single infusion, enabling rapid iron replenishment. Within the framework of Patient Blood Management, including perioperative strategies such as autologous blood donation, FCM represents a key strategy for correcting iron deficiency anemia during pregnancy. Although international evidence supports the use of FCM during pregnancy, clinical data from Japan remain scarce, and no systematic studies in pregnant women have been reported. Thus, we aimed to evaluate the efficacy and safety of FCM use during pregnancy in a Japanese tertiary perinatal center. Methods We retrospectively analyzed pregnant women who received intravenous FCM at least once at Niigata University Medical and Dental Hospital, which managed a total of 1,116 deliveries during the 3-year study period from January 2022 through December 2024. Clinical data were extracted from the medical records, including underlying diagnoses, total administered dose, estimated blood loss at delivery, and changes in hemoglobin (Hb) and mean corpuscular volume (MCV), as well as information on autologous blood donation. Results During the study period, 16 pregnant women received FCM. The median Hb level at the first administration was 8.4 (range: 7.1–11.1) g/dL, which increased to 10.3 g/dL at delivery (range: 8.5–12.2 g/dL). The median MCV increased from 84.5 (range: 64.3–102.4) fL to 91.0 (range: 67.8–103.8) fL. When limited to the 10 women who did not undergo autologous blood donation, both changes were statistically significant (p = 0.002, Wilcoxon signed-rank test). No maternal or neonatal adverse events related to FCM administration were observed. In a secondary analysis, among the six women who underwent autologous blood donation, five received FCM on the same day as the donation, and in three of them, donation was successfully performed twice. Notably, none of the five women had Hb levels below 10 g/dL at cesarean section. Conclusions FCM administration was effective and well tolerated in Japanese pregnant women, particularly among those with moderate to severe anemia. Combining FCM with autologous blood storage may be useful to maintain adequate Hb levels and enable multiple donations before cesarean delivery in high-risk pregnancies. Pregnancy Ferric Compounds Infusions Intravenous Anemia Iron Deficiency Blood Transfusion Autologous Hemoglobin Cesarean Section Figures Figure 1 Figure 2 Figure 3 Background Maternal anemia has been associated with an increased risk of adverse outcomes, including preterm birth, low birth weight, small-for-gestational age infants, postpartum hemorrhage, perinatal mortality, allogeneic blood transfusion, postpartum depression and impaired lactation, which further affects the well-being of both mother and child [ 1 – 6 ]. The leading cause of anemia in pregnancy is iron deficiency anemia (IDA) ༻7༽. Iron requirements increase substantially during pregnancy, particularly in the second and third trimesters, due to the expanding maternal blood volume, fetal development, and placental growth. While menstruation ceases during pregnancy, resulting in a temporary reduction in iron loss, the overall iron demand during gestation is estimated to be approximately 1000 mg for a woman weighing 55 kg ༻8༽. This far exceeds the amount of iron typically absorbed from a normal diet, especially in the later stages of pregnancy. Consequently, IDA is one of the most common medical complications during pregnancy, affecting an estimated 20–40% of pregnant women worldwide ༻9༽. Prompt and effective correction of IDA is therefore crucial to improve both maternal and neonatal health outcomes. Oral iron supplementation remains the standard first-line treatment for IDA during pregnancy. However, its use is often limited by gastrointestinal side effects, poor adherence, and delayed efficacy, especially in women with moderate to severe anemia or those requiring rapid iron repletion during the late second or third trimester. In such cases, intravenous iron formulations offer a more effective and faster alternative [ 9 ] . Ferric carboxymaltose (FCM) is a novel intravenous iron compound that allows administration of high doses in a single infusion, enabling rapid and efficient iron replenishment. Randomized controlled trials and meta-analyses from various countries have demonstrated the superiority of FCM over both oral iron and older intravenous formulations such as iron sucrose or iron polymaltose in improving hemoglobin (Hb) and ferritin levels in pregnant women [ 10 – 15 ]. FCM has also been associated with reduced fatigue, improved quality of life, and high patient satisfaction due to its convenient dosing regimen [ 16 ]. Moreover, these benefits have been observed in both high- and low-resource settings. In recent years, the comprehensive concept of Patient Blood Management (PBM) has gained international attention [ 17 ]. PBM is a patient-centered, evidence-based medical approach that regards the patient’s own blood as a vital organ and systematically manages and preserves it to optimize patient outcomes and safety ༻17༽. In obstetrics, PBM has also gained traction as a comprehensive framework that encompasses iron supplementation during pregnancy, strategies to minimize bleeding during delivery, and management of postpartum anemia. FCM represents one of the key interventions consistent with the principles of PBM and may play a central role in managing IDA during pregnancy ༻18༽. In Japan, autologous blood donation is commonly incorporated into obstetric care for high-risk pregnancies and represents a characteristic feature of perinatal care in the country. This practice is performed in accordance with national obstetric guidelines, including the Guidelines for the Management of Critical Obstetric Hemorrhage (2022) issued by the Japan Society of Obstetrics and Gynecology and the Guidelines for Autologous Blood Donation in Obstetrics (2020) issued by the Japanese Society of Autologous Blood Transfusion. In this context, optimization of maternal iron status using intravenous iron may contribute not only to anemia correction but also to the feasibility of autologous blood donation, which can otherwise exacerbate anemia. Japan has distinct perinatal management practices, particularly in the care of high-risk pregnancies. In this regard, Japan provides a unique clinical setting in which to examine the role of FCM in the management of IDA during pregnancy. Therefore, evaluating the clinical application of FCM in this local context may provide insights that are relevant to other healthcare systems with different perinatal care practices. While substantial international evidence supports the use of FCM during pregnancy [ 10 – 14 ], clinical data from Japan are extremely limited, and to the best of our knowledge, no published Japanese studies have systematically evaluated the use of FCM in pregnant women. Given the increasing need for safe and effective treatment options for maternal IDA in Japan, the clinical application of FCM warrants careful examination in the local context. The present study aimed to evaluate the efficacy and safety of FCM administration during pregnancy in a Japanese cohort and to explore its association with maternal and perinatal outcomes using real-world data from a single tertiary perinatal center. Methods To evaluate the efficacy and safety of FCM administration during pregnancy, we retrospectively analyzed pregnant women who received intravenous FCM at least once during pregnancy at Niigata University Medical and Dental Hospital over a 3-year period from January 2022 through December 2024. During this period, a total of 1116 deliveries were managed at this institution. A flow diagram illustrating patient selection and inclusion is shown in Fig. 1 . Pregnant women diagnosed with IDA who received FCM during the study period, as well as those who received FCM in combination with autologous blood donation, were included. IDA was diagnosed in routine clinical practice based on Hb levels of < 10.0 g/dL during pregnancy, and iron indices such as serum ferritin were not routinely measured. Patients with unavailable Hb data or peripartum blood loss, as well as those who delivered at other institutions, were excluded; however, no such cases were identified. FCM was administered intravenously at a dose of 500 mg once weekly, in accordance with approved dosing practices in Japan. The number of administrations was determined on an individual basis, primarily guided by Hb levels of < 10 g/dL, up to a maximum of three administrations. Safety was assessed by retrospective review of medical records for documented adverse events considered to be related to FCM administration, including infusion-related reactions and other clinically relevant treatment-related events during pregnancy and the peripartum period. Clinical data were extracted from the medical records, including the underlying diagnosis, total FCM dose administered, estimated blood loss in cesarean section and vaginal delivery cases, and changes in the Hb levels and mean corpuscular volume (MCV). The timing of Hb measurements varied according to clinical practice, but all measurements were obtained before FCM administration and at delivery. There were no missing data for the variables analyzed. All data were anonymized prior to analysis. The primary outcomes were changes in the Hb and MCV levels from the first administration of FCM to delivery. Autologous blood donation was evaluated as a secondary outcome. Statistical analyses were performed using the Wilcoxon signed-rank test with GraphPad Prism 8 (GraphPad Software, San Diego, CA), and p-values < 0.05 were considered statistically significant. Results A total of 16 pregnant women received at least one intravenous dose of FCM during the study period. The background characteristics of the patients are summarized in Table 1 . The median maternal age was 36 (range: 29–41) years, and the median gestational age at first FCM administration was 32 (range: 30–36) weeks. The indications for FCM administration included twin pregnancy (n = 6), abnormal placental location such as previa or accreta (n = 5), maternal anemia (n = 11), irregular antibodies (n = 1), and coexisting ovarian cancer (n = 1). The median Hb level at the time of first FCM administration was 8.4 (range: 7.1–11.1) g/dL, and the median MCV was 84.5 (range: 64.3–102.4) fL. At delivery, the median Hb had increased to 10.3 (range: 8.5–12.2) g/dL, and the MCV to 91.0 (range: 67.8–103.8) fL, and the median duration from the first administration of FCM to delivery was 34 (range: 7–61) days. The median estimated blood loss at delivery was 503 (range: 199–4085) mL. Cesarean section was performed in 15 cases, while one patient had a vaginal delivery. Table 1 Background characteristics of the study participants (n = 16) Variable Value Maternal age (years) 36 [29–41] Parity Nulliparous: 6, Multiparous: 10 Pre-pregnancy BMI (kg/m²) 21.6 [17.9–26.8] Gestational week at first FCM administration 32 [30–36] Days from first FCM administration to delivery (days) 34 [7–61] Diagnosis at time of administration Twin pregnancy: 6, Placenta previa/accreta: 5, Maternal anemia: 11, Irregular antibodies: 1, Ovarian cancer: 1 Hb at first FCM administration (g/dL) 8.4 [7.1–11.1] MCV at first FCM administration (fL) 84.5 [64.3–102.4] Hb at delivery (g/dL) 10.3 [8.5–12.2] MCV at delivery (fL) 91.0 [67.8–103.8] Mode of delivery Vaginal delivery: 1, Cesarean section: 15 Blood loss at delivery (mL) 503 [199–4085] Data are presented as median [range] or number of cases. Some patients had multiple indications at the time of ferric carboxymaltose administration. FCM, ferric carboxymaltose; MCV, mean corpuscular volume; Hb, hemoglobin. The treatment outcomes are summarized in Table 2 . FCM was administered once in seven cases, twice in eight cases, and thrice in one case. Autologous blood donation was performed in six cases; three patients underwent a single donation and three patients underwent two donations, whereas the remaining 10 cases did not undergo autologous donation. In all 16 cases, the median change in Hb from first administration to delivery was + 1.1 (range: − 1.1 to + 5.1) g/dL, and the median change in MCV was + 5.6 (range: − 0.6 to + 18.8) fL. Table.2 Maternal and neonatal outcomes following intravenous ferric carboxymaltose administration during pregnancy Variable Result Maternal outcomes (n = 16) Number of FCM administrations Once: 7, Twice: 8, Thrice: 1 Autologous blood donation Yes: 6 (Once: 3, Twice: 3), No: 10 Hb level at delivery (g/dL) 10.3 [8.5–12.2] MCV at delivery (fL) 91.0 [67.8–103.8] Change in Hb from first FCM to delivery (g/dL) 1.1 [–1.1–5.1] Change in MCV from first FCM to delivery (fL) 5.6 [–0.6–18.8] Adverse events None reported in all 16 cases Neonatal outcomes (n = 22) Birth weight (g) 2612 [1592–3896] Umbilical cord blood pH 7.26 [7.18–7.36] Apgar score (1 min / 5 min) 8 [ 1 – 9 ] / 9 [ 3 – 10 ] Neonatal complications Low birth weight: 8, RDS: 2, TTN: 1, Neonatal apnea: 2, Transient neonatal depression (after maternal general anesthesia): 1 Data are presented as median [range] or number of cases. Changes in hemoglobin and mean corpuscular volume were calculated from the first ferric carboxymaltose administration to delivery. Apgar scores are shown at 1 and 5 minutes. Some neonates had more than one complication. FCM, ferric carboxymaltose; Hb, hemoglobin; MCV, mean corpuscular volume; RDS, respiratory distress syndrome; TTN, transient tachypnea of the newborn. Figure 2 a and b illustrate these changes specifically in the 10 cases without autologous donation, showing statistically significant improvements (p = 0.002, Wilcoxon signed-rank test). In a subgroup analysis stratified by baseline Hb level, changes in Hb were analyzed in the 10 cases without autologous blood donation. Among patients with baseline Hb < 8 g/dL (n = 6), there was a significant increase in Hb following FCM administration (p = 0.031), whereas no significant change was observed in those with Hb ≥ 8 g/dL (n = 4, p = 0.125). The results of the subgroup analysis are shown in Fig. 3 . Importantly, no adverse events were observed in any of the 16 cases, indicating a favorable safety profile for FCM administration during pregnancy. Neonatal outcomes were generally favorable. The median birth weight was 2612 (range: 1592–3896) g, umbilical cord blood pH was 7.26 (range: 7.18–7.36), and Apgar scores at 1 and 5 min were 8 [ 1 – 9 ] and 9 [ 3 – 10 ], respectively. Neonatal complications included low birth weight (n = 8), respiratory distress syndrome (n = 2), transient tachypnea of the newborn (n = 1), neonatal apnea (n = 2), and transient neonatal depression after maternal general anesthesia (n = 1). No FCM-related neonatal complications were suspected, and most outcomes were consistent with the underlying obstetric risk factors, such as prematurity or multiple pregnancy. A total of six patients underwent autologous blood donation. Among them, five received FCM on the same day as autologous blood collection, constituting cases of autologous blood donation with FCM. The clinical characteristics and laboratory findings of these five cases are summarized in Table S1 . In three of the five cases, autologous blood donation was successfully performed twice in conjunction with FCM administration. Moreover, none of the five patients had Hb levels below 10 g/dL at the time of cesarean section ( Table S1 ). Discussion This study demonstrated the efficacy and favorable tolerability of FCM administration in Japanese pregnant women. Notably, significant improvements in Hb levels and MCV were observed following FCM administration, with no adverse events identified. In addition, a subgroup analysis showed a greater Hb response in women with lower baseline Hb levels, suggesting that FCM may be particularly effective in pregnant women with moderate to severe anemia. These findings provide preliminary evidence supporting FCM administration in a Japanese cohort and are consistent with reports from other countries, which have likewise demonstrated the rapid and effective correction of anemia in pregnant women with FCM [ 10 – 15 ]. An important aspect of this study is the combination of autologous blood donation with FCM administration. At our institution, multiple autologous blood donations are routinely performed for high-risk pregnant women, such as those with placenta previa, multiple pregnancy, or with clinically significant irregular antibodies; however, autologous blood donation is often precluded by anemia with Hb < 10 g/dL. In this study, among the five cases in which autologous blood donation was combined with FCM administration, multiple donations were successfully completed in three patients, whereas multiple donations were not planned in the remaining two cases. Notably, all five women had Hb levels ≥ 10 g/dL at the time of cesarean section. These findings suggest that FCM administration may facilitate multiple autologous blood donations and contribute to improved anemia management on the day of surgery. These results support the practical implementation of PBM in obstetrics. Within the PBM framework, correction of anemia, including iron deficiency during pregnancy, constitutes one of the key pillars, and the rapid improvement in Hb levels achieved with FCM administration in this study is consistent with this objective. In Japan, a previous study described the combined use of preoperative autologous blood donation and FCM, showing that administration of high-dose FCM following autologous blood donation significantly suppressed the progression of anemia before surgery [ 19 ], although pregnant women were not included in that study. These findings highlight the clinical utility of FCM in reducing allogeneic blood transfusion requirements and managing perioperative anemia, which is consistent with the principles of PBM. Our findings support the extension of this strategy to pregnant women and indicate that FCM is not only effective but also well tolerated in this context. The strength of this study is that it was conducted in Japanese pregnant women, a population in which clinical evidence regarding the use of FCM is lacking. Furthermore, this study demonstrated the potential of FCM administration to improve perioperative anemia in high-bleeding-risk pregnant women requiring autologous blood storage. This may potentially contribute not only to the avoidance of allogeneic blood transfusion but also to the reduction of postpartum anemia, which has been associated with adverse outcomes such as postpartum depression and failure to achieve exclusive breastfeeding [ 2 , 20 – 22 ] . However, this study has several limitations. First, the small sample size and retrospective design at a single tertiary perinatal center limit the generalizability of the findings. Only 16 pregnant women were included, and no comparison group, such as patients treated with oral iron or those receiving no iron therapy, was available. Therefore, the present study was not designed to allow direct comparisons with other anemia management strategies, and causal inferences should be interpreted with caution. In addition, potential confounding factors such as nutritional status, prior iron supplementation, and concomitant medications may not have been fully controlled. Second, long-term maternal and neonatal outcomes were not evaluated. Third, due to the lack of routine laboratory measurements, the assessment of hypophosphatemia was limited, and the evaluation of adverse effects relied primarily on clinical symptom monitoring. In addition, iron indices such as serum ferritin were not routinely measured, and IDA was assessed mainly based on Hb levels. Furthermore, the treatment regimen was not based on a standardized protocol, and the dosing and number of FCM administrations were determined on an individual basis according to clinical judgment. Although this study was conducted at a single tertiary perinatal center, the findings may be relevant to broader clinical settings. The benefits of FCM may be particularly applicable to institutions managing high-risk pregnancies requiring rapid correction of anemia, such as cases involving planned cesarean delivery, anticipated massive hemorrhage, or autologous blood donation. In contrast, in lower-risk settings where anemia can be adequately managed with oral iron and sufficient time is available before delivery, routine use of intravenous iron may be less clearly justified. Accordingly, these findings support a context-dependent application of FCM based on patient risk profiles, institutional resources, and existing anemia management strategies. Future prospective multicenter studies in Japanese pregnant women are warranted. In particular, the combination of FCM administration with autologous blood donation may represent a clinically relevant and practical strategy. Importantly, the present findings do not imply a need to modify current anemia management protocols. Instead, they suggest that intravenous FCM may represent a complementary strategy within existing clinical frameworks, particularly for high-risk pregnant women in whom rapid correction of anemia is required to facilitate autologous blood donation or optimize perioperative Hb levels. Conclusions Our findings provide supportive evidence for the efficacy and safety of FCM administration in Japanese pregnant women and shows that it may be particularly beneficial in cases of moderate to severe anemia. Moreover, the combination of FCM administration with autologous blood storage may serve as a potentially useful approach for maintaining sufficient Hb levels prior to cesarean section in women with high-risk pregnancy. Future large-scale, prospective studies are warranted to establish standardized protocols for FCM administration in pregnant women in Japan. Abbreviations FCM Ferric carboxymaltose Hb Hemoglobin IDA Iron deficiency anemia MCV Mean corpuscular volume Declarations Ethics approval and consent to participate: This study was approved by the Ethics Committee of the Niigata University School of Medicine (Approval No. 2023 − 0347). Informed consent was obtained by an opt-out approach, and all participants were provided the opportunity to decline participation. Consent for publication: Not applicable Competing interests: The authors declare that they have no competing interests. Authors' information The first author (HY) and the corresponding author (KY) are obstetricians at the Department of Obstetrics and Gynecology, Niigata University Medical and Dental Hospital, a tertiary perinatal medical center in Japan. Funding: Not applicable Author Contribution Conception and design: HY and KY. Data acquisition: HY, MN and KY. Writing of the manuscript: HY and KY. Manuscript review and revision: HY, MN, KY, KYh, and KN. Study supervision: KY and KN. All authors read and approved the final manuscript. Acknowledgements: We thank all physicians involved in the treatment of the patients included in this study. Additionally, we would like to express our gratitude to the local physicians who referred the patients to our institution. We would also like to thank Editage ( https://www.editage.com/ ) for the English language editing and reviewing. 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J Nutr. 2003;133(12):4139–42. Additional Declarations No competing interests reported. Supplementary Files FCMPregnancyJapanAdditionalfile20260115.xlsx Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. 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15:09:00","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-8611806/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-8611806/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":100930007,"identity":"d01b625e-a13f-4a53-aece-156b2a1c8ca4","added_by":"auto","created_at":"2026-01-23 00:39:25","extension":"docx","order_by":0,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":45134,"visible":true,"origin":"","legend":"","description":"","filename":"FCMPregnancyJapanMainTextv120260115.docx","url":"https://assets-eu.researchsquare.com/files/rs-8611806/v1/24397ec75e60356a10a7f236.docx"},{"id":100930014,"identity":"dcafd998-5d1c-4e79-b0ad-2d9d0916d8ea","added_by":"auto","created_at":"2026-01-23 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00:39:30","extension":"xml","order_by":10,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":72111,"visible":true,"origin":"","legend":"","description":"","filename":"9f82e14409574fce91c9a4775f7686e51structuring.xml","url":"https://assets-eu.researchsquare.com/files/rs-8611806/v1/ccdda45ef15cc665bc85e68d.xml"},{"id":100930057,"identity":"afcd9634-622b-45e6-ba52-c6e9d712aeda","added_by":"auto","created_at":"2026-01-23 00:39:27","extension":"html","order_by":11,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":81497,"visible":true,"origin":"","legend":"","description":"","filename":"earlyproof.html","url":"https://assets-eu.researchsquare.com/files/rs-8611806/v1/0034315ab053073cee47c068.html"},{"id":100929986,"identity":"3bde0be3-3e8d-42a8-b85b-dc5d5d80f9a4","added_by":"auto","created_at":"2026-01-23 00:39:23","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":19708,"visible":true,"origin":"","legend":"\u003cp\u003eFlow diagram of patient selection and analysis.\u003c/p\u003e","description":"","filename":"FCMPregnancyJapanFig120260115.png","url":"https://assets-eu.researchsquare.com/files/rs-8611806/v1/1a8116486868a20a0413e5e3.png"},{"id":100930068,"identity":"f1e58d81-627c-480f-8009-4a28e6a77b3e","added_by":"auto","created_at":"2026-01-23 00:39:28","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":54307,"visible":true,"origin":"","legend":"\u003cp\u003eChanges in hemoglobin and mean corpuscular volume following ferric carboxymaltose administration in pregnant women without autologous blood donation (n = 10).\u003c/p\u003e\n\u003cp\u003e(a) Hemoglobin levels before ferric carboxymaltose administration and at delivery.\u003c/p\u003e\n\u003cp\u003e(b) Mean corpuscular volume before ferric carboxymaltose administration and at delivery.\u003c/p\u003e\n\u003cp\u003eStatistical significance was assessed using the Wilcoxon signed-rank test.\u003c/p\u003e","description":"","filename":"FCMPregnancyJapanFig220260115.png","url":"https://assets-eu.researchsquare.com/files/rs-8611806/v1/a24c6e98b7215ee67fc9c955.png"},{"id":100929977,"identity":"fcf0daeb-b918-4b9f-b952-75d1043cbdd1","added_by":"auto","created_at":"2026-01-23 00:39:22","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":53356,"visible":true,"origin":"","legend":"\u003cp\u003eHemoglobin response to ferric carboxymaltose according to baseline anemia severity in pregnant women without autologous blood donation (n = 6).\u003cbr\u003e\n(a) Hemoglobin levels before ferric carboxymaltose administration and at delivery in women with baseline hemoglobin \u0026lt; 8 g/dL.\u003cbr\u003e\n(b) Hemoglobin levels before ferric carboxymaltose administration and at delivery in women with baseline hemoglobin ≥ 8 g/dL.\u003cbr\u003e\nStatistical significance was assessed using the Wilcoxon signed-rank test.\u003c/p\u003e","description":"","filename":"FCMPregnancyJapanFig320260115.png","url":"https://assets-eu.researchsquare.com/files/rs-8611806/v1/15a47c268a4c10e4cf89274f.png"},{"id":101669826,"identity":"bdeb2123-ffb8-4733-ba2f-e55cb1af6c04","added_by":"auto","created_at":"2026-02-02 12:26:48","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":681710,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8611806/v1/639e3613-1f8f-4ab5-bb87-eee835ea5545.pdf"},{"id":100930075,"identity":"846d77da-548c-4f58-b655-102421649912","added_by":"auto","created_at":"2026-01-23 00:39:28","extension":"xlsx","order_by":0,"title":"","display":"","copyAsset":false,"role":"supplement","size":10314,"visible":true,"origin":"","legend":"","description":"","filename":"FCMPregnancyJapanAdditionalfile20260115.xlsx","url":"https://assets-eu.researchsquare.com/files/rs-8611806/v1/1623f8ba53f17685fce25c9a.xlsx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Safety and Efficacy of High-Dose Intravenous Ferric Carboxymaltose for the Management of Iron Deficiency Anemia in Pregnancy: A Retrospective Study at a Tertiary Care Center in Japan","fulltext":[{"header":"Background","content":"\u003cp\u003eMaternal anemia has been associated with an increased risk of adverse outcomes, including preterm birth, low birth weight, small-for-gestational age infants, postpartum hemorrhage, perinatal mortality, allogeneic blood transfusion, postpartum depression and impaired lactation, which further affects the well-being of both mother and child [\u003cspan additionalcitationids=\"CR2 CR3 CR4 CR5\" citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. The leading cause of anemia in pregnancy is iron deficiency anemia (IDA) ༻7༽. Iron requirements increase substantially during pregnancy, particularly in the second and third trimesters, due to the expanding maternal blood volume, fetal development, and placental growth. While menstruation ceases during pregnancy, resulting in a temporary reduction in iron loss, the overall iron demand during gestation is estimated to be approximately 1000 mg for a woman weighing 55 kg ༻8༽. This far exceeds the amount of iron typically absorbed from a normal diet, especially in the later stages of pregnancy. Consequently, IDA is one of the most common medical complications during pregnancy, affecting an estimated 20\u0026ndash;40% of pregnant women worldwide ༻9༽. Prompt and effective correction of IDA is therefore crucial to improve both maternal and neonatal health outcomes.\u003c/p\u003e \u003cp\u003eOral iron supplementation remains the standard first-line treatment for IDA during pregnancy. However, its use is often limited by gastrointestinal side effects, poor adherence, and delayed efficacy, especially in women with moderate to severe anemia or those requiring rapid iron repletion during the late second or third trimester. In such cases, intravenous iron formulations offer a more effective and faster alternative [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e] .\u003c/p\u003e \u003cp\u003eFerric carboxymaltose (FCM) is a novel intravenous iron compound that allows administration of high doses in a single infusion, enabling rapid and efficient iron replenishment. Randomized controlled trials and meta-analyses from various countries have demonstrated the superiority of FCM over both oral iron and older intravenous formulations such as iron sucrose or iron polymaltose in improving hemoglobin (Hb) and ferritin levels in pregnant women [\u003cspan additionalcitationids=\"CR11 CR12 CR13 CR14\" citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. FCM has also been associated with reduced fatigue, improved quality of life, and high patient satisfaction due to its convenient dosing regimen [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. Moreover, these benefits have been observed in both high- and low-resource settings.\u003c/p\u003e \u003cp\u003eIn recent years, the comprehensive concept of Patient Blood Management (PBM) has gained international attention [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. PBM is a patient-centered, evidence-based medical approach that regards the patient\u0026rsquo;s own blood as a vital organ and systematically manages and preserves it to optimize patient outcomes and safety ༻17༽. In obstetrics, PBM has also gained traction as a comprehensive framework that encompasses iron supplementation during pregnancy, strategies to minimize bleeding during delivery, and management of postpartum anemia. FCM represents one of the key interventions consistent with the principles of PBM and may play a central role in managing IDA during pregnancy ༻18༽.\u003c/p\u003e \u003cp\u003eIn Japan, autologous blood donation is commonly incorporated into obstetric care for high-risk pregnancies and represents a characteristic feature of perinatal care in the country. This practice is performed in accordance with national obstetric guidelines, including the Guidelines for the Management of Critical Obstetric Hemorrhage (2022) issued by the Japan Society of Obstetrics and Gynecology and the Guidelines for Autologous Blood Donation in Obstetrics (2020) issued by the Japanese Society of Autologous Blood Transfusion. In this context, optimization of maternal iron status using intravenous iron may contribute not only to anemia correction but also to the feasibility of autologous blood donation, which can otherwise exacerbate anemia.\u003c/p\u003e \u003cp\u003eJapan has distinct perinatal management practices, particularly in the care of high-risk pregnancies. In this regard, Japan provides a unique clinical setting in which to examine the role of FCM in the management of IDA during pregnancy. Therefore, evaluating the clinical application of FCM in this local context may provide insights that are relevant to other healthcare systems with different perinatal care practices.\u003c/p\u003e \u003cp\u003eWhile substantial international evidence supports the use of FCM during pregnancy [\u003cspan additionalcitationids=\"CR11 CR12 CR13\" citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e], clinical data from Japan are extremely limited, and to the best of our knowledge, no published Japanese studies have systematically evaluated the use of FCM in pregnant women. Given the increasing need for safe and effective treatment options for maternal IDA in Japan, the clinical application of FCM warrants careful examination in the local context.\u003c/p\u003e \u003cp\u003eThe present study aimed to evaluate the efficacy and safety of FCM administration during pregnancy in a Japanese cohort and to explore its association with maternal and perinatal outcomes using real-world data from a single tertiary perinatal center.\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003eTo evaluate the efficacy and safety of FCM administration during pregnancy, we retrospectively analyzed pregnant women who received intravenous FCM at least once during pregnancy at Niigata University Medical and Dental Hospital over a 3-year period from January 2022 through December 2024. During this period, a total of 1116 deliveries were managed at this institution. A flow diagram illustrating patient selection and inclusion is shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003ePregnant women diagnosed with IDA who received FCM during the study period, as well as those who received FCM in combination with autologous blood donation, were included. IDA was diagnosed in routine clinical practice based on Hb levels of \u0026lt;\u0026thinsp;10.0 g/dL during pregnancy, and iron indices such as serum ferritin were not routinely measured. Patients with unavailable Hb data or peripartum blood loss, as well as those who delivered at other institutions, were excluded; however, no such cases were identified.\u003c/p\u003e \u003cp\u003eFCM was administered intravenously at a dose of 500 mg once weekly, in accordance with approved dosing practices in Japan. The number of administrations was determined on an individual basis, primarily guided by Hb levels of \u0026lt;\u0026thinsp;10 g/dL, up to a maximum of three administrations.\u003c/p\u003e \u003cp\u003eSafety was assessed by retrospective review of medical records for documented adverse events considered to be related to FCM administration, including infusion-related reactions and other clinically relevant treatment-related events during pregnancy and the peripartum period.\u003c/p\u003e \u003cp\u003eClinical data were extracted from the medical records, including the underlying diagnosis, total FCM dose administered, estimated blood loss in cesarean section and vaginal delivery cases, and changes in the Hb levels and mean corpuscular volume (MCV). The timing of Hb measurements varied according to clinical practice, but all measurements were obtained before FCM administration and at delivery. There were no missing data for the variables analyzed. All data were anonymized prior to analysis.\u003c/p\u003e \u003cp\u003eThe primary outcomes were changes in the Hb and MCV levels from the first administration of FCM to delivery. Autologous blood donation was evaluated as a secondary outcome. Statistical analyses were performed using the Wilcoxon signed-rank test with GraphPad Prism 8 (GraphPad Software, San Diego, CA), and p-values\u0026thinsp;\u0026lt;\u0026thinsp;0.05 were considered statistically significant.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eA total of 16 pregnant women received at least one intravenous dose of FCM during the study period. The background characteristics of the patients are summarized in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. The median maternal age was 36 (range: 29\u0026ndash;41) years, and the median gestational age at first FCM administration was 32 (range: 30\u0026ndash;36) weeks. The indications for FCM administration included twin pregnancy (n\u0026thinsp;=\u0026thinsp;6), abnormal placental location such as previa or accreta (n\u0026thinsp;=\u0026thinsp;5), maternal anemia (n\u0026thinsp;=\u0026thinsp;11), irregular antibodies (n\u0026thinsp;=\u0026thinsp;1), and coexisting ovarian cancer (n\u0026thinsp;=\u0026thinsp;1). The median Hb level at the time of first FCM administration was 8.4 (range: 7.1\u0026ndash;11.1) g/dL, and the median MCV was 84.5 (range: 64.3\u0026ndash;102.4) fL. At delivery, the median Hb had increased to 10.3 (range: 8.5\u0026ndash;12.2) g/dL, and the MCV to 91.0 (range: 67.8\u0026ndash;103.8) fL, and the median duration from the first administration of FCM to delivery was 34 (range: 7\u0026ndash;61) days. The median estimated blood loss at delivery was 503 (range: 199\u0026ndash;4085) mL. Cesarean section was performed in 15 cases, while one patient had a vaginal delivery.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eBackground characteristics of the study participants (n\u0026thinsp;=\u0026thinsp;16)\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"2\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVariable\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eValue\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMaternal age (years)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e36 [29\u0026ndash;41]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eParity\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNulliparous: 6, Multiparous: 10\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePre-pregnancy BMI (kg/m\u0026sup2;)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e21.6 [17.9\u0026ndash;26.8]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGestational week at first FCM administration\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e32 [30\u0026ndash;36]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDays from first FCM administration to delivery (days)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e34 [7\u0026ndash;61]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDiagnosis at time of administration\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eTwin pregnancy: 6, Placenta previa/accreta: 5, Maternal anemia: 11, Irregular antibodies: 1, Ovarian cancer: 1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHb at first FCM administration (g/dL)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e8.4 [7.1\u0026ndash;11.1]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMCV at first FCM administration (fL)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e84.5 [64.3\u0026ndash;102.4]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHb at delivery (g/dL)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e10.3 [8.5\u0026ndash;12.2]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMCV at delivery (fL)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e91.0 [67.8\u0026ndash;103.8]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMode of delivery\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eVaginal delivery: 1, Cesarean section: 15\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBlood loss at delivery (mL)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e503 [199\u0026ndash;4085]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eData are presented as median [range] or number of cases. Some patients had multiple indications at the time of ferric carboxymaltose administration. FCM, ferric carboxymaltose; MCV, mean corpuscular volume; Hb, hemoglobin.\u003c/p\u003e \u003cp\u003eThe treatment outcomes are summarized in \u003cb\u003eTable\u0026nbsp;2\u003c/b\u003e. FCM was administered once in seven cases, twice in eight cases, and thrice in one case. Autologous blood donation was performed in six cases; three patients underwent a single donation and three patients underwent two donations, whereas the remaining 10 cases did not undergo autologous donation. In all 16 cases, the median change in Hb from first administration to delivery was +\u0026thinsp;1.1 (range: \u0026minus;\u0026thinsp;1.1 to +\u0026thinsp;5.1) g/dL, and the median change in MCV was +\u0026thinsp;5.6 (range: \u0026minus;\u0026thinsp;0.6 to +\u0026thinsp;18.8) fL.\u003c/p\u003e \u003cp\u003eTable.2 Maternal and neonatal outcomes following intravenous ferric carboxymaltose administration during pregnancy\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"No\" id=\"Taba\" border=\"1\"\u003e \u003ccolgroup cols=\"2\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVariable\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eResult\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMaternal outcomes (n\u0026thinsp;=\u0026thinsp;16)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNumber of FCM administrations\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eOnce: 7, Twice: 8, Thrice: 1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAutologous blood donation\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eYes: 6 (Once: 3, Twice: 3), No: 10\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHb level at delivery (g/dL)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e10.3 [8.5\u0026ndash;12.2]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMCV at delivery (fL)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e91.0 [67.8\u0026ndash;103.8]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eChange in Hb from first FCM to delivery (g/dL)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.1 [\u0026ndash;1.1\u0026ndash;5.1]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eChange in MCV from first FCM to delivery (fL)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5.6 [\u0026ndash;0.6\u0026ndash;18.8]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAdverse events\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNone reported in all 16 cases\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eNeonatal outcomes (n\u0026thinsp;=\u0026thinsp;22)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBirth weight (g)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2612 [1592\u0026ndash;3896]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUmbilical cord blood pH\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7.26 [7.18\u0026ndash;7.36]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eApgar score (1 min / 5 min)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e8 [\u003cspan additionalcitationids=\"CR2 CR3 CR4 CR5 CR6 CR7 CR8\" citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e] / 9 [\u003cspan additionalcitationids=\"CR4 CR5 CR6 CR7 CR8 CR9\" citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNeonatal complications\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eLow birth weight: 8, RDS: 2, TTN: 1, Neonatal apnea: 2, Transient neonatal depression (after maternal general anesthesia): 1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eData are presented as median [range] or number of cases. Changes in hemoglobin and mean corpuscular volume were calculated from the first ferric carboxymaltose administration to delivery. Apgar scores are shown at 1 and 5 minutes. Some neonates had more than one complication. FCM, ferric carboxymaltose; Hb, hemoglobin; MCV, mean corpuscular volume; RDS, respiratory distress syndrome; TTN, transient tachypnea of the newborn.\u003c/p\u003e \u003cp\u003eFigure \u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003ea \u003cb\u003eand b\u003c/b\u003e illustrate these changes specifically in the 10 cases without autologous donation, showing statistically significant improvements (p\u0026thinsp;=\u0026thinsp;0.002, Wilcoxon signed-rank test).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eIn a subgroup analysis stratified by baseline Hb level, changes in Hb were analyzed in the 10 cases without autologous blood donation. Among patients with baseline Hb\u0026thinsp;\u0026lt;\u0026thinsp;8 g/dL (n\u0026thinsp;=\u0026thinsp;6), there was a significant increase in Hb following FCM administration (p\u0026thinsp;=\u0026thinsp;0.031), whereas no significant change was observed in those with Hb\u0026thinsp;\u0026ge;\u0026thinsp;8 g/dL (n\u0026thinsp;=\u0026thinsp;4, p\u0026thinsp;=\u0026thinsp;0.125). The results of the subgroup analysis are shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eImportantly, no adverse events were observed in any of the 16 cases, indicating a favorable safety profile for FCM administration during pregnancy.\u003c/p\u003e \u003cp\u003eNeonatal outcomes were generally favorable. The median birth weight was 2612 (range: 1592\u0026ndash;3896) g, umbilical cord blood pH was 7.26 (range: 7.18\u0026ndash;7.36), and Apgar scores at 1 and 5 min were 8 [\u003cspan additionalcitationids=\"CR2 CR3 CR4 CR5 CR6 CR7 CR8\" citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e] and 9 [\u003cspan additionalcitationids=\"CR4 CR5 CR6 CR7 CR8 CR9\" citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e], respectively. Neonatal complications included low birth weight (n\u0026thinsp;=\u0026thinsp;8), respiratory distress syndrome (n\u0026thinsp;=\u0026thinsp;2), transient tachypnea of the newborn (n\u0026thinsp;=\u0026thinsp;1), neonatal apnea (n\u0026thinsp;=\u0026thinsp;2), and transient neonatal depression after maternal general anesthesia (n\u0026thinsp;=\u0026thinsp;1). No FCM-related neonatal complications were suspected, and most outcomes were consistent with the underlying obstetric risk factors, such as prematurity or multiple pregnancy.\u003c/p\u003e \u003cp\u003eA total of six patients underwent autologous blood donation. Among them, five received FCM on the same day as autologous blood collection, constituting cases of autologous blood donation with FCM. The clinical characteristics and laboratory findings of these five cases are summarized in \u003cb\u003eTable \u003cspan refid=\"MOESM1\" class=\"InternalRef\"\u003eS1\u003c/span\u003e\u003c/b\u003e. In three of the five cases, autologous blood donation was successfully performed twice in conjunction with FCM administration. Moreover, none of the five patients had Hb levels below 10 g/dL at the time of cesarean section (\u003cb\u003eTable \u003cspan refid=\"MOESM1\" class=\"InternalRef\"\u003eS1\u003c/span\u003e\u003c/b\u003e).\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThis study demonstrated the efficacy and favorable tolerability of FCM administration in Japanese pregnant women. Notably, significant improvements in Hb levels and MCV were observed following FCM administration, with no adverse events identified. In addition, a subgroup analysis showed a greater Hb response in women with lower baseline Hb levels, suggesting that FCM may be particularly effective in pregnant women with moderate to severe anemia. These findings provide preliminary evidence supporting FCM administration in a Japanese cohort and are consistent with reports from other countries, which have likewise demonstrated the rapid and effective correction of anemia in pregnant women with FCM [\u003cspan additionalcitationids=\"CR11 CR12 CR13 CR14\" citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eAn important aspect of this study is the combination of autologous blood donation with FCM administration. At our institution, multiple autologous blood donations are routinely performed for high-risk pregnant women, such as those with placenta previa, multiple pregnancy, or with clinically significant irregular antibodies; however, autologous blood donation is often precluded by anemia with Hb\u0026thinsp;\u0026lt;\u0026thinsp;10 g/dL. In this study, among the five cases in which autologous blood donation was combined with FCM administration, multiple donations were successfully completed in three patients, whereas multiple donations were not planned in the remaining two cases. Notably, all five women had Hb levels\u0026thinsp;\u0026ge;\u0026thinsp;10 g/dL at the time of cesarean section. These findings suggest that FCM administration may facilitate multiple autologous blood donations and contribute to improved anemia management on the day of surgery.\u003c/p\u003e \u003cp\u003eThese results support the practical implementation of PBM in obstetrics. Within the PBM framework, correction of anemia, including iron deficiency during pregnancy, constitutes one of the key pillars, and the rapid improvement in Hb levels achieved with FCM administration in this study is consistent with this objective. In Japan, a previous study described the combined use of preoperative autologous blood donation and FCM, showing that administration of high-dose FCM following autologous blood donation significantly suppressed the progression of anemia before surgery [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e], although pregnant women were not included in that study. These findings highlight the clinical utility of FCM in reducing allogeneic blood transfusion requirements and managing perioperative anemia, which is consistent with the principles of PBM. Our findings support the extension of this strategy to pregnant women and indicate that FCM is not only effective but also well tolerated in this context.\u003c/p\u003e \u003cp\u003eThe strength of this study is that it was conducted in Japanese pregnant women, a population in which clinical evidence regarding the use of FCM is lacking. Furthermore, this study demonstrated the potential of FCM administration to improve perioperative anemia in high-bleeding-risk pregnant women requiring autologous blood storage. This may potentially contribute not only to the avoidance of allogeneic blood transfusion but also to the reduction of postpartum anemia, which has been associated with adverse outcomes such as postpartum depression and failure to achieve exclusive breastfeeding [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan additionalcitationids=\"CR21\" citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e] .\u003c/p\u003e \u003cp\u003eHowever, this study has several limitations. First, the small sample size and retrospective design at a single tertiary perinatal center limit the generalizability of the findings. Only 16 pregnant women were included, and no comparison group, such as patients treated with oral iron or those receiving no iron therapy, was available. Therefore, the present study was not designed to allow direct comparisons with other anemia management strategies, and causal inferences should be interpreted with caution. In addition, potential confounding factors such as nutritional status, prior iron supplementation, and concomitant medications may not have been fully controlled. Second, long-term maternal and neonatal outcomes were not evaluated. Third, due to the lack of routine laboratory measurements, the assessment of hypophosphatemia was limited, and the evaluation of adverse effects relied primarily on clinical symptom monitoring. In addition, iron indices such as serum ferritin were not routinely measured, and IDA was assessed mainly based on Hb levels. Furthermore, the treatment regimen was not based on a standardized protocol, and the dosing and number of FCM administrations were determined on an individual basis according to clinical judgment.\u003c/p\u003e \u003cp\u003eAlthough this study was conducted at a single tertiary perinatal center, the findings may be relevant to broader clinical settings. The benefits of FCM may be particularly applicable to institutions managing high-risk pregnancies requiring rapid correction of anemia, such as cases involving planned cesarean delivery, anticipated massive hemorrhage, or autologous blood donation. In contrast, in lower-risk settings where anemia can be adequately managed with oral iron and sufficient time is available before delivery, routine use of intravenous iron may be less clearly justified. Accordingly, these findings support a context-dependent application of FCM based on patient risk profiles, institutional resources, and existing anemia management strategies.\u003c/p\u003e \u003cp\u003eFuture prospective multicenter studies in Japanese pregnant women are warranted. In particular, the combination of FCM administration with autologous blood donation may represent a clinically relevant and practical strategy. Importantly, the present findings do not imply a need to modify current anemia management protocols. Instead, they suggest that intravenous FCM may represent a complementary strategy within existing clinical frameworks, particularly for high-risk pregnant women in whom rapid correction of anemia is required to facilitate autologous blood donation or optimize perioperative Hb levels.\u003c/p\u003e"},{"header":"Conclusions","content":"\u003cp\u003eOur findings provide supportive evidence for the efficacy and safety of FCM administration in Japanese pregnant women and shows that it may be particularly beneficial in cases of moderate to severe anemia. Moreover, the combination of FCM administration with autologous blood storage may serve as a potentially useful approach for maintaining sufficient Hb levels prior to cesarean section in women with high-risk pregnancy. Future large-scale, prospective studies are warranted to establish standardized protocols for FCM administration in pregnant women in Japan.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cdiv class=\"DefinitionList\"\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eFCM\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eFerric carboxymaltose\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eHb\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eHemoglobin\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eIDA\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eIron deficiency anemia\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eMCV\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eMean corpuscular volume\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003c/div\u003e"},{"header":"Declarations","content":" \u003cp\u003e \u003cstrong\u003eEthics approval and consent to participate:\u003c/strong\u003e \u003cp\u003e This study was approved by the Ethics Committee of the Niigata University School of Medicine (Approval No. 2023\u0026thinsp;\u0026minus;\u0026thinsp;0347). Informed consent was obtained by an opt-out approach, and all participants were provided the opportunity to decline participation.\u003c/p\u003e \u003cp\u003e \u003cstrong\u003eConsent for publication:\u003c/strong\u003e \u003cp\u003eNot applicable\u003c/p\u003e \u003ch2\u003eCompeting interests:\u003c/h2\u003e \u003cp\u003eThe authors declare that they have no competing interests.\u003c/p\u003e \u003ch2\u003eAuthors' information\u003c/h2\u003e \u003cp\u003eThe first author (HY) and the corresponding author (KY) are obstetricians at the Department of Obstetrics and Gynecology, Niigata University Medical and Dental Hospital, a tertiary perinatal medical center in Japan.\u003c/p\u003e \u003ch2\u003eFunding:\u003c/h2\u003e \u003cp\u003eNot applicable\u003c/p\u003e\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eConception and design: HY and KY. Data acquisition: HY, MN and KY. Writing of the manuscript: HY and KY. Manuscript review and revision: HY, MN, KY, KYh, and KN. Study supervision: KY and KN. All authors read and approved the final manuscript.\u003c/p\u003e\u003ch2\u003eAcknowledgements:\u003c/h2\u003e \u003cp\u003eWe thank all physicians involved in the treatment of the patients included in this study. Additionally, we would like to express our gratitude to the local physicians who referred the patients to our institution. We would also like to thank Editage (\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://www.editage.com/\u003c/span\u003e\u003cspan address=\"https://www.editage.com/\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e) for the English language editing and reviewing.\u003c/p\u003e\u003ch2\u003eData Availability\u003c/h2\u003e\u003cp\u003eData supporting the findings of this study are available upon request from the corresponding authors. The data are not publicly available because of privacy and ethical restrictions.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eAzami M, Badfar G, Khalighi Z, Qasemi P, Shohani M, Soleymani A, et al. The association between anemia and postpartum depression: A systematic review and meta-analysis. Casp J Intern Med. 2019;10(2):115\u0026ndash;24.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHorie S, Nomura K, Takenoshita S, Nakagawa J, Kido M, Sugimoto M. A relationship between a level of hemoglobin after delivery and exclusive breastfeeding initiation at a baby friendly hospital in Japan. Environ Health Prev Med. 2017;22(1):40.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKloka JA, Friedrichson B, Jasny T, Old O, Piekarski F, Zacharowski K, et al. Anemia, red blood cell transfusion and administration of blood products in obstetrics: a nationwide analysis of more than 6 million cases from 2011\u0026ndash;2020. Blood Transfus. 2024;22(1):37\u0026ndash;45.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLao TT, Wong LL, Hui SYA, Sahota DS. Iron Deficiency Anaemia and Atonic Postpartum Haemorrhage Following Labour. Reprod Sci. 2022;29(4):1102\u0026ndash;10.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLone FW, Qureshi RN, Emanuel F. Maternal anaemia and its impact on perinatal outcome. Trop Med Int Health. 2004;9(4):486\u0026ndash;90.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eYoung MF, Oaks BM, Rogers HP, Tandon S, Martorell R, Dewey KG, et al. Maternal low and high hemoglobin concentrations and associations with adverse maternal and infant health outcomes: an updated global systematic review and meta-analysis. BMC Pregnancy Childbirth. 2023;23(1):264.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePasricha SR, Tye-Din J, Muckenthaler MU, Swinkels DW. Iron deficiency. Lancet. 2021;397(10270):233\u0026ndash;48.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBothwell TH. Iron requirements in pregnancy and strategies to meet them. Am J Clin Nutr. 2000;72(1 Suppl):S257\u0026ndash;64.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePercy L, Mansour D, Fraser I. Iron deficiency and iron deficiency anaemia in women. Best Pract Res Clin Obstet Gynecol. 2017;40:55\u0026ndash;67.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGupte S, Mukhopadhyay A, Puri M, Gopinath PM, Wani R, Sharma JB et al. A meta-analysis of ferric carboxymaltose versus other intravenous iron preparations for the management of iron deficiency anemia during pregnancy. Rev Bras Ginecol Obstet. 2024;46.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eJose A, Mahey R, Sharma JB, Bhatla N, Saxena R, Kalaivani M, et al. Comparison of ferric Carboxymaltose and iron sucrose complex for treatment of iron deficiency anemia in pregnancy- randomised controlled trial. BMC Pregnancy Childbirth. 2019;19(1):54.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePasricha SR, Moya E, Ataide R, Mzembe G, Harding R, Mwangi MN, et al. Ferric carboxymaltose for anemia in late pregnancy: a randomized controlled trial. Nat Med. 2025;31(1):197\u0026ndash;206.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eShim JY, Kim MY, Kim YJ, Lee Y, Lee JJ, Jun JK, et al. Efficacy and safety of ferric carboxymaltose versus ferrous sulfate for iron deficiency anemia during pregnancy: subgroup analysis of Korean women. BMC Pregnancy Childbirth. 2018;18(1):349.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTrivedi P, Chitra S, Natarajan S, Amin V, Sud S, Vyas P, et al. Ferric Carboxymaltose in the Management of Iron Deficiency Anemia in Pregnancy: A Subgroup Analysis of a Multicenter Real-World Study Involving 1191 Pregnant Women. Obstet Gynecol Int. 2022;2022:5759740.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eVanobberghen F, Lweno O, Kuemmerle A, Mwebi KD, Asilia P, Issa A, et al. Efficacy and safety of intravenous ferric carboxymaltose compared with oral iron for the treatment of iron deficiency anaemia in women after childbirth in Tanzania: a parallel-group, open-label, randomised controlled phase 3 trial. Lancet Glob Health. 2021;9(2):e189\u0026ndash;98.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eVan Wyck DB, Mangione A, Morrison J, Hadley PE, Jehle JA, Goodnough LT. Large-dose intravenous ferric carboxymaltose injection for iron deficiency anemia in heavy uterine bleeding: a randomized, controlled trial. Transfusion. 2009;49(12):2719\u0026ndash;28.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eShander A, Hardy JF, Ozawa S, Farmer SL, Hofmann A, Frank SM, et al. A Global Definition of Patient Blood Management. Anesth Analg. 2022;135(3):476\u0026ndash;88.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSurbek D, Vial Y, Girard T, Breymann C, Bencaiova GA, Baud D, et al. Patient blood management (PBM) in pregnancy and childbirth: literature review and expert opinion. Arch Gynecol Obstet. 2020;301(2):627\u0026ndash;41.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eIkeda T, Terada R, Nagura Y, Okazaki H. High-dose intravenous iron supplementation after preoperative autologous blood donation is useful to prevent post-donation/preoperative anemia. Transfus Apher Sci. 2022;61(3):103348.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMaeda Y, Ogawa K, Morisaki N, Tachibana Y, Horikawa R, Sago H. Association between perinatal anemia and postpartum depression: A prospective cohort study of Japanese women. Int J Gynecol Obstet. 2020;148(1):48\u0026ndash;52.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eOhsuga T, Egawa M, Kii M, Ikeda Y, Ueda A, Chigusa Y, et al. Association between non-anemic iron deficiency in early pregnancy and perinatal mental health: A retrospective pilot study. J Obstet Gynaecol Res. 2022;48(11):2730\u0026ndash;7.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCorwin EJ, Murray-Kolb LE, Beard JL. Low hemoglobin level is a risk factor for postpartum depression. J Nutr. 2003;133(12):4139\u0026ndash;42.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Pregnancy, Ferric Compounds, Infusions, Intravenous, Anemia, Iron Deficiency, Blood Transfusion, Autologous, Hemoglobin, Cesarean Section","lastPublishedDoi":"10.21203/rs.3.rs-8611806/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8611806/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eFerric carboxymaltose (FCM) is a novel intravenous iron formulation that allows high-dose administration in a single infusion, enabling rapid iron replenishment. Within the framework of Patient Blood Management, including perioperative strategies such as autologous blood donation, FCM represents a key strategy for correcting iron deficiency anemia during pregnancy. Although international evidence supports the use of FCM during pregnancy, clinical data from Japan remain scarce, and no systematic studies in pregnant women have been reported. Thus, we aimed to evaluate the efficacy and safety of FCM use during pregnancy in a Japanese tertiary perinatal center.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eWe retrospectively analyzed pregnant women who received intravenous FCM at least once at Niigata University Medical and Dental Hospital, which managed a total of 1,116 deliveries during the 3-year study period from January 2022 through December 2024. Clinical data were extracted from the medical records, including underlying diagnoses, total administered dose, estimated blood loss at delivery, and changes in hemoglobin (Hb) and mean corpuscular volume (MCV), as well as information on autologous blood donation.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eDuring the study period, 16 pregnant women received FCM. The median Hb level at the first administration was 8.4 (range: 7.1\u0026ndash;11.1) g/dL, which increased to 10.3 g/dL at delivery (range: 8.5\u0026ndash;12.2 g/dL). The median MCV increased from 84.5 (range: 64.3\u0026ndash;102.4) fL to 91.0 (range: 67.8\u0026ndash;103.8) fL. When limited to the 10 women who did not undergo autologous blood donation, both changes were statistically significant (p\u0026thinsp;=\u0026thinsp;0.002, Wilcoxon signed-rank test). No maternal or neonatal adverse events related to FCM administration were observed. In a secondary analysis, among the six women who underwent autologous blood donation, five received FCM on the same day as the donation, and in three of them, donation was successfully performed twice. Notably, none of the five women had Hb levels below 10 g/dL at cesarean section.\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e \u003cp\u003eFCM administration was effective and well tolerated in Japanese pregnant women, particularly among those with moderate to severe anemia. Combining FCM with autologous blood storage may be useful to maintain adequate Hb levels and enable multiple donations before cesarean delivery in high-risk pregnancies.\u003c/p\u003e","manuscriptTitle":"Safety and Efficacy of High-Dose Intravenous Ferric Carboxymaltose for the Management of Iron Deficiency Anemia in Pregnancy: A Retrospective Study at a Tertiary Care Center in Japan","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-01-23 00:38:47","doi":"10.21203/rs.3.rs-8611806/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"7a0c7a0b-d9ad-4921-a601-211ce9c7856f","owner":[],"postedDate":"January 23rd, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2026-02-02T12:25:46+00:00","versionOfRecord":[],"versionCreatedAt":"2026-01-23 00:38:47","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8611806","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8611806","identity":"rs-8611806","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}