Clinical outcome post treatment of anemia in pregnancy with intravenous versus oral iron therapy: a systematic review and meta-analysis.

Oral iron therapy is often the most common way of treating anaemia; however intravenous iron is considered effective due to rapid iron replenishment. We have dearth of evidence on clinical outcomes post treatment of anaemia. We have searched studies published in English in PubMed, Cochrane, Scopus, ProQuest, and Google Scholar. Our study analysed the clinical outcomes amongst neonates and mother and the adverse events post treatment and assessed the mean change in maternal haemoglobin concentration in both the groups. Forest plots for the clinical outcomes are presented. From a total of 370 studies, 34 Randomized and quasi experimental studies comparing clinical outcomes post-treatment of anaemia in pregnancy were included for quantitative evidence synthesis. Pooled results of maternal clinical outcomes using random effect model [OR: 0.79 (95% CI 0.66; 0.95); 10 outcomes; 17 studies] showed statistically significant difference among both the groups [Moderate quality evidence]; however no significant difference [OR: 0.99 (95% CI 0.86; 1.14); 7 outcomes; 8 studies] have been observed for neonatal complications [Low quality evidence]. The study found that pregnant women receiving IV iron were significantly less likely to experience adverse events as compared with those receiving oral iron [OR 0.39;  (95% CI 0.26-0.60)]; 34 studies; 13,909 women; [Low quality evidence]. Findings from meta-regression analysis showed that IV iron is more likely to reduce maternal complications by 21% compared to oral iron. Increase in odds of adverse maternal outcomes was observed due to increase in gestational age and publication year but no effect for the type of drug used. IV iron increases Hb more and at a higher pace than oral iron. Intravenous iron is more likely to avert adverse maternal outcomes and adverse reactions. However, there is no conclusive evidence on its effectiveness on individual maternal outcome or neonatal outcome/s. Protocol registered with PROSPERO CRD42022368346).

The incidence, complications, and treatment of iron deficiency in pregnancy.

Iron deficiency and/or iron deficiency anemia (IDA) complicate nearly 50% of pregnancies globally, negatively impacting both maternal and fetal outcomes. Iron deficiency can cause a range of symptoms that range from aggravating to debilitating including fatigue, poor quality of life, pagophagia, and restless leg syndrome. Iron deficiency and IDA are also associated with maternal complications including preterm labor, increased rates of cesarean delivery, postpartum hemorrhage, and maternal death. Fetal complications include increased rates of low birth weight and small for gestational age newborns. Prenatal maternal anemia has also been associated with autism spectrum disorders in the neonate, although causation is not established. Deficiency in the newborn is associated with compromised memory, processing, and bonding, with some of these deficits persisting into adulthood. Despite the prevalence and consequences associated with iron deficiency in pregnancy, data show that it is routinely undertreated. Due to the physiologic changes of pregnancy, all pregnant individuals should receive oral iron supplementation. However, the bioavailability of oral iron is poor and it is often ineffective at preventing and treating iron deficiency. Likewise, it frequently causes gastrointestinal symptoms that can worsen the quality of life in pregnancy. Intravenous iron formulations administered in a single or multiple dose series are now available. There is increasing data suggesting that newer intravenous formulations are safe and effective in the second and third trimesters and should be strongly considered in pregnant individuals without optimal response to oral iron repletion.

Screening, Treatment, and Monitoring of Iron Deficiency Anemia in Pregnancy and Postpartum.

Iron deficiency anemia is the most prevalent form of anemia worldwide. In the United States, clinicians routinely screen for iron deficiency anemia upon initiation of prenatal care, at the start of the third trimester, and prior to birth. Treatment of iron deficiency anemia generally begins with oral supplementation of elemental iron, which is associated with adverse gastrointestinal effects. These adverse effects can decrease adherence, leading to subtherapeutic treatment. Newer evidence highlights the benefits of early screening for iron deficiency before the onset of anemia, as well as the use of intravenous iron to expedite the treatment of iron deficiency anemia. More research is needed on the potential consequences of over-supplementation and iron deficiency without anemia to guide treatment. This article reviews the evidence for best practices for screening, treatment, and continued monitoring of iron deficiency anemia during pregnancy and postpartum. Maternal, fetal, and neonatal implications are reviewed, as well as the risks and benefits of treatment options. Finally, an evidence-based algorithm is proposed to guide clinicians on continued monitoring after treatment.

Desiderosmia: a manifestation of iron deficiency in pregnancy.

A pregnant woman in her 20s presented with an excessive desire to smell a specific household cleaning product. She was found to have severe iron deficiency anaemia and her symptoms resolved following intravenous iron supplementation. She described symptoms of fatigue, shortness of breath and olfactory cravings. The specific scent could not be replicated with other smells and the woman had to significantly modify her lifestyle to accommodate the excessive desire. She had a similar experience during her prior pregnancy which resolved after the correction of severe iron deficiency anaemia. This unique symptom has been described as desiderosmia: iron deficiency manifesting as olfactory cravings. This underappreciated but useful symptom is defined as a separate entity to pica, as there is an absence of desire to ingest the product. Desiderosmia can harm mother and baby through inhalation of potentially harmful fumes; hence, women who describe this symptom should be assessed for iron deficiency anaemia.

Effectiveness of Health Information Package Program on Knowledge and Compliance among Pregnant Women with Anemia: A Randomized Controlled Trial.

Despite the availability of iron supplements during pregnancy for all pregnant women receiving antenatal care in Saudi Arabia, anemia remains to be a global public health concern leading to adverse maternal, fetal, and neonatal effects. We aimed to evaluate the effectiveness of the Health Information Package Program on the knowledge anemic pregnant women had about anemia, their compliance with iron and folic acid supplementation, and their hemoglobin levels. A single-blind randomized controlled trial was carried out in accordance with the Consolidated Standards of Reporting Trials (CONSORT) guidelines between January and May 2021. Pregnant women (n = 196) aged 18-45 years old and diagnosed with anemia during the first trimester of their pregnancy were randomly assigned into two groups: the intervention group (Health Information Package Program plus routine care, n = 98) and the control group (routine care only, n = 98). Knowledge, the ability to select appropriate food, and hemoglobin levels were assessed at baseline and after three months, while compliance with iron and folic acid supplementation was also measured at the end of three months. This study indicated that the post-education mean knowledge score, food selection ability score, compliance rate, and hemoglobin level were significantly higher for the intervention group than for the control group. The Health Information Package Program with regular follow-ups using the WhatsApp platform was an effective educational intervention for anemic pregnant women.

Is every other day iron supplementation effective for the treatment of the iron deficiency anemia in pregnancy?

AIM: To understand if every other day iron supplementation may be as effective as daily iron intake in anemic pregnant women. METHODS: This case-control study was conducted at a tertiary hospital in Turkey. The study randomly categorized women into two groups as daily intake (n = 124) vs every other day intake (n = 140) of 100 mg daily oral ferrous fumarate. The numbers of women recruited from the study were 13 and 34 in two groups. Thus, for analysis, there were 111 women in the daily group and 106 women in the other group. The current study obtained hemoglobin (Hb) and ferritin levels two times to evaluate the effects of treatment, noting initial levels before drug administration, and a second blood sample was obtained after two months. Two groups were compared according to the increase in Hb and ferritin levels. The study asked the women whether they experienced gastrointestinal side effects. RESULTS: The ferritin levels increased 4.9 ± 4.2 ng/mL in the daily intake group and 3.9 ± 2.9 ng/mL in every other day group (p = .215). The Hb increased 1.4 ± 0.7 g/dL in the daily intake group and 1.6 ± 0.6 g/dL in the other group (p = .021). Gastrointestinal side effects appeared in 47 (17.8%) out of 264 women. The rate of gastrointestinal side effect was lower in every other day group (41.4% vs 15.1%, p = .0057). CONCLUSION: Every other day iron supplementation is as effective as daily intake for treating iron deficiency anemia with lesser gastrointestinal side effects during pregnancy.

Oral Iron Supplementation in Pregnancy: Current Recommendations and Evidence-Based Medicine.

OBJECTIVE: To review the evidence about universal iron supplementation in pregnancy to prevent maternal anemia. METHODS: Bibliographic research of randomized and controlled clinical trials, meta-analyses, systematic reviews, and clinical guidelines, published between August 2009 and August 2019, using the MeSH terms: iron; therapeutic use; pregnancy; anemia, prevention and control. RESULTS: We included six clinical guidelines, three meta-analyses and one randomized controlled clinical trial. DISCUSSION: Most articles point to the improvement of hematological parameters and reduction of maternal anemia risk, with supplementary iron. However, they do not correlate this improvement in pregnant women without previous anemia with the eventual improvement of clinical parameters. CONCLUSION: Universal iron supplementation in pregnancy is controversial, so we attribute a SORT C recommendation strength.

OBJETIVO: Rever a evidência sobre a necessidade de suplementação universal de ferro na gravidez para prevenção de anemia materna. MéTODOS: Pesquisa bibliográfica de ensaios clínicos aleatorizados e controlados, metanálises, revisões sistemáticas e normas de orientação clínica, publicados entre agosto de 2009 e agosto de 2019, utilizando os termos MeSH: iron, terapêuticas use; pregnancy; anemia, preventivos and control. RESULTADOS: Incluímos seis normas de orientação clínica, três metanálises e um ensaio clínico randomizado e controlado. DISCUSSãO: A maioria dos artigos aponta para a melhoria dos parâmetros hematológicos e redução do risco de anemia materna por meio da suplementação com ferro. Todavia, eles não correlacionam a melhoria destes parâmetros em grávidas sem anemia prévia com a eventual melhoria de parâmetros clínicos. CONCLUSõES: A suplementação universal com ferro na gravidez é controversa, pelo que atribuímos uma força de recomendação SORT C.

Oral Iron Supplementation in Pregnancy: Current Recommendations and Evidence-Based Medicine Suplementação oral de ferro na gravidez: recomendações atuais e medicina baseada na evidência

Abstract Objective To review the evidence about universal iron supplementation in pregnancy to prevent maternal anemia. Methods Bibliographic research of randomized and controlled clinical trials, meta-analyses, systematic reviews, and clinical guidelines, published between August 2009 and August 2019, using the MeSH terms: iron; therapeutic use; pregnancy; anemia, prevention and control. Results We included six clinical guidelines, three meta-analyses and one randomized controlled clinical trial. Discussion Most articles point to the improvement of hematological parameters and reduction of maternal anemia risk, with supplementary iron. However, they do not correlate this improvement in pregnant women without previous anemia with the eventual improvement of clinical parameters. Conclusion Universal iron supplementation in pregnancy is controversial, so we attribute a SORT C recommendation strength.

Resumo Objetivo Rever a evidência sobre a necessidade de suplementação universal de ferro na gravidez para prevenção de anemia materna. Métodos Pesquisa bibliográfica de ensaios clínicos aleatorizados e controlados, metanálises, revisões sistemáticas e normas de orientação clínica, publicados entre agosto de 2009 e agosto de 2019, utilizando os termos MeSH: iron, terapêuticas use; pregnancy; anemia, preventivos and control. Resultados Incluímos seis normas de orientação clínica, três metanálises e um ensaio clínico randomizado e controlado. Discussão A maioria dos artigos aponta para a melhoria dos parâmetros hematológicos e redução do risco de anemia materna por meio da suplementação com ferro. Conclusões A suplementação universal com ferro na gravidez é controversa, pelo que atribuímos uma força de recomendação SORT C.

The effect of Lactiplantibacillus plantarum 299v together with a low dose of iron on iron status in healthy pregnant women: A randomized clinical trial.

INTRODUCTION: Iron deficiency during pregnancy is a global health problem and is associated with adverse pregnancy outcomes. The aim of this randomized, double-blind, placebo-controlled study was to evaluate the effect of Lactiplantibacillus plantarum 299v (Lp299v, 1010 colony forming units), 4.2 mg iron, 12 mg ascorbic acid and 30 µg folic acid (Lp) on iron status in healthy, non-anemic, pregnant Swedish women. MATERIAL AND METHODS: A total of 326 women were randomized to receive Lp (n = 161) or placebo (n = 165) twice daily from gestational week 10-12 until end of pregnancy or until the potential start of iron therapy. The primary endpoint was serum ferritin at week 28. RESULTS: Intake of Lp attenuated the decrease in serum ferritin from baseline to week 28 (p = 0.003) and week 35 (p Ë‚ 0.001) and resulted in reduced prevalence of iron deficiency (59% vs 78%, p = 0.017) and iron deficiency anemia (7.4% vs 21%, p = 0.023) at week 35. Intake of Lp also resulted in beneficial effects on the soluble transferrin receptor (p = 0.011) and total body iron (p Ë‚ 0.001) at week 35. Gestational length and birthweight were comparable between groups. The proportion of women reporting adverse events during the study was comparable between groups. CONCLUSIONS: Intake of Lp from early pregnancy was safe, attenuated the loss of iron stores and improved iron status in healthy pregnant women.

Slower response to treatment of iron-deficiency anaemia in pregnant women infected with HIV: a prospective cohort study.

OBJECTIVE: Antenatal anaemia is associated with increased peripartum transfusion requirement in South Africa. We studied whether HIV was associated with the response to treatment of iron-deficiency anaemia. DESIGN: Prospective cohort study. SETTING: Hospital-based antenatal anaemia clinic in South Africa. SAMPLE: Equal-sized cohorts of pregnant women testing positive for HIV (HIV+) and testing negative for HIV (HIV-) with iron-deficiency anaemia. METHODS: Haemoglobin trajectories of women with confirmed iron-deficiency anaemia (ferritin < 50 ng/ml) were estimated from the initiation of iron supplementation using mixed-effects modelling, adjusted for baseline HIV status, ferritin level, maternal and gestational ages and time-varying iron supplementation. MAIN OUTCOME MEASURES: Haemoglobin trajectories. RESULTS: Of 469 women enrolled, 51% were HIV+, 90% of whom were on antiretroviral therapy (with a mean CD4+ lymphocyte count of 403 cells/mm3 ). Anaemia diagnoses did not differ by HIV status. A total of 400 women with iron-deficiency anaemia were followed during treatment with oral or intravenous (6%) iron therapy. In multivariable analysis, haemoglobin recovery was 0.10 g/dl per week slower on average in women who were HIV+ versus women who were HIV- (P = 0.001), 0.01 g/dl per week slower in women with higher baseline ferritin (P < 0.001) and 0.06 g/dl per week faster in women who were compliant with oral iron therapy (P = 0.002). CONCLUSIONS: Compared with women who were HIV-, women who were HIV+ with iron-deficiency anaemia had slower but successful haemoglobin recovery with iron therapy. Earlier effective management of iron deficiency could reduce the incidence of peripartum blood transfusion. TWEETABLE ABSTRACT: Among pregnant women with iron-deficiency anaemia in South Africa, HIV slows haemoglobin recovery in response to oral iron therapy.

Adverse effects of iron deficiency anemia on pregnancy outcome and offspring development and intervention of three iron supplements.

Iron deficiency anemia (IDA) is a common micronutrient deficiency among pregnant women with severe consequences including impaired immuno-inflammatory system, premature birth, fetal death etc. The present study aimed to investigate the effects of three iron supplements on IDA female rats and their offspring. The IDA female rat model was established with low iron diet and the rats were then mated. After pregnancy, rats were fed diets containing different iron supplements (iron polysaccharide complex, iron protein succinylate and ferrous sulfate) until their offspring were 42 days old. Pregnancy outcomes, haematological, iron metabolism, physical and neurological development indexes were determined. The results showed that all three iron supplements improved the levels of hematological parameters of both mother and offspring rats. After iron supplementation, serum iron, transferrin saturation and serum ferritin levels were increased compared with the IDA group. The level of ferritin light chain in the liver and spleen of both mother and offspring rats in iron supplemented groups was significantly higher than that of the IDA group. The average number of born alive per litter in the iron treatment groups was significantly higher than that in the IDA group. Iron supplements also improved the physical growth and neurobehavioral development of offspring rats. It was also found that iron supplementation improved the expression of ferritin light chain and the synaptic growth associated proteins in the brain and hippocampus. No significant difference was found in the efficacy of three iron supplements. These results suggest that pregnant and postpartum IDA affects pregnancy outcomes, offspring physical development and causes neural impairment. Sufficient iron supplementation can significantly improve IDA and its adverse effects on both mother and offspring.

[Treatment of iron deficiency anemia during pregnancy with oral iron: State of practice among midwives]. / Traitement par fer oral de l'anémie ferriprive lors de la grossesse : état des pratiques chez les sages-femmes.

OBJECTIVES: Iron deficiency anemia represents a public health issue which is usually managed by midwives. Because it is associated with maternal and fetal risks, a treatment is warranted. Oral iron represents the main option for treating this condition. Despite the existence of national and international guidelines no consensus about its modality of use has emerged so far. The primary objective of this study was to analyze midwives'practice with regards to iron deficiency anemia treatment using oral iron formulations. METHODS: We conducted an observational and descriptive cross-sectional in a sample of midwives from the Gironde administrative region using a questionnaire. RESULTS: We obtained 85 questionnaires from midwives working in private or public health facilities. Doses of iron and duration of treatment seem insufficient for a majority of responders. Folic acid and vitamin C are often associated with oral iron. Most midwives assess the efficacy of oral iron at one month with hemoglobin and ferritin levels. A significant fraction of these midwives shares similar practices which are in good accordance with the literature such as patient counselling with regards to drug intake, management of gastrointestinal side effects and inefficacity of oral iron. Noticeably, some of these midwives don't follow any guidelines. CONCLUSION: The majority of participants demonstrated practices in accordance with various national guidelines although no precise therapeutic algorithm is available as reference. Larger studies on the management of iron deficiency anemia in pregnancy by health professionals and harmonization of practices are necessary.

The use of intravenous iron in pregnancy: for whom and when? A survey of Australian and New Zealand obstetricians.

BACKGROUND: Iron deficiency anaemia in pregnancy (IDAP) affects 11-18% of Australian pregnancies and is associated with adverse perinatal outcomes. National prescribing data suggests the use of intravenous iron in pregnancy is increasingly common. This study aimed to: 1) Establish the current patterns of intravenous iron use by Fellows of the Royal Australian and New Zealand College of Obstetricians (FRANZCOG) when treating iron deficiency and IDAP including immediately postpartum and; 2) Assess FRANZCOG opinions regarding potential trial of intravenous iron for first-line treatment of IDAP. METHODS: An online survey of RANZCOG Fellows practicing obstetrics was distributed in September 2018. Results were analysed descriptively and responses compared by clinician demographics using Chi-squared testing. RESULTS: Of 484 respondents (21% of FRANZCOG), 457 were currently practicing obstetrics. Most prescribed intravenous iron in pregnancy (96%) and/or postpartum (85%). Most intravenous iron was prescribed for IDAP (98%) rather than iron deficiency without anaemia (53%), and for IDAP most commonly second-line to failed oral iron supplementation and first-line in special circumstances (59%). Intravenous iron prescribing was associated with shorter time since FRANZCOG completion (p = 0.01), public hospital practice (p = 0.008) and higher hospital birth numbers (p = 0.01). Most respondents (90%) would consider a randomised controlled trial of first-line intravenous iron for IDAP, although views on appropriate thresholds differed. CONCLUSIONS: Almost all respondents prescribed intravenous iron for IDAP, and while mostly used for second-line treatment over half sometimes used it first-line. With accelerating intravenous iron use, further research is required into its optimal use in pregnancy, recognizing important clinical outcomes and cost effectiveness.

Intravenous iron isomaltoside versus oral iron supplementation for treatment of iron deficiency in pregnancy: protocol for a randomised, comparative, open-label trial.

BACKGROUND: Iron deficiency is common in pregnancy. If left untreated, iron deficiency can lead to iron deficiency anaemia, which is a condition related to maternal and neonatal morbidity. The prevalence of iron deficiency increases through the trimesters, which means that women with iron deficiency in the beginning of pregnancy also have a great risk of developing iron deficiency anaemia during pregnancy. Standard treatment is oral iron in individualised intensified doses based on screening values in 1st trimester. Maternal symptoms of iron deficiency and iron deficiency anaemia include fatigue, reduced physical performance, and restless legs syndrome (RLS). Severe anaemia may cause dizziness, dyspnea, palpitation, orthostatism, and syncope, and it decreases the woman's ability to cope with blood loss during delivery. The anaemia may also compromise contractility in the uterine musculature increasing the risk for prolonged labour, caesarean section, and postpartum haemorrhage. Foetal iron deficiency may cause low birthweight and adversely affect foetal and early childhood brain development with long-term deficits. METHODS: In this randomised comparative, open-label, single-centre, phase IV trial, 200 pregnant women between 14 and 21 weeks of gestation who have iron deficiency after 4 weeks of standard treatment will be randomised 1:1 to either a single 1000 mg dose of intravenously administered ferric derisomaltose/iron isomaltoside 1000 or a fixed dose of 100 mg oral ferrous fumarate containing 60 mg ascorbic acid. The primary endpoint is to prevent iron deficiency anaemia defined by a low level of haemoglobin throughout the trial. Other endpoints include other haematological indices of iron deficiency and anaemia, clinical outcomes by questionnaires, and collection of adverse events. Explorative endpoints by medical record follow-up include complications up to 7 days after delivery. DISCUSSION: This trial will provide evidence on how to prevent iron deficiency anaemia. The trial population represents a clinical reality where pregnant women often have sustained iron deficiency despite an increased oral iron dose. Thus, this evidence can be used to consider the optimal 2nd line of treatment in iron-deficient pregnant women. TRIAL REGISTRATION: European Union Drug Regulating Authorities Clinical Trials Database 2017-000776-29. Registered on 3 May 2017. ClinicalTrials.gov NCT03188445 . Registered on 15 June 2017.

Use of deferoxamine (DFO) in transfusion-dependent ß-thalassemia during pregnancy: A retrospective study.

OBJECTIVE: To report cases of use of chelation therapy during pregnancy which resulted in favorable outcomes for the babies. MATERIALS AND METHODS: In this retrospective cohort study, we described the evolution and outcome of 9 pregnancies in Italian thalassemic women who received deferoxamine (DFO) inadvertently during early pregnancy. RESULTS: The use of deferoxamine during first trimester did not lead to adverse effects on the fetus or cause major complications for the gestation, although an increase in iron burden was observed after suspending chelation therapy. CONCLUSION: In our experience, iron-chelation therapy might be administrated in pregnancy where the benefits to the mother outweigh the potential risks to the baby.

The Effectiveness of Different Doses of Iron Supplementation and the Prenatal Determinants of Maternal Iron Status in Pregnant Spanish Women: ECLIPSES Study.

Iron deficiency (ID), anemia, iron deficiency anemia (IDA) and excess iron (hemoconcentration) harm maternal-fetal health. We evaluated the effectiveness of different doses of iron supplementation adjusted for the initial levels of hemoglobin (Hb) on maternal iron status and described some associated prenatal determinants. The ECLIPSES study included 791 women, randomized into two groups: Stratum 1 (Hb = 110-130g/L, received 40 or 80mg iron daily) and Stratum 2 (Hb > 130g/L, received 20 or 40mg iron daily). Clinical, biochemical, and genetic information was collected during pregnancy, as were lifestyle and sociodemographic characteristics. In Stratum 1, using 80 mg/d instead of 40 mg/d protected against ID on week 36. Only women with ID on week 12 benefited from the protection against anemia and IDA by increasing Hb levels. In Stratum 2, using 20 mg/d instead of 40 mg/d reduced the risk of hemoconcentration in women with initial serum ferritin (SF) ≥ 15 µg/L, while 40 mg/d improved SF levels on week 36 in women with ID in early pregnancy. Mutations in the HFE gene increased the risk of hemoconcentration. Iron supplementation should be adjusted to early pregnancy levels of Hb and iron stores. Mutations of the HFE gene should be evaluated in women with high Hb levels in early pregnancy.

Hepcidin-guided screen-and-treat interventions against iron-deficiency anaemia in pregnancy: a randomised controlled trial in The Gambia.

BACKGROUND: WHO recommends daily iron supplementation for pregnant women, but adherence is poor because of side-effects, effectiveness is low, and there are concerns about possible harm. The iron-regulatory hormone hepcidin can signal when an individual is ready-and-safe to receive iron. We tested whether a hepcidin-guided screen-and-treat approach to combat iron-deficiency anaemia could achieve equivalent efficacy to universal administration, but with lower exposure to iron. METHODS: We did a three-arm, randomised, double-blind, non-inferiority trial in 19 rural communities in the Jarra West and Kiang East districts of The Gambia. Eligible participants were pregnant women aged 18-45 years at between 14 weeks and 22 weeks of gestation. We randomly allocated women to either WHO's recommended regimen (ie, a daily UN University, UNICEF, and WHO international multiple-micronutrient preparation [UNIMMAP] containing 60 mg iron), a 60 mg screen-and-treat approach (ie, daily UNIMMAP containing 60 mg iron for 7 days if weekly hepcidin was <2·5 µg/L or UNIMMAP without iron if hepcidin was ≥2·5 µg/L), or a 30 mg screen-and-treat approach (ie, daily UNIMMAP containing 30 mg iron for 7 days if weekly hepcidin was <2·5 µg/L or UNIMMAP without iron if hepcidin was ≥2·5 µg/L). We used a block design stratified by amount of haemoglobin at enrolment (above and below the median amount of haemoglobin on every enrolment day) and stage of gestation (14-18 weeks vs 19-22 weeks). Participants and investigators were unaware of the random allocation. The primary outcome was the amount of haemoglobin at day 84 and was measured as the difference in haemoglobin in each screen-and-treat group compared with WHO's recommended regimen; the non-inferiority margin was set at -5·0 g/L. The primary outcome was assessed in the per-protocol population, which comprised all women who completed the study. This trial is registered with the ISRCTN registry, number ISRCTN21955180. FINDINGS: Between June 16, 2014, and March 3, 2016, 498 participants were randomised, of whom 167 were allocated to WHO's recommended regimen, 166 were allocated to the 60 mg per day screen-and-treat approach, and 165 were allocated to the 30 mg per day screen-and-treat approach. 78 participants were withdrawn or lost to follow-up during the study; thus, the per-protocol population comprised 140 women assigned to WHO's recommended regimen, 133 allocated to the 60 mg screen-and-treat approach, and 147 allocated to the 30 mg screen-and-treat approach. The screen-and-treat approaches did not exceed the non-inferiority margin. Compared with WHO's recommended regimen, the difference in the amount of haemoglobin at day 84 was -2·2 g/L (95% CI -4·6 to 0·1) with the 60 mg screen-and-treat approach and -2·7 g/L (-5·0 to -0·5) with the 30 mg screen-and-treat approach. Adherence, reported side-effects, and adverse events were similar between the three groups. The most frequent side-effect was stomachache, which was similar in the 60 mg screen-and-treat group (82 cases per 1906 person-weeks) and with WHO's recommended regimen (81 cases per 1974 person-weeks; effect 1·0, 95% CI 0·7 to 1·6); in the 30 mg screen-and-treat group the frequency of stomachache was slightly lower than with WHO's recommended regimen (58 cases per 2009 person-weeks; effect 0·7, 95% CI 0·5 to 1·1). No participants died during the study. INTERPRETATION: The hepcidin-guided screen-and-treat approaches had no advantages over WHO's recommended regimen in terms of adherence, side-effects, or safety outcomes. Our results suggest that the current WHO policy for iron administration to pregnant women should remain unchanged while more effective approaches continue to be sought. FUNDING: Bill & Melinda Gates Foundation and the UK Medical Research Council.

Use of alternative methods in the treatment of anemia in pregnant women - prospective observational study.

O BJECTIVES: Anemia in pregnant women is a common condition, diagnosed when the concentration of hemoglobin falls below 11 g/dL. Taking into consideration the accounts of nephrologists about good results of treatment of secondary anemia using erythropoietin in patients with renal failure, we tried to use EPO to cure anemia in pregnant women. The aim of the study was to evaluate the results of EPO treatment on pregnant women diagnosed with iron deficiency anemia, as well as possible side effects. MATERIAL AND METHODS: The study consisted of 25 patients: Group I - treated with iron supplement administered parenterally - Ferrum Lek every two days intramuscularly. Group II - treated with recombinant human erythropoietin - 1000 j intravenously every three days, with oral iron sup- plements. RESULTS: After a week of treatment the positive response was higher in the second group (92.3% in II, vs 33.3% in I, p < 0.005). The average increase of hemoglobin and RBC was significantly higher in II group. An increase in hemoglobin did not correlate with the age of women (r = 0.07) or with the duration of pregnancy (r = 0.08). However, a negative correlation was found between basic hemoglobin level and its increase after treatment (r = 0.602). CONCLUSIONS: EPO administered with the oral dose of iron in pregnant women with anemia caused by iron deficiency shows higher effectiveness than the use of iron preparations parenterally. The usage of EPO during pregnancy is not related to any dangerous side effects for the mother or fetus.

Factors associated with adherence to iron folate supplementation among pregnant women in West Dembia district, northwest Ethiopia: a cross sectional study.

OBJECTIVE: In Ethiopia, iron folate tablets are prescribed for all pregnant mothers during their antenatal visits and given for free; however, only limited data are available on their adherence. Therefore, the aim of this study was to assess adherence to iron folate supplementation and its associated factors among pregnant women in West Dembia district, northwest Ethiopia. An institution based cross-sectional study was conducted on 348 pregnant women that had at least one antenatal care visit. Bivariate and multivariate logistic regressions were employed to identify the predictors at p-value < 0.2 and 0.05 respectively. RESULTS: Adherence to iron folate supplementation in this study was 52.9% [95% CI (47.7, 58.0%)]. Women who had good knowledge about anemia (AOR: 2.63, 95% CI 1.51, 4.59), knowledge about iron folate supplementation (AOR: 2.82, 95% CI 1.52-5.23), four and more ANC visits (AOR: 6.97, 95% CI 3.25, 14.96), and anemia history during current pregnancy (AOR: 13.87, 95% CI 3.75, 51.35) were significantly associated with adherence to iron folate supplementation. Therefore, preventing prenatal anemia, improving knowledge of women about anaemia and iron folate supplementation, and increasing ANC services are essential to increase adherence.

Lactoferrin plus health education versus total dose infusion (TDI) of low-molecular weight (LMW) iron dextran for treating iron deficiency anemia (IDA) in pregnancy: a randomized controlled trial.

BACKGROUND: Iron deficiency anemia (IDA) is one of the most common medical disorder disturbing pregnancies particularly in low resources countries, and contributes significantly to morbidities and mortalities. Thus, early diagnosis and prompt management of IDA is highly recommended. AIM: To Test the efficacy and safety of oral lactoferrin plus health education provided by a nurse versus total dose infusion (TDI) of low-molecular weight (LMW) iron dextran for treating IDA in the second and third trimester of pregnancy. DESIGN: A prospective interventional, randomized, parallel-group, single-center longitudinal study. SETTING: Woman's Health Assiut University Hospital, Assiut, Egypt, at the outpatient clinic and inpatient unit. It comprised 120 cases divided into two groups as pineapple flavored lactoferrin oral sachets 100 mg twice daily with health education (group A) and TDI of LMW iron dextran (group B). MAIN OUTCOME MEASURES: The primary efficacy parameter was clinical improvement and the amount of increase in hemoglobin concentration by 4 weeks after therapy, secondary outcome measures included measurement of the rest of RBC, and iron indices, the adverse effects related to iron therapy and the patient compliance to the treatment. RESULTS: There was insignificant difference between both groups regarding sociodemographic data, parity and mean gestational age. Both groups showed a significant clinical improvement of anemia 4 weeks post-therapy. There was no statistically significant difference in mean Hb level improvement in both groups after 1 month of therapy. However, mean corpuscular volume (MCV) and mean corpuscular hemoglobin (MCH) improved significantly more in group B than A while iron indices (serum iron and serum ferritin) were significantly more in group A than group B. CONCLUSIONS: Pineapple flavored lactoferrin oral sachets plus health education can be widely used as an alternative to TDI iron dextran supplementation due to clinical as well as laboratory improvement of IDA during pregnancy after 1 month of treatment. Proper health education of the pregnant women with nurse recommendations of balanced diet containing good sources of iron would increase awareness of pregnant women and help eradicate IDA with its serious sequel during pregnancy.