BACKGROUND AND PURPOSE:

• Current guidelines recommend invasive prenatal diagnosis using microarray analysis in the setting of fetal ultrasound anomalies
• Many women will decline invasive testing even if offered and will opt for NIPT, even though only a screening tool limited to common aneuploidies
• Beulen et al. (Ultrasound Obstet Gynecol., 2017) evaluated NIPT as an alternative to invasive diagnostic prenatal testing in pregnancies with abnormal ultrasound findings

METHODS:

• Retrospective analysis of 251 pregnancies (2014-2015)
• Included patients who received NIPT following abnormal ultrasound
• Women were counseled and offered prenatal invasive diagnosis (rapid testing for common aneuploidies and microarray)
• Sex chromosomes were not analyzed, according to the current protocol in Dutch laboratories

RESULTS:

• NIPT was performed at a median gestational age of 20 weeks
• Ultrasound findings
  • Multiple congenital anomalies (n= 13)
  • Isolated structural anomalies (n=57)
  • Increased nuchal translucency ≥ 3.5 mm (n = 58)
  • Soft markers (n = 73)
  • Growth restriction (n = 40)
  • Other anomalies (n = 10)
• NIPT results: Normal in 89% of pregnancies; inclusive in 0.4%; abnormal in 10.4%
• Analysis of discordant results (Normal NIPT results/abnormal outcome) identified the following genetic anomalies missed by NIPT in 3.1% of pregnancies
  • Trisomy 13 and monosomy X
  • 2 Subchromosomal aberrations detectable on microarray
  • 3 Monogenic aberrations (cannot be detected with microarray)
• Genetic abnormalities would have been detected in 12.7% pregnancies based on invasive testing

CONCLUSION:

• NIPT should not be recommended to determine genetic abnormalities when ultrasound anomalies are found
  • 2/5 cases of trisomy 13 were not detected with NIPT
• NIPT sensitivity and therefore negative predictive value, are inferior to conventional karyotyping and microarray analysis
• Massive Parallel Sequencing NIPT technique used in this study could detect subchromosomal changes but resolution is limited compared to microarray
• Some women despite counseling will still choose NIPT over invasive prenatal diagnosis

Learn More – Primary Sources:

Clinical utility of non-invasive prenatal testing in pregnancies with ultrasound anomalies.

Related ObG Topics:

How Accurate is NIPT as a Screening Test for Chromosomal Aneuploidies?

SMFM Guidance – The Role of Prenatal Ultrasound and NIPT 

What Is the Best Follow-Up Diagnostic Test After a High-Risk NIPT Result?