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

Jaana Marttala; Marja Kaijomaa; Jenni Ranta; Anna Dahlbacka; Pentti Nieminen; Aydin Tekay; Hannaleena Kokkonen; Paivi Laitinen; Jaakko Ignatius; Jarkko Romppanen; Seppo Heinonen; Ilkka Jarvela; Matti Heikkila; Ari Yla-Outinen; Veli-Matti Ulander; Esa Hamalainen; Markku Ryynanen

doi:10.1055/s-0031-1285095

American Journal of Perinatology, Table of Contents

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

¹Department of Obstetrics and Gynecology, Oulu University Hospital, Oulu

,

Marja Kaijomaa

²Department of Obstetrics and Gynecology, Helsinki University Hospital, Helsinki

,

Jenni Ranta

³Institute of Clinical Medicine and Eastern Finland Laboratory Centre, University, Faculty of Medicine, Kuopio

,

Anna Dahlbacka

¹Department of Obstetrics and Gynecology, Oulu University Hospital, Oulu

,

Pentti Nieminen

⁴Medical Informatics Group, University of Oulu, Oulu

,

Aydin Tekay

¹Department of Obstetrics and Gynecology, Oulu University Hospital, Oulu

,

Hannaleena Kokkonen

⁵Laboratory of Clinical Genetics, Oulu University Hospital, Oulu

,

Paivi Laitinen

⁶Laboratory of Clinical Chemistry, Oulu University Hospital, Oulu

,

Jaakko Ignatius

¹Department of Obstetrics and Gynecology, Oulu University Hospital, Oulu

¹¹Department of Clinical Genetics, Turku University Hospital, Turku

¹²Department of Medical Genetics, University of Turku, Turku, Finland

,

Jarkko Romppanen

³Institute of Clinical Medicine and Eastern Finland Laboratory Centre, University, Faculty of Medicine, Kuopio

,

Seppo Heinonen

⁷Department of Obstetrics and Gynecology, Kuopio University Hospital, Kuopio

,

Ilkka Jarvela

¹Department of Obstetrics and Gynecology, Oulu University Hospital, Oulu

,

Matti Heikkila

⁸Department of Obstetrics and Gynecology, Seinajoki Central Hospital, Seinajoki

,

Ari Yla-Outinen

⁹Department of Obstetrics and Gynecology, Pori Central Hospital, Pori

,

Veli-Matti Ulander

²Department of Obstetrics and Gynecology, Helsinki University Hospital, Helsinki

,

Esa Hamalainen

¹⁰Laboratory of Clinical Chemistry, Helsinki University Hospital, Helsinki

,

Markku Ryynanen

¹Department of Obstetrics and Gynecology, Oulu University Hospital, Oulu

› Author Affiliations

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

Full Text

References

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