Daily Oral Iron Supplementation Research Articles

Anemia ferropénica. Enfermedades por depósito de hierro

Iron deficiency is the most common cause of anemia worldwide, especially in women of childbearing age, due to gynecological losses or during pregnancy, and in older adult patients, in whom it is often the first sign of a digestive tract disease. Clinical suspicion begins with the detection of abnormalities in the blood count, such as microcytosis, and is confirmed by determining analytical parameters related to iron metabolism, such as serum ferritin. A diagnosis of iron-deficiency anemia requires an investigation into its causes, as it may be the first sign of a major underlying disease such as a neoplasm. Treatment consists of managing the underlying disease and daily fasting oral iron supplementation. This may pose problems of tolerance and adherence. In such cases, or if there is malabsorption, the intravenous route may be used. On the other hand, excess iron can have equally deleterious effects due to deposits in various organs such as the heart or liver. Its main causes are hemochromatosis and hematologic diseases with ineffective hematopoiesis. Treatment consists of phlebotomy or iron chelation.

Daily oral iron supplementation during pregnancy.

Daily oral iron supplementation during pregnancy.

Efficacy of daily versus intermittent oral iron supplementation for prevention of anaemia among pregnant women: a systematic review and meta-analysis

The World Health Organization recommends daily oral supplementation of iron for prevention of maternal anaemia. However, the adverse effects due to daily supplementation leads to poor compliance among pregnant women. Also, the mucosal block theory suggests that intermittent oral iron may be more efficient than daily iron with respect to optimum absorption. Our meta-analysis reviewed the existing clinical studies for the efficacy of daily versus intermittent oral iron supplementation. In this systematic review and meta-analysis [PROSPERO ID:CRD42024498180], we searched PubMed, Google Scholar, Scopus, Science Direct and Cochrane database for studies published from 1st January 1970 to 31st December, 2023. Studies comparing daily and intermittent iron supplementation in pregnant women were included. The median intermittent iron dose was 120mg/day and daily iron dose was 60mg/day. The primary outcome was endpoint haemoglobin levels after iron supplementation. The data was analysed using the 'meta' and 'metafor' packages in RStudio using random effects model. The heterogeneity, publication bias, risk of bias and certainty of evidence were assessed using I2 statistics, funnel plots, Cochrane Risk of Bias 2 (ROB2) tool, and the Grades of Recommendation, Assessment, Development and Evaluation (GRADE) approach respectively. Of 4615 search results, 26 studies (n=4365 participants) were included in this meta-analysis. There was no significant difference (p=0.18) between the endpoint mean haemoglobin levels of the daily versus intermittent oral iron groups (standardized mean difference (SMD): 0.51, 95% CI:-0.23 to 1.24, I2=97%, low certainty evidence) irrespective of baseline anaemic status. However, the endpoint ferritin levels were significantly higher in the daily supplementation group (SMD: 0.85, 95% CI: 0.15-1.54, p=0.02, I2=97%, low certainty evidence). The adjusted odds ratio for nausea, (adjusted odds ratio (OR) 3.56, 95% CI: 2.23-5.69, p<0.001, I2=9%, moderate certainty evidence), diarrhoea (adjusted OR 5.40, 95% CI: 1.90-15.33, p=0.002, I2=0%, low certainty evidence) and constipation (adjusted OR 1.95, 95% CI: 1.21-3.14, p=0.006, I2=0%, moderate certainty evidence) was significantly higher in daily oral iron supplementation group. Intermittent oral iron supplementation with a median dose of 120mg/day demonstrates comparable efficacy to daily oral iron supplementation median dose of 60mg/day in increasing haemoglobin levels among pregnant women with a significant reduction in adverse events. There was no funding for this study.

Iron deficiency in pregnant women: effect on offspring neuropsychic development

Increasing evidence indicates that adversities in utero and early childhood can have long-lasting effects on physiological and mental health not only in childhood but also in adulthood. Micronutrient deficiency, and in particular iron deficiency, is one of the most significant factors. Based on literature data, to determine the effect of iron deficiency in pregnant women on the neuropsychological development of infants, as well as to determine a cohort of pregnant women who need iron supplements. The search was conducted in MEDLINE (from PubMed), EMBASE (from OVID), Cochrane Library and ClinicalTrials.gov from 2010 to December 2023 without language restrictions. Data were extracted. Primary outcomes included iron deficiency, serum ferritin less than 15 μg/L in pregnant women, perinatal outcomes, and development of children in infancy. The data of serum ferritin in umbilical cord blood in newborns were compared with the serum ferritin of mothers. Data on iron supplementation and its effect on perinatal outcomes were assessed. Daily oral iron supplementation during pregnancy in women without IDA or ID reduces the incidence of iron deficiency anemia at the woman’s due date, reduces the incidence of iron deficiency in fullterm neonates, and reduces the incidence of morbidity in low-birth-weight infants. Iron supplementation during pregnancy and the postpartum period is a strategy for timely replenishment of ID and prevention of IDA to reduce cerebral iron deficiency in the fetus and newborn. The absence of side effects and high bioavailability, enhanced by ascorbic acid, allow us to recommend SunActive®Fe Bonoferlat as a daily supplement for pregnant and lactating women, according to WHO recommendations.

Stable iron (58Fe) isotopic measurements in Kenyan toddlers during 3 months of iron supplementation demonstrate that half of the iron absorbed is lost.

Increased iron loss may reduce the effectiveness of iron supplementation. The objective of this study was to determine if daily oral iron supplementation increases iron loss, measured using a stable isotope of iron (58Fe). We enrolled and dewormed 24 iron-depleted Kenyan children, 24-27 months of age, whose body iron was enriched and equilibrated with 58Fe given at least 1 year earlier. Over 3 months of supplementation (6 mg iron/kg body weight [BW]/day), mean (±SD) iron absorption was 1.10 (±0.28) mg/day. During supplementation, 0.55 (±0.36) mg iron/day was lost, equal to half of the amount of absorbed iron. Supplementation did not increase faecal haem/porphyrin or biomarkers of enterocyte damage and gut or systemic inflammation. Using individual patient data, we examined iron dose, absorption and loss among all available long-term iron isotopic studies of supplementation. Expressed in terms of body weight, daily iron loss was correlated significantly with iron absorption (Pearson's r = 0.66 [95% confidence interval 0.48-0.78]) but not with iron dose (r = 0.16 [95% CI -0.10-0.40]). The results of this study indicate that iron loss is increased with daily oral iron supplementation and may blunt the efficacy of iron supplements in children. This study was registered at ClinicalTrials.gov as NCT04721964.

IRON COMPLIANCE DURING ANTEPARTUM AND POSTPARTUM PERIOD AMONG WOMEN ATTENDING MATERNAL AND CHILD HEALTH CLINIC OF A TERTIARY HOSPITAL

Background: Daily oral iron supplementation, beginning from second trimester of pregnancy till 45 days postpartum, is recommended by national protocol to reduce risk of low birth weight, maternal anaemia and iron deficiency. The aim of the study was to assess iron compliance during antepartum and postpartum period among women attending maternal and child health clinic. Methods: A descriptive cross-sectional study was carried out among women visiting maternal and child health clinic of Tribhuvan University Teaching Hospital for first dose of infant’s pentavalent vaccine. Non-probability consecutive sampling technique was used to select 426 sample for the study. Data were collected through interview schedule using structured and semi-structured questionnaire. Data were analyzed using descriptive statistics (mean, standard deviation, etc.), and inferential statistics (simple binary logistic and multiple logistic regression). Results: Overall compliance during both pregnancy and postpartum was 61.0%. The common reason for compliance included doctors’ prescription (53.8%) followed by self-awareness (41.1%). For non-compliance, negligence or forgetfulness (16.2%) was commonest reason followed by improper information provided during pregnancy and postpartum (15.3%). Significant association was found between number of ANC visits [p=0.017,OR=0.269(0.091-0.792)], self-awareness on iron supplementation [p=&lt;0.001, OR=0.319(0.198-0.515)] and buying tablets from pharmacy rather than free supply [p=0.001, OR=0.437(0.274-0.698)]. Conclusions: Iron compliance during antenatal and postnatal period is low among women. Enhancing self-awareness on iron supplementation through education and counseling among women during antenatal and postnatal visits and regular prescription could improve iron compliance during pregnancy and postpartum period.

Iron supplements in pregnant women with normal iron status: A systematic review and meta-analysis.

Effects of daily iron supplementation in iron replete pregnancy are unclear. This systematic review aimed to assess benefits and harms of oral iron supplements in pregnant women without anemia and iron deficiency. We predefined and registered a protocol in PROSPERO (CRD42020186210) and performed the review following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) methodology. We searched for randomized clinical trials (RCTs) and observational studies comparing daily oral iron supplementation with no iron supplements in non-anemic iron replete pregnant women. Searches were conducted in MEDLINE (by PubMed), EMBASE (by OVID), Cochrane Library, and ClinicalTrials.gov from inception to September 2022 without language restrictions. Two authors independently screened records, extracted data, and assessed risk of bias using the revised Cochrane risk of bias tool (RoB2). One author read full-texts, assessed certainty of evidence by GRADE and conducted meta-analyses using a random-effects model. Primary outcomes included iron deficiency anemia, iron deficiency, hemoglobin >130 g/L, elevated iron status, small for gestational age newborns, low birthweight newborns, preterm birth, and congenital anomalies. Eight RCTs (2822 women) but no observational studies were eligible for inclusion. Daily oral iron supplementation in pregnancy probably reduces iron deficiency anemia at term (risk ratio [RR]: 0.51, 95% confidence interval [CI]: 0.38-0.70; 4 RCTs, 1670 women; I2 = 13%; moderate-certainty evidence) and the incidence of low birthweight babies (RR: 0.30, 95% CI: 0.13-0.68; 2 RCTs, 361 infants; I2 = 0%; moderate-certainty evidence). In addition, it may reduce iron deficiency at term (RR: 0.74, 95% CI: 0.60-0.92; 4 RCTs, 1663 women; I2 = 58%; low-certainty evidence) and the incidence of small for gestational age babies (RR: 0.39, 95% CI: 0.17-0.86; 1 RCT, 213 infants; I2 not estimable; low-certainty evidence). Daily iron supplementation in iron replete non-anemic pregnant women probably reduces the risk of maternal iron deficiency anemia at term and low birthweight.

Efficacy of once a week versus daily supplementation of 200 mg of ferrous sulphate for control of anaemia in school going menstruating adolescent girls

Background: Anaemia is one of the most common global public health problem among adolescents affecting developing and developed countries with major consequences for health as well as socio-economic development. India accounts for high prevalence of anaemia in adolescent girls. The objective of the study was to find the efficacy of once a week vs. daily oral iron supplementation of 200 mg of ferrous sulphate, in terms of increase in haemoglobin levels, in mild and moderate anaemic menstruating adolescent girls.Methods: Total 588 menstruating adolescent girls studying in selected eight schools of Handignur PHC were included in the study. Structured questionnaire was administered. Haemoglobin estimation was done at baseline, one, two and three months of iron supplementation. Data was analyzed by SPSS 16.0 version. Intention to treat analysis was carried out.Results: Prevalence of anaemia in menstruating adolescent girls was 94.6% (95% CI 92.83 to 96.37). There has been statistically significant increase in mean haemoglobin in daily at the end of two and three months of supplementation (p&lt;0.001). At the end of three months of iron supplementation haemoglobin values became normal at 75th percentile in daily group and at 90th percentile in weekly group.Conclusions: The present study concludes that daily iron supplementation results in much higher levels of haemoglobin at the end of three months when compared with once a week supplementation. All the adolescent girls need iron supplementation-daily for anaemic and once a week for non-anaemic girls.

The Effectiveness of Daily and Alternate Day Oral Iron Supplementation in Athletes With Suboptimal Iron Status (Part 2).

The authors compared the effectiveness of daily (DAY) versus alternate day (ALT) oral iron supplementation in athletes with suboptimal iron. Endurance-trained runners (nine males and 22 females), with serum ferritin (sFer) concentrations <50μg/L, supplemented with oral iron either DAY or ALT for 8 weeks. Serum ferritin was measured at baseline and at fortnightly intervals. Hemoglobin mass (Hbmass) was measured pre- and postintervention in a participant subset (n = 10). Linear mixed-effects models were used to assess the effectiveness of the two strategies on sFer and Hbmass. There were no sFer treatment (p = .928) or interaction (p = .877) effects; however, sFer did increase (19.7μg/L; p < .001) over the 8-week intervention in both groups. In addition, sFer was 21.2μg/L higher (p < .001) in males than females. No Hbmass treatment (p = .146) or interaction (p = .249) effects existed; however, a significant effect for sex indicated that Hbmass was 140.85g higher (p = .004) in males compared with females. Training load (p = .001) and dietary iron intake (p = .015) also affected Hbmass. Finally, there were six complaints of severe gastrointestinal side effects in DAY, but only one in ALT. In summary, both supplement strategies increased sFer in athletes with suboptimal iron status; however, the ALT approach was associated with lower incidence of gastrointestinal upset.

Effect of Daily Iron Supplementation in Healthy Exclusively Breastfed Infants: A Systematic Review with Meta-Analysis.

The literature on the iron requirements of exclusively breastfed infants contains conflicting data and contrary views. The purpose of this study was to summarize the evidence for both benefits and risks of daily oral iron supplementation with regard to hematologic, growth, cognitive parameters, and adverse effects in exclusively breastfed infants. Structured electronic searches were conducted using PubMed, Cochrane Library databases, and Google Scholar for randomized controlled trials (RCTs) involving daily iron supplementation in full-term healthy exclusively breastfed infants. Random- and fixed-effects models were used for calculating the pooled estimates. Four RCTs with 511 infants were included in the meta-analysis. Iron interventions had no significant effect on iron deficiency or iron deficiency anemia, serum ferritin level, or hemoglobin level. Iron interventions did result in a significant increase in Bayley psychomotor developmental indices in later life (mean difference [MD] = 7.00, confidence interval [95% CI] 0.99-13.01) and mean corpuscular volume (MD = 2.17 fL; 95% CI 0.99-3.35 fL). Iron supplementation was associated with slower growth during the exclusive breastfeeding period, but the long-term effect is unclear. Limited available evidence suggests that daily iron supplementation has beneficial effects on hematologic parameters and cognitive development, but may delay physical growth in healthy exclusively breastfed infants. There was no evidence to suggest that iron supplementation could cause other adverse effects.

The treatment of iron deficiency without anaemia (in otherwise healthy persons).

Iron deficiency is the most widespread and frequent nutritional disorder in the world. It affects a high proportion of children and women in developing countries and is also significantly prevalent in the industrialised world, with a clear predominance in adolescents and menstruating females. Iron is essential for optimal cognitive function and physical performance, not only as a binding site of oxygen but also as a critical constituent of many enzymes. Therefore iron deficiency at all its levels - nonanaemic iron deficiency, iron deficiency with microcytosis or hypochromia and iron deficiency anaemia - should be treated. In the presence of normal stores, however, preventative iron administration is inefficient, has side effects and seems to be harmful. In symptomatic patients with fatigue or in a population at risk for iron deficiency (adolescence, heavy or prolonged menstruation, high performance sport, vegetarian or vegan diet, eating disorder, underweight), a baseline set of blood tests including haemoglobin concentration, haematocrit, mean cellular volume, mean cellular haemoglobin, percentage of hypochromic erythrocytes and serum ferritin levels are important to monitor iron deficiency. To avoid false negative results (high ferritin levels in spite of iron deficiency), an acute phase reaction should be excluded by history and measurement of C-reactive protein. An algorithm leads through this diagnostic process and the decision making for a possible treatment. For healthy males and females aged >15 years, a ferritin cut-off of 30 µg/l is appropriate. For children from 6-12 years and younger adolescents from 12-15 years, cut-offs of 15 and 20 µg/l, respectively, are recommended. As a first step in treatment, counselling and oral iron therapy are usually combined. Integrating haem and free iron regularly into the diet, looking for enhancers and avoiding inhibitors of iron uptake is beneficial. In order to prevent reduced compliance, mainly as a result of gastrointestinal side effects of oral treatment, the use of preparations with reasonable but not excessive elemental iron content (28-50 mg) seems appropriate. Only in exceptional cases will an intravenous injection be necessary (e.g., concomitant disease needing urgent treatment, repeated failure of first-step therapy).To measure the success of treatment, the basic blood tests should be repeated after 8 to 10 weeks. Patients with repeatedly low ferritin will benefit from intermittent oral substitution to preserve iron stores and from long term follow-up, with the basic blood tests repeated every 6 or 12 months to monitor iron stores. Long-term daily oral or intravenous iron supplementation in the presence of normal or even high ferritin values is, however, not recommended and is potentially harmful.

Daily iron supplementation for improving anaemia, iron status and health in menstruating women.

Iron-deficiency anaemia is highly prevalent among non-pregnant women of reproductive age (menstruating women) worldwide, although the prevalence is highest in lower-income settings. Iron-deficiency anaemia has been associated with a range of adverse health outcomes, which restitution of iron stores using iron supplementation has been considered likely to resolve. Although there have been many trials reporting effects of iron in non-pregnant women, these trials have never been synthesised in a systematic review. To establish the evidence for effects of daily supplementation with iron on anaemia and iron status, as well as on physical, psychological and neurocognitive health, in menstruating women. In November 2015 we searched CENTRAL, Ovid MEDLINE, EMBASE, and nine other databases, as well as four digital thesis repositories. In addition, we searched the World Health Organization International Clinical Trials Registry Platform (WHO ICTRP) and reference lists of relevant reviews. We included randomised controlled trials (RCTs) and quasi-RCTs comparing daily oral iron supplementation with or without a cointervention (folic acid or vitamin C), for at least five days per week at any dose, to control or placebo using either individual- or cluster-randomisation. Inclusion criteria were menstruating women (or women aged 12 to 50 years) reporting on predefined primary (anaemia, haemoglobin concentration, iron deficiency, iron-deficiency anaemia, all-cause mortality, adverse effects, and cognitive function) or secondary (iron status measured by iron indices, physical exercise performance, psychological health, adherence, anthropometric measures, serum/plasma zinc levels, vitamin A status, and red cell folate) outcomes. We used the standard methodological procedures of Cochrane. The search strategy identified 31,767 records; after screening, 90 full-text reports were assessed for eligibility. We included 67 trials (from 76 reports), recruiting 8506 women; the number of women included in analyses varied greatly between outcomes, with endpoint haemoglobin concentration being the outcome with the largest number of participants analysed (6861 women). Only 10 studies were considered at low overall risk of bias, with most studies presenting insufficient details about trial quality.Women receiving iron were significantly less likely to be anaemic at the end of intervention compared to women receiving control (risk ratio (RR) 0.39 (95% confidence interval (CI) 0.25 to 0.60, 10 studies, 3273 women, moderate quality evidence). Women receiving iron had a higher haemoglobin concentration at the end of intervention compared to women receiving control (mean difference (MD) 5.30, 95% CI 4.14 to 6.45, 51 studies, 6861 women, high quality evidence). Women receiving iron had a reduced risk of iron deficiency compared to women receiving control (RR 0.62, 95% CI 0.50 to 0.76, 7 studies, 1088 women, moderate quality evidence). Only one study (55 women) specifically reported iron-deficiency anaemia and no studies reported mortality. Seven trials recruiting 901 women reported on 'any side effect' and did not identify an overall increased prevalence of side effects from iron supplements (RR 2.14, 95% CI 0.94 to 4.86, low quality evidence). Five studies recruiting 521 women identified an increased prevalence of gastrointestinal side effects in women taking iron (RR 1.99, 95% CI 1.26 to 3.12, low quality evidence). Six studies recruiting 604 women identified an increased prevalence of loose stools/diarrhoea (RR 2.13, 95% CI 1.10, 4.11, high quality evidence); eight studies recruiting 1036 women identified an increased prevalence of hard stools/constipation (RR 2.07, 95% CI 1.35 to 3.17, high quality evidence). Seven studies recruiting 1190 women identified evidence of an increased prevalence of abdominal pain among women randomised to iron (RR 1.55, 95% CI 0.99 to 2.41, low quality evidence). Eight studies recruiting 1214 women did not find any evidence of an increased prevalence of nausea among women randomised to iron (RR 1.19, 95% CI 0.78 to 1.82). Evidence that iron supplementation improves cognitive performance in women is uncertain, as studies could not be meta-analysed and individual studies reported conflicting results. Iron supplementation improved maximal and submaximal exercise performance, and appears to reduce symptomatic fatigue. Although adherence could not be formally meta-analysed due to differences in reporting, there was no evident difference in adherence between women randomised to iron and control. Daily iron supplementation effectively reduces the prevalence of anaemia and iron deficiency, raises haemoglobin and iron stores, improves exercise performance and reduces symptomatic fatigue. These benefits come at the expense of increased gastrointestinal symptomatic side effects.

Pre-Altitude Serum Ferritin Levels and Daily Oral Iron Supplement Dose Mediate Iron Parameter and Hemoglobin Mass Responses to Altitude Exposure.

PurposeTo investigate the influence of daily oral iron supplementation on changes in hemoglobin mass (Hbmass) and iron parameters after 2–4 weeks of moderate altitude exposure.MethodsHematological data collected from 178 athletes (98 males, 80 females) exposed to moderate altitude (1,350–3,000 m) were analysed using linear regression to determine how altitude exposure combined with oral iron supplementation influenced Hbmass, total iron incorporation (TII) and blood iron parameters [ferritin and transferrin saturation (TSAT)].ResultsAltitude exposure (mean ± s: 21 ± 3 days) increased Hbmass by 1.1% [-0.4, 2.6], 3.3% [1.7, 4.8], and 4.0% [2.0, 6.1] from pre-altitude levels in athletes who ingested nil, 105 mg and 210 mg respectively, of oral iron supplement daily. Serum ferritin levels decreased by -33.2% [-46.9, -15.9] and 13.8% [-32.2, 9.7] from pre-altitude levels in athletes who supplemented with nil and 105 mg of oral iron supplement daily, but increased by 36.8% [1.3, 84.8] in athletes supplemented with 210 mg of oral iron daily. Finally, athletes who ingested either 105 mg or 210 mg of oral iron supplement daily had a greater TII compared with non-supplemented athletes (0 versus 105 mg: effect size (d) = -1.88 [-2.56, -1.17]; 0 versus 210 mg: effect size (d) = -2.87 [-3.88, -1.66]).ConclusionOral iron supplementation during 2–4 weeks of moderate altitude exposure may enhance Hbmass production and assist the maintenance of iron balance in some athletes with low pre-altitude iron stores.

Daily oral iron supplementation during pregnancy.

Iron and folic acid supplementation has been the preferred intervention to improve iron stores and prevent anaemia among pregnant women, and it is thought to improve other maternal and birth outcomes. To assess the effects of daily oral iron supplements for pregnant women, either alone or in conjunction with folic acid, or with other vitamins and minerals as a public health intervention in antenatal care. We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (10 January 2015). We also searched the WHO International Clinical Trials Registry Platform (ICTRP) (26 February 2015) and contacted relevant organisations for the identification of ongoing and unpublished studies (26 February 2015) . Randomised or quasi-randomised trials evaluating the effects of oral preventive supplementation with daily iron, iron + folic acid or iron + other vitamins and minerals during pregnancy. We assessed the methodological quality of trials using standard Cochrane criteria. Two review authors independently assessed trial eligibility, extracted data and conducted checks for accuracy. We used the GRADE approach to assess the quality of the evidence for primary outcomes.We anticipated high heterogeneity among trials and we pooled trial results using a random-effects model and were cautious in our interpretation of the pooled results: the random-effects model gives the average treatment effect. We included 61 trials. Forty-four trials, involving 43,274 women, contributed data and compared the effects of daily oral supplements containing iron versus no iron or placebo.Preventive iron supplementation reduced maternal anaemia at term by 70% (risk ratio (RR) 0.30; 95% confidence interval (CI) 0.19 to 0.46, 14 trials, 2199 women, low quality evidence), iron-deficiency anaemia at term (RR 0.33; 95% CI 0.16 to 0.69, six trials, 1088 women), and iron deficiency at term by 57% (RR 0.43; 95% CI 0.27 to 0.66, seven trials, 1256 women, low quality evidence). There were no clear differences between groups for severe anaemia in the second or third trimester, or maternal infection during pregnancy (RR 0.22; 95% CI 0.01 to 3.20, nine trials, 2125 women, very low quality evidence; and, RR 1.21; 95% CI 0.33 to 4.46; one trial, 727 women, low quality evidence, respectively), or maternal mortality (RR 0.33; 95% CI 0.01 to 8.19, two trials, 12,560 women, very low quality evidence), or reporting of side effects (RR 1.29; 95% CI 0.83 to 2.02, 11 trials, 2423 women, very low quality evidence). Women receiving iron were on average more likely to have higher haemoglobin (Hb) concentrations at term and in the postpartum period, but were at increased risk of Hb concentrations greater than 130 g/L during pregnancy, and at term.Compared with controls, women taking iron supplements less frequently had low birthweight newborns (8.4% versus 10.3%, average RR 0.84; 95% CI 0.69 to 1.03, 11 trials, 17,613 women, low quality evidence), and preterm babies (RR 0.93; 95% CI 0.84 to 1.03, 13 trials, 19,286 women, moderate quality evidence). They appeared to also deliver slightly heavier babies (mean difference (MD) 23.75; 95% CI -3.02 to 50.51, 15 trials, 18,590 women, moderate quality evidence). None of these results were statistically significant. There were no clear differences between groups for neonatal death (RR 0.91; 95% CI 0.71 to 1.18, four trials, 16,603 infants, low quality evidence), or congenital anomalies (RR 0.88, 95% CI 0.58 to 1.33, four trials, 14,636 infants, low quality evidence).Twenty-three studies were conducted in countries that in 2011 had some malaria risk in parts of the country. In some of these countries/territories, malaria is present only in certain areas or up to a particular altitude. Only two of these studies reported malaria outcomes. There is no evidence that iron supplementation increases placental malaria. For some outcomes heterogeneity was higher than 50%. Supplementation reduces the risk of maternal anaemia and iron deficiency in pregnancy but the positive effect on other maternal and infant outcomes is less clear. Implementation of iron supplementation recommendations may produce heterogeneous results depending on the populations' background risk for low birthweight and anaemia, as well as the level of adherence to the intervention.

Ferric sodium edetate therapy in children with iron deficiency anemia

Background Iron deficiency anemia (IDA) is frequentlyfound in school-aged children. The main treatments for IDAare overcoming the causal factors and iron supplementation.Noncompliance in taking iron tablets and the possibility of ironabsorbtion or transport difficulties, can reduce efficacy of daily oraliron supplementation. Because excess iron storage in the intestinalcells can lead to mucosal blockage, twice weekly oral iron therapymay be considered instead of daily dosage.Objective To compare the effects of daily vs. twice weekly ferricsodium edetate (NaFeEDTA) on hemoglobin (Hb), hematocrit(Ht), mean corpuscular volume (MCV), mean corpuscularhemoglobin (MCH), and mean corpuscular hemoglobinconcentration (MCHC) levels on children with IDA.MethodsWe conducted an open-label, randomized, prospectivestudy in 36 children with IDA aged 5-11 years. Subjects weredivided into two groups. For a one-month period, group I receiveddaily iron therapy (NaFeEDTA) and group II received twiceweekly iron therapy. Examinations of Hb, Ht, MCV, MCH, MCHCwere performed before and after iron therapy.Results There were no significant differences in Hb, Ht, MCV,MCH or MCHC levels after therapy between the daily and twiceweekly NaFeEDTA groups (P &gt; 0.05).Conclusion Twice weekly NaFeEDTA therapy is as effective asdaily NaFeEDTA administration in children with IDA.

Effect of daily iron supplementation on health in children aged 4-23 months: a systematic review and meta-analysis of randomised controlled trials.

About 47% of preschool children worldwide are anaemic. Daily oral iron supplementation is a commonly recommended intervention for treatment and prevention of anaemia, but the efficacy and safety of iron supplementation programmes is debated. Thus, we systematically reviewed the evidence for benefit and safety of daily iron supplementation in children aged 4-23 months. We searched Scopus and Medline, from inception to Feb 5, 2013, WHO databases, theses repositories, grey literature, and references. Randomised controlled trials that assigned children 4-23 months of age to daily oral iron supplementation versus control were eligible. We calculated mean difference (MD) or standard MD (SMD) for continuous variables, risk ratios for dichotomous data, and rate ratios for rates. We quantified heterogeneity with the I(2) test and synthesised all data with a random-effects model. This review is registered with the International Prospective Register of Systematic Reviews, number CRD42011001208. Of 9533 citations identified by the search strategy, 49 articles from 35 studies were eligible; these trials included 42,306 children. Only nine studies were judged to be at low risk of bias. In children receiving iron supplements, the risk ratio for anaemia was 0·61 (95% CI 0·50-0·74; 17 studies, n=4825), for iron deficiency was 0·30 (0·15-0·60; nine studies, n=2464), and for iron deficiency anaemia was 0·14 (0·10-0·22; six studies, n=2145). We identified no evidence of difference in mental (MD 1·65, 95% CI -0·63 to 3·94; six studies, n=1093) or psychomotor development (1·05, -1·36 to 3·46; six studies, n=1086). We noted no significant differences in final length or length-for-age, or final weight or weight-for-age. Children randomised to iron had slightly lesser length (SMD -0·83, -1·53 to -0·12; eight studies, n=868) and weight gain (-1·12, -1·19 to -0·33) over the course of the studies. Vomiting (risk ratio 1·38, 95% CI 1·10-1·73) and fever (1·16, 1·02-1·31) were more prevalent in children receiving iron. In children aged 4-23 months, daily iron supplementation effectively reduces anaemia. However, the adverse effect profile of iron supplements and effects on development and growth are uncertain. Adequately powered trials are needed to establish the non-haematological benefits and risks from iron supplementation in this group. Victoria Fellowship (Government of Victoria, Australia); CRB Blackburn Scholarship (Royal Australasian College of Physicans); Overseas Research Experience Scholarship, University of Melbourne.

Paucity of Clinical Trials in Iron Deficiency: Lessons Learned From Study of VLBW Infants

* Abbreviations: VLBW — : very low birth weight Pediatricians and hematologists alike should take keen interest in the report by Taylor and Kennedy1 in this issue of Pediatrics of a randomized, placebo-controlled study of daily oral iron supplementation in very low birth weight (VLBW) infants <36 weeks’ postgestational age. Study subjects, managed according to relatively liberal transfusion guidelines, derived no benefit from the additional iron supplement of 2 mg/kg with regard to hematocrit (the primary outcome), reticulocyte count, or transfusion requirements. This result supports the concept that the need for 2 mg/kg per day of iron for low birth weight infants can be met by using iron-fortified formula or breast milk alone without medicinal iron supplementation. Two previous studies in this field2,3 were noted by Taylor and Kennedy to be inconclusive, whereas another investigation suggesting the need for iron supplementation was limited to infants whose birth weights were between 2000 and 2500 g.4 Taylor and Kennedy’s study,1 although well designed and well executed, does not provide the final word regarding the optimal method and timing of iron delivery to VLBW infants. The report failed to describe the specific types of iron used in the multivitamin with iron supplement and in the iron-fortified mother’s milk used in the study. Different forms of iron (Table 1) have different absorption profiles and toxicities. Moreover, both the benefits and potential adverse effects of medicinal iron supplements require additional study in VLBW infants, especially in settings in which transfusions are used less frequently and where outcomes other than hematocrit at 36 weeks’ postgestational age are assessed. View this table: TABLE 1 Uncertainties Regarding Treatment of Iron-Deficiency Anemia and Opportunities … Address correspondence to George R. Buchanan, MD, Department of Pediatrics, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, TX 75390-9063. E-mail: george.buchanan{at}utsouthwestern.edu

Daily oral iron supplementation during pregnancy.

Iron and folic acid supplementation has been the preferred intervention to improve iron stores and prevent anaemia among pregnant women, and it may also improve other maternal and birth outcomes. To assess the effects of daily oral iron supplements for pregnant women, either alone or in conjunction with folic acid, or with other vitamins and minerals as a public health intervention. We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (2 July 2012). We also searched the WHO International Clinical Trials Registry Platform (ICTRP) (2 July 2012) and contacted relevant organisations for the identification of ongoing and unpublished studies. Randomised or quasi-randomised trials evaluating the effects of oral preventive supplementation with daily iron, iron + folic acid or iron + other vitamins and minerals during pregnancy. We assessed the methodological quality of trials using standard Cochrane criteria. Two review authors independently assessed trial eligibility, extracted data and conducted checks for accuracy. We included 60 trials. Forty-three trials, involving more than 27,402 women, contributed data and compared the effects of daily oral supplements containing iron versus no iron or placebo.Overall, women taking iron supplements were less likely to have low birthweight newborns (below 2500 g) compared with controls (8.4% versus 10.2%, average risk ratio (RR) 0.81; 95% confidence interval (CI) 0.68 to 0.97, 11 trials, 8480 women) and mean birthweight was 30.81 g greater for those infants whose mothers received iron during pregnancy (average mean difference (MD) 30.81; 95% CI 5.94 to 55.68, 14 trials, 9385 women). Preventive iron supplementation reduced the risk of maternal anaemia at term by 70% (RR 0.30; 95% CI 0.19 to 0.46, 14 trials, 2199 women) and iron deficiency at term by 57% (RR 0.43; 95% CI 0.27 to 0.66, seven trials, 1256 women). Although the difference between groups did not reach statistical significance, women who received iron supplements were more likely than controls to report side effects (25.3% versus 9.91%) (RR 2.36; 95% CI 0.96 to 5.82, 11 trials, 4418 women), particularly at doses 60 mg of elemental iron or higher. Women receiving iron were on average more likely to have higher haemoglobin (Hb) concentrations at term and in the postpartum period, but were at increased risk of Hb concentrations greater than 130g/L during pregnancy and at term. Twenty-three studies were conducted in countries that in 2011 had some malaria risk in parts of the country. In some of these countries/territories, malaria is present only in certain areas or up to a particular altitude. Only two of these reported malaria outcomes. There is no evidence that iron supplementation increases placental malaria. For some outcomes heterogeneity was higher than 50%. Prenatal supplementation with daily iron are effective to reduce the risk of low birthweight, and to prevent maternal anaemia and iron deficiency in pregnancy. Associated maternal side effects and particularly high Hb concentrations during pregnancy at currently used doses suggest the need to update recommendations on doses and regimens for routine iron supplementation.

Effect of iron supplementation on maximal oxygen uptake in female athletes

Iron is a vital constituent of hemoglobin, myoglobin, and some mitochondrial enzymes; therefore, body iron deficiency may result in reduced aerobic capacity. The aim of this study was to evaluate the effects of daily oral iron supplementation on body iron status, and the maximal oxygen uptake (VO2max) in female athletes with latent iron deficiency, as well as with iron-deficiency anemia. A total of 37 female volleyball players were included in the study. Seventeen female athletes had latent iron deficiency, and 20 ones iron deficiency anemia. Both groups were divided into the experimental and the control group. The experimental groups received a daily oral iron supplement (200 mg ferrous sulfate), for a two-month training course. Iron status was determined by serum parameters as follows: red blood cells count, hemoglobin concentration, serum iron and ferritin levels, an unsaturated iron binding capacity, total iron binding capacity and transferrin saturation. VO2max was determined by an indirect test. Statistical difference between the latent iron deficient group versus the iron deficient anemic group was found regarding VO2max (p < 0.001). There were correlations between hemoglobin concentration and VO2max in the latent iron deficient group, as well as in the iron deficient anaemic group (p < 0.05). After two months, there was a significant increase in VO2max in all groups (from 7.0% to 18.2%). Values of VO2max at the end of training period were significantly different (45.98 +/- 1.76 vs 42.40 +/- 1.22 mL/kg/min; p < 0.001) between the experimental and the control group only in female athletes with iron deficiency anemia. After the supplementation, markers of iron status were significantly higher in supplemented groups than in the controls. VO2max was significantly lower in the iron deficient anemic group versus the latent iron deficient group. Iron supplementation during a two-month training period significantly improved body iron status in the iron deficient female athletes with or without anemia, and significantly increased VO2max only in the subjects with iron deficiency anemia.

Oral versus high dose parenteral iron supplementation in pregnancy

Objective To compare the effect of daily oral iron supplementation with two injections of high dose parenteral iron. Method A total of 220 pregnant women with a singleton pregnancy and hemoglobin between 8 to 11 g% at 16–24 weeks gestation were identified and randomly divided into two groups. Group A was started on daily oral iron therapy of 100 mg of elemental iron. Group B was given 250 mg of iron sorbitol intramuscularly and repeated at an interval of 4–6 weeks. Blood indices were evaluated at the beginning of study and at 36 weeks to see the effect after iron supplementation in the two groups. The data were analyzed using SPSS software, version 10.1. Results Definitive and comparable improvement in hemoglobin and all the blood indices (hematocrit, MCH, MCHC, MCV, Serum iron and TIBC) was observed. The absolute change in hemoglobin and hematocrit was 1.18±0.68 g% and 4.02±2.59% in oral group, 1.34±0.77 g% and 4.93±3.65% in parenteral group, respectively. Serum ferritin showed statistically significant absolute rise (10.43±7.92 μg/dl) after parenteral iron supplementation as compared to oral iron supplementation (9.76±4.78 μg/dl). Obstetric outcome was comparable in two groups. Conclusion Two treatment regimens are biologically equivalent in terms of hematological response. Two high doses of intramuscular iron can be a good substitute to meet iron requirement in pregnancy.