E. Ferrazzi

Predictors of neonatal outcome in early-onset placental dysfunction

OBJECTIVE: To identify specific estimates and predictors of neonatal morbidity and mortality in early onset fetal growth restriction due to placental dysfunction. METHODS: Prospective multicenter study of prenataly diagnosed growth-restricted liveborn neonates of less than 33 weeks of gestational age. Relationships between perinatal variables (arterial and venous Dopplers, gestational age, birth weight, acid-base status, and Apgar scores) and major neonatal complications, neonatal death, and intact survival were analyzed by logistic regression. Predictive cutoffs were determined by receiver operating characteristic curves. RESULTS: Major morbidity occurred in 35.9% of 604 neonates: bronchopulmonary dysplasia in 23.2% (n=140), intraventricular hemorrhage in 15.2% (n=92), and necrotizing enterocolitis in 12.4% (n=75). Total mortality was 21.5 % (n=130), and 58.3% survived without complication (n=352). From 24 to 32 weeks, major morbidity declined (56.6% to 10.5%), coinciding with survival that exceeded 50% after 26 weeks. Gestational age was the most significant determinant (P<.005) of total survival until 266/7 weeks (r2=0.27), and intact survival until 292/7 weeks (r2=0.42). Beyond these gestational-age cutoffs, and above birth weight of 600 g, ductus venosus Doppler and cord artery pH predicted neonatal mortality (P<.001, r2=0.38), and ductus venosus Doppler alone predicted intact survival (P<.001, r2=0.34). CONCLUSION: This study provides neonatal outcomes specific for early-onset placenta-based fetal growth restriction quantifying the impact of gestational age, birth weight, and fetal cardiovascular parameters. Early gestational age and birth weight are the primary quantifying parameters. Beyond these thresholds, ductus venosus Doppler parameters emerge as the primary cardiovascular factor in predicting neonatal outcome. LEVEL OF EVIDENCE: II

Logistic Regression Model to Distinguish Between the Benign and Malignant Adnexal Mass Before Surgery: A Multicenter Study by the International Ovarian Tumor Analysis Group

PURPOSE To collect data for the development of a more universally useful logistic regression model to distinguish between a malignant and benign adnexal tumor before surgery. PATIENTS AND METHODS Patients had at least one persistent mass. More than 50 clinical and sonographic end points were defined and recorded for analysis. The outcome measure was the histologic classification of excised tissues as malignant or benign. RESULTS Data from 1,066 patients recruited from nine European centers were included in the analysis; 800 patients (75%) had benign tumors and 266 (25%) had malignant tumors. The most useful independent prognostic variables for the logistic regression model were as follows: (1) personal history of ovarian cancer, (2) hormonal therapy, (3) age, (4) maximum diameter of lesion, (5) pain, (6) ascites, (7) blood flow within a solid papillary projection, (8) presence of an entirely solid tumor, (9) maximal diameter of solid component, (10) irregular internal cyst walls, (11) acoustic shadows, and (12) a color score of intratumoral blood flow. The model containing all 12 variables (M1) gave an area under the receiver operating characteristic curve of 0.95 for the development data set (n = 754 patients). The corresponding value for the test data set (n = 312 patients) was 0.94; and a probability cutoff value of .10 gave a sensitivity of 93% and a specificity of 76%. CONCLUSION Because the model was constructed from multicenter data, it is more likely to be generally applicable. The effectiveness of the model will be tested prospectively at different centers.

Diagnostic value of blood sampling in fetuses with growth retardation

Background Fetuses with intrauterine growth retardation are delivered if they have evidence of distress, as manifested by abnormalities in the fetal heart rate and umbilical-artery blood flow. We studied whether umbilical-blood sampling might provide further information useful for management. Methods We measured hemoglobin and lactate concentrations, oxygen content, pH, blood gas levels, and base deficit in umbilical-vein blood and correlated these measurements with the heart rate and umbilical-artery wave forms recorded by Doppler velocimetry in 56 fetuses with growth retardation. Twenty-one fetuses had normal heart rates and normal results of velocimetry, 24 had normal heart rates and abnormal results of velocimetry (indicative of decreased diastolic flow), and 11 had abnormal heart rates and abnormal results of velocimetry. Results None of the 21 fetuses with normal heart rates and velocimetry had hypoxia or acidemia. Of the 24 fetuses with normal heart rates and abnormal velocimetry, 4 (17 percent) ha...

Perinatal morbidity and mortality in early‐onset fetal growth restriction: cohort outcomes of the trial of randomized umbilical and fetal flow in Europe (TRUFFLE)

Few data exist for counseling and perinatal management of women after an antenatal diagnosis of early‐onset fetal growth restriction. Yet, the consequences of preterm delivery and its attendant morbidity for both mother and baby are far reaching. The objective of this study was to describe perinatal morbidity and mortality following early‐onset fetal growth restriction based on time of antenatal diagnosis and delivery.

2 year neurodevelopmental and intermediate perinatal outcomes in infants with very preterm fetal growth restriction (TRUFFLE): A randomised trial

BACKGROUND No consensus exists for the best way to monitor and when to trigger delivery in mothers of babies with fetal growth restriction. We aimed to assess whether changes in the fetal ductus venosus Doppler waveform (DV) could be used as indications for delivery instead of cardiotocography short-term variation (STV). METHODS In this prospective, European multicentre, unblinded, randomised study, we included women with singleton fetuses at 26-32 weeks of gestation who had very preterm fetal growth restriction (ie, low abdominal circumference [<10th percentile] and a high umbilical artery Doppler pulsatility index [>95th percentile]). We randomly allocated women 1:1:1, with randomly sized blocks and stratified by participating centre and gestational age (<29 weeks vs ≥29 weeks), to three timing of delivery plans, which differed according to antenatal monitoring strategies: reduced cardiotocograph fetal heart rate STV (CTG STV), early DV changes (pulsatility index >95th percentile; DV p95), or late DV changes (A wave [the deflection within the venous waveform signifying atrial contraction] at or below baseline; DV no A). The primary outcome was survival without cerebral palsy or neurosensory impairment, or a Bayley III developmental score of less than 85, at 2 years of age. We assessed outcomes in surviving infants with known outcomes at 2 years. We did an intention to treat study for all participants for whom we had data. Safety outcomes were deaths in utero and neonatal deaths and were assessed in all randomly allocated women. This study is registered with ISRCTN, number 56204499. FINDINGS Between Jan 1, 2005 and Oct 1, 2010, 503 of 542 eligible women were randomly allocated to monitoring groups (166 to CTG STV, 167 to DV p95, and 170 to DV no A). The median gestational age at delivery was 30·7 weeks (IQR 29·1-32·1) and mean birthweight was 1019 g (SD 322). The proportion of infants surviving without neuroimpairment did not differ between the CTG STV (111 [77%] of 144 infants with known outcome), DV p95 (119 [84%] of 142), and DV no A (133 [85%] of 157) groups (ptrend=0·09). 12 fetuses (2%) died in utero and 27 (6%) neonatal deaths occurred. Of survivors, more infants where women were randomly assigned to delivery according to late ductus changes (133 [95%] of 140, 95%, 95% CI 90-98) were free of neuroimpairment when compared with those randomly assigned to CTG (111 [85%] of 131, 95% CI 78-90; p=0.005), but this was accompanied by a non-significant increase in perinatal and infant mortality. INTERPRETATION Although the difference in the proportion of infants surviving without neuroimpairment was non-significant at the primary endpoint, timing of delivery based on the study protocol using late changes in the DV waveform might produce an improvement in developmental outcomes at 2 years of age. FUNDING ZonMw, The Netherlands and Dr Hans Ludwig Geisenhofer Foundation, Germany.

Terms, definitions and measurements to describe the sonographic features of the endometrium and intrauterine lesions: a consensus opinion from the International Endometrial Tumor Analysis (IETA) group

The IETA (International Endometrial Tumor Analysis group) statement is a consensus statement on terms, definitions and measurements that may be used to describe the sonographic features of the endometrium and uterine cavity on gray‐scale sonography, color flow imaging and sonohysterography. The relationship between the ultrasound features described and the presence or absence of pathology is not known. However, the IETA terms and definitions may form the basis for prospective studies to predict the risk of different endometrial pathologies based on their ultrasound appearance. Copyright

External Validation of Mathematical Models to Distinguish Between Benign and Malignant Adnexal Tumors: A Multicenter Study by the International Ovarian Tumor Analysis Group

Purpose: Several scoring systems have been developed to distinguish between benign and malignant adnexal tumors. However, few of them have been externally validated in new populations. Our aim was to compare their performance on a prospectively collected large multicenter data set. Experimental Design: In phase I of the International Ovarian Tumor Analysis multicenter study, patients with a persistent adnexal mass were examined with transvaginal ultrasound and color Doppler imaging. More than 50 end point variables were prospectively recorded for analysis. The outcome measure was the histologic classification of excised tissue as malignant or benign. We used the International Ovarian Tumor Analysis data to test the accuracy of previously published scoring systems. Receiver operating characteristic curves were constructed to compare the performance of the models. Results: Data from 1,066 patients were included; 800 patients (75%) had benign tumors and 266 patients (25%) had malignant tumors. The morphologic scoring system used by Lerner gave an area under the receiver operating characteristic curve (AUC) of 0.68, whereas the multimodal risk of malignancy index used by Jacobs gave an AUC of 0.88. The corresponding values for logistic regression and artificial neural network models varied between 0.76 and 0.91 and between 0.87 and 0.90, respectively. Advanced kernel-based classifiers gave an AUC of up to 0.92. Conclusion: The performance of the risk of malignancy index was similar to that of most logistic regression and artificial neural network models. The best result was obtained with a relevance vector machine with radial basis function kernel. Because the models were tested on a large multicenter data set, results are likely to be generally applicable.

Metabolomics Application in Maternal-Fetal Medicine

Metabolomics in maternal-fetal medicine is still an “embryonic” science. However, there is already an increasing interest in metabolome of normal and complicated pregnancies, and neonatal outcomes. Tissues used for metabolomics interrogations of pregnant women, fetuses and newborns are amniotic fluid, blood, plasma, cord blood, placenta, urine, and vaginal secretions. All published papers highlight the strong correlation between biomarkers found in these tissues and fetal malformations, preterm delivery, premature rupture of membranes, gestational diabetes mellitus, preeclampsia, neonatal asphyxia, and hypoxic-ischemic encephalopathy. The aim of this review is to summarize and comment on original data available in relevant published works in order to emphasize the clinical potential of metabolomics in obstetrics in the immediate future.

The use of contrasted transvaginal sonography in the diagnosis of gynecologic diseases: a preliminary study.

The purpose of this study was to evaluate the efficacy of a new contrast‐dedicated ultrasound technology, contrast‐tuned imaging (CnTI), implemented on an endovaginal probe and using the second‐generation contrast agent SonoVue (Bracco International BV, Amsterdam, the Netherlands), compared with the standard ultrasound examination in different gynecologic diseases.

Cord sampling for the evaluation of oxygenation and acid-base balance in growth-retarded human fetuses

In 14 pregnancies complicated by intrauterine growth retardation, the umbilical cord was sampled before delivery under ultrasonic guidance for rapid fetal karyotyping. Fetal blood was analyzed for respiratory gases, acid-base balance, and lactate concentrations. Two patients were excluded from the study because cord samples were diluted with amniotic fluid. In six patients (group 1), the clinical assessment warranted continuation of pregnancy. Cesarean sections were performed in the remaining eight patients (group 2) within 8 hours of cord sampling. The data from the two groups were compared with those obtained from umbilical venous blood at the time of elective repeat cesarean section in term appropriate for gestational age infants (controls). No significant difference in PO2 was found between groups 1 and 2 and controls. In contrast, there were significant differences in oxygen saturation and acid-base balance between groups 1 and 2. Lactate concentration was inversely correlated with pH and was elevated in five of six fetuses requiring a prompt cesarean section: In two of these five fetuses, nonstress fetal heart rate tracings were reactive. The results suggest that fetal blood biochemistry, and particularly lactate concentration, may represent an additional indicator of fetal well-being in pregnancies complicated by intrauterine growth retardation.