NIPT – background and clinical implication

Bo Jacobsson

Professor, MD, PhD, Department of Obstetrics and Gynecology

Sahlgrenska University Hospital Gothenburg, Sweden

Senior Reseracher

Norwegian Institute of Public Health Oslo, Norway

Fetal cells – first attempt

Problems: very few, not cleared after delivery

Cellfree fetal DNA– second attempt

©  Bo  Jacobsson  

RhD + fetal sex

Hypomethylation

Shorter fragments

SERPINB5 hypomethylation

First trisomy 21 marker

Massive parallel sequencing

Relative mutation index

2012  First whole fetal genome sequenced from maternal blood

Rapid clearance

Fetal cfDNA percentage increase with gestational age

Should be ≥ 4% for a successful test

Proportion of Samples Returning a Result by Gestational Age

Fetal cfDNA percentage decrease with increased BMI

T21

T18

T13

The important implication of this is: ALL POSITIVE NIPT SHOULD BE FOLLOWED UP BY AN INVASTIVE PROCEDURE

Response time and response rate

Response time: 5-9 working days Response rate: 2 – 6 % no response rate at first sampling 50-75% additional responses at the second What to do with the rest?

What to do with the no responses on NIPT?

No further action? Resampling Deeper sequencing Further risk assessment Invasive test

Include test failures Goes for all diagnostic tests

Intension to diagnose

Potential problems with NIPT

Other potential problems with NIPT

Potential problems with NIPT

Potential problems with NIPT

Spectrum of Genetic Disease

Autosomal recessive

Autosomal dominant

X-linked

Chromosomal

Congenital malformations

Potential problems with NIPT

Spectrum of chromosomal disorders

T18

T21

TXY

T13

45X

Others

Other potential problems with NIPT

23.4% not decteced by NIPT

16.9% not decteced by NIPT

PLUS Early 9-10 weeks High sensitivity + specificity Low screen positive rate Simple sampling procedure,

+ -

MINUS No response Twins? Vanishing twin To simple? Pre- and postsampling information