© 2017            

By Keith S. Wexler, MBA, Maternal Fetal Medicine, Prenatal Diagnosis and Biotech/Life Sciences Consultant, 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

Case Study 1: We were contacted by a patient who wanted to have her OB/GYN perform Non Invasive Prenatal Testing [NIPT] and/or Non Invasive Prenatal Screening [NIPS] by Maternal Fetal DNA in this pregnancy, since she lost her last baby near delivery and the baby was diagnosed as having Trisomy 15.

The patient was 32 years old and the patient stated that no “ultrasound markers” were seen in her last pregnancy.

The patient was now possibly eligible for Maternal Fetal DNA testing since her previous baby had Trisomy 15. This increased her maternal age related risk for another pregnancy with a chromosomal abnormality to approximately 1 per cent above her age related risk.

The risk of a 35 year for having a child with a chromosomal abnormality is 1 in 270. The patient’s risk is now 1 in 100 or 2.7 times greater than a 35 year old.

The patient wanted to have a non-invasive screening test at 10 to 11 weeks gestation and avoid Chorionic Villus Sampling (CVS) and/or amniocentesis.

Case Study 2: We were contacted by a second patient who was very concerned that she had had Non Invasive Prenatal Testing [NIPT] and/or Non Invasive Prenatal Screening [NIPS] in her last pregnancy since she was over 35 years of age, and was told that she had a low risk for the chromosomal abnormalities that were screened for.

Further she stated that she did not elect to have Chorionic Villus Sampling (CVS) and/or amniocentesis since she had a Low Risk result. She ended up miscarrying the pregnancy in her second trimester and the baby was identified with Trisomy 15.

Her first words over the phone to us were “The Maternal Fetal DNA lab told me that I had a Low Risk pregnancy for chromosomal abnormalities in spite of my age, but they were wrong. They missed my baby with Trisomy 15”.

We explained to the patient that within the current limits of technology, most of the Maternal Fetal DNA laboratories are performing testing for Trisomy 13, Trisomy 18 and Trisomy 21. Some laboratories are performing testing for Trisomy 9, Trisomy 16, Trisomy 22 and Triploidy.

Some labs are now offering sex chromosomal abnormalities:

  • 45,X – Turner Syndrome
  • 47,XXX – Trisomy X
  • 47,XXY – Klinefelter Syndrome
  • 47,XYY – Jacob Syndrome

Some labs are also offering Microdeletion Syndromes including:

  • Angelman Syndrome
  • Cri-Du-Chat Syndrome (5p-)
  • DiGeorge Syndrome (22q11.2 deletion syndrome)
  • Jacobsen Syndrome (11q23 deletion syndrome)
  • Langer-Giedion Syndrome (8q24.1 – trichorhinophalangeal syndrome Type 2)
  • 1p36 Syndrome
  • Prader-Willi Syndrome
  • Wolf Hirschhorn Syndrome (4p- syndrome)

One laboratory is looking for errors in any of the chromosomes.

Analysis: Since Non Invasive Prenatal Testing [NIPT] and/or Non Invasive Prenatal Screening [NIPS] are actually screenings tests (not diagnostic tests), patient Informed Consent or Informed Refusal is very important in these cases.

Further, both patients and their healthcare providers need to ask prior to screening if the Maternal Fetal DNA labs are screening for Trisomy 15 or the chromosome that the patient and/or healthcare provider are concerned about.

Therefore, the patient needs to be informed in writing that having the Maternal Fetal DNA screening will help lower the chances for having a child with many chromosomal abnormalities but the specific chromosomal abnormality (Trisomy 15) may not be detected without a Chorionic Villus Sampling (CVS) or amniocentesis.

Further, the patient needs to understand that screening tests have “False Positive” and “False Negative” results.

Also, the patient(s) should understand that whether the Maternal Fetal DNA testing comes back as “High Risk” or “Low Risk” and the patient wants more accuracy in diagnosis, then CVS and/or amniocentesis should be considered.

Healthcare providers must constantly walk the fine line between managing patient expectations and the limitations of Non Invasive Prenatal Testing [NIPT] and/or Non Invasive Prenatal Screening [NIPS].

Even though diagnostic testing is more likely to establish a definite diagnosis, healthcare providers should understand that No testing is 100% reliable.