Cardiovascular training versus resistance training for fatigue in people with cancer.

With prevalence estimates between 50% and 90% of people with cancer, cancer-related fatigue is one of the most common morbidities related to cancer and its treatment. Exercise is beneficial for the treatment of cancer-related fatigue. However, the efficacy of different types of exercise (i.e. cardiovascular training and resistance training) have not yet been investigated systematically and compared directly in a meta-analysis. To compare the benefits and harms of cardiovascular training versus resistance training for treatment or prevention of cancer-related fatigue in people with cancer. We searched CENTRAL, MEDLINE, Embase, and five other databases in January 2023. We searched ClinicalTrials.gov and the International Clinical Trials Registry Platform for ongoing trials. We integrated results from update searches of previously published Cochrane reviews. In total, our searches included trials from inception to October 2023. We included randomised controlled trials investigating cardiovascular training compared with resistance training, with exercise as the main component. We included studies on adults with cancer (aged 18 years and older), with or without a diagnosis of cancer-related fatigue, for any type of cancer and any type of cancer treatment, with the intervention starting before, during, or after treatment. We included trials evaluating at least one of our primary outcomes (cancer-related fatigue or quality of life). We excluded combined cardiovascular and resistance interventions, yoga, and mindfulness-based interventions. Our primary outcomes were cancer-related fatigue and quality of life. Our secondary outcomes were adverse events, anxiety, and depression. We used standard Cochrane methodology. For analyses, we pooled results within the same period of outcome assessment (i.e. short term (up to and including 12 weeks' follow-up), medium term (more than 12 weeks' to less than six months' follow-up), and long term (six months' follow-up or longer)). We assessed risk of bias using the Cochrane RoB 1 tool, and certainty of the evidence using GRADE. We included six studies with 447 participants with prostate, breast, or lung cancer who received radiotherapy or chemotherapy, had surgery, or a combination of these. All studies had a high risk of bias due to lack of blinding. Three studies had an additional high risk of bias domain; one study for attrition bias, and two studies for selection bias. Interventions in the cardiovascular training groups included training on a cycle ergometer, treadmill, an elliptical trainer, or indoor bike. Interventions in the resistance training group included a varying number of exercises using bodyweight, weights, or resistance bands. Interventions varied in frequency, intensity, and duration. None of the included studies reported including participants with a confirmed cancer-related fatigue diagnosis. The interventions in four studies started during cancer treatment and in two studies after cancer treatment. Before treatment No studies reported interventions starting before cancer treatment. During treatment The evidence was very uncertain about the effect of cardiovascular training compared with resistance training for short-term cancer-related fatigue (mean difference (MD) -0.29, 95% confidence interval (CI) -2.52 to 1.84; 4 studies, 311 participants; Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-Fatigue) scale where higher values indicate better outcome; very low-certainty evidence) and long-term cancer-related fatigue (MD 1.30, 95% CI -2.17 to 4.77; 1 study, 141 participants; FACIT-Fatigue scale; very low-certainty evidence). The evidence was very uncertain about the effect of cardiovascular training compared with resistance training for short-term quality of life (MD 1.47, 95% CI -1.47 to 4.42; 4 studies, 319 participants; Functional Assessment of Cancer Therapy - General scale where higher values indicate better outcome; very low-certainty evidence) and for long-term quality of life (MD 3.40, 95% CI -4.85 to 11.65; 1 study, 141 participants; Functional Assessment of Cancer Therapy - Anemia scale where higher values indicate better outcome; very low-certainty evidence). The evidence is very uncertain about the effect of cardiovascular training compared with resistance training on the occurrence of adverse events at any follow-up (risk ratio (RR) 2.00, 95% CI 0.19 to 21.18; 2 studies, 128 participants; very low-certainty evidence). No studies reported medium-term cancer-related fatigue or quality of life. After treatment The evidence was very uncertain about the effect of cardiovascular training compared with resistance training for short-term cancer-related fatigue (MD 1.47, 95% CI -0.09 to 3.03; 1 study, 95 participants; Multidimensional Fatigue Inventory-20 General Fatigue subscale where higher values indicate worse outcome; very low-certainty evidence). Resistance training may improve short-term quality of life compared to cardiovascular training, but the evidence is very uncertain (MD -10.96, 95% CI -17.77 to -4.15; 1 study, 95 participants; European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-C30 Global Health subscale where higher values indicate better outcome; very low-certainty evidence). No studies reported outcomes at medium-term or long-term follow-up. The evidence is very uncertain about the effects of cardiovascular training compared with resistance training on treatment of cancer-related fatigue in people with cancer. Larger, well-conducted studies including people with different cancer types receiving different treatments are needed to increase the certainty in the evidence and to better understand who may benefit most from cardiovascular or resistance training. Moreover, studies comparing the effects of cardiovascular and resistance training initiated before as well as after cancer treatment are needed to understand the prophylactic and rehabilitative effects of these exercise types on cancer-related fatigue.

Oeser A ，Messer S ，Wagner C ，Wender A ，Cryns N ，Bröckelmann PJ ，Holtkamp U ，Baumann FT ，Wiskemann J ，Monsef I ，Scherer RW ，Mishra SI ，Ernst M ，Skoetz N ... -  《Cochrane Database of Systematic Reviews》

Resistance training for fatigue in people with cancer.

Cancer-related fatigue (CRF) is one of the most common symptoms associated with cancer and its treatment. Different types of exercise have demonstrated beneficial effects on CRF. Previous evidence syntheses provided promising but inconclusive results when focusing on the effects of resistance training. To evaluate the effects of resistance training on CRF in people with cancer and, specifically, to compare the effects of resistance training with no training on CRF at: different periods of treatment in relation to anticancer therapy (before, during, or after anticancer therapy); different periods of assessment (up to 12 weeks after the intervention, between more than 12 weeks and less than six months after the intervention, or six months or longer after the intervention). Moreover, we wanted to compare the effects of resistance training with no training on quality of life (QoL), adverse events, depression, and anxiety. We performed an extensive literature search in eight databases including CENTRAL, Medline, and Embase in October 2023. We searched trial registries for ongoing studies, and we integrated results from update searches of previously published Cochrane reviews. We included randomised controlled trials (RCTs) that compared resistance training with no training in adults with any type of cancer who received resistance training initiated before, during, or after anticancer therapy. Eligible RCTs needed to evaluate CRF or QoL. Resistance training had to be structured, last for at least five sessions, and include face-to-face instruction. We excluded studies that randomised fewer than 20 participants per group. We used standard Cochrane methodology. For analyses, we pooled short-term, medium-term, and long-term effects (i.e. up to 12 weeks, between more than 12 weeks and less than six months, and six months or longer, after the intervention). We assessed risk of bias and certainty of the evidence using Cochrane's risk of bias tool (RoB 1), and the GRADE approach, respectively. We included 21 RCTs with a total of 2221 participants, with diverse types of cancer, who received resistance training initiated during (14 studies), or after (7 studies) anticancer therapy. None of the studies investigated the effects of resistance training initiated before anticancer therapy. Here, we present the results on CRF, QoL, and adverse events. Results on depression and anxiety are reported in the full review. Resistance training during anticancer therapy Resistance training probably has a beneficial effect compared with no training on short-term CRF (mean difference (MD) on Functional Assessment of Chronic Illness Therapy - Fatigue scale (FACIT-Fatigue) 3.90, 95% confidence interval (CI) 1.30 to 6.51; scale from 0 to 52, higher values mean better outcome, minimal important difference (MID) 3; 12 RCTs, 1120 participants; moderate-certainty evidence). The evidence is very uncertain about the effect of resistance training compared with no training on medium-term CRF (MD on Multidimensional Fatigue Inventory -8.33, 95% CI -18.34 to 1.68; scale from 20 to 100, higher values mean worse outcome, MID 11.5; 1 RCT, 47 participants; very low-certainty evidence). The evidence is very uncertain about the effect of resistance training compared with no training on long-term CRF (MD on FACIT-Fatigue -0.70, 95% CI -4.16 to 2.76; 1 RCT, 133 participants; very low-certainty evidence). Resistance training may have a small beneficial effect compared with no training on short-term QoL (MD on EORTC QoL Questionnaire C30 - global health (QLQ-C30) 4.93, 95% CI 2.01 to 7.85; scale from 0 to 100, higher values mean better outcome, MID 10; 12 RCTs, 1117 participants; low-certainty evidence). The evidence is very uncertain about the effect of resistance training compared with no training on medium-term QoL (MD on QLQ-C30 6.48, 95% CI -4.64 to 17.60; 1 RCT, 42 participants; very low-certainty evidence). The evidence is very uncertain about the effect of resistance training compared with no training on long-term QoL (MD on Functional Assessment of Cancer Therapy - Anemia (FACT-An) 0.50, 95% CI -8.46 to 9.46; scale from 0 to 188; higher values mean better outcome, MID 7; 1 RCT, 133 participants; very low-certainty evidence). Only two RCTs (116 participants) reported data on adverse events for both the resistance training and the control arm. The evidence is very uncertain about the effect of resistance training compared with no training on the occurrence of adverse events (very low-certainty evidence). Resistance training after anticancer therapy The evidence is very uncertain about the effect of resistance training compared with no training on short-term CRF (MD on Chalder Fatigue Scale -0.27, 95% CI -2.11 to 1.57; scale from 0 to 33, higher values mean worse outcome, MID 2.3; 3 RCTs, 174 participants; very low-certainty evidence). Resistance training may have a small beneficial effect or no effect compared with no training on short-term QoL (MD on QLQ-C30 3.87, 95% CI -1.22 to 8.97; 4 RCTs, 243 participants; low-certainty evidence). None of the studies reported data on medium-, or long-term effects on CRF or QoL. Only three RCTs (238 participants) reported data on adverse events for both the resistance training and the control arm. The evidence is very uncertain about the effect of resistance training compared with no training on the occurrence of adverse events (very low-certainty evidence). Our review demonstrates beneficial effects of resistance training during anticancer therapy compared with no training on short-term CRF and QoL for people with cancer. Resistance training after anticancer therapy may also have a small beneficial effect on short-term QoL. Data on medium-, and long-term effects are sparse. In order to facilitate evidence syntheses beyond a narrative report of the data, investigators of resistance training programmes should report adverse events more consistently and completely for all study arms, including control groups.

Ernst M ，Wagner C ，Oeser A ，Messer S ，Wender A ，Cryns N ，Bröckelmann PJ ，Holtkamp U ，Baumann FT ，Wiskemann J ，Monsef I ，Scherer RW ，Mishra SI ，Skoetz N ... -  《Cochrane Database of Systematic Reviews》

Cardiovascular training for fatigue in people with cancer.

Cancer-related fatigue (CRF) is the most prevalent and severe symptom among people with cancer. It can be attributed to the cancer itself or to anticancer therapies. CRF affects the individual physically and mentally, and cannot be alleviated by rest. Studies show a positive effect of exercise on CRF. To evaluate the effects of cardiovascular training on cancer-related fatigue (CRF), quality of life (QoL), adverse events, anxiety, and depression in people with cancer, with regard to their stage of anticancer therapy (before, during, or after), up to 12 weeks, up to six months, or longer, postintervention. We searched CENTRAL, MEDLINE, Embase, ClinicalTrials.gov and World Health Organization ICTRP to identify studies that are included in the review. The latest search date was October 2023. We included randomised controlled trials (RCTs) evaluating cardiovascular training for CRF or QoL, or both, in people with cancer. Trials were eligible if training was structured, included at least five sessions, and instruction was face-to-face (via video tools or in person). We excluded studies with fewer than 20 randomised participants per group and where only an abstract was available. Our critical outcomes were: short-, medium-, long-term CRF and QoL. Important outcomes were adverse events, and short-, medium-, long-term anxiety and depression. We used the Cochrane RoB 1 tool to assess bias in RCTs. We used standard Cochrane methodology. We synthesised results for each outcome using meta-analysis where possible (inverse variance or Mantel-Haenszel; random-effects model). We pooled data for the respective assessment periods above. We used GRADE to assess certainty of evidence for each outcome. We included 23 RCTs with 2135 participants, of whom 96.6% originated from high-income countries; 1101 participants were randomised to cardiovascular training and 1034 to no training. Studies included mostly females who were diagnosed with breast cancer. We also identified 36 ongoing and 12 completed studies that have not yet published (awaiting assessment). We only present findings on CRF, QoL and adverse events. For details regarding anxiety and depression, see full text. Cardiovascular training before anticancer therapy versus no training for people with cancer We identified no studies for inclusion in this comparison. Cardiovascular training during anticancer therapy versus no training for people with cancer We included 10 studies (1026 participants); eight studies contributed data to quantitative analyses (860 participants). Cardiovascular training probably reduces short-term CRF slightly (mean difference (MD) 2.85, 95% confidence interval (CI) 1.16 to 4.55, on the Functional Assessment of Cancer Therapy - Fatigue (FACT-F), scale 0 to 52, higher values mean better outcome; minimally important difference (MID) 3; 6 studies, 593 participants) and probably results in little to no difference in short-term QoL (MD 3.56, 95% CI 0.21 to 6.90, on the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire C30 (EORTC QLQ C-30), scale 0 to 100, higher values mean better outcome, MID 10; 6 studies, 612 participants) (both moderate-certainty evidence). We are uncertain about the effects on medium-term CRF (MD 2.67, 95% CI -2.58 to 7.92, on FACT-F; MID 3; 1 study, 62 participants), long-term CRF (MD 0.41, 95% CI -2.24 to 3.05, on FACT-F; MID 3; 2 studies, 230 participants), medium-term QoL (MD 6.79, 95% CI -4.39 to 17.97, on EORTC QLQ C-30; MID 10; 1 study, 62 participants), and long-term QoL (MD 1.51, 95% CI -3.40 to 6.42, on EORTC QLQ C-30; MID 10; 2 studies, 230 participants) (all very low-certainty evidence). For adverse events (any grade and follow-up), we did not perform meta-analysis due to heterogeneous definitions, reporting, and measurement (9 RCTs, 955 participants; very low-certainty evidence). Cardiovascular training after anticancer therapy versus no training for people with cancer We included 13 studies (1109 participants); nine studies contributed data to quantitative analyses (756 participants). We are uncertain about the effects of cardiovascular training on short-term CRF (MD 3.62, 95% CI 0 to 7.13, on FACT-F; MID 3; 6 studies, 497 participants), long-term CRF (MD -0.80, 95% CI -1.72 to 0.13, on the Fatigue Symptom Inventory (FSI), scale 1 to 10, higher values mean worse outcome; MID 1; 2 studies, 262 participants), short-term QoL (MD 3.70, 95% CI -0.14 to 7.41, on the Functional Assessment of Cancer Therapy - General (FACT-G), scale 0 to 108, higher values mean better outcome; MID 4; 8 studies, 642 participants), long-term QoL (MD 3.10, 95% CI -1.12 to 7.32, on FACT-G; MID 4; 1 study, 201 participants), and adverse events (risk ratio (RR) 2.71, 95% CI 0.58 to 12.67; 1 study, 50 participants) (all very low-certainty evidence). There were no data for medium-term CRF and QoL. Moderate-certainty evidence shows that cardiovascular training by people with cancer during their anticancer therapy slightly reduces short-term CRF and results in little to no difference in short-term QoL. We do not know whether cardiovascular training increases or decreases medium-term CRF/QoL, and long-term CRF/QoL. There is very low-certainty evidence (due to heterogeneous definitions, reporting and measurement) evaluating whether the training increases or decreases adverse events. In people with cancer who perform cardiovascular training after anticancer therapy, we are uncertain about the effects on short-term CRF/QoL, long-term CRF/QoL, and adverse events. We identified a lack of evidence concerning cardiovascular training before anticancer therapy and on safety outcomes. The 36 ongoing and 12 completed, but unpublished, studies could help close this gap, and could contribute to improving the effect estimates and certainty. This Cochrane review was funded by the Federal Ministry of Education and Research of Germany, grant number: FKZ 01KG2017. Protocol available via DOI: 10.1002/14651858.CD015211.

Wagner C ，Ernst M ，Cryns N ，Oeser A ，Messer S ，Wender A ，Wiskemann J ，Baumann FT ，Monsef I ，Bröckelmann PJ ，Holtkamp U ，Scherer RW ，Mishra SI ，Skoetz N ... -  《Cochrane Database of Systematic Reviews》

Exercise therapy for chronic fatigue syndrome.

Editorial note (19 December 2024; amended 31 January 2025): Larun L, Brurberg KG, Odgaard‐Jensen J, Price JR. Exercise therapy for chronic fatigue syndrome. Cochrane Database of Systematic Reviews 2019, Issue 10. Art. No.: CD003200. DOI: 10.1002/14651858.CD003200.pub8. Accessed 18 December 2024. This Editorial Note is for the above article, published online on 2 October 2019 on the Cochrane Library (https://www.cochranelibrary.com/), and has been issued by the Publisher, John Wiley & Sons Ltd, in agreement with the Cochrane Collaboration. The Editorial note has been agreed to inform readers that Cochrane is ceasing the production of a full update of this Cochrane review. A pilot project for engaging interest holders in the development of this Cochrane review was initiated on 2 October 2019 (see Editorial Note below) and has now been disbanded. Cochrane maintains its decision to publish this Cochrane review in 2019, which includes studies from searches up to 9 May 2014. Editorial note (2 October 2019): A statement from the Editor in Chief about this review and its planned update is available at https://www.cochrane.org/news/cfs Chronic fatigue syndrome (CFS) or myalgic encephalomyelitis (ME) is a serious disorder characterised by persistent postexertional fatigue and substantial symptoms related to cognitive, immune and autonomous dysfunction. There is no specific diagnostic test, therefore diagnostic criteria are used to diagnose CFS. The prevalence of CFS varies by type of diagnostic criteria used. Existing treatment strategies primarily aim to relieve symptoms and improve function. One treatment option is exercise therapy. The objective of this review was to determine the effects of exercise therapy for adults with CFS compared with any other intervention or control on fatigue, adverse outcomes, pain, physical functioning, quality of life, mood disorders, sleep, self-perceived changes in overall health, health service resources use and dropout. We searched the Cochrane Common Mental Disorders Group controlled trials register, CENTRAL, and SPORTDiscus up to May 2014, using a comprehensive list of free-text terms for CFS and exercise. We located unpublished and ongoing studies through the World Health Organization International Clinical Trials Registry Platform up to May 2014. We screened reference lists of retrieved articles and contacted experts in the field for additional studies. We included randomised controlled trials (RCTs) about adults with a primary diagnosis of CFS, from all diagnostic criteria, who were able to participate in exercise therapy. Two review authors independently performed study selection, 'Risk of bias' assessments and data extraction. We combined continuous measures of outcomes using mean differences (MDs) or standardised mean differences (SMDs). To facilitate interpretation of SMDs, we re-expressed SMD estimates as MDs on more common measurement scales. We combined dichotomous outcomes using risk ratios (RRs). We assessed the certainty of evidence using GRADE. We included eight RCTs with data from 1518 participants. Exercise therapy lasted from 12 weeks to 26 weeks. The studies measured effect at the end of the treatment and at long-term follow-up, after 50 weeks or 72 weeks. Seven studies used aerobic exercise therapies such as walking, swimming, cycling or dancing, provided at mixed levels in terms of intensity of the aerobic exercise from very low to quite rigorous, and one study used anaerobic exercise. Control groups consisted of passive control, including treatment as usual, relaxation or flexibility (eight studies); cognitive behavioural therapy (CBT) (two studies); cognitive therapy (one study); supportive listening (one study); pacing (one study); pharmacological treatment (one study) and combination treatment (one study). Most studies had a low risk of selection bias. All had a high risk of performance and detection bias. Exercise therapy compared with 'passive' control Exercise therapy probably reduces fatigue at end of treatment (SMD -0.66, 95% CI -1.01 to -0.31; 7 studies, 840 participants; moderate-certainty evidence; re-expressed MD -3.4, 95% CI -5.3 to -1.6; scale 0 to 33). We are uncertain if fatigue is reduced in the long term because the certainty of the evidence is very low (SMD -0.62, 95 % CI -1.32 to 0.07; 4 studies, 670 participants; re-expressed MD -3.2, 95% CI -6.9 to 0.4; scale 0 to 33). We are uncertain about the risk of serious adverse reactions because the certainty of the evidence is very low (RR 0.99, 95% CI 0.14 to 6.97; 1 study, 319 participants). Exercise therapy may moderately improve physical functioning at end of treatment, but the long-term effect is uncertain because the certainty of the evidence is very low. Exercise therapy may also slightly improve sleep at end of treatment and at long term. The effect of exercise therapy on pain, quality of life and depression is uncertain because evidence is missing or of very low certainty. Exercise therapy compared with CBT Exercise therapy may make little or no difference to fatigue at end of treatment (MD 0.20, 95% CI -1.49 to 1.89; 1 study, 298 participants; low-certainty evidence), or at long-term follow-up (SMD 0.07, 95% CI -0.13 to 0.28; 2 studies, 351 participants; moderate-certainty evidence). We are uncertain about the risk of serious adverse reactions because the certainty of the evidence is very low (RR 0.67, 95% CI 0.11 to 3.96; 1 study, 321 participants). The available evidence suggests that there may be little or no difference between exercise therapy and CBT in physical functioning or sleep (low-certainty evidence) and probably little or no difference in the effect on depression (moderate-certainty evidence). We are uncertain if exercise therapy compared to CBT improves quality of life or reduces pain because the evidence is of very low certainty. Exercise therapy compared with adaptive pacing Exercise therapy may slightly reduce fatigue at end of treatment (MD -2.00, 95% CI -3.57 to -0.43; scale 0 to 33; 1 study, 305 participants; low-certainty evidence) and at long-term follow-up (MD -2.50, 95% CI -4.16 to -0.84; scale 0 to 33; 1 study, 307 participants; low-certainty evidence). We are uncertain about the risk of serious adverse reactions (RR 0.99, 95% CI 0.14 to 6.97; 1 study, 319 participants; very low-certainty evidence). The available evidence suggests that exercise therapy may slightly improve physical functioning, depression and sleep compared to adaptive pacing (low-certainty evidence). No studies reported quality of life or pain. Exercise therapy compared with antidepressants We are uncertain if exercise therapy, alone or in combination with antidepressants, reduces fatigue and depression more than antidepressant alone, as the certainty of the evidence is very low. The one included study did not report on adverse reactions, pain, physical functioning, quality of life, sleep or long-term results. Exercise therapy probably has a positive effect on fatigue in adults with CFS compared to usual care or passive therapies. The evidence regarding adverse effects is uncertain. Due to limited evidence it is difficult to draw conclusions about the comparative effectiveness of CBT, adaptive pacing or other interventions. All studies were conducted with outpatients diagnosed with 1994 criteria of the Centers for Disease Control and Prevention or the Oxford criteria, or both. Patients diagnosed using other criteria may experience different effects.

Larun L ，Brurberg KG ，Odgaard-Jensen J ，Price JR ... -  《Cochrane Database of Systematic Reviews》

Treatment for women with postpartum iron deficiency anaemia.

Postpartum iron deficiency anaemia is caused by antenatal iron deficiency or excessive blood loss at delivery and might affect up to 50% of labouring women in low- and middle-income countries. Effective and safe treatment during early motherhood is important for maternal well-being and newborn care. Treatment options include oral iron supplementation, intravenous iron, erythropoietin, and red blood cell transfusion. To assess the benefits and harms of the available treatment modalities for women with postpartum iron deficiency anaemia. These include intravenous iron, oral iron supplementation, red blood cell transfusion, and erythropoietin. A Cochrane Information Specialist searched for all published, unpublished, and ongoing trials, without language or publication status restrictions. We searched databases including CENTRAL, MEDLINE, Embase, CINAHL, LILACS, WHO ICTRP, and ClinicalTrials.gov, together with reference checking, citation searching, and contact with study authors to identify eligible studies. We applied date limits to retrieve new records since the last search on 9 April 2015 until 11 April 2024. We included published, unpublished, and ongoing randomised controlled trials (RCTs) that compared treatments for postpartum iron deficiency anaemia with placebo, no treatment, or alternative treatments. Cluster-randomised trials were eligible for inclusion. We included RCTs regardless of blinding. Participants were women with postpartum haemoglobin ≤ 12 g/dL, treated within six weeks after childbirth. We excluded non-randomised, quasi-randomised, and cross-over trials. The critical outcomes of this review were maternal mortality and fatigue. The important outcomes included persistent anaemia symptoms, persistent postpartum anaemia, psychological well-being, infections, compliance with treatment, breastfeeding, length of hospital stay, serious adverse events, anaphylaxis or evidence of hypersensitivity, flushing/Fishbane reaction, injection discomfort/reaction, constipation, gastrointestinal pain, number of red blood cell transfusions, and haemoglobin levels. We assessed risk of bias in the included studies using the Cochrane RoB 1 tool. Two review authors independently performed study screening, risk of bias assessment, and data extraction. We contacted trial authors for supplementary data when necessary. We screened all trials for trustworthiness and scientific integrity using the Cochrane Trustworthiness Screening Tool. We conducted meta-analyses using a fixed-effect model whenever feasible to synthesise outcomes. In cases where data were not suitable for meta-analysis, we provided a narrative summary of important findings. We evaluated the overall certainty of the evidence using GRADE. We included 33 RCTs with a total of 4558 postpartum women. Most trials were at high risk of bias for several risk of bias domains. Most of the evidence was of low or very low certainty. Imprecision due to few events and risk of bias due to lack of blinding were the most important factors. Intravenous iron versus oral iron supplementation The evidence is very uncertain about the effect of intravenous iron on mortality (risk ratio (RR) 2.95, 95% confidence interval (CI) 0.12 to 71.96; P = 0.51; I² = not applicable; 3 RCTs; 1 event; 572 women; very low-certainty evidence). One woman died of cardiomyopathy, and another developed arrhythmia, both in the groups treated with intravenous iron. Intravenous iron probably results in a slight reduction in fatigue within 8 to 28 days (standardised mean difference -0.25, 95% CI -0.42 to -0.07; P = 0.006; I² = 47%; 2 RCTs; 515 women; moderate-certainty evidence). Breastfeeding was not reported. Oral iron probably increases the risk of constipation compared to intravenous iron (RR 0.12, 95% CI 0.06 to 0.21; P < 0.001; I² = 0%; 10 RCTs; 1798 women; moderate-certainty evidence). The evidence is very uncertain about the effect of intravenous iron on anaphylaxis or hypersensitivity (RR 2.77, 95% CI 0.31 to 24.86; P = 0.36; I² = 0%; 12 RCTs; 2195 women; very low-certainty evidence). Three women treated with intravenous iron experienced anaphylaxis or hypersensitivity. The trials that reported on haemoglobin at 8 to 28 days were too heterogeneous to pool. However, 5 of 6 RCTs favoured intravenous iron, with mean changes in haemoglobin ranging from 0.73 to 2.10 g/dL (low-certainty evidence). Red blood cell transfusion versus intravenous iron No women died in the only trial that reported on mortality (1 RCT; 7 women; very low-certainty evidence). The evidence is very uncertain about the effect of red blood cell transfusion on fatigue at 8 to 28 days (mean difference (MD) 1.20, 95% CI -2.41 to 4.81; P = 0.51; I² = not applicable; 1 RCT; 13 women; very low-certainty evidence) and breastfeeding more than six weeks postpartum (RR 0.43, 95% CI 0.12 to 1.57; P = 0.20; I² = not applicable; 1 RCT; 13 women; very low-certainty evidence). Constipation and anaphylaxis were not reported. Red blood cell transfusion may result in little to no difference in haemoglobin within 8 to 28 days (MD -1.00, 95% CI -2.02 to 0.02; P = 0.05; I² = not applicable; 1 RCT; 12 women; low-certainty evidence). Intravenous iron and oral iron supplementation versus oral iron supplementation Mortality and breastfeeding were not reported. One trial reported a greater improvement in fatigue in the intravenous and oral iron group, but the effect size could not be calculated (1 RCT; 128 women; very low-certainty evidence). Intravenous iron and oral iron may result in a reduction in constipation compared to oral iron alone (RR 0.21, 95% CI 0.07 to 0.69; P = 0.01; I² = not applicable; 1 RCT; 128 women; low-certainty evidence). There were no anaphylaxis or hypersensitivity events in the trials (2 RCTs; 168 women; very low-certainty evidence). Intravenous iron and oral iron may result in little to no difference in haemoglobin (g/dL) at 8 to 28 days (MD 0.00, 95% CI -0.48 to 0.48; P = 1.00; I² = not applicable; 1 RCT; 60 women; low-certainty evidence). Red blood cell transfusion versus no transfusion Mortality, fatigue at day 8 to 28, constipation, anaphylaxis, and haemoglobin were not reported. Red blood cell transfusion may result in little to no difference in breastfeeding more than six weeks postpartum (RR 0.91, 95% CI 0.78 to 1.07; P = 0.24; I² = not applicable; 1 RCT; 297 women; low-certainty evidence). Oral iron supplementation versus placebo or no treatment Mortality, fatigue, breastfeeding, constipation, anaphylaxis, and haemoglobin were not reported. Two trials reported on gastrointestinal symptoms, but did not report results by study arm. Intravenous iron probably reduces fatigue slightly in the early postpartum weeks (8 to 28 days) compared to oral iron tablets, but probably results in little to no difference after four weeks. It is very uncertain if intravenous iron has an effect on mortality and anaphylaxis/hypersensitivity. Breastfeeding was not reported. Intravenous iron may increase haemoglobin slightly more than iron tablets, but the data were too heterogeneous to pool. However, changes in haemoglobin levels are a surrogate outcome, and treatment decisions should preferentially be based on patient-relevant outcomes. Iron tablets probably result in a large increase in constipation compared to intravenous iron. The effect of red blood cell transfusion compared to intravenous iron on mortality, fatigue, and breastfeeding is very uncertain. No studies reported on constipation or anaphylaxis/hypersensitivity. Red blood cell transfusion may result in little to no difference in haemoglobin at 8 to 28 days. The effect of intravenous iron and oral iron supplementation on mortality, fatigue, breastfeeding, and anaphylaxis/hypersensitivity is very uncertain or unreported. Intravenous iron and oral iron may result in a reduction in constipation compared to oral iron alone, and in little to no difference in haemoglobin. The effect of red blood cell transfusion compared to non-transfusion on mortality, fatigue, constipation, anaphylaxis/hypersensitivity, and haemoglobin is unreported. Red blood cell transfusion may result in little to no difference in breastfeeding. The effect of oral iron supplementation on mortality, fatigue, breastfeeding, constipation, anaphylaxis/hypersensitivity, and haemoglobin is unreported. This Cochrane review had no dedicated funding. Protocol and previous versions are available: Protocol (2013) [DOI: 10.1002/14651858.CD010861] Original review (2004) [DOI: 10.1002/14651858.CD004222.pub2] Review update (2015) [DOI: 10.1002/14651858.CD010861.pub2].

Jensen MCH ，Holm C ，Jørgensen KJ ，Schroll JB ... -  《Cochrane Database of Systematic Reviews》