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.

Aspirin in the prevention of pre-eclampsia in high-risk women* Sir, We thank Dr Thornton for his interest in our article 'Aspirin in the prevention of pre-eclampsia in high-risk women' published in the January 2013 issue of BJOG. 1 He raises four points we would like to respond to: the strength of effect; sample size; exclusion of participants from the main analysis; and trial registration.Dr Thornton concludes the commentary by writing that the effect of aspirin we reported in the meta-analysis for women who also have abnormal uterine artery Doppler waveforms at 14 weeks of gestation differs little from its effect in other high-risk groups. We have difficulty in agreeing with this; in our opinion the risk ratio in our meta-analysis (RR 0.55; 95% CI 0.37-0.83) differs from those reported by the Cochrane review. 2,3 The differences are even better encapsulated by comparing the numbers needed to treat (NNTs). In our meta-analysis, the substantial reduction in risk together with the high initial risk (36%) resulted in an NNT of six for preventing preeclampsia, whereas the Cochrane review reported an NNT for pre-eclampsia of 19 for women at high risk (20% risk) and 119 for women at moderate risk (6%), and concluded that 'further information is required to assess which women are most likely to benefit, when treatment is best started, and at what dose'. The PARIS meta-analysis reported a 10% reduction and an NNT of 56 for women at high risk (18% risk) and 167 for women at moderate risk (6%).In other respects our study represents both the strengths and weaknesses of clinician-initiated trials. With limited funding, from non-commercial sources only, the participating clinicians in ten centres were able to screen 947 women whose history indicated an increased risk of pre-eclampsia, to find those whose uterine artery flow indicates a particularly high risk. As we discuss in the article, in hindsight the criterion chosen was too strict, and only 152 women could be randomised. Although Dr Thornton is correct in stating that 31 of these women discontinued the treatment for various reasons and were excluded from the main analysis, he seems to overlook our description of the intention-to-treat analysis of all randomised women (except those who had a miscarriage), which gave a similar result. We do agree about the shortcomings of the information included in the ISRCTN registration (www.controlled-trials.com/ISRCTN140 30412/), submitted by one member of the study team. For example, variables that were eventually listed in the outcomes section include predictor variables such as biochemical measurements during pregnancy. It should also be noted that the planned number of participants stated on the ISRCTN website, of 1000 women, refers to the women to be screened by Doppler ultrasound, and not those to be eventually randomised, as Dr Thornton stated in his commentary.In our conclusion we echoed the words of the Cochrane review that 'further information is required to assess which women are most likely to benefit', and proposed that...

In a prospective meta-analysis (PMA), studies are identified and determined to be eligible for inclusion before the results of the studies related to the PMA research question are known PMAs are applicable to high priority research questions where limited previous evidence exists and where new studies are expected to emerge Compared with standard systematic review and meta-analysis protocols, key adaptations should be made to a PMA protocol, including search methods to identify planned and ongoing studies, details of studies that have already been identified for inclusion, core outcomes to be measured by all studies, collaboration management, and publication policy A systematic search for planned and ongoing studies should precede a PMA, including a search of clinical trial registries and medical literature databases, and contacting relevant stakeholders in the specialty PMAs are ideally conducted by a collaboration or consortium, including a central steering and data analysis committee, and representatives from each individual study Usually PMAs collect individual participant data, but PMAs of aggregate data are also possible. PMAs can include interventional or observational studies PMAs can enable harmonised collection of core outcomes, which can be particularly useful for rare but important outcomes, such as adverse side effects Adaptive forms of PRISMA (preferred reporting items for systematic reviews and meta-analyses) and quality assessment approaches such as GRADE (grading of recommendations assessment, development, and evaluation) should be used to report and assess the quality of evidence for a PMA. The development of a standardised set of reporting guidelines and PMA specific evidence rating tools is highly desirable

Background: Childhood obesity is a significant global problem. Childhood obesity prevention interventions may be more effective when started very early in life before metabolic and behavioural patterns are established.Methods and findings: A prospectively planned, individual participant data metaanalysis of four randomized controlled trials. Participants were first-time mothers of term infants. Trial interventions commenced during pregnancy or early infancy and comprised education and support delivered via group sessions and/or home visits. Control group families accessed existing local well-child health care. The primary outcome was body mass index (BMI) z score at 18 to 24 months; 2196 mother-child dyads were available for analysis. Intervention children had lower BMI z scores at 18 to 24 months than control children (−0.12 adjusted mean; 95% confidence interval, −0.22 to −0.02, P = .017). There was some evidence that the BMI z score reduction was greater in settings with limited well-child health care programmes (interaction P value = .03).

CONTEXT: The International Liaison Committee on Resuscitation prioritized scientific review of umbilical cord management strategies at preterm birth. OBJECTIVE: To determine the effects of umbilical cord management strategies (including timing of cord clamping and cord milking) in preterm infants <34 weeks’ gestation. DATA SOURCES: Cochrane Central Register of Controlled Trials, Medline, PubMed, Embase, CINAHL, and trial registries were searched through July 2019 for randomized controlled trials assessing timing of cord clamping and/or cord milking. STUDY SELECTION: Two authors independently assessed trial eligibility, extracted data, appraised risk of bias, and assessed evidence certainty (GRADE). DATA EXTRACTION: We identified 42 randomized controlled trials (including 5772 infants) investigating 4 different comparisons of cord management interventions. RESULTS: Compared to early cord clamping, delayed cord clamping (DCC) and intact-cord milking (ICM) may slightly improve survival; however, both are compatible with no effect (DCC: risk ratio: 1.02, 95% confidence interval: 1.00 to 1.04, n = 2988 infants, moderate certainty evidence; ICM: risk ratio: 1.02, 95% confidence interval: 0.98 to 1.06, n = 945 infants, moderate certainty evidence). DCC and ICM both probably improve hematologic measures but may not affect major neonatal morbidities. LIMITATIONS: For many of the included comparisons and outcomes, certainty of evidence was low. Our subgroup analyses were limited by few researchers reporting subgroup data. CONCLUSIONS: DCC appears to be associated with some benefit for infants born <34 weeks. Cord milking needs further evidence to determine potential benefits or harms. The ideal cord management strategy for preterm infants is still unknown, but early clamping may be harmful.

ObjectivesTo analyse prospective versus retrospective trial registration trends on the Australian New Zealand Clinical Trials Registry (ANZCTR) and to evaluate the reasons for non-compliance with prospective registration.DesignPart 1: Descriptive analysis of trial registration trends from 2006 to 2015. Part 2: Online registrant survey.ParticipantsPart 1: All interventional trials registered on ANZCTR from 2006 to 2015. Part 2: Random sample of those who had retrospectively registered a trial on ANZCTR between 2010 and 2015.Main outcome measuresPart 1: Proportion of prospective versus retrospective clinical trial registrations (ie, registration before versus after enrolment of the first participant) on the ANZCTR overall and by various key metrics, such as sponsor, funder, recruitment country and sample size. Part 2: Reasons for non-compliance with prospective registration and perceived usefulness of various proposed mechanisms to improve prospective registration compliance.ResultsPart 1: Analysis of the complete dataset of 9450 trials revealed that compliance with prospective registration increased from 48% (216 out of 446 trials) in 2006 to 63% (723/1148) in 2012 and has since plateaued at around 64%. Patterns of compliance were relatively consistent across sponsor and funder types (industry vs non-industry), type of intervention (drug vs non-drug) and size of trial (n<100, 100–500, >500). However, primary sponsors from Australia/New Zealand were almost twice as likely to register prospectively (62%; 4613/7452) compared with sponsors from other countries with a WHO Network Registry (35%; 377/1084) or sponsors from countries without a WHO Registry (29%; 230/781). Part 2: The majority (56%; 84/149) of survey respondents cited lack of awareness as a reason for not registering their study prospectively. Seventy-four per cent (111/149) stated that linking registration to ethics approval would facilitate prospective registration.ConclusionsDespite some progress, compliance with prospective registration remains suboptimal. Linking registration to ethics approval was the favoured strategy among those sampled for improving compliance.

Background: Childhood obesity is a global problem. Early obesity prevention interventions are complex and differ in effectiveness. Novel frameworks, taxonomies and experience from the Early Prevention of Obesity in CHildren (EPOCH) trials were applied to unpack interventions. Objectives: Deconstruct interventions into their components (target behaviours, delivery features and behaviour change techniques [BCTs]). Identify lessons learned and future recommendations for intervention planning, delivery, evaluation and implementation. Methods: This multi-methods study deconstructed the four EPOCH interventions into target behaviours, delivery features and BCTs from unpublished and published materials using systematic frameworks. Additionally, semi-structured interviews were conducted with intervention facilitators and principal investigators. Results: Each trial targeted between 10 and 14 obesity-related behaviours. Key variations in delivery features related to intensity, delivery mode and tailoring. BCTs consistently used across trials included goal-setting, social support, shaping knowledge, role-modelling and credible source. Recommendations from interview analyses include the importance of stakeholder collaboration and consideration of implementation throughout the study process. Conclusions: The combination of frameworks, methodologies and interviews used in this study is a major step towards understanding complex early obesity prevention interventions. Future work will link systematic intervention deconstruction with quantitative models to identify which intervention components are most effective and for whom.

PROSPERO, 42016032972.