In October 2020 the American College of Obstetricians and Gynecologists (ACOG) and the Society of Maternal Fetal Medicine (SMFM) released an updated practice bulletin regarding genetic screening and testing for chromosomal abnormalities during pregnancy. You may ask, why is this important? Why or how does this impact me?
Let’s start with, who are these organizations and what is a practice bulletin? ACOG and SMFM are organizations for obstetrician-gynecologists (OB/GYNs), other physicians and providers (such as genetic counselors), and scientists who focus on the care of female reproductive systems and improving the outcomes for mothers and children before, during, and after pregnancy. A practice bulletin provides a review of current knowledge on techniques and clinical management along with practice guidelines (recommendations) that are relevant for obstetrical and gynecological care. These practice bulletins are not only used by providers but also testing labs and insurance companies to help determine what to offer and what may be considered a covered service.
The practice bulletin released in October 2020 by ACOG and SMFM is titled “Screening for Fetal Chromosomal Abnormalities”. It is also referred to as Practice Bulletin Number 226 (PB 226). The updated recommendations replace a practice bulletin about the same topic published in 2016 and reaffirmed in 2018 (Practice Bulletin Number 163, PB 163).
Chromosomal conditions refer to changes in the number and structure of the chromosomes. This may include extra or missing copies (aneuploidy), missing or extra pieces (deletions or duplications, also called copy number variations), or rearrangements (such as translocations). In the context of pregnancy, these changes to the chromosomes can lead to pregnancy loss, or a baby with a chromosomal condition which may be associated with variable health concerns, developmental delays and intellectual disabilities.
Prenatal screening and diagnostic testing for chromosomal conditions has been available for several decades. Screening may involve ultrasound (e.g. nuchal translucency, detailed anatomy scan), measurement of maternal serum analytes (e.g. first trimester screen, quadruple marker screen – “quad” screen, combined, integrated, or sequential screen), or analysis of cell-free DNA (cfDNA, also called non-invasive prenatal screening or testing, NIPS or NIPT).
Diagnostic testing involves genetic testing on samples obtained from the pregnancy via chorionic villus sampling (CVS) or amniocentesis. These options and what is included have evolved over the years, with the newest being cfDNA screening. (For more detailed information about these screens and tests you can check out our videos here).
Cell-free DNA screening was introduced into clinical care in 2011. Initially, cfDNA screening was used to screen for Down syndrome, with trisomy 18, trisomy 13 and analysis of the sex chromosomes for fetal sex prediction and sex chromosome variations was added soon thereafte. And now, depending on the testing laboratory and platform used, additional chromosomal and genetic conditions may be included.
The initial research and validation studies used to introduce cfDNA screening and used to expand the conditions screened were done in high risk populations (e.g. advanced maternal age). Since that time there have been larger studies within more general populations along with multiple meta-analyses (reviews of the varying data sets). However, much of this research has been driven by the commercial laboratories that sell these cfDNA tests. This is important as the availability and uptake in cfDNA screening over the years has been largely due to commercialization with major sales initiatives from the cfDNA laboratories.
Numerous organizations have published guidelines and commentary regarding the use of cfDNA screening — particularly in respect to who should be offered this screening and what conditions should be included. The majority of organizations have indicated that the option of cfDNA screening should be at least reviewed with patients. But, there has not been agreement as to whether this screen should be offered initially to all patients or if it should only be offered to women with the highest probability of certain chromosome conditions in a pregnancy.
Most notably, in 2015, ACOG and SMFM published an opinion piece that states: “Given the performance of conventional screening methods and the limitations of cfDNA, conventional screening methods (i.e. ultrasound and long available tests that look at hormone markers in the blood) remain the most appropriate choice for first-line screening for most women in the general obstetric population” (Committee Opinion 640, Sept 2015).
Later in 2015, SMFM published the statement: “SMFM recognizes the value of cfDNA screening for women at higher risk for aneuploidy but considers that cfDNA screening is not the appropriate choice for first-line screening for the low-risk obstetric population at the present time” (SMFM special report, Dec 2015)
Then in 2016 and reaffirmed in 2018, ACOG and SMFM published a practice bulletin regarding screening in general for fetal chromosomal abnormalities (Practice Bulletin 163, PB 163). This practice bulletin reviewed all available screening options, including the benefits and limitations of each. The organizations emphasized that: “All women should be offered the option of aneuploidy screening –or- diagnostic testing for fetal genetic disorders, regardless of maternal age” (Practice Bulletin 163, reaffirmed 2018). But it is also important for other factors regarding the patient, pregnancy, and screen to be considered. The option of cfDNA screening is reviewed similar to other screening options, but it is not explicitly called out.
Following these publications, clinics and providers have varied in their approaches on what screening is offered and to whom specific screening options are offered. Particularly given SMFM’s more direct stance in 2015 and given available data, many continued or transitioned to only offering cfDNA screening to those with a higher chance of aneuploidy (e.g. women over 35 at the time of delivery, or prior pregnancy with aneuploidy).
The recent published practice bulletin by ACOG and SMFM about screening for aneuploidies (which replaces the previous bulletin), focuses on the importance of patients making informed decisions with pre- and post-test counseling being an essential part of that process. More specifically, they state that all patients should be offered the option of both screening and diagnostic testing, and based on this information patients can make an informed decision about what is best for them:
- “Prenatal genetic screening (serum screening with or without nuchal translucency [NT] ultrasound or cell-free DNA screening) and diagnostic testing (CVS or amniocentesis) options should be discussed and offered to all pregnant patients regardless of age or risk for chromosomal abnormality. After review and discussion, every patient has the right to pursue or decline prenatal genetic screening and diagnostic testing.”
And,
- “Given the personal nature of prenatal testing decision making as well as the inefficiency of offering testing only to patients at high risk, the current recommendation is that all patients should be offered both screening and diagnostic testing options.”
There has been a progression by ACOG and SMFM in their opinions toward and acceptance of cfDNA screening over the years — this is in part due to more research becoming available for review and more general experience with the screen. Because of this growth in knowledge, in this new practice bulletin, more time is spent reviewing the ins and outs of cfDNA screening. This includes acknowledgement that it has advantages over serum screening. For example, it may be able to provide information about the pregnancy that would not otherwise be detected via serum screening, and for many patients it may be the more sensitive and specific tool for screening for aneuploidies. Further, the bulletin states that “a patient’s baseline risk for chromosomal abnormalities should not limit testing options” — expanding on the point that providers may elect to offer the option of cfDNA screening to their patients
Based on all of this, at first glance, it may appear that cfDNA screening is being recommended for all pregnancies — this is what testing laboratories want providers, patients, and insurance companies to focus on. BUT, in reading the wording carefully, the guideline recommends that all women be offered screening options – exactly what options are offered is left to the discretion of the provider.
The change in language of this practice bulletin is only acknowledging cfDNA screening as one of several options that may be considered by patients — it does not state that it should be routinely ordered for all pregnant women. ACOG and SMFM recommend that patients be educated and provided the option to decide what prenatal testing, if any, is best for them. Throughout the practice bulletin the importance of allowing patients to make autonomous informed decisions about testing is emphasized. Pre-test discussion and testing options should consider a patient’s individual background, values, interests as well as access to care. In the end, they are advocating for patient education and patient autonomy .
Additionally, there is acknowledgement of the limitations of cfDNA screening. First, and foremost, it is still a screening tool. There is a possibility of a false positive or false negative result for all patients who undergo screening. And, for some pregnancies, other screens or diagnostic testing may be the better option — due to factors related to the pregnancy (e.g. multiples), the patient (e.g. maternal conditions that impact the ability to get an accurate result), or the technology itself. ACOG and SMFM address these points and the importance that patients be well aware of all of this before making a decision.
Genetic Support Foundation has a wealth of resources to help support informed patient decisions regarding prenatal genetic screening and testing options including educational videos and written materials. Learn more at www.geneticsupportfoundation.org