False-Negative NIPT Result for Trisomy 21

The determination of fetal cell-free DNA in the mother’s blood in screening for aneuploidy has a big influence in prenatal medicine. The term, “noninvasive prenatal testing (NIPT)”, suggests to the pregnant woman that the test is “non-hazardous”. NIPT, which is a valuable screening method, has become a competitor to first-trimester screening.

NIPT has a detection rate for trisomy 21, 18 and 13 of up to 99 %, 90 % and 89 %, respectively, with a very low false-positive rate [1] [2]. Medical societies such as DEGUM [3] [4] and the International Society of Ultrasound in Obstetrics and Gynecology [5] [6] have recently published recommendations stating that a pregnant woman should only be offered an NIPT test after undergoing a proper first-trimester ultrasound examination.

We report a case of a false-negative NIPT result to emphasize once again the importance of fetal ultrasound.

The 40-year-old woman, 3G 1P (height 165 cm, weight 69.1 kg, body mass index 25.4) decided because of her age to have an NIPT Harmony Test (Cenata) in the 12 + 1 gestational week. The physician took blood without first referring the woman to an ultrasound specialist (level II or III). The result was inconspicuous, with the following values: “Fetal proportion of the cell-free DNA 14.7 %, trisomy 21 < 0.01 %, trisomy 18 < 0.01 %, trisomy 13 < 0.01 % and genotype for sex chromosomes XX, risk X-/Y- chromosomal abnormality inconspicuous, sex of fetus female.”

At 21 gestational weeks, the patient was referred for second-trimester screening (DEGUM Level II). The diagnosis of an atrioventricular defect (AVSD) was made. In addition, the fetus had brachycephaly, a shortened humerus and femur and polyhydramnios. The recommended amniocentesis confirmed trisomy 21 (47,XX,+ 21). Following counselling, the patient decided to have the child. In the 38th week of pregnancy the girl was born with the typical Down syndrome features and the cardiac defect. The correction of the heart defect is intended for the fifth month.

While the NIPT is a high-grade “screening method” in the search for certain chromosomal abnormalities, it cannot be equated with a “diagnostic test” [7] [8]. This case shows why medical societies such as DEGUM, ÖGUM and SGUM recommend that a precondition for an NIPT is always a proper ultrasound examination satisfying DEGUM II/III.

• References

• 1 Palomaki GE. et al. Genet Med Advance 2016; 194: 1-9
• 2 Gil MM. et al. Ultrasound Obstet Gynecol 2015; 45: 249-266
• 3 von Kaisenberg C. et al. Ultraschall in Med 2016; 37: 297-302
• 4 Schmid M. et al. Ultraschall in Med 2015; 36: 507-510
• 5 ISUOG. Consensus statement. Ultrasound Obstet Gynecol 2014; 44: 122-123
• 6 Kagan KO. et al. Screening for chromosomal abnormalities by first trimester combined screening and noninvasive testing.. Ultraschall in Med 2015; 36: 40-46
• 7 Merz E. Can Prenatal Testing in the First Trimester be Performed without Ultrasound?. Ultraschall in Med 2017; 38: 126-128
• 8 Wagner P. et al. gynäkologie + geburtshilfe. 2017; 22: 14-20