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Am J Perinatol 2012; 29(03): 211-216
DOI: 10.1055/s-0031-1285095
Original Article
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

False-Negative Results in Routine Combined First-Trimester Screening for Down Syndrome in Finland

Jaana Marttala
1   Department of Obstetrics and Gynecology, Oulu University Hospital, Oulu
,
Marja Kaijomaa
2   Department of Obstetrics and Gynecology, Helsinki University Hospital, Helsinki
,
Jenni Ranta
3   Institute of Clinical Medicine and Eastern Finland Laboratory Centre, University, Faculty of Medicine, Kuopio
,
Anna Dahlbacka
1   Department of Obstetrics and Gynecology, Oulu University Hospital, Oulu
,
Pentti Nieminen
4   Medical Informatics Group, University of Oulu, Oulu
,
Aydin Tekay
1   Department of Obstetrics and Gynecology, Oulu University Hospital, Oulu
,
Hannaleena Kokkonen
5   Laboratory of Clinical Genetics, Oulu University Hospital, Oulu
,
Paivi Laitinen
6   Laboratory of Clinical Chemistry, Oulu University Hospital, Oulu
,
Jaakko Ignatius
1   Department of Obstetrics and Gynecology, Oulu University Hospital, Oulu
11   Department of Clinical Genetics, Turku University Hospital, Turku
12   Department of Medical Genetics, University of Turku, Turku, Finland
,
Jarkko Romppanen
3   Institute of Clinical Medicine and Eastern Finland Laboratory Centre, University, Faculty of Medicine, Kuopio
,
Seppo Heinonen
7   Department of Obstetrics and Gynecology, Kuopio University Hospital, Kuopio
,
Ilkka Jarvela
1   Department of Obstetrics and Gynecology, Oulu University Hospital, Oulu
,
Matti Heikkila
8   Department of Obstetrics and Gynecology, Seinajoki Central Hospital, Seinajoki
,
Ari Yla-Outinen
9   Department of Obstetrics and Gynecology, Pori Central Hospital, Pori
,
Veli-Matti Ulander
2   Department of Obstetrics and Gynecology, Helsinki University Hospital, Helsinki
,
Esa Hamalainen
10   Laboratory of Clinical Chemistry, Helsinki University Hospital, Helsinki
,
Markku Ryynanen
1   Department of Obstetrics and Gynecology, Oulu University Hospital, Oulu
› Author Affiliations
Further Information

Publication History

20 February 2011

06 June 2011

Publication Date:
10 August 2011 (online)

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Abstract

We analyzed the frequency and possible causes of false-negative (Fn) screening results in first-trimester combined Down syndrome screening in Finland. During the study period (May 1, 2002, to December 31, 2008), 76,949 voluntary women with singleton pregnancies participated in screening. Maternal age at screening, week of gestation, levels of pregnancy-associated plasma protein-A (PAPP-A), free β-human chorionic gonadotropin (fβ-hCG), and nuchal translucency (NT) measurement were compared and statistically analyzed between true-positive (Tp) and Fn cases. There were a total of 188 Down syndrome cases (1:409) in the screened population; 154 confirmed Tp and 34 Fn cases. Most Fn cases (n = 25) occurred at 12 + 0 to 13 + 6 weeks' gestation and only nine Fn cases presented between 10 and 11 weeks' gestation. According to the logistic regression analysis, the NT measurement was the most powerful discriminating factor in Fn screening results and accounted for 37.2% of Fn results. The second most important factor was fβ-hCG, adding 14.0% to R 2, followed by PAPP-A, which contributed a further 14.3%. The chosen parameters explain 83.9% of Fn results, but 16.1% remain due to unknown factor(s). All investigated parameters contributed to Fn screening results, but fetal NT was the most discriminating factor leading to an Fn screening result.

Keywords

Down syndrome - combined screening - true positive - false negative
 

  • References

  • 1 Wald NJ, Rodeck C, Hackshaw AK, Rudnicka A. SURUSS in perspective. BJOG 2004; 111: 521-531
    PubMedGoogle Scholar
  • 2 Malone FD, Canick JA, Ball RH , et al. First-trimester or second-trimester screening, or both, for Down's syndrome. N Engl J Med 2005; 353: 2001-2011
    CrossrefPubMedGoogle Scholar
  • 3 Wald NJ, Rodeck C, Hackshaw AK, Walters J, Chitty L, Mackinson AM SURUSS Research Group. First and second trimester antenatal screening for Down's syndrome: the results of the Serum, Urine and Ultrasound Screening Study (SURUSS). Health Technol Assess 2003; 7: 1-77
    PubMedGoogle Scholar
  • 4 Hall S, Bobrow M, Marteau TM. Psychological consequences for parents of false negative results on prenatal screening for Down's syndrome: retrospective interview study. BMJ 2000; 320: 407-412
    CrossrefPubMedGoogle Scholar
  • 5 Malin M, Gissler M. Maternal care and birth outcomes among ethnic minority women in Finland. BMC Public Health 2009; 9: 84-
    CrossrefPubMedGoogle Scholar
  • 6 Cuckle HS, van Lith JM. Appropriate biochemical parameters in first-trimester screening for Down syndrome. Prenat Diagn 1999; 19: 505-512
    CrossrefPubMedGoogle Scholar
  • 7 Reynolds TM, Penney MD. The mathematical basis of multivariate risk screening: with special reference to screening for Down's syndrome associated pregnancy. Ann Clin Biochem 1990; 27 (Pt 5) 452-458
    PubMedGoogle Scholar
  • 8 Tsukerman GL, Gusina NB, Cuckle HS. Maternal serum screening for Down syndrome in the first trimester: experience from Belarus. Prenat Diagn 1999; 19: 499-504
    CrossrefPubMedGoogle Scholar
  • 9 Wald NJ, Hackshaw AK. Combining ultrasound and biochemistry in first-trimester screening for Down's syndrome. Prenat Diagn 1997; 17: 821-829
    CrossrefPubMedGoogle Scholar
  • 10 Nagelkerke NJD. A note on a general definition of the coefficient of determination. Biometrika 1991; 78: 691-692
    CrossrefPubMedGoogle Scholar
  • 11 Terveyden ja Hyvinvoinnin Laitos. Births and newborns 2009. Available at: www.stakes.fi/tilastot/tilastotiedotteet/2010/Tr26_10pdf . Accessed November 25, 2009
    PubMedGoogle Scholar
  • 12 Kirkegaard I, Petersen OB, Uldbjerg N, Tørring N. Improved performance of first-trimester combined screening for trisomy 21 with the double test taken before a gestational age of 10 weeks. Prenat Diagn 2008; 28: 839-844
    CrossrefPubMedGoogle Scholar
  • 13 Kuc S, Koster MP, Visser GH, Schielen PC. Performance of first-trimester serum screening for trisomy 21 before and from 11 + 0 weeks of gestational age in The Netherlands. Prenat Diagn 2010; 30: 906-908
    CrossrefPubMedGoogle Scholar
  • 14 Merz E, Thode C, Alkier A , et al. A new approach to calculating the risk of chromosomal abnormalities with first-trimester screening data. Ultraschall Med 2008; 29: 639-645
    Article in Thieme ConnectPubMedGoogle Scholar
  • 15 Niemimaa M, Suonpää M, Perheentupa A , et al. Evaluation of first trimester maternal serum and ultrasound screening for Down's syndrome in Eastern and Northern Finland. Eur J Hum Genet 2001; 9: 404-408
    CrossrefPubMedGoogle Scholar
  • 16 Schmidt P, Staboulidou I, Elsässer M, Vaske B, Hillemanns P, Scharf A. How imprecise may the measurement of fetal nuchal translucency be without worsening first-trimester screening?. Fetal Diagn Ther 2008; 24: 291-295
    CrossrefPubMedGoogle Scholar