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 for all women? Sex chromosomes? Microdeletions and microduplications? Multiple gestations?

ASHG/
ESHG  

Yes No No n/a
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 Yes? n/a n/a n/a
ACOG Yes? n/a 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. They state that no one screening test is superior to other screening tests, and that screening for aneuploidy should be an informed patient choice, with an underlying foundation of shared decision-making that fits the patient’s clinical circumstances, values, interests, and goals. This document provides an excellent overview of some of the potential benefits, drawbacks and limitations of various screening technologies. 

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 advises against testing in low-risk women. 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 pregnant patients. NSGC advocates that qualified providers should communicate the benefits and limitations of cfDNA screening to patients prior to testing and because many factors influence cfDNA screening performance it may not be the most appropriate option for every pregnancy. Prior to undergoing cfDNA screening, patients should have the opportunity to meet with qualified providers who can facilitate an individualized discussion of patient’s values and needs including the option to decline all screening or proceed directly to diagnostic testing. Patients whose cfDNA results indicate increased-risk should receive post-test genetic counseling from clinicians with expertise in prenatal screening, such as genetic counselors, and be given the option of diagnostic testing to facilitate informed decision making. 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.