Discrepancies between NIPT and results of amniotic fluid testing and birth outcomes

Correlation of NIPT results with amniocentesis results①
（21, 18 and 13 trisomy）

検査結果の相関表

Of the 67 cases that underwent NIPT at the clinic and tested positive for 21 trisomy and proceeded to amniotic fluid testing, 62 were confirmed to have a 21 trisomy (positive result rate: 92.5%). (positive predictive rate 92.5 %).

Similarly, for 18 trisomy, out of 26 positive NIPT results, 17 confirmed diagnoses of 18 trisomy were made (positive predictive value: 65.5%). (positive predictive value 65.4 %).

For 13 trisomy, out of 12 positive NIPT results, there were 5 confirmed 13 trisomy. (positive predictive value 41.7 %)

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Correlation of NIPT results with amniocentesis results②
（RAA）

検査結果の相関表

Of the positive NIPT results other than 21, 18 and 13 trisomy, 7, 8 and 16 trisomy were confirmed for the same disease on amniocentesis.

It is important to note that NIPT is a screening test and that the positive predictive value depends on the prevalence of the disease. In general, the lower the number of people with the disease in the overall population, the lower the positive predictive value.

This is why NIPT, which is considered to have high sensitivity and specificity, has a low positive predictive value: 21 trisomy is the most prevalent disease in medicine today, and the prevalence rate decreases with 18 trisomy, 13 trisomy and other aneuploidies.

Correlation of NIPT results with amniocentesis results③
（SCA）

検査結果の相関表

For sex chromosomes, the overall population data is still small, but positive predictive values of 100% for XXY, 63.6% for XO, 50% for XYY and 100% for XXX have been obtained.

Correlation of NIPT results with amniocentesis results④
（Structural abnormality）

検査結果の相関表

For structural abnormalities, the data population is also small, but several diseases have been definitively diagnosed in amniotic fluid tests.

‘Positive results for low-prevalence and rare diseases without missing them’ – this is an important performance in screening tests.

Let’s replace this with a common screening test. Imagine a cancer screening test. Many people are tested, but only a handful of them actually have cancer, so the positive predictive value is quite low.

Isn’t it more important not to miss the handful who should go on to a full screening than to have a high positive predictive value? This relationship between cancer screening and a thorough examination is the relationship between NIPT and a definitive test (e.g. amniotic fluid test).

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What is an outcome discrepancy?

  • For discrepancies between NIPT results and amniocentesis (definitive diagnosis) results, all are NIPT false positives (as of 10 February 2023)
  • Almost all of the discrepancies between NIPT results and birth outcomes are strictly difficult to prove a link with NIPT results
  • The information obtained from the postnatal questionnaire includes a mixture of diseases and abnormalities that are not due to chromosomal abnormalities, and there is no way of confirming chromosomal abnormalities
  • This can be a powerful decision-making tool with regard to gender discrepancies. To date, three gender discrepancies have been reported

Q&A

  • Q
    What is the positive predictive rate of chromosomal abnormalities in NIPT?
    Positive predictive values of approximately 92.5% have been reported for 21 trisomies, 65.4% for 18 trisomies and 41.7% for 13 trisomies. Depending on the prevalence rate (a figure indicating the proportion of people with a particular disease or health problem in a given area or population), the positive predictive rate varies.
  • Q
    If a positive NIPT result is given, what can be done next?
    If a positive result is obtained from NIPT, it is recommended that a confirmatory diagnostic test, such as an amniotic fluid test, is performed. This is to confirm the results of the screening test, NIPT.
  • Q
    What support is available after receiving the results of the NIPT?
    Hiro Clinic offers amniotic fluid test support for a fee of JPY 3,000 (excluding tax). By using this service, patients with a positive test result can receive a subsidy of up to JPY 200,000, including tax, for the cost of an amniotic fluid test.
  • Q
    Are there any psychological coping strategies if I receive a positive result from NIPT?
    It is natural to feel anxious about the results. You can reduce the psychological burden by using genetic counseling and discussing your future options with your doctor.
  • Q
    How should I tell my family and partner about the results after a positive NIPT result?
    Calmly communicate the facts and share your professional opinion so that you can proceed with your family and partner to make an appropriate decision.
  • Q
    What are the necessary procedures and timelines after a positive NIPT result?
    You will need to plan for a definitive diagnosis, such as an amniotic fluid test. It is important to schedule the test in consideration of the time period during which the test is available and the time it takes to get the results.
  • Q
    What is the difference between a positive result and a false positive for NIPT?
    A positive test indicates a high probability of disease, but is not a definitive diagnosis. A false positive is a case in which a positive result is given even though there is no actual disease.
  • Q
    If I test positive for NIPT, what kind of support will I receive until the birth of my child?
    Some testing centers may offer medical consultation, genetic counseling, and financial support. Check the available support in advance.
  • Q
    What are the risks of not receiving a confirmed diagnosis after a positive NIPT result?
    If you do not receive a definitive diagnosis, you will proceed with the pregnancy without knowing the health status of the fetus. Uncertainty can place a psychological burden on the pregnant woman and her family.
  • Q
    Are there any cases where a fetus that tested positive for NIPT was actually healthy?
    Yes, NIPT is a screening test and false positives can occur. In some cases, a confirmed diagnosis confirms that the fetus is healthy.
  • Q
    Why does the NIPT positivity rate vary from disease to disease?
    The positive predictive value varies depending on the prevalence of each disease and the characteristics of the placenta-derived DNA. 21 trisomies have a high positive predictive value, while 13 trisomies have a relatively low positive predictive value.
  • Q
    How can the health of the fetus be confirmed after a positive NIPT result?
    Amniotic fluid and chorionic villus examinations can be performed to definitively diagnose fetal chromosomal abnormalities and genetic disorders.
  • Q
    How can I prepare for postpartum support after a positive NIPT result?
    It is important to research available systems in advance, such as medical institutions, local government support, and welfare services for disabled children.
  • Q
    Is there anything in particular I should pay attention to after a positive NIPT result?
    Although it can be upsetting to receive the results, it is important to calmly sort through the information and use the confirmed diagnosis and expert opinion to decide what to do next.
  • Q
    Is it possible to consult with another medical provider after a positive NIPT result?
    Yes, you can seek a second opinion for further advice and support.
  • Q
    If I choose to have a baby after receiving a positive NIPT result, do I need any special medical support?
    Depending on the condition of the fetus, you may need specific treatment and support after delivery. It is important to consult with your medical provider and make preparations.
  • Q
    Are there ways to reduce the cost burden after receiving a positive NIPT result?
    Some facilities offer a system to subsidize the cost of amniotic fluid testing. Check the details of the support before taking the test.
  • Q
    How should I spend the waiting period after a positive NIPT test until the test results are available?
    It is an anxious period, but it is helpful to talk with a specialist, utilize family support, and plan for your next steps.
  • Q
    How should I deal with the psychological impact of a positive NIPT result on the pregnant woman and her family?
    If the psychological burden is significant, counseling and support at medical institutions can help reduce anxiety.
  • Q
    Can I refer to blogs or testimonials about a positive NIPT result?
    While other people's experiences can be helpful, it is important to consult with a medical specialist before making a final decision, as not all cases are the same.