Unexplained False Negative Results in Noninvasive Prenatal Testing: Two Cases Involving Trisomies 13 and 18

Area of Science:

• Genetics
• Prenatal Diagnostics
• Reproductive Medicine

Background:

• Noninvasive prenatal testing (NIPT) demonstrates high accuracy for detecting common trisomies.
• False negative NIPT results are infrequently reported but can lead to adverse outcomes.
• Clinical management of discordant NIPT results requires careful consideration.

Purpose of the Study:

• To report and analyze two cases of false negative noninvasive prenatal testing (NIPT) results.
• To investigate potential causes for discrepancies between NIPT and definitive fetal karyotyping.
• To emphasize the importance of collaborative patient care and result clarification.

Main Methods:

• Case report of two pregnancies with false negative NIPT results for trisomy 13 and trisomy 18.
• Fetal anomaly scans at 20 weeks gestation.
• Karyotyping of cultured amniocytes and cytogenetic investigation of placental biopsies.

Main Results:

• NIPT incorrectly reported negative results for trisomy 13 and trisomy 18.
• Karyotyping confirmed nonmosaic trisomies in both cases.
• Low proportions of non-trisomic cells in placental biopsies did not fully explain the NIPT discrepancy.

Conclusions:

• The root cause for these false negative NIPT results could not be identified.
• Discordant results pose significant challenges for patient counseling and acceptance.
• Collaboration among healthcare providers is crucial for clarifying NIPT discrepancies and improving patient care pathways.