| Background:Birth defects are becoming an outstanding public health concern in the whole world. It is estimated that 800-1,200 thousand new babies are born with any birth defect every year, sharing 4%-6% of total births annually in China. The World Health Organization (WHO) reported that birth defects are going to be an important factor leading to children death, premature death, morbidity, disability and low quality of life.70% of birth defects are caused by genetic fators. Chromosomal aberrations are the most common genetic factors that lead to birth defects, and Down Syndrome(DS) is the most common chromosomal disease, of which morbidity in the neonatal about 1/600-1/1000. The clinic feature with DS is congenital dysnoesia, unusual facies, developmental lag in psycho-physical build, even with other serious multiple abnormalities,and So far there is no medical way to cure. In China, according to China Healthy Birth Science Association, approximately 20 million newborns each year, about 26,600 children born with Down syndrome. Now 600 thousand more DS are born in China, causing more than 2 billion of economic burden.Prenatal screening and diagnosis can screen the serious defects of fetuses, and make timely intervention so as to reduce birth defects in children. American College of Medical Genetics(ACMG) in 1993 pointed out standard chromosomal analysis serving as the primary diagnostic and confirmatory evaluation for chromosomal disease. However, standard chromosomal analysis takes a long time to get the result, to have more complicated operation, and at the same time so many factors can influence the samples to collect and culture that the final results could not be confirmed. Flourescence in situ hybridization (FISH) is the new technology combining Molecular Biology (probe) and cytogenetic (chromosome) to detection chromosomal aberrations. Today, FISH testing has become the number of chromosome abnormalities and rapid second trimester prenatal diagnosis of the most effective methods. Compared with karyotype analysis, FISH testing has many advantages, such as rapid, simple, accurate, reliable, high-sensitivity and specificity and so on. FISH testing study reported that it just need 24 hours or shorter to detect 80%-95% of chromosomal abnormalities, as well as more than 99.8% reliability in the second trimester of pregnancy. More and more clinical application, FISH testing application in prenatal diagnosis has been changed ACMG Guide. The Guide reported that the recommendation of technique is from "needing additional assessment " to " relatively mature" and of application is from "only in conjunction with standard cytogenetic analysis" to "make the same role with conventional chromosome analysis techniques to some extent".Comprehensive analysis of advantages and disadvantages of FISH technology and karyotyping, it is the confusing problems that how to use those diagnostic methods for rational clinical decision-making. In our country, prenatal diagnosis is in the initial stage, and the development is not balanced. Medical standards in different regions, economic conditions vary considerably. Therefore, the emphasis on prenatal diagnosis, the application level are not the same, there is a specific implementation of the process of doubt and misunderstanding.Following the widely improvement of FISH technique, FISH commercial kits are developped and can well meet the high requirement clinically, because of its high stability, low cost, robotization and specilization. In the old days, the prenatal diagnosis center mostly depended on imported probe to finish experimen reserch and clinical application. Nowadays, to extensively broaden medical market, the government more and more attach importance to develop and publicize our own probe technique.OBJECTIVE:To deal with the problem that how to use rationally both FISH technique and karyotype analysis in prenatal diagnosis, it is collected 435 cases of high-risk pregnant women from Southern Hospital with prenatal diagnosis, by suming up the indications of prenatal diagnosis, clinical information and the implementation of the relationship between prenatal diagnosis program for aneuploidy, as well as taking FISH techniques and karyotype analysis as their primary diagnosis for chromosome aneuploidy. It is made the research to chromosome aneuploidy for prenatal diagnosis, so as to provide some objective basis to form a consensus for prenatal diagnosis.This study make comparative analysis of clinical effect and Health Economics for two different prenatal diagnostic kits from both Abbott Vysis Inc. and GPhr companies. In order to make objective recognition of the advantages and disadvantages for the reagents and optimize the domestic FISH technology.METHODS:1. From January 2008 to April 2009, a retrospective analysis for clinic application of 435 high-risk pregnant women from the Prenatal Diagnosis and Genetics Center in Southern Hospital, including their ages, history, gravidity indications and other information. All the data were made statistical analysis by SPSS13.0-software Involving x2-test, t-test and Logistic Regression Analysis, so as to establish the regression model for prenatal diagnosis program of chromosomal aberration.2. In accordance with the principle of random data table,40 cases of amniotic fluid samples were randomly selected from high-risk pregnant women in 435. Amniotic fluid samples were analyzed in parallel by karyotyping analysis and FISH testing by Abbott Vysis reagents and GPhr reagents to detect. the detection rates of indicators such as hybridization, signal strength, rate of clinical diagnosis. the time, cost and so on were analyzed. Statistical data processing are applied by SPSS 13.0 software.RESULTS:1. all of the 97 cases using FISH testing are successful to hybriding, as well as the clearly signals and easy-to-analysis.213 cases by karyotype analysis showed false mosaic in 2 cases, failed in 4 cases and maternal cell contamination in 2 cases. The abnormal results of 435 cases are thalassemia in 76,21-trisomy in 9 cases,18-trisomy in 4 cases,13-trisomy in 1 case,92, xxxx/46, xx in 2 cases and 2 cases of balanced translocation chromosome.2. Make retrospective analysis the clinical data from 435 high-risk pregnant women for prenatal diagnosis. There are 310 cases for prenatal diagnosis of chromosomal abnormalities with FISH testing and karyotype analysis. To select 10 factors closely related with prenatal diagnosis, It was made Pearsonχ2, t-test and Logistic regression analysis to set up Logistic regression model for prenatal diagnosis of chromosomal abnormalities Y=-2.234+1.685X3-0.543X5+0.845X6. The Regression equation was significant (χ2=4.321, df=1, P=0.0038).3. Detected by FISH cost 2 times higher than the karyotype analysis per person, and two combined diagnostic methods would make the cost higher than 3 times. Gene detection of thalassemia for high-risk pregnant women, when screening for aneuploidy, which methods to choose, karyotype analysis or FISH, the cost would increased by 1-2 times. The report would take one week for karyotyping more than FISH testing by fetal blood. Time-costly, FISH testing for amniotic fluid is better than karyotyping, but effect-costly, karyotyping for blood is better than FISH testing.4. It was reported that the rate of FISH hybridization between two reagents was significantly different. (21 and 13 reagents P< 0.001,18xy kits, P＜0.001。) Diagnostic kit designed by Abbott Vysis Inc. the effect of hybridization is much better (21 and 13 kits,0.968±0.012; 18xy kits,0.985±0.010).The weakness of GPhr probes is mainly on 21 and 13 kits, but hybridization of 18xy kits could reach more than 90%.5. Signal strength of both Abbott Vysis Inc. and GPhr probes is compared in the research. The result reported that there was significant difference (P<0.001) with signal strength of 21-13 probes, from which showed that the singal with 21-13 probe designed by Abbott Vysis Inc. is better than GPhr's. However, there was no statistically significant difference with the signal strength of 18xy probe. It is thought that the 18xy probe designed by GPhr could have the same signal strength to the Abbott Vysis Inc.6. It took nearly one hour less than GPhr's for FISH testing by the Abbott Vysis reagents, which followed the protocol of the hybrid instrument and rapid washing operation. while according to the cost, Abbott Vysis reagents 1386 yuan per person, GPhr. reagent 1114 yuan per person, indicating that the GPhr. had lower cost.CONCLUSION:1. The prenatal diagnosic model of chromosomal aberration indicated that the pregnant women with gestational weeks and anomaly of ultrasound would prefer to choose karyotyping to diagnosis, while women with high risk in biochemistry preferred to FISH testing. There is no difference for pregnant women with maternal age to choose whether FISH testing or karyotype analysis. Clinicians with the use of models and based on evidence-based medicine could make the reasonable prenatal diagnosis, avoiding the bad diagnosis based on subjective experience and several abnormal indicators. For prenatal diagnosis of chromosome abnormalities, the fee pricing gap between non-invasive and invasive diagnostic screening is small, so as to make pregnant women to easy to choose invasive diagnosis. FISH detection of prenatal diagnosis is more quick and easy, as well as accurate. However, the costs of FISH testing is higher than the karyotype analysis, so it is restricted to widely application. It is recommended that fetal blood with karyotype analysis and amniotic fluid samples with FISH testing as the third trimester prenatal diagnosis program.2. Excluding maternal blood contamination, FISH testing can make up the weakness, which it would develop false mosaic from amniotic fluid cells in vitro and failed to get enough cell to karyotyping, as well as dectecting low-level mosaicism by reasonable cut-off for statistics signals. So, FISH technique is not only a fast and reliable method of distinguishing between true and false mosaic, it is the way to detect the number of chromosome abnormalities and rapid second trimester prenatal diagnosis of the most effective methods.3. FISH prenatal diagnosis kit designed by Abbott Vysis company showed better hybrid rate, signal strength and time-cost than the kits designed by GPhr. However, lower price and the light signal concentration, less dispersion from chromosome 18 probe were the goodness of GPhr. |
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