"Screening for small-for-gestational age neonates at early third trimester in a high-risk population for preeclampsia".

BACKGROUND: Strategies to improve prenatal detection of small-for-gestational age (SGA) neonates are necessary because its association with poorer perinatal outcome. This study evaluated, in pregnancies with first trimester high risk of early preeclampsia, the performance of a third trimester screening for SGA combining biophysical and biochemical markers. METHODS: This is a prospective longitudinal study on 378 singleton pregnancies identified at high risk of early preeclampsia according to a first trimester multiparametric algorithm with the cutoff corresponding to 15% false positive rate. This cohort included 50 cases that delivered SGA neonates with birthweight < 10th centile (13.2%) and 328 cases with normal birthweight (86.8%). At 27-30 weeks' gestation, maternal weight, blood pressure, estimated fetal weight, mean uterine artery pulsatility index and maternal biochemical markers (placental growth factor and soluble FMS-Like Tyrosine Kinase-1) were assessed. Different predictive models were created to evaluate their performance to predict SGA neonates. RESULTS: For a 15% FPR, a model that combines maternal characteristics, estimated fetal weight, mean uterine artery pulsatility index and placental growth factor achieved a detection rate (DR) of 56% with a negative predictive value of 92.2%. The area under receiver operating characteristic curve (AUC) was 0.79 (95% confidence interval (CI), 0.72-0.86). The DR of a model including maternal characteristics, estimated fetal weight and mean uterine artery pulsatility index was 54% (AUC, 0.77 (95% CI, 0.70-0.84)). The DR of a model that includes maternal characteristics and placental growth factor achieved a similar performance (DR 56%, AUC 0.75, 95% CI (0.67-0.83)). CONCLUSIONS: The performance of screening for SGA neonates at early third trimester combining biophysical and biochemical markers in a high-risk population is poor. However, a high negative predictive value could help in reducing maternal anxiety, avoid iatrogenic interventions and propose a specific plan for higher risk patients.

Nuchal translucency thickness in the prediction of unbalanced translocations.

OBJECTIVE: The aim of this study was to assess the role of nuchal translucency (NT) in the prediction of unbalanced translocation in offspring of couples in which one of the parents is a balanced translocation carrier. MATERIAL AND METHODS: From January 1996 to December 2012, fetal NT was measured before chorionic villus sampling in 86 pregnancies referred because of parental balanced translocation. RESULTS: No significant differences in pregnancy characteristics and in NT expressed in millimetres or in multiples of the median (MoMs) were observed between the 41 fetuses with a normal karyotype [1.72 mm, 95% confidence interval (CI): 1.49-1.96; 1.14 MoM; 95% CI: 1.01-1.26], the 38 fetuses with balanced translocations (1.78 mm, 95% CI: 1.44-2.12; 1.22 MoM; 95% CI: 1.01-1.43) and the 7 fetuses with unbalanced translocations (2.21 mm, 95% CI: 1.33-3.09; 1.59 MoM; 95% CI: 0.72-2.45). The proportions of fetuses with NT above 95th centile in the three groups were 9.1% in fetuses with normal karyotype, 18.4% in balanced translocations and 28.6% in unbalanced translocations, not significantly different. CONCLUSION: Although a trend to an increased NT was observed in fetuses with unbalanced translocation, no significant differences were reached. According to our results, a normal NT evaluation should not preclude the performance of CVS in pregnancies of balanced translocation parents.

Performance of a first-trimester screening of preeclampsia in a routine care low-risk setting.

OBJECTIVE: We sought to evaluate the effectiveness of an integrated first-trimester screening test to predict preeclampsia (PE). STUDY DESIGN: A prospective cohort of singleton pregnancies underwent routine first-trimester screening from 2009 through 2011 (n = 5759). A logistic regression-based predictive model for early- and late-onset PE was constructed based on: maternal characteristics; levels of pregnancy-associated plasma protein-A and free ß-human chorionic gonadotropin at 8-12 weeks; and blood pressure and uterine artery Doppler at 11.0-13.6 weeks. RESULTS: Of the 5170 enrolled participants, 136 (2.6%) developed PE (early PE: 26 [0.5%]; late PE: 110 [2.1%]). At 5% and 10% false-positive rates, detection rates were 69.2% and 80.8% for early PE (area under the curve, 0.95; 95% confidence interval, 0.94-0.98) and 29.4% and 39.6% for late PE (area under the curve, 0.71; 95% confidence interval, 0.66-0.76), respectively. CONCLUSION: First-trimester screening combining maternal factors with uterine artery Doppler, blood pressure, and pregnancy-associated plasma protein-A is useful to predict PE in a routine care setting.

Likelihood ratios to apply for nasal bone, ductus venosus and tricuspid flow at the 11-13 weeks' scan in down syndrome screening.

OBJECTIVE: To assess the feasibility of nasal bone (NB), ductus venosus (DV) and tricuspid flow (TF) at the 11-13 weeks' scan, calculate likelihood ratios for each of the markers and evaluate their efficacy in expanded and contingent screening strategies for Down syndrome. MATERIAL AND METHODS: NB, DV and TF were assessed in 11,261 singleton fetuses undergoing first trimester combined screening. For each marker, Down syndrome detection rate (DR), false positive rate (FPR), positive, negative and isolated likelihood ratios (PLR, NLR and iLR) were calculated. Likelihood ratios were multiplied to the combined test risk either to the entire population or to the intermediate risk group (expanded and sequential strategies, respectively). RESULTS: Down syndrome was diagnosed in 101 pregnancies. Feasibility for marker assessment ranged from 71 to 97%, DRs for isolated markers from 20 to 54% and FPRs from 1.3 to 5.3%. PLR ranged from 10 to 15, NLR from 0.5 to 0.8 and iLR from 3.9 to 5.6. When ultrasound markers were added to both strategies, a significant FPR reduction was observed. CONCLUSION: The application of NB, DV and TF likelihood ratios to the combined test risk, either in an expanded or contingent strategy, result in a FPR reduction.

Increased fetal brain perfusion and neonatal neurobehavioral performance in normally grown fetuses.

OBJECTIVE: To explore the association between fetal cerebroplacental ratio (CPR) and frontal brain perfusion at third trimester with neonatal neurobehavioral performance in normally grown fetuses. METHODS: CPR and frontal brain perfusion measured by fractional moving blood volume (FMBV) were assessed in 258 consecutive healthy fetuses at routine third trimester scan (32-35.6 weeks). Neonates were evaluated with the Neonatal Behavioral Assessment Scale. The association between Doppler parameters and neurobehavior was analyzed by MANCOVA (multiple analysis of covariance) and logistic regression, with adjustment for smoking, socioeconomic class, mode of delivery, gestational age at birth, postnatal days at examination and gender. RESULTS: Fetuses with increased FMBV (in the upper quartile) had lower neurobehavioral scores in all areas, reaching significance in motor (5.6 vs. 5.8; p = 0.049), social (6 vs. 6.4; p = 0.006) and attention (5.3 vs. 5.9; p = 0.032). Fetuses with increased FMBV had higher risk of abnormal (<10th centile) motor (OR 3.3; 95% CI 1.36-8.1), social (OR 2.9; 95 CI% 1.33-6.5) and attention (OR 2.5; 95% CI 1.1-5.8) scores. Fetuses with lower CPR (in the lower quartile) did not differ in their neurobehavioral scores from those with normal values. CONCLUSIONS: Normally grown fetuses with increased frontal brain perfusion have poorer neurobehavioral competences, suggesting a disrupted neurological maturation. The results support the existence of forms of placental insufficiency not detected by current definitions of growth restriction.

Angiogenic factors assessment in pre-eclampsia high-risk population for the prediction of small-for-gestational age neonates: A prospective longitudinal study.

OBJECTIVE: The authors aimed to compare cross-sectional versus longitudinal models for prediction of small-for-gestational age (SGA) neonates among pregnancies with high risk of early pre-eclampsia (PE). METHODS: A prospective longitudinal study was performed in Hospital Universitari Dexeus, Barcelona. The study population included 390 pregnancies with a high risk of early PE according to the first trimester algorithm. Cross-sectional models combining first trimester risk plus placental growth factor and FMS-like tyrosine kinase 1/placental growth factor ratio, respectively, were created at 19-22, 24-26, and 27-30 weeks and compared with a model assessing longitudinal changes of these parameters. Models adding mean uterine artery pulsatility index and abdominal circumference were evaluated. SGA neonates were defined as having a birth weight less than the tenth centile. RESULTS: The predictive performance of a model assessing longitudinal changes of angiogenic factors was similar to that of single evaluations at the second and early third trimesters. The performance of the models combining angiogenic factors with mean uterine artery pulsatility index and abdominal circumference was better than those using only biochemical markers. However, the longitudinal evaluation of biochemical and biophysical parameters did not perform better than cross-sectional evaluations. CONCLUSIONS: Evaluation of angiogenic factors are useful for prediction of SGA neonates in a high-risk population for early PE. However, longitudinal models do not increase their predictive capacity.

Use of fetal nuchal translucency in the first trimester to predict single-gene disorders.

OBJECTIVE: To assess the predictive value of fetal nuchal translucency (NT) measurement in the prenatal diagnosis of single-gene disorders. METHODS: From January 1996 to December 2006, fetal NT was prospectively measured before chorionic villi sampling in 169 pregnancies at high risk for a single-gene disorder at 11 to 13 weeks of pregnancy. RESULTS: No differences were found between the 63 affected and 116 nonaffected fetuses in pregnancy demographic characteristics, in mean NT measurements, expressed either in millimetres [1.8 (95% CI:1.6-1.9) vs 1.7 (95% CI:1.6-1.8)] or in multiples of the median [1.19 (95%CI: 1.04-1.35) vs 1.14 (95%CI: 1.05-1.23)], or in median NT. The percentage of increased NT above the 95(th) percentile was similar for affected (9.5%) and nonaffected (11.2%) fetuses. CONCLUSION: Not all single-gene disorders are associated with enlarged NT, therefore NT cannot be regarded as a generic marker for single-gene disorder but only for a limited number of these conditions.

Prognostic role of uterine artery Doppler in patients with preeclampsia.

OBJECTIVES: To evaluate the predictive capacity of umbilical, cerebral and uterine artery Doppler in women admitted for preeclampsia (PE). METHODS: 190 consecutive singleton pregnancies admitted with PE were included. Umbilical, cerebral and uterine artery Dopplers were performed. The association with adverse perinatal outcome was evaluated from 2 x 2 tables and multivariately by logistic regression. RESULTS: A total of 82 (43%) women had an abnormal uterine artery Doppler on admission, being more prevalent in early-onset (<32 weeks) than in the late-onset PE (62 vs. 27%, p < 0.05). In both early- and late-onset forms, uterine artery Doppler showed a greater capacity than umbilical and middle cerebral artery Doppler for predicting adverse perinatal outcome. CONCLUSION: Uterine artery Doppler was the best predictive parameter for perinatal outcome in pregnancies with PE and may be included as a primary surveillance test.

Strategies for the prediction of late preeclampsia.

Objectives: To evaluate different strategies for the prediction of late preeclampsia. Methods: A retrospective study was undertaken. A predictive model including maternal parameters (maternal age, maternal BMI, maternal history of preeclampsia or intrauterine growth restriction (PE/IUGR) or maternal chronic disease, and maternal arterial pressure) and mean pulsatility index (PI) of uterine Doppler was created. It was evaluated as an independent model in each trimester, considering 11-13.6 weeks, 20-22.6 weeks and 32-33.6 weeks consequently, and as an integrated model. Results: In the group of late preeclampsia, patients were more obese and had higher incidence of chronic hypertension. Uterine artery pulsatility index (UtA PI) and mean blood pressure were increased in all three trimesters. When evaluating all three models independently, third trimester model performed better than the other two with a sensitivity of 79% and specificity of 82%. The area under the receiver-operating characteristic (ROC) curve (AUC) was 0.86. The integration of all three determinations did not improve third trimester's model. Conclusion: Prediction of late preeclampsia at third trimester seems to be possible if maternal characteristics, blood pressure and UtA Doppler are included.

Transcervical chorionic villus sampling: a practical guide.

First trimester screening for fetal aneuploidies has made the implementation of diagnostic techniques essential. Chorionic villus sampling (CVS) is the method of choice for obtaining chorionic villi for molecular and cytogenetic analysis in the first trimester. Two techniques have been developed, a transcervical and a transabdominal. The selection criteria have been based historically on factors, such as placental location, parity, maternal weight and preference of the operator. In our institution, we developed an elevated level of expertise in the field of transcervical approach, resulting in good quality of samples and comparable fetal loss rate to other approaches. Despite three decades of transcervical CVS performance, little consensus in terms of its technique and clinical guidelines exists. Considering the expertise and the volume of procedures performed at our center, we suggest a practical clinical guideline for transcervical CVS.

Colposcopy prediction of progression in human papillomavirus infections with minor cervical lesions.

OBJECTIVES: To evaluate the risk of progression to cervical intraepithelial neoplasia (CIN) grade 2 or 3 in women with positive human papillomavirus (HPV) testing and low-grade (low-grade squamous intraepithelial lesions), borderline (atypical squamous cells of undetermined significance), or no cervical lesions, and to determine the accuracy of initial colposcopy to predict progression. METHODS: Women with HPV infection and low-grade squamous intraepithelial lesions, atypical squamous cells, or normal cytology were recruited and grouped according to cytologic or histologic diagnosis. Exclusion criteria were histologic CIN 2 or 3, previous cervical cancer and HPV infection, cervical disease, or treatment for CIN 2 or 3 in the past 3 years. Four-hundred sixty-five women were included and monitored by cytology, Hybrid Capture-2 test, and colposcopy every 6 months. Colposcopy results were described as normal, with minor or major changes, and lesion size was recorded in quadrants. RESULTS: Forty-three women (9.3%) had progression to CIN 2 or 3. No significant differences were found in rate of progression between women with low-grade squamous intraepithelial lesions, atypical squamous cells, or negative results (8.2%, 13.4%, and 9.8%, respectively; P=.679). Neither colposcopy pattern (P=.284) nor lesion size (P=.170) at recruitment provided any information on the risk of progression. History of cervical lesion and worsening of the colposcopy pattern during follow-up were associated with progression (P<.001). CONCLUSION: Initial colposcopy findings do not provide relevant information on the risk of progression in HPV-positive women with minor or no cervical lesions. These women have a similar risk of progression and should benefit from the same follow-up strategies.

Aportación del Doppler de la arteria cerebral media y del genotipado RHD fetal en el manejo de la isoinmunización / Contribution of middle cerebral artery Doppler and fetal RHD genotype in the management of alloimmunization

Objetivo. Evaluar la aplicación clínica de los métodos no invasivos en el manejo de la isoinmunización, durante el período de 2006-2010. Sujetos y métodos. Se estudiaron 70 gestaciones con riesgo de anemia fetal en las que se realizó el estudio Doppler de la velocidad sistólica de la arteria cerebral media (VS-ACM). Se comparó la eficacia de la VS-ACM después de una, 2 o 3 transfusiones intrauterinas. El genotipado fetal RHD en sangre materna se realizó en las gestaciones seguidas en nuestro centro. Resultados. Se practicó cordocentesis en 22 de gestaciones y en 20 se practicó transfusión intrauterina. Las tasas de detección y de falsos positivos de la VS-ACM en la predicción de anemia fetal moderada o severa fueron del 89 y el 15% en gestaciones sin transfusión previa, del 100 y el 41% en los casos con una transfusión previa y del 40 y el 24% cuando se practicaron más de una transfusión. Conclusiones. La VS-ACM mantiene una sensibilidad alta en una transfusión previa aunque su especificidad disminuye (AU)

Objective. To assess the clinical application of non-invasive methods in the management of alloimmunization from 2006 to 2010. Subjects and methods. Seventy pregnancies with risk of fetal anemia were studied by fetal middle cerebral artery peak systolic velocity (MCA-PSV). The efficacy of MCA-PSV was compared between the first, second and third transfusions. Prenatal testing of fetal RHD blood group using maternal blood was performed in pregnancies followed-up in our center. Results. Fetal blood sampling was performed in 22 pregnancies; of these, fetal transfusion was carried out in 20. Detection rates and the false-positive rate of MCA-PSV in the prediction of severe or moderate fetal anemia were 89% and 15% in pregnancies with no previous transfusions, 100% and 41% in patients with one previous transfusion, and 40% and 24% when more than one transfusion was performed. Conclusion. MCA-PSV has high sensitivity when there is one previous fetal transfusion but its specificity is lower (AU)

Biopsia corial transcervical: guía práctica / Chorionic villous sampling: a practice guideline

La anticipación del cribado de las aneuploidías fetales al primer trimestre ha requerido implementar técnicas diagnósticas en este momento de la gestación. La biopsia de vellosidades coriales (BVC) es un procedimiento diagnóstico invasivo en Medicina Materno-Fetal, que consiste en la obtención de vellosidades coriales para estudio citogenético, molecular o bioquímico. Existen dos vías para la realización de la BVC, la transcervical y la transabdominal. La preferencia por una de las dos vías se ha basado históricamente en factores como son la localización placentaria, paridad, peso materno, preferencias del operador, etc. En nuestra institución pasamos a utilizar la vía transcervical de manera casi exclusiva, con resultados ventajosos para la gestante y el laboratorio. Todo ello, sin diferencias en cuanto a la tasa de pérdida gestacional u otras complicaciones. A pesar de 3 décadas de uso de la BVC transcervical, existe poco consenso en cuanto a su técnica y las guías clínicas específicas para su realización son escasas. Aprovechando la experiencia y el volumen acumulado de procedimientos realizados en nuestro centro, hemos planteado una guía clínica eminentemente práctica para la realización de BVC transcervical (AU)

Early screening for foetal aneuploidies in the first trister has required the introduction of diagnostic procedures appropriate for this period of pregnancy. Chorionic villi sampling(CVS) is an invasive diagnostic procedure in Maternal-Foetal Medicine to obtain chorionic villi for cytogenetic, molecular or biochemical analysis. There are two routes for CVS, transcervical and transabdominal. Preference for one of two routes has been historically based on factors such as, placental location, parity, maternal weight, operator preferences, etc. Our institution switched to using the transcervical approach almost exclusively, with advantages for the patients and laboratory with no differences in the pregnancy loss rate and other complications. Despite 3 decades of CVS use, there is no consensus as regards its application, and practice guidelines are few. Taking advantage of our experience with a large amount of procedures, we propose this practice guideline (AU)