External validation of prognostic models to predict stillbirth using the International Prediction of Pregnancy Complications (IPPIC) Network database: an 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. (c) 2021 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.Peer reviewe

External validation of prognostic models predicting pre-eclampsia : individual participant data meta-analysis

Abstract 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

Racemic Adrenaline and Inhalation Strategies in Acute Bronchiolitis

Acute bronchiolitis in infants, which frequently leads to hospitalization and sometimes requires ventilatory support, is occasionally fatal; it is usually viral in origin, with respiratory syncytial virus being the most common cause. The clinical disease is characterized by nasal flaring, tachypnea, dyspnea, chest retractions, crepitations, and wheezing. Bronchodilators are not recommended but are often used in the treatment of bronchiolitis, as are saline inhalations. Adrenaline reduces mucosal swelling, giving it an edge over the β2-adrenergic agonists, and has led to the frequent use of inhaled adrenaline, which has improved symptoms and reduced the need for hospitalization in outpatients with acute bronchiolitis. Among inpatients, however, inhaled adrenaline has not been found to reduce the length of the hospital stay. Assessment of the possible influences of age, sex, and status with respect to an asthma predisposition on the effect of inhaled adrenaline requires large multicenter studies. Inhaled nebulized solutions can be prescribed for use on demand or on a fixed schedule. We were unable to find documentation on the comparative efficacy of these two strategies in children with acute bronchiolitis. We tested the hypothesis that inhaled racemic adrenaline is superior to inhaled saline in the treatment of acute bronchiolitis in infancy and that administration on a fixed schedule is superior to administration on demand. We also assessed whether age, sex, or status with respect to allergic diseases influenced treatment efficacy. Including: Letter to the Editor. Skjerven Håvard Ove, Carlsen Kai-Håkon og Carlsen Karin C Lødrup. Inhaled adrenaline in acute bronchiolitis. The New England Journal of Medicine 2013;369:1076-7. http://dx.doi.org/10.1056/NEJMc130896

Recurrence of hypertensive disorders of pregnancy: an individual patient data metaanalysis

OBJECTIVE: We performed an individual participant data (IPD) metaanalysis to calculate the recurrence risk of hypertensive disorders of pregnancy (HDP) and recurrence of individual hypertensive syndromes. STUDY DESIGN: We performed an electronic literature search for cohort studies that reported on women experiencing HDP and who had a subsequent pregnancy. The principal investigators were contacted and informed of our study; we requested their original study data. The data were merged to form one combined database. The results will be presented as percentages with 95% confidence interval (CI) and odds ratios with 95% CI. RESULTS: Of 94 eligible cohort studies, we obtained IPD of 22 studies, including a total of 99,415 women. Pooled data of 64 studies that used published data (IPD where available) showed a recurrence rate of 18.1% (n ¼ 152,213; 95% CI, 17.9e18.3%). In the 22 studies that are included in our IPD, the recurrence rate of a HDP was 20.7% (95% CI, 20.4e20.9%). Recurrence manifested as preeclampsia in 13.8% of the studies (95% CI,13.6e14.1%), gestational hypertension in 8.6% of the studies (95% CI, 8.4e8.8%) and hemolysis, elevated liver enzymes and low platelets (HELLP) syndrome in 0.2% of the studies (95% CI, 0.16e0.25%). The delivery of a small-for-gestational-age child accompanied the recurrent HDP in 3.4% of the studies (95% CI, 3.2e3.6%). Concomitant HELLP syndrome or delivery of a smallfor- gestational-age child increased the risk of recurrence of HDP. Recurrence increased with decreasing gestational age at delivery in the index pregnancy. If the HDP recurred, in general it was milder, regarding maximum diastolic blood pressure, proteinuria, the use of oral antihypertensive and anticonvulsive medication, the delivery of a small-for-gestational-age child, premature delivery, and perinatal death. Normotensive women experienced chronic hypertension after pregnancy more often after experiencing recurrence (odds ratio, 3.7; 95% CI, 2.3e6.1). CONCLUSION: Among women that experience hypertension in pregnancy, the recurrence rate in a next pregnancy is relatively low, and the course of disease is milder for most women with recurrent disease. These reassuring data should be used for shared decision-making in women who consider a new pregnancy after a pregnancy that was complicated by hypertension.Miriam F. van Oostwaard ... Ben Willem J. Mol ... et al

Geburtseinleitung

Die Geburtseinleitung ist ein häufig angewendetes Vorgehen, wenn eine Entbindung vor dem Einsetzen spontaner Wehen angestrebt werden soll, sie betrifft etwa 20-25 % aller Schwangerschaften. Da die Einleitung den natürlichen Verlauf der Schwangerschaft beeinflusst, muss eine entsprechende Aufklärung über die Vor- und Nachteile und die unterschiedlichen Einleitungsmethoden erfolgen und dokumentiert werden. Neben medizinischen Indikationen kann auch eine elektive "Wunscheinleitung" gerechtfertigt sein. Die unterschiedlichen Einleitungsverfahren, wie Oxytocin, Prostaglandine und mechanische Methoden, müssen abhängig von den Vorbedingungen sorgfältig gegeneinander abgewogen werden. Vor Beginn einer Einleitung muss neben der Überprüfung des fetalen und maternalen Zustands die Einleitungsindikation, das Gestationsalter und der Cervixbefund beurteilt werden