The potential impact of NIPT as a second-tier screen on the outcomes of high-risk pregnancies with rare chromosomal abnormalities.

Abstract

AIM:

To describe the potential impact of using noninvasive prenatal testing (NIPT) as a second-tier test, on the diagnosis and outcomes of pregnancies identified as high risk through first trimester screening (FTS) in a cohort of real pregnancies.

MATERIALS AND METHODS:

Western Australian FTS and diagnostic data (2007-2009) were linked to pregnancy outcomes. Karyotype results from invasive prenatal testing in high-risk women were analysed. The outcomes of abnormal results that would not be detected by NIPT, assuming a panel of trisomy 21/18/13 and sex chromosome aneuploidies, and the likelihood of diagnosis in a screening model using NIPT as a second-tier test are described.

RESULTS:

Abnormal karyotype results were reported in 224 of 1488 (15%) women with high-risk pregnancies having invasive diagnostic testing. NIPT potentially would have identified 85%. The 33 abnormalities unidentifiable by NIPT were triploidies (n = 7, 21%), balanced (n = 8, 24%) and unbalanced rearrangements (n = 10, 30%) and level III mosaicisms (n = 8, 24%). For conditions not identifiable by NIPT, fetal sonographic appearance was likely to have led to invasive testing for 10 of 17 (59%) pathogenic abnormalities. If a policy was adopted recommending invasive testing for FTS risk >1:50 and/or ultrasound detected abnormality, the residual risk of an unidentified pathogenic chromosomal abnormality in those without a diagnosis would have been 0.33% (95% CI 0.01-0.65%).

CONCLUSIONS:

A screening model with NIPT as a second-tier for high-risk pregnancies would be unlikely to have changed the outcome for the majority of pregnancies. Optimising the diagnosis of rare pathogenic abnormalities requires clear indicators for invasive testing over NIPT.

• Authors: Susannah Maxwell, Jan E Dickinson, Ashleigh Murch, Peter O'Leary
• Journal: The Australian & New Zealand journal of obstetrics & gynaecology (Aust N Z J Obstet Gynaecol) Vol. 55 Issue 5 Pg. 420-6 (Oct 2015) ISSN: 1479-828X [Electronic] Australia
• PMID: 26286670 (Publication Type: Journal Article)
• Copyright: © 2015 The Royal Australian and New Zealand College of Obstetricians and Gynaecologists.

Topics

• Adult
• Chromosome Aberrations
• Chromosome Disorders
• Chromosomes, Human, Pair 13
• Databases, Factual
• Down Syndrome
• Female
• Humans
• Incidence
• Karyotyping
• Maternal Age
• Nuchal Translucency Measurement (methods)
• Pregnancy
• Pregnancy Outcome
• Pregnancy Trimester, First
• Pregnancy, High-Risk
• Prenatal Diagnosis (methods)
• Retrospective Studies
• Risk Assessment
• Trisomy
• Trisomy 13 Syndrome
• Western Australia