Fetal aneuploidy screening by non-invasive prenatal testing of maternal plasma DNA sequencing with "false negative" result due to confined placental mosaicism: A case report.

rationaleNon-invasive prenatal testing (NIPT) is an accurate screening method with high specificity and sensitivity and a low false-positive rate of trisomy 21, 18, and 13. However, false-negative NIPT results could also limit the clinical application of NIPT. PATIENT CONCERNS: A 34-year-old primigravida woman who underwent NIPT at 16 + 3 weeks' gestation was identified as being at high risk for fetal trisomy X (47, XXX). Fetal cardiac defect and hand posture were observed during prenatal ultrasound examination at the 23rd week of gestation. DIAGNOSES: Amniocentesis conducted at the 24th week of gestation. Fetal karyotyping and FISH identified karyotype 48, XXX, + 18, which indicated that the NIPT failed to detect trisomy 18 in this case.

interventionsThe couple decided to terminate pregnancy at the 26th week of gestation and was willing to undergo further examinations. OUTCOMES: Discordant results between fetus with trisomy 18 and placenta with mosaic T18 were further identified with massive parallel sequencing, which might be due to that the fetal cell-free DNA in maternal plasma for NIPT that was assessed principally originated from the trophoblast cells. LESSONS: The presence of trisomy 18 mosaicism in the placenta might be the reason for the false-negative NIPT result in this case of double aneuploidy with 48, XXX, + 18, karyotype. Although the NIPT is a valuable screening method that has evident advantages in prenatal aneuploidy screening for certain chromosomal abnormalities compared to other methods, it is not a "diagnostic test" yet.