Among the advancements in antenatal care, Non-invasive Prenatal Testing (NIPT) has emerged as a significant tool within obstetrics. Offering a highly accurate and non-invasive method to screen for specific chromosomal conditions, NIPT provides crucial information early in pregnancy for both parents and healthcare professionals.
This blog post will explore what NIPT is, how it differs from other antenatal tests, the conditions it screens for, and its overall importance in modern obstetric care as you continue on your journey to motherhood.
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Table of Contents
NIPT 101
Non-invasive Prenatal Testing (NIPT) is an advanced screening method that assesses the likelihood of certain foetal chromosomal conditions from a simple maternal blood sample, typically taken after 10-11 weeks of pregnancy. This modern technique analyses fragments of the fetus’s DNA (known as cell-free DNA or cfDNA) that naturally circulate in the mother’s bloodstream. By analysing this cfDNA, NIPT can identify if there is a higher chance of certain chromosomal conditions.
A key benefit of NIPT is that it poses no direct risk to the pregnancy, unlike invasive diagnostic tests such as amniocentesis or chorionic villus sampling (CVS).
NIPT has a higher accuracy rate for common trisomies compared to traditional screening methods, such as OSCAR screening, which reduces the chance of receiving an incorrect result. It can be performed early in the pregnancy, providing reassurance or allowing for earlier planning if required. It is important to remember that NIPT is a screening test that provides a personalised risk score; it is not a definitive “yes” or “no” diagnosis.
NIPT and First-Trimester OSCAR Screening: A Comparison
While NIPT has become a leading method for prenatal screening, many expectant parents are also familiar with the OSCAR (One-Stop Clinic for Assessment of Risk) screening. Understanding the differences between these two approaches is key to making an informed decision.
The OSCAR test calculates a risk score by combining three measurements:
- A nuchal translucency (NT) ultrasound scan, which measures the fluid-filled space at the back of the foetus’s neck.
- A maternal blood test for two hormone markers: free beta-human chorionic gonadotropin (β-hCG) and pregnancy-associated plasma protein-A (PAPP-A).
- Maternal age, which is a baseline risk factor.
OSCAR screens for the three most common trisomies: Trisomy 21 (Down’s syndrome), Trisomy 18 (Edwards’ syndrome), and Trisomy 13 (Patau’s syndrome). While it has been a long-standing and valuable tool, NIPT offers significant advantages in accuracy.
The key difference lies in what is being measured. OSCAR assesses hormonal and ultrasound markers, which are indirect indicators of risk. In contrast, NIPT directly analyses the foetal cfDNA circulating in the mother’s blood. This fundamental difference leads to notable distinctions in performance.
| FEATURE | NON-INVASIVE PRENATAL TESTING (NIPT) | FIRST-TRIMESTER OSCAR SCREENING |
|---|---|---|
| METHOD | Directly analyses foetal cfDNA from a maternal blood sample. | Combines an NT ultrasound with a maternal blood test for hormone markers (β-hCG & PAPP-A). |
| SENSITIVITY FOR T21 | > 99% (misses fewer than 1 in 100 cases). | ~ 90% (misses about 1 in 10 cases). |
| FALSE POSITIVE RATE FOR T21 | Significantly lower. For example, with some NIPTs, only 1 in 20 high-risk results for Trisomy 21 is a false positive. | Higher (~5%). For every 20 women screened, about 1 will receive a high-risk result. For some traditional screens, as many as 17 out of 18 high-risk results are false positives. |
| PREDICTIVE VALUE | The Positive Predictive Value (PPV) is high, meaning a high-risk result is very likely to be a true positive. | The PPV is lower and highly dependent on the patient’s individual risk factors, particularly maternal age. |
The higher sensitivity and lower false-positive rate of NIPT mean it provides a more accurate assessment of risk. This reduces the number of parents who receive a worrying high-risk result and must then consider invasive follow-up tests, such as amniocentesis or CVS, to confirm the screening result.
SOURCE: NIPT DIAGRAM FROM NATERA.COM
Sensitivity, Specificity & Predictive Values
When discussing the reliability of any screening test, it is important to understand terms like sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV).
- Sensitivity refers to the test’s ability to correctly identify those with the condition (a true positive). For example, the Panorama™ NIPT has a sensitivity of 99% for Down Syndrome (Trisomy 21), meaning it correctly identifies more than 99% of cases.
- Specificity is its ability to correctly identify those without the condition (a true negative).
- The Positive Predictive Value (PPV) is the probability that a person with a positive (high-risk) test result actually has the condition. For instance, with a high-risk result for Down Syndrome from the Panorama™ test, there is a 95% chance the fetus is affected. This also means there is a 5% chance it is a false positive.
- The Negative Predictive Value (NPV) is the probability that a person with a negative (low-risk) result truly does not have the condition. For instance, if the NPV is >99.9% for Down syndrome, it means that a negative test is extremely reassuring that we can rule out this condition.
While NIPT generally boasts high sensitivity and specificity for the common trisomies, the PPV for rarer conditions, particularly those in microdeletion panels, can be lower. Because these conditions are less prevalent, a positive result for a rare syndrome might have a higher chance of being a false positive.
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What Conditions Does NIPT Screen For?
The basic NIPT panel focuses on screening for the most common chromosomal abnormalities. This typically includes Trisomy 21 (Down’s syndrome), Trisomy 18 (Edwards’ syndrome), and Trisomy 13 (Patau’s syndrome). Furthermore, the basic panel often assesses for conditions affecting the sex chromosomes, such as Monosomy X (Turner syndrome), as well as XXX, XXY, and XYY conditions. NIPT can also identify the fetus’s sex.
Some NIPTs offer extended panels that screen for microdeletions—tiny missing pieces of a chromosome. While individually uncommon, their collective prevalence is notable. These can screen for genetic conditions such as:
- 22q11.2 deletion syndrome (DiGeorge syndrome): Prevalence of approximately 1 in 2,000 births.
- 1p36 deletion syndrome: Prevalence of approximately 1 in 5,000 births.
- Prader-Willi syndrome: Prevalence of approximately 1 in 10,000 births.
- Angelman syndrome: Prevalence of approximately 1 in 12,000 births.
- Cri-du-chat syndrome: Prevalence of approximately 1 in 20,000 births.
It is crucial for expecting parents to understand that microdeletion panels have a much lower Positive Predictive Value (PPV) compared to screening for common trisomies. For example, the PPV for some of these rare conditions can be:
- 22q11.2 deletion syndrome: 53%
- 1p36 deletion syndrome: 7-17%
- Prader-Willi syndrome: 5%
- Angelman syndrome: 10%
- Cri-du-chat syndrome: 2-5%
This means that for a condition like Cri-du-chat syndrome, a high-risk result has only a 2-5% chance of being a true positive, while there is a 95-98% chance it is a false positive. This can lead to significant anxiety and the need for follow-up invasive diagnostic tests, which carry a small miscarriage risk, to confirm the result. The decision to undertake this extended screening which is more costly but has limited accuracy is a personal one, best made in consultation with your doctor.
NIPT Availability and Considerations
In Singapore, various NIPT options are available to expectant parents. These tests differ in the scope of conditions they screen for and the underlying technology they use.
Basic NIPT panels screen for the most common trisomies and sex chromosome conditions. More comprehensive or “extended” panels are also available, which include screening for selected microdeletions.
Advanced NIPT options, such as the Panorama™ test, offer further benefits. Some testing technologies can differentiate between maternal and foetal DNA, which may enhance accuracy. The fetal fraction of DNA is included which reports the percentage of cfDNA in the patient’s blood that originates from the fetus. It is a reflection of validity of the results as the amount of cfDNA needs to be high enough for accurate reporting.
Certain tests can also be used for twin pregnancies to determine if the twins are identical (monozygotic) or fraternal (dizygotic) and the gender of each twin..
Additionally, some NIPTs can screen for the baby’s Rhesus (Rh) blood type, which is important information for Rh-negative mothers. These rhesus negative mothers (e.g. O neg, A neg, B neg, Ab neg) will need an additional injection called Rhogam immunoglobulin to prevent the mother from generating antibodies against the rhesus positive baby. This is usually given at 28 weeks gestation and after delivery.
The turnaround time for results varies between different tests but is generally available within one to two weeks after the sample is received by the laboratory. Your obstetrician can explain the tests available and help you decide which, if any, is appropriate for you.
What Happens If You Receive a High-Risk Result?
Receiving a “high-risk” NIPT result can be concerning, but it is essential to remember that it is a screening result, not a definitive diagnosis. It indicates an increased chance of a chromosomal issue that requires further investigation.
Your doctor will provide counselling and likely recommend a confirmatory test, such as Chorionic Villus Sampling (CVS), typically done between 11-14 weeks , or Amniocentesis, usually performed after week 15. These tests provide a definitive diagnosis by analysing the placental/ foetal cells with very high accuracy.
Making an Informed Decision About Antenatal Testing
Navigating the landscape of antenatal testing can feel overwhelming, but understanding the available options is a crucial step in your pregnancy journey. Understanding what NIPT can and cannot do empowers you to make choices that align with your personal values and medical needs.
The best approach is a well-informed one, made in partnership with your healthcare professional. They can offer personalised guidance based on your individual circumstances, helping you make the most appropriate decision for your pregnancy. For a personalised discussion about your antenatal care options, please feel free to contact our clinic at +65 9039 1000 to arrange a consultation or send us a message.
SOURCES:
- PanoramaTM brochure – https://www.innoquest.com.sg/wp-content/uploads/Panorama-Brochure.pdf
- Roche harmonytest – https://harmonytest.roche.com/global/en/home.html
- PanoramaTM test specs – https://www.natera.com/panorama-test/test-specs
- NIPT diagram – https://www.natera.com/resource-library/panorama/understanding-noninvasive-prenatal-testing-nipt/