Single Nucleotide Polymorphism-Based Analysis of Cell-Free Fetal DNA in 3000 Cases from Germany and Austria.

BACKGROUND & PATIENT: Data from 3 008 patients, who underwent single-nucleotide-polymorphism (SNP)-based noninvasive prenatal testing (NIPT) are presented. METHOD: The PanoramaTM test (Natera, San Carlos, CA) was used to analyze cell-free fetal DNA from maternal blood for trisomies 21, 18, and 13, triploidy and sex-chromosome aneuploidies. RESULT: In 2 942 (97.8%) cases, a result was obtained. The average fetal fraction was 10.2%. A high-risk result for fetal aneuploidy was made for 65 (2.2%) cases. In 59 (90.8%) of these cases, invasive testing confirmed the aneuploidy. There were 6 false-positive cases. In the false-positive group, the fetal fraction was significantly lower. The overall positive predictive value was 90.8%. No false-negative cases were reported but many patients in this study have not delivered yet. Therefore, exact data cannot be given for potential false-negative cases. CONCLUSION: SNP-based NIPT is a reliable screening method for evaluating the risk of aneuploidies of chromosomes 21, 18 and 13. By using NIPT, the number of invasive procedures may be reduced significantly compared to maternal age and first-trimester screening.

Sonographical integrated test for detection of chromosomal aberrations.

PURPOSE: Different sonographical and biochemical methods for the detection of an elevated risk of chromosomal abnormality are used. The aim of our study was to establish a diagnostic scheme with the highest sensitivity by means of an algorithm incorporating all parameters. MATERIALS AND METHODS: In a group of 1490 pregnant women, ultrasound examination including nuchal translucency and nasal bone measurement was performed in the first trimester. Then, in the early second trimester, a second ultrasound examination combined with measuring nuchal thickness and nasal bone was carried out. RESULTS: The combination of the NT and NB measurement showed the highest sensitivity (94.7%), specificity (99.21%), PPV (85.7%) and NPV (99.73%). CONCLUSION: The proposed integrated test is characterised by a high predictive value for the detection of chromosomal abnormalities, low cost of performance and absolute safety for the foetus and could be offered to all pregnant women. The combination of two ultrasound examinations and biochemistry greatly increased the value of the test.

Feto-amniotic shunting -- experience of six centres.

AIM: Foeto-amniotic shunting is an ultrasound-guided, therapeutic intervention for drainage of persistent intracavital fluid retention in severely affected foetuses with a high risk of mortality. In order to weigh up the comparatively high risk of intervention against the possible benefit, we evaluated the value of different indications, the complication rate and the time span of drains in situ. PATIENTS AND METHODS: We made a survey of all level III ultrasound centres of German-speaking countries from 1993 to 2001. Six level III centres returned the questionnaire: forty-seven foeto-amniotic shunting procedures were performed in 30 foetuses [megacystis in 18 foetuses (three of these with urinary ascites), hydrothorax in eight foetuses, hydronephrosis in two foetuses, cystic adenomatoid malformation of the lung in one foetus, ovarian cyst in one foetus]. RESULTS: The median gestational age at time of shunting was 23.5 (range 16 - 33) weeks, at time of delivery 35 (range 23 - 41) weeks. The median time span of drains in situ was 19 (range 0 - 170) days. Altogether 18 of 30 foetuses (60 %) had a benefit of foeto-amniotic shunting. CONCLUSION: The best possible selection of pregnancies which might profit from foeto-amniotic shunting is required. The decisive criteria are the underlying defect as well as the severity and progression of the disorder.

The clinical impact of magnetic resonance imaging in fetuses with central nervous system anomalies on ultrasound scan.

OBJECTIVES: Magnetic resonance imaging (MRI) was performed on fetuses with sonographically diagnosed central nervous system (CNS) anomalies to determine frequency and type of cases in which fetal MRI adds clinically relevant information. PATIENTS AND METHODS: Forty-three cases presenting with CNS anomalies by ultrasonography were investigated by MRI. The potential effect of MRI on parental counseling and pre- or postnatal management were the main endpoints. RESULTS: Fetal MRI confirmed the sonographic diagnosis in 28 of 43 cases, showed additional findings in 14 of 43 cases, and was inferior to sonography in 1 of 43 cases. The MRI diagnosis had therapeutic consequences in 11 of 43 patients, with the fetal MRI diagnosis influencing parental counseling in 8 of these 11 patients. Prenatal patient care was not influenced by the additional investigation with fetal MRI. CONCLUSION: MRI is well suited as additional imaging method in fetuses with CNS anomalies. Additional fetal MRI is particularly indicated if the findings might have a therapeutic consequence.

Fetal skeletal deformities - the diagnostic accuracy of prenatal ultrasonography and fetal magnetic resonance imaging.

OBJECTIVE: To evaluate the diagnostic accuracy of prenatal ultrasonography and fetal magnetic resonance imaging (MRI) in fetuses with skeletal deformities (SD). METHODS: Fourteen pregnant women of 21 - 34 weeks of gestation whose fetuses had SD on prenatal ultrasound (seven fetuses with spina bifida, four with complex malformation syndrome, two with scoliosis, and one with chondrodysplasia) were additionally investigated by fetal MRI using a 1.5T superconducting system with T1-and T2-weighted sequences in three section-planes. Main outcome measures were diagnostic accuracy, potential effect on parental counselling and influence on perinatal management of the additional investigation with fetal MRI. RESULTS: In 10 cases ultrasound had a better diagnostic accuracy than MRI concerning the diagnosis of SD. In four cases with spina bifida MRI provided additional information towards preoperative evaluation for neurosurgery. In five cases parental counselling was improved. There was no influence on perinatal management. CONCLUSION: MRI may provide additional information to ultrasound scan in fetuses with spina bifida and consecutive neurosurgery; in fetuses with other skeletal deformities additional information may be expected only in rare cases.

Verification of anomalies of the central nervous system detected by prenatal ultrasound.

OBJECTIVE: The accuracy of fetal ultrasound (US) in diagnosing central nervous system (CNS) malformations was assessed with the aim to define in which cases US is reliable enough to assist in decisions on medical indication for abortions without resorting to magnetic resonance imaging (MRI). DESIGN: Retrospective analysis of the course of 69 fetuses with anomalies of the CNS detected on prenatal US in a university hospital. SETTING: General Hospital of Vienna, University of Vienna, Austria. METHOD: Prenatal US diagnosis was verified by postpartal US, MRI or computed tomography (CT) in the live births, and by autopsy of the fetus in cases of pregnancy termination. RESULTS: Abortion was induced in 40 fetuses for anencephaly (n = 4), exencephaly (n = 6), dorsal dysraphism (n = 6), encephalocele (n = 3), pronounced hydrocephaly (n = 11), holoprosencephaly (n = 4), Dandy Walker cyst (n = 5), and 1 complex syndrome - all confirmed on autopsy. In 29 live births, hydrocephaly, meningomyelocele, and microcephaly had always been correctly identified prenatally. Four Chiari malformations had been missed. Agenesis of the corpus callosum had remained unnoticed in 4 out of 14 cases and been erroneously reported in 5. Diagnostic errors were frequent for Dandy-Walker cyst and great cerebellomedullary cistern. CONCLUSION: Transabdominal fetal US did not lead to unjustified interventions. Inaccuracy in diagnosing abnormalities of the posterior fossa and the median telencephalon as well as aetiological clarification of hydrocephalus require additional MRI of the fetal CNS in patients selected accordingly.

Prenatal diagnosis of a giant foetal lymphangioma and haemangiolymphoma in the second trimester using 2D and 3D ultrasound.

Lymphangiomas are benign tumours of the lymphatic system. Early prenatal diagnosis is important to permit a planned delivery and provide adequate postnatal care. It thereby improves prognosis and allows the option of terminating the pregnancy if poor outcome is predicted. We report two cases, a giant haemangiolymphoma and a lymphangioma. 2D and 3D US findings are presented and differential diagnosis, therapeutic options and prognosis are discussed.

Magnetic resonance imaging in foetuses with bilateral moderate ventriculomegaly and suspected anomaly of the corpus callosum on ultrasound scan.

OBJECTIVE: The diagnosis of anomalies of the corpus callosum (ACC) in foetuses with bilateral moderate ventriculomegaly (BMV) is difficult by means of ultrasound scan. The aim of this study was to examine the value of the additional investigation with magnetic resonance imaging (MRI) in foetuses with BMV and suspected ACC on ultrasound scan. Pathogenesis and clinical presentation of BMV and ACC are discussed. METHODS: 41 foetuses with central nervous system (CNS) anomalies on ultrasound scan were assessed by ultrasonography and MRI from 1999 to 2001. Eight of these 41 foetuses presented with BMV and suspected ACC on ultrasound scan and were prospectively included in the study. Foetal investigations with sonography and MRI were analysed with regard to diagnostic confidence; results were correlated with post partum findings. Six of these 41 foetuses presented with BMV without suspected ACC on ultrasound scan and were retrospectively analysed. RESULTS: Ultrasonography suspected ACC in 8 foetuses with BMV. MRI confirmed the presence of ACC in 4 of these 8 cases. MRI additionally showed ACC in two of the six retrospectively analysed foetuses with BMV without suspected ACC on ultrasound scan. Prenatal MRI diagnosis was confirmed after delivery in all cases. CONCLUSION: MRI is more sensitive than ultrasonography in the evaluation of ACC in foetuses with BMV. For prenatal screening ultrasound still remains the investigation of choice.

Prenatal diagnosis of a de novo inversion of chromosome (2)(p21q11).

Prenatal diagnosis of "apparently balanced" chromosomal rearrangements, if not inherited from a parent, are problematic for genetic counsellors and families. Although the parents need to be informed about the increased risk of multiple congenital anomalies, the anomalies that the fetus is at risk can not be discussed unless a similar breakpoint and accompanying phenotype have been reported in the literature. In the reported case prenatal ultrasound examination revealed a massive hydrocephalus internus and IUGR. The karyotype of the fetus was inv(2)(p21q11) de novo. Postmortem examination revealed short palpebral fissures, hypertelorism, atypical nasiolabial configuration, microgenia, extended position of the fingers, atypical proximal inserted first toe, hydrocephalus internus, hypoplasia of the cerebellum and bulbi olfactorii, bilateral hypoplastic lungs, atrial septal defect II, small right ventricle, dysplasia of the pulmonary valve, hypoplastic pulmonary artery, right proximal ureterostenosis, hypoplastic gall bladder. This is the first description of a de novo inversion (2)(p21q11) in a fetus with multiple malformations.

Prenatal diagnosis of a supernumerary aberrant chromosome 9.

For counselling of parents, as well as to basically understand how chromosome aneuploidies affect embryonic or fetal development, it is of great importance to analyse and collect genotypes of fetuses with clinical anomalies. This report describes the first prenatal diagnosis of a supernumerary chromosome 9 with deletion of the chromosome region 9q34. Ultrasound examination in the 13th week of gestation detected increased nuchal translucency of 6.9 mm, fetal ascites and a pronounced facial anomaly. Hysteroscopic examination before curettage made it possible to describe this facial anomaly as a double-sided, median defect of the superior lip with protrusion of parts of intersegments. This report provides evidence that the absence of trisomy 9 in 9q34 does not prevent abnormal facial development.

Fetal ovarian cysts: development and neonatal outcome.

INTRODUCTION: The aim of the study was to evaluate the outcome of fetal ovarian cysts in relation to their size and ultrasonic appearance. METHODS: We retrospectively analysed pre- and postnatal charts of 61 infants with a prenatal diagnosis of ovarian cysts between 1991 and 2000. RESULTS: In a total of 61 fetuses 65 ovarian cysts were detected by transabdominal ultrasound: 35 (57 %) cysts on the left side, 22 (36 %) on the right side and 4 fetuses (7 %) had bilateral cysts. Three patients with uncomplicated cysts were lost to follow-up and one fetus with bilateral cysts died in the 27th week of gestation. In 17 cysts treatment was necessary. 14 cysts (all complicated) were operated after delivery because of persistence or enlargement. The histological results were either follicular or theca lutein cysts in 12 cases, one lymphangioma and one teratoma. Two cysts were aspirated in utero and one after delivery. In the remaining 40 fetuses, 43 cysts where only controlled by ultrasound. 8 cysts regressed before delivery and 35 cysts after delivery independent of their sonographic appearance. The mean diameter of cysts that required treatment was significantly different from the mean diameter of cysts that resolved spontaneously (6.8 [SD 2.4] cm vs. 3.3 [SD 0.8] cm; p < 0.01). CONCLUSION: Complicated cysts which do not regress should be treated either by laparotomy or laparoscopically after delivery. Uncomplicated cysts which exceed 5 cm could be treated by in utero aspiration or aspiration after delivery to avoid further complications. Cysts smaller than 5 cm, presenting the tendency to regress, should be left untouched independent of their sonographic appearance.

[The intrauterine rupture of the fetal bladder as a complication of low urinary tract obstruction]. / Die intrauterine Blasenruptur als Komplikation infravesikaler Harnentleerungsstörungen beim Feten.

Lower urinary tract obstruction in fetuses causes megacystis, megaureter and hydronephrosis. The spontaneous rupture of the fetal bladder represents a rare complication in cases of total bladder outlet obstruction. We report about two different cases, present pre- and postnatal therapeutic regimes and discuss the possibility of spontaneous healing of a ruptured fetal bladder before delivery.

The twin-twin transfusion syndrome - an unsolved problem.

AIM: We analysed the data of pregnancies with twin-twin transfusion syndrome (TTTS) in order to identify clinical factors present at the time of diagnosis which can be used to predict the outcome of the pregnancy. METHOD: We report prenatal sonographic findings, interventions and outcomes of 28 TTTS pregnancies over a three-year period. Patients were classified into stages of TTTS as follows: Stage I: bladder of donor visible, normal Doppler studies; Stage II: bladder of donor not visible, normal Doppler studies; Stage III: abnormal Doppler studies; Stage IV: hydrops. RESULTS: In nine pregnancies the infants did not survive the perinatal period (the first 28 days after delivery): the median gestational age at delivery was 24 (range 21 - 29) weeks; six of these nine pregnancies (66 %) were classified as stages III or IV. In five pregnancies one infant survived the perinatal period: the median gestational age at delivery was 28 (range 27 - 32) weeks; four of these five pregnancies (80 %) were classified as stages III or IV. In 14 pregnancies both infants survived the perinatal period: the median gestational age at delivery was 30.5 (range 28 - 39) weeks; two of these 14 pregnancies (14 %) were classified as stages III or IV. CONCLUSION: In pregnancies complicated by TTTS, the results of Doppler studies at the time of diagnosis represent the most important clinical factor predicting the outcome of the pregnancy. At the time of delivery, however, the predicted outcome is most directly linked to the gestational age.

Dandy-Walker malformation as sonographic marker for fetal triploidy.

Fetal triploidy is a frequent reason for early abortion, and only few fetuses survive into the second trimester of pregnancy. Common sonographic markers for triploidy in the second trimester are severe asymmetric growth restriction (triploidy of maternal origin) and partial molar changes of the placenta (triploidy of paternal origin), together with structural fetal malformations. We report prenatal sonographic findings of thirteen triploid fetuses between 18 and 34 weeks' gestational age (eleven fetuses with 69, XXX, and two fetuses with 69, XXY). Intrauterine growth restriction (11/13 fetuses), oligohydramnios (8/13), bilateral cerebral ventriculomegaly (6/13), structural heart defects (4/13), and Dandy-Walker malformation or Dandy-Walker variant (4/13) were the most frequent findings. We conclude that the Dandy-Walker malformation and Dandy-Walker variant should be considered as additional sonographic markers for fetal triploidy.

Duodeno-jejunal atresia with volvulus, absent dorsal mesentery, and absent superior mesenteric artery: a hereditary compound structure in duodenal atresia?

Duodenal atresia predominantly represents an isolated entity, but could also be part of a complexly structured intestinal malformation. We report four children, including two from one family, with duodeno-jejunal atresia associated with malrotation, volvulus, and absent parietal attachment of the mesentery. Gross absence of the mesentery and absence of distal parts of the superior mesenteric artery were the most remarkable findings. The small intestine was supplied retrogradely from the right colic artery. Consideration of embryological theories of this malformation takes into account the important role of the duodeno-jejunal flexure during the process of entry of the small bowel loops into the abdomen. Familial occurrence suggests autosomal recessive inheritance. We propose differentiating the pathoanatomical findings in our patients from classical apple peel small bowel syndrome (APSB).

Evaluation of first trimester pregnancy in cases of threatened abortion by means of doppler sonography.

OBJECTIVE: Threatened abortion is one of the major problems in Obstetrics and applies to (1/3) of all pregnancies. The aim of this study was to establish normal ranges for Doppler indices of the flow velocity waveforms in uterine arteries (S/D, RI, PI) and ss-hCG serum concentrations in a control group in the first trimester of pregnancy. The obtained values were compared with those obtained in pregnancies threatened by abortion (6 - 11 weeks). METHODS: Investigated groups: 55 controls and 47 with symptoms of threatened abortion, 27 of them aborted. Ultrasound examinations were carried out by means of an endovaginal probe. Serum ss-hCG was determined by immunoenzymatic method. The standards for measured values were established based on means from measurements obtained in the control group in the corresponding week of pregnancy. RESULTS: We observed negative correlation between gestational age and RI and negative tendencies for S/D and PI indices in the control group. Positive correlation (p < 0.05) was found between ss-hCG serum concentration and gestational age (up to 9(th) week) and significant differences in ss-hCG concentrations between both examined groups. There were also statistical differences for S/D, RI and PI indices in both analyzed groups for each week of pregnancy. CONCLUSION: We conclude that measurement of the quality parameters of the flow velocity waveforms in uterine arteries and calculation of beta-hCG concentration in serum are useful methods in diagnosis of threatened abortion in the first trimester of pregnancy.