Deferred cord clamping, cord milking, and immediate cord clamping at preterm birth: a systematic review and individual participant data meta-analysis.

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.

Short, medium, and long deferral of umbilical cord clamping compared with umbilical cord milking and immediate clamping at preterm birth: a systematic review and network meta-analysis with individual participant data.

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.

Eating Disorders In weight-related Therapy (EDIT) Collaboration: rationale and study design.

The cornerstone of obesity treatment is behavioural weight management, resulting in significant improvements in cardio-metabolic and psychosocial health. However, there is ongoing concern that dietary interventions used for weight management may precipitate the development of eating disorders. Systematic reviews demonstrate that, while for most participants medically supervised obesity treatment improves risk scores related to eating disorders, a subset of people who undergo obesity treatment may have poor outcomes for eating disorders. This review summarises the background and rationale for the formation of the Eating Disorders In weight-related Therapy (EDIT) Collaboration. The EDIT Collaboration will explore the complex risk factor interactions that precede changes to eating disorder risk following weight management. In this review, we also outline the programme of work and design of studies for the EDIT Collaboration, including expected knowledge gains. The EDIT studies explore risk factors and the interactions between them using individual-level data from international weight management trials. Combining all available data on eating disorder risk from weight management trials will allow sufficient sample size to interrogate our hypothesis: that individuals undertaking weight management interventions will vary in their eating disorder risk profile, on the basis of personal characteristics and intervention strategies available to them. The collaboration includes the integration of health consumers in project development and translation. An important knowledge gain from this project is a comprehensive understanding of the impact of weight management interventions on eating disorder risk.

PROspective Meta-analysis Of Trials of Initial Oxygen in preterm Newborns (PROMOTION): Protocol for a systematic review and prospective meta-analysis with individual participant data on initial oxygen concentration for resuscitation of preterm infants.

BACKGROUND: Clinicians favour low oxygen concentrations when resuscitating preterm infants immediately after birth despite inconclusive evidence to support this practice. Prospective meta-analysis (PMA) is a novel approach where studies are identified as eligible for inclusion in the meta-analysis before their results are known. AIMS: To explore whether high (60%) or low (30%) oxygen is associated with greater efficacy and safety for the initial resuscitation (immediately after birth) of preterm infants born at <29 weeks' gestation. METHODS: We will conduct a prospective meta-analysis (PMA) with individual participant data (IPD). We will perform a systematic search to identify ongoing RCTs including infants <29 weeks' gestation randomised to high (60%) or low (30%) oxygen for initial resuscitation after birth. IPD will be sought for all infants randomised for the purpose of meta-analysis. We will employ a one-stage random-effects approach to IPD meta-analysis. Potential heterogeneity and the differential effect of high or low oxygen will be explored through subgroup and interaction analyses. The primary outcome of this study is all-cause mortality prior to hospital discharge. There will be a follow-up analysis of neurodevelopmental outcomes once available. RESULTS/CONCLUSION: The results of neonatal outcomes at hospital discharge are expected by 2025, and neurodevelopmental outcomes by 2027.

Core outcome set for early intervention trials to prevent obesity in childhood (COS-EPOCH): Agreement on "what" to measure.

BACKGROUND: Heterogeneity in the outcomes collected and reported in trials of interventions to prevent obesity in the first five years of life highlights the need for a core outcome set to streamline intervention evaluation and synthesis of effects. This study aimed to develop a core outcome set for use in early childhood obesity prevention intervention studies in children from birth to five years of age (COS-EPOCH). METHODS: The development of the core outcome set followed published guidelines and consisted of three stages: (1) systematic scoping review of outcomes collected and reported in early childhood obesity prevention trials; (2) e-Delphi study with stakeholders to prioritise outcomes; (3) meeting with stakeholders to reach consensus on outcomes. Stakeholders included parents/caregivers of children aged ≤ five years, policy-makers/funders, researchers, health professionals, and community and organisational stakeholders interested in obesity prevention interventions. RESULTS: Twenty-two outcomes from nine outcome domains (anthropometry, dietary intake, sedentary behaviour, physical activity, sleep, outcomes in parents/caregivers, environmental, emotional/cognitive functioning, economics) were included in the core outcome set: infant tummy time; child diet quality, dietary intake, fruit and vegetable intake, non-core food intake, non-core beverage intake, meal patterns, weight-based anthropometry, screentime, time spent sedentary, physical activity, sleep duration, wellbeing; parent/caregiver physical activity, sleep and nutrition parenting practices; food environment, sedentary behaviour or physical activity home environment, family meal environment, early childhood education and care environment, household food security; economic evaluation. CONCLUSIONS: The systematic stakeholder-informed study identified the minimum outcomes recommended for collection and reporting in early childhood obesity prevention trials. Future work will investigate the recommended instruments to measure each of these outcomes. The core outcome set will standardise guidance on the measurement and reporting of outcomes from early childhood obesity prevention interventions, to better facilitate evidence comparison and synthesis, and maximise the value of data collected across studies.

Landscape of clinical trial activity focusing on Indigenous health in Australia: an overview using clinical trial registry data from 2008-2018.

BACKGROUND: Aboriginal and Torres Strait Islander peoples (hereafter respectfully referred to as Indigenous Australians) represent about 3% of the total Australian population. Major health disparities exist between Indigenous and Non-Indigenous Australians. To address this, it is vital to understand key health priorities and knowledge gaps in the current landscape of clinical trial activity focusing on Indigenous health in Australia. METHODS: Australian-based clinical trials registered on the Australian New Zealand Clinical Trials Registry or ClinicalTrials.gov from 2008 to 2018 were analysed. Australian clinical trials with and without a focus on Indigenous health were compared in terms of total numbers, participant size, conditions studied, design, intervention type and funding source. RESULTS: Of the 9206 clinical trials included, 139 (1.5%) focused on Indigenous health, with no proportional increase in Indigenous trials over the decade (p = 0.30). Top conditions studied in Indigenous-focused trials were mental health (n = 35, 28%), cardiovascular disease (n = 20, 20%) and infection (n = 16, 16%). Compared to General Australian trials, Indigenous-focused trials more frequently studied ear conditions (OR 20.26, 95% CI 10.32-37.02, p < 0.001), infection (OR 3.11, 95% CI 1.88-4.85, p < 0.001) and reproductive health (OR 2.59, 95% CI 1.50-4.15, p < 0.001), and less of musculoskeletal conditions (OR 0.09, 95% CI 0.00-0.37, p < 0.001), anaesthesiology (OR 0.16, 95% CI 0.01-0.69, p = 0.021) and surgery (OR 0.17, 95% CI 0.01-0.73, p = 0.027). For intervention types, Indigenous trials focused more on prevention (n = 48, 36%) and screening (n = 18, 13%). They were far less involved in treatment (n = 72, 52%) as an intervention than General Australian trials (n = 6785, 75%), and were less likely to be blinded (n = 48, 35% vs n = 4273, 47%) or have industry funding (n = 9, 7% vs 1587, 17%). CONCLUSIONS: Trials with an Indigenous focus differed from General Australian trials in the conditions studied, design and funding source. The presented findings may inform research prioritisation and alleviate the substantial burden of disease for Indigenous population.

Antiplatelet agents for preventing pre-eclampsia and its complications.

BACKGROUND: Pre-eclampsia is associated with deficient intravascular production of prostacyclin, a vasodilator, and excessive production of thromboxane, a vasoconstrictor and stimulant of platelet aggregation. These observations led to the hypotheses that antiplatelet agents, low-dose aspirin in particular, might prevent or delay development of pre-eclampsia. OBJECTIVES: To assess the effectiveness and safety of antiplatelet agents, such as aspirin and dipyridamole, when given to women at risk of developing pre-eclampsia. SEARCH METHODS: For this update, we searched Cochrane Pregnancy and Childbirth's Trials Register, ClinicalTrials.gov, the WHO International Clinical Trials Registry Platform (ICTRP) (30 March 2018), and reference lists of retrieved studies. We updated the search in September 2019 and added the results to the awaiting classification section of the review. SELECTION CRITERIA: All randomised trials comparing antiplatelet agents with either placebo or no antiplatelet agent were included. Studies only published in abstract format were eligible for inclusion if sufficient information was available. We would have included cluster-randomised trials in the analyses along with individually-randomised trials, if any had been identified in our search strategy. Quasi-random studies were excluded. Participants were pregnant women at risk of developing pre-eclampsia. Interventions were administration of an antiplatelet agent (such as low-dose aspirin or dipyridamole), comparisons were either placebo or no antiplatelet. DATA COLLECTION AND ANALYSIS: Two review authors assessed trials for inclusion and extracted data independently. For binary outcomes, we calculated risk ratio (RR) and its 95% confidence interval (CI), on an intention-to-treat basis. For this update we incorporated individual participant data (IPD) from trials with this available, alongside aggregate data (AD) from trials where it was not, in order to enable reliable subgroup analyses and inclusion of two key new outcomes. We assessed risk of bias for included studies and created a 'Summary of findings' table using GRADE. MAIN RESULTS: Seventy-seven trials (40,249 women, and their babies) were included, although three trials (relating to 233 women) did not contribute data to the meta-analysis. Nine of the trials contributing data were large (> 1000 women recruited), accounting for 80% of women recruited. Although the trials took place in a wide range of countries, all of the nine large trials involved only women in high-income and/or upper middle-income countries. IPD were available for 36 trials (34,514 women), including all but one of the large trials. Low-dose aspirin alone was the intervention in all the large trials, and most trials overall. Dose in the large trials was 50 mg (1 trial, 1106 women), 60 mg (5 trials, 22,322 women), 75mg (1 trial, 3697 women) 100 mg (1 trial, 3294 women) and 150 mg (1 trial, 1776 women). Most studies were either low risk of bias or unclear risk of bias; and the large trials were all low risk of bas. Antiplatelet agents versus placebo/no treatment The use of antiplatelet agents reduced the risk of proteinuric pre-eclampsia by 18% (36,716 women, 60 trials, RR 0.82, 95% CI 0.77 to 0.88; high-quality evidence), number needed to treat for one women to benefit (NNTB) 61 (95% CI 45 to 92). There was a small (9%) reduction in the RR for preterm birth <37 weeks (35,212 women, 47 trials; RR 0.91, 95% CI 0.87 to 0.95, high-quality evidence), NNTB 61 (95% CI 42 to 114), and a 14% reduction infetal deaths, neonatal deaths or death before hospital discharge (35,391 babies, 52 trials; RR 0.85, 95% CI 0.76 to 0.95; high-quality evidence), NNTB 197 (95% CI 115 to 681). Antiplatelet agents slightly reduced the risk of small-for-gestational age babies (35,761 babies, 50 trials; RR 0.84, 95% CI 0.76 to 0.92; high-quality evidence), NNTB 146 (95% CI 90 to 386), and pregnancies with serious adverse outcome (a composite outcome including maternal death, baby death, pre-eclampsia, small-for-gestational age, and preterm birth) (RR 0.90, 95% CI 0.85 to 0.96; 17,382 women; 13 trials, high-quality evidence), NNTB 54 (95% CI 34 to 132). Antiplatelet agents probably slightly increase postpartum haemorrhage > 500 mL (23,769 women, 19 trials; RR 1.06, 95% CI 1.00 to 1.12; moderate-quality evidence due to clinical heterogeneity), and they probably marginally increase the risk of placental abruption, although for this outcome the evidence was downgraded due to a wide confidence interval including the possibility of no effect (30,775 women; 29 trials; RR 1.21, 95% CI 0.95 to 1.54; moderate-quality evidence). Data from two large trials which assessed children at aged 18 months (including results from over 5000 children), did not identify clear differences in development between the two groups. AUTHORS' CONCLUSIONS: Administering low-dose aspirin to pregnant women led to small-to-moderate benefits, including reductions in pre-eclampsia (16 fewer per 1000 women treated), preterm birth (16 fewer per 1000 treated), the baby being born small-for-gestational age (seven fewer per 1000 treated) and fetal or neonatal death (five fewer per 1000 treated). Overall, administering antiplatelet agents to 1000 women led to 20 fewer pregnancies with serious adverse outcomes. The quality of evidence for all these outcomes was high. Aspirin probably slightly increased the risk of postpartum haemorrhage of more than 500 mL, however, the quality of evidence for this outcome was downgraded to moderate, due to concerns of clinical heterogeneity in measurements of blood loss. Antiplatelet agents probably marginally increase placental abruption, but the quality of the evidence was downgraded to moderate due to low event numbers and thus wide 95% CI. Overall, antiplatelet agents improved outcomes, and at these doses appear to be safe. Identifying women who are most likely to respond to low-dose aspirin would improve targeting of treatment. As almost all the women in this review were recruited to the trials after 12 weeks' gestation, it is unclear whether starting treatment before 12 weeks' would have additional benefits without any increase in adverse effects. While there was some indication that higher doses of aspirin would be more effective, further studies would be warranted to examine this.

Association Between Oxygen Saturation Targeting and Death or Disability in Extremely Preterm Infants in the Neonatal Oxygenation Prospective Meta-analysis Collaboration.

Importance: There are potential benefits and harms of hyperoxemia and hypoxemia for extremely preterm infants receiving more vs less supplemental oxygen. Objective: To compare the effects of different target ranges for oxygen saturation as measured by pulse oximetry (Spo2) on death or major morbidity. Design, Setting, and Participants: Prospectively planned meta-analysis of individual participant data from 5 randomized clinical trials (conducted from 2005-2014) enrolling infants born before 28 weeks' gestation. Exposures: Spo2 target range that was lower (85%-89%) vs higher (91%-95%). Main Outcomes and Measures: The primary outcome was a composite of death or major disability (bilateral blindness, deafness, cerebral palsy diagnosed as ≥2 level on the Gross Motor Function Classification System, or Bayley-III cognitive or language score <85) at a corrected age of 18 to 24 months. There were 16 secondary outcomes including the components of the primary outcome and other major morbidities. Results: A total of 4965 infants were randomized (2480 to the lower Spo2 target range and 2485 to the higher Spo2 range) and had a median gestational age of 26 weeks (interquartile range, 25-27 weeks) and a mean birth weight of 832 g (SD, 190 g). The primary outcome occurred in 1191 of 2228 infants (53.5%) in the lower Spo2 target group and 1150 of 2229 infants (51.6%) in the higher Spo2 target group (risk difference, 1.7% [95% CI, -1.3% to 4.6%]; relative risk [RR], 1.04 [95% CI, 0.98 to 1.09], P = .21). Of the 16 secondary outcomes, 11 were null, 2 significantly favored the lower Spo2 target group, and 3 significantly favored the higher Spo2 target group. Death occurred in 484 of 2433 infants (19.9%) in the lower Spo2 target group and 418 of 2440 infants (17.1%) in the higher Spo2 target group (risk difference, 2.8% [95% CI, 0.6% to 5.0%]; RR, 1.17 [95% CI, 1.04 to 1.31], P = .01). Treatment for retinopathy of prematurity was administered to 220 of 2020 infants (10.9%) in the lower Spo2 target group and 308 of 2065 infants (14.9%) in the higher Spo2 target group (risk difference, -4.0% [95% CI, -6.1% to -2.0%]; RR, 0.74 [95% CI, 0.63 to 0.86], P < .001). Severe necrotizing enterocolitis occurred in 227 of 2464 infants (9.2%) in the lower Spo2 target group and 170 of 2465 infants (6.9%) in the higher Spo2 target group (risk difference, 2.3% [95% CI, 0.8% to 3.8%]; RR, 1.33 [95% CI, 1.10 to 1.61], P = .003). Conclusions and Relevance: In this prospectively planned meta-analysis of individual participant data from extremely preterm infants, there was no significant difference between a lower Spo2 target range compared with a higher Spo2 target range on the primary composite outcome of death or major disability at a corrected age of 18 to 24 months. The lower Spo2 target range was associated with a higher risk of death and necrotizing enterocolitis, but a lower risk of retinopathy of prematurity treatment.

Australian clinical trial activity and burden of disease: an analysis of registered trials in National Health Priority Areas.

OBJECTIVE: To assess whether Australian clinical trials activity in National Health Priority Areas (NHPAs) reflects the relative disease burden. DESIGN AND SETTING: Analysis of trials registered on the Australian New Zealand Clinical Trials Registry (ANZCTR) or ClinicalTrials.gov from January 2008 to December 2012 that planned recruitment in Australia and investigated interventions for NHPA conditions (cancer control, cardiovascular health, mental health, obesity, injury prevention/control, diabetes mellitus, arthritis and musculoskeletal conditions, dementia and asthma). Australian estimates of disability-adjusted life-years (DALYs) were used to quantify the burden of disease for each NHPA. MAIN OUTCOME MEASURES: For each NHPA, the total number of registered trials, planned recruitment, and the predicted numbers based on disability-adjusted life-years expressed as a proportion of the total burden of disease in Australia (%DALY). RESULTS: 5143 trials with Australian sites were registered in the 5-year study period with total planned recruitment of 2 404 609 participants. Of these, 3032 trials (59%) with planned recruitment of 1 532 064 participants (64%) investigated NHPA conditions. Trial numbers and planned recruitment were highest for cancer, cardiovascular and mental health - reflecting their higher disease burden. In contrast, planned recruitment into obesity and dementia trials was ≤ 50% of that predicted from total trial activity based on their relative disease burden. The number of registered trials for these conditions was also lower than predicted. Overall, of 3032 NHPA trials, 2335 (77%) used randomisation and 1520 (50%) planned to recruit > 100 participants. CONCLUSIONS: Australian clinical trial activity for obesity and dementia interventions is lower that would be expected based on their relative disease burden. Trial registries provide a valuable public database to identify and monitor gaps in research activity.

Initial Oxygen Concentration for the Resuscitation of Infants Born at Less Than 32 Weeks' Gestation: A Systematic Review and Individual Participant Data Network Meta-Analysis.

Importance: Resuscitation with lower fractional inspired oxygen (FiO2) reduces mortality in term and near-term infants but the impact of this practice on very preterm infants is unclear. Objective: To evaluate the relative effectiveness of initial FiO2 on reducing mortality, severe morbidities, and oxygen saturations (SpO2) in preterm infants born at less than 32 weeks' gestation using network meta-analysis (NMA) of individual participant data (IPD). Data Sources: MEDLINE, Embase, CENTRAL, CINAHL, ClinicalTrials.gov, and WHO ICTRP from 1980 to October 10, 2023. Study Selection: Eligible studies were randomized clinical trials enrolling infants born at less than 32 weeks' gestation comparing at least 2 initial oxygen concentrations for delivery room resuscitation, defined as either low (≤0.3), intermediate (0.5-0.65), or high (≥0.90) FiO2. Data Extraction and Synthesis: Investigators from eligible studies were invited to provide IPD. Data were processed and checked for quality and integrity. One-stage contrast-based bayesian IPD-NMA was performed with noninformative priors and random effects and adjusted for key covariates. Main Outcomes and Measures: The primary outcome was all-cause mortality at hospital discharge. Secondary outcomes were morbidities of prematurity and SpO2 at 5 minutes. Results: IPD were provided for 1055 infants from 12 of the 13 eligible studies (2005-2019). Resuscitation with high (≥0.90) initial FiO2 was associated with significantly reduced mortality compared to low (≤0.3) (odds ratio [OR], 0.45; 95% credible interval [CrI], 0.23-0.86; low certainty) and intermediate (0.5-0.65) FiO2 (OR, 0.34; 95% CrI, 0.11-0.99; very low certainty). High initial FiO2 had a 97% probability of ranking first to reduce mortality. The effects on other morbidities were inconclusive. Conclusions and Relevance: High initial FiO2 (≥0.90) may be associated with reduced mortality in preterm infants born at less than 32 weeks' gestation compared to low initial FiO2 (low certainty). High initial FiO2 is possibly associated with reduced mortality compared to intermediate initial FiO2 (very low certainty) but more evidence is required.

A survey of experts to identify methods to detect problematic studies: Stage 1 of the INSPECT-SR Project.

Background: Randomised controlled trials (RCTs) inform healthcare decisions. Unfortunately, some published RCTs contain false data, and some appear to have been entirely fabricated. Systematic reviews are performed to identify and synthesise all RCTs which have been conducted on a given topic. This means that any of these 'problematic studies' are likely to be included, but there are no agreed methods for identifying them. The INSPECT-SR project is developing a tool to identify problematic RCTs in systematic reviews of healthcare-related interventions. The tool will guide the user through a series of 'checks' to determine a study's authenticity. The first objective in the development process is to assemble a comprehensive list of checks to consider for inclusion. Methods: We assembled an initial list of checks for assessing the authenticity of research studies, with no restriction to RCTs, and categorised these into five domains: Inspecting results in the paper; Inspecting the research team; Inspecting conduct, governance, and transparency; Inspecting text and publication details; Inspecting the individual participant data. We implemented this list as an online survey, and invited people with expertise and experience of assessing potentially problematic studies to participate through professional networks and online forums. Participants were invited to provide feedback on the checks on the list, and were asked to describe any additional checks they knew of, which were not featured in the list. Results: Extensive feedback on an initial list of 102 checks was provided by 71 participants based in 16 countries across five continents. Fourteen new checks were proposed across the five domains, and suggestions were made to reword checks on the initial list. An updated list of checks was constructed, comprising 116 checks. Many participants expressed a lack of familiarity with statistical checks, and emphasized the importance of feasibility of the tool. Conclusions: A comprehensive list of trustworthiness checks has been produced. The checks will be evaluated to determine which should be included in the INSPECT-SR tool.

Optimizing cord management for each preterm baby - Challenges of collating individual participant data and recommendations for future collaborative research.

The optimal cord management strategy at birth for each preterm baby is still unknown, despite more than 100 randomized controlled trials (RCTs) undertaken on this question. To address this, we brought together all RCTs examining cord management strategies at preterm birth in the iCOMP (individual participant data on COrd Management at Preterm birth) Collaboration, to perform an individual participant data network meta-analysis. In this paper, we describe the trials and tribulations around obtaining individual participant data to resolve controversies around cord clamping, and we derive key recommendations for future collaborative research in perinatology. To reliably answer outstanding questions, future cord management research needs to be collaborative and coordinated, by aligning core protocol elements, ensuring quality and reporting standards are met, and carefully considering and reporting on vulnerable sub-populations. The iCOMP Collaboration is an example of the power of collaboration to address priority research questions, and ultimately improve neonatal outcomes worldwide.

Protocol for the development of a tool (INSPECT-SR) to identify problematic randomised controlled trials in systematic reviews of health interventions.

Introduction: Randomised controlled trials (RCTs) inform healthcare decisions. It is now apparent that some published RCTs contain false data and some appear to have been entirely fabricated. Systematic reviews are performed to identify and synthesise all RCTs that have been conducted on a given topic. While it is usual to assess methodological features of the RCTs in the process of undertaking a systematic review, it is not usual to consider whether the RCTs contain false data. Studies containing false data therefore go unnoticed and contribute to systematic review conclusions. The INSPECT-SR project will develop a tool to assess the trustworthiness of RCTs in systematic reviews of healthcare related interventions. Methods and analysis: The INSPECT-SR tool will be developed using expert consensus in combination with empirical evidence, over five stages: 1) a survey of experts to assemble a comprehensive list of checks for detecting problematic RCTs, 2) an evaluation of the feasibility and impact of applying the checks to systematic reviews, 3) a Delphi survey to determine which of the checks are supported by expert consensus, culminating in 4) a consensus meeting to select checks to be included in a draft tool and to determine its format, 5) prospective testing of the draft tool in the production of new health systematic reviews, to allow refinement based on user feedback. We anticipate that the INSPECT-SR tool will help researchers to identify problematic studies, and will help patients by protecting them from the influence of false data on their healthcare.

Eating disorders in weight-related therapy (EDIT): Protocol for a systematic review with individual participant data meta-analysis of eating disorder risk in behavioural weight management.

The Eating Disorders In weight-related Therapy (EDIT) Collaboration brings together data from randomised controlled trials of behavioural weight management interventions to identify individual participant risk factors and intervention strategies that contribute to eating disorder risk. We present a protocol for a systematic review and individual participant data (IPD) meta-analysis which aims to identify participants at risk of developing eating disorders, or related symptoms, during or after weight management interventions conducted in adolescents or adults with overweight or obesity. We systematically searched four databases up to March 2022 and clinical trials registries to May 2022 to identify randomised controlled trials of weight management interventions conducted in adolescents or adults with overweight or obesity that measured eating disorder risk at pre- and post-intervention or follow-up. Authors from eligible trials have been invited to share their deidentified IPD. Two IPD meta-analyses will be conducted. The first IPD meta-analysis aims to examine participant level factors associated with a change in eating disorder scores during and following a weight management intervention. To do this we will examine baseline variables that predict change in eating disorder risk within intervention arms. The second IPD meta-analysis aims to assess whether there are participant level factors that predict whether participation in an intervention is more or less likely than no intervention to lead to a change in eating disorder risk. To do this, we will examine if there are differences in predictors of eating disorder risk between intervention and no-treatment control arms. The primary outcome will be a standardised mean difference in global eating disorder score from baseline to immediately post-intervention and at 6- and 12- months follow-up. Identifying participant level risk factors predicting eating disorder risk will inform screening and monitoring protocols to allow early identification and intervention for those at risk.

Exploring the application of behaviour change technique taxonomies in childhood obesity prevention interventions: A systematic scoping review.

Behaviour change technique (BCT) taxonomies provide one approach to unpack the complexity of childhood obesity prevention interventions. This scoping review sought to examine how BCT taxonomies have been applied to understand childhood obesity prevention interventions targeting children aged 12 years or under and/or their caregivers. A systematic search was conducted in Medline, Embase, PsycINFO, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, CINAHL and PROSPERO, to capture all eligible research up to February 2021. No limits were placed on country, language, publication dates, or full text availability. Eligible studies included any study design that applied a BCT taxonomy and evaluated behavioural childhood obesity prevention interventions targeting children aged 12 years or under and/or their parents or caregivers. Sixty-three records, describing 54 discrete studies were included; 32 applied a BCT taxonomy prospectively (i.e., to design interventions) and 23 retrospectively (i.e., to assess interventions), 1 study did both. There was substantial variation in the methods used to apply BCT taxonomies and to report BCT-related methods and results. There was a paucity of detail reported in how BCTs were selected in studies applying BCT taxonomies prospectively. Our review provides important insight into the application of BCT taxonomies in childhood obesity prevention and several ongoing challenges, pointing to the need for best practice reporting guidance.

A scoping review of outcomes commonly reported in obesity prevention interventions aiming to improve obesity-related health behaviors in children to age 5 years.

This scoping review was undertaken as the first stage of development of the Core Outcome Sets for Early Prevention of Obesity in CHildhood (COS-EPOCH). The aim of this review is to identify the outcomes collected and reported in randomized controlled trials of early childhood obesity prevention interventions. A systematic scoping review was undertaken following published guidelines. Trial registries and Medline were searched, and records retrieved were screened by two reviewers. Included trials aimed to prevent childhood obesity in the first 5 years of life and were randomized. Data were extracted using a standardized form. Outcomes were assigned to outcome domains, and similar definitions within each domain were merged, based on key literature and expert consensus. Outcome and domain frequencies were estimated and presented in outcome matrices. Eighteen outcome domains were identified from 161 included studies: "anthropometry," "dietary intake," "physical activity," "sedentary behaviour," "emotional functioning/wellbeing," "feeding," "cognitive/executive functioning," "sleep," "other," "study-related," "parenting practices," "motor skill development," "environmental," "blood and lymphatic system," "perceptions and preferences," "quality of life," and "economic," "oral health." The most frequently reported outcome domain was anthropometry (92% of studies), followed by dietary intake (77%) and physical activity (60%). 221 unique outcomes were identified, indicating a high degree of heterogeneity. Body mass index was the only outcome reported in >50% of studies. The considerable heterogeneity in outcomes supports the need for the development of COS-EPOCH.