Prenatal reflex DNA screening for trisomies 21, 18, and 13.

Abstract

PURPOSE:

The purpose of the study was to determine the screening performance of prenatal reflex DNA screening for trisomies 21 (T21), 18 (T18), and 13 (T13) as part of a routine service at five hospitals.

METHODS:

Women who accepted screening had a first-trimester combined test (pregnancy-associated plasma protein A, free β-human chorionic gonadotropin, nuchal translucency interpreted with maternal age). Those with a risk of having an affected pregnancy ≥1 in 800 were reflexed to a DNA sequencing test using stored plasma from the original blood sample, thereby avoiding the need to recall them.

RESULTS:

Of 22,812 women screened (including 106 with affected pregnancies), 2,480 (10.9%) were reflexed to DNA testing; 101/106 were detected (69/73 T21, 24/25 T18, and 8/8 T13), a 95% detection rate (95% confidence interval 89-98%) with four false positives (0.02%, 95% confidence interval 0.00-0.05%). The odds of being affected given a positive result were 25:1. Of the 105 screen-positive pregnancies, 91 (87%) had an invasive diagnostic test. Reflex DNA screening avoided up to 530 invasive diagnostic tests compared with using the combined test.

CONCLUSION:

Reflex DNA screening was successfully implemented in routine care, achieving a high detection rate, low false-positive rate, and, consequently, greater safety with fewer invasive diagnostic tests than other methods of screening.

• Authors: Nicholas J Wald, Wayne J Huttly, Jonathan P Bestwick, Robert Old, Joan K Morris, Ray Cheng, Joe Aquilina, Elisabeth Peregrine, Devender Roberts, Zarko Alfirevic
• Journal: Genetics in medicine : official journal of the American College of Medical Genetics (Genet Med) Vol. 20 Issue 8 Pg. 825-830 (08 2018) ISSN: 1530-0366 [Electronic] United States
• PMID: 29120460 (Publication Type: Journal Article)

Chemical References

• Chorionic Gonadotropin, beta Subunit, Human
• DNA
• Pregnancy-Associated Plasma Protein-A

Topics

• Adult
• Chorionic Gonadotropin, beta Subunit, Human
• DNA (blood)
• Diagnostic Tests, Routine (methods)
• Down Syndrome (diagnosis, genetics)
• Female
• Humans
• Maternal Age
• Nuchal Translucency Measurement
• Pregnancy
• Pregnancy Trimester, First (blood)
• Pregnancy-Associated Plasma Protein-A
• Prenatal Diagnosis (methods)
• Sequence Analysis, DNA (methods)
• Trisomy (diagnosis, genetics)
• Trisomy 13 Syndrome (diagnosis, genetics)
• Trisomy 18 Syndrome (diagnosis, genetics)