Diagnostic accuracy of prenatal ultrasound in coarctation of aorta: systematic review and individual participant data meta‐analysis

Objective: To determine the diagnostic accuracy of prenatal ultrasound in detecting coarctation of the aorta (CoA). Methods: An individual participant data meta-analysis was performed to report on the strength of association and diagnostic accuracy of different ultrasound signs in detecting CoA prenatally. MEDLINE, EMBASE and CINAHL were searched for studies published between January 2000 and November 2021. Inclusion criteria were fetuses with suspected isolated CoA, defined as ventricular and/or great vessel disproportion with right dominance on ultrasound assessment. Individual participant-level data were obtained by two leading teams. PRISMA-IPD and PRISMA-DTA guidelines were used for extracting data, and the QUADAS-2 tool was used for assessing quality and applicability. The reference standard was CoA, defined as narrowing of the aortic arch, diagnosed after birth. The most commonly evaluated parameters on ultrasound, both in B-mode and on Doppler, constituted the index test. Summary estimates of sensitivity, specificity, diagnostic odds ratio (DOR) and likelihood ratios were computed using the hierarchical summary receiver-operating-characteristics model. Results: The initial search yielded 72 studies, of which 25 met the inclusion criteria. Seventeen studies (640 fetuses) were included. On random-effects logistic regression analysis, tricuspid valve/mitral valve diameter ratio > 1.4 and > 1.6, aortic isthmus/arterial duct diameter ratio 1.4 (P = 0.048) and bidirectional flow at the foramen ovale (P = 0.012) were independently associated with CoA. Redundant foramen ovale was inversely associated with CoA (P = 0.037). Regarding diagnostic accuracy, tricuspid valve/mitral valve diameter ratio > 1.4 had a sensitivity of 72.6% (95% CI, 48.2-88.3%), specificity of 65.4% (95% CI, 46.9-80.2%) and DOR of 5.02 (95% CI, 1.82-13.9). The sensitivity and specificity values were, respectively, 75.0% (95% CI, 61.1-86.0%) and 39.7% (95% CI, 27.0-53.4%) for pulmonary artery/ascending aorta diameter ratio > 1.4, 47.8% (95% CI, 14.6-83.0%) and 87.6% (95% CI, 27.3-99.3%) for aortic isthmus diameter Z-score of < -2 in the sagittal view and 74.1% (95% CI, 58.0-85.6%) and 62.0% (95% CI, 41.6-78.9%) for aortic isthmus diameter Z-score of < -2 in the three-vessel-and-trachea view. Hypoplastic aortic arch had a sensitivity of 70.0% (95% CI, 42.0-88.6%), specificity of 91.3% (95% CI, 78.6-96.8%) and DOR of 24.9 (95% CI, 6.18-100). The diagnostic yield of prenatal ultrasound in detecting CoA did not change significantly when considering multiple categorical parameters. Five of the 11 evaluated continuous parameters were independently associated with CoA (all P < 0.001) but all had low-to-moderate diagnostic yield. Conclusions: Several prenatal ultrasound parameters are associated with an increased risk for postnatal CoA. However, diagnostic accuracy is only moderate, even when combinations of parameters are considered. © 2024 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.Depto. de MedicinaDepto. de Salud Pública y Materno - InfantilFac. de MedicinaTRUEpubAPC financiada por la UC

The role of the T-cell mediated immune response to Cytomegalovirus infection in intrauterine transmission

IntroductionPrognostic markers for fetal transmission of Cytomegalovirus (CMV) infection during pregnancy are poorly understood. Maternal CMV-specific T-cell responses may help prevent fetal transmission and thus, we set out to assess whether this may be the case in pregnant women who develop a primary CMV infection. MethodsA multicenter prospective study was carried out at 8 hospitals in Spain, from January 2017 to April 2020. Blood samples were collected from pregnant women at the time the primary CMV infection was diagnosed to assess the T-cell response. Quantitative analysis of interferon producing specific CMV-CD8(+)/CD4(+) cells was performed by intracellular cytokine flow cytometry. ResultsIn this study, 135 pregnant women with a suspected CMV infection were evaluated, 60 of whom had a primary CMV infection and samples available. Of these, 24 mothers transmitted the infection to the fetus and 36 did not. No association was found between the presence of specific CD4 or CD8 responses against CMV at the time maternal infection was diagnosed and the risk of fetal transmission. There was no transmission among women with an undetectable CMV viral load in blood at diagnosis. ConclusionsIn this cohort of pregnant women with a primary CMV infection, no association was found between the presence of a CMV T-cell response at the time of maternal infection and the risk of intrauterine transmission. A detectable CMV viral load in the maternal blood at diagnosis of the primary maternal infection may represent a relevant biomarker associated with fetal transmission.Instituto de Salud Carlos III Spanish Government (19/01333)DBG, from Spanish Ministry of Science and Innovation Instituto de Salud Carlos III (INT20/00086)3.7 Q2 JCR 20220.885 Q1 SJR 2022No data IDR 2022UE

Prediction of postnatal circulation in pulmonary atresia/critical stenosis with intact ventricular septum: systematic review and external validation of models

ObjectiveA favorable postnatal prognosis in cases ofpulmonary atresia/critical stenosis with intact ventricu-lar septum (PA/CS-IVS) is generally equated with thepossibility of achieving biventricular (BV) repair. Identi-fication of fetuses that will have postnatal univentricular(UV) circulation is key for prenatal counseling, opti-mization of perinatal care and decision-making regardingfetal therapy. We aimed to evaluate the accuracy ofCorrespondence to:Dr C. Villala ́ın, Department of Obstetrics and Gynecology, Hospital Universitario 12 de Octubre, Avenida de C ́ordoba,Madrid 28041, Spain (e-mail: [email protected])Accepted: 23 January 2023published models for predicting postnatal circulation inPA/CS-IVS using a large internationally derived validationcohort.MethodsThis was a systematic review of publisheduni- and multiparametric models for the predictionof postnatal circulation based on echocardiographicfindings at between 20 and 28 weeks of gestation.Models were externally validated using data fromthe International Fetal Cardiac Intervention Registry.Sensitivity, specificity, predictive values, area underthe receiver-operating-characteristics curves (AUCs) andproportion of cases with truevspredicted outcome werecalculated.ResultsEleven published studies that reported prog-nostic parameters of postnatal circulation were iden-tified. Models varied widely in terms of the mainoutcome (UV (n=3), non-BV (n=3), BV (n=3),right-ventricle-dependent coronary circulation (n=1) ortricuspid valve size at birth (n=1)) and in terms ofthe included predictors (single parameters only (n=6),multiparametric score (n=4) or both (n=1)), and weredeveloped on small sample sizes (range, 15 – 38). Ninemodels were validated externally given the availability ofthe required parameters in the validation cohort. Tricus-pid valve diameterZ-score, tricuspid regurgitation, ratiosbetween right and left cardiac structures and the presence. Postnatal circulation in pulmonary atresia15of ventriculocoronary connections (VCC) were the mostcommonly evaluated parameters. Multiparametric mod-els including up to four variables (ratios between rightand left structures, right ventricular inflow duration, pres-ence of VCC and tricuspid regurgitation) had the bestperformance (AUC, 0.80 – 0.89). Overall, the risk of UVoutcome was underestimated and that of BV outcomewas overestimated by most models.ConclusionsCurrent prenatal models for the predictionof postnatal outcome in PA/CS-IVS are heterogeneous.Multiparametric models for predicting UV and non-BVcirculation perform well in identifying BV patients buthave low sensitivity, underestimating the rate of fetusesthat will ultimately have UV circulation. Until betterdiscrimination can be achieved, fetal interventions mayneed to be limited to only those cases in which non-BVpostnatal circulation is certain.Objetivo.Un pron ́ostico postnatal favorable en casos de atresia pulmonar/estenosis cr ́ıtica con tabique interventricularintacto (PA/CS-IVS, por sus siglas en ingl ́es) se equipara generalmente con la posibilidad de lograr una reparaci ́onbiventricular (BV). La identificaci ́on de los fetos que tendr ́an circulaci ́on univentricular (UV) postnatal es clave parael asesoramiento prenatal, la optimizaci ́on de los cuidados perinatales y la toma de decisiones relativas a la terapiafetal. El objetivo fue evaluar la precisi ́on de los modelos publicados para predecir la circulaci ́on postnatal en casos dePA/CS-IVS utilizando para ello una gran cohorte de validaci ́on estimada a partir de datos internacionales.M ́etodos.El estudio consisti ́oenunarevisi ́on sistem ́atica de los modelos uni- y multiparam ́etricos publicados para lapredicci ́on de la circulaci ́on postnatal basados en los hallazgos ecocardiogr ́aficos entre las semanas 20 y 28 de gestaci ́on.Los modelos se validaron externamente utilizando datos del Registro Internacional de Intervenciones Card ́ıacas Fetales.Se calcularon la sensibilidad, la especificidad, los valores predictivos, el ́area bajo las curvas (ABC) de caracter ́ısticasoperativas del receptor y la proporci ́on de casos con resultado verdadero frente a resultado pronosticado.Resultados.Se identificaron once estudios publicados en los que se hab ́ıan reportado par ́ametros pron ́osticos de lacirculaci ́on postnatal. Los modelos variaron ampliamente en cuanto al resultado principal (UV (n=3), no-BV (n=3), BV(n=3), la circulaci ́on coronaria dependiente del ventr ́ıculo derecho (n=1)oeltama ̃no de la v ́alvula tric ́uspide al nacer(n=1)) y en cuanto a los predictores incluidos (s ́olo par ́ametros ́unicos (n=6), puntuaci ́on multiparam ́etrica (n=4) oambos (n=1)), y se desarrollaron a partir de muestras peque ̃nas (rango, 15 – 38).Dada la disponibilidad de los par ́ametros requeridos en la cohorte de validaci ́on, se validaron externamente nuevemodelos. La puntuaci ́on est ́andar (Z) del di ́ametro de la v ́alvula tric ́uspide, la insuficiencia tricusp ́ıdea, los cocientesentre las estructuras card ́ıacas derecha e izquierda y la presencia de conexiones ventr ́ıculo-coronarias (CVC) fueronlos par ́ametros evaluados con mayor frecuencia. El mejor desempe ̃no (ABC, 0,80 – 0,89) correspondi ́o a los modelosmultiparam ́etricos que inclu ́ıan hasta cuatro variables (cocientes entre las estructuras derecha e izquierda, duraci ́on delinflujo ventricular derecho, presencia de CVC e insuficiencia tricusp ́ıdea). En general, en la mayor ́ıa de los modelos sesubestim ́o el riesgo del resultado UV y se sobreestim ́oeldelresultadoBV.Conclusiones.Los modelos prenatales actuales para la predicci ́on del resultado postnatal en la PA/CS-IVS sonheterog ́eneos. Los modelos multiparam ́etricos para predecir la circulaci ́on UV y no-BV funcionan bien para laidentificaci ́on de pacientes BV, pero tienen una sensibilidad baja, que subestima la tasa de fetos que finalmente tendr ́ancirculaci ́on UV. Hasta que se consiga una mejor forma para poder discriminar entre casos, puede ser necesario limitarlas intervenciones fetales ́unicamente a aquellos en los que est ́e asegurado que la circulaci ́on postnatal es no-BV.©2023 The Authors.Ultrasound in Obstetrics & Gynecologypublished by John Wiley &SYSTEMATIC REVIEWSons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.Depto. de MedicinaFac. de MedicinaTRUEpubAPC financiada por la UC