Iron Salts, High Levels of Hemoglobin and Ferritin in Pregnancy, and Development of Gestational Diabetes: A Systematic Review / Sais de ferro, níveis elevados de hemoglobina e ferritina na gravidez e o desenvolvimento de diabetes gestacional: Uma revisão sistemática

Abstract Objective The aim of this study was to systematically review literature on the use of iron supplements (not including iron derived from diet), increased levels of hemoglobin and/or ferritin, and the risk of developing gestational diabetes mellitus (GDM). Data source The following databases were searched, from the study's inception to April 2021: PUBMED, Cochrane, Web of Science, Scopus, Embase, Cinahl and Lilacs. Selection of studies A total of 6,956 titles and abstracts were reviewed, 9 of which met the final inclusion criteria, with 7,560 women in total. Data collection Data extraction was performed by two independent reviewers and disagreements were resolved by a third researcher. Data synthesis Methodological quality in controlled trials were assessed according to the Cochrane Collaboration tools (ROB-2 and ROBINS-1) and for the observational studies, the National Institutes of Health's (NIH) quality assessment tool was used. Among the 5 observational studies, women with a higher hemoglobin or ferritin level were more likely to develop GDM when compared with those with lower levels of these parameters. Among the 3 randomized clinical trials, none found a significant difference in the incidence of GDM among women in the intervention and control groups. However, we identified many risks of bias and great methodological differences among them. Conclusion Based on the studies included in this review, and due to the important methodological problems pointed out, more studies of good methodological quality are needed to better establish the association between iron supplementation and GDM.

Resumo Objetivo O objetivo deste estudo foi revisar sistematicamente a literatura sobre o uso de suplementos de ferro (não incluindo o ferro derivado da dieta), aumento dos níveis de hemoglobina e/ou ferritina e o risco de desenvolver diabetes mellitus gestacional (DMG). Fontes dos dados as bases de dados PUBMED, Cochrane, Web of Science, Scopus, Embase, Cinahl e Lilacs foram pesquisadas até abril de 2021. Seleção dos estudos Foram revisados 6.956 títulos e resumos, dos quais 9 preencheram os critérios finais de inclusão, totalizando 7.560 mulheres. Coleta de dados A extração de dados foi realizada por dois revisores independentes e as divergências foram resolvidas por um terceiro revisor. Síntese dos dados A qualidade metodológica dos ensaios controlados foi avaliada de acordo com as ferramentas da Colaboração Cochrane (ROB-2 e ROBINS-1) e para os estudos observacionais, foi utilizada a ferramenta de avaliação de qualidade do National Institutes of Health (NIH). Entre os 5 estudos observacionais, as mulheres com maiores níveis de hemoglobina ou ferritina apresentaram maior probabilidade de desenvolver DMG quando comparadas àquelas com níveis mais baixos nesses parâmetros. Entre os 3 ensaios clínicos randomizados, nenhum deles encontrou diferença significativa na incidência de DMG entre as mulheres dos grupos de intervenção e controle. No entanto, identificamos muitos riscos de viés e enormes diferenças metodológicas entre eles. Conclusão Com base nos estudos incluídos nesta revisão e devido aos importantes problemas metodológicos apontados, são necessários mais estudos de boa qualidade metodológica para melhor estabelecer a associação entre suplementação de ferro e DMG.

Association between iron intake from different sources and risk of gestational diabetes mellitus： a retrospective cohort study / 上海预防医学

ObjectiveTo explore the association between total iron， iron supplements， dietary total iron， heme iron intake and the risk of gestational diabetes mellitus（GDM）. MethodsA total of 668 pregnant women who gave birth in one hospital in Shanghai during January 2020 to July 2021 were included in a retrospective cohort study. Baseline characteristics and data of iron supplements in second trimester were collected through a questionnaire. A simplified dietary frequency questionnaire was used to quantify the food intake in second trimester. Total iron， iron supplements， dietary total iron， and heme iron intake was classified into groups by quintile and median. The association between iron intake from different sources and risk of GDM was determined using logistic regression analysis. ResultsAfter correction for age， family history of diabetes， overweight / obesity before pregnancy， hemoglobin（Hb）in first trimester， energy， carbohydrate energy， protein， and free sugar， it showed no association between total iron intake and risk of GDM （P>0.05）， while elevated risk of GDM among women with high iron supplements intake （OR=1.65； 95%CI： 1.14‒2.39）， and decreased risk of GDM among those with high dietary total iron intake （OR=0.53； 95%CI： 0.35‒0.81）. However， no association was found between heme iron intake and risk of GDM （P>0.05）. ConclusionHigh dietary total iron intake may be a protective factor， while high iron supplements may be a risk factor for GDM. It suggests that pregnant women should carefully choose high-dose iron-containing supplements in the absence of iron deficiency， as dietary iron intake should be the priority.

Development and Validation of a Questionnaire to Predict Intention to Comply to Iron Supplement during Pregnancy

@#Introduction The World Health Organisation (WHO) has recommended iron supplementation to overcome anaemia in pregnancy. In Malaysia, half of pregnant women with anaemia do not comply to iron supplement. The purpose of this study is to develop, assess psychometric properties (via Exploratory Factor Analysis) and validation (via Confirmatory Factor Analysis) of a questionnaire that evaluates attitude towards adherence to iron supplement based on Theory of Planned Behaviour (TPB). Methods Based on the guidelines for construction of the TPB based questionnaire, 18 items were created initially by using the findings from a semi-quantitative survey, literature reviews and experts’ opinion. From content validity by 3 experts, 15 items with content validity ratio (CVR) of ≥0.99 were retained. From a pilot test for exploratory factor analysis (EFA), total of 12 items were retained, and classified into 3 components and termed as “Attitude”, “Subjective Norms” and “Perceived Behaviour Control”. Results Cronbach Alpha for the 12 items was 0.814, and for each component were 0.844, 0.813 and 0.901 respectively, which indicates acceptable internal consistency. During the Confirmatory Factor Analysis (CFA), a final 10 items were retained. Conclusions The construct validity was good where the Fitness Index have achieved the threshold (p-value >0.05, RMSEA <0.08, CFI >0.90 and the ChiSq/df ratio <3.00). The convergent validity and composite reliability were good i.e. Average Variance Extracted (AVE) ≥0.50, and Composite Reliability (CR) ≥0.60 respectively. As a conclusion, this newly developed questionnaire was validated and potentially reliable in assessing attitude and predicting adherence to iron supplement among pregnant women specifically in Malaysia.

Efficacy and Safety of Jianpi Shengxue Granule Alone or Combined with Iron Supplement versus Iron Supplement Alone in the Treatment of Iron Deficiency Anemia in Children ：A Meta-analysis / 中国药房

OBJECTIVE： To systematically review the efficacy and safety of Jianpi shengxue granule alone or combined with iron supplement versus iron supplement alone in the treatment of iron deficiency anemia in children， and to provide evidence-based reference for iron deficiency anemia in children. METHODS： Retrieved from PubMed， Embase， Medline， Scifinder， Cochrane library， CJFD， VIP and Wanfang database during database establishment to Nov. 2018， RCT about efficacy and safety of Jianpi shengxue granule alone or combined with iron supplement （trial group） versus iron supplement alone （control group） in the treatment of iron deficiency anemia in children were collected. After the data were extracted from clinical studies that met the inclusion criteria， and the quality was evaluated with Cochrane System Evaluator Manual 5.1.0， Meta-analysis was conducted by using Rev Man 5.3 statistical software for total response rate， cure rate， the levels of hemoglobin （HB）， mean corpuscular volume （MCV）， mean corpuscular hemoglobin （MCH）， serum iron （SI）， serum ferritin （SF） elevation， the incidence of ADR. RESULTS： Totally 19 RCTs were enrolled， involving 2 259 patients. Results of Meta-analysis showed that total response rate [OR＝6.73， 95％CI （4.68， 9.68）， P＜0.001]， cure rate [OR＝2.51， 95％CI （2.06，3.06）， P＜0.001]， HB increased levels [MD＝8.91， 95％CI （6.13，11.68）， P＜0.001]， MCV increased levels [MD＝9.13， 95％CI （5.32，12.95）， P＜0.001]， MCH increased levels [MD＝2.95， 95％CI （1.75，4.15）， P＜0.001]， SI increased levels [MD＝3.66， 95％CI （2.77， 4.55）， P＜0.001]， SF increased levels [MD＝10.82， 95％CI （9.18，12.45）， P＜0.001] and the incidence of ADR [OR＝0.49， 95％CI （0.33，0.71）， P＝0.000 2] in trial group were all better than control group， with statistical significance. CONCLUSIONS： Jianpi shengxue granule alone or combined with iron supplement versus iron supplement alone can improve total response rate， cure rate， the levels of HB， MCV， MCH， SI and SF in children with iron deficiency anemia， and also decrease the incidence of ADR.

Altered Biodistribution of (99m)Tc-DPD on Bone Scan After Intravenous Iron Supplement / 대한핵의학회잡지

We report a casewith altered biodistribution of (99m)Tc-dicarboxypropane diphosphonate ((99m)Tc-DPD) on whole body bone scan after intravenous iron supplement therapy. A 47-year-old male patient who had recently been detected with a hepatic mass suggestive of hepatocellular carcinoma underwent bone scan as staging work-up before surgery. Bone scan images at 3 h after injection of (99m)Tc-DPD demonstrated unusually increased blood pool activities in the heart, liver, and spleen with usual skeletal uptakes. The patient had been treated for severe anemia from hemorrhoid with two intravenous administration of ferric hydroxide carboxymaltose complex at approximately 22 h and 2 h prior to the (99m)Tc-DPD injection, which we consider as themost probable cause of altered biodistribution of (99m)Tc-DPD.

Studies on the preparation, properties of alginate-iron (III) complex / 中国药学杂志

OBJECTIVE: To study preparation technology and properties of a new kind of iron-supplement of alginate-iron (III) complex. METHODS: The preparation parameters of polysaccharide iron (III) complex with sodium alginate and ferric trichloride were optimized by means of the single factor and response surface design. Alginate-iron (III) complex was characterized by IR and DSC. Its reducibility and drug release percentage were determined in simulated gastrointestinal liquid. RESULTS: Optimum condition follows; alginate sodium to ferric trichloride with mass ratio of 1:3.2 and alginate sodium to sodium citrate with mass ratio of 1:1.4, which were reacted in pH 6.95 of reaction liquid and at 80℃ of water bath lasting for 3. 29 h and generated alginate-iron (III) complex with the 19.57% of iron content. The IR and DSC indicated that the hydroxyl groups of alginate was combined with Fe(III). The alginate-iron (III) complex could be dissolved and reduced easily by vitamin C in physiological pH conditions. And the cumulative release percentage was more than 80% within 60 min in stimulated gastrointestinal liquid. CONCLUSION: The preparation technology of alginate-iron (III) complex was feasible. The product is high iron content and the solubility. And it can meet with the fundamental functions as a new kind of is supplement source.

Estado nutricional del hierro en gestantesadolescentes, MedellÝn, Colombia / Nutritional status of iron in pregnant adolescents, MedellÝn, Colombia

Objetivo: analizar el estado nutricional del hierro en gestantesadolescentes de tercer trimestre. MetodologÝa: estudioanalÝtico de corte transversal con 276 adolescentes entre 10 y19 a±os, en tercer trimestre de gestaci¾n de la Empresa Socialdel Estado (ese) Metrosalud (MedellÝn, 2011-2012), con datosde hemoglobina, volumen corpuscular medio, concentraci¾nde hemoglobina corpuscular media e ingesta de suplementode hierro. La ferritina sÚrica se analiz¾ en 178 gestantes,controlada por proteÝna C-reactiva. Se utilizaron medidas detendencia central, dispersi¾n, porcentajes y pruebas de Chi2,anova, Kruskal-Wallis y U de Mann-Whitney. Resultados:la prevalencia de anemia fue 17,1% en el tercer trimestrede gestaci¾n y por deficiencia de hierro, 51%. La medianade ferritina sÚrica fue 13,3 Ág/L (RQ: 7,7 Ág/L-17,9 Ág/L);s¾lo el 5,6% (n = 9) present¾ valores adecuados de ferritina.Las madres que tomaron suplemento de hierro diariamentepresentaron mejores concentraciones de hemoglobina yferritina, frente a aquellas que no lo hicieron, Hb 12,1g/dL vs.11,7 g/dL (p = 0,019) y ferritina sÚrica 14,6 Ág/L vs. 7,0 Ág/L(p = 0,000). Discusi¾n: hubo altas prevalencias de anemia yferropenia en las gestantes, asociadas con la no adherencia alsuplemento de hierro...

Objective: to analyze the nutritional status of iron in pregnantadolescents in their third trimester. Methodology: a crosssectionalanalytical study with 276 adolescents between theages of 10 and 19 in the third trimester of pregnancy fromthe ESE Metrosalud State Social Enterprise (MedellÝn 2011-2012). Data was collected for hemoglobin, mean corpuscularvolume, mean corpuscular concentration and the ingestionof iron supplements. Serum ferritin levels were analyzed in178 pregnant adolescents and were controlled by C-reactiveprotein. Central tendency measures, dispersion, percentagesand Chi 2, anova, Kruskal-Wallis and Mann-Witney U testswere employed. Results: anemia prevalence was 17.1% inthe third trimester, 51% because of iron deficiency. Medianserum ferritin was 13.3 Ág/L (RQ: 7.7 Ág/L-17.9 Ág/L); only5.6% (n=9) showed adequate ferritin levels. Mothers who tookdaily iron supplements exhibited greater concentrations ofhemoglobin and ferritin when compared with those who did nottake any supplement, Hb: 12.1g/dL vs 11.7 g/dL ( p = 0.019) andserum ferritin 14.6 Ág/L vs7.0 Ág/L (p = 0.000). Discussion:there was high prevalence of anemia and iron deficiency inthe expectant mothers, which was associated with a lack ofadherence to the iron supplement...

The Use of Iron Supplements of Pregnant Women and Pregnancy Outcome / 대한지역사회영양학회지

It is known that Korean pregnant women take iron supplements at a higher than the recommended level. This study was designed to provide data on current iron intake levels both from food sources and supplement to better guide iron supplement use during pregnancy. We also explored associations of iron supplement intake levels with varioussociocultural factors and pregnancy outcomes. Dietary intakes of 510 pregnant women were assessed by a validated 102- item food frequency questionnaire, and information on types and amounts of nutritional supplement intakes were also attained. While dietary intake levels of most nutrients exceeded the KDRIs (Korea Dietary Reference Intakes: EAR: Estimated Average Requirements), folate fell short of the KDRIs. A total of 428 women (83.9%) reported to take iron supplement. The pregnant women were divided into the three groups (group I: Fe supplement intake or = 3rd pregnancy: 94.4 +/- 63.8 mg/day, p< 0.005). However, no significant difference was found between iron supplement intake levels and various pregnancy outcomes including birth weight, birth height, gestational age, weight gain during pregnancy, and jaundice. It is worrisome that iron intake by supplement use greatly exceeded the EAR, suggesting the need of appropriate guidelines for iron supplement intake during pregnancy. Thus iron overdose from supplements in pregnancy should be considered as a serious condition.

Iron Nutritional Status by ALAD Genotype and Intervention Study for Rural Area Residents / 대한지역사회영양학회지

Previous studies have suggested that delta-aminolevulinic acid dehydratase (ALAD) phenotype differently affect mineral metabolism. The objective of this study was to determine the effectiveness of 6-month iron supplementation as syrup of NaFeEDTA in improvement of iron status according to ALAD genotype. One hundred thirty adult women living in rural areas of Asan were provided NaFeEDTA syrup once a week for 6 months at the dose of 64mg Fe/week. Three hundred control subjects were observed during the study period. Fasting blood was obtained for analyzing hemoglobin (Hb) and zinc protophorphyrin (ZPP) and serum was analyzed for ferritin, iron and total iron capacity (TIBC) levels before and after iron supplementation. Ninety percent of ALAD 1-1 (ALAD1) and 10% of ALAD 1-2 (ALAD2) genotype were observed in the control group. However, in the intervention group, 98% showed ALAD1 while only 2% was ALAD2, which is significantly lower proportions of ALAD2 compared to the control group (p<0.01). The iron status of intervention group significantly improved except for ferritin and TIBC regardless of ALAD genotype, while the control group did not show any changes in iron status except for ZPP. ZPP concentration of the control group significantly increased in both ALAD1 and 2 while the intervention group showed significantly decreased ZPP after supplementation in ALAD1. Iron supplementation in the form of NaFeEDTA seems to be effective in reduction of ZPP levels although ALAD2 did not show significant changes due to the small number. However, it is difficult to make a conclusion from these results, and more specified further investigation is needed with more participants.

A Case of Pseudomelanosis Duodeni / 대한소화기내시경학회지

Pseudomelanosis duodeni is a rare benign condition in which dark pigments accumulate in macrophages located in the lamina propria of the duodenal mucosa. Most reported cases had hypertension with or without chronic renal failure, and were taking antihypertensive agents and iron supplements. Therefore, it has been assumed that pseudomelanosis duodeni is associated with these medications. Our case was a 77 year-old female patient diagnosed as having hypertension, congestive heart failure, iron deficiency anemia, and depression, who had been treated with antihypertensive agents and iron supplement. Upper gastrointestinal endoscopy revealed many tiny discrete dark macules scattered throughout the first and second portions of the duodenum. Endoscopic mucosal biopsy disclosed macrophages with Prussian blue and Fontana-Masson stain positive pigments, which suggested that the nature of pigment was iron sulfide.

Comparison of Hemoglobin Levels between Iron-Supplemented Group and Non-Iron-Supplemented Group in Pregnancy / 대한산부인과학회잡지

OBJECTIVE: Anemia associated with pregnancy is keen of interest to both the mother and the obstetrician and oral iron supplementation for iron deficiency anemia(IDA) during pregnancy is commonpiece. The purpose of this study is to compare the changes in hematologic parameters between iron supplemented and non-iron supplemented women just prior to and 24 hours after delivery. METHODS: A comparative study was conducted concerning the difference in hematologic changes between 30 iron-supplemented and non-iron-supplemented women, who have delivered at Yonsei University Medical School Yongdong Severance Hospital from 1999. 11. 1 from 2000. 1. 18. RESULTS: Between the iron-supplemented and the non-iron-supplemented group, no statistically significant difference was observed for the duration of gestation, neonatal birth weight and maternal age. However, the mean hemoglobin levels were 11.78mg% and 10.34mg% prior to delivery(p<0.001) and 10.52mg% and 9.59mg% 24 hours after delivery, respectively, thus showing a statistically significant decrease in the non-iron-supplemented group(p<0.001). CONCLUSION: Adequate iron supplementation during the antenatal period significantly improves the hematologic status of the mother.

PREPARATION OF A NEW NUTRITIONAL IRON SUPPLEMENT AND STUDY ON ITS BIOAVAILABILITY / 营养学报

Objective: Auricularid auricula polysaccharide was isolated from Auricularia auricula, and then iron(Ⅲ)-Auricularia auricula polysaccharide complex(APC) was prepared. Methods: APC was synthesized with FeCl 3 and its physico-chemical property and bioavailability were determined. Results: APC was able to dissolve in water and its solution assumed neutral, and this complex did not precipitate at pH from 3 to 11 in water solution, so APC was very stable. Fe(Ⅲ) in APC could be reduced to Fe(Ⅱ) by ascorbic acid. Extracorporeal dissolubility showed Fe(Ⅲ) in APC could be exhibited in 6 h. Bioavailabity studies showed the iron from APC could be well absorbed and maintained longer in serum concentration. Conclusion: APC was able to have better bioavilability as an iron supplement.