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Background: Infants born preterm compared with infants born at term are at an increased risk of dying and of serious morbidities in early life, and those who survive have higher rates of neurological impairments. It remains unclear whether exposure to repeat courses of prenatal corticosteroids can reduce these risks. This individual participant data (IPD) meta-analysis (MA) assessed whether repeat prenatal corticosteroid treatment given to women at ongoing risk of preterm birth in order to benefit their infants is modified by participant or treatment factors.Methods and Findings: Trials were eligible for inclusion if they randomised women considered at risk of preterm birth who had already received an initial, single course of prenatal corticosteroid seven or more days previously and in which corticosteroids were compared with either placebo or no placebo. The primary outcomes for the infants were serious outcome, use of respiratory support, and birth weight z-scores; for the children, they were death or any neurosensory disability; and for the women, maternal sepsis. Studies were identified using the Cochrane Pregnancy and Childbirth search strategy. Date of last search was 20 January 2015. IPD were sought from investigators with eligible trials. Risk of bias was assessed using criteria from the Cochrane Collaboration. IPD were analysed using a one-stage approach. Eleven trials, conducted between 2002 and 2010, were identified as eligible, with five trials being from the United States, two from Canada, and one each from Australia and New Zealand, Finland, India, and the United Kingdom. All 11 trials were included, with 4,857 women and 5,915 infants contributing data. The mean gestational age at trial entry for the trials was between 27.4 weeks and 30.2 weeks. There was no significant difference in the proportion of infants with a serious outcome (relative risk [RR] 0.92, 95% confidence interval [CI] 0.82 to 1.04, 5,893 infants, 11 trials, p = 0.33 for heterogeneity). There was a reduction in the use of respiratory support in infants exposed to repeat prenatal corticosteroids compared with infants not exposed (RR 0.91, 95% CI 0.85 to 0.97, 5,791 infants, 10 trials, p = 0.64 for heterogeneity). The number needed to treat (NNT) to benefit was 21 (95% CI 14 to 41) women/fetus to prevent one infant from needing respiratory support. Birth weight z-scores were lower in the repeat corticosteroid group (mean difference -0.12, 95%CI -0.18 to -0.06, 5,902 infants, 11 trials, p = 0.80 for heterogeneity). No statistically significant differences were seen for any of the primary outcomes for the child (death or any neurosensory disability) or for the woman (maternal sepsis). The treatment effect varied little by reason the woman was considered to be at risk of preterm birth, the number of fetuses in utero, the gestational age when first trial treatment course was given, or the time prior to birth that the last dose was given. Infants exposed to between 2-5 courses of repeat corticosteroids showed a reduction in both serious outcome and the use of respiratory support compared with infants exposed to only a single repeat course. However, increasing numbers of repeat courses of corticosteroids were associated with larger reductions in birth z-scores for weight, length, and head circumference. Not all trials could provide data for all of the prespecified subgroups, so this limited the power to detect differences because event rates are low for some important maternal, infant, and childhood outcomes.Conclusions: In this study, we found that repeat prenatal corticosteroids given to women at ongoing risk of preterm birth after an initial course reduced the likelihood of their infant needing respiratory support after birth and led to neonatal benefits. Body size measures at birth were lower in infants exposed to repeat prenatal corticosteroids. Our findings suggest that to provide clinical benefit with the least effect on growth, the number of repeat treatment courses should be limited to a maximum of three and the total dose to between 24 mg and 48 mg. [ABSTRACT FROM AUTHOR]

Objective: To compare the effects of immediate delivery an expectant management among women whose pregnancies were complicated by preterm prelabor rupture of membranes (PROM) in the late preterm period (from 34 0/7 weeks until 36 6/7 weeks of gestation).Data Sources: PubMed, Scopus, ClinicalTrials.gov, EMBASE, and the Cochrane Central Register of Controlled Trials were searched from inception until December 2016.Methods Of Study Selection: We included all randomized controlled trials with individual participant data reporting on late preterm PROM with randomization to immediate delivery or expectant management. The primary outcome was a composite of adverse neonatal outcomes: probable or definitive neonatal sepsis, necrotizing enterocolitis, respiratory distress syndrome, stillbirth, or neonatal death.Tabulation, Integration and Results: Of eight eligible trials (total n=3,203 mothers), three (2,563 mothers, 2,572 neonates) had individual participant data available. The composite adverse neonatal outcome occurred in 9.6% of neonates in the immediate delivery group and 8.3% in the expectant management group (relative risk [RR] 1.20, 95% CI 0.94-1.55). Neonatal sepsis rates were 2.6% and 3.5%, respectively (RR 0.74, 95% CI 0.47-1.15). Neonates in the immediate delivery group were more likely to be diagnosed with respiratory distress syndrome (RR 1.47, 95% CI 1.10-1.97), and to be admitted to the neonatal intensive care unit or special care nursery (RR 1.17, 95% CI 1.11-1.23) and had longer admissions. Mothers randomized to immediate delivery were less likely to have an antepartum hemorrhage (RR 0.57, 95% CI 0.34-0.95) or chorioamnionitis (RR 0.21, 95% CI 0.13-0.35), but more likely to undergo cesarean delivery (RR 1.26, 95% CI 1.08-1.47).Conclusion: In women with late preterm PROM, immediate delivery and expectant management resulted in comparable rates of the composite of adverse neonatal outcomes. Effects on individual secondary maternal and neonatal outcomes were mixed.Systematic Review Registration: PROSPERO, 42016032972. [ABSTRACT FROM AUTHOR]

Background: Babies born preterm are at an increased risk of dying in the first weeks of life, and those who survive have a higher rate of cerebral palsy (CP) compared with babies born at term. The aim of this individual participant data (IPD) meta-analysis (MA) was to assess the effects of antenatal magnesium sulphate, compared with no magnesium treatment, given to women at risk of preterm birth on important maternal and fetal outcomes, including survival free of CP, and whether effects differed by participant or treatment characteristics such as the reason the woman was at risk of preterm birth, why treatment was given, the gestational age at which magnesium sulphate treatment was received, or the dose and timing of the administration of magnesium sulphate.Methods and Findings: Trials in which women considered at risk of preterm birth (<37 weeks' gestation) were randomised to magnesium sulphate or control treatment and where neurologic outcomes for the baby were reported were eligible for inclusion. The primary outcomes were infant death or CP and severe maternal outcome potentially related to treatment. Studies were identified based on the Cochrane Pregnancy and Childbirth search strategy using the terms [antenatal or prenatal] and [magnesium] and [preterm or premature or neuroprotection or 'cerebral palsy']. The date of the last search was 28 February 2017. IPD were sought from investigators with eligible trials. Risk of bias was assessed using criteria from the Cochrane Collaboration. For each prespecified outcome, IPD were analysed using a 1-stage approach. All 5 trials identified were included, with 5,493 women and 6,131 babies. Overall, there was no clear effect of magnesium sulphate treatment compared with no treatment on the primary infant composite outcome of death or CP (relative risk [RR] 0.94, 95% confidence interval (CI) 0.85 to 1.05, 6,131 babies, 5 trials, p = 0.07 for heterogeneity of treatment effect across trials). In the prespecified sensitivity analysis restricted to data from the 4 trials in which the intent of treatment was fetal neuroprotection, there was a significant reduction in the risk of death or CP with magnesium sulphate treatment compared with no treatment (RR 0.86, 95% CI 0.75 to 0.99, 4,448 babies, 4 trials), with no significant heterogeneity (p = 0.28). The number needed to treat (NNT) to benefit was 41 women/babies to prevent 1 baby from either dying or having CP. For the primary outcome of severe maternal outcome potentially related to magnesium sulphate treatment, no events were recorded from the 2 trials providing data. When the individual components of the composite infant outcome were assessed, no effect was seen for death overall (RR 1.03, 95% CI 0.91 to 1.17, 6,131 babies, 5 trials) or in the analysis of death using only data from trials with the intent of fetal neuroprotection (RR 0.95, 95% CI 0.80 to 1.13, 4,448 babies, 4 trials). For cerebral palsy in survivors, magnesium sulphate treatment had a strong protective effect in both the overall analysis (RR 0.68, 95% CI 0.54 to 0.87, 4,601 babies, 5 trials, NNT to benefit 46) and the neuroprotective intent analysis (RR 0.68, 95% CI 0.53 to 0.87, 3,988 babies, 4 trials, NNT to benefit 42). No statistically significant differences were seen for any of the other secondary outcomes. The treatment effect varied little by the reason the woman was at risk of preterm birth, the gestational age at which magnesium sulphate treatment was given, the total dose received, or whether maintenance therapy was used. A limitation of the study was that not all trials could provide the data required for the planned analyses so that combined with low event rates for some important clinical events, the power to find a difference was limited.Conclusions: Antenatal magnesium sulphate given prior to preterm birth for fetal neuroprotection prevents CP and reduces the combined risk of fetal/infant death or CP. Benefit is seen regardless of the reason for preterm birth, with similar effects across a range of preterm gestational ages and different treatment regimens. Widespread adoption worldwide of this relatively inexpensive, easy-to-administer treatment would lead to important global health benefits for infants born preterm. [ABSTRACT FROM AUTHOR]

Background There are major health disparities between Indigenous and non-Indigenous Australians. To address this, it is vital to understand the landscape of Indigenous trial activity. Methods We extracted data from all Australian trials registered between 2008-2018 on the Australian New Zealand Clinical Trials Registry or ClinicalTrials.gov. Indigenous-focused trials were identified by searching for relevant terms such as 'Indigenous' and 'Aboriginal'. Indigenous versus non-Indigenous trials and Australian trials overall were compared by conditions studied, intervention type, study design and funding. Results Of the 9206 included trials, 139 (1.5%) focused on Indigenous health, and these were mostly in 'Public Health' (n = 69, 50%), 'Mental Health' (n = 35, 25%) and 'Cardiovascular' (n = 25, 18%) (Figure). Compared to other Australian trials, Indigenous trials more frequently studied ear conditions (OR 16.47, 95%CI=8.43-29.99) and public health (OR 4.87, 95%CI=3.65-6.41), and were more likely to focus on screening (OR 3.57, 95%CI=2.10-5.70) and prevention (OR 2.24, 95%CI=1.61-3.08) rather than treatment (OR 0.40, 95%CI =0.30-0.52). They were less likely to be blinded (OR 1.72, 95%CI=1.20-2.49), or have any industry involvement (OR 2.52, 95%CI=1.54-4.43). Conclusions Indigenous trials differed from other Australian trials in health conditions studied, intervention focus, blinding and industry involvement. Relative to population size and burden of disease, the number of trials focusing on Indigenous health is low. Key messages Trial registries can be used to explore whether research appropriately addresses diverse populations such as Indigenous Australians. This can inform future research prioritisation. [ABSTRACT FROM AUTHOR]

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.)

Objective: To predict birth weight at various potential gestational ages of delivery based on data routinely available at the first antenatal visit., Design: Individual participant data meta-analysis., Data Sources: Individual participant data of four cohorts (237 228 pregnancies) from the International Prediction of Pregnancy Complications (IPPIC) network dataset., Eligibility Criteria for Selecting Studies: Studies in the IPPIC network were identified by searching major databases for studies reporting risk factors for adverse pregnancy outcomes, such as pre-eclampsia, fetal growth restriction, and stillbirth, from database inception to August 2019. Data of four IPPIC cohorts (237 228 pregnancies) from the US (National Institute of Child Health and Human Development, 2018; 233 483 pregnancies), UK (Allen et al, 2017; 1045 pregnancies), Norway (STORK Groruddalen research programme, 2010; 823 pregnancies), and Australia (Rumbold et al, 2006; 1877 pregnancies) were included in the development of the model., Results: The IPPIC birth weight model was developed with random intercept regression models with backward elimination for variable selection. Internal-external cross validation was performed to assess the study specific and pooled performance of the model, reported as calibration slope, calibration-in-the-large, and observed versus expected average birth weight ratio. Meta-analysis showed that the apparent performance of the model had good calibration (calibration slope 0.99, 95% confidence interval (CI) 0.88 to 1.10; calibration-in-the-large 44.5 g, -18.4 to 107.3) with an observed versus expected average birth weight ratio of 1.02 (95% CI 0.97 to 1.07). The proportion of variation in birth weight explained by the model (R 2 ) was 46.9% (range 32.7-56.1% in each cohort). On internal-external cross validation, the model showed good calibration and predictive performance when validated in three cohorts with a calibration slope of 0.90 (Allen cohort), 1.04 (STORK Groruddalen cohort), and 1.07 (Rumbold cohort), calibration-in-the-large of -22.3 g (Allen cohort), -33.42 (Rumbold cohort), and 86.4 g (STORK Groruddalen cohort), and observed versus expected ratio of 0.99 (Rumbold cohort), 1.00 (Allen cohort), and 1.03 (STORK Groruddalen cohort); respective pooled estimates were 1.00 (95% CI 0.78 to 1.23; calibration slope), 9.7 g (-154.3 to 173.8; calibration-in-the-large), and 1.00 (0.94 to 1.07; observed v expected ratio). The model predictions were more accurate (smaller mean square error) in the lower end of predicted birth weight, which is important in informing clinical decision making., Conclusions: The IPPIC birth weight model allowed birth weight predictions for a range of possible gestational ages. The model explained about 50% of individual variation in birth weights, was well calibrated (especially in babies at high risk of fetal growth restriction and its complications), and showed promising performance in four different populations included in the individual participant data meta-analysis. Further research to examine the generalisability of performance in other countries, settings, and subgroups is required., Trial Registration: PROSPERO CRD42019135045., Competing Interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/disclosure-of-interest/ and declare: support from the National Institute for Health and Care Research Health Technology Assessment UK programme for the submitted work; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work., (Copyright © Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: Preterm birth, defined as birth before 37 weeks of gestation, is a leading cause of perinatal and infant mortality throughout the world. Preterm birth is also associated with long-term neurological disabilities and other significant health issues in children. A short cervix in the second trimester has been noted to be one of the strongest predictors of subsequent spontaneous preterm birth in both singleton and multiple pregnancies. Some studies have shown that cervical support in the form of an Arabin pessary lowers the risk of preterm birth in women with a singleton gestation and short cervical length; however, other studies have conflicting results. Our objective was to form an international collaborative of planned or ongoing randomized trials of pessary in singleton and twin gestations with a short cervix., Study Design: In November 2014, an international group of investigators, who had initiated or were planning randomized trials of pessary for pregnant people with a short cervix and singleton or twin gestation to prevent preterm birth, formed a collaboration to plan a prospective individual patient data (IPD) meta-analysis of randomized trials (PROspective Meta-analysis of Pessary Trials [PROMPT]). The PROMPT investigators agreed on meta-analysis IPD hypotheses for singletons and twins, eligibility criteria, and a set of core baseline and outcome measures. The primary outcome is a composite of fetal death or preterm delivery before 32 weeks' gestation. Secondary outcomes include maternal and neonatal morbidities. The PROMPT protocol may be viewed as a written agreement among the study investigators who make up the PROMPT consortium (PROSPERO ID# CRD42018067740)., Results: Results will be published in phases as the individual participating studies are concluded and published. Results of the first phase of singleton and twin pessary trials are expected to be available in late 2022. Updates are planned as participating trials are completed and published., Key Points: · Short cervical length predicts preterm birth.. · Results of prior cervical pessary trials are mixed.. · Meta-analysis of pessary trials protocol.., Competing Interests: None declared., (Thieme. All rights reserved.)

Objectives: To compare severity and clinical outcomes from Omicron as compared with the Delta variant and to compare outcomes between Omicron sublineages., Methods: We searched the WHO COVID-19 Research database for studies that compared clinical outcomes for patients with Omicron variant and the Delta variant, and separately Omicron sublineages BA.1 and BA.2. A random-effects meta-analysis was used to pool estimates of relative risk (RR) between variants and sublineages. Heterogeneity between studies was assessed using the I 2 index. Risk of bias was assessed using the tool developed by the Clinical Advances through Research and Information Translation team., Results: Our search identified 1494 studies and 42 met the inclusion criteria. Eleven studies were published as preprints. Of the 42 studies, 29 adjusted for vaccination status; 12 had no adjustment; and for 1, the adjustment was unclear. Three of the included studies compared the sublineages of Omicron BA.1 versus BA.2. As compared with Delta, individuals infected with Omicron had 61% lower risk of death (RR 0.39, 95% CI 0.33 to 0.46) and 56% lower risk of hospitalisation (RR 0.44, 95% CI 0.34 to 0.56). Omicron was similarly associated with lower risk of intensive care unit (ICU) admission, oxygen therapy, and non-invasive and invasive ventilation. The pooled risk ratio for the outcome of hospitalisation when comparing sublineages BA.1 versus BA.2 was 0.55 (95% 0.23 to 1.30)., Discussion: Omicron variant was associated with lower risk of hospitalisation, ICU admission, oxygen therapy, ventilation and death as compared with Delta. There was no difference in the risk of hospitalisation between Omicron sublineages BA.1 and BA.2., Prospero Registration Number: CRD42022310880., Competing Interests: Competing interests: None declared., (© World Health Organization 2023. Licensee BMJ.)

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., Competing Interests: Disclosure All authors are secretariat members of the iCOMP Collaboration. There are no financial conflicts of interest to disclose. The iCOMP Collaboration is funded by a National Health and Medical Research Council (NHMRC) Project Grant (GNT1163585). ALS is funded by an NHMRC Investigator grant (GNT2009432)., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Different forms of vaccines have been developed to prevent the SARS-CoV-2 virus and subsequent COVID-19 disease. Several are in widespread use globally.  OBJECTIVES: To assess the efficacy and safety of COVID-19 vaccines (as a full primary vaccination series or a booster dose) against SARS-CoV-2., Search Methods: We searched the Cochrane COVID-19 Study Register and the COVID-19 L·OVE platform (last search date 5 November 2021). We also searched the WHO International Clinical Trials Registry Platform, regulatory agency websites, and Retraction Watch., Selection Criteria: We included randomized controlled trials (RCTs) comparing COVID-19 vaccines to placebo, no vaccine, other active vaccines, or other vaccine schedules., Data Collection and Analysis: We used standard Cochrane methods. We used GRADE to assess the certainty of evidence for all except immunogenicity outcomes.  We synthesized data for each vaccine separately and presented summary effect estimates with 95% confidence intervals (CIs).  MAIN RESULTS: We included and analyzed 41 RCTs assessing 12 different vaccines, including homologous and heterologous vaccine schedules and the effect of booster doses. Thirty-two RCTs were multicentre and five were multinational. The sample sizes of RCTs were 60 to 44,325 participants. Participants were aged: 18 years or older in 36 RCTs; 12 years or older in one RCT; 12 to 17 years in two RCTs; and three to 17 years in two RCTs. Twenty-nine RCTs provided results for individuals aged over 60 years, and three RCTs included immunocompromized patients. No trials included pregnant women. Sixteen RCTs had two-month follow-up or less, 20 RCTs had two to six months, and five RCTs had greater than six to 12 months or less. Eighteen reports were based on preplanned interim analyses. Overall risk of bias was low for all outcomes in eight RCTs, while 33 had concerns for at least one outcome. We identified 343 registered RCTs with results not yet available.  This abstract reports results for the critical outcomes of confirmed symptomatic COVID-19, severe and critical COVID-19, and serious adverse events only for the 10 WHO-approved vaccines. For remaining outcomes and vaccines, see main text. The evidence for mortality was generally sparse and of low or very low certainty for all WHO-approved vaccines, except AD26.COV2.S (Janssen), which probably reduces the risk of all-cause mortality (risk ratio (RR) 0.25, 95% CI 0.09 to 0.67; 1 RCT, 43,783 participants; high-certainty evidence). Confirmed symptomatic COVID-19 High-certainty evidence found that BNT162b2 (BioNtech/Fosun Pharma/Pfizer), mRNA-1273 (ModernaTx), ChAdOx1 (Oxford/AstraZeneca), Ad26.COV2.S, BBIBP-CorV (Sinopharm-Beijing), and BBV152 (Bharat Biotect) reduce the incidence of symptomatic COVID-19 compared to placebo (vaccine efficacy (VE): BNT162b2: 97.84%, 95% CI 44.25% to 99.92%; 2 RCTs, 44,077 participants; mRNA-1273: 93.20%, 95% CI 91.06% to 94.83%; 2 RCTs, 31,632 participants; ChAdOx1: 70.23%, 95% CI 62.10% to 76.62%; 2 RCTs, 43,390 participants; Ad26.COV2.S: 66.90%, 95% CI 59.10% to 73.40%; 1 RCT, 39,058 participants; BBIBP-CorV: 78.10%, 95% CI 64.80% to 86.30%; 1 RCT, 25,463 participants; BBV152: 77.80%, 95% CI 65.20% to 86.40%; 1 RCT, 16,973 participants). Moderate-certainty evidence found that NVX-CoV2373 (Novavax) probably reduces the incidence of symptomatic COVID-19 compared to placebo (VE 82.91%, 95% CI 50.49% to 94.10%; 3 RCTs, 42,175 participants). There is low-certainty evidence for CoronaVac (Sinovac) for this outcome (VE 69.81%, 95% CI 12.27% to 89.61%; 2 RCTs, 19,852 participants). Severe or critical COVID-19 High-certainty evidence found that BNT162b2, mRNA-1273, Ad26.COV2.S, and BBV152 result in a large reduction in incidence of severe or critical disease due to COVID-19 compared to placebo (VE: BNT162b2: 95.70%, 95% CI 73.90% to 99.90%; 1 RCT, 46,077 participants; mRNA-1273: 98.20%, 95% CI 92.80% to 99.60%; 1 RCT, 28,451 participants; AD26.COV2.S: 76.30%, 95% CI 57.90% to 87.50%; 1 RCT, 39,058 participants; BBV152: 93.40%, 95% CI 57.10% to 99.80%; 1 RCT, 16,976 participants). Moderate-certainty evidence found that NVX-CoV2373 probably reduces the incidence of severe or critical COVID-19 (VE 100.00%, 95% CI 86.99% to 100.00%; 1 RCT, 25,452 participants). Two trials reported high efficacy of CoronaVac for severe or critical disease with wide CIs, but these results could not be pooled. Serious adverse events (SAEs) mRNA-1273, ChAdOx1 (Oxford-AstraZeneca)/SII-ChAdOx1 (Serum Institute of India), Ad26.COV2.S, and BBV152 probably result in little or no difference in SAEs compared to placebo (RR: mRNA-1273: 0.92, 95% CI 0.78 to 1.08; 2 RCTs, 34,072 participants; ChAdOx1/SII-ChAdOx1: 0.88, 95% CI 0.72 to 1.07; 7 RCTs, 58,182 participants; Ad26.COV2.S: 0.92, 95% CI 0.69 to 1.22; 1 RCT, 43,783 participants); BBV152: 0.65, 95% CI 0.43 to 0.97; 1 RCT, 25,928 participants). In each of these, the likely absolute difference in effects was fewer than 5/1000 participants. Evidence for SAEs is uncertain for BNT162b2, CoronaVac, BBIBP-CorV, and NVX-CoV2373 compared to placebo (RR: BNT162b2: 1.30, 95% CI 0.55 to 3.07; 2 RCTs, 46,107 participants; CoronaVac: 0.97, 95% CI 0.62 to 1.51; 4 RCTs, 23,139 participants; BBIBP-CorV: 0.76, 95% CI 0.54 to 1.06; 1 RCT, 26,924 participants; NVX-CoV2373: 0.92, 95% CI 0.74 to 1.14; 4 RCTs, 38,802 participants). For the evaluation of heterologous schedules, booster doses, and efficacy against variants of concern, see main text of review., Authors' Conclusions: Compared to placebo, most vaccines reduce, or likely reduce, the proportion of participants with confirmed symptomatic COVID-19, and for some, there is high-certainty evidence that they reduce severe or critical disease. There is probably little or no difference between most vaccines and placebo for serious adverse events. Over 300 registered RCTs are evaluating the efficacy of COVID-19 vaccines, and this review is updated regularly on the COVID-NMA platform (covid-nma.com). Implications for practice Due to the trial exclusions, these results cannot be generalized to pregnant women, individuals with a history of SARS-CoV-2 infection, or immunocompromized people. Most trials had a short follow-up and were conducted before the emergence of variants of concern. Implications for research Future research should evaluate the long-term effect of vaccines, compare different vaccines and vaccine schedules, assess vaccine efficacy and safety in specific populations, and include outcomes such as preventing long COVID-19. Ongoing evaluation of vaccine efficacy and effectiveness against emerging variants of concern is also vital., (Copyright © 2022 The Authors. Cochrane Database of Systematic Reviews published by John Wiley & Sons, Ltd. on behalf of The Cochrane Collaboration.)

Background: Eczema and food allergy are common health conditions that usually begin in early childhood and often occur in the same people. They can be associated with an impaired skin barrier in early infancy. It is unclear whether trying to prevent or reverse an impaired skin barrier soon after birth is effective for preventing eczema or food allergy., Objectives: Primary objective To assess the effects of skin care interventions such as emollients for primary prevention of eczema and food allergy in infants. Secondary objective To identify features of study populations such as age, hereditary risk, and adherence to interventions that are associated with the greatest treatment benefit or harm for both eczema and food allergy., Search Methods: We performed an updated search of the Cochrane Skin Specialised Register, CENTRAL, MEDLINE, and Embase in September 2021. We searched two trials registers in July 2021. We checked the reference lists of included studies and relevant systematic reviews, and scanned conference proceedings to identify further references to relevant randomised controlled trials (RCTs).  SELECTION CRITERIA: We included RCTs of skin care interventions that could potentially enhance skin barrier function, reduce dryness, or reduce subclinical inflammation in healthy term (&gt; 37 weeks) infants (≤ 12 months) without pre-existing eczema, food allergy, or other skin condition. Eligible comparisons were standard care in the locality or no treatment. Types of skin care interventions could include moisturisers/emollients; bathing products; advice regarding reducing soap exposure and bathing frequency; and use of water softeners. No minimum follow-up was required., Data Collection and Analysis: This is a prospective individual participant data (IPD) meta-analysis. We used standard Cochrane methodological procedures, and primary analyses used the IPD dataset. Primary outcomes were cumulative incidence of eczema and cumulative incidence of immunoglobulin (Ig)E-mediated food allergy by one to three years, both measured at the closest available time point to two years. Secondary outcomes included adverse events during the intervention period; eczema severity (clinician-assessed); parent report of eczema severity; time to onset of eczema; parent report of immediate food allergy; and allergic sensitisation to food or inhalant allergen., Main Results: We identified 33 RCTs comprising 25,827 participants. Of these, 17 studies randomising 5823 participants reported information on one or more outcomes specified in this review.  We included 11 studies, randomising 5217 participants, in one or more meta-analyses (range 2 to 9 studies per individual meta-analysis), with 10 of these studies providing IPD; the remaining 6 studies were included in the narrative results only.   Most studies were conducted at children's hospitals. Twenty-five studies, including all those contributing data to meta-analyses, randomised newborns up to age three weeks to receive a skin care intervention or standard infant skin care. Eight of the 11 studies contributing to meta-analyses recruited infants at high risk of developing eczema or food allergy, although the definition of high risk varied between studies. Durations of intervention and follow-up ranged from 24 hours to three years. All interventions were compared against no skin care intervention or local standard care. Of the 17 studies that reported information on our prespecified outcomes, 13 assessed emollients. We assessed most of the evidence in the review as low certainty and had some concerns about risk of bias. A rating of some concerns was most often due to lack of blinding of outcome assessors or significant missing data, which could have impacted outcome measurement but was judged unlikely to have done so. We assessed the evidence for the primary food allergy outcome as high risk of bias due to the inclusion of only one trial, where findings varied based on different assumptions about missing data. Skin care interventions during infancy probably do not change the risk of eczema by one to three years of age (risk ratio (RR) 1.03, 95% confidence interval (CI) 0.81 to 1.31; risk difference 5 more cases per 1000 infants, 95% CI 28 less to 47 more; moderate-certainty evidence; 3075 participants, 7 trials) or time to onset of eczema (hazard ratio 0.86, 95% CI 0.65 to 1.14; moderate-certainty evidence; 3349 participants, 9 trials). Skin care interventions during infancy may increase the risk of IgE-mediated food allergy by one to three years of age (RR 2.53, 95% CI 0.99 to 6.49; low-certainty evidence; 976 participants, 1 trial) but may not change risk of allergic sensitisation to a food allergen by age one to three years (RR 1.05, 95% CI 0.64 to 1.71; low-certainty evidence; 1794 participants, 3 trials). Skin care interventions during infancy may slightly increase risk of parent report of immediate reaction to a common food allergen at two years (RR 1.27, 95% CI 1.00 to 1.61; low-certainty evidence; 1171 participants, 1 trial); however, this was only seen for cow's milk, and may be unreliable due to over-reporting of milk allergy in infants. Skin care interventions during infancy probably increase risk of skin infection over the intervention period (RR 1.33, 95% CI 1.01 to 1.75; risk difference 17 more cases per 1000 infants, 95% CI one more to 38 more; moderate-certainty evidence; 2728 participants, 6 trials) and may increase the risk of infant slippage over the intervention period (RR 1.42, 95% CI 0.67 to 2.99; low-certainty evidence; 2538 participants, 4 trials) and stinging/allergic reactions to moisturisers (RR 2.24, 95% 0.67 to 7.43; low-certainty evidence; 343 participants, 4 trials), although CIs for slippages and stinging/allergic reactions were wide and include the possibility of no effect or reduced risk. Preplanned subgroup analyses showed that the effects of interventions were not influenced by age, duration of intervention, hereditary risk, filaggrin (FLG) mutation, chromosome 11 intergenic variant rs2212434, or classification of intervention type for risk of developing eczema. We could not evaluate these effects on risk of food allergy. Evidence was insufficient to show whether adherence to interventions influenced the relationship between skin care interventions and eczema or food allergy development., Authors' Conclusions: Based on low- to moderate-certainty evidence, skin care interventions such as emollients during the first year of life in healthy infants are probably not effective for preventing eczema; may increase risk of food allergy; and probably increase risk of skin infection. Further study is needed to understand whether different approaches to infant skin care might prevent eczema or food allergy., (Copyright © 2022 The Authors. Cochrane Database of Systematic Reviews published by John Wiley & Sons, Ltd. on behalf of The Cochrane Collaboration.)

Introduction: Behavioural interventions in early life appear to show some effect in reducing childhood overweight and obesity. However, uncertainty remains regarding their overall effectiveness, and whether effectiveness differs among key subgroups. These evidence gaps have prompted an increase in very early childhood obesity prevention trials worldwide. Combining the individual participant data (IPD) from these trials will enhance statistical power to determine overall effectiveness and enable examination of individual and trial-level subgroups. We present a protocol for a systematic review with IPD meta-analysis to evaluate the effectiveness of obesity prevention interventions commencing antenatally or in the first year after birth, and to explore whether there are differential effects among key subgroups., Methods and Analysis: Systematic searches of Medline, Embase, Cochrane Central Register of Controlled Trials, Cumulative Index to Nursing and Allied Health Literature (CINAHL), PsycInfo and trial registries for all ongoing and completed randomised controlled trials evaluating behavioural interventions for the prevention of early childhood obesity have been completed up to March 2021 and will be updated annually to include additional trials. Eligible trialists will be asked to share their IPD; if unavailable, aggregate data will be used where possible. An IPD meta-analysis and a nested prospective meta-analysis will be performed using methodologies recommended by the Cochrane Collaboration. The primary outcome will be body mass index z-score at age 24±6 months using WHO Growth Standards, and effect differences will be explored among prespecified individual and trial-level subgroups. Secondary outcomes include other child weight-related measures, infant feeding, dietary intake, physical activity, sedentary behaviours, sleep, parenting measures and adverse events., Ethics and Dissemination: Approved by The University of Sydney Human Research Ethics Committee (2020/273) and Flinders University Social and Behavioural Research Ethics Committee (HREC CIA2133-1). Results will be relevant to clinicians, child health services, researchers, policy-makers and families, and will be disseminated via publications, presentations and media releases., Prospero Registration Number: CRD42020177408., Competing Interests: Competing interests: AB, ALS, BJJ, KEH, MA, RKG, SL and LPS reports grants from NHMRC Ideas Grant TOPCHILD (Transforming Obesity Prevention for CHILDren) (GNT1186363); APE and CGA reports grants administered by the Inter-American Development Bank from The Government of Japan and The PepsiCo Foundation; ALT reports grants from National Institute of Health; BJT reports grants from NZ Health Research Council; EO reports grants from the US National Institutes of Health, and the Canadian Institutes for Health Research; IMP reports grants from NIH/NIDDK; JSS reports grants from PCORI, NIH NIDDK and NHLBI, and personal fees from Danone Organic, American Academy of Pediatrics, and Lets Move Maine; LTK and JKL reports grants from Fonds NutsOhra; MCR reports grants from National Institute on Minority Health and Health Disparities-National Institutes of Health/Center for Collaborative Research in Health Disparities, and personal fees from Rhythm Pharmaceuticals; RSG reports grants from US Department of Agriculture and NIH/NICHD., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Little is known about how early (eg, commencing antenatally or in the first 12 months after birth) obesity prevention interventions seek to change behaviour and which components are or are not effective. This study aims to (1) characterise early obesity prevention interventions in terms of target behaviours, delivery features and behaviour change techniques (BCTs), (2) explore similarities and differences in BCTs used to target behaviours and (3) explore effectiveness of intervention components in preventing childhood obesity., Methods and Analysis: Annual comprehensive systematic searches will be performed in Epub Ahead of Print/MEDLINE, Embase, Cochrane (CENTRAL), CINAHL, PsycINFO, as well as clinical trial registries. Eligible randomised controlled trials of behavioural interventions to prevent childhood obesity commencing antenatally or in the first year after birth will be invited to join the Transforming Obesity in CHILDren Collaboration. Standard ontologies will be used to code target behaviours, delivery features and BCTs in both published and unpublished intervention materials provided by trialists. Narrative syntheses will be performed to summarise intervention components and compare applied BCTs by types of target behaviours. Exploratory analyses will be undertaken to assess effectiveness of intervention components., Ethics and Dissemination: The study has been approved by The University of Sydney Human Research Ethics Committee (project no. 2020/273) and Flinders University Social and Behavioural Research Ethics Committee (project no. HREC CIA2133-1). The study's findings will be disseminated through peer-reviewed publications, conference presentations and targeted communication with key stakeholders., Prospero Registration Number: CRD42020177408., Competing Interests: Competing interests: AB, ALS, BJJ, KEH, MA, RG, SL and LPS reports grants from NHMRC Ideas Grant TOPCHILD (Transforming Obesity Prevention for CHILDren) (GNT1186363); APE and CGA reports grants administered by the Inter-American Development Bank from The Government of Japan and The PepsiCo Foundation; AT reports grants from National Institute of Health; BJT reports grants from NZ Health Research Council; EO reports grants from the US National Institutes of Health, and the Canadian Institutes for Health Research; IMP reports grants from NIH/NIDDK; JS reports grants from PCORI, NIH NIDDK and NHLBI, and personal fees from Danone Organic, American Academy of Pediatrics and Lets Move Maine; LTK and JL reports grants from Fonds NutsOhra; MR reports grants from National Institute on Minority Health and Health Disparities-National Institutes of Health/Center for Collaborative Research in Health Disparities, and personal fees from Rhythm Pharmaceuticals; RSG reports grants from US Department of Agriculture and NIH/NICHD., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

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.)

Data unavailability impedes research transparency and is a major problem for individual participant data (IPD) meta-analyses as it reduces statistical power, increases risk of bias, and may even preclude completion. The primary objectives of this study were to determine IPD sharing plans reported in recently registered clinical trial registration records, how data sharing commitment relates to clinical trial characteristics, and principal investigators' attitudes, motivations and barriers to data sharing. The secondary objective was to derive recommendations to overcome identified barriers to data sharing. This was a retrospective cohort study of all interventional trials registered on the Australian New Zealand Clinical Trials Registry (ANZCTR) from 1 December 2018 to 30 November 2019, and an online cross-sectional survey of their principal investigators. In the cohort study of all clinical trials registered on the ANZCTR in the study period (n = 1517), commitment to share data was low (22%, 329/1517). In the cross-sectional survey (n = 281, 23% response rate), principal investigators showed strong support for the concept of data sharing (77%, 216/281) but a substantially lower intention to actually share data from their clinical trials (40%, 111/281). Major barriers to data sharing included lacking informed consent to share data, protecting participant confidentiality and preventing misinterpretation of data or misleading secondary analyses. There is a gap between high in-principle support for data sharing, and low in-practice intention from investigators to share data from their own clinical trials. Multiple pathways exist to bridge this gap by addressing the identified barriers to data sharing., (© 2021 John Wiley & Sons Ltd.)

Background: Preterm and low birth weight infants are born with low stores in zinc, which is a vital trace element for growth, cell differentiation and immune function. Preterm infants are at risk of zinc deficiency during the postnatal period of rapid growth. Systematic reviews in the older paediatric population have previously shown that zinc supplementation potentially improves growth and positively influences the course of infectious diseases. In paediatric reviews, the effect of zinc supplementation was most pronounced in those with low nutritional status, which is why the intervention could also benefit preterm infants typically born with low zinc stores and decreased immunity., Objectives: To determine whether enteral zinc supplementation, compared with placebo or no supplementation, affects important outcomes in preterm infants, including death, neurodevelopment, common morbidities and growth., Search Methods: Our searches are up-to-date to 20 February 2020. For the first search, we used the standard search strategy of Cochrane Neonatal to search the Cochrane Central Register of Controlled Trials (CENTRAL 2017, Issue 8), MEDLINE via PubMed (1966 to 29 September 2017), Embase (1980 to 29 September 2017), and CINAHL (1982 to 29 September 2017). We also searched clinical trials databases, conference proceedings, and the reference lists of retrieved articles for randomised controlled trials (RCTs) and quasi-RCTs. We ran an updated search from 1 January 2017 to 20 February 2020 in the following databases: CENTRAL via CRS Web, MEDLINE via Ovid, and CINAHL via EBSCOhost., Selection Criteria: We included RCTs and quasi-RCTs that compared enteral zinc supplementation versus placebo or no supplementation in preterm infants (gestational age < 37 weeks), and low birth weight babies (birth weight < 2500 grams), at any time during their hospital admission after birth. We included zinc supplementation in any formulation, regimen, or dose administered via the enteral route. We excluded infants who underwent gastrointestinal (GI) surgery during their initial hospital stay, or had a GI malformation or another condition accompanied by abnormal losses of GI juices, which contain high levels of zinc (including, but not limited to, stomas, fistulas, and malabsorptive diarrhoea)., Data Collection and Analysis: We used the standard methods of Cochrane Neonatal. Two review authors separately screened abstracts, evaluated trial quality and extracted data. We synthesised effect estimates using risk ratios (RR), risk differences (RD), and standardised mean differences (SMD). Our primary outcomes of interest were all-cause mortality and neurodevelopmental disability. We used the GRADE approach to assess the certainty of evidence., Main Results: We included five trials with a total of 482 preterm infants; there was one ongoing trial. The five included trials were generally small, but of good methodological quality. Enteral zinc supplementation compared to no zinc supplementation Enteral zinc supplementation started in hospitalised preterm infants may decrease all-cause mortality (between start of intervention and end of follow-up period) (RR 0.55, 95% CI 0.31 to 0.97; 3 studies, 345 infants; low-certainty evidence). No data were available on long-term neurodevelopmental outcomes at 18 to 24 months of (post-term) age. Enteral zinc supplementation may have little or no effect on common morbidities such as bronchopulmonary dysplasia (RR 0.66, 95% CI 0.31 to 1.40, 1 study, 193 infants; low-certainty evidence), retinopathy of prematurity (RR 0.14, 95% CI 0.01 to 2.70, 1 study, 193 infants; low-certainty evidence), bacterial sepsis (RR 1.11, 95% CI 0.60 to 2.04, 2 studies, 293 infants; moderate-certainty evidence), or necrotising enterocolitis (RR 0.08, 95% CI 0.00 to 1.33, 1 study, 193 infants; low-certainty evidence). The intervention probably improves weight gain (SMD 0.46, 95% CI 0.28 to 0.64; 5 studies, 481 infants; moderate-certainty evidence); and may slightly improve linear growth (SMD 0.75, 95% CI 0.36 to 1.14, 3 studies, 289 infants; low-certainty evidence), but may have little or no effect on head growth (SMD 0.21, 95% CI -0.02 to 0.44, 3 studies, 289 infants; moderate-certainty evidence)., Authors' Conclusions: Enteral supplementation of zinc in preterm infants compared to no supplementation or placebo may moderately decrease mortality and probably improve short-term weight gain and linear growth, but may have little or no effect on common morbidities of prematurity. There are no data to assess the effect of zinc supplementation on long-term neurodevelopment., (Copyright © 2021 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

Objective: Eczema and food allergy start in infancy and have shared genetic risk factors that affect skin barrier. We aimed to evaluate whether skincare interventions can prevent eczema or food allergy., Design: A prospectively planned individual participant data meta-analysis was carried out within a Cochrane systematic review to determine whether skincare interventions in term infants prevent eczema or food allergy., Data Sources: Cochrane Skin Specialised Register, CENTRAL, MEDLINE, Embase and trial registries to July 2020., Eligibility Criteria for Selected Studies: Included studies were randomized controlled trials of infants <1 year with healthy skin comparing a skin intervention with a control, for prevention of eczema and food allergy outcomes between 1 and 3 years., Results: Of the 33 identified trials, 17 trials (5823 participants) had relevant outcome data and 10 (5154 participants) contributed to IPD meta-analysis. Three of seven trials contributing to primary eczema analysis were at low risk of bias, and the single trial contributing to primary food allergy analysis was at high risk of bias. Interventions were mainly emollients, applied for the first 3-12 months. Skincare interventions probably do not change risk of eczema by age 1-3 years (RR 1.03, 95% CI 0.81, 1.31; I 2 =41%; moderate certainty; 3075 participants, 7 trials). Sensitivity analysis found heterogeneity was explained by increased eczema in a trial of daily bathing as part of the intervention. It is unclear whether skincare interventions increase risk of food allergy by age 1-3 years (RR 2.53, 95% CI 0.99 to 6.47; very low certainty; 996 participants, 1 trial), but they probably increase risk of local skin infections (RR 1.34, 95% CI 1.02, 1.77; I 2 =0%; moderate certainty; 2728 participants, 6 trials)., Conclusion: Regular emollients during infancy probably do not prevent eczema and probably increase local skin infections., (© 2021 John Wiley & Sons Ltd.)

Clinical Question: What is the role of drugs in preventing covid-19? WHY DOES THIS MATTER?: There is widespread interest in whether drug interventions can be used for the prevention of covid-19, but there is uncertainty about which drugs, if any, are effective. The first version of this living guideline focuses on the evidence for hydroxychloroquine. Subsequent updates will cover other drugs being investigated for their role in the prevention of covid-19., Recommendation: The guideline development panel made a strong recommendation against the use of hydroxychloroquine for individuals who do not have covid-19 (high certainty)., How This Guideline Was Created: This living guideline is from the World Health Organization (WHO) and provides up to date covid-19 guidance to inform policy and practice worldwide. Magic Evidence Ecosystem Foundation (MAGIC) provided methodological support. A living systematic review with network analysis informed the recommendations. An international guideline development panel of content experts, clinicians, patients, an ethicist and methodologists produced recommendations following standards for trustworthy guideline development using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach., Understanding the New Recommendation: The linked systematic review and network meta-analysis (6 trials and 6059 participants) found that hydroxychloroquine had a small or no effect on mortality and admission to hospital (high certainty evidence). There was a small or no effect on laboratory confirmed SARS-CoV-2 infection (moderate certainty evidence) but probably increased adverse events leading to discontinuation (moderate certainty evidence). The panel judged that almost all people would not consider this drug worthwhile. In addition, the panel decided that contextual factors such as resources, feasibility, acceptability, and equity for countries and healthcare systems were unlikely to alter the recommendation. The panel considers that this drug is no longer a research priority and that resources should rather be oriented to evaluate other more promising drugs to prevent covid-19., Updates: This is a living guideline. New recommendations will be published in this article and signposted by update notices to this guideline., Readers Note: This is the first version of the living guideline for drugs to prevent covid-19. It complements the WHO living guideline on drugs to treat covid-19. When citing this article, please consider adding the update number and date of access for clarity., Competing Interests: Competing interests: All guideline panel members have completed the WHO interest disclosure form. All authors have completed the BMJ Rapid Recommendations interest of disclosure form. The WHO, MAGIC, and The BMJ judged that no panel member had any financial conflict of interest. Professional and academic interests are minimised as much as possible, while maintaining necessary expertise on the panel to make fully informed decisions. MAGIC and TheBMJ assessed declared interests from other co-authors of this publication and found no conflicts of interests., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Background: Eczema and food allergy are common health conditions that usually begin in early childhood and often occur together in the same people. They can be associated with an impaired skin barrier in early infancy. It is unclear whether trying to prevent or reverse an impaired skin barrier soon after birth is effective in preventing eczema or food allergy., Objectives: Primary objective To assess effects of skin care interventions, such as emollients, for primary prevention of eczema and food allergy in infants Secondary objective To identify features of study populations such as age, hereditary risk, and adherence to interventions that are associated with the greatest treatment benefit or harm for both eczema and food allergy., Search Methods: We searched the following databases up to July 2020: Cochrane Skin Specialised Register, CENTRAL, MEDLINE, and Embase. We searched two trials registers and checked reference lists of included studies and relevant systematic reviews for further references to relevant randomised controlled trials (RCTs). We contacted field experts to identify planned trials and to seek information about unpublished or incomplete trials., Selection Criteria: RCTs of skin care interventions that could potentially enhance skin barrier function, reduce dryness, or reduce subclinical inflammation in healthy term (> 37 weeks) infants (0 to 12 months) without pre-existing diagnosis of eczema, food allergy, or other skin condition were included. Comparison was standard care in the locality or no treatment. Types of skin care interventions included moisturisers/emollients; bathing products; advice regarding reducing soap exposure and bathing frequency; and use of water softeners. No minimum follow-up was required., Data Collection and Analysis: This is a prospective individual participant data (IPD) meta-analysis. We used standard Cochrane methodological procedures, and primary analyses used the IPD dataset. Primary outcomes were cumulative incidence of eczema and cumulative incidence of immunoglobulin (Ig)E-mediated food allergy by one to three years, both measured by the closest available time point to two years. Secondary outcomes included adverse events during the intervention period; eczema severity (clinician-assessed); parent report of eczema severity; time to onset of eczema; parent report of immediate food allergy; and allergic sensitisation to food or inhalant allergen., Main Results: This review identified 33 RCTs, comprising 25,827 participants. A total of 17 studies, randomising 5823 participants, reported information on one or more outcomes specified in this review. Eleven studies randomising 5217 participants, with 10 of these studies providing IPD, were included in one or more meta-analysis (range 2 to 9 studies per individual meta-analysis). Most studies were conducted at children's hospitals. All interventions were compared against no skin care intervention or local standard care. Of the 17 studies that reported our outcomes, 13 assessed emollients. Twenty-five studies, including all those contributing data to meta-analyses, randomised newborns up to age three weeks to receive a skin care intervention or standard infant skin care. Eight of the 11 studies contributing to meta-analyses recruited infants at high risk of developing eczema or food allergy, although definition of high risk varied between studies. Durations of intervention and follow-up ranged from 24 hours to two years. We assessed most of this review's evidence as low certainty or had some concerns of risk of bias. A rating of some concerns was most often due to lack of blinding of outcome assessors or significant missing data, which could have impacted outcome measurement but was judged unlikely to have done so. Evidence for the primary food allergy outcome was rated as high risk of bias due to inclusion of only one trial where findings varied when different assumptions were made about missing data. Skin care interventions during infancy probably do not change risk of eczema by one to two years of age (risk ratio (RR) 1.03, 95% confidence interval (CI) 0.81 to 1.31; moderate-certainty evidence; 3075 participants, 7 trials) nor time to onset of eczema (hazard ratio 0.86, 95% CI 0.65 to 1.14; moderate-certainty evidence; 3349 participants, 9 trials). It is unclear whether skin care interventions during infancy change risk of IgE-mediated food allergy by one to two years of age (RR 2.53, 95% CI 0.99 to 6.47; 996 participants, 1 trial) or allergic sensitisation to a food allergen at age one to two years (RR 0.86, 95% CI 0.28 to 2.69; 1055 participants, 2 trials) due to very low-certainty evidence for these outcomes. Skin care interventions during infancy may slightly increase risk of parent report of immediate reaction to a common food allergen at two years (RR 1.27, 95% CI 1.00 to 1.61; low-certainty evidence; 1171 participants, 1 trial). However, this was only seen for cow's milk, and may be unreliable due to significant over-reporting of cow's milk allergy in infants. Skin care interventions during infancy probably increase risk of skin infection over the intervention period (RR 1.34, 95% CI 1.02 to 1.77; moderate-certainty evidence; 2728 participants, 6 trials) and may increase risk of infant slippage over the intervention period (RR 1.42, 95% CI 0.67 to 2.99; low-certainty evidence; 2538 participants, 4 trials) or stinging/allergic reactions to moisturisers (RR 2.24, 95% 0.67 to 7.43; low-certainty evidence; 343 participants, 4 trials), although confidence intervals for slippages and stinging/allergic reactions are wide and include the possibility of no effect or reduced risk. Preplanned subgroup analyses show that effects of interventions were not influenced by age, duration of intervention, hereditary risk, FLG mutation,  or classification of intervention type for risk of developing eczema. We could not evaluate these effects on risk of food allergy. Evidence was insufficient to show whether adherence to interventions influenced the relationship between skin care interventions and risk of developing eczema or food allergy., Authors' Conclusions: Skin care interventions such as emollients during the first year of life in healthy infants are probably not effective for preventing eczema, and probably increase risk of skin infection. Effects of skin care interventions on risk of food allergy are uncertain. Further work is needed to understand whether different approaches to infant skin care might promote or prevent eczema and to evaluate effects on food allergy based on robust outcome assessments., (Copyright © 2021 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

Background: Associations between kidney disease and periodontal disease are not well documented among Aboriginal people of Australia. The purpose of this investigation was to report and compare demographic, oral health, anthropometric and systemic health status of Aboriginal Australians with kidney disease and to compare against relevant Aboriginal Australians and Australian population estimates. This provides much needed evidence to inform dental health service provision policies for Aboriginal Australians with kidney disease., Methods: Sample frequencies and means were assessed in adults represented in six datasets including: (1) 102 Aboriginal Australians with kidney disease residing in Central Australia who participated in a detailed oral health assessment; (2) 312 Aboriginal participants of the Northern Territory's PerioCardio study; (3) weighted estimates from 4775 participants from Australia's National Survey of Adult Oral Health (NSAOH); (4) Australian 2016 Census (all Australians); (5) National Health Survey 2017-2018 (all Australians) and; (6) Australian Health Survey: Biomedical Results for Chronic Diseases, 2011-2012 (all Australians). Oral health status was described by periodontal disease and experience of dental caries (tooth decay). Statistically significant differences were determined via non-overlapping 95% confidence intervals., Results: Aboriginal Australians with kidney disease were significantly older, less likely to have a tertiary qualification or be employed compared with both PerioCardio study counterparts and NSAOH participants. Severe periodontitis was found in 54.3% of Aboriginal Australians with kidney disease, almost 20 times the 2.8% reported in NSAOH. A higher proportion of Aboriginal Australians with kidney disease had teeth with untreated caries and fewer dental restorations when compared to NSAOH participants. The extent of periodontal attachment loss and periodontal pocketing among Aboriginal Australians with kidney disease (51.0%, 21.4% respectively) was several magnitudes greater than PerioCardio study (22.0%, 12.3% respectively) and NSAOH (5.4%, 1.3% respectively) estimates., Conclusions: Aboriginal Australians with kidney disease exhibited more indicators of poorer oral health than both the general Australian population and a general Aboriginal population from Australia's Northern Territory. It is imperative that management of oral health among Aboriginal Australians with kidney disease be included as part of their ongoing medical care.

Background: Pre-eclampsia is a leading cause of maternal and perinatal mortality and morbidity. Early identification of women at risk is needed to plan management., Objectives: To assess the performance of existing pre-eclampsia prediction models and to develop and validate models for pre-eclampsia using individual participant data meta-analysis. We also estimated the prognostic value of individual markers., Design: This was an individual participant data meta-analysis of cohort studies., Setting: Source data from secondary and tertiary care., Predictors: We identified predictors from systematic reviews, and prioritised for importance in an international survey., Primary Outcomes: Early-onset (delivery at < 34 weeks' gestation), late-onset (delivery at ≥ 34 weeks' gestation) and any-onset pre-eclampsia., Analysis: We externally validated existing prediction models in UK cohorts and reported their performance in terms of discrimination and calibration. We developed and validated 12 new models based on clinical characteristics, clinical characteristics and biochemical markers, and clinical characteristics and ultrasound markers in the first and second trimesters. We summarised the data set-specific performance of each model using a random-effects meta-analysis. Discrimination was considered promising for C -statistics of ≥ 0.7, and calibration was considered good if the slope was near 1 and calibration-in-the-large was near 0. Heterogeneity was quantified using I 2 and τ 2 . A decision curve analysis was undertaken to determine the clinical utility (net benefit) of the models. We reported the unadjusted prognostic value of individual predictors for pre-eclampsia as odds ratios with 95% confidence and prediction intervals., Results: The International Prediction of Pregnancy Complications network comprised 78 studies (3,570,993 singleton pregnancies) identified from systematic reviews of tests to predict pre-eclampsia. Twenty-four of the 131 published prediction models could be validated in 11 UK cohorts. Summary C -statistics were between 0.6 and 0.7 for most models, and calibration was generally poor owing to large between-study heterogeneity, suggesting model overfitting. The clinical utility of the models varied between showing net harm to showing minimal or no net benefit. The average discrimination for IPPIC models ranged between 0.68 and 0.83. This was highest for the second-trimester clinical characteristics and biochemical markers model to predict early-onset pre-eclampsia, and lowest for the first-trimester clinical characteristics models to predict any pre-eclampsia. Calibration performance was heterogeneous across studies. Net benefit was observed for International Prediction of Pregnancy Complications first and second-trimester clinical characteristics and clinical characteristics and biochemical markers models predicting any pre-eclampsia, when validated in singleton nulliparous women managed in the UK NHS. History of hypertension, parity, smoking, mode of conception, placental growth factor and uterine artery pulsatility index had the strongest unadjusted associations with pre-eclampsia., Limitations: Variations in study population characteristics, type of predictors reported, too few events in some validation cohorts and the type of measurements contributed to heterogeneity in performance of the International Prediction of Pregnancy Complications models. Some published models were not validated because model predictors were unavailable in the individual participant data., Conclusion: For models that could be validated, predictive performance was generally poor across data sets. Although the International Prediction of Pregnancy Complications models show good predictive performance on average, and in the singleton nulliparous population, heterogeneity in calibration performance is likely across settings., Future Work: Recalibration of model parameters within populations may improve calibration performance. Additional strong predictors need to be identified to improve model performance and consistency. Validation, including examination of calibration heterogeneity, is required for the models we could not validate., Study Registration: This study is registered as PROSPERO CRD42015029349., Funding: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment ; Vol. 24, No. 72. See the NIHR Journals Library website for further project information.

Background: Pre-eclampsia is a leading cause of maternal and perinatal mortality and morbidity. Early identification of women at risk during pregnancy is required to plan management. Although there are many published prediction models for pre-eclampsia, few have been validated in external data. Our objective was to externally validate published prediction models for pre-eclampsia using individual participant data (IPD) from UK studies, to evaluate whether any of the models can accurately predict the condition when used within the UK healthcare setting., Methods: IPD from 11 UK cohort studies (217,415 pregnant women) within the International Prediction of Pregnancy Complications (IPPIC) pre-eclampsia network contributed to external validation of published prediction models, identified by systematic review. Cohorts that measured all predictor variables in at least one of the identified models and reported pre-eclampsia as an outcome were included for validation. We reported the model predictive performance as discrimination (C-statistic), calibration (calibration plots, calibration slope, calibration-in-the-large), and net benefit. Performance measures were estimated separately in each available study and then, where possible, combined across studies in a random-effects meta-analysis., Results: Of 131 published models, 67 provided the full model equation and 24 could be validated in 11 UK cohorts. Most of the models showed modest discrimination with summary C-statistics between 0.6 and 0.7. The calibration of the predicted compared to observed risk was generally poor for most models with observed calibration slopes less than 1, indicating that predictions were generally too extreme, although confidence intervals were wide. There was large between-study heterogeneity in each model's calibration-in-the-large, suggesting poor calibration of the predicted overall risk across populations. In a subset of models, the net benefit of using the models to inform clinical decisions appeared small and limited to probability thresholds between 5 and 7%., Conclusions: The evaluated models had modest predictive performance, with key limitations such as poor calibration (likely due to overfitting in the original development datasets), substantial heterogeneity, and small net benefit across settings. The evidence to support the use of these prediction models for pre-eclampsia in clinical decision-making is limited. Any models that we could not validate should be examined in terms of their predictive performance, net benefit, and heterogeneity across multiple UK settings before consideration for use in practice., Trial Registration: PROSPERO ID: CRD42015029349 .

Competing Interests: Competing interests: We have read and understood the BMJ Group policy on declaration of interests and declare the following: all authors are convenors or members of the Cochrane PMA Methods Group and have been involved in numerous prospective meta-analyses. LA, DG, and JAB have published several methods articles on prospective meta-analyses and are authors of the prospective meta-analysis chapter in the Cochrane Handbook for Systematic Reviews of Interventions. LA manages the Australian New Zealand Clinical Trials Registry (ANZCTR). ALS and KEH work for the ANZCTR. JAB is a full time employee of Johnson & Johnson.

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: Maternal supine going-to-sleep position has been associated with increased risk of late stillbirth (≥ 28 weeks), but it is unknown if the risk differs between right and left side, and if some pregnancies are more vulnerable., Methods: Systematic searches were undertaken for an individual-level participant data (IPD) meta-analysis of case-control studies, prospective cohort studies and randomised trials undertaken up until 26 Jan, 2018, that reported data on maternal going-to-sleep position and stillbirth. Participant inclusion criteria included gestation ≥ 28 weeks', non-anomalous, singleton pregnancies. The primary outcome was stillbirth. A one-stage approach stratified by study and site was used for the meta-analysis. The interaction between supine going-to-sleep position and fetal vulnerability was assessed by bi-variable regression. The multivariable model was adjusted for a priori confounders. Registration number: PROSPERO, CRD42017047703., Findings: Six case-control studies were identified, with data obtained from five (cases, n = 851; controls, n = 2257). No data was provided by a sixth study (cases, n = 100; controls, n = 200). Supine going-to-sleep position was associated with increased odds of late stillbirth (adjusted odds ratio [aOR] 2.63, 95% CI 1.72-4.04, p < 0.0001) compared with left side. Right side had similar odds to left (aOR 1.04, 95% CI 0.83-1.31, p = 0.75). There were no significant interactions between supine going-to-sleep position and assessed indicators of fetal vulnerability, including small-for-gestational-age infants (p = 0.32), maternal obesity (p = 0.08), and smoking (p = 0.86). The population attributable risk for supine going-to-sleep position was 5.8% (3.2-9.2)., Interpretation: This IPD meta-analysis confirms that supine going-to-sleep position is independently associated with late stillbirth. Going-to-sleep on left or right side appears equally safe. No significant interactions with our assessed indicators of fetal vulnerability were identified, therefore, supine going-to-sleep position can be considered a contributing factor for late stillbirth in all pregnancies. This finding could reduce late stillbirth by 5.8% if every pregnant woman ≥ 28 weeks' gestation settled to sleep on her side.

Objective: To assess the accuracy of the National Institute of Health and Care Excellence (NICE) and United States Preventive Services Task Force (USPSTF) guidelines for predicting pre-eclampsia in pregnancy to guide aspirin prophylaxis., Study Design: We conducted an individual participant data meta-analysis using the Perinatal Antiplatelet Review of International Studies (PARIS) dataset. This dataset includes randomised controlled trials (RCTs) of antiplatelet therapy for primary prevention of pre-eclampsia conducted in international antenatal care settings. RCTs were eligible if they enrolled pregnant women up to 28 weeks'gestation, reported risk factors, and assessed pre-eclampsia. Women assigned to the control arm (no antiplatelet agent) were included. Both guidelines recommend aspirin if ≥1 high-risk factors or ≥2 moderate-risk factors. Two moderate-risk factors (body mass index and pregnancy interval) were unavailable. Pre-eclampsia was the primary outcome. The secondary outcomes were pre-eclampsia defined by gestational age at delivery (<37 weeks versus ≥37 weeks; <34 weeks versus ≥34 weeks). We assessed the performance of the NICE and USPSTF approaches for parous and nulliparous women by estimating sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) for predicting pre-eclampsia, the number-needed-to-screen (NNS) and the number-needed-to-treat (NNT) to prevent one pre-eclampsia event., Results: Three RCTs were eligible (4524 women, 221 pre-eclampsia cases). Using the NICE guidelines, 9.4% of 1020 parous women were classified as screen-positive with a sensitivity of 26.4% (95% confidence interval 16.4-39.6%), specificity 91.5% (89.6-93.1%), PPV 14.6% (8.9-23.0%) and NPV 95.8% (94.3-96.9%). The NNS was 729 and NNT 69. For 3504 nulliparous women, 3% were classified as screen-positive with a sensitivity of 8.9% (5.5-14.4%), specificity 97.2% (96.6-97.8%), PPV 14.2% (8.7-21.9%), NPV 95.5% (94.8-96.1%). The NNS was 2336 and NNT 71. The USPSTF approach demonstrated similar performance., Conclusion: The NICE and USPSTF guidelines offer a simple and specific approach for recommending aspirin prophylaxis for women at high-risk of pre-eclampsia where more advanced screening methods are not available. However, the low detection rate limits its value in clinical practice, in particular for nulliparous women, and raises the need for development of an improved simple risk prediction tool., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: Specialised surveillance using total body photography and digital dermoscopy to monitor people at very high risk of developing a second or subsequent melanoma has been reported as cost effective., Objectives: We aimed to estimate the 5-year healthcare budget impact of providing specialised surveillance for people at very high risk of subsequent melanoma from the perspective of the Australian healthcare system., Methods: A budget impact model was constructed to assess the costs of monitoring and potential savings compared with current routine care based on identification of patients at the time of a melanoma diagnosis. We used data from a published cost-effectiveness analysis of specialised surveillance, and Cancer Registry data, to estimate the patient population and healthcare costs for 2017-2021., Results: When all eligible patients, estimated at 18% of patients with melanoma diagnosed annually in Australia, received specialised surveillance rather than routine care, the cumulative 5-year cost was estimated at $93.5 million Australian dollars ($AU) ($US 64 million) for specialised surveillance compared with $AU 120.7 million ($US 82.7 million) for routine care, delivering savings of $AU 27.2 million ($US 18.6 million). With a staggered introduction of 60% of eligible patients accessing surveillance in year 1, increasing to 90% in years 4 and 5, the cumulative cost over 5 years was estimated at $AU 98.1 million ($US 67.2 million), amounting to savings of $AU 22.6 million ($US 15.5 million) compared with routine care., Conclusions: Specialised melanoma surveillance is likely to provide substantial cost savings for the Australian healthcare system.

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 preferred timing of umbilical-cord clamping in preterm infants is unclear., Methods: We randomly assigned fetuses from women who were expected to deliver before 30 weeks of gestation to either immediate clamping of the umbilical cord (≤10 seconds after delivery) or delayed clamping (≥60 seconds after delivery). The primary composite outcome was death or major morbidity (defined as severe brain injury on postnatal ultrasonography, severe retinopathy of prematurity, necrotizing enterocolitis, or late-onset sepsis) by 36 weeks of postmenstrual age. Analyses were performed on an intention-to-treat basis, accounting for multiple births., Results: Of 1634 fetuses that underwent randomization, 1566 were born alive before 30 weeks of gestation; of these, 782 were assigned to immediate cord clamping and 784 to delayed cord clamping. The median time between delivery and cord clamping was 5 seconds and 60 seconds in the respective groups. Complete data on the primary outcome were available for 1497 infants (95.6%). There was no significant difference in the incidence of the primary outcome between infants assigned to delayed clamping (37.0%) and those assigned to immediate clamping (37.2%) (relative risk, 1.00; 95% confidence interval, 0.88 to 1.13; P=0.96). The mortality was 6.4% in the delayed-clamping group and 9.0% in the immediate-clamping group (P=0.03 in unadjusted analyses; P=0.39 after post hoc adjustment for multiple secondary outcomes). There were no significant differences between the two groups in the incidences of chronic lung disease or other major morbidities., Conclusions: Among preterm infants, delayed cord clamping did not result in a lower incidence of the combined outcome of death or major morbidity at 36 weeks of gestation than immediate cord clamping. (Funded by the Australian National Health and Medical Research Council [NHMRC] and the NHMRC Clinical Trials Centre; APTS Australian and New Zealand Clinical Trials Registry number, ACTRN12610000633088 .).

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.)

Objective: Spontaneous preterm birth is an important cause of neonatal mortality and morbidity. An increasing body of evidence suggests that uteroplacental ischemia plays an important role in the etiology of spontaneous preterm birth. We aimed to study whether antiplatelet agents reduce the risk of spontaneous preterm birth., Data Sources: We included data from an individual participant data meta-analysis of studies that had evaluated the effect of antiplatelet agents to reduce preeclampsia (Perinatal Antiplatelet Review of International Studies Individual Participant Data)., Methods of Study Selection: The meta-analysis included 31 studies that randomized women to low-dose aspirin-dipyridamole or placebo-no treatment as a primary preventive strategy for preeclampsia. For the current study we analyzed data from 17 trials (28,797 women) that supplied data on type of delivery (spontaneous compared with indicated birth)., Tabulation, Integration, and Results: Primary endpoints were spontaneous preterm birth at less than 37 weeks, less than 34 weeks, and less than 28 weeks of gestation. We analyzed outcomes for each trial separately using χ statistics and combined in an individual participant data meta-analysis using a binary logistic regression model. Women assigned to antiplatelet treatment compared with placebo or no treatment had a lower risk of spontaneous preterm birth at less than 37 weeks (relative risk [RR] 0.93, 95% confidence interval [CI] 0.86-0.996) and less than 34 weeks of gestation (RR 0.86, 95% CI 0.76-0.99). The RR of having a spontaneous preterm birth at less than 37 weeks of gestation was 0.83 (95% CI 0.73-0.95) for women who have had a previous pregnancy and 0.98 (95% CI 0.89-1.09) for women in their first pregnancy. The treatment effect was stable in all other prespecified subgroups., Conclusion: Antiplatelet agents reduce spontaneous preterm birth in pregnant women at risk for preeclampsia.

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: The clinically appropriate range for oxygen saturation in preterm infants is unknown. Previous studies have shown that infants had reduced rates of retinopathy of prematurity when lower targets of oxygen saturation were used., Methods: In three international randomized, controlled trials, we evaluated the effects of targeting an oxygen saturation of 85 to 89%, as compared with a range of 91 to 95%, on disability-free survival at 2 years in infants born before 28 weeks' gestation. Halfway through the trials, the oximeter-calibration algorithm was revised. Recruitment was stopped early when an interim analysis showed an increased rate of death at 36 weeks in the group with a lower oxygen saturation. We analyzed pooled data from patients and now report hospital-discharge outcomes., Results: A total of 2448 infants were recruited. Among the 1187 infants whose treatment used the revised oximeter-calibration algorithm, the rate of death was significantly higher in the lower-target group than in the higher-target group (23.1% vs. 15.9%; relative risk in the lower-target group, 1.45; 95% confidence interval [CI], 1.15 to 1.84; P=0.002). There was heterogeneity for mortality between the original algorithm and the revised algorithm (P=0.006) but not for other outcomes. In all 2448 infants, those in the lower-target group for oxygen saturation had a reduced rate of retinopathy of prematurity (10.6% vs. 13.5%; relative risk, 0.79; 95% CI, 0.63 to 1.00; P=0.045) and an increased rate of necrotizing enterocolitis (10.4% vs. 8.0%; relative risk, 1.31; 95% CI, 1.02 to 1.68; P=0.04). There were no significant between-group differences in rates of other outcomes or adverse events., Conclusions: Targeting an oxygen saturation below 90% with the use of current oximeters in extremely preterm infants was associated with an increased risk of death. (Funded by the Australian National Health and Medical Research Council and others; BOOST II Current Controlled Trials number, ISRCTN00842661, and Australian New Zealand Clinical Trials Registry numbers, ACTRN12605000055606 and ACTRN12605000253606.).