Reference Charts for Fetal Cerebellar Vermis Height: A Prospective Cross-Sectional Study of 10605 Fetuses.

OBJECTIVE: To establish reference charts for fetal cerebellar vermis height in an unselected population. METHODS: A prospective cross-sectional study between September 2009 and December 2014 was carried out at ALTAMEDICA Fetal-Maternal Medical Centre, Rome, Italy. Of 25203 fetal biometric measurements, 12167 (48%) measurements of the cerebellar vermis were available. After excluding 1562 (12.8%) measurements, a total of 10605 (87.2%) fetuses were considered and analyzed once only. Parametric and nonparametric quantile regression models were used for the statistical analysis. In order to evaluate the robustness of the proposed reference charts regarding various distributional assumptions on the ultrasound measurements at hand, we compared the gestational age-specific reference curves we produced through the statistical methods used. Normal mean height based on parametric and nonparametric methods were defined for each week of gestation and the regression equation expressing the height of the cerebellar vermis as a function of gestational age was calculated. Finally the correlation between dimension/gestation was measured. RESULTS: The mean height of the cerebellar vermis was 12.7mm (SD, 1.6mm; 95% confidence interval, 12.7-12.8mm). The regression equation expressing the height of the CV as a function of the gestational age was: height (mm) = -4.85+0.78 x gestational age. The correlation between dimension/gestation was expressed by the coefficient r = 0.87. CONCLUSION: This is the first prospective cross-sectional study on fetal cerebellar vermis biometry with such a large sample size reported in literature. It is a detailed statistical survey and contains new centile-based reference charts for fetal height of cerebellar vermis measurements.

What Is the Rate of Incomplete Fetal Anatomic Surveys During a Second-Trimester Scan? Retrospective Observational Study of 4000 Nonobese Pregnant Women.

OBJECTIVES: The purpose of this study was to estimate the rate of incomplete fetal anatomic surveys during a second-trimester scan due to an unfavorable fetal position in a nonobese population. METHODS: All pregnant women who came to the Altamedica Fetal-Maternal Medical Center, a specialized center for prenatal diagnosis, for a routine second-trimester scan between January 2012 and April 2013 were retrospectively included in the analysis. Patients with a body mass index higher than 30.0 kg/m(2) or anterior fibroids larger than 5 cm were not included in the study. RESULTS: Of 4000 pregnant women admitted for a second-trimester scan, 169 (4.2%) came back within 2 weeks to complete the examination because of an unfavorable fetal position. In particular, 104 (2.6%) needed visualization of only 1 view, and 65 (1.6%) needed more than 1 view. The most difficult organ to visualize was the corpus callosum, in 73 cases (1.8%); the face was not visualized in 69 cases (1.7%); the cerebellar vermis was not seen in 47 fetuses (1.1%); and the heart could not be completely examined in 40 fetuses (1.0%). Of the 4000 women, 169 (4.2%) had a nonexhaustive scan; 149 (3.7%) needed a second scan to complete the second-trimester survey; 14 (0.35%) needed a third scan; and 2 (0.05%) remained with a not completely exhaustive scan. CONCLUSIONS: There is always a small percentage of incomplete fetal anatomic surveys during a second-trimester scan, which cannot be modified by the sonographer's skill or by technical sonographic innovations.

Reference charts for fetal corpus callosum length: a prospective cross-sectional study of 2950 fetuses.

OBJECTIVES: The purpose of this study was to establish reference charts for fetal corpus callosum length in a convenience sample. METHODS: A prospective cross-sectional study was conducted at the Artemisia Fetal-Maternal Medical Center between December 2008 and January 2012. Among 16,975 fetal biometric measurements between 19 weeks and 37 weeks 6 days' gestation, 3438 measurements of the corpus callosum (20.3%) were available. After excluding 488 measurements (14.2%), a total of 2950 fetuses (85.8%) were considered and analyzed only once. Parametric and nonparametric quantile regression models were used for the statistical analysis. To evaluate the robustness of the proposed reference charts with respect to various distributional assumptions on the sonographic measurements at hand, we compared the gestational age (GA)-specific reference curves produced by the statistical methods used. RESULTS: The mean corpus callosum length was 26.18 mm (SD, 4.5 mm; 95% confidence interval, 26.01-26.34 mm). The linear regression equation expressing the length of the corpus callosum as a function of GA was length (mm) = -11.17 + 1.62 × GA. The correlation between the dimension and gestation was expressed by the coefficient r = 0.83. Normal mean lengths according the parametric and nonparametric methods were defined for each week of gestation. CONCLUSIONS: This work provides new quantile-based reference charts for corpus callosum length measurements that may be useful for diagnosis of congenital corpus callosum anomalies in fetal life.

Retrospective study evaluating the performance of a first-trimester combined screening for trisomy 21 in an Italian unselected population.

OBJECTIVES: to assess the performance of a combined first-trimester screening for trisomy 21 in an unselected Italian population referred to a specialized private center for prenatal medicine. METHODS: a retrospective validation of first-trimester screening algorithms [risk calculation based on maternal age and nuchal translucency (NT) alone, maternal age and serum parameters (free ß-hCG and PAPP-A) alone and a combination of both] for fetal aneuploidies evaluated in an unselected Italian population at Artemisia Fetal-Maternal Medical Centre in Rome. All measurements were performed between 11(+0) and 13(+6) weeks of gestation, between April 2007 and December 2008. RESULTS: of 3,610 single fetuses included in the study, we had a complete follow-up on 2,984. Fourteen of 17 cases of trisomy 21 were detected when a cut-off of 1:300 was applied [detection rate (DR) 82.4%, 95% confidence interval (CI) 64.2-100; false-positive rate (FPR) 4.7%, 95% CI 3.9-5.4; false-negative rate (FNR) 17.6%, 95% CI 0-35.8%]. CONCLUSION: in our study population the detection rate for trisomy 21, using the combined risk calculation based on maternal age, fetal NT, maternal PAPP-A and free ß-hCG levels, was superior to the application of either parameter alone. The algorithm has been validated for first trimester screening in the Italian population.

Oxidative stress occurs early in Down syndrome pregnancy: A redox proteomics analysis of amniotic fluid.

PURPOSE: The present study aims to evaluate a set of oxidative stress biomarkers in the amniotic fluid (AF) of women carrying Down syndrome (DS) fetuses that could prove in vivo the early occurrence of oxidative damage in DS. EXPERIMENTAL DESIGN: To assess the extent of protein oxidation in DS AF, we measured protein carbonylation and protein-bound HNE by slot-blot analysis, total and oxidized GSH levels by enzymatic assay and heat shock proteins (HSPs) thioredoxin (Trx) induction by Western blot. Further, by a redox proteomics approach specific targets of protein carbonylation were identified. RESULTS: We found increased levels of oxidative stress, as indexed by increased protein oxidation, lipid peroxidation, reduction of GSH and Trx levels and induction of the HSP response. By a redox proteomics approach, we identified selective proteins which showed increased oxidation in DS fetuses compared with healthy controls. The identified proteins are involved in iron homeostasis (ceruloplasmin and transferin), lipid metabolism (zinc-α2-glycoprotein, retinol-binding protein 4 and apolipoprotein A1) and inflammation (complement C9, α-1B-glycoprotein, collagen α-1V chain) with critical relevance in the clinical outcome of DS. CONCLUSIONS AND CLINICAL RELEVANCE: Our results indicate that oxidative damage is an early event in the DS pathogenesis and might contribute to the development of deleterious DS phenotypes, including abnormal development and AD-like neuropathology.

Prenatal Diagnosis of a Fetus with de novo Supernumerary Ring Chromosome 16 Characterized by Array Comparative Genomic Hybridization.

A fetus with de novo ring chromosome 16 is presented. At 20 weeks' gestation, ultrasound examination demonstrated bilateral clubfoot, bilateral renal pyelectasis, hypoplasia of the corpus callosum, and transposition of the great vessel. Amniocentesis was performed. Chromosome analysis identified a ring chromosome 16 [47,XY,r(16)] and array comparative genomic hybridization (a-CGH) demonstrated that the ring included the euchromatic portion 16p11.2. Postmortem examination confirmed prenatal findings. This is the first case of de novo ring chromosome 16 diagnosed prenatally with a new phenotypic pattern and also reinforces the importance of offering amniocentesis with a-CGH if fetal anomalies are detected.

The role of ultrasonography in the diagnosis of fetal isolated complete agenesis of the corpus callosum: a long-term prospective study.

OBJECTIVE: To evaluate the role of a dedicated neurosonographer in prenatal diagnosis of isolated complete agenesis of the corpus callosum (iCACC) and to asses the postnatal outcome of these infants. METHODS: Prospective study between January 2004 to December 2004 at Fetal Maternal Medical Centre 'Artemisia', Rome, Italy. A detailed ultrasound scan was performed in fetuses affected by iCACC by a dedicated fetal neurosonographer (CG). In all cases, magnetic resonance imaging (MRI) within 5 weeks and 13-15 months after birth was performed. A comparison was made between prenatal findings following the ultrasound scan and postnatal MRI. In these cases, a follow-up of 4-years was performed with a neurological evaluation. RESULTS: Among 23 cases of ACC diagnosed at our centre in the study period, CACC was diagnosed in 17 fetuses. Two were then excluded due to associated malformations, one was lost at follow-up and one patient opted to terminate her pregnancy. Newborn MRI confirmed the ultrasonographic diagnosis of iCACC in all 13 cases. A regular development was present in 92.3% of prenatally diagnosed iCACC. CONCLUSION: A dedicated neurosonographer could diagnose the iCACC with the same accuracy as MRI and in up to 90% of cases the newborn will have a regular development.

Shoulder dystocia: an Evidence-Based approach.

Shoulder Dystocia (SD) is the nightmare of obstetricians. Despite its low incidence, SD still represents a huge risk of morbidity for both the mother and fetus. Even though several studies showed the existence of both major and minor risk factors that may complicate a delivery, SD remains an unpreventable and unpredictable obstetric emergency. When it occurs, SD is difficult to manage due to the fact that there are not univocal algorithms for its management.Nevertheless, even if it is appropriately managed, SD is one of the most litigated cause in obstetrics, because it is frequently associated with permanent birth-related injuries and mother complications.All the physicians should be prepared to manage this obstetric emergency by attending periodic training, even if SD is difficult to teach for its rare occurrence and because in clinical practice it is often handled by experienced obstetricians.THE PURPOSE OF THIS STUDY IS TO REVIEW THE LITERATURE CONCERNING THE EVERLASTING PROBLEMS OF SD: identification of risk factors for the early detection of delivery at high risk of SD and a systematic management of this terrifying obstetric emergency in order to avoid the subsequent health, medico-legal and economic complications.

Proteomic analysis for the study of amniotic fluid protein composition.

Amniotic fluid (AF), routinely used for prenatal diagnosis, contains large amounts of proteins produced by the amnion epithelial cells, fetal tissues, fetal excretions and placental tissuesAlthough many amniotic fluid proteins have been identified and are currently used to detect potential fetal anomalies, little is known about the functions of these proteins and how they interact with one another. Identification of changes in the protein content of amniotic fluid, therefore, may be used to detect a particular type of pathology, or to ascertain a specific genetic disorder. In the present work we used a proteomic approach, combining 2DE and MS, in order to study the protein composition of AFS.

Reference interval for fetal biometry in Italian population.

OBJECTIVES: To validate new references charts and equations for fetal biometry in an Italian unselected population. METHODS: A cross-sectional study involving 4896 women with singleton viable pregnancies, at Artemisia Fetal Maternal Medical Centre between May 2009 and December 2009. Each woman was scanned only once, between 14+0 and 40+0 weeks of gestation. The fetal standard biometric measurements were recorded. For each parameter, regression models were fitted to estimate the percentile at each gestational age. In order to be compared to other reference equations, the fetal biometric measurements at each gestational age were expressed as Z-scores. RESULTS: New fetal charts and references equations for Italian population were developed according to the recommend multistep statistical procedure. CONCLUSION: To our knowledge this is the first Italian study with the largest sample size ever reported in the literature. In addiction, our newer charts of reference centiles for fetal biometric measurements are useful in the obstetrical clinical practice for the Italian population.

Analysis of fetal biometric measurements in the last 30 years.

OBJECTIVES: To compare fetal biometric measurements with standard growth charts for ultrasound parameters existing from the last 30 years. STUDY DESIGN: A preliminary prospective study. SETTING: Artemisia Mean Centre of Perinatal Diagnosis, Rome,Italy. MATERIAL AND METHOD: A cross sectional study involving 1000 pregnant women with uncomplicated singleton pregnancy between 14(th) and 41(th) weeks of gestation from 1 January to 30 June 2008. All recruited pregnant women enrolled had an abdominal ultrasonography for fetal biometry. For each measurement, regression models were fitted to estimate the mean and SD. The results were compared with existing references from the last 30 years using Student's T distribution. Moreover, neonatal weights were obtained from 1977 to 2008 by ISTAT. RESULTS: One thousand normal fetuses from pregnant women, between 22(th) and 23(th) weeks, between 32(th) and 33(th) weeks and at 38(th) week, were thoroughly measured. THERE WERE SIGNIFICANT DIFFERENCES FROM THE COMPARISON WITH OUR DATA FOR EACH GESTATIONAL AGE: femur length and homer length, abdominal circumference, head circumference and occipitofrontal diameter were longer than all parameters of existing references from the last 30 years. The analysis of neonatal weights on ISTAT data from 1977 to 2007 demonstrated a significant increment through the years. CONCLUSION: Fetus is grown up across the years. It is necessary to modify the standard growth charts for ultrasound parameters existing from the last 30 years with actually fetal biometric measurements. It is helpful for a correct clinical approach and for an appropriate management mother-fetus.