Prenatal Serum Marker Screening in Korea: Survey Results

Sollip Kim; Yun Hee Kim; Won-Ki Min

doi:10.3343/kjlm.2007.27.1.28

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Kim, Kim, and Min: Prenatal Serum Marker Screening in Korea: Survey Results

Original Article

Korean J Leg Med 2007;27(1):28-33.

Published online: 10 February 2007

DOI: https://doi.org/10.3343/kjlm.2007.27.1.28

Prenatal Serum Marker Screening in Korea: Survey Results

Sollip Kim, M.D., Yun Hee Kim, M.D., Won-Ki Min, M.D.

Department of Laboratory Medicine, Asan Medical Center and University of Ulsan College of Medicine, Seoul, Korea

Received 13 July 2006 Revised 14 January 2007 Accepted 15 January 2007

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Background

Maternal serum triple marker screening has been covered by the medical insurance system in Korea since December 2004. The number of tests is on the increase, but an external quality control program and a basic survey have not been established yet. The aim of this study was to report the survey of prenatal screening tests.

Methods

Three different quality control specimens were prepared using the sera obtained from 100 women who were in the 15th to 20th week of pregnancy and visited Asan Medical Center during May 2005. We assumed that the three specimens belonged to the first day of 15 weeks, third day of 16 weeks, and second day of 19 weeks, respectively, and sent them to 10 laboratories. Nine laboratories replied to the survey. We analyzed concentrations, multiples of medians (MoMs), and risk estimates.

Results

The coefficients of variance of MoM were 32.1–32.6% for α-fetoprotein, 15.3–19.8% for unconjugated estriol, 6.3–12.5% for human chorionic gonadotropin, and 12.9–18.2% for inhibin-A. In Down syndrome risk estimation for specimen-2, six of the eight laboratories that used the triple test reported the screen positive, but two laboratories reported negative. Three of five laboratories using the quadruple test reported the screen positive, and two laboratories reported negative. In case of neural tube defect, all laboratories except one reported all specimens the screen negative. In case of Edward syndrome, all laboratories reported all specimens the screen negative.

Conclusions

Since MoMs and risk estimates showed a wide variation among the participating laboratories in this survey, an external quality control and the standardization of the variables seemed warranted.

Keywords: Prenatal screening test, Survey, MoM

References

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Table 1.

Basic presumptive information on 3 quality control specimens

Specimen	Date of mother's birth	Gastational age	Date of specimen collection	Weight (kg)	Single or twin pregnancy	Race	DM/previous examination/reinspection/smoke
Specimen-1	1975–10–15	Third day of the 16 weeks	2005–03–08	63.0	Single	Korean	All negative
Specimen-2	1970–06–20	Second day of the 19 weeks	2005–03–08	67.0	Single	Korean	All negative
Specimen-3	1978–08–10	First day of the 15 weeks	2005–03–08	59.0	Single	Korean	All negative

Table 2.

Instruments (principle) used in 9 laboratories

Laboratory	AFP	uE3	Total hCG	Inhibin-A
1	Bayer, ADVIA Centaur (ECLIA)	Perkin Elmer, Auto DELFIA (FIA)	Bayer, ADVIA Centaur (ECLIA)	DSL, Active inhibin ELISA
2	DPC, Immulite2000 (CLIA)	DPC, Immulite2000 (CLIA)	DPC, Immulite2000 (CLIA)	DSL, Active inhibin ELISA
3	Perkin Elmer, Auto DELFIA (FIA)	Perkin Elmer, Auto DELFIA (FIA)	Perkin Elmer, Auto DELFIA (FIA)	DSL, Active inhibin ELISA
4	Biosewoom, Absolute AFP (EIA)	Biosewoom, Absolute E3 (EIA)	Biosewoom, Absolute hCG (EIA)	DSL, Active inhibin ELISA
5	DiaSorin, IRMA-mat AFP	Beckman, Immunotech (RIA)	Beckman, Immunotech (RIA)	DSL, Active inhibin ELISA
6	Beckman, Access (CLIA)	Beckman, Access (CLIA)	Beckman, Access (CLIA)	Not performed
7	DPC, Immulite2000 (CLIA)	DPC, Immulite2000 (CLIA)	DPC, Immulite2000 (CLIA)	Not performed
8	Ortho, Vitros ECi (CLIA)	Advanced laboratory diagnostic system, ADALTIS	Ortho, Vitros ECi (CLIA)	Not performed
9	Beckman, Immunotech (RIA)	Beckman, Immunotech (RIA)	Beckman, Immunotech (RIA)	Not performed

Abbreviations: AFP, α-feto protein; uE3, unconjugated estriol; hCG, human chorionic gonadotropin; ECLIA, electrochemiluninescence immunoassay; FIA, fluorescence immunoassay; ELISA, enzyme linked immunoassay; DPC, Diagnostic Products Corporation; DSL, Diagnostic System Laboratory Inc.; EIA, enzyme immunoassay; RIA, radioimmunoassay.

Table 3.

Software programs for risk calculation used in 8 laboratories

Laboratory	Triple test	Quadruple test
1	Prenatal AFP (Robert Maciel associates, Inc., USA)	Prenatal AFP (Robert Maciel associates, Inc., USA)
2	Prisca (DPC and Typolog, Germany)	Hit (Hamchoon Inc., Korea)
3	AFP expert (Benetech Inc., Canada)	AFP expert (Benetech Inc., Canada)
4	MPIS (RMA, USA)	Hit (Hamchoon Inc., Korea)
5	Hit (Hamchoon Inc., Korea)	Hit (Hamchoon Inc., Korea)
6	Tri-cal (Hanyang Univ. GURI hospital, Korea)	Not performed
7	AFP expert (Benetech Inc., Canada)	Not performed
8	Alpha-program (LMS, England)	Not performed

Table 4.

Performance of analytes

Analytes	Specimen	Concentration		MoM
Analytes	Specimen	Mean±SD	CV (%)	Mean±SD	CV (%)
AFP	1	38.9±3.6	9.2	1.3±0.4	32.6
	2	39.2±3.9	9.9	1.0±0.3	32.5
	3	41.3±4.5	10.8	1.6±0.5	32.1
uE3	1	6.7±2.5	37.8	1.1±0.2	19.0
	2	8.1±3.3	40.1	0.7±0.1	19.8
	3	8.1±3.0	36.9	1.8±0.3	15.3
hCG	1	38.3±11.0	28.7	1.1±0.1	6.3
	2	40.8±13.7	33.7	1.7±0.2	12.5
	3	31.8±9.0	28.3	0.6±0.1	10.6
Inhibin-A	1	228.5±40.9	17.9	1.1±0.2	18.2
	2	251.4±29.5	11.7	1.2±0.2	12.9
	3	216.3±27.2	12.6	1.0±0.2	16.3

Abbreviations: SD, standard deviation; CV, coefficient variation; MoM, multiples of median.

Table 5.

Risk estimates for neural tube defect, Down syndrome, and Edward syndrome at 8 participating laboratories

	Laboratory	Specimen 1			Specimen 2			Specimen 3
	Laboratory	Neural tube defect	Down syndrome	Edward syndrome	Neural tube defect	Down syndrome	Edward syndrome	Neural tube defect	Down syndrome	Edward syndrome
Triple	1	1.1 MoM	1:5,900	1:20,993	0.8 MoM	1:52^*	1:2,021	1.4 MoM	1:70,000	1:56,262
	2	1.3 MoM	1:4,290	1:90,000	0.9 MoM	1:112^*	1:25,100	1.5 MoM	1:10,187	1:90,000
	3	1.0 MoM	1:5,550	1:206,000	0.7 MoM	1:65^*	1:18,000	1.3 MoM	1:31,700	1:190,000
	4	2.0 MoM	1:11,461	1:99,999	1.4 MoM	1:266^*	1:99,999	2.4 MoM	1:88,173	1:99,999
	5	1.2 MoM	1:14,732	1:75,504	0.8 MoM	1:284	1:20,483	1.5 MoM	1:91,123	1:67,249
	6	1.0 MoM	1:4,878	Not calculated	0.7 MoM	1:221^*	Not calculated	1.2 MoM	1:25,620	Not calculated
	7	1.1 MoM	1:2,100	Not calculated	0.8 MoM	1:101^*	Not calculated	1.2 MoM	1:28,200	Not calculated
	8	1.2 MoM	1:4,600	Not calculated	0.8 MoM	1:290	Not calculated	1.4 MoM	1:20,000	Not calculated
Quadruple	1	1.1 MoM	1:24,000	1:20,993	0.8 MoM	1:92^*	1:2,021	1.4 MoM	1:99,000	1:56,262
	2	1.2 MoM	1:6,981	1:91,123	0.8 MoM	1:56^*	1:12,254	1.5 MoM	1:91,123	1:91,123
	3	1.0 MoM	1:6,810	1:206,000	0.7 MoM	1:58^*	1:18,000	1.3 MoM	1:48,400	1:190,000
	4	2.2 MoM	1:25,105	1:91,123	1.5 MoM	1:406	1:35,096	2.6 MoM^*	1:91,123	1:84,098
	5	1.2 MoM	1:17,094	1:75,504	0.8 MoM	1:483	1:20,483	1.5 MoM	1:91,123	1:67,249

^* screen positive.

Abbreviation: MoM, multiples of median.

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