Parenteral iron therapy in children with iron deficiency anemia

Iron deficiency anemia(IDA)continues to be a global public health problem.Oral iron is the universally accepted first-line therapy,and most children have a prompt and favorable response to oral formulations.In subsets of children who fail to respond due to intolerance,poor adherence,or inadequate intestinal absorption,parenteral iron is indicated.Despite numerous studies in adults with IDA of diverse etiologies,pediatric studies on parenteral iron use are very limited.Although mostly retrospective and small,these studies have documented the efficacy and safety profile of intravenous iron formulations.In this editorial the author comments on the most important published data and underscores the need to seriously consider parenteral iron use in children unresponsive to oral therapy.

Iron-Deficiency Anemia Management in Gynecological Surgery: A Review of Current Evidence and Best Practices

Purpose: Due to the high prevalence of iron deficiency anemia in women undergoing gynecological surgeries and its association with worse postoperative results, it is necessary to identify and treat anemia preoperatively. However, although anemia and iron deficiency are significant global health problems, there are still disparities in the recognition and implementation of “Patient Blood Management” (PBM) as a comprehensive approach to mitigating the risks associated with these diseases. The purpose of the study is to review best practices for the treatment of anemia based on the Enhanced Recovery After Surgery (ERAS) protocol and PBM recommendations. Methods: This study reviewed the literature on preoperative iron deficiency anemia in patients undergoing gynecological surgery. We identified references through searches in PubMed using relevant search terms. Results: Among the various strategies used in PBM, perhaps the most important is the early detection and management of anemia. In gynecological surgery, there are several approaches to reducing perioperative blood loss, highlighting the use of gonadotropin-releasing hormone (GnRH) agonists (aGnRh) and antifibrinolytics. Oral and intravenous iron supplementation can be performed in addition to blood transfusion to treat anemia. Conclusion: Addressing preoperative and postoperative anemia through systematic correction, following the guidelines of the ERAS protocol and PBM guidelines, is essential to improving perioperative outcomes in women undergoing gynecological surgery.

Role of iron deficiency anemia in inflammatory bowel disease

Inflammatory bowel disease(IBD)is a relapsing chronic inflammatory disorder of the small and large gut with rising incidence and prevalence worldwide.Iron deficiency anemia is one of the most common extraintestinal manifestations of IBD,which correlates with the disease activity and tendency to relapse even after successful management.Anemia affects various aspects of quality of life,such as physical,cognitive,emotional,and workability,as well as healthcare costs.The anemia in IBD can be due to iron deficiency(ID)or chronic disease.The relative frequency of ID in IBD is 60%,according to some studies,and only 14%receive treatment.The evaluation of ID is also tricky as ferritin,being an inflammatory marker,also rises in chronic inflammatory diseases like IBD.The review of anemia in IBD patients involves other investigations like transferrin saturation and exploration of other nutritional deficiencies to curb the marker asthenia with which these patients often present.It underscores the importance of timely investigation and treatment to prevent long-term sequelae.We can start oral iron therapy in certain circumstances.Still,as inflammation of the gut hampers iron absorption,an alternative route to bypass the inflamed gut is usually recommended to avoid the requirement for blood transfusions.

Inpatient management of iron deficiency anemia in pediatric patients with inflammatory bowel disease: A single center experience

BACKGROUND Screening for iron deficiency anemia(IDA)is important in managing pediatric patients with inflammatory bowel disease(IBD).Concerns related to adverse reactions may contribute to a reluctance to prescribe intravenous(IV)iron to treat IDA in this population.AIM To track the efficacy and safety of IV iron therapy in treating IDA in pediatric IBD patients admitted to our center.METHODS A longitudinal observational cohort study was performed on 236 consecutive pediatric patients admitted to our tertiary IBD care center between September 2017 and December 2019.92 patients met study criteria for IDA,of which 57 received IV iron,17 received oral iron,and 18 were discharged prior to receiving iron therapy.RESULTS Patients treated with IV iron during their hospitalization experienced a significant increase of 1.9(±0.2)g/dL in mean(±SE)hemoglobin(Hb)concentration by the first ambulatory follow-up,compared to patients who received oral iron 0.8(±0.3)g/dL or no iron 0.8(±0.3)g/dL(P=0.03).One out of 57(1.8%)patients that received IV iron therapy experienced an adverse reaction.CONCLUSION Our findings demonstrate that treatment with IV iron therapy is safe and efficacious in improving Hb and iron levels in pediatric patients with IDA and active IBD.

Efficacy and Safety of Iron Isomaltoside Compared with an Oral Iron Supplement in the Management of Patients with Iron Deficiency Anemia

Objective: To evaluate the treatment outcome of iron isomaltoside compared with an oral iron supplement in the management of iron deficiency anemia (IDA). Methods: The study included patients with IDA who visited the Outpatient Clinic of the Department of Hematology, the Affiliated Hospital of Qingdao University from October 2021 to August 2022 and met the inclusion and exclusion criteria. According to the actual application of iron supplementation, the patients were divided into two groups: iron isomaltoside treatment group and oral iron treatment group. Baseline measurements were collected before the start of treatment, and measurements were collected subsequently at intervals of 1 week, 1 month, and 3 months. The hematological parameters analyzed included Hemoglobin (Hb), Mean corpuscular hemoglobin (MCH), Mean Hemoglobin content (MCH), Mean corpuscular Hemoglobin concentration (MCHC), and Platelet (Plt). Safety data and adverse event profiles were recorded. Results: Intra-group comparisons: After 1 month of treatment, the Hb significantly improved (P 0.05). Inter-group comparisons: The biochemical parameters were significantly improved (P 0.05) in the iron isomaltoside group compared with those in the oral iron group after 1 month of iron supplementation in patients with mild and moderate anemia. Adverse reactions were tolerable for the patients in both iron isomaltoside group and oral iron group. Only 1 patient in iron isomaltoside group developed anaphylactic shock during medication and recovered after aggressive rescue. Conclusions: Iron isomaltoside which increases Hb more rapidly compared with the oral iron supplementation has few adverse reactions and good acceptance.

Treatment of iron deficiency anemia associated with gastrointestinal tract diseases

The gastrointestinal (GI) tract is a common site of bleeding that may lead to iron deficiency anemia (IDA). Treatment of IDA depends on severity and acuity of patients’ signs and symptoms. While red blood cell transfusions may be required in hemodynamically unstable patients, transfusions should be avoided in chronically anemic patients due to their potential side effects and cost. Iron studies need to be performed after episodes of GI bleeding and stores need to be replenished before anemia develops. Oral iron preparations are efficacious but poorly tolerated due to non-absorbed iron-mediated GI side effects. However, oral iron dose may be reduced with no effect on its efficacy while decreasing side effects and patient discontinuation rates. Parenteral iron therapy replenishes iron stores quicker and is better tolerated than oral therapy. Serious hypersensitive reactions are very rare with new intravenous preparations. While data on worsening of inflammatory bowel disease (IBD) activity by oral iron therapy are not conclusive, parenteral iron therapy still seems to be advantageous in the treatment of IDA in patients with IBD, because oral iron may not be sufficient to overcome the chronic blood loss and GI side effects of oral iron which may mimic IBD exacerbation. Finally, we believe the choice of oral vs parenteral iron therapy in patients with IBD should primarily depend on acuity and severity of patients’ signs and symptoms.

A guide to diagnosis of iron deficiency and iron deficiency anemia in digestive diseases

Iron deficiency （ID）, with or without anemia, is often caused by digestive diseases and should always be investigated, except in very specific situations, as its causes could be serious diseases, such as cancer. Diagnosis of ID is not always easy. Low serum levels of ferritin or transferrin saturation, imply a situation of absolute or functional ID. It is sometimes difficult to differentiate ID anemia from anemia of chronic diseases, which can coexist. In this case, other parameters, such as soluble transferrin receptor activity can be very useful. After an initial evaluation by clinical history, urine analysis, and serological tests for celiac disease, gastroscopy and colonoscopy are the key diagnostic tools for investigating the origin of ID, and will detect the most important and prevalent diseases. If both tests are normal and anemia is not severe, treatment with oral iron can be indicated, along with stopping any treatment with non-steroidal anti-inflammatory drugs. In the absence of response to oral iron, or if the anemia is severe or clinical suspicion of important disease persists, we must insist on diagnostic evaluation. Repeat endoscopic studies should be considered in many cases and if both still show normal results, investigating the small bowel must be considered. The main techniques in this case are capsule endoscopy, followed by

Role of small bowel capsule endoscopy in the diagnosis and management of iron deficiency anemia in elderly: A comprehensive review of the current literature

Iron deficiency anemia(IDA)is common and often under recognized problem in the elderly.It may be the result of multiple factors including a bleeding lesion in the gastrointestinal tract.Twenty percent of elderly patients with IDA have a negative upper and lower endoscopy and two-thirds of these have a lesion in the small bowel(SB).Capsule endoscopy(CE)provides direct visualization of entire SB mucosa,which was not possible before.It is superior to push enteroscopy,enteroclysis and barium radiography for diagnosing clinically significant SB pathology resulting in IDA.Angioectasia is one of the commonest lesions seen on the CE in elderly with IDA.The diagnostic yield of CE for IDA progressively increases with advancing age,and is highest among patients over 85 years of age.Balloon assisted enteroscopy is used to treat the lesions seen on CE.CE has some limitations mainly lack of therapeutic capability,inability to provide precise location of the lesion and false positive results.Overall CE is a very safe and effective procedure for the evaluation of IDA in elderly.

Electrophysiological changes of autonomic cells in left ventricular outflow tract in guinea pigs with iron deficiency anemia complicated with chronic heart failure

Objective: To investigate the electrophysiological changes of autonomic cells in left ventricular outflow tract in guinea pigs with iron deficiency anemia complicated with chronic heart failure.Methods: Guinea pigs model of iron deficiency anemia complicated with chronic heart failure in 10 guinea pigs of the experimental group was made by feeding a low iron diet,pure water and subcutaneous injection of isoproterenol. The control group consisting of 11 guinea pigs was given normal food, normal water and injected with normal saline. The left ventricular outflow tract model specimen was also prepared. The standard microelectrode technique was used to observe electrophysiological changes of autonomic cells in the outflow tract of left ventricular heart failure complicated with iron deficiency anemia in guinea pig model. The indicators of observation were maximal diastolic potential, action potential amplitude, 0 phase maximal depolarization velocity, 4 phase automatic depolarization velocity, repolarization 50% and 90%, and spontaneous discharge frequency.Results: Compared with the control group, 4 phase automatic depolarization velocity,spontaneous discharge frequency and 0 phase maximal depolarization velocity decreased significantly(P < 0.01) and action potential amplitude reduced(P < 0.01) in model group. Moreover, repolarization 50% and 90% increased(P < 0.01).Conclusions: There are electrophysiological abnormalities of the left ventricular outflow tract in guinea pigs with iron deficiency anemia complicated with heart failure.

Iron deficiency anemia in inflammatory bowel disease

Anemia is a common extraintestinal manifestation of inflammatory bowel disease(IBD) and is frequently overlooked as a complication. Patients with IBD are commonly found to have iron deficiency anemia(IDA) secondary to chronic blood loss, and impaired iron absorption due to tissue inflammation. Patients with iron deficiency may not always manifest with signs and symptoms; so, hemoglobin levels in patients with IBD must be regularly monitored for earlier detection of anemia. IDA in IBD is associated with poor quality of life, necessitating prompt diagnosis and appropriate treatment. IDA is often associated with inflammation in patients with IBD. Thus, commonly used labora-tory parameters are inadequate to diagnose IDA, and newer iron indices, such as reticulocyte hemoglobin content or percentage of hypochromic red cells or zinc protoporphyrin, are required to differentiate IDA from anemia of chronic disease. Oral iron preparations are available and are used in patients with mild disease activity. These preparations are inexpensive and con-venient, but can produce gastrointestinal side effects, such as abdominal pain and diarrhea, that limit their use and patient compliance. These preparations are partly absorbed due to inflammation. Non-absorbed iron can be toxic and worsen IBD disease activity. Although cost-effective intravenous iron formulations are widely available and have improved safety profiles, physicians are reluctant to use them. We present a review of the pathophysiologic mechanisms of IDA in IBD, improved diagnostic and therapeutic strategies, efficacy, and safety of iron replacement in IBD.

Effects of H pylori therapy on erythrocytic and iron parameters in iron deficiency anemia patients with H pylori-positive chronic gastristis

AIM： To elucidate the influences of Hpylori infection on oral iron treatment for iron deficiency anemia （IDA）.METHODS： A total of 86 patients were divided into two groups： group A, receiving ferrous succinate combined with triple therapy for H pylori eradication, and group B （control）, treated with ferrous succinate only. During treatment of IDA, dynamic changes in hemoglobin （Hb） level, mean corpuscular volume （MCV）, mean corpuscular hemoglobin （MCH）, serum iron （SI）, and serum ferritin （SF） were compared between the groups.RESULTS： Hb was slightly higher in group A at d 14 alter the start of triple therapy for H pylori eradication （P 〉 0.05）. After the therapy, the increase of Hb in group A became significantly faster than that in group B （P 〈 0.05）. At d 56, the mean Hb in group A returned to the normal level, however, in group B, it was lower than that in group A （P 〈 0.05） although it had also increased compared with that before oral iron treatment. The MCV and MCH in group A recovered to the normal level, and were much higher than those in group B （P 〈 0.05） at d 21. In Group B, the MCV and MCH remained at lower than normal levels until d 42 alter the start of therapy. And then, they reached a plateau in both groups and the differences disappeared （P 〉 0.05）. The SF in group A was higher than that in group B （P 〈 0.05） 28 d alter the treatment and its improvement was quicker in group A （P 〈 0.05）, and the difference between the two groups was even more significant （P 〈 0.01） at d 56. The SI in group A was higher than that in group B （P 〈 0.05） at d 14 and this persisted until d 56 when the follow-up of this research was finished.CONCLUSION： Treatment of H pylori can enhance the efficacy of ferrous succinate therapy in IDA patients with Hpylori-positive chronic gastritis.

Iron deficiency anemia in celiac disease

Iron is an important micronutrient that may be depleted in celiac disease. Iron deficiency and anemia may complicate well-established celiac disease,but may also be the presenting clinical feature in the absence of diarrhea or weight loss. If iron deficiency anemia occurs,it should be thoroughly evaluated,even if celiac disease has been defined since other superimposed causes of iron deficiency anemia may be present. Most often,impaired duodenal mucosal uptake of iron is evident since surface absorptive area in the duodenum is reduced,in large part,because celiac disease is an immune-mediated disorder largely focused in the proximal small intestinal mucosa. Some studies have also suggested that blood loss may occur in celiac disease,sometimes from superimposed small intestinal disorders,including ulceration or neoplastic diseases,particularly lymphoma. In addition,other associated gastric or colonic disorders may be responsible for blood loss. Rarely,an immune-mediated hemolytic disorder with increased urine iron loss may occur that may respond to a gluten-free diet. Reduced expression of different regulatory proteins critical in iron uptake has also been defined in the presence and absence of anemia. Finally,other rare causes of microcytic anemia may occur in celiac disease,including a sideroblastic form of anemia reported to have responded to a gluten-free diet.

A new iron free treatment with oral fish cartilage polysaccharide for iron deficiency chronic anemia in inflammatory bowel diseases:A pilot study

AIM： To investigate the effect of a new oral preparation, highly concentrated in fish cartilage, in a group of inflammatory bowel diseases （IBD） patients with chronic iron deficient anemia. METHODS： In an open label pilot study, we supplemented a group of 25 patients （11 with Crohn＇s disease and 14 with ulcerative colitis） in stable clinical conditions and chronic anemia with a food supplement which does not contain iron but contains a standardized fraction of fish cartilage glycosaminoglycans and a mixture of antioxidants （Captafer Medestea, Turin, Italy）. Patients received 500 mg, twice a day during meals, for at least 4 mo. Patients were suggested to maintain their alimentary habit. At time 0 and after 2 and 4 too, emocrome, sideremia and ferritin were examined. Paired data were analyzed with Student＇s t test. RESULTS： Three patients relapsed during the study （2 in the 3^rd too, 1 in the 4^th too）, two patients were lost to follow up and two patients dropped out （1 for orticaria, 1 for gastric burning）. Of the remaining 18 patients, levels of serum iron started to rapidly increase within the 2^nd mo of treatment, P 〈 0.05）, whereas serum ferritin and hemoglobin needed a longer period to significantly improve their serum levels （too 4） P 〈 0.05. The product was safe, easy to administer and well tolerated by patients. CONCLUSION： These data suggest a potential new treatment for IBD patients with iron deficiency chronic anemia and warrant further larger controlled studies.

Autoimmune gastritis presenting as iron deficiency anemia in childhood

AIM: To characterize clinical, laboratorial, and histological profile of pediatric autoimmune gastritis in the setting of unexplained iron deficiency anemia investigation.

Anemia and iron deficiency in gastrointestinal and liver conditions

Iron deficiency anemia(IDA) is associated with a number of pathological gastrointestinal conditions other than inflammatory bowel disease, and also with liver disorders. Different factors such as chronic bleeding, malabsorption and inflammation may contribute to IDA. Although patients with symptoms of anemia are frequently referred to gastroenterologists, the approach to diagnosis and selection of treatment as well as follow-up measures is not standardized and suboptimal. Iron deficiency, even without anemia, can substantially impact physical and cognitive function and reduce quality of life. Therefore, regular iron status assessment and awareness of the clinical consequences of impaired iron status are critical. While the range of options for treatment of IDA is increasing due to the availability of effective and well-tolerated parenteral iron preparations, a comprehensive overview of IDA and its therapy in patients with gastrointestinal conditions is currently lacking. Furthermore, definitions and assessment of iron status lack harmonization and there is a paucity of expert guidelines on this topic. This review summarizes current thinking concerning IDA as a common co-morbidity in specific gastrointestinal and liver disorders, and thus encourages a more unified treatment approach to anemia and iron deficiency, while offering gastroenterologists guidance on treatment options for IDA in everyday clinical practice.

Gluten sensitive enteropathy in patients with iron deficiency anemia of unknown origin

AIM: To determine the prevalence of gluten sensitive enteropathy (GSE) in a large group of patients with iron deficiency anemia (IDA) of obscure origin. METHODS: In this cross-sectional study, patients with IDA of obscure origin were screened for GSE. Anti- endomysial antibody (EMA) and tissue transglutamin- ase antibody (tTG) levels were evaluated and duodenal biopsies were taken and scored according to the Marsh classification. The diagnosis of GSE was based on a positive serological test and abnormal duodenal histol- ogy. Gluten free diet (GFD) was advised for all the GSE patients. RESULTS: Of the 4120 IDA patients referred to our Hematology departments, 206 (95 male) patients were found to have IDA of obscure origin. Thirty out of 206 patients (14.6%) had GSE. The mean age of GSE pa- tients was 34.6 ± 17.03 (range 10-72 years). The female to male ratio was 1.3:1. Sixteen patients had Marsh 3,12 had Marsh 2, and 2 had Marsh 1 lesions. The sever- ity of anemia was in parallel with the severity of duode- nal lesions. Twenty-two GSE patients (73.3%) had no gastrointestinal symptoms. Fourteen GSE patients who adhered to GFD without receiving iron supplementation agreed to undergo follow up visits. After 6 mo of GFD, their mean hemoglobin levels (Hb) increased from 9.9 ± 1.6 to 12.8 ± 1.0 g/dL (P < 0.01). Interestingly, in 6 out of 14 patients who had Marsh 1/2 lesions (e.g. no villous atrophy) on duodenal biopsy, mean Hb increased from 11.0 ± 1.1 to 13.1 ± 1.0 g/dL (P < 0.01) while they did not receive any iron supplementation. CONCLUSION: There is a high prevalence (e.g. 14.6%) of GSE in patients with IDA of obscure origin. Gluten free diet can improve anemia in GSE patients who have mild duodenal lesions without villous atrophy.

Does Helicobacter pylori infection play a role in iron deficiency anemia? A meta-analysis

AIM:To perform a meta-analysis of observational studies and randomized controlled trials(RCTs)on the association between Helicobacter pylori(H.pylori)and iron deficiency anemia(IDA).METHODS:A defined search strategy was used to search Medline,Embase,the Cochrane Library,Clinical Trials,Cochrane Central Register of Controlled Trials,Premedline and Healthstar.Odds ratio(OR)was used to evaluate observational epidemiology studies,and weighted mean difference(WMD)was used to demonstrate the difference between control and intervention groups.RESULTS:Fifteen observational studies and 5 RCTs were identified and used for calculation.The pooled OR for observational studies was 2.22(95%CI:1.52-3.24,P<0.0001).The WMD for hemoglobin(HB) was 4.06 g/L(95%CI:-2.57-10.69,P=0.01),and the WMD for serum ferritin(SF)was 9.47μg/L(95%CI:-0.50-19.43,P<0.0001).Results were heterogeneous for all comparisons.CONCLUSION:This meta-analysis on observational studies suggests an association between H.pylori and IDA.In RCTs,eradication of H.pylori can improve HB and SF levels but not significantly.

Emerging causes of iron deficiency anemia refractory to oral iron supplementation

While oral iron supplementation is commonly used throughout many clinical setting,treatment with intravenous(IV) iron has historically been reserved for specific settings,such as chronic kidney disease,gynecologic issues,and anemia associated with cancer and its treatments.However,the use of IV iron has begun to gain popularity in the treatment of iron deficiency anemia(IDA) associated with two conditions that are being seen more frequently than in years past:patients who are status post gastric bypass procedure and those with inflammatory bowel disease(IBD).The Roux-en-Y procedure involves connecting a gastric pouch to the jejunum,creating a blind loop consisting of distal stomach,duodenum,and proximal jejunum that connects to the Roux limb to form a common tract.IDA occurs in 6%-50% of patients who have undergone a gastric bypass,the etiology being multifactorial.The proximal gastric pouch,the primary site of gastric acid secretion,is bypassed,resulting in a decreased ability to metabolize molecular iron.Once metabolized,most iron is absorbed in the duodenum,which is entirely bypassed.After undergoing bypass procedures,most patients significantly limit their intake of red meat,another factor contributing to post-bypass IDA.Chronic anemia occurs in approximately 1/3 of patients who suffer from IBD,and almost half of all IBD patients are iron deficient.IBD leads to IDA through multiple mechanisms,including chronic intestinal blood loss,decreased absorption capabilities of the duodenum secondary to inflammation,and an inability of many IBD patients to tolerate the side effects of oral ferrous sulfate.In this study,we reviewed the charts of all patients who received IV iron at Sylvester Comprehensive Cancer Center/University of Miami Hospital Clinic from January 2007 to May 2012.The most common indications for IV iron were for issues related to cancer and its treatment(21.9%),IBD(20.1%),and gastric bypass(15.0%).Of the 262 patients who received IV iron,230 received iron sucrose and 36 received iron dextran.While doses of 100,200,300,and 400 mg of iron sucrose were given,100 and 200 mg were by far the most common dosages used,122 and 120 times,respectively.The number of dosages of iron sucrose given ranged from 1 to 46,with a mean of 5.5 and a median of 4 doses.The average dose of iron dextran given was 870.5 mg,with 1000 mg being the most common dosage used.Most patients(22 of 36) who received iron dextran only received one dose.While patients with traditional indications for IV iron,such as gynecologic issues and kidney disease,still were represented in this study,we expect to see a continued increase in physicians using IV iron for emerging gastrointestinal indications,especially considering the increased safety of new low-molecular formulations.

γ⁃Fe2O3@carboxymethyl Cellulose as Potential Oral Nanomedicine for Iron Deficiency Anemia Treatment on Rats

Oral iron supplements such as ferrous iron salts are major treatment agents for iron deficiency anemia(IDA)due to the convenience of large dose administration and good patient compliance.However,the gastrointestinal adverse impact caused by Fe2+stimulus and low bioavailability severely impedes its therapeutic effects.In recent years,it has been found that nano iron⁃based nanoparticles with high surface⁃to⁃volume ratio and low iron ion leakage can alleviate the toxic effect and improve the gastrointestinal absorbance.For further clinical development,nano materials need to meet the pharmaceutical quality demand.Carboxymethyl cellulose(CMC)is a significant pharmaceutical ingredient applied in approved drug formulations,and polyglucosorbitol carboxymethylether(PSC)has been utilized in iron⁃based nanomedicine ferumoxytol synthesis,both of which can be firmly anchored on iron oxide by carboxyl chelation.In this work,iron oxide nanoparticles(NPs)modified with CMC were designed and synthesized,and the structure composition and physicochemical properties were distinctly characterized.Oral supplement effects on rat IDA were investigated and compared with other recently reported iron supplements including NPs modified with PSC.Results show that the oral nano iron supplement achieved the recovery of hemoglobin and serum iron level in only two weeks with high safety.The nano iron oxide modified with pharmaceutical excipients provides new potential approach for oral iron supplement available in clinics.

Single vs. Double Dose Iron Supplementation for Prevention of Iron Deficiency Anemia in Twin Pregnancy: A Randomized Controlled Clinical Trial

Introduction: It is estimated that about 18% of pregnant women suffer from iron deficiency anemia throughout their whole pregnancy. In twin pregnancy, owing to the relatively greater feto-placental requirements and greater expansion in maternal plasma volume and red cell mass, iron requirements are magnified 1.8 times compared to singleton pregnancies. However, for prevention of iron deficiency in twin pregnancy, only sparse data exist regarding the sufficiency of the standard antenatal iron supplementation dose used in singleton pregnancies to meet the increased iron demand. In this study, we investigate the effect of single and double dose iron supplementation for prevention of iron deficiency anemia in twin pregnancy. Methods: A randomized controlled clinical trial was conducted at our center in the period between February 2019 and October 2020, and included 450 eligible healthy non-anemic women aged 18 - 35 years, with twin pregnancy at 12 - 16 weeks of gestation. After informed consent, eligible women were randomized to receive either single dose 27 mg, or double dose 54 mg elemental iron supplementation. Monitoring of hemoglobin concentration was done at fixed time points during gestation: at enrollment, 24 weeks, 32 weeks and before delivery. The primary outcome of the study was the incidence of iron deficiency anemia during follow up until delivery. Results: The incidence of iron deficiency anemia in the two groups did not differ significantly between the single dose group (19.1%) and the double dose group (24.0%). In women who did not develop Iron Deficiency Anemia, hemoglobin concentration varied significantly along the different gestational ages during the follow up period. In contrast, they did not show an overall statistically significant difference in the hemoglobin concentrations between the single or double dose groups. Conclusion: This clinical trial did not demonstrate an added benefit for doubling prophylactic iron supplementation dose in non-anemic women with twin pregnancy.