Prenatal testing certification system
Executive committee

Executive Committee for the prenatal testing certification system website『Let's consider together about the different tests for your baby』

Non-invasive prenatal genetic testing

A site for pregnant women and their families. We provide information on various types of prenatal
testing, where to consult, opinions of those who have undergone testing and those who chose
not to, as well as information on living with a child with a congenital disease and information
about welfare services.
For NIPT affiliated facilities: We are affiliated with the following facilities (core facilities).
Facility:
Doctor:Address:
Consulation contact:
You can talk directly to a pediatrician (prenatal consultation pediatrician) before or after the test.
The prenatal consultation pediatricians who collaborate with our facility are as follows.
Doctor:Prenatal testing certification system
Executive committee

Facility:
Contact:
This booklet was produced in cooperation with the Japan Society of Obstetrics and Gynecology

2021 Ministry of Health, Labor and Welfare Research Grant

and the Japanese Society of Human Genetics.

(Next-Generation Development Fundamental Research Project for Overcoming
Sept 2022

Childhood Diseases)「Research on creating a system for providing prenatal diagnosis」

1

Introduction

What are chromosomes?

Amniocentesis and chorionic villus sampling are methods to reliably determine whether the⚫

baby in the uterus has a chromosomal disorder or not before birth, however they carry with

Most people have 46 chromosomes, consisting of a pair of autosomes (chromosomes 1to 22) and a pair of chromosomes (XY chromosomes) that differ according to sex.

them risks such as miscarriage (due to puncture of the uterus with a needle). Therefore noninvasive methods to test for chromosomal disorders in babies have been developed, one of⚫

which is NIPT (non-invasive prenatal genetic testing).

Chromosomes are packed with many genes (blueprints for the human body andfunctions).

This document describes the information that you should know and be aware of in order to⚫

decide whether or not to undergo NIPT.
Outline of NIPT

Changes in the number or form of chromosomes can affect growth and development
and can result in congenital diseases and distinct physical features.

⚫

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⚫

"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.

pregnant woman and cfDNA (fragmented chromosomes) floating in the blood areanalyzed 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 chorionicvillus cells is required. In addition, in the case of "pending", it is necessary to consult withthe doctor again about what to do next.

Fig. chromosomes (46, XY)

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What we can learn and what we cannot learn from NIPT⚫

NIPT is a test that checks for possible chromosomal disorders such as trisomy
21, trisomy 18, and trisomy 13, but it does not detect other disorders.

➢About 3 to 5 out of 100 babies are born with congenital diseases.

➢

In that number, chromosomal causes account for about 25%, and the three
chromosomal disorders covered by NIPT account for another 70%. Doing themath, the number of babies born with the three chromosomal disorders coveredby NIPT is about 0.7 in 100.

The frequency of the disease increases with the age of the pregnant woman, but if the maximum value on thevertical axis is set to 100%, the upward trend is not clear. If you expand it like the graph on the right, you can
see the upward trend.

Fig. Birth rates of infants with chromosomal disorders by maternal age at birth(Morris JK et al., J Med Screen 9:2-6,2002; Morris JK et at., Prenat Diagn 25:275-278,2005; Appendix in Savva GM et al.,Prenat
Diagn 30:57-64,2010)

Our Diversity and Congenital Diseases
Fig. Frequency of congenital disorders and chromosomal disorders⚫

Anyone can have a baby with a congenital disorder, including birth defects caused by(Thompson & Thompson Genetics in Medicine 8th Edition Saunders 2016; Wellesley D, et al. Eur J Humchromosomal changes. This can make your baby different from most people, but that's aGenet 2012:20:521)

characteristic of human diversity and individuality.

Relationship between maternal age and birth frequency of trisomic infants⚫

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⚫

It is known that as maternal

happiness or unhappiness is not only determined by such characteristics.

age increases, the frequency⚫

of births of babies withare provided in order to create a society that recognizes and helps all individuals.

trisomy also increases.
⚫

For

other

Regardless of our circumstances, we are all members of society, and public welfare services⚫

chromosomal

On the other hand, for various reasons, some people may decide not to give birth and thatchoice is also respected. .There are also organizations that provide peer support by thosedisorders, the effect is not

who have experience in these situations.

clear.

■ Association for supporting the future of parents and children(https://fetalhotline.fab-support.org/)
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Characteristics of diseases that are tested
Trisomy 21 (Down Syndrome)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),⚫

In general, it is said to occur in 1 in 600 to 800 births.

and there are support systems such as medical care, welfare, and the community of the⚫

Physical and language development after birth is generally slow, but growth and development

person concerned.

can be encouraged in an appropriate environment (by therapy).

■ Trisomy 18 Association (http://18trisomy.com/)⚫

They may have issues such as heart disease and digestive problems.

■ Team 18 (https://team-18.jimdofree.com/)⚫

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 communityTrisomy 13 (Patau Syndrome)

while receiving support from the government, and various support services are available⚫

Generally, it is said to occur in 1 in 5,000 - 10,000 births.

throughout their lives.

⚫

Ultrasound examinations performed during prenatal checkups may detect diseases such as⚫

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 theheart disease, central nervous system disorders, and morphological changes.
⚫

person concerned.
⚫

Babies may be born with multiple ailments and may require medical attention early in life,including respiratory and feeding support.

In each region, there are places for information exchange such as parent meetings and circle⚫

activities, and welfare support systems are also in place.

They may die soon after birth due to illnesses such as heart disease and respiratory failure.
On the other hand, aggressive medical intervention is reported to improve life span and■ Japan Down Syndrome Association (https://www.jdss.or.jp)

prospects, and some people live longer, reaching adulthood.

■ Yokohama Project (https://livingwds.info/)⚫

They rarely learn to walk or speak on their own, but tend to grow and develop slowly.

Trisomy 18 (Edwards' Syndrome)⚫

It is certified as a specified chronic childhood disease (see the site at the bottom of page 7),⚫

Generally, it is said to occur in 1 in 4,000 - 10,000 births.

and there are support systems such as medical care, welfare, and the community of the⚫

Ultrasound examinations performed during prenatal checkups may reveal abnormal growth

person concerned.

⚫

⚫

⚫

in the baby, heart disease, digestive system disease, morphological changes in the limbs, etc.

■ Children with Trisomy 13☆PROJECT13☆(http://trisomy13.blog.jp/)

Babies may be born with multiple ailments and may require medical attention early in life,■ Association of Parents Supporting Children with Trisomy 13

including respiratory and feeding support.

(http://www.13trisomy.com/next.html)

They may die soon after birth due to illnesses such as heart disease and respiratory failure.
On the other hand, aggressive medical intervention is reported to improve life span and■ Specified Chronic Diseases in Pediatrics "Overview of Countermeasures forprospects, and some people live longer, reaching adulthood.

Specified Chronic Diseases in Pediatrics Ministry of Health, Labor and Welfare”

Although there is a delay in motor skills and intellectual aspects, by attending special support(mhlw.go.jp)

6

7

⚫

Things to reconfirm before undergoing the test⚫

NIPT can be performed only by drawing blood from pregnant women, but it is atest to check for chromosomal disorders in babies before birth.

Any resultor “negative”.
➢other than "negative" can lead to various difficulties.
⚫

NIPT can be said to be a test that pregnant women who are worried about⚫
➢➢(repeat NIPT, give up on the NIPT test, undergo amniocentesis, etc.).
⚫

trisomy disorders.

development cannot be clearly determined because there are individualThis test cannot confirm the diagnosis. In order to confirm the diagnosis, it isdifferences. In addition, this test is not directly related to the treatment of any

necessary to undergo amniocentesis or chorionic villus sampling, but sincedisorder.
⚫

➢

in the baby, chromosomal disorders and malignant tumors in the pregnant

The test result may be positive, but the chromosomal disorder may not be

woman may also be discovered during this test.
⚫

Before you decide whether to undergo the test, make sure you understand thewoman is "trisomy 21 positive", there is about a 20% chance that the baby willprocess well through pre-test genetic counseling and consider whether it is

not have Down's syndrome.

necessary for you and your partner.

If the test is "positive", genetic counseling should be sought for further⚫

Regardless of whether you decide to undergo NIPT or not, your well-thought out
decision will be respected.

A NIPT "negative" result means that the probability of one of the three trisomy⚫

We are always available to discuss any concerns or worries about the future ofdisorders is low.

your baby or family. If you would like a more detailed explanation, we can refer

The probability that it is not one of the three trisomies is over 99.9%, but they

you to an on-site pediatrician or an appropriate outside facility.

cannot be 100% ruled out. Although very rare, it is possible to have a➢

Although the original purpose of the test is to investigate chromosomal disorders

there is a 1 in 300 probability of miscarriage.

explanation of the results and follow-up.
⚫

Even if the test reveals the possibility of a chromosomal disorder in the baby in
the uterus, the actual symptoms of the baby and the state of subsequent

present (called a false positive). For example, even if a 35-year-old pregnant➢

In this case you will need to consult with the doctor again about what to do next

A NIPT “positive” result means that there is a high probability of one of the 3

these examinations involve inserting a needle into the uterus from the abdomen,➢According to national data, there is a 0.3 to 0.4% chance that the result will be"pending".

whether to undergo invasive tests with a risk of miscarriage, such asamniocentesis, can undergo as a basis for deciding whether to do so or not.

A NIPT “pending” result is when the result cannot be determined as “positive”⚫

Don't forget that even if your baby has some form of congenital disease, there

chromosomal disorder even with a negative result (false negative).

are always support services who will work together with you to find the best way

There are many congenital disorders other than trisomal disorders, so a

forward for your baby, such as medical and welfare services.

"negative" test does not mean the baby is free of any disease.

89

References
Types of tests for examining chromosome disorders in babies during pregnancy
Inconclusive test (non-invasive test)

Conclusive test (invasive test)

Ultrasound marker test

Maternal serum

NIPT(combined test)

marker test

Non-invasive prenatal genetic testing

Timing

11 - 13 wks

15 - 18 wks

9 - 10 wks and beyond

Chromosomal disease

Trisomy 21

Trisomy 21

Trisomy 21

Trisomy 18

Trisomy 18

Trisomy 18(Trisomy 13)
MethodUltrasound (NT etc.)

Chorionic villus sampling

Amniocentesis

11 - 14 wks

15 - 16 wks and beyond

General chromosomal disorders

General chromosomal(Trisomy 13)

disorders

Blood sampling only

Blood sampling only

Chorionic puncture

Amniocentesis

80%

99%

99.9%

99.9%

Positive/negative/pending

Chromosome photo/Karyotype

Chromosome⋆Combined test requires blood sampling

Detection rate (sensitivity)

NT: about 60%

for trisomy 21

Combined test: 80%

How results are shown

Probability (1/○○○) orProbability (1/○○○)

positive/negativeor positive/negative

Test characteristics

photo/Karyotype

Many false positives

Many false positives

High positive predictive value

Risk of miscarriage (1%)

Risk of miscarriage (0.3%)

No risk of miscarriage

No risk of miscarriage

No risk of miscarriage

Limited facilities

Relatively many facilities

Limited facilities

Many facilities

Limited facilities

Early implementation

Inexpensive

Inexpensive

ExpensiveAffected by placental mosaicism⋆

Early implementation

Early implementation⋆Placental mosaicism: A difference in the number of chromosomes between the placenta and fetus.
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