Abstract
Background
Maternal serum triple marker screening (alpha-fetoprotein, human chorionic gonadotropin, and unconjugated estriol) can detect 60–70% of Down syndrome and 60% of Edwards syndrome. Previous studies have reported that positive serum screening is related to other fetal chromosomal abnormalities, pregnancy complications, and adverse outcomes. We determined the incidence and karyotype of chromosomal abnormalities in screen positive women and evaluated a relationship between chromosomal and ultrasonographic abnormalities.
Methods
Of the 49,806 pregnant women between 15 and 23 weeks' gestational age who received prenatal serum screening with a cut-off value (a risk of 1:270 for Down and 1:100 for Edwards syndrome), 2,116 (4.2%) and 196 (0.4%) were screen positive for Down syndrome and for Edwards syndrome, respectively. Chromosomal analysis in amniotic fluid was performed for 1,893 (89.5%) of the Down positive and 140 (71.4%) of the Edwards positive pregnant women. Ultrasonographic examination was performed to detect fetal abnormalities.
Results
Eighty-three cases of chromosomal abnormalities including 40 trisomy 21 (2.1%) and 43 other chromosomal abnormalities (2.3%) were identified in the Down screen positive. Other chromosomal abnormalities included 9 numerical and 34 structural abnormalities. Ten cases of chromosomal abnormalities (9 trisomy 18 and 1 trisomy 9) were detected in the Edwards screen positive. Ultra-sonographic abnormalities were found more frequently in the women who had chromosomal aberrations.
Conclusions
These data suggest that 4.4% of the Down screen and 7.1% of the Edwards screen positive pregnancy have fetal chromosomal abnormalities. Positive Down screening results reflect a relatively high probability of other abnormalities except trisomy 21. Edwards screen positive group show a low frequency of other chromosomal abnormalities except trisomy 18. A simultaneous use of maternal serum screening and ultrasonograms could be useful for the diagnosis of fetal abnormalities.
References
1. Merkatz IR, Nitowsky HM, Macri JN, Johnson WE. An association between low maternal serum alpha-fetoprotein and fetal chromosomal abnormalities. Am J Obstet Gynecol. 1984; 148:886–94.
2. Chao AS, Chung CL, Wu CD, Chang SD, Cheng PJ, Lin YT, et al. Second trimester maternal serum screening using alpha fetoprotein, free beta human chorionic gonadotropin and maternal age specific risk: result of chromosomal abnormalities detected in screen positive for Down syndrome in an Asian population. Acta Obstet Gynecol Scand. 1999; 78:393–7.
![crossref](/image/icon/bnr_ref_cross.gif)
![crossref](/image/icon/bnr_ref_cross.gif)
3. Haddow JE, Palomaki GE, Knight GJ, Williams J, Pulkkinen A, Canick JA, et al. Prenatal screening for Down's syndrome with use of maternal serum markers. N Engl J Med. 1992; 327:588–93.
![crossref](/image/icon/bnr_ref_cross.gif)
![crossref](/image/icon/bnr_ref_cross.gif)
4. Benn PA, Horne D, Briganti S, Greenstein RM. Prenatal diagnosis of diverse chromosome abnormalities in a population of patients identified by triple-marker testing as screen positive for Down syndrome. Am J Obstet Gynecol. 1995; 173:496–501.
![crossref](/image/icon/bnr_ref_cross.gif)
![crossref](/image/icon/bnr_ref_cross.gif)
5. Suzumori K, Tanemura M, Murakami I, Okada S, Natori M, Tanaka M, et al. A retrospective evaluation of maternal serum screening for the detection of fetal aneuploidy. Prenat Diagn. 1997; 17:861–6.
![crossref](/image/icon/bnr_ref_cross.gif)
![crossref](/image/icon/bnr_ref_cross.gif)
6. Ogle R, Jauniaux E, Pahal GS, Dell E, Sheldrake A, Rodeck C. Serum screening for Down syndrome and adverse pregnancy outcomes: A case-controlled study. Prenat Diagn. 2000; 20:96–9.
![crossref](/image/icon/bnr_ref_cross.gif)
![crossref](/image/icon/bnr_ref_cross.gif)
7. Cha YJ, Yang JS, Chae SL, Park AJ. An evaluation of prenatal triple marker screening. Korean J Lab Med. 2003; 23:199–204.
8. Gardner RJM, Sutherland GR. Chromosome abnormalities and genetic counseling. 2nd ed.New York: Oxford University Press;1996. p. 349–52.
9. Dimaio MS, Baumgarten A, Greenstein RM, Saal HM, Mahoney MJ. Screening for fetal Down's syndrome in pregnancy by measuring maternal serum alpha-fetoprotein levels. N Engl J Med. 1987; 317:342–6.
![crossref](/image/icon/bnr_ref_cross.gif)
![crossref](/image/icon/bnr_ref_cross.gif)
10. Bogart MH, Pandian MR, Jones OW. Abnormal maternal serum chorionic gonadotropin levels in pregnancies with fetal chromosome abnormalities. Prenat Diagn. 1987; 7:623–30.
![crossref](/image/icon/bnr_ref_cross.gif)
![crossref](/image/icon/bnr_ref_cross.gif)
11. Saller DN Jr, Canick JA, Schwartz S, Blitzer MG. Multiple marker screening in pregnancies with hydropic and nonhydropic Turner syndrome. Am J Obstet Gynecol. 1992; 167:1021–4.
12. Hogge WA, Fraer L, Melegari T. Maternal serum screening for fetal trisomy 18: benefits of patient-specific risk protocol. Am J Obstet Gynecol. 2001; 185:289–93.
![crossref](/image/icon/bnr_ref_cross.gif)
![crossref](/image/icon/bnr_ref_cross.gif)
13. Zanini R, Tarantini M, Cerri V, Jacobello C, Bellotti D, Lancetti S, et al. 'Dual positivity'for neural tube defects and down syndrome at maternal serum screening: gestational outcome. Fetal Diagn Ther. 1998; 13:106–10.
14. Summers AM, Huang T, Wyatt PR. Pregnancy outcomes of women with positive serum screening results for Down syndrome and trisomy 18. Prenat Diagn. 2002; 22:269–71.
![crossref](/image/icon/bnr_ref_cross.gif)
![crossref](/image/icon/bnr_ref_cross.gif)
15. Yang YH, Yang ES, Park YW, Kim SK, Kim IK, Son YS. Clinical and cytogenetic study on 3,672 genetic amniocentesis: YUMC 20 years experience from 1985 to 2004 years. Korean J Obstet Gynecol. 2005; 48:1663–72.
16. Chen CP, Chern SR, Tsai FJ, Lin CY, Lin YH, Wang W. A comparison of maternal age, sex ratio and associated major anomalies among fetal trisomy 18 case with different cell division of error. Prenat Diagn. 2005; 25:327–30.
17. Borrell A, Gonce A, Martinez JM, Borobio V, Fortuny A, Coll O, et al. First-trimester screening for Down syndrome with ductus venosus Doppler studies inaddition to nuchal translucency and serum markers. Prenat Diagn. 2005; 25:901–5.
Table 1.
Age and gestational age distribution
Table 2.
Median concentration of AFP, HCG and uE3 during pregnancy
Table 3.
Summary for prenatal screening
Total (n=49,806) | <35 years (n=43,731) | ≥35 years (n=6,075) | P-value* | |
---|---|---|---|---|
Trisomy 21 screen positive | 2,116 | 1,509 | 607 | <0.001 |
(4.2%) | (3.5%) | (10.0%) | ||
Trisomy 18 screen positive | 196 | 127 | 69 | <0.001 |
(0.4%) | (0.3%) | (1.1%) | ||
Trisomy 21 & 18 screen positive | 10 | 0 | 10 | <0.001 |
(0.02%) | (0.0%) | (0.2%) |
Table 4.
Cytogenetic results in positive down syndrome screening
Table 5.
Comparison of parameters between groups with normal and abnormal chromosome results in positive Down syndrome screening
Normal (n=1,810) | Down syndrome (n=41) | Other chromosome abnormalities (n=42) | |
---|---|---|---|
Maternal age | |||
<35 years | 1,409 | 28 | 31 |
≥35 years | 401 | 13 | 11 |
P-value* | 0.18 | 0.57 | |
Ultrasonogram | |||
Normal | 1,792 | 16 | 32 |
Abnormal | 18 | 25 | 10 |
P-value* | <0.001 | <0.001 | |
Family history | |||
Negative | 1,805 | 41 | 42 |
Positive | 5 | 0 | 0 |
P-value* | 1.00 | 1.00 | |
Previous fetal abnormalities & spontaneous abortion | |||
Negative | 1,773 | 39 | 40 |
Positive | 67 | 2 | 2 |
P-value* | 0.66 | 0.66 |
Table 6.
Comparison of parameters between groups with normal and abnormal chromosome results in positive Edward syndrome screening
Normal (n=130) | Abnormal (n=10) | P-value* | |
---|---|---|---|
Maternal age | |||
<35 years | 92 | 6 | |
≥35 years | 38 | 4 | 0.49 |
Ultrasonogram | |||
Normal | 127 | 5 | |
Abnormal | 3 | 5 | <0.001 |
Family history | |||
Negative | 127 | 10 | |
Positive | 3 | 0 | 1.00 |
Previous fetal abnormalities & spontaneous abortion | |||
Negative | 118 | 9 | |
Positive | 12 | 1 | 1.00 |