Externally validated prediction models for pre-eclampsia: systematic review and meta-analysis.

OBJECTIVE: This systematic review and meta-analysis aimed to evaluate the performance of existing externally validated prediction models for pre-eclampsia (specifically for any- early- late-onset and preterm pre-eclampsia). METHODS: A systematic search was conducted in five databases (MEDLINE, Embase, Emcare, CINAHL, and Maternity and Infant Care Database) to identify studies based on Population, Index model, Comparator, Outcome, Timing, and Setting (PICOTS) approach until May 20, 2023. We extracted data using the CHARMS checklist and appraised risk of bias using PROBAST tool. Discrimination and calibration performance were meta-analysed when appropriate. RESULTS: Twenty-three publications reported 52 externally validated prediction models on pre-eclampsia (twenty any-onset, seventeen early-onset, fourteen late-onset, and one preterm pre-eclampsia). No model had the same set of predictors. Fifteen, two, and three any-onset pre-eclampsia models were externally validated once, twice, and thrice, respectively, and the Fetal Medicine Foundation (FMF) preterm model was widely validated in sixteen different settings. The most common predictors were maternal characteristics (pre-pregnancy BMI, prior pre-eclampsia, family history of pre-eclampsia, chronic medical conditions, and ethnicity) and biomarkers (uterine artery pulsatility index and pregnancy-associated plasma protein-A). The model for preterm pre-eclampsia (triple test FMF) had the best performances with a pooled area under the receiver operating characteristics curve (AUROC) of 0.90 (95% prediction interval (PI) 0.76 - 0.96) and was well-calibrated. The other models generally had poor to fair discrimination performance (AUROC median 0.66, range 0.53 to 0.77) and were overfitted in calibration after external validation. Apart from the FMF model, only the two most validated models in any-onset pre-eclampsia using isolated maternal characteristics, produced reasonable pooled AUROCs of 0.71 (95% PI 0.66 - 0.76) and 0.73 (0.55 - 0.86). CONCLUSION: Existing externally validated prediction models for any-, early-, and late-onset pre-eclampsia have limited discrimination and calibration performance with inconsistent input variables. The triple test FMF model had excellent discrimination performance in predicting preterm pre-eclampsia in numerous settings, but the inclusion of specialised biomarkers may limit feasibility and implementation outside of high-resource settings. This article is protected by copyright. All rights reserved.

External validation of prognostic models to predict stillbirth using International Prediction of Pregnancy Complications (IPPIC) Network database: individual participant data meta-analysis.

OBJECTIVE: Stillbirth is a potentially preventable complication of pregnancy. Identifying women at high risk of stillbirth can guide decisions on the need for closer surveillance and timing of delivery in order to prevent fetal death. Prognostic models have been developed to predict the risk of stillbirth, but none has yet been validated externally. In this study, we externally validated published prediction models for stillbirth using individual participant data (IPD) meta-analysis to assess their predictive performance. METHODS: MEDLINE, EMBASE, DH-DATA and AMED databases were searched from inception to December 2020 to identify studies reporting stillbirth prediction models. Studies that developed or updated prediction models for stillbirth for use at any time during pregnancy were included. IPD from cohorts within the International Prediction of Pregnancy Complications (IPPIC) Network were used to validate externally the identified prediction models whose individual variables were available in the IPD. The risk of bias of the models and cohorts was assessed using the Prediction study Risk Of Bias ASsessment Tool (PROBAST). The discriminative performance of the models was evaluated using the C-statistic, and calibration was assessed using calibration plots, calibration slope and calibration-in-the-large. Performance measures were estimated separately in each cohort, as well as summarized across cohorts using random-effects meta-analysis. Clinical utility was assessed using net benefit. RESULTS: Seventeen studies reporting the development of 40 prognostic models for stillbirth were identified. None of the models had been previously validated externally, and the full model equation was reported for only one-fifth (20%, 8/40) of the models. External validation was possible for three of these models, using IPD from 19 cohorts (491 201 pregnant women) within the IPPIC Network database. Based on evaluation of the model development studies, all three models had an overall high risk of bias, according to PROBAST. In the IPD meta-analysis, the models had summary C-statistics ranging from 0.53 to 0.65 and summary calibration slopes ranging from 0.40 to 0.88, with risk predictions that were generally too extreme compared with the observed risks. The models had little to no clinical utility, as assessed by net benefit. However, there remained uncertainty in the performance of some models due to small available sample sizes. CONCLUSIONS: The three validated stillbirth prediction models showed generally poor and uncertain predictive performance in new data, with limited evidence to support their clinical application. The findings suggest methodological shortcomings in their development, including overfitting. Further research is needed to further validate these and other models, identify stronger prognostic factors and develop more robust prediction models. © 2021 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Can risk prediction models help us individualise stillbirth prevention? A systematic review and critical appraisal of published risk models.

BACKGROUND: Stillbirth prevention is an international priority - risk prediction models could individualise care and reduce unnecessary intervention, but their use requires evaluation. OBJECTIVES: To identify risk prediction models for stillbirth, and assess their potential accuracy and clinical benefit in practice. SEARCH STRATEGY: MEDLINE, Embase, DH-DATA and AMED databases were searched from inception to June 2019 using terms relevant to stillbirth, perinatal mortality and prediction models. The search was compliant with Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. SELECTION CRITERIA: Studies developing and/or validating prediction models for risk of stillbirth developed for application during pregnancy. DATA COLLECTION AND ANALYSIS: Study screening and data extraction were conducted in duplicate, using the CHARMS checklist. Risk of bias was appraised using the PROBAST tool. RESULTS: The search identified 2751 citations. Fourteen studies reporting development of 69 models were included. Variables consistently included were: ethnicity, body mass index, uterine artery Doppler, pregnancy-associated plasma protein and placental growth factor. For almost all models there were significant concerns about risk of bias. Apparent model performance (i.e. in the development dataset) was highest in models developed for use later in pregnancy and including maternal characteristics, and ultrasound and biochemical variables, but few were internally validated and none were externally validated. CONCLUSIONS: Almost all models identified were at high risk of bias. There are first-trimester models of possible clinical benefit in early risk stratification; these require validation and clinical evaluation. There were few later pregnancy models but, if validated, these could be most relevant to individualised discussions around timing of birth. TWEETABLE ABSTRACT: Prediction models using maternal factors, blood tests and ultrasound could individualise stillbirth prevention, but existing models are at high risk of bias.

Prediction of stillbirth: an umbrella review of evaluation of prognostic variables.

BACKGROUND: Stillbirth accounts for over 2 million deaths a year worldwide and rates remains stubbornly high. Multivariable prediction models may be key to individualised monitoring, intervention or early birth in pregnancy to prevent stillbirth. OBJECTIVES: To collate and evaluate systematic reviews of factors associated with stillbirth in order to identify variables relevant to prediction model development. SEARCH STRATEGY: MEDLINE, Embase, DARE and Cochrane Library databases and reference lists were searched up to November 2019. SELECTION CRITERIA: We included systematic reviews of association of individual variables with stillbirth without language restriction. DATA COLLECTION AND ANALYSIS: Abstract screening and data extraction were conducted in duplicate. Methodological quality was assessed using AMSTAR and QUIPS criteria. The evidence supporting association with each variable was graded. RESULTS: The search identified 1198 citations. Sixty-nine systematic reviews reporting 64 variables were included. The most frequently reported were maternal age (n = 5), body mass index (n = 6) and maternal diabetes (n = 5). Uterine artery Doppler appeared to have the best performance of any single test for stillbirth. The strongest evidence of association was for nulliparity and pre-existing hypertension. CONCLUSION: We have identified variables relevant to the development of prediction models for stillbirth. Age, parity and prior adverse pregnancy outcomes had a more convincing association than the best performing tests, which were PAPP-A, PlGF and UtAD. The evidence was limited by high heterogeneity and lack of data on intervention bias. TWEETABLE ABSTRACT: Review shows key predictors for use in developing models predicting stillbirth include age, prior pregnancy outcome and PAPP-A, PLGF and Uterine artery Doppler.

Association between chorionicity and preterm birth in twin pregnancies: a systematic review involving 29 864 twin pregnancies.

BACKGROUND: The perinatal mortality and morbidity among twins vary by chorionicity. Although it is considered that monochorionicity is associated with an increased risk of preterm birth in twin pregnancies, no systematic review exists evaluating this association. OBJECTIVES: This systematic review was undertaken to assess the association between preterm birth and chorionicity in twin pregnancies. SEARCH STRATEGY: We searched the electronic databases from January 1990 to July 2019 without language restrictions. SELECTION CRITERIA: All studies on twin pregnancies where chorionicity and preterm birth were evaluated were included. DATA COLLECTION AND ANALYSIS: Findings are reported as odds ratios with 95% confidence intervals. The estimates are pooled using random-effects meta-analysis. MAIN RESULTS: From 13 156 citations, we included 39 studies (29 864 pregnancies). Monochorionicity was significantly associated with increased risk of preterm birth at ≤28, ≤32, ≤34 and <37 weeks in women asymptomatic and symptomatic for preterm labour (odds ratio [OR] 2.14, 95% CI 1.52-3.02, I2  = 46%, OR 1.55, 95% CI 1.27-1.89 I2  = 68%, OR 1.47, 95% CI 1.27-1.69, I2  = 60%, OR 1.66, 95% CI 1.43-1.93, I2  = 65%, respectively). Among those asymptomatic for preterm labour, significantly increased odds of preterm birth were seen for monochorionicity at gestations ≤34 weeks (OR 1.85, 95% CI 1.42-2.40, I2  = 25%) and <37 weeks (OR 1.75, 95% CI 1.22-2.53, I2  = 61%). Sensitivity analysis showed significantly increased odds of spontaneous preterm birth at ≤34 and <37 weeks for monochorionicity (OR 1.25, 95% CI 1.01-1.55, I2  = 0% and OR 1.41, 95% CI 1.13-1.78, I2  = 0%). CONCLUSIONS: Monochorionicity is significantly associated with preterm birth at all gestations. TWEETABLE ABSTRACT: In twin pregnancies, monochorionicity is associated with an increased risk of preterm birth at all gestations.

A core outcome set for pre-eclampsia research: an international consensus development study.

OBJECTIVE: To develop a core outcome set for pre-eclampsia. DESIGN: Consensus development study. SETTING: International. POPULATION: Two hundred and eight-one healthcare professionals, 41 researchers and 110 patients, representing 56 countries, participated. METHODS: Modified Delphi method and Modified Nominal Group Technique. RESULTS: A long-list of 116 potential core outcomes was developed by combining the outcomes reported in 79 pre-eclampsia trials with those derived from thematic analysis of 30 in-depth interviews of women with lived experience of pre-eclampsia. Forty-seven consensus outcomes were identified from the Delphi process following which 14 maternal and eight offspring core outcomes were agreed at the consensus development meeting. Maternal core outcomes: death, eclampsia, stroke, cortical blindness, retinal detachment, pulmonary oedema, acute kidney injury, liver haematoma or rupture, abruption, postpartum haemorrhage, raised liver enzymes, low platelets, admission to intensive care required, and intubation and ventilation. Offspring core outcomes: stillbirth, gestational age at delivery, birthweight, small-for-gestational-age, neonatal mortality, seizures, admission to neonatal unit required and respiratory support. CONCLUSIONS: The core outcome set for pre-eclampsia should underpin future randomised trials and systematic reviews. Such implementation should ensure that future research holds the necessary reach and relevance to inform clinical practice, enhance women's care and improve the outcomes of pregnant women and their babies. TWEETABLE ABSTRACT: 281 healthcare professionals, 41 researchers and 110 women have developed #preeclampsia core outcomes @HOPEoutcomes @jamesmnduffy. [Correction added on 29 June 2020, after first online publication: the order has been corrected.].

Correction: Evidence-Based Guideline on Laparoscopy in Pregnancy: Commissioned by the British Society for Gynaecological Endoscopy (BSGE) Endorsed by the Royal College of Obstetricians & Gynaecologists (RCOG).

[This corrects the article on p. 5 in vol. 11, PMID: 31695854.].

Effects of oral probiotic supplements on vaginal microbiota during pregnancy: a randomised, double-blind, placebo-controlled trial with microbiome analysis.

OBJECTIVE: To determine the effects on the vaginal microbiota of an oral probiotic preparation administered from early pregnancy. DESIGN: Randomised, double blind, placebo-controlled trial. SETTING: Four maternity units in the UK. POPULATION: Women aged 16 years or older recruited at 9-14 weeks' gestation. METHODS: Participants were randomly allocated to receive oral capsules of probiotic containing Lactobacillus rhamnosus GR-1 and Lactobacillus reuteri RC-14 each at 2.5 × 109 colony-forming units (CFUs) or placebo once daily from recruitment until the end of pregnancy. MAIN OUTCOME MEASURE: Rates of bacterial vaginosis (BV, defined as Nugent score ≥7) at 18-20 weeks' gestation compared by logistic regression adjusted for possible confounders. RESULTS: The primary analysis included 78% (238/304) of participants who initially consented (probiotic group 123, placebo group 115). Of these participants, 95% (227/238) reported an intake of 93% or more of the required number of capsules. The rates of BV did not differ between groups at 18-20 weeks' gestation (15% (19/123) in the probiotic group vs. 9% (10/115) in the placebo group, adjusted odds ratio 1.82, 95% confidence interval 0.64-5.19). There were also no differences between the groups in the proportion of women colonised with the probiotic strains, Escherichia coli, group B streptococci or other vaginal microbiota. There were no differences in the alpha diversity or composition of the bacterial communities between or within the probiotic and placebo groups at 9-14 and 18-20 weeks' gestation. CONCLUSIONS: Oral probiotics taken from early pregnancy did not modify the vaginal microbiota. TWEETABLE ABSTRACT: The oral probiotic preparation used in this study does not prevent BV in pregnant women.

Evidence-Based Guideline on Laparoscopy in Pregnancy: Commissioned by the British Society for Gynaecological Endoscopy (BSGE) Endorsed by the Royal College of Obstetricians & Gynaecologists (RCOG).

Laparoscopy is widely utilised to diagnose and treat acute and chronic, gynaecological and general surgical conditions. It has only been in recent years that laparoscopy has become an acceptable surgical alternative to open surgery in pregnancy. To date there is little clinical guidance pertaining to laparoscopic surgery in pregnancy. This is why the BSGE commissioned this guideline. MEDLINE, EMBASE, CINAHL and the Cochrane library were searched up to February 2017 and evidence was collated and graded following the NICE-approved process. The conditions included in this guideline are laparoscopic management of acute appendicitis, acute gall bladder disease and symptomatic benign adnexal tumours in pregnancy. The intended audience for this guideline is obstetricians and gynaecologists in secondary and tertiary care, general surgeons and anaesthetists. However, only laparoscopists who have adequate laparoscopic skills and who perform complex laparoscopic surgery regularly should undertake laparoscopy in pregnant women, since much of the evidence stems from specialised centres.

Evidence summaries and recommendations from the international evidence-based guideline for the assessment and management of polycystic ovary syndrome: assessment and treatment of infertility.

STUDY QUESTION: What is the recommended assessment and management of infertile women with polycystic ovary syndrome (PCOS), based on the best available evidence, clinical expertize and consumer preference? SUMMARY ANSWER: International evidence-based guidelines, including 44 recommendations and practice points, addressed prioritized questions to promote consistent, evidence-based care and improve the experience and health outcomes of infertile women with PCOS. WHAT IS KNOWN ALREADY: Previous guidelines on PCOS lacked rigorous evidence-based processes, failed to engage consumer and multidisciplinary perspectives or were outdated. The assessment and management of infertile women with PCOS are inconsistent. The needs of women with PCOS are not being adequately met and evidence practice gaps persist. PARTICIPANTS/MATERIALS SETTING METHODS: Governance included a six continent international advisory and a project board, a multidisciplinary international guideline development group (GDG), consumer and translation committees. Extensive health professional and consumer engagement informed the guideline scope and priorities. The engaged international society-nominated panel included endocrinology, gynaecology, reproductive endocrinology, obstetrics, public health and other experts, alongside consumers, project management, evidence synthesis and translation experts. Thirty-seven societies and organizations covering 71 countries engaged in the process. Extensive online communication and two face-to-face meetings over 15 months addressed 19 prioritized clinical questions involving nine evidence-based reviews and 10 narrative reviews. Evidence-based recommendations (EBRs) were formulated prior to consensus voting within the guideline panel. STUDY DESIGN SIZE DURATION: International evidence-based guideline development engaged professional societies and consumer organizations with multidisciplinary experts and women with PCOS directly involved at all stages. A (AGREE) II-compliant processes were followed, with extensive evidence synthesis. The Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) framework was applied across evidence quality, desirable and undesirable consequences, feasibility, acceptability, cost, implementation and ultimately recommendation strength. The guideline was peer-reviewed by special interest groups across our partner and collaborating societies and consumer organizations, was independently assessed against AGREE II criteria and underwent methodological review. This guideline was approved by all members of the GDG and has been approved by the NHMRC. MAIN RESULTS AND THE ROLE OF CHANCE: The quality of evidence (QOE) for the EBRs in the assessment and management of infertility in PCOS included very low (n = 1), low (n = 9) and moderate (n = 4) quality with no EBRs based on high-quality evidence. The guideline provides 14 EBRs, 10 clinical consensus recommendations (CCRs) and 20 clinical practice points on the assessment and management of infertility in PCOS. Key changes in this guideline include emphasizing evidence-based fertility therapy, including cheaper and safer fertility management. LIMITATIONS REASONS FOR CAUTION: Overall evidence is generally of low to moderate quality, requiring significantly greater research in this neglected, yet common condition. Regional health systems vary and a process for adaptation of this guideline is provided. WIDER IMPLICATIONS OF THE FINDINGS: The international guideline for the assessment and management of infertility in PCOS provides clinicians with clear advice on best practice based on the best available evidence, expert multidisciplinary input and consumer preferences. Research recommendations have been generated and a comprehensive multifaceted dissemination and translation program supports the guideline with an integrated evaluation program. STUDY FUNDING/COMPETING INTERESTS: The guideline was primarily funded by the Australian National Health and Medical Research Council of Australia (NHMRC) supported by a partnership with ESHRE and the American Society for Reproductive Medicine (ASRM). GDG members did not receive payment. Travel expenses were covered by the sponsoring organizations. Disclosures of conflicts of interest were declared at the outset and updated throughout the guideline process, aligned with NHMRC guideline processes. Dr Costello has declared shares in Virtus Health and past sponsorship from Merck Serono for conference presentations. Prof. Norman has declared a minor shareholder interest in the IVF unit Fertility SA, travel support from Merck and grants from Ferring. Prof. Norman also has scientific advisory board duties for Ferring. The remaining authors have no conflicts of interest to declare.This article was not externally peer-reviewed by Human Reproduction Open.

Prediction of pre-eclampsia: review of reviews.

OBJECTIVE: Primary studies and systematic reviews provide estimates of varying accuracy for different factors in the prediction of pre-eclampsia. The aim of this study was to review published systematic reviews to collate evidence on the ability of available tests to predict pre-eclampsia, to identify high-value avenues for future research and to minimize future research waste in this field. METHODS: MEDLINE, EMBASE and The Cochrane Library including DARE (Database of Abstracts of Reviews of Effects) databases, from database inception to March 2017, and bibliographies of relevant articles were searched, without language restrictions, for systematic reviews and meta-analyses on the prediction of pre-eclampsia. The quality of the included reviews was assessed using the AMSTAR tool and a modified version of the QUIPS tool. We evaluated the comprehensiveness of search, sample size, tests and outcomes evaluated, data synthesis methods, predictive ability estimates, risk of bias related to the population studied, measurement of predictors and outcomes, study attrition and adjustment for confounding. RESULTS: From 2444 citations identified, 126 reviews were included, reporting on over 90 predictors and 52 prediction models for pre-eclampsia. Around a third (n = 37 (29.4%)) of all reviews investigated solely biochemical markers for predicting pre-eclampsia, 31 (24.6%) investigated genetic associations with pre-eclampsia, 46 (36.5%) reported on clinical characteristics, four (3.2%) evaluated only ultrasound markers and six (4.8%) studied a combination of tests; two (1.6%) additional reviews evaluated primary studies investigating any screening test for pre-eclampsia. Reviews included between two and 265 primary studies, including up to 25 356 688 women in the largest review. Only approximately half (n = 67 (53.2%)) of the reviews assessed the quality of the included studies. There was a high risk of bias in many of the included reviews, particularly in relation to population representativeness and study attrition. Over 80% (n = 106 (84.1%)) summarized the findings using meta-analysis. Thirty-two (25.4%) studies lacked a formal statement on funding. The predictors with the best test performance were body mass index (BMI) > 35 kg/m2 , with a specificity of 92% (95% CI, 89-95%) and a sensitivity of 21% (95% CI, 12-31%); BMI > 25 kg/m2 , with a specificity of 73% (95% CI, 64-83%) and a sensitivity of 47% (95% CI, 33-61%); first-trimester uterine artery pulsatility index or resistance index > 90th centile (specificity 93% (95% CI, 90-96%) and sensitivity 26% (95% CI, 23-31%)); placental growth factor (specificity 89% (95% CI, 89-89%) and sensitivity 65% (95% CI, 63-67%)); and placental protein 13 (specificity 88% (95% CI, 87-89%) and sensitivity 37% (95% CI, 33-41%)). No single marker had a test performance suitable for routine clinical use. Models combining markers showed promise, but none had undergone external validation. CONCLUSIONS: This review of reviews calls into question the need for further aggregate meta-analysis in this area given the large number of published reviews subject to the common limitations of primary predictive studies. Prospective, well-designed studies of predictive markers, preferably randomized intervention studies, and combined through individual-patient data meta-analysis are needed to develop and validate new prediction models to facilitate the prediction of pre-eclampsia and minimize further research waste in this field. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd.

Predicción de la preeclampsia: revisión de revisiones OBJETIVO: Los estudios primarios y las revisiones sistemáticas proporcionan estimaciones de precisión variable para diferentes factores en la predicción de la preeclampsia. El objetivo de este estudio fue revisar las revisiones sistemáticas publicadas para recopilar evidencia sobre la capacidad de las pruebas disponibles para predecir la preeclampsia, identificar avenidas de investigación futura valiosas y minimizar el desperdicio futuro de investigación en este campo. MÉTODOS: Se realizaron búsquedas de artículos relevantes en bibliografías sobre el tema y en las bases de datos MEDLINE, EMBASE y The Cochrane Library, incluida DARE (Database of Abstracts of Reviews of Effects), desde el inicio de cada base de datos hasta marzo de 2017, sin restricciones de idioma, para obtener revisiones sistemáticas y metaanálisis sobre la predicción de la preeclampsia. La calidad de las revisiones incluidas se evaluó utilizando la herramienta AMSTAR y una versión modificada de la herramienta QUIPS. Se evaluó la amplitud de la búsqueda, el tamaño de la muestra, las pruebas y los resultados evaluados, los métodos de síntesis de datos, las estimaciones de la capacidad de predicción, el riesgo de sesgo relacionado con la población estudiada, la medición de los predictores y los resultados, la deserción del estudio y el ajuste por confusión. RESULTADOS: De las 2444 citas identificadas, se incluyeron 126 revisiones, que informaron sobre más de 90 predictores y 52 modelos de predicción para la preeclampsia. Alrededor de un tercio (n=37 (29,4%)) de todas las revisiones investigaron únicamente marcadores bioquímicos para predecir la preeclampsia, 31 (24,6%) investigaron asociaciones genéticas con la preeclampsia, 46 (36,5%) informaron sobre las características clínicas, cuatro (3,2%) evaluaron sólo marcadores ecográficos y seis (4,8%) estudiaron una combinación de pruebas; dos (1,6%) revisiones adicionales evaluaron los estudios primarios que investigaron cualquier prueba de diagnóstico de la preeclampsia. Las revisiones incluyeron entre dos y 265 estudios primarios, que incluyeron hasta 25 356 688 mujeres en la revisión más grande. Sólo aproximadamente la mitad (n=67 (53,2%)) de las revisiones evaluaron la calidad de los estudios incluidos. En muchas de las revisiones incluidas hubo un alto riesgo de sesgo, particularmente en relación con la representatividad de la población y la deserción de los estudios. Más del 80% (n=106 (84,1%)) resumió los hallazgos utilizando el metaanálisis. Treinta y dos (25,4%) estudios carecían de una declaración formal sobre la financiación. Los predictores con el mejor rendimiento de la prueba fueron el índice de masa corporal (IMC) >35 kg.m-2 , con una especificidad del 92% (IC 95%, 89-95%) y una sensibilidad del 21% (IC 95%, 12-31%); IMC >25 kg.m-2 , con una especificidad del 73% (IC 95%: 64-83%) y una sensibilidad del 47% (IC 95%: 33-61%); índice de pulsatilidad de la arteria uterina en el primer trimestre o índice de resistencia >90° percentil (especificidad del 93% (IC 95%: 90-96%) y sensibilidad del 26% (IC 95%: 23-31%)); factor de crecimiento placentario (especificidad 89% (IC 95%, 89-89%) y sensibilidad 65% (IC 95%, 63-67%)); y proteína placentaria 13 (especificidad 88% (IC 95%, 87-89%) y sensibilidad 37% (IC 95%, 33-41%)). Ningún marcador por sí solo tuvo un rendimiento de la prueba adecuado para el uso clínico rutinario. Los modelos que combinan marcadores son prometedores, pero ninguno fue sometido a una validación externa. CONCLUSIONES: Esta revisión de revisiones ha puesto en duda la necesidad de un metaanálisis agregado adicional en esta área, dado el gran número de revisiones publicadas sujetas a las limitaciones comunes de los estudios predictivos primarios. Se necesitan estudios prospectivos bien diseñados de marcadores predictivos, preferiblemente en estudios de intervención aleatorios, y combinados mediante el metaanálisis de datos de pacientes individuales, para desarrollar y validar nuevos modelos predictivos que faciliten la predicción de la preeclampsia y minimicen el desperdicio de investigación adicional en este campo.

Development of a core outcome set for trials on induction of labour: an international multistakeholder Delphi study.

OBJECTIVE: To develop a set of core outcomes to be minimally reported in trials on induction of labour. DESIGN: Two-round Delphi survey and consensus meeting. POPULATION: Four stakeholder groups: midwives, obstetricians, neonatologists, and women's representatives. METHODS: Protocol registered with COMET (Registration Number: 695). Stakeholders rated reported outcomes for importance (1-limited to 9-critical). The median rating of each outcome was calculated. The consensus criteria to include outcomes were as follows: ≥70% participants rated outcomes as critical and <15% rated outcomes as limited importance. Outcomes that did not achieve consensus were taken to round two and, if there was still no consensus, to the final consensus meeting. MAIN OUTCOME MEASURES: Outcomes in trials of induction of labour. RESULTS: Of the 159 invited participants, 54% (86/159) completed the first round, and 83% completed the second round (71/86). The core outcome set included 28 core outcomes in four domains: Short-term maternal outcomes (n = 18)-cardiorespiratory arrest, damage to internal organs, death, haemorrhage, hysterectomy, infection, intensive care admission, length of hospital stay, mode of delivery, need for more than one induction agent, oxytocin augmentation, postnatal depression, pulmonary embolus, satisfaction with care, stroke, time from induction to delivery, uterine hyperstimulation, uterine scar dehiscence/rupture; short-term offspring outcomes (n = 8)-admission to the neonatal unit, birth trauma, death, hypoxic ischaemic encephalopathy/need for therapeutic hypothermia, meconium aspiration syndrome, need for respiratory support, infection, and seizures; long-term maternal outcomes (n = 1)-operative pelvic floor repair; long-term offspring outcomes (n = 1)-disability including neurodevelopmental delay. CONCLUSION: Trials on induction of labour should include this core outcome set to standardise reporting. TWEETABLE ABSTRACT: International multistakeholder Delphi study identifies a core outcome set for trials on induction of labour.

Inositol treatment of anovulation in women with polycystic ovary syndrome: a meta-analysis of randomised trials.

Polycystic ovary syndrome is a common cause of anovulation and infertility, and a risk factor for development of metabolic syndrome and endometrial cancer. Systematic review and meta-analysis of randomised controlled trials (RCT) that evaluated the effects of inositol as an ovulation induction agent. We searched MEDLINE, EMBASE, Cochrane and ISI conference proceedings, Register and Meta-register for RCT and WHO trials' search portal. We included studies that compared inositol with placebo or other ovulation induction agents. Quality of studies was assessed for risk of bias. Results were pooled using random effects meta-analysis and findings were reported as relative risk or standardised mean differences. We included ten randomised trials. A total of 362 women were on inositol (257 on myo-inositol; 105 on di-chiro-inositol), 179 were on placebo and 60 were on metformin. Inositol was associated with significantly improved ovulation rate (RR 2.3; 95% CI 1.1-4.7; I2 = 75%) and increased frequency of menstrual cycles (RR 6.8; 95% CI 2.8-16.6; I2 = 0%) compared with placebo. One study reported on clinical pregnancy rate with inositol compared with placebo (RR 3.3; 95% CI 0.4-27.1), and one study compared with metformin (RR 1.5; 95% CI 0.7-3.1). No studies evaluated live birth and miscarriage rates. Inositol appears to regulate menstrual cycles, improve ovulation and induce metabolic changes in polycystic ovary syndrome; however, evidence is lacking for pregnancy, miscarriage or live birth. A further, well-designed multicentre trial to address this issue to provide robust evidence of benefit is warranted. TWEETABLE ABSTRACT: Inositols improve menstrual cycles, ovulation and metabolic changes in polycystic ovary syndrome.

Cognitive, motor, behavioural and academic performances of children born preterm: a meta-analysis and systematic review involving 64 061 children.

BACKGROUND: Preterm birth may leave the brain vulnerable to dysfunction. Knowledge of future neurodevelopmental delay in children born with various degrees of prematurity is needed to inform practice and policy. OBJECTIVE: To quantify the long-term cognitive, motor, behavioural and academic performance of children born with different degrees of prematurity compared with term-born children. SEARCH STRATEGY: PubMed and Embase were searched from January 1980 to December 2016 without language restrictions. SELECTION CRITERIA: Observational studies that reported neurodevelopmental outcomes from 2 years of age in children born preterm compared with a term-born cohort. DATA COLLECTION AND ANALYSIS: We pooled individual estimates of standardised mean differences (SMD) and odds ratios (OR) with 95% confidence intervals using a random effects model. MAIN RESULTS: We included 74 studies (64 061 children). Preterm children had lower cognitive scores for FSIQ (SMD: -0.70; 95% CI: -0.73 to -0.66), PIQ (SMD: -0.67; 95% CI: -0.73 to -0.60) and VIQ (SMD: -0.53; 95% CI: -0.60 to -0.47). Lower scores for preterm children in motor skills, behaviour, reading, mathematics and spelling were observed at primary school age, and this persisted to secondary school age, except for mathematics. Gestational age at birth accounted for 38-48% of the observed IQ variance. ADHD was diagnosed twice as often in preterm children (OR: 1.6; 95% CI: 1.3-1.8), with a differential effect observed according to the severity of prematurity (I2 = 49.4%, P = 0.03). CONCLUSIONS: Prematurity of any degree affects the cognitive performance of children born preterm. The poor neurodevelopment persists at various ages of follow up. Parents, educators, healthcare professionals and policy makers need to take into account the additional academic, emotional and behavioural needs of these children. TWEETABLE ABSTRACT: Adverse effect of preterm birth on a child's neurodevelopment persists up to adulthood.

Epilepsy and Pregnancy: For healthy pregnancies and happy outcomes. Suggestions for service improvements from the Multispecialty UK Epilepsy Mortality Group.

Between 2009 and 2012 there were 26 epilepsy-related deaths in the UK of women who were pregnant or in the first post-partum year. The number of pregnancy-related deaths in women with epilepsy (WWE) has been increasing. Expert assessment suggests that most epilepsy-related deaths in pregnancy were preventable and attributable to poor seizure control. While prevention of seizures during pregnancy is important, a balance must be struck between seizure control and the teratogenic potential of antiepileptic drugs (AEDs). A range of professional guidance on the management of epilepsy in pregnancy has previously been issued, but little attention has been paid to how optimal care can be delivered to WWE by a range of healthcare professionals. We summarise the findings of a multidisciplinary meeting with representation from a wide group of professional bodies. This focussed on the implementation of optimal pregnancy epilepsy care aiming to reduce mortality of epilepsy in mothers and reduce morbidity in babies exposed to AEDs in utero. We identify in particular -What stage to intervene - Golden Moments of opportunities for improving outcomes -Which Key Groups have a role in making change -When - 2020 vision of what these improvements aim to achieve. -How to monitor the success in this field We believe that the service improvement ideas developed for the UK may provide a template for similar initiatives in other countries.

Development of a core outcome set for epilepsy in pregnancy (E-CORE): a national multi-stakeholder modified Delphi consensus study.

OBJECTIVE: To develop a set of core outcomes for studies on pregnant women with epilepsy. DESIGN: Delphi consensus study. POPULATION: Healthcare professionals, and patient representatives with lived experience of epilepsy in the UK. METHODS: We used a modified Delphi method and a consultation meeting to achieve consensus. Potential outcomes were identified by systematic review, and were scored using a Likert scale anchored between 1 (least important) and 5 (most important). We included outcomes that scored ≥4 by >70% of participants, and outcomes that scored ≤2 by <15% of participants. MAIN OUTCOME MEASURES: Outcomes in studies on epilepsy in pregnancy. RESULTS: Seventy-five healthcare professionals completed the first round, 48 (64%) completed the second round, and 37 (49%) completed the third round of the survey. Twenty-four patient representatives participated. The final core outcome set included 31 outcomes in three domains: neurological, offspring, and obstetric. Outcomes in the neurological domain were seizure control in pregnancy and postpartum, status epilepticus, maternal mortality, drowning, sudden unexpected death in epilepsy, postnatal depression, and quality of life. Offspring domain included congenital abnormalities (major and minor), fetal anticonvulsant syndrome, neurodevelopment, autism disorder, neonatal clinical complications, admission to a neonatal intensive care unit, and anthropometric measurements. The obstetric domain included live birth, stillbirth, miscarriage, ectopic, termination of pregnancy, admission to a high dependency or intensive care unit, breastfeeding, mode of delivery, preterm birth, pre-eclampsia, and eclampsia. Outcomes specific for studies on anti-epileptic drugs (AEDs) included maternal AED toxicity, AED compliance, neonatal withdrawal symptoms, and neonatal haemorrhagic disease. CONCLUSION: Embedding this core set in future clinical trials will promote the standardisation of reporting to inform clinical practice. TWEETABLE ABSTRACT: A Delphi method identifying core outcomes for epilepsy in pregnancy. Final core set includes 31 outcomes.

Development of composite outcomes for individual patient data (IPD) meta-analysis on the effects of diet and lifestyle in pregnancy: a Delphi survey.

OBJECTIVE: To develop maternal, fetal, and neonatal composite outcomes relevant to the evaluation of diet and lifestyle interventions in pregnancy by individual patient data (IPD) meta-analysis. DESIGN: Delphi survey. SETTING: The International Weight Management in Pregnancy (i-WIP) collaborative network. Sample Twenty-six researchers from the i-WIP collaborative network from 11 countries. METHODS: A two-generational Delphi survey involving members of the i-WIP collaborative network (26 members in 11 countries) was undertaken to prioritise the individual outcomes for their importance in clinical care. The final components of the composite outcomes were identified using pre-specified criteria. MAIN OUTCOME MEASURES: Composite outcomes considered to be important for the evaluation of the effect of diet and lifestyle in pregnancy. RESULTS: Of the 36 maternal outcomes, nine were prioritised and the following were included in the final composite: pre-eclampsia or pregnancy-induced hypertension, gestational diabetes mellitus (GDM), elective or emergency caesarean section, and preterm delivery. Of the 27 fetal and neonatal outcomes, nine were further evaluated, with the final composite consisting of intrauterine death, small for gestational age, large for gestational age, and admission to a neonatal intensive care unit (NICU). CONCLUSIONS: Our work has identified the components of maternal, fetal, and neonatal composite outcomes required for the assessment of diet and lifestyle interventions in pregnancy by IPD meta-analysis.