© 2018, GENASSIST, Inc.     

By Keith S. Wexler, MBA, CFO, Business Development Director, GENASSIST, Inc.

Paul Wexler, M.D., F.A.C.O.G., Medical Director, GENASSIST, Inc.

Clinical Professor, Department of OB/GYN, University of Colorado Health Sciences Center

Clinical Professor, Division of Genetics/Dept. of Pediatrics, Univ. of Colorado/The Children’s Hospital

OVERVIEW: We have known for years that children with chromosomal abnormalities and some structural abnormalities may demonstrate subtle differences on clinical examination. Likewise, the mother’s age at conception, and the mode of conception [i.e. Invitro Fertilization (IVF) and the use of frozen eggs] can affect the calculated risk for a child with a chromosomal abnormality.

Just as the ethnic background can affect the likelihood of specific disorders (i.e. Cystic Fibrosis, Sickle Cell Anemia, Tay Sachs, Thalassemia etc) these differences can affect the ultrasound findings (e.g. biochemical blood results and fetal nasal bone).

Even with Maternal Fetal DNA testing, “ultrasound markers” will continue to be useful for early fetuses at “risk” in addition to screening for aneuploidy:

  • Crown Rump Length (CRL): Small differences in the CRL can affect risk and should be measured with a fetus in a neutral position.
  • Ductus Venosus: This measurement is also difficult to get at 11-14 weeks gestation. The ductus venosus connects the fetal umbilical cord to the inferior vena cava at the level of the diaphragm. The “a” wave is reversed in 3% of chromosomally normal fetuses and approximately 65% of fetuses with Trisomy 21. It is also associated with cardiac defects.
  • Fetal Heart Rate (FHR): Fetal heart rate is slightly increased in fetuses with Trisomy 21 (Down Syndrome). It may be much higher in fetuses with Trisomy 13 (75% of fetuses with Trisomy 13 have a FHR >175 beats per minutes). Not all labs use FHR in their calculations. Labs that use FHR in their calculations will increase the risk for Trisomy 13 even if the FHR increase is only due to increased fetal movement.
  • Fronto Maxillary Facial Angle: 50% of fetuses with Trisomy 21 have an increased angle which is measured from a line drawn from the upper surface of the palate and interior aspect of the maxilla to the external surface of the frontal bones of the forehead in a midsagital view of the face.
  • Nasal Bone: The fetal nasal bone is visualized at 11-13 weeks in 98% of chromosomally normal fetuses and 35% of Trisomy 21 fetuses. Rescan in one week will usually identify a nasal bone in a chromosomally normal fetus. Visualization of a nasal bone in a fetus in a “face down” position may difficult or impossible.
  • Nuchal Translucency (NT): The NT is increased in 95% of Trisomy 21 fetuses, 70% of Trisomy 18 fetuses, 85% of Trisomy 13 fetuses and 5% of chromosomally normal fetuses. Chromosomally normal fetuses with an increased NT (>3.5 mm) have a higher risk for cardiac defects, musculo-skeletal abnormalities, infections, rare genetic syndromes and fetal death. If an increased NT resolves by 20 weeks gestation, the prognosis is good.

A fetal echocardiogram at 22-24 weeks gestation should be considered in chromosomally normal fetuses with increased NT and all fetuses with chromosomal abnormalities.

Tricuspid Regurgitation: Tricuspid regurgitation may be difficult to measure and is seen in approximately 1% of chromosomally normal fetuses and 55% of fetuses with Trisomy 21. It is also seen in fetuses with cardiac defects. As with fetuses with increased NT, a fetal echocardiogram at 22-24 weeks gestation should be considered.


1st Trimester Aneuploidy Screening & “Ultrasound Markers” are still an important Non Invasive Prenatal Testing [NIPT] tool for the healthcare provider. 1st Trimester screening should continue to be used to help evaluate the “low risk” patient who is not a candidate for Maternal Fetal DNA testing and the “high risk” patient who declines having invasive testing, i.e. CVS or amniocentesis, even when indicated.  

Maternal Fetal DNA testing usually will not identify structural problems unrelated to a chromosomal abnormality.