Screening vs Diagnostic Testing
What is the difference between a screening test and a diagnostic test?
Let’s go through this one carefully. It is often misunderstood and extremely important to understand before making a decision about which test is right for you.
Screening and diagnostic tests are found throughout the field of medicine and pregnancy is no different. Screening tests typically have several common characteristics that include the following: they are cost effective, population based, non-invasive, socially acceptable and are relatively accurate. Diagnostic tests on the other hand tend to be less cost effective (on a population basis), are usually more invasive than a screening test, and unlike screening tests that are relatively accurate – diagnostic tests are extremely accurate.
Here are a few comparative examples to highlight the differences in pregnancy.
A 35 year old woman undergoes a Non-Invasive Prenatal Test (NIPT). This test screens for 4 common chromosome abnormalities – trisomy 13, 18, 21 and the sex chromosomes. The test has a 99% chance of detecting trisomy 21 (Down syndrome), an approximately 80% chance of detecting trisomy 18 and an approximately 67% chance of detecting trisomy 13. It will miss only 1/100 cases of trisomy 21, 20/100 cases of trisomy 18 and 33/100 cases of trisomy 13. It will miss all cases of abnormalities in the other 19 chromosomes not interrogated and microdeletions/duplications on all chromosomes.
Instead, the same 35 year old woman undergoes diagnostic CVS (or amniocentesis) for fetal karyotype with the following test results – “Normal female karyotype – 46, X,X”. Not only did this test definitively demonstrate this pregnancy is not affected with Down syndrome nor Edwards syndrome but it also evaluated the structure and number of 21 other pairs of chromosomes not evaluated in the screening test example. Alternatively, this same 35 year old woman may choose to have the CVS (or amniocentesis) sample tested for microarray abnormalities. Not only will this test definitively determine all chromosomes are correct but also definitively rule out any small deletions or duplications of genetic material.
Which test is right for me?
The standard screening test through the California Prenatal Screening Program or through a private lab after September 19, 2022 is the Non-Invasive Prenatal Test (NIPT). This type of screening test is marketed by several labs including Sequenom’s MaterniT 21, Ariosa’s Harmony Prenatal 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 screening tests.
There are advantages and disadvantages to 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. The NIPT relies on a single blood 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.
Even though the NT is not a formal part of the 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. While difficult, this discussion 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. Please read the section on diagnostic testing to understand the differences between testing for chromosomes numbers and genetic conditions/syndromes/deletions/duplications.
In general, people who want to know their baby is definitively healthy rather than more than likely/probably should strongly consider undergoing diagnostic testing. This type of testing eliminates the risk of the false negative (test result that says pregnancy is not affected with Down syndrome when really it is) and does so in a much more detailed manner. In the case of a karyotype (or chromosome analysis) – all chromosomes are evaluated rather than just a few with NIPT or serum screening and in the case of a microarray analysis the individual sections of each and every chromosome are evaluated. For a more detailed description of diagnostic tests – click on the “Patient Resources” tab on the home page and then “Diagnostic Tests”.
One of the most important decisions you will make about your pregnancy.
You will be faced with numerous decisions during your pregnancy. After choosing your primary obstetrical care provider, decisions you make about what screening/diagnostic tests to undergo are probably the second most important decision you will make about your pregnancy.
Will you undergo a screening test or a diagnostic test to tell you about the health of your pregnancy?
Most people have an array of resources from which to base a decision including friends, family social media and the internet to name just a few. On the one hand, more resources may mean more information to make a correct informed decision while on the other hand, a the correct decision for someone may be difficult to make if peer and social pressure impact their decision. I have often been asked by patients what my wife and I decided to do for our pregnancy – screening or diagnostic testing. You will be hard pressed to find a patient out of the last 14 years that has heard me answer that question because I don’t. The decision that was right for me and my wife may or may not be right for someone else. I have no interest in biasing an individuals decision about what testing strategy is right for them. Get genetic counseling, talk it over with your husband/wife/partner and find out what is right for you – not someone else.
Why is an ultrasound exam so important in pregnancy?
— During the first trimester, a fetal ultrasound determines the health of an early pregnancy with the measurement of the nuchal translucency.
— During the second trimester, a fetal ultrasound rules out most birth defects with a comprehensive evaluation of the fetal anatomy.
— During the third trimester, a fetal ultrasound evaluates the size of the developing baby and identifies pregnancies with abnormal growth.