J Korean Med Sci.  2011 Dec;26(12):1619-1624. 10.3346/jkms.2011.26.12.1619.

Korean-Specific Parameter Models for Calculating the Risk of Down Syndrome in the Second Trimester of Pregnancy

• Kwon JY
• Park IY
• Park YG
• Lee Y
• Lee G
• Shin JC

• KMID: 1786019
• DOI: http://doi.org/10.3346/jkms.2011.26.12.1619

Abstract

The purpose of the current study was to propose a Korean-specific parameter set for calculating the risk of Down syndrome in the second trimester of pregnancy and to determine the screening performances of triple and quadruple tests in Korean women. Using the data on triple or quadruple screening from three hospitals in Korea during 7 yr, we re-converted the concentrations of four serum markers to multiple of median values according to gestational age and maternal weight. After re-calculating the risk of Down syndrome in each pregnancy by multiplying maternal age-specific risk by the likelihood ratio values for the serum markers, screening performances and optimal cut-off values of triple and quadruple tests were analyzed. Among 16,077 pregnancies, 23 cases had Down syndrome (1.4/1,000 deliveries). Compared to the previous program, the tests with new parameters had improved screening performance. The triple and quadruple tests had detection rates of 65.2% and 72.7%, respectively, at a false-positive rate of 5%. The optimal cut-off value for the quadruple and triple tests was 1:250. We have presented a Korean-specific parameter set for Down syndrome screening. The proposed screening test using this parameter set may improve the performance of Down syndrome screening for Korean women.

Keyword

Down Syndrome; Korean-Specific; Second Trimester Screening; Triple Test; Quadruple Test; Serum Marker

MeSH Terms

Adult
Asian Continental Ancestry Group
Biological Markers/blood
Down Syndrome/blood/*diagnosis
Female
Genetic Testing/*methods
Humans
Predictive Value of Tests
Pregnancy
*Pregnancy Trimester, Second
Prenatal Diagnosis/*methods
Republic of Korea
Risk

Figure

• 

  Fig. 1 Screening perfomances of triple and quadruple screening for Down syndrome risk. (A) ROC curve of quadruple screening (AUROC, 0.966; 95% confidence interval [CI], 0.940-0.991) and triple screening (AUROC, 0.955; 95% CI, 0.927-0.983) for Down syndrome risk. (B) Down syndrome detection and false-positive rates for quaduple and triple test.

Reference

1. Centers for Disease Control and Prevention (CDC). Down syndrome prevalence at birth: Unitied States, 1983-1990. MMWR Morb Mortal Wkly Rep. 1994. 43:617–622.

2. Lau TK, Fung HY, Rogers MS, Cheung KL. Racial variation in incidence of trisomy 21: survey of 57,742 Chinese deliveries. Am J Med Genet. 1998. 75:386–388.

3. Brambati B, Tului L. Chorionic villus sampling and amniocentesis. Curr Opin Obstet Gynecol. 2005. 17:197–201.

4. Cuckle HS, Wald NJ, Thompson SG. Estimating a woman's risk of having a pregnancy associated with Down's syndrome using her age and serum alpha-fetoprotein level. Br J Obstet Gynaecol. 1987. 94:387–402.

5. Bogart MH, Pandian MR, Jones OW. Abnormal maternal serum chorionic gonadotropin levels in pregnancies with fetal chromosome abnormalities. Prenat Diagn. 1987. 7:623–630.

6. Canick JA, Knight GJ, Palomaki GE, Haddow JE, Cuckle HS, Wald NJ. Low second trimester maternal serum unconjugated oestriol in pregnancies with Down's syndrome. Br J Obstet Gynaecol. 1988. 95:330–333.

7. Cuckle HS, Holding S, Jones R, Groome NP, Wallace EM. Combining inhibin A with existing second-trimester markers in maternal serum screening for Down's syndrome. Prenat Diagn. 1996. 16:1095–1100.

8. Benn PA, Fang M, Egan JF, Horne D, Collins R. Incorporation of inhibin-A in second-trimester screening for Down syndrome. Obstet Gynecol. 2003. 101:451–454.

9. Choi YK, Kim MY, Han JY, Ryu HM, Yang JH, Kim ES, Lee HB, Han IS, Ko MI, Han HW. A study about the effectiveness of triple marker test as a screening test for chromosomal aneuploidy. Korean J Obstet Gynecol. 1999. 42:1935–1942.

10. Han KC, Kim DW, Jeong SM, Yang WK, Park CB, Shin BK, Shin JH, Hong SY. Clinical analysis of triple marker screening test for fetal Down syndrome in midtrimester of pregnancy: low sensitivity of triple marker screening test. Korean J Obstet Gynecol. 1999. 42:1914–1918.

11. O'Brien JE, Dvorin E, Drugan A, Johnson MP, Yaron Y, Evans MI. Raceethnicity-specific variation in multiple-marker biochemical screening: alpha-fetoprotein, hCG, and estriol. Obstet Gynecol. 1997. 89:355–358.

12. Watt HC, Wald NJ, Smith D, Kennard A, Densem J. Effect of allowing for ethnic group in prenatal screening for Down's syndrome. Prenat Diagn. 1996. 16:691–698.

13. Wang YY, Luo J, Zhu MW, Liu LN, Ma X. Second-trimester double or triple screening for Down syndrome: a comparison of Chinese and Caucasian populations. Int J Gynaecol Obstet. 2006. 94:67–72.

14. Park IY, Kwon JY, Kim YH, Kim M, Shin JC. Maternal age-specific rates of fetal chromosomal abnormalities at 16-20 weeks' gestation in Korean pregnant women ≥ 35 years of age. Fetal Diagn Ther. 2010. 27:214–221.

15. Spencer K, Heath V, El-Sheikhah A, Ong CY, Nicolaides KH. Ethnicity and the need for correction of biochemical and ultrasound markers of chromosomal anomalies in the first trimester: a study of Oriental, Asian and Afro-Caribbean populations. Prenat Diagn. 2005. 25:365–369.

16. MacRae AR, Gardner HA, Allen LC, Tokmakejian S, Lepage N. Outcome validation of the Beckman Coulter access analyzer in a second-trimester Down syndrome serum screening application. Clin Chem. 2003. 49:69–76.

17. Wald NJ, Rodeck C, Hackshaw AK, Walters J, Chitty L, Mackinson AM. First and second trimester antenatal screening for Down's syndrome: the results of the Serum, Urine and Ultrasound Screening Study (SURUSS). J Med Screen. 2003. 10:56–104.

18. Malone FD, Canick JA, Ball RH, Nyberg DA, Comstock CH, Bukowski R, Berkowitz RL, Gross SJ, Dugoff L, Craigo SD, Timor-Tritsch IE, Carr SR, Wolfe HM, Dukes K, Bianchi DW, Rudnicka AR, Hackshaw AK, Lambert-Messerlian G, Wald NJ, D'Alton ME. First- and Second-Trimester Evaluation of Risk (FASTER) Research Consortium. First-trimester or second-trimester screening, or both, for Down's syndrome. N Engl J Med. 2005. 353:2001–2011.

19. Bryant-Greenwood PK, O'Brien JE, Huang X, Yaron Y, Ayoub M, Johnson MP, Evans MI. Maternal weight differences do not explain ethnic differences in biochemical screening. Fetal Diagn Ther. 1998. 13:46–48.

20. Spencer K, Ong CY, Liao AW, Nicolaides KH. The influence of ethnic origin on first trimester biochemical markers of chromosomal abnormalities. Prenat Diagn. 2000. 20:491–494.

21. Wald NJ, Kennard A, Hackshaw A, McGuire A. Antenatal screening for Down's syndrome. J Med Screen. 1997. 4:181–246.

22. Wald NJ, Cuckle HS, Densem JW, Kennard A, Smith D. Maternal serum screening for Down's syndrome: the effect of routine ultrasound scan determination of gestational age and adjustment for maternal weight. Br J Obstet Gynaecol. 1992. 99:144–149.

23. Wald NJ, Watt HC, George L. Maternal serum inhibin-A in pregnancies with insulin-dependent diabetes mellitus: implications for screening for Down's syndrome. Prenat Diagn. 1996. 16:923–926.

24. Crossley JA, Berry E, Aitken DA, Connor JM. Insulin-dependent diabetes mellitus and prenatal screening results: current experience from a regional screening programme. Prenat Diagn. 1996. 16:1039–1042.

25. Palomaki GE, Knight GJ, Haddow JE, Canick JA, Wald NJ, Kennard A. Cigarette smoking and levels of maternal serum alpha-fetoprotein, unconjugated estriol, and hCG: impact on Down syndrome screening. Obstet Gynecol. 1993. 81:675–678.