Noninvasive Prenatal Testing (NIPT) through analysis of cell free DNA (cfDNA) was first introduced in 2011 as a screening test for Down syndrome (trisomy 21). The list of conditions that cfDNA can screen for has grown to include trisomy 18, trisomy 13, sex chromosome conditions, and several microdeletion conditions. Several professional organizations have published practices guidelines and statements regarding cfDNA including:

 

This grid can provide a hard and fast breakdown regarding basic recommendations from each organization.

Group First-tier test? Sex chromosomes? Microdeletions and microduplications? Multiple gestations?
ACOG No If requested by patient No No
ACMG Yes Let patient know it’s available Let patient know it’s available Check with lab first
SMFM No n/a n/a n/a
ISPD Yes? Should be offered Yes Yes
NSGC No n/a n/a n/a
ASHG/ESHG Yes No No n/a

ALL guidelines advocate the following:

  • Patients should have the opportunity to make an informed choice to decline or accept testing
  • Pre and post-test counseling regarding the overall benefits, risks, and limitations is essential

Other important guideline information:

  • In 2016, ACMG updated their cfDNA policy: ‘New evidence strongly suggests that NIPS can replace conventional screening for Patau, Edwards, and Down syndromes across the maternal age spectrum, for a continuum of gestational age beginning at 9–10 weeks, and for patients who are not significantly obese.’
  • When comparing cfDNA to other screening methods, AGOG and SMFM state ‘no one screening test is superior to other screening tests in all test characteristics. Each test has relative advantages and disadvantages.’
  • The ISPD discourages the use of maternal age as an indicator of prior risk and states that cfDNA is one possible primary screening approach for women, regardless of age or other risk factors.

 

Below we provide a brief ‘to the point’ summary from each organization. Click on one to get a more detailed breakdown of their position statement.

American College of Obstetrics and Gynecology (ACOG)

To the point…

In May of 2016, The American College of Obstetricians and Gynecologists partnered with the Society for Maternal-Fetal Medicine on Practice Bulletin number 163: Screening for Fetal Aneuploidy. In this guideline, ACOG and SMFM recommend that all women should be offered the option of screening tests for aneuploidy, and cfDNA screening is one testing option. This document provides an excellent overview of some of the potential benefits, drawbacks and limitations of various screening technologies. In June of 2015, ACOG and SMFM published Committee Opinion #640, Committee Opinion #640 Cell-free DNA Screening for Fetal Aneuploidy . The Committee Opinion states that cfDNA should not be considered “routine” and advocate that careful pretest counseling including discussion of the test’s limitations, risks, and alternatives is necessary. The statement advises against the use of this testing as a first-line test in the general obstetric population, as well as in pregnancies with multiple gestations. Furthermore, they advise against routine screening for microdeletion conditions with cfDNA.

American College of Medical Genetics (ACMG)

To the point… 

The ACMG published a Statement on Noninvasive Prenatal Screening for aneuploidy. Unlike other professional organizations, ACMG does not recommend that cfDNA be restricted to women at increased risk. ACMG emphasizes that cfDNA should not be considered a routine prenatal test, as well as the importance of pre- and post-test counseling. There are specific scenarios in which cfDNA is not considered the best option (i.e. a case of fetal anomalies that is suggestive of a single gene disorder). The guideline states that cfDNA does not replace the need for first trimester ultrasound or maternal serum alpha-fetoprotein in the second trimester as screening for neural tube defects. There are a number of patient resources references in this guideline.

Society for Maternal-Fetal Medicine (SMFM)

To the point…

SMFM has been active in releasing professional guidance regarding cfDNA, and have taken a strong position that cfDNA should only be used in pregnancies determined to be high-risk for aneuploidy (35 or older, high risk result on other aneuploidy screen, past pregnancy with a trisomy condition, parental Robertsonian translocation involving chromosome 21 or 13). The statement cautions that this test should not be considered “routine” and advocates that careful pretest counseling including discussion of the test’s limitations is necessary. Furthermore, SMFM does not support routine inclusion of microdeletion conditions on cfDNA panels, and advises against testing in low-risk women as well as in pregnancies with multiple gestations. The statement advocates that all women who receive a positive test result or a failed result from cfDNA should receive follow-up counseling from a qualified medical professional, as well as the availability to undergo diagnostic testing for patients desiring a more definitive result. 

The International Society for Prenatal Diagnosis (ISPD)

To the point… 

The International Society for Prenatal Diagnosis (ISPD) released a position statement regarding cell-free DNA (cfDNA) in April 2015 from the Chromosome Abnormality Screening Committee on Behalf of the Board of the International Society for Prenatal Diagnosis. Unlike the previous statement by the ISPD in 2013, this document suggests that cfDNA may be used as a primary screening for all pregnant women as one of many possible approaches that may be considered by a screening program. The ISPD also supports biochemical as well as combined biochemical and ultrasound screening as primary testing options. They suggest cfDNA may be used as a secondary screen for intermediate or high-risk women as determined by other screening methods. and they emphasize that diagnostic testing is only possible through amniocentesis or CVS. The ISPD recommends development of prenatal screening protocols that best meet the resources and needs of individual communities.

National Society of Genetic Counselors (NSGC)

To the point…

The NSGC currently supports the use of cfDNA as an option for patients who are considered to be at an increased risk for aneuploidy. NSGC advocates that cfDNA should only be offered in the context of informed consent, education, and counseling by a qualified provider, such as a certified genetic counselor. Patients whose cfDNA results are abnormal, or who have other factors suggestive of a chromosome abnormality, should receive genetic counseling and be given the option of standard confirmatory diagnostic testing. The NSGC has a white paper on the topic of cfDNA as well as fact sheets to assist providers in pre- and post-test counseling regarding cfDNA results.

American Society of Human Genetics (ASHG) & European Society of Human Genetics (ESHG)

To the point… 

The European Society of Human Genetics (ESHG) and the American Society of Human Genetics (ASHG) released a joint statement on cfDNA in March 2015. Similar to other organizations the ESHG/ASHG statement emphasizes the cfDNA is a screening test and the importance of pretest information and counseling is highlighted. Many ethical issues of the expanding role of cfDNA to include condition such as microdeletions and sex chromosome conditions are discussed in detail and ultimately the statement advises against the use of cfDNA for conditions apart from trisomy 21, trisomy 18, and trisomy 13.