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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