Prenatal genetic counseling and consanguinity.

OBJECTIVES: To evaluate the prevalence of consanguineous patients at a Western European prenatal genetic counseling clinic and to describe demographic as well as health-related characteristics of this patient group. METHOD: Retrospective analysis of 1964 primary consultations at the Prenatal Genetic Counseling Outpatient Clinic at the Medical University of Vienna General Hospital in Austria. Characteristics of consanguineous patients were compared with those of a control group of not-related unions. RESULTS: A total of 8.9% (174/1964) of all patients lived in a consanguineous union, meaning they were related as second cousin or closer [78.7% (137/174) first cousin, 14.4% (25/174) second cousin, 6.3% (11/174) first cousin once removed or 0.6% (1/174) uncle/niece]. Consanguineous patients were significantly younger (26.6 ± 5.4 vs 30.4 ± 6.5, p < 0.01) and of non-Austrian background [92.5% (161/174) vs 32.8% (57/174), p < 0.01] than not-related controls. Forty-six per cent (80/174) were referred during an ongoing pregnancy. The main counseling issue was family history of consanguinity (ICD Z84.3) in 31.6% (55/174) of cases. CONCLUSIONS: Estimations of the prevalence of consanguinity among the general population in Western Europe likely highly underestimate the evaluated prevalence among patients referred for prenatal genetic counseling. Counseling strategies need to take into consideration that consanguineous patients are more likely to be young and have an immigrant background.

Prenatal genetic diagnosis using microarray analysis in fetuses with congenital heart defects.

OBJECTIVE: To evaluate the use of microarray analysis as a tool for the detection of submicroscopic chromosomal aberrations in prenatal diagnosis. METHODS: Twelve consecutive singleton fetuses with congenital heart defects but normal karyotype and normal fluorescence in situ hybridization results for the DiGeorge region were examined for chromosomal aberrations by genomic microarray analysis. Results were confirmed by fluorescence in situ hybridization and quantitative real time-polymerase chain reaction. RESULTS: At 1 Mb resolution, potentially causal copy number variations were identified in 3 out of 12 fetuses (25%) comprising a 9 Mb q terminal deletion on chromosome 15, a 3.5 Mb duplication in the critical region for the Potocki-Lupski syndrome on chromosome 17 and a mosaic trisomy 7. At higher resolution, aberrations with uncertain significance were identified in a further three cases (25%). CONCLUSION: In our study, the application of microarray analysis in prenatal testing proved to be a valuable tool for the identification of submicroscopic chromosomal aberrations where conventional cytogenetic methods failed. Selection of appropriate resolution was found to be critical to obtain reliable, diagnostically conclusive data.

Magnetic resonance imaging of the normal placenta.

The goal of this study was to provide a representative description of the normal placenta with contrast medium-free magnetic resonance imaging (MRI) in order to determine a standard of reference. One hundred consecutive singleton pregnancies were investigated by MRI without application of a contrast medium. The mean gestational age (GA) at the time of investigation was 29.5 weeks (range 19-40). Patients with suspected utero-placental insufficiency (UPI) or placental anomalies were excluded. Signal intensities were assessed and correlated with the respective GA. Antenatal MRI without contrast medium was able to depict placental status and morphological changes during gestation. A regular homogeneous structure was found in weeks 19-23. Subsequently, sporadic, slightly marked lobules appeared, which increased in number and markedness with ongoing gestation. Stratification of the lobules was observed after 36 weeks. The ratio of placental and amniotic fluid signal intensities decreased significantly with higher GA and with placental grading. MRI is well suited as an imaging method for the placenta. Our data may be used as a reference in the assessment of the placenta on MRI, and may have further clinical impact with respect to the determination of UPI.

Timing of referral for prenatal genetic counselling.

OBJECTIVE: To evaluate the timing of referrals for prenatal genetic counselling. METHOD: The data of 406 consecutive patients referred because of a family history of genetic disease or a suspected risk factor for genetic disease other than an unfavourable first trimester screening outcome were retrospectively analysed. RESULTS: In 37.2% (151/406) of included patients, a pregnancy was already ongoing. The mean gestational age at first contact was 13.6 weeks (SD 5.5 weeks). The main counselling issues were previous pregnancy with abortive outcome (ICD O00-O08) 23.9% (97/406), chromosomal abnormalities (ICD Q90-Q99) 16.7% (68/406) and metabolic disorders (ICD E70-E90) 9.9% (40/406). As a result of prenatal genetic counselling, invasive prenatal diagnostic procedures were performed in 11.3% (46/406) of all patients. CONCLUSION: Patients are often referred to prenatal genetic counselling when prenatal diagnosis of a familial genetic condition is no longer feasible, preventive measures are limited and alternative reproductive options have become impossible. Healthcare providers are challenged to improve services so prenatal genetic counselling can take place before conception.

Magnetic resonance imaging and ultrasound in the assessment of the fetal central nervous system.

Ultrasound is the screening modality of choice for evaluation of the fetal central nervous system (CNS). However, in cases of difficult diagnosis further fetal investigation is desirable. Due to ultrafast magnetic resonance imaging (MRI) techniques artifacts from fetal motions are minimized. MRI involves no exposure to radiation and hence appears to be safe. Due to the better soft tissue contrast, additional investigation by MRI may extend the sonographic diagnosis of fetal CNS-anomalies. Ultrasound and MRI are complementary imaging methods in the evaluation of the fetal CNS. The most important indications for ultrasound are screening for CNS anomalies and serial assessment of the dynamic of the disorder. The most important indications for fetal MRI are the "second opinion" and investigation by fetal MRI instead of postpartum MRI (especially in cases of planned postpartum intervention). In this article the indications and limitations of ultrasound and magnetic resonance imaging in the evaluation of the fetal CNS are discussed.

Fetal and early postnatal magnetic resonance imaging--is there a difference?

AIM: To evaluate whether fetal magnetic resonance imaging (MRI) could replace early postnatal MRI in fetuses with central nervous system (CNS) anomalies. METHODS: Thirteen pregnancies presenting with fetal CNS anomalies were investigated using MRI. Indications included ventriculomegaly combined with additional CNS anomaly (n=5), isolated ventriculomegaly (n=2), arachnoid cyst (n=2), holoprosencephaly (n=1), complex malformation syndrome (n=1), Dandy walker malformation (n=1) and midline cyst (n=1). Early postnatal MRI followed within the first six weeks of life. RESULTS: Investigation with early postnatal MRI confirmed the fetal MRI diagnosis in all cases. Investigation with postnatal MRI presented additional information in two cases. However, there was no change in patient care. CONCLUSIONS: Fetal MRI should replace early postnatal MRI in infants with CNS anomalies.

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.