scholarly journals The Effect of Probiotics, Prebiotics, and Synbiotics on CD4 Counts in HIV-Infected Patients: A Systematic Review and Meta-Analysis

2020 ◽  
Vol 2020 ◽  
pp. 1-11
Author(s):  
Yuan-Sheng Fu ◽  
Qin-Shu Chu ◽  
Akililu Alemu Ashuro ◽  
Dong-Sheng Di ◽  
Qi Zhang ◽  
...  
Keyword(s):  
Systematic Review ◽  
Publication Bias ◽  
Weighted Mean Difference ◽  
Meta Analysis ◽  
Risk Of Bias ◽  
Controlled Trials ◽  
Cochrane Central Register ◽  
Cd4 Counts ◽  
Cell Counts ◽  
Significant Difference

Background. Probiotics as a potential adjuvant therapy may improve the restoration of the intestinal CD4+ T-cell population in HIV-infected patients, whereas findings from clinical trials are inconsistent. This systematic review and meta-analysis of randomized controlled trials (RCTs) was performed to quantify the effects of probiotic, prebiotic, and synbiotic supplementation on CD4 counts in HIV-infected patients. Methods. We searched PubMed, Embase, Web of Science, Scopus, and the Cochrane Central Register of Controlled Trials for relevant articles published up to March 20, 2020. Two authors independently performed the study selection, data extraction, and risk of bias assessment. Data were pooled by using the random effects model, and weighted mean difference (WMD) was considered the summary effect size. Publication bias was evaluated by a funnel plot and Egger’s test. Results. The search strategy identified 1712 citations. After screening, a total of 16 RCTs with 19 trials were included in the meta-analysis. Pooling of the extracted data indicated no significant difference between the probiotics/prebiotics/synbiotics and placebo groups on CD4 counts ( WMD = 3.86 , 95% confidence interval (CI) -24.72 to 32.45, P = 0.791 ). In subgroup analysis, a significant increase in CD4 counts was found in the study with high risk of bias ( WMD = 188 , 95% CI 108.74 to 227.26, P ≤ 0.001 ). Egger’s test showed no evidence of significant publication bias ( P = 0.936 ). Conclusions. In summary, the evidence for the efficacy of probiotics, prebiotics, and synbiotics in improving HIV-infected patients’ CD4 counts as presented in currently published RCTs is insufficient. Therefore, further comprehensive studies are needed to reveal the exact effect of probiotics, prebiotics, and synbiotics on CD4+ cell counts.

scholarly journals Impact of levothyroxine in women with positive thyroid antibodies on pregnancy outcomes: a systematic review and meta-analysis of randomised controlled trials

BMJ Open ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. e043751
Author(s):  
Lorraine Lau ◽  
Jamie L Benham ◽  
Patricia Lemieux ◽  
Jennifer Yamamoto ◽  
Lois E Donovan
Keyword(s):  
Systematic Review ◽  
Preterm Delivery ◽  
Pregnancy Outcomes ◽  
Randomised Controlled Trials ◽  
Meta Analysis ◽  
Risk Of Bias ◽  
Controlled Trials ◽  
Cochrane Central Register ◽  
Significant Difference ◽  
Randomised Controlled

ObjectiveTo evaluate the effect of levothyroxine therapy on pregnancy outcomes compared with placebo or no treatment in women without overt hypothyroidism with presence of thyroid peroxidase antibodies (TPOAb) and/or thyroglobulin antibodies (TgAb).DesignSystematic review and meta-analysis of randomised controlled trialsStudy eligibility criteriaPrespecified criteria for inclusion were: randomised trials of levothyroxine versus control (placebo or no treatment) among women with positive TPOAb or TgAb who were pregnant or considering conception.Data sourcesOvid MEDLINE, EMBASE, CINAHL, Cochrane Database of Systematic Reviews and Cochrane Central Register of Controlled Trials were searched from 1980 to 5 November 2020.Outcome measuresPrespecified data elements were extracted and where appropriate, meta-analyses were conducted. Main outcomes include pregnancy achieved, miscarriage, preterm delivery and live birth.Risk of bias assessmentCochrane Risk of Bias Tool for Quality Assessment of Randomised Controlled Trials.ResultsFrom 3023 citations, 79 citations were identified for full-text review. Of these, six trials (total of 2263 women) were included for qualitative and quantitative analyses. Risk of bias was deemed low for only one trial. There was no significant difference in the relative risk (RR) of pregnancy achieved (RR 1.03; 95% CI 0.93 to 1.13), miscarriage (RR 0.93; 95% CI 0.76 to 1.14), preterm delivery (RR 0.66; 95% CI 0.39 to 1.10) or live births (RR 1.01; 95% CI 0.89 to 1.16) in thyroid autoimmune women treated with levothyroxine compared with controls. Sensitivity analyses of preterm birth identified study quality and timing of levothyroxine initiation as sources of heterogeneity.ConclusionsAmong pregnant women or women planning conception, with thyroid autoimmunity, there is a lack of evidence of benefit for levothyroxine use (moderate to high Grading of Recommendations, Assessment, Development and Evaluations). Recommendations to use levothyroxine in this setting need to be reconsidered.PROSPERO registration numberCRD42019130459.

scholarly journals Effectiveness of probiotics on the duration of illness in healthy children and adults who develop common acute respiratory infectious conditions: a systematic review and meta-analysis

2014 ◽  
Vol 112 (1) ◽  
pp. 41-54 ◽  
Author(s):  
Sarah King ◽  
Julie Glanville ◽  
Mary Ellen Sanders ◽  
Anita Fitzgerald ◽  
Danielle Varley
Keyword(s):  
Systematic Review ◽  
Systematic Reviews ◽  
Weighted Mean Difference ◽  
Meta Analysis ◽  
Risk Of Bias ◽  
Mean Difference ◽  
Controlled Trials ◽  
Cochrane Central Register ◽  
Healthy Children ◽  
Duration Of Illness

Recent systematic reviews have reported a positive, although modest, effect of probiotics in terms of preventing common cold symptoms. In this systematic review, the effect of probiotics, specifically Lactobacillus and Bifidobacterium strains, on the duration of acute respiratory infections in otherwise healthy children and adults was evaluated. To identify relevant trials, eight databases, including MEDLINE, Embase, the Cochrane Database of Systematic Reviews (CDSR), the Cochrane Central Register of Controlled Trials (CENTRAL), the Database of Abstracts of Reviews of Effects (DARE), Health Technology Assessment (HTA), Science Citation Index (SCI) and OAISTER, were searched from inception to 20 July 2012. Details regarding unpublished studies/databases were also obtained from probiotic manufacturers. Study selection, data extraction and quality assessment were carried out by two reviewers. Risk of bias was assessed using criteria adapted from those published by the Centre for Reviews and Dissemination. In this review, twenty randomised controlled trials (RCT) were included, of which twelve were considered to have a low risk of bias. Meta-analysis revealed significantly fewer numbers of days of illness per person (standardised mean difference (SMD) − 0·31 (95 % CI − 0·41, − 0·11), I2= 3 %), shorter illness episodes by almost a day (weighted mean difference − 0·77 (95 % CI − 1·50, − 0·04), I2= 80 %) (without an increase in the number of illness episodes), and fewer numbers of days absent from day care/school/work (SMD − 0·17 (95 % CI − 0·31, − 0·03), I2= 67 %) in participants who received a probiotic intervention than in those who had taken a placebo. Reasons for heterogeneity between the studies were explored in subgroup analysis, but could not be explained, suggesting that the effect sizes found may differ between the population groups. This systematic review provides evidence from a number of good-quality RCT that probiotics reduce the duration of illness in otherwise healthy children and adults.

scholarly journals Short Segment versus Long Segment Pedicle Screws Fixation in Management of Thoracolumbar Burst Fractures: Meta-Analysis

2017 ◽  
Vol 11 (1) ◽  
pp. 150-160 ◽  
Author(s):  
Tarek Ahmed Aly
Keyword(s):  
Pedicle Screw ◽  
Screw Fixation ◽  
Meta Analysis ◽  
Pedicle Screw Fixation ◽  
Risk Of Bias ◽  
Controlled Trials ◽  
Cochrane Central Register ◽  
Thoracolumbar Burst Fractures ◽  
Burst Fractures ◽  
Significant Difference

<p>Posterior pedicle screw fixation has become a popular method for treating thoracolumbar burst fractures. However, it remains unclear whether additional fixation of more segments could improve clinical and radiological outcomes. This meta-analysis was performed to evaluate the effectiveness of fixation levels with pedicle screw fixation for thoracolumbar burst fractures. MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, Springer, and Google Scholar were searched for relevant randomized and quasirandomized controlled trials that compared the clinical and radiological efficacy of short versus long segment for thoracolumbar burst fractures managed by posterior pedicle screw fixation. Risk of bias in included studies was assessed using the Cochrane Risk of Bias tool. Based on predefined inclusion criteria, Nine eligible trials with a total of 365 patients were included in this meta-analysis. Results were expressed as risk difference for dichotomous outcomes and standard mean difference for continuous outcomes with 95% confidence interval. Baseline characteristics were similar between the short and long segment fixation groups. No significant difference was identified between the two groups regarding radiological outcome, functional outcome, neurologic improvement, and implant failure rate. The results of this meta-analysis suggested that extension of fixation was not necessary when thoracolumbar burst fracture was treated by posterior pedicle screw fixation. More randomized controlled trials with high quality are still needed in the future.</p>

scholarly journals Effectiveness of orthodontic temporary anchorage devices in canine retraction and anchorage preservation during the two-step technique: a systematic review and meta-analysis

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Haonan Tian ◽  
Congman Xie ◽  
Min Lin ◽  
Hongmei Yang ◽  
Aishu Ren
Keyword(s):  
Systematic Review ◽  
Meta Analysis ◽  
Risk Of Bias ◽  
Controlled Trials ◽  
Cochrane Central Register ◽  
Canine Retraction ◽  
Temporary Anchorage Devices ◽  
The Mean ◽  
Mean Differences ◽  
Implant Anchorage

Abstract Background Temporary anchorage devices have been used for decades in orthodontic practice for many applications. The aim of this systematic review was to assess the effectiveness of orthodontic temporary anchorage devices in canine retraction during the two-step technique. Methods A search was systematically performed for articles published prior to June 30, 2019 in five electronic databases (PubMed, Embase, Cochrane Central Register of Controlled Trials, Web of Science, Scopus). The risk of bias was assessed using the Cochrane risk of bias tool for randomized controlled trials (RCTs) and the risk of bias in nonrandomized studies of interventions (ROBINS-I) tool for controlled clinical trials (CCTs). The Grading of Recommendation, Assessment, Development and Evaluation (GRADE) approach was used for the quality assessment. Data concerning the mean difference in mesial molar movement and extent of canine retraction were extracted for statistical analysis. The mean differences and 95% confidence intervals were analyzed for continuous data. A meta-analysis with a random-effects model for comparable outcomes was carried out. Results Three RCTs and five CCTs were finally included. Meta-analysis showed a significant increase not only in anchorage preservation in the implant anchorage group in both the maxilla (1.56 mm, 95% CI: 1.14 to 1.98, P < 0.00001) and the mandible (1.62 mm, 95% CI: 1.24 to 2.01, P < 0.00001) but also in canine retraction in the implant anchorage group in both the maxilla (0.43 mm, 95% CI: 0.16 to 0.69, P = 0.001) and the mandible (0.26 mm, 95% CI: 0.02 to 0.49, P = 0.03). Conclusions There is very low-quality evidence showing that implant anchorage is more efficient than conventional anchorage during canine retraction. Additional high-quality studies are needed.

scholarly journals Relationship between hormonal contraceptives and sleep among women of reproductive age: a systematic review protocol

BMJ Open ◽  
2021 ◽  
Vol 11 (10) ◽  
pp. e045819
Author(s):  
Jinhui Ma ◽  
Megan Cheng ◽  
Lehana Thabane ◽  
Caihong Ma ◽  
Ning Zhang ◽  
...  
Keyword(s):  
Systematic Review ◽  
Meta Analysis ◽  
Research Question ◽  
Risk Of Bias ◽  
Reproductive Age ◽  
Hormonal Contraceptives ◽  
Controlled Trials ◽  
Cochrane Central Register ◽  
Women Of Reproductive Age

IntroductionThe aetiology of sleep disruptions is unknown, but hormonal fluctuations during the menstrual cycle, pregnancy and menopause have been shown to potentially affect how well a woman sleeps. The aim of this systematic review was to investigate whether hormonal contraceptives are associated with a decreased quality of sleep and increased sleep duration in women of reproductive age.MethodsThis review will analyse data from randomised controlled trials or non-randomised comparative studies investigating the association between hormonal contraceptives and sleep outcomes among women of reproductive age. Reviews addressing the same research question with similar eligibility criteria will be included. A literature search will be performed using the MEDLINE, Embase and Cochrane Central Register of Controlled Trials databases from inception to 7 March 2021. The Cochrane Collaboration’s Risk of Bias for Randomised Trials V.2.0 and The Risk of Bias for Non-randomised Studies of Interventions tool will be used to assess risk of bias for each outcome in eligible studies. Two reviewers will independently assess eligibility of studies and risk of bias and extract the data. All extracted data will be presented in tables and narrative form. For sleep measures investigated by two or more studies with low heterogeneity, we will conduct random-effects meta-analysis to estimate the magnitude of the overall effect of hormonal contraceptives. If studies included in this systematic review form a connected network, a network meta-analysis will be conducted to estimate the comparative effect of different contraceptives. The Grading of Recommendations, Assessment, Development, and Evaluation approach will be used to summarise the quality of evidence. Our protocol follows the Preferred Reporting Items for Systematic Reviews and Meta-Analyses for Protocols 2015 guidelines.Ethics and disseminationEthics approval is not required as data were sourced from previously reported studies. The findings of this review will be published in a peer-reviewed journal and presented at relevant conferences.PROSPERO registration numberCRD42020199958.

scholarly journals Psychological interventions for chronic non-specific low back pain: protocol of a systematic review with network meta-analysis

BMJ Open ◽  
2020 ◽  
Vol 10 (9) ◽  
pp. e034996
Author(s):  
Emma Ho ◽  
Manuela Ferreira ◽  
Lingxiao Chen ◽  
Milena Simic ◽  
Claire Ashton-James ◽  
...  
Keyword(s):  
Systematic Review ◽  
Low Back Pain ◽  
Back Pain ◽  
Meta Analysis ◽  
Risk Of Bias ◽  
Psychological Interventions ◽  
Controlled Trials ◽  
Cochrane Central Register ◽  
Low Back ◽  
Fear Avoidance

IntroductionPsychological factors such as fear avoidance beliefs, depression, anxiety, catastrophic thinking and familial and social stress, have been associated with high disability levels in people with chronic low back pain (LBP). Guidelines endorse the integration of psychological interventions in the management of chronic LBP. However, uncertainty surrounds the comparative effectiveness of different psychological approaches. Network meta-analysis (NMA) allows comparison and ranking of numerous competing interventions for a given outcome of interest. Therefore, we will perform a systematic review with a NMA to determine which type of psychological intervention is most effective for adults with chronic non-specific LBP.Methods and analysisWe will search electronic databases (MEDLINE, Embase, PsycINFO, Cochrane Central Register of Controlled Trials, Web of Science, SCOPUS and CINAHL) from inception until 22 August 2019 for randomised controlled trials comparing psychological interventions to any comparison interventions in adults with chronic non-specific LBP. There will be no restriction on language. The primary outcomes will include physical function and pain intensity, and secondary outcomes will include health-related quality of life, fear avoidance, intervention compliance and safety. Risk of bias will be assessed using the Revised Cochrane risk-of-bias tool for randomised trials (RoB 2) tool and confidence in the evidence will be assessed using the Confidence in NMA (CINeMA) framework. We will conduct a random-effects NMA using a frequentist approach to estimate relative effects for all comparisons between treatments and rank treatments according to the mean rank and surface under the cumulative ranking curve values. All analyses will be performed in Stata.Ethics and disseminationNo ethical approval is required. The research will be published in a peer-reviewed journal.PROSPERO registration numberCRD42019138074.

Use of Prophylaxis for Prevention of Venous Thromboembolism in Patients with Isolated Foot or Ankle Surgery: A Systematic Review and Meta-Analysis

2019 ◽  
Vol 119 (10) ◽  
pp. 1686-1694 ◽  
Author(s):  
Bavand Bikdeli ◽  
Renuka Visvanathan ◽  
David Jimenez ◽  
Manuel Monreal ◽  
Samuel Z. Goldhaber ◽  
...  
Keyword(s):  
Systematic Review ◽  
Venous Thromboembolism ◽  
Meta Analysis ◽  
Evidence Base ◽  
Controlled Trials ◽  
Cochrane Central Register ◽  
Foot And Ankle ◽  
Vte Prophylaxis ◽  
Ankle Surgery ◽  
Significant Difference

AbstractAlthough prophylaxis for venous thromboembolism (VTE) is recommended after many surgeries, evidence base for use of VTE prophylaxis after foot or ankle surgery has been elusive, leading into varying guidelines recommendations and notable practice variations. We conducted a systematic review of the literature to determine if use of VTE prophylaxis decreased the frequency of subsequent VTE, including deep vein thrombosis (DVT) or pulmonary embolism (PE), compared with control. We searched PubMed, the Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov through May 2018, for randomized controlled trials (RCTs) or prospective controlled observational studies of VTE prophylaxis in patients undergoing foot and ankle surgery. Our search retrieved 263 studies, of which 6 were finally included comprising 1,600 patients. Patients receiving VTE prophylaxis had lower risk for subsequent DVT (risk ratio [RR]: 0.72; 95% confidence interval [CI]: 0.55–0.94) and subsequent VTE (RR: 0.72; 95% CI: 0.55–0.94). There was only one case of nonfatal PE, no cases of fatal PE, and no change in all-cause mortality (RR: 3.51; 95% CI: 0.14–84.84). There was no significant difference in the risk for bleeding (RR: 2.12; 95% CI: 0.53–8.56). Very few RCTs exist regarding the efficacy and safety of VTE prophylaxis in foot and ankle surgery. Prophylaxis appears to reduce the risk of subsequent VTE, but the event rates are low and symptomatic events are rare. Future studies should determine the subgroups of patients undergoing foot or ankle surgery in whom prophylaxis may be most useful.

scholarly journals Blinding integrity in randomized sham-controlled trials of repetitive transcranial magnetic stimulation for major depression: a systematic review and meta-analysis

2013 ◽  
Vol 16 (5) ◽  
pp. 1173-1181 ◽  
Author(s):  
Marcelo T. Berlim ◽  
Hannah J. Broadbent ◽  
Frederique Van den Eynde
Keyword(s):  
Systematic Review ◽  
Transcranial Magnetic Stimulation ◽  
Major Depression ◽  
Magnetic Stimulation ◽  
Repetitive Transcranial Magnetic Stimulation ◽  
Meta Analysis ◽  
Controlled Trials ◽  
Cochrane Central Register ◽  
Treatment Allocation ◽  
Significant Difference

Abstract Repetitive transcranial magnetic stimulation (rTMS) is a safe and effective treatment for major depression (MD). However, the perceived lack of a suitable sham rTMS condition might have compromised the success of blinding procedures in clinical trials. Thus, we conducted a systematic review and meta-analysis of randomized, double-blind and sham-controlled trials (RCTs) on high frequency (HF-), low frequency (LF-) and bilateral rTMS for MD. We searched the literature from January 1995 to July 2012 using Medline, EMBASE, PsycINFO, Cochrane Central Register of Controlled Trials and Scopus. The main outcome measure was participants' ability to correctly guess their treatment allocation at study end. We used a random-effects model and risk difference (RD). Overall, data were obtained from seven and two RCTs on HF- and bilateral rTMS, respectively. No RCT on LF-rTMS reporting on blinding success was found. HF- and bilateral rTMS trials enrolled 396 and 93 depressed subjects and offered an average of approximately 13 sessions. At study end, 52 and 59% of subjects receiving HF-rTMS and sham rTMS were able to correctly guess their treatment allocation, a non-significant difference (RD = −0.04; z = −0.51; p = 0.61). Furthermore, 63.3 and 57.5% of subjects receiving bilateral and sham rTMS were able to correctly guess their treatment allocation, also a non-significant difference (RD = 0.05; z = 0.49; p = 0.62). In addition, the use of angulation and sham coil in HF-rTMS trials produced similar results. In summary, existing sham rTMS interventions appear to result in acceptable levels of blinding regarding treatment allocation.

scholarly journals Effectiveness of orthodontic temporary anchorage devices in canine retraction and anchorage preservation during the two-step technique: A systematic review and meta-analysis

2020 ◽  
Author(s):  
Haonan Tian ◽  
Congman Xie ◽  
Min Lin ◽  
Hongmei Yang ◽  
Aishu Ren
Keyword(s):  
Systematic Review ◽  
Meta Analysis ◽  
Risk Of Bias ◽  
Mean Difference ◽  
Controlled Trials ◽  
Cochrane Central Register ◽  
Canine Retraction ◽  
Temporary Anchorage Devices ◽  
The Mean ◽  
Implant Anchorage

Abstract Background: Temporary anchorage devices have been used for decades in orthodontic practice for many applications. The aim of this systematic review was to assess the effectiveness of orthodontic temporary anchorage devices in canine retraction during the two-step technique. Methods: A search was systematically performed for articles published prior to June 30, 2019 in five electronic databases (PubMed, Embase, Cochrane Central Register of Controlled Trials, Web of Science, Scopus). The risk of bias was assessed using the Cochrane risk of bias tool for randomized controlled trials (RCTs) and the risk of bias in nonrandomized studies of interventions (ROBINS-I) tool for controlled clinical trials (CCTs) . The Grading of Recommendation, Assessment, Development and Evaluation (GRADE) approach was used for the quality assessment. Data concerning the mean difference in mesial molar movement and extent of canine retraction were extracted for statistical analysis. The mean difference s and 95% confidence intervals were analyzed for continuous data. A meta-analysis with a random-effects model for comparable outcomes was carried out. Results: Three RCTs and five CCTs were finally included. Meta-analysis showed a significant increase not only in anchorage preservation in the implant anchorage group in both the maxilla (1. 56 mm , 95% CI: 1.14 to 1.98, P <0.00001 ) and the mandible (1.62 mm , 95% CI: 1.24 to 2.01, P <0.00001 ) but also in canine retraction in the implant anchorage group in both the maxilla (0.43 mm , 95% CI: 0.16 to 0.69, P =0.001 ) and the mandible (0.26 mm , 95% CI: 0.02 to 0.49, P =0.03 ). Conclusions: There is very low-quality evidence showing that implant anchorage is more efficient than conventional anchorage during canine retraction. Additional high-quality studies are needed. Keywords: Orthodontic implants; Canine retraction; Systematic review; Meta-analysis

scholarly journals Vitamin D in Breastfed Infants: Systematic Review of Alternatives to Daily Supplementation

2019 ◽  
Author(s):  
Karen M O'Callaghan ◽  
Mahgol Taghivand ◽  
Anna Zuchniak ◽  
Akpevwe Onoyovwi ◽  
Jill Korsiak ◽  
...  
Keyword(s):  
Systematic Review ◽  
Vitamin D ◽  
Vitamin D Deficiency ◽  
Weighted Mean Difference ◽  
Meta Analysis ◽  
Pooled Analysis ◽  
Vitamin D Supplementation ◽  
Controlled Trials ◽  
Cochrane Central Register ◽  
Term Infants

ABSTRACT Daily oral vitamin D supplementation (400 IU) is recommended for breastfeeding infants (≤1 y). Recent studies have examined alternative approaches to preventing vitamin D deficiency in this population. This systematic review and meta-analysis aimed to estimate the effects of maternal postpartum (M-PP) or infant intermittent (I-INT) vitamin D supplementation on infant 25-hydroxyvitamin D [25(OH)D] concentrations in comparison to routine direct infant daily (I-D) oral supplementation (400 IU). MEDLINE, MEDLINE In-Process, Embase, the Cochrane Database of Systematic Reviews, and the Cochrane Central Register of Controlled Trials were searched up to December 2018. Inclusion criteria consisted of published, peer-reviewed, vitamin D intervention trials involving lactating women and/or exclusively or partially breastfed term infants. Two reviewers independently extracted study characteristics (e.g., sample size, intervention dose, and duration and mode of administration) and related biochemical and clinical outcomes. Of 28 included trials, 5 randomized controlled trials were incorporated in meta-analyses examining infant 25(OH)D. Overall, M-PP supplementation resulted in modestly lower infant 25(OH)D compared with I-D supplementation (weighted mean difference = −8.1 nmol/L; 95% CI: −15.4, −0.9; I2 = 45%; P = 0.14; 3 trials), but the 2 most recent trials found M-PP to achieve similar infant 25(OH)D as I-D. Comparison of I-INT with I-D was confined to 2 trials with contradictory findings, and it was considered inappropriate for pooled analysis. Meta-analysis was therefore limited by a small number of eligible trials with variable quality of analytically derived 25(OH)D data and inconsistent reporting of safety outcomes, including effects on calcium homeostasis. Considering all 28 included trials, this systematic review highlights M-PP and I-INT regimens as plausible substitutes for routine daily infant vitamin D supplementation, but evidence remains too weak to support a policy update. Dose-ranging, adequately powered trials are required to establish the efficacy, safety, and feasibility of alternative strategies to prevent vitamin D deficiency in breastfeeding infants. This review was registered with PROSPERO as CRD42017069905.

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