Research
Print page Print page
Switch language
The Capital Region of Denmark - a part of Copenhagen University Hospital
Published

Contingent first-trimester screening for aneuploidies with cell-free DNA in a Danish clinical setting

Research output: Contribution to journalJournal articleResearchpeer-review

DOI

  1. Neurodevelopmental disorder in children believed to have isolated mild ventriculomegaly prenatally

    Research output: Contribution to journalJournal articleResearchpeer-review

  2. New intrauterine shunt for treatment of fetal fluid accumulation: single-center experience of first 17 cases

    Research output: Contribution to journalLetterResearchpeer-review

  3. Use of ultrasound simulators for assessment of trainee competence: trendy toys or valuable instruments?

    Research output: Contribution to journalJournal articleResearchpeer-review

  4. Clinicians should stop prescribing sildenafil for fetal growth restriction (FGR): comment from the STRIDER Consortium

    Research output: Contribution to journalJournal articleResearchpeer-review

  1. Physical activity during pregnancy and intelligence in sons; A cohort study

    Research output: Contribution to journalJournal articleResearchpeer-review

  2. Neurodevelopmental disorder in children believed to have isolated mild ventriculomegaly prenatally

    Research output: Contribution to journalJournal articleResearchpeer-review

  3. Genomisk medicin til præimplantations-, 
præ- og postnatal diagnostik

    Research output: Contribution to journalJournal articleResearchpeer-review

  4. Outcomes of monoamniotic twin pregnancies managed primarily in outpatient care-A Danish multicenter study

    Research output: Contribution to journalJournal articleResearchpeer-review

View graph of relations

OBJECTIVES: The primary aim was to compare the screening performance for Trisomy 21, of standard combined first trimester screening with referral to invasive testing at a cut-off at 1 in 300, with a contingent testing, consisting of referral to invasive testing at a 1 in 100 cut-off and referral to cell-free DNA (cfDNA) testing for a risk between 1 in 100 and 1 in 1000.

METHODS: Singleton pregnant women with a combined first trimester risk ≥ 1 in 1000 were consecutively recruited from two Danish hospitals between August 2014 and May 2015. First trimester combined screening was based on maternal and gestational age, nuchal translucency thickness, and levels of PAPP-A and ß-hCG. Blood samples for cfDNA testing were analysed using the Harmony Prenatal Test® giving risks for Trisomy 21, 18 and 13, and sex chromosomal aneuploidies. The cfDNA analysis was blinded from the combined risk assessment, karyotype results and pregnancy outcome. Pregnancy outcome and pre- and postnatal karyotypes were obtained from the Danish Fetal Medicine Database.

RESULTS: Among 6449 women who had a combined first trimester screening, 869 (13.5%) had a risk ≥ 1 in 1000 and 597 were included for cfDNA testing. Among these there were 15 cases of Trisomy 21, one case of Trisomy 18 and two cases of Trisomy 13. The sensitivity for Trisomy 21 was 100% using both screening scenarios, while specificity increased significantly from 97.0% to 98.8% (p < 0.001) using the contingent approach. The sensitivity for Trisomy 21, 18 and 13 increased from 94.4% to 100% with overlapping confidence intervals, while specificity increased significantly from 97.1% to 98.9% (p < 0.0001). In seven pregnancies, the risk of a sex chromosomal aneuploidy was increased with cfDNA testing but discordant with the karyotype, corresponding to a false-positive rate of 1.2%.

CONCLUSIONS: In a clinical setting with an efficient combined first trimester screening, a contingent screening offering women with a combined first trimester risk ≥ 1 in 100 an invasive test and women with a risk from 1 in 100 to 1 in 1000 a cfDNA test had the same sensitivity for Trisomy 21, 18 and 13, but significantly increased the specificity, when compared to offering an invasive test to all women with a risk ≥ 1 in 300. Implementing a contingent screening would therefore significantly reduce the number of invasive tests at no loss of sensitivity.

Original languageEnglish
JournalUltrasound in obstetrics & gynecology : the official journal of the International Society of Ultrasound in Obstetrics and Gynecology
Volume51
Issue number4
Pages (from-to)470-79
ISSN0960-7692
DOIs
Publication statusPublished - 2018

    Research areas

  • Journal Article

ID: 51603681