Prenatal sonographic diagnosis of skeletal dysplasias.

OBJECTIVE: To assess the types and numbers of cases, gestational age at specific prenatal diagnosis and diagnostic accuracy of the diagnosis of skeletal dysplasias in a prenatal population from a single tertiary center. METHODS: This was a retrospective database review of type, prenatal and definitive postnatal diagnoses and gestational age at specific prenatal diagnosis of all cases of skeletal dysplasias from a mixed referral and screening population between 1985 and 2007. Prenatal diagnoses were grouped into 'correct ultrasound diagnosis' (complete concordance with postnatal pediatric or pathological findings) or 'partially correct ultrasound diagnosis' (skeletal dysplasias found postnatally to be a different one from that diagnosed prenatally). RESULTS: We included 178 fetuses in this study, of which 176 had a prenatal ultrasound diagnosis of 'skeletal dysplasia'. In 160 cases the prenatal diagnosis of a skeletal dysplasia was confirmed; two cases with skeletal dysplasias identified postnatally had not been diagnosed prenatally, giving 162 fetuses with skeletal dysplasias in total. There were 23 different classifiable types of skeletal dysplasia. The specific diagnoses based on prenatal ultrasound examination alone were correct in 110/162 (67.9%) cases and partially correct in 50/162 (30.9%) cases, (160/162 overall, 98.8%). In 16 cases, skeletal dysplasia was diagnosed prenatally, but was not confirmed postnatally (n = 12 false positives) or the case was lost to follow-up (n = 4). The following skeletal dysplasias were recorded: thanatophoric dysplasia (35 diagnosed correctly prenatally of 40 overall), osteogenesis imperfecta (lethal and non-lethal, 31/35), short-rib dysplasias (5/10), chondroectodermal dysplasia Ellis-van Creveld (4/9), achondroplasia (7/9), achondrogenesis (7/8), campomelic dysplasia (6/8), asphyxiating thoracic dysplasia Jeune (3/7), hypochondrogenesis (1/6), diastrophic dysplasia (2/5), chondrodysplasia punctata (2/2), hypophosphatasia (0/2) as well as a further 7/21 cases with rare or unclassifiable skeletal dysplasias. CONCLUSION: Prenatal diagnosis of skeletal dysplasias can present a considerable diagnostic challenge. However, a meticulous sonographic examination yields high overall detection. In the two most common disorders, thanatophoric dysplasia and osteogenesis imperfecta (25% and 22% of all cases, respectively), typical sonomorphology accounts for the high rates of completely correct prenatal diagnosis (88% and 89%, respectively) at the first diagnostic examination.

3D ultrasound in fetal spina bifida.

3D ultrasound can be used to study the fetal spine, but skeletal mode can be inconclusive for the diagnosis of fetal spina bifida. We illustrate a diagnostic approach using 2D and 3D ultrasound and indicate possible pitfalls.

The nasal bone in fetuses with trisomy 21: sonographic versus pathomorphological findings.

OBJECTIVE: To compare the sonographic findings of the nasal bone in fetuses with trisomy 21 with pathomorphological findings to determine whether the bone is truly absent. METHODS: Seventeen first-trimester fetuses with trisomy 21 were identified; the median gestational age was 12 weeks (range, 11-14) and the median maternal age was 38 (range, 27-47) years. Transabdominal ultrasound examination, preceding transabdominal chorionic villus sampling (TA-CVS) for karyotyping, included assessment of the fetal nose. The nasal bone was determined to be 'hypoplastic' or 'absent' and its length was measured. All pregnancies underwent termination after diagnosis. Serial sagittal sectioning with hematoxylin and eosin-staining of formalin fixed tissue was performed. RESULTS: Of the 17 cases, the nasal bone was sonographically evident, but with severe hypoplasia in 10 cases, absent in six, and in the remaining case it was not able to be assessed due to fetal position. Histomorphologically, in 16 cases a nasal bone was present, detectable by the evidence of an ossification center, and in one case the ossification structure was not clearly visualized. Retrospective review of ultrasound images could identify nasal bones in five of the six cases in which they were initially reported as being absent on ultrasound examination. These were visible, but less distinct and had decreased echogenicity, hence misinterpretation led to the false finding of an absent nasal bone when it was in fact present but hypoplastic. CONCLUSION: Sonographic assessment of the fetal nasal bone should not distinguish between 'present' and 'absent', but instead between 'normal' and 'hypoplastic'. For reproducible results it is necessary to standardize the sonographic examination. The sonographic landmarks of the fetal nose are: the nasal bone, the skin above and the cartilaginous tip of the nose.

Trisomy 18 in chorionic villus sampling: problems and consequences.

Among 1547 patients undergoing first-trimester prenatal diagnosis, 100 fetal chromosome aberrations were detected. Thirteen of these involved chromosome 18. In two structural abnormalities of chromosome 18, the aberration could be excluded in amniotic fluid cells and two healthy infants were born. Trisomy 18 was not confirmed in amniotic fluid cells in three trisomy 18 mosaics. In eight non-mosaic trisomy 18 first-trimester diagnoses, the diagnosis was excluded by amniotic fluid cells or fetal cultures in four, and confirmed in the remaining four. Diagnosis of chromosome 18 aberrations in the direct preparation should be confirmed in the long-term culture of the chorionic villus sample or by amniotic fluid cultures.

Parvovirus B19 infection of the fetus. Histology and in situ hybridization.

Fetal tissues from 16 spontaneous abortions, two terminations, and one perinatal death, 18 of which were associated with maternal human parvovirus B19 infection, were examined for B19 infection by histology and in situ hybridization using a digoxigenin-labeled B19-DNA probe. In 15 spontaneous abortions and one termination, erythroblasts with intranuclear inclusions (lantern cells) reacted with B19-DNA by in situ hybridization. No internal or external fetal malformations were observed. Because 13 (86.7%) spontaneous abortions with lantern cells occurred between the 20th and 28th weeks of gestation, it is postulated that B19 infection may be a particular threat to the fetus during this stage of gestation.

[Diagnostic and clinical value of Doppler sonography of fetal blood vessels]. / Der diagnostische und klinische Stellenwert der Dopplersonographie fetaler Gefässe.

Fetal Dopplersonography is a not generally applicable additive method in prenatal care. Its main value is the non-invasive access to the fetal cardiovascular system. Previous studies show a diagnostic gain in sonographically and clinically pathologic pregnancies, mainly those with intrauterine growth retardation. The validity of a general screening of all pregnant women is poor. The examination of fetal physiology, pathophysiology as well as of the influence of drugs on fetuses and pregnant women will profit from Dopplersonography and fetal blood sampling.

Successful intrauterine treatment of fetal hydrops caused by parvovirus B19 infection.

The infection with parvovirus B19 during pregnancy causes in 1/3 of the cases an aplastic crisis in the fetus and consecutively generalized fetal hydrops as a result of severe anemia. Some cases of fetal hydrops and intrauterine death are reported. In our two cases, the fetal therapy by intrauterine intravasal transfusion was successful and the children developed normal. The techniques and indications for fetal blood sampling and the method of intrauterine intravasal transfusion are explained.

[Molecular biological demonstration of parvovirus infection in fetal tissue]. / Molekularbiologischer Nachweis einer Parvovirusinfektion in fetalem Gewebe.

We report on the morphological findings in 16 fetuses with serologically confirmed maternal parvovirus B19 infection. Typical routine morphological findings of the hydropic fetuses were the presence of abnormal erythroblasts with typical nuclear inclusions. These infected cells positively stained immunohistochemically with antibodies against a recombinant virus protein, as well as they ultrastructurally contained virus particles. Using in-situ hybridization techniques, we were able to demonstrate the presence of parvovirus B19 genome in the infected cells, while no other cell type was shown to contain virus genome. According to our results the differential diagnosis of fetal parvovirus B19 infection should be considered in each case with hydrops fetalis of unknown origin. The careful routine microscopic examination of fetal tissue may provide evidence for parvovirus infection which should be confirmed by in-situ hybridization analysis.