Should Amniocentesis or Chorionic Villus Sampling Be Offered to All Pregnant Women?

Learning Objectives and CME/Disclosure Information

This activity is intended for healthcare providers delivering care to women and their families.

After completing this activity, the participant should be better able to:

1. Describe the limitations of genetic screening tests compared to diagnostic testing with amniocentesis or CVS
2. Counsel patients regarding the use of microarray technology in the setting of invasive prenatal testing

Estimated time to complete activity: 0.25 hours

Faculty:

Susan J. Gross, MD, FRCSC, FACOG, FACMG
President and CEO, The ObG Project

Disclosure of Conflicts of Interest

Postgraduate Institute for Medicine (PIM) requires instructors, planners, managers and other individuals who are in a position to control the content of this activity to disclose any real or apparent conflict of interest (COI) they may have as related to the content of this activity. All identified COI are thoroughly vetted and resolved according to PIM policy. PIM is committed to providing its learners with high quality CME activities and related materials that promote improvements or quality in healthcare and not a specific proprietary business interest of a commercial interest.

Faculty: Susan J. Gross, MD, receives consulting fees from Genoox, Inc., and has financial interest in The ObG Project, Inc.

Planners and Managers: The PIM planners and managers, Trace Hutchison, PharmD, Samantha Mattiucci, PharmD, CHCP, Judi Smelker-Mitchek, MBA, MSN, RN, and Jan Schultz, MSN, RN, CHCP have nothing to disclose.

Method of Participation and Request for Credit

Fees for participating and receiving CME credit for this activity are as posted on The ObG Project website. During the period from Dec 31 2017 through Dec 31 2019, participants must read the learning objectives and faculty disclosures and study the educational activity.

If you wish to receive acknowledgment for completing this activity, please complete the post-test and evaluation. Upon registering and successfully completing the post-test with a score of 100% and the activity evaluation, your certificate will be made available immediately.

For Pharmacists: Upon successfully completing the post-test with a score of 100% and the activity evaluation form, transcript information will be sent to the NABP CPE Monitor Service within 4 weeks.

Joint Accreditation Statement

In support of improving patient care, this activity has been planned and implemented by the Postgraduate Institute for Medicine and The ObG Project. Postgraduate Institute for Medicine is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.

Physician Continuing Medical Education

Postgraduate Institute for Medicine designates this enduring material for a maximum of 0.25 AMA PRA Category 1 Credit(s)™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Continuing Nursing Education

The maximum number of hours awarded for this Continuing Nursing Education activity is 0.2 contact hours.

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CLINICAL ACTIONS:

Invasive prenatal diagnostic testing usually refers to amniocentesis (analysis of amniotic fluid cells) or chorionic villus sampling (placental cells). Prenatal healthcare providers should

Offer all patients the option of prenatal invasive testing or prenatal screening
Counsel patients that unlike invasive tests which cover all chromosomal abnormalities, traditional screening tests or even the newer cfDNA (NIPS / NIPT) tests will only screen for specific and limited chromosomal abnormalities
- although cfDNA has superior detection for Down syndrome, traditional first-trimester combined screening can detect additional structural and anatomical anomalies because of the ultrasound component of the test
Identify the following risk factors for fetal aneuploidy and consider referral to genetic counseling and high risk OB services if patient requires more in depth counseling or has additional concerns
- Maternal age of 35 or older at EDD: the risk for chromosomal aneuploidy increases throughout the reproductive lifespan, not just after age 35
- If either parent of the fetus has an unusual chromosome makeup or aneuploidy, such as an additional X or Y chromosome
ACOG states

Each test has advantages and disadvantages that should be discussed with each patient, with the appropriate test offered based on her concerns, needs and values

ACMG recommends

Allowing patients to select diagnostic or screening approaches for the detection of fetal aneuploidy and/or genomic changes that are consistent with their personal goals and preferences

Informing all pregnant women that diagnostic testing (CVS or amniocentesis) is an option for the detection of chromosome abnormalities and clinically significant CNVs

SYNOPSIS:

The cells obtained from amniocentesis or CVS are analyzed to determine if the number of chromosomes are correct (46) and whether there are structural changes such as deletions or duplications. Routine karyotyping is done using light microscopy. If changes are smaller than the resolution of a microscope, then molecular techniques are required and these small alterations are called microduplications or microdeletions (see ‘Related ObG Topics’ below). Presently, despite major advances in screening technologies, diagnosis of fetal aneuploidy still requires an invasive test.

KEY POINTS:

Miscarriage Risks

In expert hands, there is a 0.1 to 0.3% chance of miscarriage associated with invasive prenatal testing
Cochrane Review (Alfirevic et al., 2017) has released its review on amnio/CVS safety
- 2nd trimester amnio increased risk of pregnancy loss, but it was not possible to quantify the loss rate, based on one study that is now over 30 years old
- Early amnio (11w0d-12w6d) is associated with pregnancy loss and clubfoot compared to 2nd trimester amnio (15w0d-16w6d)
- Transcervical CVS may be associated with higher loss rate compared to 2nd trimester amnio but the quality of the evidence was downgraded due to heterogeneity between studies
Wulff et al. (Ultrasound Obstet Gynecol, 2016), using propensity scoring on a nationwide database of approximately 150,000 women, did not find an increased risk of miscarriage or stillbirth due to amnio or CVS when indications for the procedures were taken in to account (see Related OBG Topics below for review of this paper and other recent papers on this subject of procedure related fetal loss)

Routine Karyotyping or Microarray?

Abnormal prenatal ultrasound with structural abnormality
- A chromosomal microarray analysis that can detect submicroscopic changes is recommended
- Standard karyotype may miss 6% of important chromosome changes
Normal prenatal ultrasound
- A chromosomal microarray can be offered because 1.7% of significant chromosome changes will not be detected on a standard karyotype approach

Microarray limitations to discuss with patients (see ‘Related ObG Topics’ below for more on the benefits and limitations of microarray analysis)
- In a small number of cases, the laboratory may identify copy number variants of uncertain significance (VUS), also referred to as variants of uncertain significance (VOUS)
  - Over time, as databases grow, VUSs can be re-categorized as benign or pathogenic
- Microarrays cannot detect low levels of mosaicism (more than one cell line) or balanced translocations
  - Small risk that while overall DNA appears balanced on a microarray, the breaks involved in the translocation may have disrupted a gene and lead to abnormal protein production

Additional Considerations

A patient who would not terminate a pregnancy
- Important information that may impact the management of a pregnancy may be obtained on invasive testing beyond termination of pregnancy
- Therefore, all patients should be offered the option of screening or invasive testing and have the option of accepting or declining testing irrespective of future reproductive choices
Diagnosis code: diagnosis code will vary depending on indication
- Procedure codes: amniocentesis- 59000; sono guidance for amniocentesis- 76946
- Procedure codes: CVS- 59015; sono guidance for CVS-76945