-
1.
Iron preparations for women of reproductive age with iron deficiency anaemia in pregnancy (FRIDA): a systematic review and network meta-analysis.
Rogozińska, E, Daru, J, Nicolaides, M, Amezcua-Prieto, C, Robinson, S, Wang, R, Godolphin, PJ, Saborido, CM, Zamora, J, Khan, KS, et al
The Lancet. Haematology. 2021;(7):e503-e512
-
-
Free full text
-
Abstract
BACKGROUND Numerous iron preparations are available for the treatment of iron deficiency anaemia in pregnancy. We aimed to provide a summary of the effectiveness and safety of iron preparations used in this setting. METHODS We did a systematic review and network meta-analysis of randomised trials. We searched MEDLINE, Embase, Cochrane Central Register of Controlled Trials, trial registers, and grey literature for trials published in any language from Jan 1, 2011, to Feb 28, 2021. We included trials including pregnant women with iron deficiency anaemia and evaluating iron preparations, irrespective of administration route, with at least 60 mg of elemental iron, in comparison with another iron or non-iron preparation. Three authors independently selected studies, extracted data, and did a risk of bias assessment using the Cochrane tool (version 1.0). The primary outcome was the effectiveness of iron preparations, evaluated by changes in haemoglobin concentration at 4 weeks from baseline. The secondary outcomes were change in serum ferritin concentration at 4 weeks from baseline and treatment-related severe and non-severe adverse events. We did random-effects pairwise and network meta-analyses. Side-effects were reported descriptively for each trial. This study is registered with PROSPERO, CRD42018100822. FINDINGS Among 3037 records screened, 128 full-text articles were further assessed for eligibility. Of the 53 eligible trials (reporting on 9145 women), 30 (15 interventions; 3243 women) contributed data to the network meta-analysis for haemoglobin and 15 (nine interventions; 1396 women) for serum ferritin. The risk of bias varied across the trials contributing to network meta-analysis, with 22 of 30 trials in the network meta-analysis for haemoglobin judged to have a high or medium global risk of bias. Compared with oral ferrous sulfate, intravenous iron sucrose improved both haemoglobin (mean difference 7·17 g/L, 95% CI 2·62-11·73; seven trials) and serum ferritin (mean difference 49·66 μg/L, 13·63-85·69; four trials), and intravenous ferric carboxymaltose improved haemoglobin (mean difference 8·52 g/L, 0·51-16·53; one trial). The evidence for other interventions compared with ferrous sulfate was insufficient. The most common side-effects with oral iron preparations were gastrointestinal effects (nausea, vomiting, and altered bowel movements). Side-effects were less common with parenteral iron preparations, although these included local pain, skin irratation, and, on rare occasions, allergic reactions. INTERPRETATION Iron preparations for treatment of iron deficiency anaemia in pregnancy vary in effectiveness, with good evidence of benefit for intravenous iron sucrose and some evidence for intravenous ferric carboxymaltose. Clinicians and policy makers should consider the effectiveness of individual preparations before administration, to ensure effective treatment. FUNDING None.
-
2.
Can Double Fortification of Salt with Iron and Iodine Reduce Anemia, Iron Deficiency Anemia, Iron Deficiency, Iodine Deficiency, and Functional Outcomes? Evidence of Efficacy, Effectiveness, and Safety.
Larson, LM, Cyriac, S, Djimeu, EW, Mbuya, MNN, Neufeld, LM
The Journal of nutrition. 2021;(Suppl 1):15S-28S
-
-
Free full text
-
Abstract
BACKGROUND Anemia, iron deficiency, and iodine deficiency are problems of important public health concern in many parts of the world, with consequences for the health, development, and work capacity of populations. Several countries are beginning to implement double fortified salt (DFS) programs to simultaneously address iodine and iron deficiencies. OBJECTIVE Our objective was to summarize the evidence for efficacy and effectiveness of DFS on the full range of status and functional outcomes and across different implementation and evaluation designs essential to successful interventions. METHODS We conducted a systematic review and meta-analysis of published and gray literature examining the effects of DFS on nutritional status, cognition, work productivity, development, and morbidity of all population groups. We searched for articles in Medline, Embase, CINAHL, Cochrane Central Register, and ProQuest for randomized trials, quasi-randomized trials, and program effectiveness evaluations. RESULTS A total of 22 studies (N individuals = 52,758) were included. Efficacy studies indicated a significant overall positive effect on hemoglobin concentration [standardized mean difference (95% CI): 0.33 (0.18, 0.48)], ferritin [0.42 (0.08, 0.76)], anemia [risk ratio (95% CI): 0.80 (0.70, 0.92)], and iron deficiency anemia [0.36 (0.24, 0.55)]. Effects on urinary iodine concentration were not significantly different between DFS and iodized salt. The impact on functional outcomes was mixed. Only 2 effectiveness studies were identified. They reported programmatic challenges including low coverage, suboptimal DFS quality, and storage constraints. CONCLUSIONS Given the biological benefits of DFS across several populations in efficacy research, additional evaluations of robust DFS programs delivered at scale, which consider effective implementation and measure appropriate biomarkers, are needed.
-
3.
Effects of dietary polyphenol supplementation on iron status and erythropoiesis: a systematic review and meta-analysis of randomized controlled trials.
Xu, T, Zhang, X, Liu, Y, Wang, H, Luo, J, Luo, Y, An, P
The American journal of clinical nutrition. 2021;(2):780-793
-
-
Free full text
-
Abstract
BACKGROUND The iron-chelating activities of polyphenols raise concern whether there is a risk of iron deficiency or anemia induced by polyphenol supplementation. Results from clinical trials regarding the effects of polyphenol supplementation on iron status and erythropoiesis are inconclusive. OBJECTIVE We performed a systematic review and meta-analysis of randomized controlled trials to determine the effects of polyphenol supplementation on iron status and erythropoiesis. METHODS Published articles were searched between May 1988 and 7 December, 2020. Finally, we identified 34 randomized controlled trials. Random-effects meta-analyses were performed to obtain the weighted mean difference of serum iron (SI), transferrin saturation (TS), ferritin, and hemoglobin concentration. Funnel plots and Egger's test were used to determine the risk of bias. The robustness of the effect sizes was examined by sensitivity analysis. RESULTS Polyphenol supplementation had an inhibitory effect on the SI concentration (-13.72 μg/dL; 95% CI: -20.74, -6.71) and TS (-3.10%; 95% CI: -4.93, -1.27), with no effect on ferritin (-9.34 ng/mL; 95% CI: -28.55, 9.87). Polyphenols increased the hemoglobin concentration (8.53 g/L; 95% CI: 3.33, 13.73). In healthy participants, polyphenol reduced the TS (-3.83%; 95% CI: -7.47, -0.19) and increased the hemoglobin concentration (12.87 g/L; 95% CI: 1.61, 24.14). Similarly, polyphenol reduced the SI concentration (-8.60 μg/dL; 95% CI: -16.10, -1.10) and increased the hemoglobin concentration (8.50 g/L; 95% CI: 0.86, 16.15) in patients with metabolic diseases. In patients with β-thalassemia, polyphenol decreased the SI concentration (-23.19 μg/dL; 95% CI: -35.84, -10.55), TS (-3.23%; 95% CI: -5.54, -0.91), and ferritin concentration (-223.62 ng/mL; 95% CI: -359.32, -87.91), but had no effect on the hemoglobin concentration. CONCLUSION Healthy individuals and patients with metabolic diseases may benefit from the positive impact of polyphenols on erythropoiesis. Patients with β-thalassemia may benefit from the effect of polyphenols on reducing SI. This trial was registered at PROSPERO (International prospective register of systematic reviews) as CRD42020161983.
-
4.
Helicobacter pylori infection and micronutrient deficiency in pregnant women: a systematic review and meta-analysis.
Afsar, MNA, Jhinu, ZN, Bhuiyan, MAI, Islam, Z, Siddiqua, TJ
BMJ open gastroenterology. 2020;(1)
Abstract
BACKGROUND Over the last few years, epidemiological studies have shown that infection with Helicobacter pylori has a major effect on micronutrient deficiency as well as on adverse pregnancy outcomes. Importantly, there are gaps in understanding the linkage of H. pylori infection with micronutrients deficiency in pregnant women. OBJECTIVE We conducted a systematic review and meta-analysis to estimate the association between H. pylori infection and micronutrient deficiencies in pregnant women. METHODS A systematic literature search was conducted for relevant articles using PubMed, Web of Science, and Scopus database from inception to March 2020. The OR with 95% CIs was determined by meta-analysis of data extracted from the selected studies. RESULTS From 2384 primary articles, 6 studies were selected for systematic reviews and 4 studies distinctively (with 1274 participants: 553 cases and 721 controls) were selected for meta-analysis. The meta-analysed fixed effect model estimated the odds of having H. pylori infection was not significantly higher among pregnant women with micronutrient deficiencies than those without deficiencies (OR=1.12, 95% CI 0.88 to 1.42, p=0.37). In the subgroup analysis, no correlation was found between H. pylori infection and vitamin B12 (OR=0.74, 95% CI 0.45 to 1.21, p=0.22), folate (OR=1.07, 95% CI 0.73 to 1.58, p=0.73), and ferritin (OR=0.81, 95% CI 0.51 to 1.31, p=0.4). However, a positive correlation was found between iron-deficiency anaemia (IDA) and H. pylori infection (OR=16.23, 95% CI 4.19 to 62.93, p<0.0001) during pregnancy. CONCLUSION H. pylori infection is associated with increased risk of IDA but not with deficiency of other micronutrients in pregnancy. PROSPERO REGISTRATION NUMBER CRD42019135683.
-
5.
Association of maternal iron deficiency anemia with the risk of gestational diabetes mellitus: a meta-analysis.
Tiongco, RE, Arceo, E, Clemente, B, Pineda-Cortel, MR
Archives of gynecology and obstetrics. 2019;(1):89-95
Abstract
PURPOSE The aim of the study was to conduct a meta-analysis investigating the association of maternal iron deficiency anemia (IDA) and risk of gestational diabetes mellitus (GDM). METHODS Literature search was conducted in various database websites such as PubMed, Cochrane Library, and Web of Science up to 17 June 2018 for related publications written in English. Selected data were extracted from the included studies and were subjected to statistical analysis. Odds ratios (ORs) and 95% confidence intervals (CIs) were computed, pooled, and interpreted. Subgroup analysis by ethnicity (Asians vs. Caucasians) was also performed. RESULTS Six studies with a total sample size of 15,157 from various countries were included in this meta-analysis. Pooled ORs of all publications included show that pregnant women with IDA have a reduced risk of developing GDM (OR 0.61; 95% CI 0.47-0.80; PA = 0.0003). Subgroup analysis, on the other hand, showed significant associations among Asians (OR 0.60; 95% CI 0.45-0.79; PA = 0.0003) than Caucasians (OR 0.76; 95% CI 0.32-1.76; PA = 0.52). CONCLUSION Results of this meta-analysis suggests that pregnant women with IDA are 39% less likely to develop GDM. However, more studies are needed to confirm the claims of our results.
-
6.
Intermittent iron supplementation for reducing anaemia and its associated impairments in adolescent and adult menstruating women.
Fernández-Gaxiola, AC, De-Regil, LM
The Cochrane database of systematic reviews. 2019;(1):CD009218
-
-
Free full text
-
Abstract
BACKGROUND Anaemia is a condition in which the number of red blood cells is insufficient to meet physiologic needs; it is caused by many conditions, particularly iron deficiency. Traditionally, daily iron supplementation has been a standard practice for preventing and treating anaemia. However, its long-term use has been limited, as it has been associated with adverse side effects such as nausea, constipation, and teeth staining. Intermittent iron supplementation has been suggested as an effective and safer alternative to daily iron supplementation for preventing and reducing anaemia at the population level, especially in areas where this condition is highly prevalent. OBJECTIVES To assess the effects of intermittent oral iron supplementation, alone or in combination with other nutrients, on anaemia and its associated impairments among menstruating women, compared with no intervention, a placebo, or daily supplementation. SEARCH METHODS In February 2018, we searched CENTRAL, MEDLINE, Embase, nine other databases, and two trials registers. In March 2018, we also searched LILACS, IBECS and IMBIOMED. In addition, we examined reference lists, and contacted authors and known experts to identify additional studies. SELECTION CRITERIA Randomised controlled trials (RCTs) and quasi-RCTs with either individual or cluster randomisation. Participants were menstruating women; that is, women beyond menarche and prior to menopause who were not pregnant or lactating and did not have a known condition that impeded the presence of menstrual periods. The intervention was the use of iron supplements intermittently (one, two or three times a week on non-consecutive days) compared with placebo, no intervention, or the same supplements provided on a daily basis. DATA COLLECTION AND ANALYSIS Both review authors independently assessed the eligibility of studies against the inclusion criteria, extracted data from included studies, checked data entry for accuracy, assessed the risk of bias of the included studies, and rated the quality of the evidence using GRADE. MAIN RESULTS We included 25 studies involving 10,996 women. Study methods were not well described in many of the included studies and thus assessing risk of bias was difficult. The main limitations of the studies were lack of blinding and high attrition. Studies were mainly funded by international organisations, universities, and ministries of health within the countries. Approximately one third of the included studies did not provide a funding source.Although quality across studies was variable, the results consistently showed that intermittent iron supplementation (alone or with any other vitamins and minerals) compared with no intervention or a placebo, reduced the risk of having anaemia (risk ratio (RR) 0.65, 95% confidence interval (CI) 0.49 to 0.87; 11 studies, 3135 participants; low-quality evidence), and improved the concentration of haemoglobin (mean difference (MD) 5.19 g/L, 95% CI 3.07 to 7.32; 15 studies, 2886 participants; moderate-quality evidence), and ferritin (MD 7.46 μg/L, 95% CI 5.02 to 9.90; 7 studies, 1067 participants; low-quality evidence). Intermittent regimens may also reduce the risk of having iron deficiency (RR 0.50, 95% CI 0.24 to 1.04; 3 studies, 624 participants; low-quality evidence), but evidence was inconclusive regarding iron deficiency anaemia (RR 0.07, 95% CI 0.00 to 1.16; 1 study, 97 participants; very low-quality evidence) and all-cause morbidity (RR 1.12, 95% CI 0.82 to 1.52; 1 study, 119 participants; very low-quality evidence). Women in the control group were less likely to have any adverse side effects than those receiving intermittent iron supplements (RR 1.98, 95% CI 0.31 to 12.72; 3 studies, 630 participants; moderate-quality evidence).In comparison with daily supplementation, results showed that intermittent supplementation (alone or with any other vitamins and minerals) produced similar effects to daily supplementation (alone or with any other vitamins and minerals) on anaemia (RR 1.09, 95% CI 0.93 to 1.29; 8 studies, 1749 participants; moderate-quality evidence). Intermittent supplementation may produce similar haemoglobin concentrations (MD 0.43 g/L, 95% CI -1.44 to 2.31; 10 studies, 2127 participants; low-quality evidence) but lower ferritin concentrations on average (MD -6.07 μg/L, 95% CI -10.66 to -1.48; 4 studies, 988 participants; low-quality evidence) compared to daily supplementation. Compared to daily regimens, intermittent regimens may also reduce the risk of having iron deficiency (RR 4.30, 95% CI 0.56 to 33.20; 1 study, 198 participants; very low-quality evidence). Women receiving iron supplements intermittently were less likely to have any adverse side effects than those receiving iron supplements daily (RR 0.41, 95% CI 0.21 to 0.82; 6 studies, 1166 participants; moderate-quality evidence). No studies reported on the effect of intermittent regimens versus daily regimens on iron deficiency anaemia and all-cause morbidity.Information on disease outcomes, adherence, economic productivity, and work performance was scarce, and evidence about the effects of intermittent supplementation on these outcomes unclear.Overall, whether the supplements were given once or twice weekly, for less or more than three months, contained less or more than 60 mg of elemental iron per week, or given to populations with different degrees of anaemia at baseline did not seem to affect the findings. Furthermore, the response did not differ in areas where malaria was frequent, although very few trials were conducted in these settings. AUTHORS' CONCLUSIONS Intermittent iron supplementation may reduce anaemia and may improve iron stores among menstruating women in populations with different anaemia and malaria backgrounds. In comparison with daily supplementation, the provision of iron supplements intermittently is probably as effective in preventing or controlling anaemia. More information is needed on morbidity (including malaria outcomes), side effects, work performance, economic productivity, depression, and adherence to the intervention. The quality of this evidence base ranged from very low to moderate quality, suggesting that we are uncertain about these effects.
-
7.
A Systematic Review and Meta-Analysis on the Effects of Probiotic Species on Iron Absorption and Iron Status.
Vonderheid, SC, Tussing-Humphreys, L, Park, C, Pauls, H, OjiNjideka Hemphill, N, LaBomascus, B, McLeod, A, Koenig, MD
Nutrients. 2019;(12)
Abstract
BACKGROUND Strategies to prevent iron deficiency anemia (IDA) have varying effectiveness. The purpose of this systematic review of the literature and meta-analysis was to examine the effects of probiotics on iron absorption and iron status-related markers in humans. METHODS We followed the preferred reporting items for systematic reviews and meta-analyses (PRISMA) reporting guidelines. Relevant articles were identified from Embase, Pubmed, Scopus, and CINAHL from inception to February, 2019. We conducted a meta-analysis for eight studies examining the effect of the probiotic Lactobacillus plantarum 299v (Lp299v) on iron absorption. RESULTS Fifteen studies reported in 12 articles were identified (N = 950). Our meta-analysis of eight studies using a random-effects model demonstrated a significant increase in iron absorption following administration of the probiotic Lp299v with a pooled standardized mean difference (an average intervention effect size) of 0.55 (95% CI 0.22-0.88, p = 0.001). Of the seven randomized clinical trials (RCTs) and nonrandomized clinical trials examining a range of probiotic species on iron status, only one study supplementing with Lp299v showed improvement in serum iron; no other studies reported improvement in iron status-related indices with probiotic treatment. CONCLUSIONS Lp299v significantly improved iron absorption in humans. Future research should include the assessment of Lp299v effect on iron absorption and iron status in populations at high risk of IDA, including pregnant women.
-
8.
Lactoferrin or ferrous salts for iron deficiency anemia in pregnancy: A meta-analysis of randomized trials.
Abu Hashim, H, Foda, O, Ghayaty, E
European journal of obstetrics, gynecology, and reproductive biology. 2017;:45-52
Abstract
This systematic review and meta-analysis aimed to evaluate the efficacy of daily oral bovine lactoferrin versus daily oral ferrous iron preparations for treatment of iron deficiency anemia (IDA) during pregnancy. Searches were conducted on PubMed, ScienceDirect, ClinicalTrials.gov and CENTRAL databases from inception to February 2017 and the bibliographies of retrieved articles were screened. The PRISMA Statement was followed. Published English language randomized trials comparing lactoferrin with oral ferrous iron preparations in pregnant women with iron deficiency anemia were included. Quasi-randomized, non- randomized or studies including other known cause of anemia, gestational or pre-existent maternal diseases were excluded. Accordingly, 4 eligible trials (600 women) were analyzed. Primary outcome was change in hemoglobin level at 4 weeks of treatment. Secondary outcomes were; change in serum ferritin and iron, rates of gastrointestinal side effects, preterm birth, low birthweight, neonatal death and mean birthweight. Quality assessment was performed by the Cochrane risk of bias tool. Odds ratio and mean difference were used to integrate dichotomous and continuous outcomes respectively. Pooled estimates for change in hemoglobin levels at four weeks favored daily oral lactoferrin over daily oral ferrous sulphate (mean difference 0.77; 95% confidence interval [CI] 0.04-1.55; P=0.04, 4 trials, 600 women). However, after subgroup analysis (degree of anemia), no significant difference in hemoglobin levels were found between both groups in mild anemia (mean difference 0.80; 95% CI -0.21 to 1.82, 3 trials, 372 women), but a significant increase favoring lactoferrin was reported in moderate anemia (mean difference 0.68; 95% CI 0.53-0.83; P<0.00001, one trial, 228 women). Significantly less gastrointestinal side effects were reported with lactoferrin treatment. No significant differences existed with regard to other outcomes. In conclusion, for pregnant women with IDA, daily oral bovine lactoferrin is just as good as ferrous sulfate in improving hematological parameters with fewer gastrointestinal side effects. Thereby, lactoferrin should be the iron replacement agent of choice for treatment of IDA in pregnancy.
-
9.
Intravenous Iron Sucrose versus Oral Iron in the Treatment of Pregnancy with Iron Deficiency Anaemia: A Systematic Review.
Shi, Q, Leng, W, Wazir, R, Li, J, Yao, Q, Mi, C, Yang, J, Xing, A
Gynecologic and obstetric investigation. 2015;(3):170-8
Abstract
BACKGROUND Intravenous iron sucrose and oral iron therapy are the main therapies for iron deficiency anaemia (IDA), but there is still a debate regarding their efficacy and especially as to which one is the best choice during pregnancy. METHODS A meta-analysis of randomised controlled trials comparing patients treated with intravenous iron sucrose (intravenous group) with those treated with oral iron (oral group) for IDA during pregnancy was performed. The primary outcomes of interest were mean maternal haemoglobin and serum ferritin levels at the end of treatment. Secondary outcomes were treatment-related adverse events and foetal birth weight. RESULTS Six randomised controlled trials, involving a total of 576 women, were included in the present review. Significant increases in haemoglobin [mean difference (MD), 0.85; 95% confidence interval (CI), 0.31-1.39; p = 0.002] and ferritin levels (MD, 63.32; 95% CI, 39.46-87.18; p < 0.00001) were observed in the intravenous group. Compared with the oral group, there were fewer adverse events in the intravenous group (risk ratio, 0.50; 95% CI, 0.34-0.73; p = 0.0003). There was no significant difference in birth weight between the two groups. CONCLUSION For pregnant women who could not tolerate the side effects of oral treatment or required a rapid replacement of iron stores, intravenous iron sucrose was associated with fewer adverse events and was more effective than regular oral iron therapy.
-
10.
The safety of intravenous iron preparations: systematic review and meta-analysis.
Avni, T, Bieber, A, Grossman, A, Green, H, Leibovici, L, Gafter-Gvili, A
Mayo Clinic proceedings. 2015;(1):12-23
Abstract
OBJECTIVE To amass all available evidence regarding the safety of intravenous (IV) iron preparations to provide a true balance of efficacy and safety. METHODS Systematic review and meta-analysis of all randomized clinical trials comparing IV iron to another comparator. All electronic databases until January 1, 2014, were reviewed. Primary outcome was occurrence of severe adverse events (SAEs). Secondary outcomes included all-cause mortality and other adverse events (AEs). Subgroup analysis was performed on the basis of type of IV iron, comparator, treated condition, and system involved. RESULTS A total of 103 trials published between 1965 through 2013 were included. A total of 10,390 patients were treated with IV iron compared with 4044 patients treated with oral iron, 1329 with no iron, 3335 with placebo, and 155 with intramuscular iron. There was no increased risk of SAEs with IV iron (relative risk [RR], 1.04; 95% CI, 0.93-1.17; I(2)=9%). Subgroup analysis revealed a decreased rate of SAEs when IV iron was used to treat heart failure (RR, 0.45; 95% CI, 0.29-0.70; I(2)=0%). Severe infusion reactions were more common with IV iron (RR, 2.47; 95% CI, 1.43-4.28; I(2)=0%). There was no increased risk of infections with IV iron. Gastrointestinal AEs were reduced with IV iron. CONCLUSION Intravenous iron therapy is not associated with an increased risk of SAEs or infections. Infusion reactions are more pronounced with IV iron.