The NIPT (= “non-invasive prenatal testing”, NIPT or “Non-Intrusive Pregnancy Diagnostic Test”. NIPDT; non-invasive prenatal test; synonyms: Harmony test; Harmony Prenatal Test) is a molecular genetic blood test for the detection of cell-free DNA (cfDNA test, cell-free DNA test). Cell-free DNA are DNA fragments from chromosomes that circulate freely in maternal blood during pregnancy. They originate from both the fetus and the mother. The pregnant woman should be at or above 10+0 weeks of gestation (SSW).As a screening test in prenatal diagnosis (PND; prenatal diagnosis), NIPT is used to assess risk for:
- Chromosomal disorders – chromosomal abnormalities that may affect the number of chromosomes (numerical chromosomal abnormality: one chromosome too many or too few) or the structure of chromosomes (structural chromosomal abnormality):
- Trisomy (unusual meiosis (maturation division) of oocyte (egg cell) or sperm (sperm cell) that results in a chromosome or part of a chromosome being present in triplicate (trisome) rather than in duplicate (disome) in all or some of the body’s cells)
- Trisomy 21 (Down syndrome; synonyms: “mongolism”)
- Triplication of the genetic material of chromosome 21.
- Children have weak to moderate mental retardation
- Often malformations of internal organs (eg vitia / heart defects).
- Most common trisomy: 1 in 740 newborns is affected.
- Trisomy 18 (Edwards syndrome; synonyms: E1 trisomy, trisomy E).
- Triplication of the genetic material of chromosome 18.
- High miscarriage rate (miscarriage rate).
- Children are born with severe malformations
- Short life expectancy
- 1 in 5,000 newborns is affected
- Trisomy 13 (Patau syndrome; synonyms: Patau syndrome, Bartholin-Patau syndrome, D1 trisomy).
- Triplication of the genetic material of chromosome 13.
- High miscarriage rate (miscarriage rate).
- Children are born with severe congenital (congenital) vitia (heart defects)
- Usually die within the first year of life
- 1 in 16,000 newborns is affected
- Trisomy 21 (Down syndrome; synonyms: “mongolism”)
- Trisomy (unusual meiosis (maturation division) of oocyte (egg cell) or sperm (sperm cell) that results in a chromosome or part of a chromosome being present in triplicate (trisome) rather than in duplicate (disome) in all or some of the body’s cells)
- Disorders/maldistribution of sex chromosomes X, Y and resulting hereditary diseases.
- Klinefelter syndrome – gonosome (sex chromosome) abnormality of the male sex resulting in primary hypogonadism (gonadal hypofunction). It occurs approximately once in 500 male newborns.
- Turner syndrome (synonym: Ullrich-Turner syndrome) – girls/females with this disorder have only one functional X chromosome instead of the usual two (monosomy X); it is the only viable monosomy in humans and occurs approximately once in 2500 female newborns.
- Triple X syndrome (XXX) / Trisomy X: In triple X syndrome, the X chromosome is present three times. This disorder affects only girls and occurs approximately once in 1,000 female newborns
- XYY syndrome / Diplo Y syndrome: In diplo Y syndrome, which also affects only boys, there is an extra Y chromosome in the cells. It occurs circa once in 1,000 births of male newborns.
Furthermore, the NIPT can be used to determine the sex of the unborn. The accuracy here is > 99%.
Before the examination
The NIPT requires medical information and genetic counseling in accordance with the German Genetic Diagnostics Act (GenDG). The NIPT currently allows reliable statements on the probability of trisomy 21, 18, 13, but no statements on structural malformations. However, these make up the majority of perinatally relevant anomalies. Also, most other chromosomal defects and syndromal conditions cannot be detected. Note: In twin pregnancies, after artificial insemination, and in obesity, NIPT has a higher failure rate and there are limited data on test performance.
The procedure
The test is a noninvasive molecular genetic prenatal diagnostic test to determine fetal trisomies (see above). Furthermore, it can be used to detect disorders/maldistribution of sex chromosomes. Scientific studies show that the rates for false-positive and false-negative results were significantly lower in contrast to other non-invasive screening tests [[6-11].In particular, the detection rate for trisomy 21 has been significantly improved using this test. In the Next study, the results from NIPT (Harmony test) were compared with those from first trimester screening (18,056 pregnant women). Under Harmony testing, all 36 trisomy 21 cases were detected. The false positive rate for the Harmony test was 0.06%, which is approximately five times lower than other methods (e.g., first trimester screening). Consequently, the NIPT is a risk-free alternative compared to conventional invasive screening methods (amniocentesis (amniocentesis) or chorionic villus sampling/tissue collection from the fetal (child) portion of the placenta). Note: NIPT is also suitable for twin pregnancies as well as IVF pregnancies after egg donation. However, a limited detection rate (approx. 93%) must be expected for twin pregnancies. Material needed
- Blood serum – 2 x 10 ml venous blood.
- Two blood collection tubes
Preparation of the patient
- Not necessary
Disruptive factors
- None
Indications (areas of application)
- Pregnant women, from 10+0 weeks of gestation (SSW), who have an increased risk of chromosomal changes as well as disorders/maldistribution of sex chromosomes in the unborn child
- Determination of fetal sex (notification of the result may be made only after the 14th SSW post menstruationem).
Interpretation
- NIPT is a screening test. If NIPT is abnormal, diagnostic puncture must be offered obligatorily. The indication for termination of pregnancy must not be based on an isolated NIPT finding.
- A positive result should always be confirmed by means of a second, usually then invasive method such as amniocentesis or chorionic villus sampling (CVS) and subsequent chromosomal analysis. This is especially true for trisomy 13, whose false negative rate is increased compared to the other trisomies. With the Harmony test, only 8 out of 10 trisomy 13 cases were detected.
- An inconclusive NIPT is a finding that requires clarification. In this collective, more chromosomal defects are found, especially trisomies 13 and 18 and triploidies.
Further notes
- In terms of detecting the common chromosomal abnormalities (trisomy 13, 18, and 21), NIPT is clearly superior to first trimester screening (ETS; taking into account maternal age, nuchal translucency, and the biochemical markers free-β-HCG and PAPP-A).
