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Introduction: The optimal duration of magnesium administration postpartum for prevention of eclampsia has not yet been established. Our objective was to investigate the effect of early discontinuation of postpartum magnesium on the rates of postpartum eclampsia compared to continuation for 24-hours postpartum., Material and Methods: Searches were performed using keywords related to "preeclampsia" and "magnesium sulfate" from inception of database until August 2023. Randomized controlled trials of women with preeclampsia were included if they received magnesium prior to delivery and were randomized to early discontinuation versus 24-hours of magnesium postpartum. The primary outcome was the rate of postpartum eclampsia., Results: Nine RCTs with 2183 women were included with five different magnesium administration time frames. In total, seven patients with postpartum eclampsia were reported in three studies. Eclampsia rates were not different between the two groups (5/1088 (0.5 %) after early discontinuation, versus 2/1095 (0.2 %) in the 24-hour group; RR 2.25, 95 % CI 0.5-9.9, I 2  = 0 %, 8 studies, 2183 participants). A number needed to treat was calculated; 374 women would need to receive 24-hours of magnesium postpartum to prevent one episode of postpartum eclampsia. The early discontinuation group had a significant decrease in time to ambulation (-9.1 h, 95 % CI -14.7 - (-3.6), I 2  = 98 %, 3 studies, 1509 participants) and breastfeeding (-8.4 h, 95 % CI -12.0 - (-4.8), I 2  = 98 %, 2 studies, 1397 participants)., Conclusions: Early magnesium discontinuation postpartum, usually ≤6 h or none at all, did not significantly increase the rate of postpartum eclampsia, however this study is likely underpowered to demonstrate a difference. The number needed to treat is similar to the number needed to treat for antepartum preeclampsia without severe features, for which magnesium is not recommended. The largest proportion of women did not receive magnesium postpartum after receiving at least 8 h of magnesium intrapartum (e.g., loading and maintenance dose). Thus, it is reasonable to consider not using magnesium postpartum, particularly if a woman has received similar adequate dose prior to delivery., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Dr. Ben Willem Mol is supported by a NHMRC Practitioner Fellowship (GNT1082548). Dr. Ben Willem Mol reports consultancy for ObsEva, Merck Merck KGaA and Guerbet. Dr Jack Ludmir and Dr Paulino Vigil-de Gracia were both authors on included randomized trials. The other authors did not report any potential conflicts of interest., (Copyright © 2024 International Society for the Study of Hypertension in Pregnancy. Published by Elsevier B.V. All rights reserved.)

Background: Deferred (also known as delayed) cord clamping can improve survival of infants born preterm (before 37 weeks of gestation), but the optimal duration of deferral remains unclear. We conducted a systematic review and individual participant data network meta-analysis with the aim of comparing the effectiveness of umbilical cord clamping strategies with different timings of clamping or with cord milking for preterm infants., Methods: We searched medical databases and trial registries from inception until Feb 24, 2022 (updated June 6, 2023) for randomised controlled trials comparing cord clamping strategies for preterm infants. Individual participant data were harmonised and assessed for risk of bias and quality. Interventions were grouped into immediate clamping, short deferral (≥15 s to <45 s), medium deferral (≥45 s to <120 s), long deferral (≥120 s), and intact cord milking. The primary outcome was death before hospital discharge. We calculated one-stage, intention-to-treat Bayesian random-effects individual participant data network meta-analysis. This study was registered with PROSPERO, CRD42019136640., Findings: We included individual participant data from 47 trials with 6094 participants. Of all interventions, long deferral reduced death before discharge the most (compared with immediate clamping; odds ratio 0·31 [95% credibility interval] 0·11-0·80; moderate certainty). The risk of bias was low for 10 (33%) of 30 trials, 14 (47%) had some concerns, and 6 (20%) were rated as having a high risk of bias. Heterogeneity was low, with no indication of inconsistency., Interpretation: This study found that long deferral of clamping leads to reduced odds of death before discharge in preterm infants. In infants assessed as requiring immediate resuscitation, this finding might only be generalisable if there are provisions for such care with the cord intact. These results are based on thoroughly cleaned and checked individual participant data and can inform future guidelines and practice., Funding: Australian National Health and Medical Research Council., Competing Interests: Declaration of interests iCOMP trial representatives comprised principal investigators of studies included in this meta-analysis. Trial representatives did not input on study eligibility, data integrity assessments, data extraction, or risk of bias assessments for their own studies. Trial representatives did not make final decisions on certainty of evidence ratings. ALS reports Australian National Health and Medical Research Council (NHMRC) project and Investigator grants (funds paid directly to the University of Sydney). JXS reports travel grants and scholarships from the Association of Interdisciplinary Meta-science and Open-Science, Pediatric Academic Societies, and the Perinatal Society of Australia and New Zealand. KEH reports NHMRC funding paid directly to the University of Sydney. All other authors declare no competing interests. The full list of iCOMP Collaborators and their declaration of interests are noted in the appendix (pp 318–21)., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: Umbilical cord clamping strategies at preterm birth have the potential to affect important health outcomes. The aim of this study was to compare the effectiveness of deferred cord clamping, umbilical cord milking, and immediate cord clamping in reducing neonatal mortality and morbidity at preterm birth., Methods: We conducted a systematic review and individual participant data meta-analysis. We searched medical databases and trial registries (from database inception until Feb 24, 2022; updated June 6, 2023) for randomised controlled trials comparing deferred (also known as delayed) cord clamping, cord milking, and immediate cord clamping for preterm births (<37 weeks' gestation). Quasi-randomised or cluster-randomised trials were excluded. Authors of eligible studies were invited to join the iCOMP collaboration and share individual participant data. All data were checked, harmonised, re-coded, and assessed for risk of bias following prespecified criteria. The primary outcome was death before hospital discharge. We performed intention-to-treat one-stage individual participant data meta-analyses accounting for heterogeneity to examine treatment effects overall and in prespecified subgroup analyses. Certainty of evidence was assessed with Grading of Recommendations Assessment, Development, and Evaluation. This study is registered with PROSPERO, CRD42019136640., Findings: We identified 2369 records, of which 48 randomised trials provided individual participant data and were eligible for our primary analysis. We included individual participant data on 6367 infants (3303 [55%] male, 2667 [45%] female, two intersex, and 395 missing data). Deferred cord clamping, compared with immediate cord clamping, reduced death before discharge (odds ratio [OR] 0·68 [95% CI 0·51-0·91], high-certainty evidence, 20 studies, n=3260, 232 deaths). For umbilical cord milking compared with immediate cord clamping, no clear evidence was found of a difference in death before discharge (OR 0·73 [0·44-1·20], low certainty, 18 studies, n=1561, 74 deaths). Similarly, for umbilical cord milking compared with deferred cord clamping, no clear evidence was found of a difference in death before discharge (0·95 [0·59-1·53], low certainty, 12 studies, n=1303, 93 deaths). We found no evidence of subgroup differences for the primary outcome, including by gestational age, type of delivery, multiple birth, study year, and perinatal mortality., Interpretation: This study provides high-certainty evidence that deferred cord clamping, compared with immediate cord clamping, reduces death before discharge in preterm infants. This effect appears to be consistent across several participant-level and trial-level subgroups. These results will inform international treatment recommendations., Funding: Australian National Health and Medical Research Council., Competing Interests: Declaration of interests iCOMP trial representatives comprised principal investigators of studies included in this meta-analysis. Trial representatives did not have input on study eligibility, data integrity assessments, data extraction, or risk of bias assessments for their own studies. Trial representatives did not make final decisions on certainty of evidence ratings. ALS is a recipient of Australian National Health and Medical Research Council (NHMRC) project and investigator grants (funds paid directly to the University of Sydney). JXS reports travel grants and scholarships from the Association of Interdisciplinary Meta-science and Open-Science, Pediatric Academic Societies, and the Perinatal Society of Australia and New Zealand. KEH is a recipient of NHMRC funding paid directly to the University of Sydney. The full list of iCOMP Collaborators and their declaration of interests are noted in the appendix (pp 371–374). All other authors have no competing interests., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Objective: To propose a taxonomy and framework that identifies and presents actionable statements in guidelines., Study Design and Setting: We took an iterative approach reviewing case studies of guidelines produced by the World Health Organization and the American Society of Hematology to develop an initial conceptual framework. We then tested it using randomly selected recommendations from published guidelines addressing COVID-19 from different organizations, evaluated its results, and refined it before retesting. The urgency and availability of evidence for development of these recommendations varied. We consulted with experts in research methodology and guideline developers to improve the final framework., Results: The resulting taxonomy and framework distinguishes five types of actional statements: formal recommendations; research recommendations; good practice statements; implementation considerations, tools and tips; and informal recommendations. These statements should respond to a priori established criteria and require a clear structure and recognizable presentation in a guideline. Most importantly, this framework identifies informal recommendations that differ from formal recommendations by how they consider evidence and in their development process., Conclusion: The identification, standardization and explicit labelling of actionable statements according to the framework may support guideline developers to create actionable statements with clear intent, avoid informal recommendations and improve their understanding and implementation by users., (Copyright © 2021. Published by Elsevier Inc.)

Objectives: The objective of this study was to determine the prevalence of trial registration in health research, whether trial registration status and timing vary depending on trial characteristics, and the relationship between trial registration status and risk of bias., Study Design and Setting: We systematically reviewed all clinical trials published from January to June 2017 in 28 high- and low-impact factor general and specialty medicine journals., Results: We identified 370 trials and assessed risk of bias in 183 trials. Trial registration rates were high; 95% of trials were registered prospectively or retrospectively before enrollment completion. Larger sample size, multiple recruitment countries, and primary industry funding were all predictors of earlier trial registration. Prospectively registered trials had a significantly lower risk of bias compared to unregistered trials across all domains. Prospectively registered trials had a similar risk of bias compared to retrospectively registered trials across four out of six domains, and a lower risk of bias across the remaining two domains., Conclusion: Trial registration is an imperfect proxy for risk of bias. Systematic reviewers should assess risk of bias on a case-by-case basis and conduct sensitivity analyses excluding high risk of bias studies. In the longer term, mechanisms should be implemented to facilitate prospective registration of all trials., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: The effects of delayed cord clamping of the umbilical cord in preterm infants are unclear., Objective: We sought to compare the effects of delayed vs early cord clamping on hospital mortality (primary outcome) and morbidity in preterm infants using Cochrane Collaboration neonatal review group methodology., Study Design: We searched MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, and Chinese articles, cross-referencing citations, expert informants, and trial registries to July 31, 2017, for randomized controlled trials of delayed (≥30 seconds) vs early (<30 seconds) clamping in infants born <37 weeks' gestation. Before searching the literature, we specified that trials estimated to have cord milking in >20% of infants in any arm would be ineligible. Two reviewers independently selected studies, assessed bias, and extracted data. Relative risk (ie, risk ratio), risk difference, and mean difference with 95% confidence intervals were assessed by fixed effects models, heterogeneity by I 2 statistics, and the quality of evidence by Grading of Recommendations, Assessment, Development, and Evaluations., Results: Eighteen randomized controlled trials compared delayed vs early clamping in 2834 infants. Most infants allocated to have delayed clamping were assigned a delay of ≥60 seconds. Delayed clamping reduced hospital mortality (risk ratio, 0.68; 95% confidence interval, 0.52-0.90; risk difference, -0.03; 95% confidence interval, -0.05 to -0.01; P = .005; number needed to benefit, 33; 95% confidence interval, 20-100; Grading of Recommendations, Assessment, Development, and Evaluations = high, with I 2  = 0 indicating no heterogeneity). In 3 trials in 996 infants ≤28 weeks' gestation, delayed clamping reduced hospital mortality (risk ratio, 0.70; 95% confidence interval, 0.51-0.95; risk difference, -0.05; 95% confidence interval, -0.09 to -0.01; P = .02, number needed to benefit, 20; 95% confidence interval, 11-100; I 2  = 0). In subgroup analyses, delayed clamping reduced the incidence of low Apgar score at 1 minute, but not at 5 minutes, and did not reduce the incidence of intubation for resuscitation, admission temperature, mechanical ventilation, intraventricular hemorrhage, brain injury, chronic lung disease, patent ductus arteriosus, necrotizing enterocolitis, late onset sepsis or retinopathy of prematurity. Delayed clamping increased peak hematocrit by 2.73 percentage points (95% confidence interval, 1.94-3.52; P < .00001) and reduced the proportion of infants having blood transfusion by 10% (95% confidence interval, 6-13%; P < .00001). Potential harms of delayed clamping included polycythemia and hyperbilirubinemia., Conclusion: This systematic review provides high-quality evidence that delayed clamping reduced hospital mortality, which supports current guidelines recommending delayed clamping in preterm infants. This review does not evaluate cord milking, which may also be of benefit. Analyses of individual patient data in these and other randomized controlled trials will be critically important in reliably evaluating important secondary outcomes., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: The optimum time for commencing antiplatelet therapy for the prevention of preeclampsia and its complications is unclear. Aggregate data meta-analyses suggest that aspirin is more effective if given prior to 16 weeks' gestation, but data are limited because of an inability to place women in the correct gestational age subgroup from relevant trials., Objective: The objective of the study was to use the large existing individual participant data set from the Perinatal Antiplatelet Review of International Studies Collaboration to assess whether the treatment effects of antiplatelet agents on preeclampsia and its complications vary based on whether treatment is started before or after 16 weeks' gestation., Study Design: A meta-analysis of individual participant data including 32,217 women and 32,819 babies recruited to 31 randomized trials comparing low-dose aspirin or other antiplatelet agents with placebo or no treatment for the prevention of preeclampsia has been published previously. Using this existing data set, we performed a prespecified subgroup analysis based on gestation at randomization to antiplatelet agents before 16 weeks, compared with at or after 16 weeks, for 4 of the main outcomes prespecified in the Perinatal Antiplatelet Review of International Studies protocol: preeclampsia, death of baby, preterm birth before 34 weeks, and small-for-gestational-age baby. Individual participant data for the subgroups were combined in a meta-analysis using RevMan software. Heterogeneity was assessed with the I 2 statistic. The χ 2 test for interaction was used to assess statistically significant (P < .05) differences in treatment effect between subgroups., Results: There was no significant difference in the effects of antiplatelet therapy for women randomized before 16 weeks' gestation compared with those randomized at or after 16 weeks for any of the 4 prespecified outcomes: preeclampsia, relative risk, 0.90, (95% confidence interval, 0.79-1.03; 17 trials, 9241 women) for <16 weeks and relative risk, 0.90 (95% confidence interval, 0.83-0.98; 22 trials, 21,429 women) for ≥16 weeks (interaction test, P = .98); death of baby, relative risk, 0.89 (95% confidence interval, 0.73-1.09; 15 trials, 8626 women) for <16 weeks and relative risk, 0.92 (95% confidence interval, 0.79-1.07; 21 trials, 22,336 women) for ≥16 weeks (interaction test, P = .80); preterm birth prior to 34 weeks, relative risk, 0.90 (95% confidence interval, 0.77-1.04; 19 trials, 9155 women) for <16 weeks and relative risk, 0.91 (95% confidence interval, 0.82-1.00; 25 trials, 22,117 women) for ≥16 weeks (interaction test, P = .91); and small-for-gestational-age baby, relative risk, 0.76 (95% confidence interval, 0.61-0.94; 13 trials, 6393 women) for <16 weeks and relative risk, 0.95 (95% confidence interval, 0.84-1.08; 18 trials, 14,996 women) for ≥16 weeks (interaction test, P = .08)., Conclusion: The effect of low-dose aspirin and other antiplatelet agents on preeclampsia and its complications is consistent, regardless of whether treatment is started before or after 16 weeks' gestation. Women at an increased risk of preeclampsia should be offered antiplatelet therapy, regardless of whether they are first seen before or after 16 weeks' gestation., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Systematic reviews and meta-analyses are at the top of the 'evidence hierarchy' when assessing the effectiveness of health interventions. As such, they are important sources of synthesized information for decision-makers including consumers, clinicians, funders, payers, regulators, and researchers. The main reasons for undertaking systematic reviews and meta-analyses are to minimize bias and to maximize data by collating all the relevant, available evidence on a particular topic. In order to correctly inform decision-makers, but not mislead them, a number of key methodological conditions need to be met when undertaking these types of analysis. In this article we first review the history of systematic reviews and meta-analyses and then outline those conditions that may lead to the correct, or incorrect, use of these types of study. Also, new variations on standard systematic review methods are explored, with the pros and cons of each outlined., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Objectives: To demonstrate how individual participant data (IPD) meta-analyses have impacted directly on the design and conduct of trials and highlight other advantages IPD might offer., Study Design and Setting: Potential examples of the impact of IPD meta-analyses on trials were identified at an international workshop, attended by individuals with experience in the conduct of IPD meta-analyses and knowledge of trials in their respective clinical areas. Experts in the field who did not attend were asked to provide any further examples. We then examined relevant trial protocols, publications, and Web sites to verify the impacts of the IPD meta-analyses. A subgroup of workshop attendees sought further examples and identified other aspects of trial design and conduct that may inform IPD meta-analyses., Results: We identified 52 examples of IPD meta-analyses thought to have had a direct impact on the design or conduct of trials. After screening relevant trial protocols and publications, we identified 28 instances where IPD meta-analyses had clearly impacted on trials. They have influenced the selection of comparators and participants, sample size calculations, analysis and interpretation of subsequent trials, and the conduct and analysis of ongoing trials, sometimes in ways that would not possible with systematic reviews of aggregate data. We identified additional potential ways that IPD meta-analyses could be used to influence trials., Conclusions: IPD meta-analysis could be better used to inform the design, conduct, analysis, and interpretation of trials., (Crown Copyright © 2015. Published by Elsevier Inc. All rights reserved.)

Background: Population and study design heterogeneity has confounded previous meta-analyses, leading to uncertainty about effectiveness and safety of elective high-frequency oscillatory ventilation (HFOV) in preterm infants. We assessed effectiveness of elective HFOV versus conventional ventilation in this group., Methods: We did a systematic review and meta-analysis of individual patients' data from 3229 participants in ten randomised controlled trials, with the primary outcomes of death or bronchopulmonary dysplasia at 36 weeks' postmenstrual age, death or severe adverse neurological event, or any of these outcomes., Findings: For infants ventilated with HFOV, the relative risk of death or bronchopulmonary dysplasia at 36 weeks' postmenstrual age was 0.95 (95% CI 0.88-1.03), of death or severe adverse neurological event 1.00 (0.88-1.13), or any of these outcomes 0.98 (0.91-1.05). No subgroup of infants (eg, gestational age, birthweight for gestation, initial lung disease severity, or exposure to antenatal corticosteroids) benefited more or less from HFOV. Ventilator type or ventilation strategy did not change the overall treatment effect., Interpretation: HFOV seems equally effective to conventional ventilation in preterm infants. Our results do not support selection of preterm infants for HFOV on the basis of gestational age, birthweight for gestation, initial lung disease severity, or exposure to antenatal corticosteroids., Funding: Nestlé Belgium, Belgian Red Cross, and Dräger International.

Background: Pre-eclampsia is a major cause of mortality and morbidity during pregnancy and childbirth. Antiplatelet agents, especially low-dose aspirin, might prevent or delay pre-eclampsia, and thereby improve outcome. Our aim was to assess the use of antiplatelet agents for the primary prevention of pre-eclampsia, and to explore which women are likely to benefit most., Methods: We did a meta-analysis of individual patient data from 32,217 women, and their 32,819 babies, recruited to 31 randomised trials of pre-eclampsia primary prevention., Findings: For women assigned to receive antiplatelet agents rather than control, the relative risk of developing pre-eclampsia was 0.90 (95% CI 0.84-0.97), of delivering before 34 weeks was 0.90 (0.83-0.98), and of having a pregnancy with a serious adverse outcome was 0.90 (0.85-0.96). Antiplatelet agents had no significant effect on the risk of death of the fetus or baby, having a small for gestational age infant, or bleeding events for either the women or their babies. No particular subgroup of women was substantially more or less likely to benefit from antiplatelet agents than any other., Interpretation: Antiplatelet agents during pregnancy are associated with moderate but consistent reductions in the relative risk of pre-eclampsia, of birth before 34 weeks' gestation, and of having a pregnancy with a serious adverse outcome.

Objectives: To assess how trial information reported in conference abstracts differs to their subsequent full publication., Methods: Randomized trials reported at the American Society of Clinical Oncology conference (1992) were identified. CENTRAL and PubMed (December 2002) were searched to identify corresponding full publications. A checklist (based on CONSORT) was used to compare abstracts for 37 trials with their full publication., Results: Some aspects were well reported. Ninety-five percent of study objectives, 92% of participant eligibility, 100% of trial interventions, and 84% of primary outcomes were the same in both abstract and full publication. Other areas were more discrepant. Forty-six percent reported the same number of participants randomized in the abstract and full publication; only 22% reported the same number analyzed (median number analyzed per trial was 96 for abstracts and 117 for full publications). Eighty-two percent of trials were closed to follow-up in the full publication compared to 19% of abstracts. Lack of information was a major problem in assessing trial quality: no abstracts reported on allocation concealment, 16% reported on blinding and 14% reported intention to treat analysis. These figures were 49, 19, and 46%, respectively, for full publications., Conclusion: The information given for trials in conference proceedings can be unstable, especially for trials presenting early or preliminary results, and needs to be improved.

Chronic lung disease is common in extremely preterm infants born in Australasia. In 2002, 53% of surviving infants born before 28 weeks' gestation remained either oxygen-dependent or on other respiratory support at 36 weeks' postmenstrual age. In the first weeks of life oxygenation should be kept generally "lower", although what is the most appropriate level remains uncertain. During the mid-phase of the neonatal course, functional oxygen saturation levels around 90-95% probably confer the best benefit/risk balance. The most appropriate target saturation range for infants on home oxygen also remains uncertain. Definitive data to guide clinical practice is lacking regarding the use of postnatal corticosteroids, bronchodilators, and diuretics for either the treatment or prevention of chronic lung disease. Home oxygen programmes are effective in avoiding prolonged hospitalisation for infants with chronic lung disease, but require the coordination of a large, multidisciplinary team.