Interpreting False-Positive or Atypical Prenatal Cell-Free DNA Results

Area of Science:

• Genetics
• Obstetrics
• Molecular Biology

Background:

• Cell-free DNA (cfDNA) screening, also known as non-invasive prenatal testing (NIPT), analyzes circulating placental DNA in maternal plasma.
• NIPT has revolutionized prenatal screening for fetal aneuploidies like trisomies 21, 18, and 13.
• Despite high accuracy, false-positive cfDNA screening results can occur, necessitating a thorough understanding of their causes and implications.

Purpose of the Study:

• To review the common causes of false-positive cfDNA screening results.
• To discuss the clinical implications and appropriate follow-up for these results.
• To provide guidance for healthcare providers managing cfDNA screening scenarios.

Main Methods:

• Literature review of studies on cfDNA screening and false-positive results.
• Analysis of biological causes including confined placental mosaicism, vanishing twin syndrome, and maternal factors.
• Discussion of unexplained and nonreportable results.

Main Results:

• Common causes of false positives include confined placental mosaicism, vanishing twin syndrome, maternal mosaicism, and malignancies.
• Unexplained and nonreportable results also present challenges in prenatal care.
• Understanding these scenarios is crucial for accurate interpretation and patient management.

Conclusions:

• False-positive cfDNA screening results, though infrequent, have significant implications.
• Appropriate follow-up strategies are essential for accurate diagnosis and patient counseling.
• Clinical vignettes aid healthcare providers in navigating complex cfDNA screening cases.