Frontonasal facial angle in chromosomally normal fetuses at 11+0 to 13+6 weeks.

AIM: To establish the normal range of frontonasal angle (FNA) at 11+0 to 13+6 weeks of gestation and the feasibility of FNA measurement, evaluate the correlation of such a parameter with crown-rump length (CRL) and nuchal translucency (NT) and assess the potential of FNA in improving the performance of first trimester sonographic and biochemical screening for trisomy 21. METHODS: We conducted a prospective study in 400 singleton uncomplicated pregnancies. FNA was obtained during maternal screening for trisomy 21. NT thickness and FNA were measured by 2D ultrasound in a midsagittal plane of the fetal profile. FNA was measured between the line along the upper surface of the frontal bone and the superior edge of the nasal profile until the echogenic tip. Determination of maternal serum free ß-human chorionic gonadotropin (ß-hCG) and pregnancy-associated plasma protein-A (PAPP-A) was committed and concomitantly evaluated by blood sample. Patient-specific risk was calculated using Fetal Medicine Foundation software (Astraia Software GMBH, Munich, Germany). RESULTS: Mean FNA increased with CRL from 119.80° at CRL 45 mm to 125.85° at CRL 84 mm. A significant association between the FNA and NT thickness was detected, while no significant association was found between FNA and serum PAPP-A or ß-hCG. CONCLUSION: At 11+0 to 13+6 weeks FNA increases with fetal CRL and NT thickness. Such an increase is not related to serum biochemistry.

Prenatal diagnosis of genomic disorders and chromosome abnormalities using array-based comparative genomic hybridization.

Cytogenetic analysis is a crucial tool of prenatal diagnosis. The ability to rapidly detect aneuploidy and identify small structural abnormalities of foetal chromosomes has been greatly improved by the use of molecular cytogenetic technologies. Microarray-based Comparative Genomic Hybridization (aCGH) has been recently employed in postnatal diagnosis of cryptic chromosomal aberrations, but use in prenatal diagnosis is still limited.We set-up a diagnostic protocol which uses aCGH technology on genomic DNA isolated from uncultured chorionic villus sampled at 11-12 week's gestation. We used a commercially targeted microarray (MDTelArray, Technogenetics Srl - Bouty Group, Sesto S. Giovanni, Milan, Italy) constituted by 167 genomic clones corresponding to 34 critical regions frequently involved in microdeletions and microduplications and 126 subtelomeric clones. Array validation has been carried-out via retrospective analysis of DNA isolated from a series of cytogenetically normal chorionic villus samples (CVS) and of DNA isolated from cytogenetically abnormal cultured amniocytes, CVS or peripheral blood. A pilot prospective study was undertaken analyzing 25 CVS obtained from foetuses at risk for chromosomal aberrations. aCGH results both for retrospective and prospective studies were in agreement with data obtained using "classical" cytogenetic analysis, and/or FISH analysis or DNA testing. Although these preliminary data support the usefulness of aCGH in prenatal diagnosis, further prospective studies are required to verify the feasibility of introducing this technique as part of the diagnostic armamentarium for identify affected foetuses.