Risk Estimation of Down’s Syndrome and Economic Evaluation for Its Screening

• Main Authors: Hsiao-Lin Hwa, 華筱玲
• Other Authors: Tony Hsiu-Hsi Chen
• Format: Others
• Language: en_US
• Published: 2004
• Online Access: http://ndltd.ncl.edu.tw/handle/78556589581537745835

博士 === 國立臺灣大學 === 流行病學研究所 === 92 === Down’s syndrome (trisomy 21) is the most common chromosomal anomaly worldwide, and the most commonly recognized genetic cause of mental retardation. The incidence of Down’s syndrome (DS) is 1.2-1.7 per 1000 live born, and the total prevalence was about 1.5 per 1000 live birth and fetal deaths. Because there is no treatment for this condition, prevention with early prenatal diagnosis and termination of the pregnancy is the only available method. Etiology and risk factors have been discussed from many aspects. Advanced maternal age is the only dominant risk factor in general population. Prenatal diagnosis with invasive procedures and cytogenetic analysis has been offered to pregnant women based on maternal age (≧ 35y/o) since 1970’s in many developed countries. However, less than 30% DS fetuses would be identified by this screening policy in a population with 5% pregnant women above 35 years old. The maternal serum screening for DS with biomarkers was introduced in 1980s. The alpha-fetoprotein (AFP), human chorionic gonadotrophin (hCG), and unconjugated estriol (uE3) were the most commonly used markers in the second trimester. With variable combination of biochemical markers with maternal age at second trimester, the detection rates of serum screening ranged from 35 to 70% at different cut-off points (1:200-1:300) and false positive rates. In Taiwan, the reported incidence of Down’s syndrome is 0.118%. Maternal serum screening with double test (AFP and hCG) was introduced in Taiwan in 1992, and was generally undertaken by pregnant women now. The impact was presented in the decreased ratio of live-birth to stillbirth of Down’s syndrome fetuses in young women thereafter. However, Risk estimation for Down’s syndrome in serum screening with maternal age and multiple serum biomarkers is usually complicated and computationally intensive. It is necessary to construct a relatively simple and flexible scoring system. The detection rate of maternal serum screening in younger pregnant women is relatively low. It can be improved by changing the cut-off point. Double test and triple test have been the two most commonly used methods in mid-trimester. The cost-effectiveness with adding uE3 is controversy. Much discussion about performance of the screening has been provoked, with little known about how women benefit from it. We intended to adopt WTP to assess the value pregnant women attach to the benefits related to screening for Down’s syndrome. The major aims of this thesis are: (1)To develop a risk estimation method of serum screening using logistic regression with simple scoring system. (2)To determine the optimal cut off risk for maternal serum screening in young women (<35y/o) with Receiver Operating Characteristics Curve using method in (1). (3)To perform a cost-effectiveness analysis for comparison of different serum screening methods using method in (1) and (2). (4)To identify the willingness-to-pay for screening of pregnant women and the influencing factors. The study population was pregnant women who visited a medical center in Taipei for prenatal care during October 1993 to June 2002. For each woman, basic data about this pregnancy and measurements of biomarkers were collected. For willingness-to-pay evaluation, questionnaires concerning willingness-to-pay for Down’s syndrome screening were collected at out-patient department of this center. Univariate and multivariate logistic regression models were established with maternal age, and biomarker levels. A simple scoring system with Spiegelhalter-Knill-Jones (S-KJ) approach was developed. Sensitivity and specificity at different cut off points were calculated. Receiver Operating Characteristics (ROC) curves for different models were plotted to determine the optimal cut-off value. For cost-effectiveness analysis, costs of serum screening, amniocentesis and termination of pregnancy were determined. The average and incremental cost-effectiveness ratios were calculated for double and triple test. Sensitivity analyses for cost-effectiveness at different costs, detection rates, and amniocentesis up-taken rates were performed. For analysis of willingness-to-pay for antenatal screening for Down’s syndrome, univariate and multivariate linear regressions were performed to identify factors influencing the value of willingness to pay. The major results include: Firstly, a predictive model for Down’s syndrome pregnancy based on maternal age and serum levels of alpha-fetoprotein and human chromic gonadotrophin was developed using logistic regression. A simple scoring system for risk estimation of maternal serum screening was developed with S-KJ approach. The efficiency of this scoring system was validated. Secondly, the optimal cut off risk estimated from Receiver Operating Characteristics curve was 1:499 for women under 35y/o, with a sensitivity of 90.0% and false positive rate of 17.8%. Thirdly, adding uE3, the triple test was more cost-effective than double test in this series. Fourthly, the average amount of willingness-to-pay for serum screening of Down’s syndrome of pregnancy women was estimated to be 1911 NTD, which was more than the current fee for screening. In a multivariate linear regression analysis, the willingness to pay was positively correlated to family income and maternal age. In conclusion, predictive model for Down’s syndrome based on maternal age and serum levels of AFP and hCG was developed using logistic regression. The S-KJ scoring system is a simple, and efficient method for risk estimation. According to ROC curve analysis, the optimal cut-off risk for young pregnant women could be estimated. With higher sensitivity, triple test is more cost-effective than double test. Pregnant women with more family income and advanced age are willing to pay more for screening for Down’s syndrome.