Clinical phenotypes for risk stratification in small-for-gestational-age fetuses.

OBJECTIVE: To evaluate whether clinical phenotypes of small-for-gestational-age (SGA) fetuses can be identified and used for adverse perinatal outcome risk stratification to facilitate clinical decision-making. METHODS: This was a multicenter observational cohort study conducted in two tertiary care university hospitals. SGA fetuses were classified according to maternal, fetal and placental conditions using a two-step cluster algorithm, in which fetuses with more than one condition were assigned to the cluster associated with the highest mortality risk. Delivery and perinatal outcomes were compared using chi-square test among SGA clusters, and the associations between outcomes and each cluster were evaluated by calculating odds ratios (OR), adjusted for gestational age. RESULTS: The study included 17 631 consecutive singleton pregnancies, of which 1274 (7.2%) were defined as SGA at birth according to INTERGROWTH-21st standards. Nine SGA clinical phenotypes were identified using a predefined conceptual framework. All delivery and perinatal outcomes analyzed were significantly different among the nine phenotypes. The whole SGA cohort had a three-times higher risk of perinatal mortality compared with non-SGA fetuses (1.4% vs 0.4%; P < 0.001). SGA clinical phenotypes exhibited three patterns of perinatal mortality risk: the highest risk was associated with congenital anomaly (8.3%; OR, 17.17 (95% CI, 2.17-136.12)) and second- or third-trimester hemorrhage (8.3%; OR, 9.94 (95% CI, 1.23-80.02)) clusters; medium risk was associated with gestational diabetes (3.8%; OR, 9.59 (95% CI, 1.27-72.57)), preterm birth (3.2%; OR, 4.65 (95% CI, 0.62-35.01)) and intrauterine growth restriction (3.1%; OR, 5.93 (95% CI, 3.21-10.95)) clusters; and the lowest risk was associated with the remaining clusters. Perinatal mortality rate did not differ between SGA fetuses without other clinical conditions (54.1% of SGA fetuses) and appropriate-for-gestational-age fetuses (0.1% vs 0.4%; OR, 0.41 (95% CI, 0.06-2.94); P = 0.27). SGA combined with other obstetric pathologies increased significantly the risk of perinatal mortality, as demonstrated by the increased odds of perinatal death in SGA cases with gestational diabetes compared to non-SGA cases with the same condition (OR, 24.40 (95% CI, 1.31-453.91)). CONCLUSIONS: We identified nine SGA clinical phenotypes associated with different patterns of risk for adverse perinatal outcome. Our findings suggest that considering clinical characteristics in addition to ultrasound findings could improve risk stratification and decision-making for management of SGA fetuses. Future clinical trials investigating management of fetuses with SGA should take into account clinical information in addition to Doppler parameters and estimated fetal weight. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.

Advanced maternal age and adverse pregnancy outcomes: A cohort study.

OBJECTIVES: To assess the association between advanced maternal age and adverse perinatal outcomes in single pregnancies. MATERIALS AND METHODS: A cohort study was conducted using data from 27,455 singleton births attended at our hospital between 2007 and 2018. Three maternal age groups were established, and perinatal outcomes were compared between-groups (<35 years (n = 19,429; 70.7%), 35-40 years (n = 7189; 26.2%), and >40 years (n = 846; 3.1%). The data were compared using chi-square analysis and the results were adjusted using a logistic regression model. Decision trees were designed to examine the fetal mortality and caesarean section variables. We used the SPSS 23 statistical software program for the statistical analysis. RESULTS: The mean age of the women was 31.21 years. No differences were found associated with age for neonatal acidosis, an Apgar score <7 at 5 min after birth, threatened preterm labour, preterm rupture of membranes, or high-grade perineal tear. The analyses found statistically significant increases in the rates of hypertensive disorders, diabetes mellitus, induction of labour, and caesarean section, after 35 years of age. The risks of fetal death, neonatal admission, small for gestational age, placenta previa, instrument delivery, maternal ICU admission, and postpartum haemorrhage were greater after 40 years of age. CONCLUSIONS: The results of our study indicated that women >35 years of age had worse perinatal outcomes, compared with younger women. This finding was more evident in patients >40 years of age, which highlighted the greater risk of fetal death and serious maternal complications in this group.

SARS-CoV-2 immunochromatographic IgM/IgG rapid test in pregnancy: A false friend?

BACKGROUND: An increasing body of evidence has revealed that SARS-CoV-2 infection in pregnant women could increase the risk of adverse maternal and fetal outcomes. Careful monitoring of pregnancies with COVID-19 and measures to prevent neonatal infection are warranted. Therefore, rapid antibody tests have been suggested as an efficient screening tool during pregnancy. CASES: We analysed the clinical performance during pregnancy of a rapid, lateral-flow immunochromatographic assay for qualitative detection of SARS-CoV-2 IgG/IgM antibodies. We performed a universal screening including 169 patients during their last trimester of pregnancy. We present a series of 14 patients with positive SARS-CoV-2 immunochromatographic assay rapid test result. Immunochromatographic assay results were always confirmed by chemiluminescent microparticle immunoassays for quantitative detection of SARS-CoV-2 IgG and IgM+IgA antibodies as the gold standard. We observed a positive predictive value of 50% and a false positive rate of 50% in pregnant women, involving a significantly lower diagnostic performance than reported in non-pregnant patients. DISCUSSION: Our data suggest that although immunochromatographic assay rapid tests may be a fast and profitable screening tool for SARS-CoV-2 infection, they may have a high false positive rate and low positive predictive value in pregnant women. Therefore, immunochromatographic assay for qualitative detection of SARS-CoV-2 IgG/IgM antibodies must be verified by other test in pregnant patients.

Clinical impact of Doppler reference charts on management of small-for-gestational-age fetuses: need for standardization.

OBJECTIVE: To assess clinical variability in the management of small-for-gestational-age (SGA) fetuses according to different published Doppler reference charts for umbilical artery (UA) and fetal middle cerebral artery (MCA) Doppler indices and cerebroplacental ratio (CPR). METHODS: We performed a systematic search of MEDLINE, EMBASE, CINAHL and the Web of Science databases from 1954 to 2018 for studies with the sole aim of creating fetal Doppler reference values for UA, MCA and CPR. The top cited articles for each Doppler parameter were included. Variability in Doppler values at the following clinically relevant cut-offs was assessed: UA-pulsatility index (PI) > 95th percentile; MCA-PI < 5th percentile; and CPR < 5th percentile. Variability was calculated for each week of gestation and expressed as the percentage difference between the highest and lowest Doppler value at the clinically relevant cut-offs. Simulation analysis was performed in a cohort of SGA fetuses (n = 617) to evaluate the impact of this variability on clinical management. RESULTS: From a total of 40 studies that met the inclusion criteria, 19 were analyzed (13 for UA-PI, 10 for MCA-PI and five for CPR). Wide discrepancies in reported Doppler reference values at clinically relevant cut-offs were found. MCA-PI showed the greatest variability, with differences of up to 51% in the 5th percentile value at term. Variability in the 95th percentile of UA-PI and the 5th percentile of CPR at each gestational week ranged from 21% to 41% and 15% to 33%, respectively. As expected, on simulation analysis, these differences in Doppler cut-off values were associated with significant variation in the clinical management of SGA fetuses, despite using the same protocol. CONCLUSIONS: The choice of Doppler reference chart can result in significant variation in the clinical management of SGA fetuses, which may lead to suboptimal outcomes and inaccurate research conclusions. Therefore, an attempt to standardize fetal Doppler reference ranges is needed. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

An objective scoring method to evaluate image quality of middle cerebral artery Doppler.

Objective: To validate an objective scoring system for middle cerebral artery (MCA) pulsed wave Doppler images.Method: From an image database of routine 36-week scans, a random sample of MCA Doppler images was selected. Two reviewers rated the images subjectively as acceptable or unacceptable. Subsequently they used an objective 6-point image scoring system and awarded one point for each of the following: (1) anatomical site, (2) magnification, (3) angle of insonation, (4) image clarity, (5) sweep speed adjustment, and (6) velocity scale and baseline adjustment. Image scores 4-6 were defined as good quality whereas 0-3 as poor. The subjective and objective agreement between the two reviewers was compared using the adjusted Kappa statistic.Results: A total of 124 images were assessed. Using objective scoring the agreement rate between reviewers increased to 91.9% (κ = 0.839) compared to subjective agreement 75.8% (κ = 0.516). The agreement for each criterion was: anatomical site 91.1% (κ = 0.823), magnification 95.2% (κ = 0.903), clarity 83.9% (κ = 0.677), angle 96.0% (κ = 0.919), sweep speed 98.4% (κ = 0.968), and velocity scale and baseline 94.4% (κ = 0.887).Conclusion: Objective assessment of MCA Doppler images using a 6-point scoring system has greater interobserver agreement than subjective assessment and could be used for MCA Doppler quality assurance.

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.