NIPT

Non-Invasive Prenatal Genetic Testing

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You have probably heard of prenatal tests called “amniocentesis” and “chorionic villus sampling” (CVS), which are bothconventional methods used to detect chromosomal diseases in babies before birth. These tests are definitive, but invasive(including needle insertion into the uterus); therefore, the risk of miscarriage cannot be ruled out.
NIPT has been developed as a non-invasive screening test — i.e., without any invasion of the pregnancy — and offers a means
to test for the risks of a baby having a chromosomal disorder.
This instruction contains important information for expectant mothers and their families considering whether to undergo NIPT.

OverviewofNIPT●NIPT is a test used to estimate the possibility of fetus having chromosomal anomalies called trisomies — such as trisomy 21,trisomy 18, and trisomy 13.
●The test is available from 9-10 weeks of pregnancy. It only requires 10-20 ml of blood from the mother.
●NIPT is a screening test that examines small fragments of DNA (cell-free DNA, cfDNA) circulating in the blood of pregnant women.
●Approximately 10% of the cfDNA floating in the mother’s blood is of placental origin. As it does not always match the DNA of thefetus itself, the results may be slightly less accurate. Therefore, the NIPT is considered a highly accurate test; however, it can only
tell you how likely it is that your baby has a chromosomal difference.
●The results are reported as “positive,” “negative,” or “inconclusive.” “Positive” indicates a high probability of chromosomal disorders.
●If you test “positive” for NIPT, it is necessary to have a definitive test (amniocentesis or CVS) performed, while in the case of“inconclusive,” you need to consult again on the possible subsequent actions that can be taken.

What areChromosomes?

●Most individuals have 46 chromosomes, consisting of 22 pairs of autosomes (numbered 1-22) and a pair of sex chromosomes (XXor XY).
●Each chromosome contains a large number of genes that provide a blueprint for the body’s structure and function.
●Changes in the number or structure of chromosomes can affect fetal growth and development, which can result in birth defects andphysical characteristics.
●Chromosomes normally occur in pairs. Trisomy means that a person has three chromosomes instead of two. For example, trisomy
21 indicates that a baby has 3 copies of chromosome 21. (“Tri”- is Greek for “three”)

What NIPT
can and cannot
tell us●NIPT is a test performed to estimate the possibilityof trisomy 21, 18, and 13. No other abnormalities
are detected.
▶ About 3-5 out of every 100 babies are born withcongenital diseases.
▶ Of these, chromosomal abnormalities account for
approximately 25% of all the diseases. Moreover,
70% of these abnormalities are trisomy 21, 18,
or 13. According to the calculation, 0.7 out of 100
babies have one of those trisomies.

Teratogen
5%

Multifactorial
40%

Congenital diseases
3～5%

Copy number
variants
10%

Chromosome
anomalies
25%

Single-gene
defects
20%

Others16%
Sex chromosome
abnormalities
13%

Trisomy 21(Down syndrome)53%

Trisomy 13
5%
Trisomy 18
13%

Figure. Frequency of congenital diseases and chromosome anomalies.
（Thompson & Thompson Genetics in Medicine 8th Edition Saunders 2016;
Wellesley D, et al. Eur J Hum Genet 2012: 20:521）

Maternal ageand trisomy●It has been reported that the risk for trisomy
increases with maternal age.
●Not every kind of chromosomal anomaly shows aclear correlation with maternal age.

Congenital
disorders
as diversity●Any baby can be born with a congenital disorderthat is sometimes caused by chromosomal
anomalies. Congenital disorders may give theTable. The frequency of trisomy in relation to maternal age
baby unique characteristics which can be regarded
as a part of their individuality, and what is more,human diversity as a whole.
●It would be a challenge to live with some congenital abnormalities, but this is not a
critical factor in deciding whether or not you are happy.
●Whatever situation you are in, don’t forget that you are never alone. The government
has attempted to build a mutually supportive and acceptable society that provides
public services.
●Individual choice should be respected, including the decision to terminate orcontinue pregnancy. Some groups provide peer support to mothers and theirNPO for Family and Baby Wellness
https://fetalhotline.fab-support.org/
families to help them make more informed decisions.

Maternal age at delivery
202530354045For prenatal testing, we are in collaboration with the facility (core hospital) below.

Facility Name:
Physician in charge:
Facility Address:
Contact:

Trisomy 21
1/14411/1383
1/959
1/338
1/84
1/30

Trisomy 18
1/10000
1/83001/72001/36001/740

Trisomy 13
1/14300
1/12500
1/11100
1/53001/1400Pediatricians could also be consulted before and after the test.
We collaborate with a “prenatal consult pediatrician” below.

Physician Name:
Facility Name:
Contact:

Health Labour Science Research Grant Project in FY2021 (Basic Research on Raising Next-Generation Children, including Overcoming Children’s Diseases)“Research on the Establishment of a System for Providing Prenatal Diagnoses”

Trisomy 21 (Down syndrome)●Trisomy 21 occurs in approximately one in every 600–800 live births.
●Physical growth and language development are relatively slow in children with down syndrome.
However, an appropriate environment (including therapeutic rehabilitation) can promotedevelopment.
●Some children with Down syndrome might have health problems, such as heart defects andgastrointestinal disorders.
●Many of them attend local schools and special support schools.
●Adults with Down syndrome sometimes need nursing care for daily activities, but many live intheir own local communities with support from the government. Throughout their lives, they canreceive various types of public support services.
●Down syndrome is listed by the Minister of Health, Labor and Welfare as one among many
“specific pediatric chronic diseases.” Patients with specific pediatric chronic diseases can receivegovernment support and welfare in several ways.
●You can find circles and group activities for parents and children with trisomy 21 across thecountry, from which you can obtain welfare services and opportunities to exchange information.

Japan Down Syndrome Society
https://www.jdss.or.jp

Yokohama Project
https://yokohamapj.org/

Trisomy 18 (Edwards syndrome)

Characteristicsof three targetedtrisomies●Trisomy 18 occurs in approximately 1 in every 4,000–10,000 live births.
●A fetal ultrasounds during pregnancy can show features suggestive of trisomy 18 — such as
growth deficiencies, heart defects, gastrointestinal disorders, and changes in limb morphology.
●Babies with trisomy 18 are often born with numerous difficulties, including breathing and feeding,which require medical management during the early postnatal period.
●Due to the presence of several medical problems, such as heart disease and respiratory
failure, babies with trisomy 18 sometimes die shortly after birth. However, aggressive medical
interventions have been reported to improve patients’ lives and life expectancies. With this, someindividuals can even reach adulthood.
●Patients may show motor and intellectual delays after birth. However, receiving suitable medical
treatment and attending special support schools will promote their development slowly, butsteadily.
●Trisomy 18 is listed by the Minister of Health, Labor and Welfare as one of a range of “specificpediatric chronic diseases.” Patients with specific pediatric chronic diseases can receive
government support and welfare in several ways.

Trisomy 18 Support Group
http://18trisomy.com/

Team18https://team-18.jimdofree.com/

Trisomy 13 (Patau syndrome)●Trisomy 13 occurs in approximately 1 in 5,000–10,000 live births.
●Fetal ultrasounds performed during pregnancy can show features suggestive of trisomy 13 —such as heart defects, central nervous system abnormalities, gastrointestinal disorders, andchanges in body morphology.
●Babies with trisomy 13 are often born with numerous difficulties, including breathing and feeding,which require medical management during the early postnatal period.
●Due to the presence of several medical problems, such as heart disease and respiratory
failure, infants with trisomy 13 sometimes die shortly after birth. However, aggressive medical
interventions have been reported to improve patients’ lives and life expectancies. With this, someindividuals can reach adulthood.
●Children with trisomy 13 may not learn how to do things that typical children do, such as walking
or talking. However, they are able to learn and develop at their own pace.
●Trisomy 13 is listed by the Minister of Health, Labor and Welfare as one among a number of“specific pediatric chronic diseases.” Patients with specific pediatric chronic diseases can receive
government support and welfare in several ways.

☆ PROJECT13 ☆
http://trisomy13.blog.jp/

Parents' Association for Childrenwith Trisomy 13
http://www.13trisomy.com/next.html

Before you make a final decision on having NIPT, please note the following●NIPT is a non-invasive test used to screen for chromosomal abnormalities in
the fetus by using maternal blood. Please keep in mind that you will have asignificant hurdle to overcome if you test either as “positive” or “inconclusive.”●This non-invasive test can provide an important indication of whether you will
undergo further invasive procedures, such as amniocentesis, which carries
a risk of fetal loss.
●A “positive” result means that there is a higher chance for the baby to havetrisomy 21, trisomy 18, or trisomy 13.
▶ NIPT does not give you a definitive answer. The only way to be sure is tohave a diagnostic test, such as amniocentesis or CVS. During this invasive
procedure, a needle is inserted through the belly into the uterus, increasing
the risk of miscarriage by up to 1 in 300.
▶ Sometimes NIPT gives a “positive” result when the fetus does not actually
have the chromosomal disorder (a so-called “false positive”). For example,
if a 35-year-old pregnant woman receives a positive result for Down
syndrome, there is a 6.4% chance that the result is wrong and that the fetus
does not have the condition.
▶ Any individuals with “positive” results should be provided genetic counselingfor a discussion of NIPT results, and what to do next.
●A “negative” result means the chance for the baby to have trisomy 21,
trisomy 18, or trisomy 13 is generally very low.
▶ Although the negative predictive value for those three trisomies is greaterthan 99.9%, NIPT is not 100% accurate. The test has a very small chance
for a “false negative” (a baby who tests “negative” for NIPT but born with thecondition).
▶ Since trisomies are not the only kind of congenital disorders that occur
in babies, a “negative” result does not indicate that the baby is free ofdiseases.

●An “inconclusive” result indicates that the test did not provide clear positiveor negative results.
▶ Japanese data shows that there is about a 0.3-0.4% chance of getting an“inconclusive” result.
▶ When receiving an “inconclusive” result, it is necessary to consult again
on possible subsequent actions (e.g., having a repeat NIPT, receiving
diagnostic testing, or having no further tests conducted).
●NIPT reveals the possibility of chromosomal disorders in your baby.
However, it cannot tell you precisely what kind of symptoms your baby will
be born with or how it will grow after birth, since these can vary considerably
between babies. The test also does not tell you how to treat the disorder.
●Although NIPT is designed to detect chromosomal disorders in fetuses,
it may incidentally detect maternal chromosomal abnormalities, including
malignant diseases.
●In order to make a fully informed decision, genetic counseling is essential
before undergoing NIPT in order to make fully-informed decisions. With a fullunderstanding of the test, please think again if it is necessary, for you andyour partner.
●Whatever conclusion you and your partner come to after carefulconsideration, the decision will be respected as much as possible.
●If you have fears concerning the future of your baby and family, pleasefeel free to contact us for consultation. We can also make referrals topediatricians in our facility, or even to appropriate outside facilities, ifneeded.
●Even if you are told that your baby has a congenital disorder, there is noneed to feel helpless. There are various support groups in the country, andyou can receive continuous medical and social support from the government.
September 2022