First Trimester Screening And Diagnosis For Fetal Chromosome Aneuploidy Abnormalities

ObjectOn the basis of first trimester combined screening test by maternal age,NT thickness, maternal serum β-hCG and PAPP-A, to explore non-invisive prenatal screening and diagnosis by free fetal nucleic acid in maternal plasma and proteomics and to solve the defects of late screening, low detection rate and invasive in screening fetal chromosome aneuploidy abnormalities.Methods1. A total of5000cases of pregnant women at11-13+6weeks in our hospital from January1,2010to December31,2011, all women have an ultrasound scan to measure fetal NT and perform other ultrasound markers, including nasal bone, ductus venosus blood flow, tricuspid blood flow, at the same time maternal serum free β-hCG and PAPP-A as part of screening for chromosomal abnormalities. The datas were entered into the database, according to patient age, body mass, race, smoking history, pregnancy weeks, using the software to calculate the risk value of pregnant women. Risk cutoff1:270.2. High-risk pregnant women were performed invasive prenatal diagnosis by transabdominal chorionic villus sampling(TACVS) and amniocentesis. For those termination of pregnancy, apoblema was detected by fluorescence in situ hybridization(FISH).3.37cases cffDNA and16cases cffRNA single nucleotide polymorphism in maternal plasma were detected, including two cases of Rh negative blood type women.4. We used a4-plex iTRAQ labelling in conjunction with a2D-LC-MS/MS approach to examine plasma samples from5cases with DS in comparison to4matching controls to detect quantitative differences.Results1.5000cases of pregnant women were detected, including4983normal cases,9with trisomy21,1with triploidy and trisomy13respectively,2with trisomy18.4with Turner syndrome.2. Detection rate were89%and false positive rate were2.3%for trisomy21.3. Of fetuses with trisomy21,55.6%with absent nasal bone,55.6%with tricuspid regurgitation and44.4%with abnormal ductus venosus blood flow pattern,33.3%with absent nasal bone and tricuspid regurgitation and reversed a-wave in the ductus venosus.4. Tricuspid regurgitation was found in80%and abnormal ductus venosus blood flow was found in75%normal karyotype fetuses with congenital heart deficient.5. By cffDNA assay, six cases of chromosome aneuploidy abnormalities were found, including two cases of trisomy21, a case of trisomy18, a case of trisomy13, two cases of45X0, which was consistent with cytogenetic method.6. Two cases of trisomy21and14normal fetuses of pregnant women were not detected fetal chromosomal abnormalities by plasma PLAC4RNA-SNP alleles G/A ratio (1.055vs.1.00, P＞0.05).7. we detected29over-expressed proteins in DS groups as potential markers.Conclusion1. Combined screening test has high detection rate and low false positive rate at11-13+6week of gestation and can be used widely.2. It is the feasibility of using excess ultrasound markers to increase detection rate for aneuploidies at11-13+6week of gestation,but we need further study.3. Ultrasound markers abnormalities (NT, DV, TR) may be associated with congenital heart disease at11-13+6week of gestation.4. By maternal fetal DNA detection for diagnosing fetal chromosomal aneuploidy is feasible, which has good negative predictive value and can be used as prenatal screening and diagnostic tools for special populations.5. Protein biomarkers and cffRNA can be new biomarkers for DS in the future.