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...

Tomosynthesis improves CDR and reduces recall; however, effects are dependent on screening setting, with greater improvement in CDR in European/Scandinavian studies (biennial screening) and reduction in recall in US studies with high baseline recall.

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.

An interval breast cancer is a cancer that emerges following a negative mammographic screen. This overview describes the epidemiology, and the radiological and biological characteristics of interval breast cancers in population mammography screening. Notwithstanding possible differences in ascertainment of interval breast cancers, there was broad variability in reported interval breast cancer rates (range 7.0 to 49.3 per 10,000 screens) reflecting heterogeneity in underlying breast cancer rates, screening rounds (initial or repeat screens), and the length and phase of the inter-screening interval. The majority of studies (based on biennial screening) reported interval breast cancer rates in the range of 8.4 to 21.1 per 10,000 screens spanning the two-year interval with the larger proportion occurring in the second year. Despite methodological limitations inherent in radiological surveillance (retrospective mammographic review) of interval breast cancers, this form of surveillance consistently reveals that the majority of interval cancers represent either true interval or occult cancers that were not visible on the index mammographic screen; approximately 20–25% of interval breast cancers are classified as having been missed (false-negatives). The biological characteristics of interval breast cancers show that they have relatively worse tumour prognostic characteristics and biomarker profile, and also survival outcomes, than screen-detected breast cancers; however, they have similar characteristics and prognosis as breast cancers occurring in non-screened women. There was limited evidence on the effect on interval breast cancer frequency and outcomes following transition from film to digital mammography screening.

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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).