Excluding ultrasound (which is also a type of screening test), there used to be two common screening tests for the most chromosome abnormalities (trisomy 13, 18 and 21) available to women in pregnancy.
The first is the most widely undertaken before September 19, 2022 (and by law had to be offered to all women in the state of California) was the California Prenatal Screening Program. This test consisted of a first trimester blood test measuring two biochemical analytes, a first trimester ultrasound to measure the nuchal translucency (NT) and a second trimester blood test measuring 4 biochemical analytes. The detection rate for Down syndrome was approximately 93% and for trisomy 18 – approximately 80%.
Effective September 19, 2022 the state of California has altered their screening program, eliminating serum screening and now employing Non-Invasive Prenatal Testing (NIPT). This type of screening test is marketed by several labs including Sequenom’s MaterniT 21, Ariosa’s Harmnony Prental Test, Genesis’ Serenity Prenatal Test, Natera’s Panorama Prenatal Screen, and Labcorp’s InformaSeq Prenatal Test. While the molecular methodology for each test varies slightly – the basis for each of these tests is the same. As a pregnancy develops, cells from the developing placenta (which is fetal in origin and therefore representative of the fetal genetic makeup) undergo a process called apoptosis (cell turnover) that results in some of the content of those placental cells, including fragments of the nuclear DNA, being released into the maternal circulation. This DNA – called “cell-free DNA” can then be quantified from a maternal blood sample. Unfortunately, because it is fragmented and diluted in a sea of maternal DNA, there is an error rate associated with interpreting the result therefore the test is a screening test and not a diagnostic test.
The Perinatologist’s perspective on NIPT.
There are advantages and disadvantages to a screening test – and to make things more confusing – those advantages and disadvantages are different depending on the age of the expecting mom. For purposes of my narrative, I will exclude the cost of each test since each person’s insurance, deductible and maximum out of pocket expense are different.
The obvious advantage is the non-invasive nature of the test. For many women, an invasive procedure such as an amniocentesis or CVS is frightening and anxiety provoking – while a blood test is relatively routine.
While the NIPT has the advantage of being non-invasive, it does have disadvantages relative to diagnostic tests. NIPT becomes a statistically better test the older the patient. That stems from the fact that the chromosome abnormalities screened for with NIPT are more common in women who are advance maternal age. Unfortunately, younger women are more likely to have a child with a genetic abnormality that NIPT does not detect. To put this into perspective, genetic abnormalities know as copy number variants or microdeletions/microduplications (where a small piece of genetic material is lost or duplicated in the process of embryogenesis – and not inherited/familial) occurs in approximately 1 in every 65 pregnancies. For those women approximately 38 years or older, their risk of a child with a chromosome abnormality is greater than this risk (1/65). However, for someone who is 32, their risk of a microarray abnormality is approximately 10 times greater than a chromosome abnormality detected by NIPT.
Even though the NT is not a formal part of California Prenatal Screening Program, there are two reasons it should be performed on all women, even those undergoing NIPT or those choosing not to undergo any type of serum screening. First, it accurately dates or confirms the due date of the pregnancy to within 3-5 days. This becomes critical later in pregnancy when assigned gestational age affects decisions made by your care provider. If the assigned due date is off by say 10 days…your pregnancy may be delivered 10 days too early … 10 days too late. Alternatively, your pregnancy may be treated as a growth restricted pregnancy (as a result of incorrect dating) when really it is not. The second, and probably the most compelling reason for undergoing a nuchal translucency is peace of mind. In addition to visualizing the nuchal translucency, a tremendous amount of fetal anatomy can be seen at the exam and if a problem exists, it can be discussed. Keep in mind, structural abnormalities seen on ultrasound are far more common than abnormalities detected with NIPT. While difficult, a discussion about a structural abnormality is better at 12 weeks rather than 20 weeks at the detailed anatomic survey ultrasound.
The main strength of NIPT is its detection rate for trisomy 21 (Down syndrome) with every company providing this test reporting a greater than 98% detection rate. The main disadvantage of this test (and it isn’t really a fault of the test) is patient’s understanding of what the test tells them. It seems more common than not that once a patient received a reassuring result from an NIPT – they assume everything is perfect. The reality is NIPT has screened for the correct number of several chromosomes and left 19 other chromosomes uninterrogated. Furthermore, with screening tests we are only talking about chromosome abnormalities and not genetic conditions (previously discussed microarray abnormalities). Please read diagnostic testing to understand the differences between testing for chromosomes numbers and genetic conditions/syndromes/deletions/duplications.
A Perinatologist’s Perspective:
Non-invasive prenatal tests (NIPT) are screening tests. They are good, but not perfect at identifying a few chromosome abnormalities (they screen for 4 of 23 pairs of chromosomes that make up our genetic blueprint). If you are comfortable with a risk assessment – a screening test (NIPT) may be the right decision for you. If you need to know definitively – a diagnostic test is probably the right choice.