Trisomy 18: Fetal ultrasound findings at different gestational ages.

The aim of this article is evaluate the sonograhic findings in fetuses with trisomy 18 at different gestational ages. The cases were recruited from pregnant women, who underwent to prenatal diagnosis in the period from October 1995 to September 2006. Seventy-one fetuses with trisomy 18 were diagnosed. On review of the sonograms the majority of these cases had ultrasound anomalies (sensitivity of 91.5%). The most frequent anomalies were abnormalities of extremities (40.8%) and fetal growth restriction (35.2%). More frequently (54.9%) two or more anomalies were present. Nearly all fetuses with trisomy 18 had sonographic abnormalities. Likely improved high-resolution equipment and attention to details by skilled operators led to the detection of most anomalies to trisomy 18. Knowledge of types of specific ultrasound findings can improve prenatal diagnosis in order to provide invasive procedures only when indicated, and to avoid amniocentesis when ultrasound signs are not observed in women at high risk from positive biochemical testing.

First-trimester fetal heart block and increased nuchal translucency: an indication for early fetal echocardiography.

Prevalence of congenital heart disease increases with nuchal translucency (NT) thickness. First-trimester fetal bradycardia may result from heart block associated with complex congenital heart disease. We report two cases detected in the first trimester of pregnancy, in which both fetuses showed an increased nuchal translucency and bradycardia. Fetal karyotype was normal in both fetuses. First-trimester fetal echocardiography was performed and, in both cases, complex congenital heart disease was diagnosed. We discuss the added role of fetal heart rate in first-trimester ultrasound screening, in fetuses with increased nuchal translucency and normal karyotype. We stress, as well, the importance of echocardiography performed in the first trimester as a potential tool for early diagnosis in selected cases.

Fetal nasal bone and trisomy 21 in the second trimester.

OBJECTIVES: To assess the feasibility of measuring nasal bone length in the second trimester of pregnancy and to confirm if fetal nasal bone absence or hypoplasia is a marker for Down syndrome. METHODS: Fetal nasal bone assessment was performed in 439 consecutive singleton pregnancies at high risk of Down syndrome between 15 and 21 weeks. All ultrasound examinations were performed transabdominally by five skilled sonographers. If the nasal bone was present, its length was measured. The biparietal diameter: nasal bone length ratio (BPD/NBL) was also calculated. RESULTS: Nasal bone assessment was successfully achieved in all fetuses. The nasal bone was absent in 2(0.47%) of the 417 unaffected fetuses and in 10(55.5%) of the 18 fetuses with trisomy 21. Of the 8 Down syndrome cases with a nasal bone present, 4 had nasal bone hypoplasia and 4 had a normal nasal bone. BPD/NBL was 9 or greater in 7 of the 8 fetuses affected by trisomy 21 with nasal bone present and in 86 (20.6%) of the 417 normal fetuses; it was 10 or greater in 5 of the 8 (62.5%) fetuses affected by trisomy 21 and in 41 of the 417 (9.8%) euploid fetuses. CONCLUSIONS: Nasal bone absence is a marker for Down syndrome in the second trimester of pregnancy. Inclusion of nasal bone length into the second-trimester screening protocol could potentially obviate the false-negative cases from other screening tests. The measurement of nasal bone length in the second trimester seems to provide additional benefits beyond the assessment of the presence or absence of the nasal bone.

Rapid prenatal diagnosis of common chromosome aneuploidies by QF-PCR. Assessment on 18,000 consecutive clinical samples.

The quantitative fluorescent PCR (QF-PCR) assay, introduced during the last few years, allows prenatal diagnoses of common chromosome aneuploidies in a few hours after sampling. We report the first assessment of QF-PCR performed on a large cohort of 18,000 consecutive clinical specimens analysed in two different Centres. All samples were analysed by QF-PCR using several selected STR markers together with amelogenin and, occasionally, SRY for fetal sexing. Results were compared with those obtained by conventional cytogenetic analysis. In 17,129 tests, normal fetuses were detected by QF-PCR. No false positives were observed. All 732 cases of trisomy 21, 18, 13, triploidies, double trisomies as well as all but one fetuses with X and Y aneuploidies were correctly diagnosed. Chromosome mosaicism could also be suspected in several samples. In some cases of in vitro culture failures, QF-PCR was the only evidence of fetal X, Y, 21, 18 and 13 chromosome complement. QF-PCR proved to be efficient and reliable in detecting major numerical chromosome disorders. The main advantages of the molecular assay are its very low cost, speed and automation enabling a single operator to perform up to 40 assays per day. QF-PCR relieves anxiety of most parents within 24 h from sampling and accelerates therapeutic interventions in the case of an abnormal result. In countries where large scale conventional cytogenetics is hampered by its high cost and lack of technical expertise, QF-PCR may be used as the only prenatal diagnostic test.

Anomalies of the fetal venous system: a report of 26 cases and review of the literature.

OBJECTIVE: To evaluate sonographic appearance, natural history, and neonatal outcome of fetal venous anomalies. METHODS: We performed an observational study, including all fetuses affected by abnormalities of the venous system diagnosed by ultrasound during the prenatal period. RESULTS: 26 fetuses were identified. Other malformations were present in 5 cases (19.2%), 1 fetus had trisomy 21, and 1 fetus had intrauterine growth retardation (IUGR). Twenty-five pregnancies ended in liveborn infants, and there was 1 case of unexplained intrauterine death in the fetus with IUGR affected by varix of the umbilical vein. CONCLUSIONS: Fetal venous anomalies are very rare and may be associated with fetal malformations or IUGR. Conservative management appears to be an adequate medical practice in the absence of other fetal problems, but in the presence of a varix of the umbilical vein, serial follow-up scans are needed to exclude the onset of hydrops or thrombosis of the varix.

Feasibility study for a microchip-based approach for noninvasive prenatal diagnosis of genetic diseases.

Fetal DNA in maternal plasma may represent a source of genetic material for prenatal noninvasive diagnosis of genetic diseases. We evaluated a cohort of physiological pregnancies to determine if fetal DNA can be retrieved at any gestational week in sufficient quantity to be analyzed with advanced mutation detection technologies. We performed fetal DNA quantification by real-time polymerase chain reaction (PCR) on the SRY gene in 356 women sampled from 6 to 40 gestational weeks. Fetal DNA was retrieved at any week. All female fetuses were correctly identified. In 5 of 188 (2.6%) male-bearing pregnancies, no amplification was obtained. For noninvasive testing, complete clearance of fetal DNA after delivery is mandatory. Long-term persistence was not detected in women with previous sons or abortions. These findings confirm that maternal plasma may represent the optimal source of fetal genetic material. For noninvasive diagnosis of genetic diseases, we evaluated microchip technology. The detection limit for a minority allele determined by diluting a mutated DNA into a wild-type plasma sample was 5 genome equivalents, indicating that the test might be applied to the identification of paternally inherited fetal alleles in maternal plasma. The addition of peptide nucleic acids (PNAs) to either the PCR reaction or the chip hybridization mixture allowed approximately 50% inhibition of wild-type allele signals.

Screening-detected breast carcinoma in a patient with Cowden syndrome.

Cowden syndrome is a hereditary genetic disease whose incidence is still not precisely defined; it is due to a germline mutation in the PTEN gene. We reported a case of breast tumor caused by a PTEN gene mutation, which was detected within a National Screening Program; the diagnosis of Cowden syndrome was made on the basis of patient's particular clinical history. The identification of new genetic mutations has allowed clarification of some of the mechanisms that increase the risk of developing some types of tumors. Furthermore, new kind of mutations recently reported in the literature raise questions about their prognostic significance and how their carriers can be better screened, counseled and managed. These problematic issues will be encountered with increasing frequency in the near future, since many other more mutations are sure to be discovered. The PTEN gene mutation has been implicated in various human tumors, mainly in the breast and the thyroid gland. In the course of a screening program, the early identification of patients affected by a genetic mutation, which is rare, improves the definition of the prognosis and the therapeutic options.

Ultrasound evaluation of fetal nasal bone at 11 to 14 weeks in a consecutive series of 1906 fetuses.

OBJECTIVE: The aim of this study is to evaluate the significance of nasal bone ossification as a marker for trisomy 21 at 11 to 14 weeks' gestation in an unselected obstetric population referred to our Centre. METHODS: A total of 1906 consecutive fetuses undergoing nuchal translucency scan at 11 to 14 weeks' gestation were evaluated for the presence of hypoplasia/absence of nasal bone. The data obtained were correlated with fetal karyotype. RESULTS: A successful view of the fetal profile was obtained in 1752 fetuses (91.9%). The nasal bone was hypoplastic/absent in 12 of 19 fetuses with chromosomal abnormalities. There were 10 cases of trisomy 21, in 8 of which hypoplastic/absent nasal bone was observed. Furthermore, absence of nasal bone was recorded in 24 of 1733 chromosomally normal fetuses. CONCLUSIONS: Nasal bone evaluation may improve the detection of trisomy 21 in the first trimester in an unselected obstetric population. Although numerically limited, our experience confirms that delayed nasal bone ossification (hypoplasia/absence of nasal bone) is rarely observed in chromosomally normal fetuses (1.4%). An appropriate training of operators is mandatory in order to achieve an acceptable performance.

Measurement of nasal bone length at 11-14 weeks of pregnancy and its potential role in Down syndrome risk assessment.

OBJECTIVES: To assess the feasibility of measuring nasal bone length in first-trimester pregnancy and to confirm if the absence of a fetal nasal bone is a marker for Down syndrome. METHODS: Fetal nasal bone assessment was attempted in 1089 consecutive singleton pregnancies between 11 and 14 weeks' gestation. All ultrasound examinations were performed transabdominally in three separate centers. If the nasal bone was present, nasal bone length was measured. RESULTS: Nasal bone assessment was successfully achieved in 1027 of 1089 (94.3%) ultrasound examinations. Within this group nasal bone was absent in 10 of 1000 (1.0%) unaffected cases, 10 of 15 (66.7%) Down syndrome cases and 5 of 12 (41.7%) cases with other pathological conditions. Regression analysis showed a significant increase (P < 0.0001) in nasal bone length from 2.48 mm at a crown-rump length of 45 mm to 3.12 mm at a crown-rump length of 84 mm. The nasal bone length in the five cases of Down syndrome in which the nasal bone was present was less than the median measurement of unaffected cases. Using modeling, the combination of nasal bone with maternal age, nuchal translucency, free beta-human chorionic gonadotropin (hCG) and pregnancy associated plasma protein-A (PAPP-A) achieved a detection rate of 95% with a false-positive rate of 2.9%. At a fixed 1% false-positive rate, the detection rate was 91%. CONCLUSIONS: Absence of the nasal bone can be used as a marker for Down syndrome in the first trimester of pregnancy. Inclusion of the nasal bone in the current first-trimester screening protocol along with nuchal translucency, free beta-hCG and PAPP-A can achieve high detection at a very low false-positive rate. Large datasets are needed to confirm whether the measurement of nasal bone length provides additional benefits beyond the assessment of the presence or absence of the nasal bone.

Prenatal diagnosis of isolated unilateral pulmonary agenesis in the second trimester.

Unilateral pulmonary agenesis is a very rare developmental malformation that is often associated with other anomalies including non-immune hydrops. We describe a case of isolated unilateral pulmonary agenesis diagnosed in the second trimester by gray-scale and color Doppler ultrasound.

Three-dimensional ultrasound evaluation of short-rib polydactyly syndrome type II in the second trimester: a case report.

Prenatal diagnosis of short-rib polydactyly syndrome is possible and has been reported in literature, but a precise ultrasound diagnosis is not easy. We report a case in which three-dimensional ultrasound was used in the evaluation of the disorder. The contribution and potential application of three-dimensional sonography in the prenatal diagnosis of short-rib polydactyly syndrome and other fetal skeletal malformations is discussed.

Minor sonographic signs of trisomy 21 at 15-20 weeks' gestation in fetuses born without malformations: a prospective study.

A prospective study was performed on 2119 pregnancies that underwent genetic amniocentesis. Indications for amniocentesis were either maternal age (> or =35) or triple-test results (risk> or =1/380). The study covered a 36-month period and assessed the prevalence of minor ultrasound markers both in fetuses with Down syndrome and normal control fetuses at 15-19 week' gestation. Only fetuses with normal karyotype or trisomy 21 were considered. Six minor sonographic markers were considered: nuchal thickness, pyelectasia, femur observed/expected and humerus observed/expected ratios, bowel echogenicity, and choroid plexus cysts. One or more ultrasound soft markers were present in 23 out of 33 fetuses with Down syndrome (70%) and in 572 out of 2069 normal fetuses (28%).

Ultrasonographic detection of fetal cranio-facial hemangioma: case report and review of the literature.

A case of an isolated cranio-facial vascular anomaly, extending from the left parietal bone to the lateral margin of the omolateral orbit is presented. Detection and differential diagnosis of fetal hemangioma is important for a variety of reasons. First, it allows the prenatal growth of the mass to be evaluated. Second, it enables appropriate arrangements for delivery to be made including its timing and selection of the appropriate clinical team necessary to support the neonate. After birth these cranio-facial anomalies can regress spontaneously, but plastic surgery is often necessary.

Arteriovenous fistulas of the placenta in a singleton fetus with large atrial septal defect and anomalous connection of the umbilical veins.

Arteriovenous fistulas of the placenta rarely occur in singleton pregnancies. This report describes the fetal and neonatal hemodynamic pattern in a singleton gestation in which multiple placental artery-to-vein anastomoses were associated with a large atrial septal defect and a single umbilical artery with an anomalous connection of the persistent right and left umbilical veins. Possible links between the extracardiac vascular malformation and the congenital heart defect are discussed.

Cost-effectiveness ratio of chorionic villi biopsy for the prenatal diagnosis of chromosomal aberrations as compared with amniocentesis.

The observed cost of amniocentesis for the prenatal diagnosis of chromosomal aberrations in pregnancies at risk because of advanced maternal age was compared with the estimated cost of chorionic villi biopsy (CVB). The cost of CVB was estimated to be 22% less than that of amniocentesis when the cost of the sampling procedure, the laboratory charges and the cost of spontaneous and therapeutic abortions were considered.