Non-invasive Prenatal Testing (NIPT)
“An Update on Prenatal Screening”
Dr Annette UWINEZA,MD
Phd in Human Genetics
Procedures undertaken to diagnose genetic abnormalities and structural
anomalies often
early embryo and fetus in order to undertake timely prenatal counseling and
appropriate interventions .
Prenatal genetic testing
Main types of prenatal genetic tests?
There are two general types of prenatal tests for genetic disorders:
Prenatal screening tests.
Prenatal diagnostic tests
Done on cells from the fetus or placenta obtained
through amniocentesis or chorionic villus sampling (CVS).
Frequency of fetal aneuploidies
Aneuploidy Syndrome
Frequency (live births)
Trisomy 21 Down syndrome
1 in 700
Trisomy 18 Edwards syndrome
1 in 5,000
Trisomy 13
Patau syndrome
1 in 16,000
Risk Down syndrome versus Maternal Age
Age Frequency (live births)
30 0.1 %
40 1 %
50 10%
Prenatal screening tests for Down syndrome
PAPPA: pregnancy-associated plasma protein A
Classical Down syndrome screening
NT (mm)
Normal : 2.0
T21 : 3.4
T18 : 5.5
T13 : 4.0
B-HCG (MoM)
Normal : 1.0
T21 : 2.0
T18 : 0.2
T13 : 0.5
PAPP-A (MoM)
Normal : 1.0
T21 : 0.5
T18 : 0.2
T13 : 0.3
Nicolaides et al 2008
If positive : invasive prenatal diagnosis
Chorionic Villus Sampling (CVS)
Early (11 – 14 weeks of pregnancy)
Transabdominal
Transcervical
Amniocentesis
Midtrimester ( > 14 weeks of pregnancy)
Purpose of Invasive prenatal diagnosis
Sample (Amniotic fluid/ chorionic villi )
Karyotype
Array-CGH
Inborn error of metabolism
DNA sequencing
Down syndrome Karyotype
Non invasive prenatal testing (NIPT)
Cell-free fetal DNA (cff DNA)
Both the mother and the fetal-placental unit
produce cfDNA.
“Fetal" cfDNA is from apoptosis of placental cells
“Maternal cfDNA ” is from hematopoietic cells .
< 1 % of total DNA in maternal circulation is fetal
1-30 % of cell-free DNA (cfDNA) in maternal
circulation is fetal
Non-invasive Prenatal Testing (NIPT)
Methods : Next-generation sequencing technologies (DNA sequencing)
Table : Cell-free DNA Test Performance Characteristics in Patients Who Receive an Interpretable Result
1.Committee Opinion No. 640: Cell-free DNA Screening for Fetal Aneuploidy. Obstet Gynecol. 2015;126(3):e31-37.
Comparison of Options
Compari
son of O
ptions
CVSAm
nioSeq
uential
MSS
NIPT
Timing
11-13 w
eeks
≥16 we
eks10-2
2 week
s≥ 10 weeks
Risk of
miscarr
iage
<1%~0.
2%Non
eNon
e
Sensitiv
ity>99
% all
aneuplo
idies
>99% a
ll
aneuplo
idies
90% tri 2
1>98
% tri 21
Falsepo
sitive
Rate
<2% all
<1% all
5% tri 2
1<0.5
% tri 21
Failure
Rates
<1%<1%
<1%1-5%
Costs
~$2,000
~$1500
~$400
$800-$3
,000
300$-800$
CVS: chorionic villus sampling
MSS: Sequential maternal screening is a 2-part test, with 1st and 2nd trimester screening .
NIPT results
1. Normal result : no specific follow up necessary,
unless ultrasound examination of the fetus reveals anomalies
2. Test failure : in < 1% pregnancies not enough fetal DNA
3. Abnormal NIPT result : confirmation by amniocentesis or chorion biopsy
.
NIPT essentials
1. TEST : trisomy 21 (Down syndrome), trisomy 18 (Edwards syndrome), trisomy 13 (Patau syndrome). Also sex of the fetus is determined, upon request.
3. TIMING: From week 11
4. TURNAROUND TIME: 1 week
5. RELIABILITY: > 99% for trisomy 21
6. INDICATIONS: Although NIPT can be performed in every pregnancy, it is especially indicated:
• If the triple test or first trimester screening indicates an increased risk
• Advanced maternal age
• Anxiety for invasive procedures
7. CONTRAINDICATIONS: NIPT is not the test of choice when there is :
• Fetal anomalies on ultrasound
• Severely elevated NT (nuchal translucency < 3.5 mm) with normal PAPP-A and free B HCG
• A triplet pregnancy
What is done in Rwanda
Karyotype
Need to develop First trimester combined screening :
Maternal age combined with NT, free beta-hCG and PAPP-A
Why not
NIPT
Thank you