If You Test Positive on a Definitive Diagnostic Test — Amniocentesis or CVS

Rewritten on: August 6, 2025

If NIPT returns a high-risk result, a definitive diagnostic test — CVS (chorionic villus sampling) or amniocentesis — is essential. NIPT is not 100% accurate, so a definitive diagnosis is needed to determine with certainty whether a chromosomal abnormality is present, and to carefully weigh the options that follow.

Definitive testing is essential

NIPT (Non-Invasive Prenatal Testing) screens for chromosomal abnormalities in the fetus by analyzing cell-free fetal DNA (cfDNA) circulating in the mother's blood. However, even when NIPT flags a chromosome-number abnormality as high risk, not everyone goes on to have a definitive diagnostic test during the pregnancy. Some people decide to give birth without a definitive diagnosis, have a miscarriage before reaching that point, or choose to terminate the pregnancy.[ref:1]

NIPT is ultimately a screening test, and it is not 100% accurate. Some reports suggest that combining NIPT with ultrasound can raise accuracy to nearly 100%, but a definitive diagnostic test — either before or after birth — is required to accurately confirm whether a genetic condition involving a chromosome-number abnormality is actually present. The Steering Committee for the Prenatal Testing Accreditation System also treats a definitive diagnosis as mandatory, and does not recommend making a final decision based on NIPT results alone.[ref:2]

That said, a definitive diagnosis during pregnancy is not necessary in every case. For example, with a condition like Jacobsen syndrome, where about 85% of affected people go through daily life without ever noticing symptoms because they are so mild, and where the clinical impact is limited, a definitive prenatal diagnosis may not be considered necessary. Even in such cases, however, consulting a genetic counselor or specialist is still generally recommended. Genetic counseling provides an expert explanation of what the test results mean, the risks involved, and the options available going forward.

Reasons some choose not to have definitive testing during pregnancy

Even after receiving a high-risk NIPT result, some people choose not to undergo a definitive diagnostic test. The main reasons include the following.

• Believing NIPT is nearly 100% accurate and assuming a definitive test is unnecessary
• Not wanting to undergo amniocentesis or CVS because of the risk of permanent harm to the baby or miscarriage associated with these definitive tests
• Having already decided to continue the pregnancy regardless of the test outcome
• Being reluctant to undergo additional testing because of the emotional burden involved

However, it is worth questioning whether the accuracy figures for NIPT published on the websites of many domestic testing providers can simply be taken at face value. NIPT's accuracy varies depending on the type of chromosomal abnormality being screened for, as well as the mother's condition, gestational age, and the proportion of fetal-derived cfDNA (fetal fraction).[ref:3]

seeDNA developed the first prenatal DNA testing service in Japan back in 2016, and has since accumulated more than eight years of experience conducting prenatal testing on fetuses. Based on this extensive track record and expertise, we can say with confidence that there is always some risk of error in NIPT results, and it is not a test that can guarantee 100% accuracy. False positives — cases where a high-risk result is given even though no chromosomal abnormality is actually present — occur at a certain rate, and without a definitive diagnosis it is impossible to know the true situation. In fact, large-scale studies have shown that NIPT's positive predictive value (PPV) varies considerably depending on the condition being screened for and the mother's age; while PPV is relatively high for trisomy 21, it tends to be lower for trisomy 13 and trisomy 18.[ref:4] [ref:10]

For this reason, we strongly recommend that anyone who receives a high-risk (positive) NIPT result be sure to undergo a definitive diagnostic test.

Part of the reason this misunderstanding persists is that the Japanese term for NIPT is literally translated as "new-generation prenatal 'diagnosis'." In English it is "Non-Invasive Prenatal Testing" — it is only ever "testing." If the Japanese term were instead rendered as "new-generation prenatal 'screening'," it might help spread the correct understanding that NIPT is a screening test rather than a definitive diagnosis, and reduce this kind of confusion.

As more organizations have begun offering NIPT recently, some even claim 100% accuracy, but NIPT is not 100% accurate. Providers that make such claims should not be trusted. The Japan Association of Obstetricians and Gynecologists has also issued warnings about the limitations of NIPT, noting that interpreting the results correctly requires specialized expertise.[ref:5] [ref:6] [ref:7]

About the results of definitive testing

There are two main types of definitive diagnostic test: CVS (chorionic villus sampling) and amniocentesis. Here we take a detailed look at CVS, which can be performed in early pregnancy (typically around weeks 10–13).

The CVS process and how long results take

In CVS, a small sample of chorionic villus tissue — part of the placenta — is collected and the chromosomes are examined directly. Results are typically reported in two stages.

1. Rapid CVS result (about 3 days later): A "rapid CVS" result is reported first, covering only whether trisomy 13, 18, or 21 (chromosomal abnormalities) is present. Using rapid analysis techniques such as FISH or QF-PCR, it is possible to confirm the presence or absence of the major chromosomal abnormalities within about three days.
2. Full CVS result (within about 2 weeks): A detailed karyotype analysis covering all chromosomes is performed, providing a more comprehensive result that also includes whether any microdeletion syndromes are present.
3. Consultation with a doctor and deciding next steps: If both the rapid CVS result and the ultrasound findings suggest the baby may have a condition, the doctor will promptly discuss the options going forward.

Unlike conditions related to everyday lifestyle factors, autosomal aneuploidies (such as trisomies) identified through CVS have no fundamental cure, so the options that follow need to be considered carefully. Making a decision after receiving the results is an extremely weighty matter for the individual, their partner, and their family, so it is important to consult thoroughly with a genetic counselor and the attending physician.

How reliable are the results

CVS testing is reported to give a definitive result in 99 out of 100 women tested, putting its accuracy at over 99%. In a small number of cases, a phenomenon called confined placental mosaicism (CPM) can occur, in which the chromosomal makeup of the chorionic villus tissue differs from that of the fetus itself. In such cases it may not be possible to fully confirm whether the baby actually has the condition being tested for, but the likelihood that a CVS result will later prove to be wrong during pregnancy is very low, and it is considered the most accurate test currently available.[ref:8] [ref:11]

Based on the results obtained, one of the following options generally needs to be considered.

■ Continuing the pregnancy

It is important to gather as much information as possible about the condition the baby may have, and to prepare thoroughly. This includes checking what medical care will be needed after birth, how to access welfare services, and connecting with other families raising children with the same condition — gathering information from many angles and building a support system. It is also recommended to start considering, early on, which hospital to give birth at (for example, one with NICU facilities).[ref:8]

■ Ending the pregnancy (termination)

This is an extremely difficult decision. After receiving broad-ranging advice from a genetic counselor and the attending physician about the symptoms the child may have and the treatment and support that may be needed, the partner and family need to discuss the matter thoroughly and reach a decision together. In Japan, induced abortion under the Maternal Health Act is legally permitted only before 22 weeks of pregnancy. Because of this, it is important to factor in the time needed for definitive testing and subsequent decision-making, and to act promptly.

Limits of definitive testing and the possibility of diagnostic error

Definitive testing is highly accurate, but because it is still a test performed by people, it is not realistically possible to guarantee 100% accurate results. Besides the confined placental mosaicism mentioned above, there is also a nonzero chance of problems arising in how the sample is handled or cultured.

In fact, there have been cases in Japan where a diagnostic error during definitive testing led to a court awarding damages. Cases like this are rare, but it is important to recognize that even a definitive diagnosis is not infallible.[ref:4]

In Japan, as a project commissioned by the Children and Families Agency, information is provided not only on prenatal tests such as NIPT and on medical institutions, but also a wide range of information useful during pregnancy and after birth. Reliable information about life with a child who has a disability, and about the lives of the families around them, is also available there.

Comparing types of definitive testing: CVS vs. amniocentesis

There are two definitive diagnostic methods — CVS and amniocentesis — and they differ in when they can be performed and in their characteristics. The main differences are summarized below.

The biggest advantage of CVS is that it can be performed earlier in pregnancy than amniocentesis. Getting results sooner leaves more time for making subsequent decisions. Amniocentesis, on the other hand, is less affected by confined placental mosaicism, so it is sometimes used as a follow-up test when a CVS result is uncertain. Both tests carry a small miscarriage risk (roughly 0.1–0.5%), so it is important to receive a thorough explanation before undergoing either one.[ref:3] [ref:9] [ref:12]

Avoiding the misunderstanding that NIPT is a "diagnosis"

As reflected in its English name, "Non-Invasive Prenatal Testing," NIPT is fundamentally just a "test (screening)." Because the Japanese term is translated as new-generation prenatal "diagnosis," many people end up mistakenly believing that the NIPT result alone constitutes a definitive diagnosis.

What NIPT detects is the estimated "level of risk" for a chromosomal abnormality, based on the proportion of fetal-derived cfDNA in the mother's blood — it is not a result from directly analyzing the fetus's own cells. That is why, even when NIPT returns a high-risk result, a definitive diagnostic test is essential to rule out the possibility of a false positive. This is especially true for trisomy 13 and trisomy 18, where the false-positive rate tends to be somewhat higher than for trisomy 21, making it risky to draw conclusions without a definitive diagnosis.[ref:10]

For those who receive a high-risk NIPT result, seeDNA offers support that helps cover the cost of genetic counseling and of undergoing a definitive diagnostic test. Our specialist staff are available to provide consistent support so you can make decisions based on accurate information — please feel free to contact us.

Frequently Asked Questions

Q1. If NIPT comes back high risk (positive), should I always get a definitive diagnostic test?

A. Yes. NIPT is a screening test and does not guarantee 100% accuracy. Because false positives (a positive result even when no abnormality is actually present) are possible, anyone who receives a high-risk result is strongly advised to undergo a definitive diagnostic test such as CVS or amniocentesis. The Steering Committee for the Prenatal Testing Accreditation System also treats a definitive diagnosis as mandatory.[ref:1]

Q2. Which should I choose — CVS or amniocentesis?

A. CVS can be performed around weeks 10–13 of pregnancy, and amniocentesis around weeks 15–18. CVS has the advantage of returning results earlier, but carries a slight risk of being affected by confined placental mosaicism. Amniocentesis is considered less susceptible to this. Which test is appropriate depends on gestational age and individual circumstances, so it's best to discuss this thoroughly with your doctor or a genetic counselor.[ref:3]

Q3. What is the miscarriage risk when undergoing a definitive diagnostic test?

A. Both CVS and amniocentesis carry a reported miscarriage risk of roughly 0.1–0.5%. This risk can vary depending on the technique used and the experience of the medical facility, so it's important to be tested at an institution with a solid track record. Many people worry about the miscarriage risk, but we recommend weighing it alongside the importance of getting accurate information from a definitive diagnosis, and making an overall judgment.[ref:3] [ref:9] [ref:12]

Q4. What is the difference in accuracy between NIPT and definitive testing?

A. NIPT is a screening test that evaluates the "level of risk" for a chromosomal abnormality. Its sensitivity (the ability not to miss an abnormality) is high, but false positives can occur. Definitive testing (CVS or amniocentesis), on the other hand, directly analyzes the fetus's own cells, allowing chromosomal abnormalities to be determined with over 99% accuracy. It may help to think of NIPT as the "initial screen" and definitive testing as the "final determination."[ref:2]

Q5. What kind of support is available if a definitive diagnosis comes back positive?

A. If a definitive diagnostic test comes back positive, counseling from a genetic counselor or specialist can provide detailed information about the condition, the options going forward, and the support programs available. seeDNA also offers support that helps cover the cost of counseling and of the definitive diagnostic test itself after a high-risk result.

Q6. Can a definitive diagnosis ever be less than 100% accurate?

A. Definitive testing is considered the most accurate test currently available, but because it is still performed by people, 100% accuracy can never be guaranteed. Confined placental mosaicism (CPM) can play a role, and in very rare cases problems can arise in how the sample is processed. There are court cases in Japan where damages were awarded over a diagnostic error during definitive testing. If you ever have doubts about a result, consider getting a second opinion.[ref:4]

Q7. What is confined placental mosaicism (CPM)?

A. Confined placental mosaicism refers to a phenomenon in which the chromosomal makeup of the placental tissue differs from that of the fetus itself. Because CVS involves sampling only part of the placenta, this phenomenon can, in rare cases, cause the result to differ from the fetus's actual chromosomal makeup. If CPM is suspected, it is recommended that amniocentesis be performed as a follow-up to confirm the result.[ref:8] [ref:11]