© 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 the introduction of Maternal Fetal DNA testing, “Markers” will continue to be useful for early fetuses at “risk” in addition to screening for aneuploidy.


  • Choroid Plexus Cysts (cysts in the baby’s brain blood supply)
  • Echogenic Cardiac Focus/Echogenic Papillary Muscle (bright ultrasound echo in one or both large chambers of the baby’s heart)
  • Hydronephrosis/Pyelectasis (fluid in the baby’s kidneys)

Minor markers are found more commonly in fetuses with chromosomal abnormalities than in normal fetuses.

However, most fetuses with “minor markers” only, usually have normal chromosomes. The absence of any “ultrasound markers”, minor or major is reassuring and multiple minor markers or the presence of one or more minor markers in association with a major marker(s) increases the risk.

Except for the association of Choroid Plexus Cyst(s) in Trisomy 18 or less likely Trisomy 21, the other minor markers are associated most with Trisomy 21.


  • Atrial Septal Defect/ASD (hole in the septum that divides the small chambers of the baby’s heart). ASD increases the risk for Trisomy 21.
  • Diaphragmatic Hernia (defect in the diaphragm that separates the fetal chest from the abdomen). Diaphragmatic Hernia increases risk for Trisomy 18.
  • Exomphalos (hernia of baby’s bowel into umbilical cord). Exomphalos increases risk for Trisomy 13 & 18.
  • Holoprosenencephaly (abnormal frontal brain development of the baby). Holoprosenencephaly increases risk for Trisomy 13

Multiple abnormalities in a fetus increase the likelihood of Trisomy 13 and Trisomy 18 more than Trisomy 21.


  • Free Beta HCG may be increased in Trisomy 13 or Trisomy 18 and is usually increased in Trisomy 21. In Triploidy (due to ovum defects), beta HCG may be low. If due to paternal etiology, beta HCG is usually increased. Beta HCG levels are usually normal in sex chromosomal abnormalities.
  • Pregnancy Associated Plasma Protein-A (PAPP-A) is usually low in Trisomy 13, Trisomy 18, Trisomy 21, sex chromosomal abnormalities and Triploidy. Maternal Triploidy may show the lowest PAPP-A values. Low PAPP-A (less than 0.3 MoM’s) are associated with preterm delivery, fetal growth restriction and fetal death.

Preeclampsia and Fetal Intrauterine Growth Restriction (IUGR).

Preeclampsia is more common in nulliparous and black women, women with a history of hypertension, preeclampsia in a prior pregnancy and women with a high Body Mass Index (BMI).

Combining maternal history with uterine artery doppler pulsatility index and PAPP-A at 11-14 weeks may help detect up to 80% of women who will develop preeclampsia before 34 weeks gestation and 40% of women who will develop later preeclampsia.

This compares with 30% detection using maternal history alone. These values can also be used to help predict IUGR.


1st Trimester Aneuploidy Screening & “Markers” are still important non-invasive prenatal testing [NIPT] tools 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.