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To evaluate the diagnostic performance of third trimester ultrasound for the diagnosis of clinically significant Placenta accreta spectrum disorder (PAS) in women with a low-lying placenta (less than 20 mm from the internal cervical os) or placenta praevia (covering the os) METHODS: Pregnant women with a low-lying placenta or placenta praevia, age ≥ 18 years and gestational age at ultrasound ≥ 26+0/7 weeks of gestation were prospectively included in the study. Ultrasound suspicion of PAS was raised in the presence of at least one of these signs: (1) obliteration of the hypoechoic space between the uterus and the placenta; (2) interruption of the hyperechoic interface between the uterine serosa and the bladder wall; (3) abnormal placental lacunae. In order to assess the ability of ultrasound to detect clinically significant PAS, a composite outcome comprehensive of both active management at delivery and histopathological confirmation of PAS was considered as the reference standard. PAS was considered of clinical significance if, in addition to histological confirmation, at least one of these procedures was carried out after delivery: use of hemostatic intrauterine balloon, compressive uterine suture, peripartum hysterectomy, uterine/hypogastric artery ligation, uterine artery embolization.

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.

Due to a technical error, the author list at the end of this article is unfortunately incorrect. Elif Gül Yapar Eyi is not a co-author, and therefore, his name and affiliation should not appear in the list. The correct author list and affiliations read as follows: Daniele Di Mascio, Cihat Sen, Gabriele Saccone, Alberto Galindo, Amos Grünebaum, Jun Yoshimatsu, Milan Stanojevic, AsimKurjak, Frank Chervenak, María Jos´e Rodríguez Suárez, Zita Maria Gambacorti-Passerini, María de los Angeles Anaya Baz, Esther Vanessa Aguilar Galán, Yolanda Cuñarro López, Juan Antonio De León Luis, Ignacio Cueto Hernández, Ignacio Herraiz, Cecilia Villalain, Roberta Venturella, Giuseppe Rizzo, Ilenia Mappa, Giovanni Gerosolima, Lars Hellmeyer, Josefine Königbauer, Giada Ameli, Tiziana Frusca, Nicola Volpe, Giovanni Battista Luca Schera, Stefania Fieni, Eutalia Esposito, Giuliana Simonazzi, Gaetana Di Donna, Aly Youssef, Anna Nunzia Della Gatta, Mariano Catello Di Donna, Vito Chiantera, Natalina Buono, Giulio Sozzi, Pantaleo Greco, Danila Morano, Beatrice Bianchi, Maria Giulia Lombana Marino, Federica Laraud, Arianna Ramone, Angelo Cagnacci, Fabio Barra, Claudio Gustavino, Simone Ferrero, Fabio Ghezzi, Antonella Cromi, Antonio Simone Laganá, Valentina Laurita Longo, Francesca Stollagli, Angelo Sirico, Antonio Lanzone, Lorenza Driul, Fabiana Cecchini D, Serena Xodo, Brian Rodriguez, Felipe Mercado-Olivares, Deena Elkafrawi, Giovanni Sisti, Rosanna Esposito, Antonio Coviello, Marco Cerbone, Maddalena Morlando, Antonio Schiattarella, Nicola Colacurci, Pasquale De Franciscis, Ilaria Cataneo, Marinella Lenzi, Fabrizio Sandri, Riccardo Buscemi, Giorgia Gattei, Francesca della Sala, Eleonora Valori, Maria Cristina Rovellotti, Elisa Done, Gilles Faron, Leonardo Gucciardo, Valentina Esposito, Flaminia Vena, Antonella Giancotti, Roberto Brunelli, Ludovico Muzii, Luigi Nappi, Felice Sorrentino, Lorenzo Vasciaveo, Marco Liberati, Danilo Buca, Martina Leombroni, Francesca Di Sebastiano, Luciano Di Tizio, Diego Gazzolo, Massimo Franchi, Quintino Cesare Ianniciello, Simone Garzon, Giuliano Petriglia, Leonardo Borrello, Albaro Jos´e Nieto-Calvache, Juan Manuel Burgos-Luna, Caroline Kadji, Andrew Carlin, Elisa Bevilacqua, Marina Moucho, Pedro Viana Pinto, Rita Figueiredo, Jos´e Morales Roselló, Gabriela Loscalzo, Alicia Martinez-Varea, Vincente Diago, Jesús S Jimenez Lopez, Alicia Yeliz Aykanat, Stefano Cosma, Andrea Carosso, Chiara Benedetto, Amanda Bermejo, Otto Henrique May Feuerschuette, Ozlem Uyaniklar, Sakine Rahimli Ocakouglu, Zeliha Atak, Reyhan Gündüz, Esra Tustas Haberal, Bernd Froessler, Anupam Parange, Peter Palm, Igor Samardjiski, Chiara Taccaliti, Erhan Okuyan, George Daskalakis, Renato Augusto Moreira de Sa, Alejandro Pittaro, Maria Luisa Gonzalez-Duran, Ana Concheiro Guisan, Serife Özlem Genç, Blanka Zlatohlávková, Anna Luengo Piqueras, Dolores Esteban Oliva, Aylin Pelin Cil, Olus Api, Panos Antsaklis, Liana Ples, Ioannis Kyvernitakis, Holger Maul, Marcel Malan, Albert Lila, Roberta Granese, Alfredo Ercoli, Giuseppe Zoccali, Andrea Villasco, Nicoletta Biglia, Ciuhodaru Madalina, Elena Costa, Caroline Daelemans, Axelle Pintiaux, Elisa Cueto, Eran Hadar, Sarah Dollinger, Noa A. Brzezinski Sinai, Erasmo Huertas, Pedro Arango, Amadeo Sanchez, Javier Alfonso Schvartzman, Liviu Cojocaru, Sifa Turan, Ozhan Turan, Maria Carmela Di Dedda, Rebeca Garrote Molpeceres, Snezana Zdjelar, Tanja Premru-Srsen, Lilijana Kornhauser Cerar, Mirjam Druškovic, Valentina De Robertis, Vedran Stefanovic, Irmeli Nupponen, Kaisa Nelskylä, Zulfiya Khodjaeva, Ksenia A. Gorina, Gennady T. Sukhikh, Giuseppe Maria Maruotti, Silvia Visentin, Erich Cosmi, Jacopo Ferrari, Alessandra Gatti, Daniela Luvero, Roberto Angioli, Ludovica Puri, Marco Palumbo, Giusella D’Urso, Francesco Colaleo, Agnese Maria Chiara Rapisarda, Ilma Floriana Carbone, Antonio Mollo, Giovanni Nazzaro, Mariavittoria Locci, Maurizio Guida, Attilio Di Spiezio Sardo, Pierluigi Benedetti Panici, Vincenzo Berghella, Maria Elena Flacco, Lamberto Manzoli, Giuseppe Bifulco, Giovanni Scambia, Fulvio Zullo and Francesco D’Antonio Flaminia Vena, Antonella Giancotti, Roberto Brunelli, Ludovico Muzii and Pierluigi Benedetti Panici, Department of Maternal and Child Health and Urological Sciences, Sapienza University of Rome, Rome, Italy Rosanna Esposito, Antonio Coviello, Marco Cerbone, Giuseppe Maria Maruotti, Giovanni Nazzaro, Mariavittoria Locci, Maurizio Guida, Attilio Di Spiezio Sardo, Giuseppe Bifulco and Fulvio Zullo, Department of Neuroscience, Reproductive Sciences and Dentistry, School of Medicine, University of Naples Federico II, Naples, Italy Ignacio Herraiz and Cecilia Villalain, Department of Obstetrics and Gynaecology, Fetal Medicine Unit, Maternal and Child Health and Development Network, University Hospital 12 de Octubre, Complutense University of Madrid, Madrid, Spain María Jos´e Rodríguez Suárez, Hospital Universitario Central de Asturias, Asturias, Spain Zita Maria Gambacorti-Passerini, Department of Obstetrics and Gynaecology, Ciudad Real University General Hospital, Ciudad Real, Spain María de los Angeles Anaya Baz and Esther Vanessa Aguilar Galán, Department of Obstetrics and Gynaecology, Ciudad Real University General Hospital, Ciudad Real, Spain; University of Castilla-La Mancha, Ciudad Real, Spain Yolanda Cuñarro López, Juan Antonio De León Luis and Ignacio Cueto Hernández, Department of Obstetrics and Gynaecology, Fetal Medicine Unit, Maternal and Child Health and Development Network, Gregorio Marañón Hospital, Complutense University of Madrid, Madrid, Spain Roberta Venturella, Department of Obstetrics and Gynaecology, School of Medicine, Magna Graecia University of Catanzaro, Catanzaro, Italy Giuseppe Rizzo, University of Roma Tor Vergata, Division of Maternal Fetal Medicine, Ospedale Cristo Re Roma, Rome, Italy; Department of Obstetrics and Gynaecology, The First I.M. Sechenov Moscow State Medical University, Moscow, Russia Ilenia Mappa, University of Roma Tor Vergata, Division of Maternal Fetal Medicine, Ospedale Cristo Re Roma, Rome, Italy Giovanni Gerosolima, Department of Obstetrics and Gynaecology, Ospedale AOSG Moscati, Avellino, Italy Lars Hellmeyer, Josefine Königbauer and Giada Ameli, Department of Gynaecology and Obstetrics, Vivantes Klinikum im Friedrichshain, Berlin, Germany Tiziana Frusca, Nicola Volpe, Giovanni Battista Luca Schera and Stefania Fieni, Department of Obstetrics and Gynaecology, University of Parma, Parma, Italy Eutalia Esposito, Department of Obstetrics and Gynaecology, Ospedale di San Leonardo, Castellammare di Stabia, Italy Giuliana Simonazzi, Gaetana Di Donna, Aly Youssef and Anna Nunzia Della Gatta, Department of Obstetrics and Gynaecology, University of Bologna, Sant’Orsola- Malpighi University Hospital, Bologna, Italy Mariano Catello Di Donna, Vito Chiantera, Natalina Buono and Giulio Sozzi, Department of Gynaecologic Oncology, University of Palermo, Palermo, Sicilia, Italy Pantaleo Greco, Danila Morano, Beatrice Bianchi and Maria Giulia Lombana Marino, Department ofMedical Sciences, Section of Obstetrics and Gynaecology, Azienda Ospedaliera-Universitaria Sant’Anna, University of Ferrara, Ferrara, Italy Federica Laraud, Arianna Ramone, Angelo Cagnacci, Fabio Barra, Claudio Gustavino and Simone Ferrero, Academic Unit of Obstetrics and Gynaecology, IRCCS Ospedale Policlinico, San Martino, Genova, Italy Fabio Ghezzi, Antonella Cromi and Antonio Simone Laganà, Department of Obstetrics and Gynaecology, “Filippo Del Ponte” Hospita University of Insubria, Varese, Italy Valentina Laurita Longo, Department of Obstetrics and Gynaecology, Fondazione Policlinico Universitario A Gemelli IRCCS – Università Cattolica del Sacro Cuore, Rome, Italy; Istituto di Clinica Ostetrica e Ginecologica, Università Cattolica del Sacro Cuore, Rome, Italy; and Queen Margaret University, Institute for Global Health and Development, Edinburgh, UK Francesca Stollagli and Ludovica Puri, Istituto di Clinica Ostetrica e Ginecologica, Università Cattolica del Sacro Cuore, Rome, Italy Angelo Sirico and Giovanni Scambia, Department of Obstetrics and Gynaecology, Fondazione Policlinico Universitario A Gemelli IRCCS – Università Cattolica del Sacro Cuore, Rome, Italy Antonio Lanzone, Department of Obstetrics and Gynaecology, Fondazione Policlinico Universitario A Gemelli IRCCS – Università Cattolica del Sacro Cuore, Rome, Italy; Istituto di Clinica Ostetrica e Ginecologica, Università Cattolica del Sacro Cuore, Rome, Italy Lorenza Driul, Fabiana Cecchini D and Serena Xodo, Clinic of Obstetrics and Gynaecology, University of Udine, Udine, Italy Brian Rodriguez, Felipe Mercado-Olivares, Deena Elkafrawi and Giovanni Sisti, Department of Obstetrics and Gynaecology, New York Health and Hospitals/Lincoln Bronx, The Bronx, NY, USA Maddalena Morlando, Antonio Schiattarella, Nicola Colacurci and Pasquale De Franciscis, Department of Woman, Child and General and Specialized Surgery, University of Campania Luigi Vanvitelli, Naples, Italy Ilaria Cataneo, Marinella Lenzi and Fabrizio Sandri, Unit of Obstetrics and Gynaecology, Ospedale Maggiore, Bologna, Italy Riccardo Buscemi, Giorgia Gattei, Francesca della Sala and Maria Cristina Rovellotti, Department of Translational Medicine, University of Eastern Piedmont, Novara, Italy Eleonora Valori, Department of Translational Medicine, University of Eastern Piedmont, Novara, Italy; Hospital Castelli, Verbania, Italy Elisa Done, Gilles Faron and Leonardo Gucciardo, UZ Brussel, Universitair Ziekenhuis, Brussel, Belgium Valentina Esposito, University of Milan, Milan, Italy Luigi Nappi, Felice Sorrentino and Lorenzo Vasciaveo, Department of Obstetrics and Gynaecology, Department of Medical and Surgical Sciences, University of Foggia, Foggia, Italy.

Objective To assess the performance of fetal magnetic resonance imaging (MRI) in detecting associated anomalies in fetuses diagnosed with isolated corpus callosal (CC) anomaly on multiplanar ultrasound evaluation of the fetal brain (neurosonography). Methods This was a multicenter, retrospective cohort study involving 14 fetal medicine centers in Italy, UK, Portugal, Canada, Austria and Spain. Inclusion criteria were fetuses with an apparently isolated CC anomaly, defined as an anomaly of the CC and no other additional central nervous system (CNS) or extra-CNS abnormality detected on expert ultrasound, including multiplanar neurosonography; normal karyotype; maternal age >= 18 years; and gestational age at diagnosis >= 18 weeks. The primary outcome was the rate of additional CNS abnormalities detected exclusively on fetal MRI within 2 weeks following neurosonography. The secondary outcomes were the rate of additional abnormalities according to the type of CC abnormality (complete (cACC) or partial (pACC) agenesis of the CC) and the rate of additional anomalies detected only on postnatal imaging or at postmortem examination. Results A total of 269 fetuses with a sonographic prenatal diagnosis of apparently isolated CC anomalies (207 with cACC and 62 with pACC) were included in the analysis. Additional structural anomalies of the CNS were detected exclusively on prenatal MRI in 11.2% (30/269) of cases, with malformations of cortical development representing the most common type of anomaly. When stratifying the analysis according to the type of CC anomaly, the rate of associated anomalies detected exclusively on MRI was 11.6% (24/207) in cACC cases and 9.7% (6/62) in pACC cases. On multivariate logistic regression analysis, only maternal body mass index was associated independently with the likelihood of detecting associated anomalies on MRI (odds ratio, 1.07 (95% CI, 1.01-1.14); P = 0.03). Associated anomalies were detected exclusively after delivery and were missed on both types of prenatal imaging in 3.9% (8/205) of fetuses with prenatal diagnosis of isolated anomaly of the CC. Conclusion In fetuses with isolated anomaly of the CC diagnosed on antenatal neurosonography, MRI can identify a small proportion of additional anomalies, mainly malformations of cortical development, which are not detected on ultrasound. (c) 2021 International Society of Ultrasound in Obstetrics and Gynecology.

To investigate the effects of the antenatal administration of betamethasone on fetal Doppler and short term fetal heart rate variation (CTG-STV) in early growth restricted (FGR) fetuses. Post hoc analysis of data derived from the TRUFFLE study, a prospective, multicenter, randomized management trial of severe early onset FGR. Repeat Doppler and CTG-STV measurements between the last recording within 48 hours before the first dose of betamethasone (baseline value) and for 10 days after were evaluated. Multilevel analysis was performed to analyze the longitudinal course of the umbilico-cerebral ratio (UC ratio), the ductus venosus pulsatility index (DVPIV) and CTG-STV. We included 115 fetuses. A significant increase from baseline in CTG-STV was found on day + 1 (p = 0.019) but no difference thereafter. The DVPIV was not significantly different from baseline in any of the 10 days following the first dose of betamethasone (p = 0.167). Multilevel analysis revealed that, over 10 days, the time elapsed from antenatal administration of betamethasone was significantly associated with a decrease in CTG-STV (p = 0.045) and an increase in the DVPIV (p = 0.001) and UC ratio (p 0.001). Although steroid administration in early FGR has a minimal effect on increasing CTG-STV one day afterwards, the effects on Doppler parameters were extremely slight with regression coefficients of small magnitude suggesting no clinical significance, and were most likely related to the deterioration with time in FGR. Hence, arterial and venous Doppler assessment of fetal health remains informative following antenatal steroid administration to accelerate fetal lung maturation.ZIEL: Untersuchung des Effekts der antenatalen Gabe von Betamethason auf den fetalen Doppler und die Kurzzeitvariation der fetalen Herzfrequenz (CTG-STV) bei Föten mit früher Wachstumsrestriktion (FGR). Post-hoc-Analyse von Daten der TRUFFLE-Studie, einer prospektiven, multizentrischen, randomisierten Managementstudie bei schwerer, früh einsetzender FGR. Wiederholte Doppler- und CTG-STV-Messungen zwischen der letzten Aufnahme innerhalb von 48 Stunden vor der ersten Betamethason-Dosis (Ausgangswert) und über 10 Tage wurden bewertet. Eine mehrstufige Analyse erfolgte, um den longitudinalen Verlauf der umbilikal-zerebralen Ratio (UC-Ratio), des Pulsatilitätsindex des Ductus venosus (DVPIV) und der CTG-STV zu analysieren. Wir haben 115 Föten eingeschlossen. Ein signifikanter Anstieg der CTG-STV gegenüber dem Ausgangswert wurde am Tag + 1 (p = 0,019) ermittelt, danach gab es keinen Unterschied. Der DVPIV unterschied sich an keinem der 10 Tage nach erster Betamethason-Dosis signifikant vom Ausgangswert (p = 0,167). Eine mehrstufige Analyse ergab, dass die verstrichene Zeit nach der antenatalen Betamethason-Gabe über 10 Tage hinweg signifikant mit der Abnahme der CTG-STV (p = 0,045) und der Zunahme des DVPIV (p = 0,001) und der UC-Ratio (p 0,001) assoziiert war. Obwohl die Steroidverabreichung bei früher FGR eine kleine Auswirkung auf den Anstieg der CTG-STV 1 Tag darauf hatte, waren die Effekte auf die Doppler-Parameter äußerst gering mit Regressionskoeffizienten von geringer Höhe, die nicht auf klinische Signifikanz schließen lassen. Sie stehen höchstwahrscheinlich in Zusammenhang mit der Verschlechterung bei FGR im Laufe der Zeit. Daher bleibt die Beurteilung der arteriellen und venösen Doppler bezüglich des Gesundheitszustandes des Fötus aussagekräftig, nachdem diesem zur Beschleunigung der fetalen Lungenreifung antenatal Steroide verabreicht wurden.

Background Implementation of high-quality national audits for perinatal mortality are needed to improve the registration of all perinatal deaths and the identification of the causes of death. This study aims to evaluate the implementation of a Regional Audit System for Stillbirth in Emilia-Romagna Region, Italy. Methods For each stillbirth (≥ 22 weeks of gestation, ≥ 500 g) occurred between January 1, 2014 to December 1, 2016 (n = 332), the same diagnostic workup was performed and a clinical record with data about mother and stillborn was completed. Every case was discussed in a multidisciplinary local audit to assess both the cause of death (ReCoDe classification) and the quality of care. Data were reviewed by the Regional Audit Group. Stillbirth rates, causes of death and the quality of care were established for each case. Results Total stillbirth rate was 3.09 per 1000 births (332/107,528). Late stillbirth rate was 2.3 per 1000 (251/107,087). Sixteen stillbirths were not registered by the Regional Birth Register. The most prevalent cause of death was placental disorder (33.3%), followed by fetal (17.6%), cord (14.2%) and maternal disorders (7.6%). Unexplained cases were 14%. Compared to local audits, the regional group attributed different causes of death in 17% of cases. At multivariate analysis, infections were associated with early stillbirths (OR 3.38, CI95% 1.62–7.03) and intrapartum cases (OR 6.64, CI95% 2.61–17.02). Placental disorders were related to growth restriction (OR 1.89, CI95% 1.06–3.36) and were more frequent before term (OR 1.86, CI95% 1.11–3.15). Stillbirths judged possibly/probably preventable with a different management (10.9%) occurred more frequently in non-Italian women and were mainly related to maternal disorders (OR 6.64, CI95% 2.61–17.02). Conclusions Regional Audit System for Stillbirth improves the registration of stillbirth and allows to define the causes of death. Moreover, sub-optimal care was recognized, allowing to identify populations which could benefit from preventive measures.

This study reviewed the literature about the diagnosis, antepartum surveillance, and time of delivery of fetuses suspected to be small for gestational age or growth restricted. Several guidelines have been issued by major professional organizations, including the International Society of Ultrasound in Obstetrics and Gynecology and the Society for Maternal-Fetal Medicine. The differences in recommendations, in particular about Doppler velocimetry of the ductus venosus and middle cerebral artery, have created confusion among clinicians, and this review has intended to clarify and highlight the available evidence that is pertinent to clinical management. A fetus who is small for gestational age is frequently defined as one with an estimated fetal weight of

OBJECTIVES: First, to compare published Doppler reference charts of the ratios of flow in the fetal middle cerebral and umbilical arteries (i.e. the cerebroplacental ratio (CPR) and umbilicocerebral ratio (UCR)). Second, to assess the association of thresholds of CPR and UCR based on these charts with short-term composite adverse perinatal outcome in a cohort of pregnancies considered to be at risk of late preterm fetal growth restriction. METHODS: Studies presenting reference charts for CPR or UCR were searched for in PubMed. Formulae for plotting the median and the 10th percentile (for CPR) or the 90th percentile (for UCR) against gestational age were extracted from the publication or calculated from the published tables. Data from a prospective European multicenter observational cohort study of singleton pregnancies at risk of fetal growth restriction at 32 + 0 to 36 + 6 weeks' gestation, in which fetal arterial Doppler measurements were collected longitudinally, were used to compare the different charts. Specifically, the association of UCR and CPR thresholds (CPR

OBJECTIVES: To explore the association between fetal umbilical and middle cerebral artery (MCA) Doppler abnormalities and outcome in late preterm pregnancies at risk of fetal growth restriction. METHODS: This was a prospective cohort study of singleton pregnancies at risk of fetal growth restriction at 32 + 0 to 36 + 6 weeks of gestation, enrolled in 33 European centers between 2017 and 2018, in which umbilical and fetal MCA Doppler velocimetry was performed. Pregnancies were considered at risk of fetal growth restriction if they had estimated fetal weight and/or abdominal circumference (AC)

Objective: Stillbirth is a potentially preventable complication of pregnancy. Identifying women at risk can guide decisions on closer surveillance or timing of birth to prevent fetal death.Prognostic models have been developed to predict the risk of stillbirth, but none have yet been externally validated. We externally validated published prediction models for stillbirth using individual participant data (IPD) meta-analysis to assess their predictive performance. Methods: We searched Medline, EMBASE, DH-DATA and AMED databases from inception to December 2020 to identify stillbirth prediction models. We included studies that developed or updated prediction models for stillbirth for use at any time during pregnancy. IPD from cohorts within the International Prediction of Pregnancy Complication (IPPIC) Network were used to externally validate the identified prediction models whose individual variables were available in the IPD. We assessed the risk of bias of the models and IPD using PROBAST, and reported discriminative performance using the C-statistic, and calibration performance using calibration plots, calibration slopeand calibration-in-the-large. We estimated performance measures separately in each study, and then summarised across studies using random-effects meta-analysis. Clinical utility was assessed using net benefit. Results: We identified 17 studies reporting the development of 40 prognostic models for stillbirth. None of the models were previously externally validated, and only a fifth (20%, 8/40) reported the full model equation. We were able to validate three of these models using the IPD from 19 cohort studies (491,201 pregnant women) within the IPPIC Network database. Based on evaluating their development studies, all three models had an overall high risk of bias according to PROBAST. In our IPD meta-analysis, the models had summary C-statistics ranging from 0.53 to 0.65; summary calibration slopes of 0.40to 0.88, and generally with observed risks predictions that were too extreme compared to observed risks; and little to no clinical utility as assessed by net benefit. However, there remained uncertainty in performance for some models due to small available sample sizes. Conclusion: The three validated models generally showed poor and uncertain predictive performancein new data, with limited evidence to support their clinical application. Findings suggest methodological shortcomings in their development including overfitting of models. Further research is needed to further validate these and other models, identify stronger prognostic factors, and to develop more robust prediction models