Non-Invasive Prenatal Testing and Fetal Echocardiography Guidelines

Understanding NIPT and Its Limitations

NIPT is a screening test, not a diagnostic test, and diagnostic testing is recommended as follow-up for any positive NIPT result, according to the American College of Medical Genetics and Genomics 1, 2, 3
The fetal contribution of cell-free DNA studied by NIPT is of presumed placental origin and may not always be representative of the fetus, with a strength of evidence level of moderate 1, 4

For positive NIPT results for trisomies 13, 18, 21, or other aneuploidies, diagnostic testing through amniocentesis or CVS is recommended by the American College of Medical Genetics and Genomics, with a high level of evidence 1, 2
Mosaic CVS results should not be considered confirmation of a positive NIPT result; follow-up amniocentesis is recommended, with a moderate level of evidence 1, 4

Prenatal sonography performed in the midtrimester has historically been used to adjust risk for fetal trisomies by assessing for the presence of "soft markers", according to the American College of Obstetricians and Gynecologists 6
For fetuses with abnormal physical examination findings on ultrasound that are consistent with the aneuploidy in question, additional evaluation may be warranted, which could include fetal echocardiography if cardiac anomalies are suspected, with a moderate level of evidence 2, 3

SCAs detected by NIPT have varying positive predictive values: 29.5% for monosomy X (Turner syndrome), 54% for XXX, 74% for XXY, and 74.5% for XYY, according to the American College of Medical Genetics and Genomics 7, 8
Turner syndrome (45,X) is associated with cardiac defects, particularly coarctation of the aorta, which may warrant fetal echocardiography if confirmed by diagnostic testing, with a high level of evidence 8

The American College of Medical Genetics and Genomics suggests that NIPT for 22q11.2 deletion syndrome be offered to all patients (conditional recommendation), with a moderate level of evidence 7, 8
22q11.2 deletion syndrome is associated with conotruncal cardiac defects, and if confirmed by diagnostic testing, fetal echocardiography would be indicated, with a high level of evidence 7

Confirm positive NIPT results with diagnostic testing (amniocentesis or CVS), according to the American College of Medical Genetics and Genomics, with a high level of evidence 1, 2
If diagnostic testing confirms chromosomal abnormality, consider fetal echocardiography if the confirmed abnormality is associated with cardiac defects (e.g., trisomy 21, 18, 13, Turner syndrome, 22q11.2 deletion), with a moderate level of evidence 1, 4