Reference ranges for Doppler indices of umbilical and fetal middle cerebral arteries and cerebroplacental ratio: systematic review.

OBJECTIVE: To assess studies reporting reference ranges for umbilical artery (UA) and fetal middle cerebral artery (MCA) Doppler indices and cerebroplacental ratio (CPR), using a set of predefined methodological quality criteria for study design, statistical analysis and reporting methods. METHODS: This was a systematic review of observational studies in which the primary aim was to create reference ranges for UA and MCA Doppler indices and CPR in fetuses of singleton gestations. A search for relevant articles was performed in MEDLINE, EMBASE, CINAHL, Web of Science (from inception to 31 December 2016) and references of the retrieved articles. Two authors independently selected studies, assessed the risk of bias and extracted the data. Studies were scored against a predefined set of independently agreed methodological criteria and an overall quality score was assigned to each study. Linear multiple regression analysis assessing the association between quality scores and study characteristics was performed. RESULTS: Thirty-eight studies met the inclusion criteria. The highest potential for bias was noted in the following fields: 'ultrasound quality control measures', in which only two studies demonstrated a comprehensive quality-control strategy; 'number of measurements taken for each Doppler variable', which was apparent in only three studies; 'sonographer experience', in which no study on CPR reported clearly the experience or training of the sonographers, while only three studies on UA Doppler and four on MCA Doppler did; and 'blinding of measurements', in which only one study, on UA Doppler, reported that sonographers were blinded to the measurement recorded during the examination. Sample size estimations were present in only seven studies. No predictors of quality were found on multiple regression analysis. Reference ranges varied significantly with important clinical implications for what is considered normal or abnormal, even when restricting the analysis to the highest scoring studies. CONCLUSIONS: There is considerable methodological heterogeneity in studies reporting reference ranges for UA and MCA Doppler indices and CPR, and the resulting references have important implications for clinical practice. There is a need for the standardization of methodologies for Doppler velocimetry and for the development of reference standards, which can be correctly interpreted and applied in clinical practice. We propose a set of recommendations for this purpose. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd.

Intervalos de referencia para los índices Doppler de la arterias umbilical y cerebral media del feto y la relación cerebroplacentaria: una revisión sistemática OBJETIVO: Evaluar los estudios que informan sobre intervalos de referencia para los índices Doppler y la relación cerebroplacentaria (RCP) de la arteria umbilical (AU) y la arteria cerebral media (ACM) del feto, mediante un conjunto de criterios de calidad metodológica predefinidos para el diseño del estudio, el análisis estadístico y los métodos de notificación. MÉTODOS: Esta fue una revisión sistemática de estudios observacionales en los que el objetivo principal fue crear intervalos de referencia para los índices Doppler de la AU y la ACM y la RCP de fetos de gestaciones con feto único. Se realizó una búsqueda de artículos relevantes en MEDLINE, EMBASE, CINAHL, Web of Science (desde el inicio hasta el 31 de diciembre de 2016) y en las referencias de los artículos recuperados. Dos autores, de forma independiente, seleccionaron los estudios, evaluaron el riesgo de sesgo y extrajeron los datos. Los estudios se calificaron según un conjunto predefinido de criterios metodológicos acordados de forma independiente y se asignó una puntuación de calidad global a cada estudio. Se realizó un análisis de regresión múltiple lineal para evaluar la asociación entre las puntuaciones de calidad y las características del estudio. RESULTADOS: Un total de 38 estudios cumplieron los criterios de inclusión. El mayor potencial de sesgo se observó en los siguientes casos: 'medidas de control de calidad del ultrasonido', donde sólo dos estudios demostraron una estrategia integral de control de calidad; 'número de mediciones tomadas para cada variable Doppler', que solo fue aparente en tres estudios; 'experiencia del ecografista', puesto que ningún estudio sobre la RCP informó claramente sobre la experiencia o la formación de los ecografistas, y tan solo lo hicieron tres estudios sobre el Doppler de la AU y cuatro sobre el Doppler de la ACM; y 'mediciones a ciegas', donde tan sólo un estudio sobre el Doppler de la AU comunicó que los ecografistas no tuvieron acceso a la medición registrada durante el estudio. Las estimaciones del tamaño de la muestra sólo se comunicaron en siete estudios. No se encontraron predictores de calidad en el análisis de regresión múltiple. Los intervalos de referencia variaron significativamente con implicaciones clínicas importantes para lo que se considera normal o anómalo, incluso cuando se restringió el análisis a los estudios con mayor puntuación. CONCLUSIONES: Existe una heterogeneidad metodológica considerable en los estudios que informan sobre los intervalos de referencia para los índices Doppler de la AU y la ACM y la RCP, y las referencias resultantes tienen implicaciones importantes para la práctica clínica. Es necesario estandarizar las metodologías de la velocimetría Doppler y desarrollar estándares de referencia que puedan ser interpretados y aplicados correctamente en la práctica clínica. Se propone una serie de recomendaciones para este fin.

Modeling Pulsatility Index nomograms from different maternal and fetal vessels by quantile regression at 24-40 weeks of gestation: a prospective cross-sectional study.

OBJECTIVE: Recent evidences highlight a considerable heterogeneity in the methodology of previously published studies reporting reference ranges for maternal and fetal Dopplers, which may have relevant implications in clinical practice. In view of these limitations, a standardized methodology to construct Doppler charts has been proposed. The aim of this study was to develop charts for pulsatility index (PI) of maternal and fetal Dopplers based upon the recently proposed standardized methodology and using quantile regression. METHODS: Prospective cross-sectional study including 2516 low-risk singleton pregnancies between 24 and 40 weeks of gestation. The mean uterine, umbilical (UA), middle cerebral (MCA) and their ratio (cerebroplacental ratio, CPR) centile values were established by quantile regression in the considered gestational interval. Interclass correlation coefficient (ICC) of each maternal and fetal vessel was also computed to assess the intra- and inter-observer agreement of the results. RESULTS: There was a good intra- and inter-observer agreement for each of the explored vessels (ICC >0.92 and >0.91 for a single and two observers, respectively). The 5th, 10th, 50th, 90th and 95th centiles of the reference range for gestation were constructed by quantile regression and compared to previously established reference charts. All the Doppler indices significantly changed with gestation. Second-degree polynomial regression models better described the changes with gestation in PCR and MCA PI values while a linear model better predicted the changes of other Doppler indices with advancing gestation. When compared to other studies reporting reference ranges for maternal and fetal Dopplers, the present charts showed similar median values but different distribution from the median. CONCLUSIONS: We provided prospective charts of maternal and fetal Dopplers based upon a previously proposed standardized methodology and using quantile regression. When compared to previously published studies, these new charts showed similar median values but different deviations from the median which may help in better differentiating cases at higher risk of placental insufficiency and adverse perinatal outcome.