Prenatal testing certification system
Executive committee

Amniocentesis and chorionic villus sampling are methods to reliably determine whether the baby in the uterus has achromosomal disorder or not before birth, however they carry with them risks such as miscarriage (due to puncture of theuterus with a needle). Therefore non-invasive methods to test for chromosomal disorders in babies have been developed,
one of which is NIPT (non-invasive prenatal genetic testing). This document describes the information that you should knowand be aware of in order to decide whether or not to undergo NIPT.

NIPTOutline●NIPT is a test to determine whether the baby in the uterus has a chromosomal disorder.
●The chromosomal disorders tested are trisomy 21, trisomy 18 and trisomy 13.
●After about 9 to 10 weeks of pregnancy, 10 to 20 ml of blood is collected from the pregnant woman and cfDNA (fragmentedchromosomes) floating in the blood are analyzed in order to obtain results.
●Results are reported as “Positive”, “Negative” or “Pending”. "Positive" means that there is a high possibility of that disease.
●About 10% of the cfDNA floating in the blood of pregnant women comes from the baby, or more precisely from the placenta.
Therefore, although NIPT is a highly accurate test, it only determines the likelihood of a chromosomal disorder.
●If the test result is "positive", a confirmatory test using amniotic fluid cells or chorionic villus cells is required. In addition, in thecase of "pending", it is necessary to consult with the doctor again about what to do next.

What arechromosomes●Most people have 46 chromosomes, consisting of a pair of autosomes (chromosomes 1 to 22) and a pair of chromosomes (XYchromosomes) that differ according to sex.
●Chromosomes are packed with many genes (blueprints for the human body and functions).
●Changes in the number or form of chromosomes can affect growth and development and can result in congenital diseases anddistinct physical features.
●"Trisomy" is a condition in which there are 3 chromosomes instead of 2 (a pair). For example, trisomy 21 is a condition in which
there are 3 chromosome 21s.

What wecan andcannot
learnfromNIPT
Maternalage andbirth rateoftrisomicinfantsOur
diversityandcongenit
aldiseases●NIPT is a test that checks for possible chromosomal disorders such as
trisomy 21, trisomy 18, and trisomy 13, but it does not detect otherdisorders➢ About 3 to 5 out of 100 babies are born with congenital diseases.
➢ In that number, chromosomal causes account for about 25%, and thethree chromosomal disorders covered by NIPT account for another
70%. Doing the math, the number of babies born with the three
chromosomal disorders covered by NIPT is about 0.7 in 100.

(Thompson & Thompson Genetics in Medicine 8th
Edition Saunders 2016; Wellesley D. et al. Eur J Hum Genet 2012; 20:521●It is known that as maternal age increases, the frequencyof births of babies with trisomy also increases.
●For other chromosomal disorders, the effect is not clear.

●Anyone can have a baby with a congenital disorder, including birth defects caused by chromosomal changes. This can make yourbaby different from most people, but that's a characteristic of uman diversity and individuality.
●It cannot be denied that having characteristics different from other people due to congenital disorders may lead to a more difficult
life. On the other hand, it can also be said that a person's happiness or unhappiness is not only determined by such characteristics.
●Regardless of our circumstances, we are all members of society, and public welfare services are provided in order to create asociety that recognizes and helps all individuals.
●On the other hand, for various reasons, some people may decide not to give birth and that choice is also respected.
There are also organizations that provide peer support by those who have experience in these situations.
https://fetalhotline.fab-support.org/

For NIPT affiliated facilities: We are affiliated with the following
facilities (core facilities).
Facility:
Doctor:Address:
Consultation contact:

You can talk directly to a pediatrician (prenatal consultationpediatrician) before or after the test. The prenatal consultation
pediatricians who collaborate with our facility are as follows.
Doctor:Facility:
Contact:

2012 Ministry of Health, Labor and Welfare Research Grant (Next-generation Development Fundamental Project for Overcoming ChildhoodDiseases) “Research for creating a system for providing prenatal diagnosis”

Trisomy 21 (Down Syndrome)

Characteristicof diseases
that are tested⚫ In general, it is said to occur in 1 in 600 to 800 births.
⚫ Physical and language development after birth is generally slow, but growth and development can beencouraged in an appropriate environment (by therapy).
⚫ They may have issues such as heart disease and digestive problems.
⚫ During school age, they attend local schools and special needs schools.
⚫ After becoming adults, they may need nursing care, but many of them live in the community while
receiving support from the government, and various support services are available throughout theirlives.
⚫ It is certified as a specified chronic childhood disease (see the site at the bottom of page 7), and there
are support systems such as medical care, welfare, and the community of the person concerned.
⚫ In each region, there are places for information exchange such as parent meetings and circle activities,
and welfare support systems are also in place.

Japan Down Syndrome Association

Yokohama Project

Trisomy 18 (Edwards' Syndrome)⚫ Generally, it is said to occur in 1 in 4,000 - 10,000 births.
⚫ Ultrasound examinations performed during prenatal checkups may reveal abnormal growth in thebaby, heart disease, digestive system disease, morphological changes in the limbs, etc.
⚫ Babies may be born with multiple ailments and may require medical attention early in life, including
respiratory and feeding support.
⚫ They may die soon after birth due to illnesses such as heart disease and respiratory failure. On theother hand, aggressive medical intervention is reported to improve life span and prospects, and somepeople live longer, reaching adulthood.
⚫ Although there is a delay in motor skills and intellectual aspects, by attending special support schools
and continued medical management, these skills will develop slowly as they grow.
⚫ It is certified as a specified chronic childhood disease (see the site at the bottom of page 7), and there
are support systems such as medical care, welfare, and the community of the person concerned.

Trisomi 18 Association

Trisomy 13 (Patau Syndrome)⚫ Generally, it is said to occur in 1 in 5,000 - 10,000 births.
⚫ Ultrasound examinations performed during prenatal checkups may detect diseases such as heartdisease, central nervous system disorders, and morphological changes.
⚫ Babies may be born with multiple ailments and may require medical attention early in life, including
respiratory and feeding support.
⚫ They may die soon after birth due to illnesses such as heart disease and respiratory failure. On theother hand, aggressive medical intervention is reported to improve life span and prospects, and somepeople live longer, reaching adulthood.
⚫ They rarely learn to walk or speak on their own, but tend to grow and develop slowly.
⚫ It is certified as a specified chronic childhood disease (see the site at the bottom of page 7), and there
are support systems such as medical care, welfare, and the community of the person concerned.

Children with Trisomy 13

Association of Parents SupportingChildren with Trisomy 13

Things to reconfirm before undergoing the test
⚫ NIPT can be performed only by drawing blood from pregnant
women, but it is a test to check for chromosomal disorders in babies
before birth. Any result other than "negative" can lead to various
difficulties.
⚫ NIPT can be said to be a test that pregnant women who are worried
about whether to undergo invasive tests with a risk of miscarriage,
such as amniocentesis, can undergo as a basis for deciding whether
to do so or not.
⚫ A NIPT “positive” result means that there is a high probability of
one of the 3 trisomy disorders.This test cannot confirm the diagnosis.
In order to confirm the diagnosis, it is necessary to undergo
amniocentesis or chorionic villus sampling, but since these
examinations involve inserting a needle into the uterus from theabdomen, there is a 1 in 300 probability of miscarriage.
➢ The test result may be positive, but the chromosomal disorder may
not be present (called a false positive). For example, even if a 35year-old pregnant woman is "trisomy 21 positive", there is about a
20% chance that the baby will not have Down's syndrome.
➢If the test is "positive", genetic counseling should be sought for
further explanation of the results and follow-up.
⚫ A NIPT "negative" result means that the probability of one of thethree trisomy disorders is low.
➢ The probability that it is not one of the three trisomies is over
99.9%, but they cannot be 100% ruled out. Although very rare, it
is possible to have a chromosomal disorder even with a negative
result (false negative).
➢ There are many congenital disorders other than trisomal disorders,so a "negative" test does not mean the baby is free of any disease.
⚫ A NIPT “pending” result is when the result cannot be determined as“positive” or “negative”.
➢ According to national data, there is a 0.3 to 0.4% chance that theresult will be "pending".
➢ In this case you will need to consult with the doctor again about
what to do next (repeat NIPT, give up on the NIPT test, undergo
amniocentesis, etc.).
⚫ Even if the test reveals the possibility of a chromosomal disorder inthe baby in the uterus, the actual symptoms of the baby and the stateof subsequent development cannot be clearly determined because
there are individual differences. In addition, this test is not directly
related to the treatment of any disorder.
⚫ Although the original purpose of the test is to investigate
chromosomal disorders in the baby, chromosomal disorders andmalignant tumors in the pregnant woman may also be discovered
during this test.
⚫ Before you decide whether to undergo the test, make sure you
understand the process well through pre-test genetic counseling andconsider whether it is necessary for you and your partner.
⚫ Regardless of whether you decide to undergo NIPT or not, yourwell-thought out decision will be respected.
⚫ We are always available to discuss any concerns or worries about thefuture of your baby or family. If you would like a more detailed
explanation, we can refer you to an on-site pediatrician or anappropriate outside facility.
⚫ Don't forget that even if your baby has some form of congenital
disease, there are always support services who will work together
with you to find the best way forward for your baby, such as medical
and welfare services.
September 2022