Pharmacological interventions for the treatment of depression in chronic obstructive pulmonary disease.

Pollok J ，van Agteren JE ，Carson-Chahhoud KV 《Cochrane Database of Systematic Reviews》

Pharmacological treatments in panic disorder in adults: a network meta-analysis.

A panic attack is a discrete period of fear or anxiety that has a rapid onset and reaches a peak within 10 minutes. The main symptoms involve bodily systems, such as racing heart, chest pain, sweating, shaking, dizziness, flushing, churning stomach, faintness and breathlessness. Other recognised panic attack symptoms involve fearful cognitions, such as the fear of collapse, going mad or dying, and derealisation (the sensation that the world is unreal). Panic disorder is common in the general population with a prevalence of 1% to 4%. The treatment of panic disorder includes psychological and pharmacological interventions, including antidepressants and benzodiazepines. To compare, via network meta-analysis, individual drugs (antidepressants and benzodiazepines) or placebo in terms of efficacy and acceptability in the acute treatment of panic disorder, with or without agoraphobia. To rank individual active drugs for panic disorder (antidepressants, benzodiazepines and placebo) according to their effectiveness and acceptability. To rank drug classes for panic disorder (selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs), mono-amine oxidase inhibitors (MAOIs) and benzodiazepines (BDZs) and placebo) according to their effectiveness and acceptability. To explore heterogeneity and inconsistency between direct and indirect evidence in a network meta-analysis. We searched the Cochrane Common Mental Disorders Specialised Register, CENTRAL, CDSR, MEDLINE, Ovid Embase and PsycINFO to 26 May 2022. We included randomised controlled trials (RCTs) of people aged 18 years or older of either sex and any ethnicity with clinically diagnosed panic disorder, with or without agoraphobia. We included trials that compared the effectiveness of antidepressants and benzodiazepines with each other or with a placebo. Two authors independently screened titles/abstracts and full texts, extracted data and assessed risk of bias. We analysed dichotomous data and continuous data as risk ratios (RRs), mean differences (MD) or standardised mean differences (SMD): response to treatment (i.e. substantial improvement from baseline as defined by the original investigators: dichotomous outcome), total number of dropouts due to any reason (as a proxy measure of treatment acceptability: dichotomous outcome), remission (i.e. satisfactory end state as defined by global judgement of the original investigators: dichotomous outcome), panic symptom scales and global judgement (continuous outcome), frequency of panic attacks (as recorded, for example, by a panic diary; continuous outcome), agoraphobia (dichotomous outcome). We assessed the certainty of evidence using threshold analyses. Overall, we included 70 trials in this review. Sample sizes ranged between 5 and 445 participants in each arm, and the total sample size per study ranged from 10 to 1168. Thirty-five studies included sample sizes of over 100 participants. There is evidence from 48 RCTs (N = 10,118) that most medications are more effective in the response outcome than placebo. In particular, diazepam, alprazolam, clonazepam, paroxetine, venlafaxine, clomipramine, fluoxetine and adinazolam showed the strongest effect, with diazepam, alprazolam and clonazepam ranking as the most effective. We found heterogeneity in most of the comparisons, but our threshold analyses suggest that this is unlikely to impact the findings of the network meta-analysis. Results from 64 RCTs (N = 12,310) suggest that most medications are associated with either a reduced or similar risk of dropouts to placebo. Alprazolam and diazepam were associated with a lower dropout rate compared to placebo and were ranked as the most tolerated of all the medications examined. Thirty-two RCTs (N = 8569) were included in the remission outcome. Most medications were more effective than placebo, namely desipramine, fluoxetine, clonazepam, diazepam, fluvoxamine, imipramine, venlafaxine and paroxetine, and their effects were clinically meaningful. Amongst these medications, desipramine and alprazolam were ranked highest. Thirty-five RCTs (N = 8826) are included in the continuous outcome reduction in panic scale scores. Brofaromine, clonazepam and reboxetine had the strongest reductions in panic symptoms compared to placebo, but results were based on either one trial or very small trials. Forty-one RCTs (N = 7853) are included in the frequency of panic attack outcome. Only clonazepam and alprazolam showed a strong reduction in the frequency of panic attacks compared to placebo, and were ranked highest. Twenty-six RCTs (N = 7044) provided data for agoraphobia. The strongest reductions in agoraphobia symptoms were found for citalopram, reboxetine, escitalopram, clomipramine and diazepam, compared to placebo. For the pooled intervention classes, we examined the two primary outcomes (response and dropout). The classes of medication were: SSRIs, SNRIs, TCAs, MAOIs and BDZs. For the response outcome, all classes of medications examined were more effective than placebo. TCAs as a class ranked as the most effective, followed by BDZs and MAOIs. SSRIs as a class ranked fifth on average, while SNRIs were ranked lowest. When we compared classes of medication with each other for the response outcome, we found no difference between classes. Comparisons between MAOIs and TCAs and between BDZs and TCAs also suggested no differences between these medications, but the results were imprecise. For the dropout outcome, BDZs were the only class associated with a lower dropout compared to placebo and were ranked first in terms of tolerability. The other classes did not show any difference in dropouts compared to placebo. In terms of ranking, TCAs are on average second to BDZs, followed by SNRIs, then by SSRIs and lastly by MAOIs. BDZs were associated with lower dropout rates compared to SSRIs, SNRIs and TCAs. The quality of the studies comparing antidepressants with placebo was moderate, while the quality of the studies comparing BDZs with placebo and antidepressants was low. In terms of efficacy, SSRIs, SNRIs (venlafaxine), TCAs, MAOIs and BDZs may be effective, with little difference between classes. However, it is important to note that the reliability of these findings may be limited due to the overall low quality of the studies, with all having unclear or high risk of bias across multiple domains. Within classes, some differences emerged. For example, amongst the SSRIs paroxetine and fluoxetine seem to have stronger evidence of efficacy than sertraline. Benzodiazepines appear to have a small but significant advantage in terms of tolerability (incidence of dropouts) over other classes.

Guaiana G ，Meader N ，Barbui C ，Davies SJ ，Furukawa TA ，Imai H ，Dias S ，Caldwell DM ，Koesters M ，Tajika A ，Bighelli I ，Pompoli A ，Cipriani A ，Dawson S ，Robertson L ... -  《Cochrane Database of Systematic Reviews》

Conservative, physical and surgical interventions for managing faecal incontinence and constipation in adults with central neurological diseases.

People with central neurological disease or injury have a much higher risk of both faecal incontinence (FI) and constipation than the general population. There is often a fine line between the two symptoms, with management intended to ameliorate one risking precipitating the other. Bowel problems are observed to be the cause of much anxiety and may reduce quality of life in these people. Current bowel management is largely empirical, with a limited research base. The review is relevant to individuals with any disease directly and chronically affecting the central nervous system (post-traumatic, degenerative, ischaemic or neoplastic), such as multiple sclerosis, spinal cord injury, cerebrovascular disease, Parkinson's disease and Alzheimer's disease. This is an update of a Cochrane Review first published in 2001 and subsequently updated in 2003, 2006 and 2014. To assess the effects of conservative, physical and surgical interventions for managing FI and constipation in people with a neurological disease or injury affecting the central nervous system. We searched the Cochrane Incontinence Specialised Register (searched 27 March 2023), which includes searches of the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, MEDLINE In-Process, MEDLINE Epub Ahead of Print, ClinicalTrials.gov, WHO ICTRP as well as handsearching of journals and conference proceedings; and all reference lists of relevant articles. We included randomised, quasi-randomised (where allocation is not strictly random), cross-over and cluster-randomised trials evaluating any type of conservative, physical or surgical intervention against placebo, usual care or no intervention for the management of FI and constipation in people with central neurological disease or injury. At least two review authors independently assessed the risk of bias in eligible trials using Cochrane's 'Risk of bias' tool and independently extracted data from the included trials using a range of prespecified outcome measures. We produced summary of findings tables for our main outcome measures and assessed the certainty of the evidence using GRADE. We included 25 studies with 1598 participants. The studies were generally at high risk of bias due to lack of blinding of participants and personnel to the intervention. Half of the included studies were also at high risk of bias in terms of selective reporting. Outcomes were often reported heterogeneously across studies, making it difficult to pool data. We did not find enough evidence to be able to analyse the effects of interventions on individual central neurological diseases. Additionally, very few studies reported on the primary outcomes of self-reported improvement in FI or constipation, or Neurogenic Bowel Dysfunction Score. Conservative interventions compared with usual care, no active treatment or placebo Thirteen studies assessed this comparison. The interventions included assessment-based nursing, holistic nursing, probiotics, psyllium, faecal microbiota transplantation, and a stepwise protocol of increasingly invasive evacuation methods. Conservative interventions may result in a large improvement in faecal incontinence (standardised mean difference (SMD) -1.85, 95% confidence interval (CI) -3.47 to -0.23; 3 studies; n = 410; low-certainty evidence). We interpreted SMD ≥ 0.80 as a large effect. It was not possible to pool all data from studies that assessed improvement in constipation, but the evidence suggested that conservative interventions may improve constipation symptoms (data not pooled; 8 studies; n = 612; low-certainty evidence). Conservative interventions may lead to a reduction in mean time taken on bowel care (data not pooled; 5 studies; n = 526; low-certainty evidence). The evidence is uncertain about the effects of conservative interventions on condition-specific quality of life and adverse events. Neurogenic Bowel Dysfunction Score was not reported. Physical therapy compared with usual care, no active treatment or placebo Twelve studies assessed this comparison. The interventions included massage therapy, standing, osteopathic manipulative treatment, electrical stimulation, transanal irrigation, and conventional physical therapy with visceral mobilisation. Physical therapies may make little to no difference to self-reported faecal continence assessed using the St Mark's Faecal Incontinence Score, where the minimally important difference is five, or the Cleveland Constipation Score (MD -2.60, 95% CI -4.91 to -0.29; 3 studies; n = 155; low-certainty evidence). Physical therapies may result in a moderate improvement in constipation symptoms (SMD -0.62, 95% CI -1.10 to -0.14; 9 studies; n = 431; low-certainty evidence). We interpreted SMD ≥ 0.5 as a moderate effect. However, physical therapies may make little to no difference in Neurogenic Bowel Dysfunction Score as the minimally important difference for this tool is 3 (MD -1.94, 95% CI -3.36 to -0.51; 7 studies; n = 358; low-certainty evidence). We are very uncertain about the effects of physical therapies on the time spent on bowel care, condition-specific quality of life and adverse effects (all very low-certainty evidence). Surgical interventions compared with usual care, no active treatment or placebo No studies were found for surgical interventions that met the inclusion criteria for this review. There remains little research on this common and, for patients, very significant issue of bowel management. The available evidence is almost uniformly of low methodological quality. The clinical significance of some of the research findings presented here is difficult to interpret, not least because each intervention has only been addressed in individual trials, against control rather than compared against each other, and the interventions are very different from each other. Understanding whether there is a clinically-meaningful difference from the results of available trials is largely hampered by the lack of uniform outcome measures. This is due to an absence of core outcome sets, and development of these needs to be a research priority to allow studies to be compared directly. Some studies used validated constipation, incontinence or condition-specific measures; however, others used unvalidated analogue scales to report effectiveness. Some studies did not use any patient-reported outcomes and focused on physiological outcome measures, which is of relatively limited significance in terms of clinical implementation. There was evidence in favour of some conservative interventions, but these findings need to be confirmed by larger, well-designed controlled trials, which should include evaluation of the acceptability of the intervention to patients and the effect on their quality of life.

Todd CL ，Johnson EE ，Stewart F ，Wallace SA ，Bryant A ，Woodward S ，Norton C ... -  《Cochrane Database of Systematic Reviews》

Antioxidants for female subfertility.

M.G. Showell, R. Mackenzie‐Proctor, V. Jordan, and R.J. Hart, “Antioxidants for Female Subfertility,” Cochrane Database of Systematic Reviews, no. 8 (2020): CD007807, https://doi.org/10.1002/14651858.CD007807.pub4 This Editorial Note is for the above article, published online on August 27, 2020, in Cochrane Library (cochranelibrary.com), and has been issued by the Publisher, John Wiley & Sons Ltd, in agreement with Cochrane. The Editorial note has been agreed due to concerns discovered by the Cochrane managing editor regarding the retraction of six studies in the Review (Badawy et al. 2006, 10.1016/j.fertnstert.2006.02.097; El Refaeey et al. 2014, 10.1016/j.rbmo.2014.03.011; El Sharkwy & Abd El Aziz 2019a, https://doi.org/10.1002/ijgo.12902; Gerli et al. 2007, https://doi.org/10.26355/eurrev_202309_33752, full text: https://europepmc.org/article/MED/18074942; Ismail et al. 2014, http://dx.doi.org/10.1016/j.ejogrb.2014.06.008; Hashemi et al. 2017, https://doi.org/10.1080/14767058.2017.1372413). In addition, expressions of concern have been published for two studies (Jamilian et al. 2018, https://doi.org/10.1007/s12011-017-1236-3; Zadeh Modarres 2018, https://doi.org/10.1007/s12011-017-1148-2). The retracted studies will be moved to the Excluded Studies table, and their impact on the review findings will be investigated and acted on accordingly in a future update. Initial checks indicate that removal of the six retracted studies did not make an appreciable difference to the results. Likewise, the studies for which Expressions of Concern were issued will be moved to the Awaiting classification table; they did not report any review outcomes, so removal will have no impact on the review findings. A couple may be considered to have fertility problems if they have been trying to conceive for over a year with no success. This may affect up to a quarter of all couples planning a child. It is estimated that for 40% to 50% of couples, subfertility may result from factors affecting women. Antioxidants are thought to reduce the oxidative stress brought on by these conditions. Currently, limited evidence suggests that antioxidants improve fertility, and trials have explored this area with varied results. This review assesses the evidence for the effectiveness of different antioxidants in female subfertility. To determine whether supplementary oral antioxidants compared with placebo, no treatment/standard treatment or another antioxidant improve fertility outcomes for subfertile women. We searched the following databases (from their inception to September 2019), with no language or date restriction: Cochrane Gynaecology and Fertility Group (CGFG) specialised register, CENTRAL, MEDLINE, Embase, PsycINFO, CINAHL and AMED. We checked reference lists of relevant studies and searched the trial registers. We included randomised controlled trials (RCTs) that compared any type, dose or combination of oral antioxidant supplement with placebo, no treatment or treatment with another antioxidant, among women attending a reproductive clinic. We excluded trials comparing antioxidants with fertility drugs alone and trials that only included fertile women attending a fertility clinic because of male partner infertility. We used standard methodological procedures expected by Cochrane. The primary review outcome was live birth; secondary outcomes included clinical pregnancy rates and adverse events. We included 63 trials involving 7760 women. Investigators compared oral antioxidants, including: combinations of antioxidants, N-acetylcysteine, melatonin, L-arginine, myo-inositol, carnitine, selenium, vitamin E, vitamin B complex, vitamin C, vitamin D+calcium, CoQ10, and omega-3-polyunsaturated fatty acids versus placebo, no treatment/standard treatment or another antioxidant. Only 27 of the 63 included trials reported funding sources. Due to the very low-quality of the evidence we are uncertain whether antioxidants improve live birth rate compared with placebo or no treatment/standard treatment (odds ratio (OR) 1.81, 95% confidence interval (CI) 1.36 to 2.43; P < 0.001, I2 = 29%; 13 RCTs, 1227 women). This suggests that among subfertile women with an expected live birth rate of 19%, the rate among women using antioxidants would be between 24% and 36%. Low-quality evidence suggests that antioxidants may improve clinical pregnancy rate compared with placebo or no treatment/standard treatment (OR 1.65, 95% CI 1.43 to 1.89; P < 0.001, I2 = 63%; 35 RCTs, 5165 women). This suggests that among subfertile women with an expected clinical pregnancy rate of 19%, the rate among women using antioxidants would be between 25% and 30%. Heterogeneity was moderately high. Overall 28 trials reported on various adverse events in the meta-analysis. The evidence suggests that the use of antioxidants makes no difference between the groups in rates of miscarriage (OR 1.13, 95% CI 0.82 to 1.55; P = 0.46, I2 = 0%; 24 RCTs, 3229 women; low-quality evidence). There was also no evidence of a difference between the groups in rates of multiple pregnancy (OR 1.00, 95% CI 0.63 to 1.56; P = 0.99, I2 = 0%; 9 RCTs, 1886 women; low-quality evidence). There was also no evidence of a difference between the groups in rates of gastrointestinal disturbances (OR 1.55, 95% CI 0.47 to 5.10; P = 0.47, I2 = 0%; 3 RCTs, 343 women; low-quality evidence). Low-quality evidence showed that there was also no difference between the groups in rates of ectopic pregnancy (OR 1.40, 95% CI 0.27 to 7.20; P = 0.69, I2 = 0%; 4 RCTs, 404 women). In the antioxidant versus antioxidant comparison, low-quality evidence shows no difference in a lower dose of melatonin being associated with an increased live-birth rate compared with higher-dose melatonin (OR 0.94, 95% CI 0.41 to 2.15; P = 0.89, I2 = 0%; 2 RCTs, 140 women). This suggests that among subfertile women with an expected live-birth rate of 24%, the rate among women using a lower dose of melatonin compared to a higher dose would be between 12% and 40%. Similarly with clinical pregnancy, there was no evidence of a difference between the groups in rates between a lower and a higher dose of melatonin (OR 0.94, 95% CI 0.41 to 2.15; P = 0.89, I2 = 0%; 2 RCTs, 140 women). Three trials reported on miscarriage in the antioxidant versus antioxidant comparison (two used doses of melatonin and one compared N-acetylcysteine versus L-carnitine). There were no miscarriages in either melatonin trial. Multiple pregnancy and gastrointestinal disturbances were not reported, and ectopic pregnancy was reported by only one trial, with no events. The study comparing N-acetylcysteine with L-carnitine did not report live birth rate. Very low-quality evidence shows no evidence of a difference in clinical pregnancy (OR 0.81, 95% CI 0.33 to 2.00; 1 RCT, 164 women; low-quality evidence). Low quality evidence shows no difference in miscarriage (OR 1.54, 95% CI 0.42 to 5.67; 1 RCT, 164 women; low-quality evidence). The study did not report multiple pregnancy, gastrointestinal disturbances or ectopic pregnancy. The overall quality of evidence was limited by serious risk of bias associated with poor reporting of methods, imprecision and inconsistency. In this review, there was low- to very low-quality evidence to show that taking an antioxidant may benefit subfertile women. Overall, there is no evidence of increased risk of miscarriage, multiple births, gastrointestinal effects or ectopic pregnancies, but evidence was of very low quality. At this time, there is limited evidence in support of supplemental oral antioxidants for subfertile women.

Showell MG ，Mackenzie-Proctor R ，Jordan V ，Hart RJ ... -  《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》