Test di screening per le anomalie cromosomiche nel 2018 ... fileTest di screening per le anomalie...

Test di screening per le anomalie cromosomiche nel 2018:

come condurre il counselling, come documentare le scelte

Dipartimento di Ostetricia e Ginecologia

Università di Brescia / ASST Spedali Civili di Brescia

[email protected]

Federico Prefumo

Primi anni 2010

Ecografia + biochimica

Test invasivi

Studio osservazionale multicentrico sul ricorso alle procedure di valutazione del rischio e/o di diagnosi prenatale Tesi di dottorato di SIMONA FUMAGALLI SCUOLA DI DOTTORATO IN SCIENZE FISIOPATOLOGICHE, NEUROPSICOBIOLOGICHE E ASSISTENZIALI DEL CICLO DELLA VITA Università di Milano A.A. 2010/2011

SERVIZIO IN GRAVIDANZA

128

29

19

72

52

0

20

40

60

80

100

120

140

160

ginecologo privato consultorio ambulatorioospedaliero

patologia

fisiologia

ostetriche

Rischio, probabilità e scelta

Royal College of Obstetricians and Gynaecologists. Clinical Governance Advice No. 7, 2008

http://onlinelibrary.wiley.com/doi/10.1111/1471-0528.12544/full


Zipkin DA et al. Ann Intern Med. 2014;161:270-280.

http://onlinelibrary.wiley.com/doi/10.1111/1471-0528.12544/full


OAPR: odds of being affected after a positive result Dopo uno screening a rischio, si conferma che il feto è affetto ogni X amniocentesi/villocentesi eseguite

Screening su cffDNA

Results

Analysis of cell-free DNA in maternal blood in screening for aneuploidies: updated meta-

analysis MM Gil et al., UOG 2017

Aneuploidy No. of studies

No. of affected fetuses

No. of unaffected fetuses

Pooled detection rate (95% CI)

Pooled false-positive rate (95% CI)

Trisomy 21

30 1963 223 932 99.7% (99.1 to 99.9%) 0.04% (0.02 to 0.07%)

Trisomy 18 25 563 222 013 97.9% (94.9 to 99.1%) 0.04% (0.03 to 0.07%)

Trisomy 13 23 119 212 883

99.0% (65.8 to 100%) 0.04% (0.02 to 0.07%)

Monosomy X

11 36 7676

95.8% (70.3 to 99.5%) 0.004% (0.0 to 0.08%)

Other sex aneuploidies

8 17 5403

100% (83.5 to 100.0%) 0.004% (0.0 to 0.08%)

Trisomy 21 in twins

5 24 1111 100% (95.2 to 100.0%) 0.0% (0.0 to 0.003%)

Screening su cffDNA - fallimento

Wang E et al. Prenatal Diagnosis 2013, 33, 662–666

Integrare NT+biochimica e cffDNA

First-line screening by cfDNA testing alone in a population of 100000 pregnancies,

including 294 with trisomy 21

First-trimester contingent screening for trisomy 21 by biomarkers and maternal blood

cell-free DNA testing Nicolaides et al., UOG 2013

100,000 pregnancies

Unaffected n=99,706 Trisomy 21 n=294

Maternal blood cfDNA testing

Positive n=96

Result n=95,718

No result N=3,988

Chorionic villus sampling 471 / 100,000 (0.47%)

False positive rate 180 / 99,706 (0.18%)

Positive n=281

No result n=12

Positive n=10

Result n=282

Detection rate 291 / 294 (99.0%)

4% 4%

0.1% 99.5%

85.2%

Combined test

risk ≥ 1:100

Positive n=84 2.1%

Contingent screening by combined test and cfDNA testing in pregnancies with a risk

of ≥ 1:3000 in a population of 100000, including 294 with trisomy 21

First-trimester contingent screening for trisomy 21 by biomarkers and maternal blood

cell-free DNA testing Nicolaides et al., UOG 2013

100,000 pregnancies

Unaffected n=99,706 Trisomy 21 n=294 Risk >1:3,000 in screening by:

MA, fetal NT, ß-hCG, PAPP-A

Unaffected n=24,229 Trisomy 21 n=288

Maternal blood cfDNA testing 24,517 / 100,000 (24.5%)

Positive n=83

Result n=23,260

Positive n=23

No result n=23,260

Chorionic villus sampling 391 / 100,000 (0.39%)

False positive rate 106 / 99,706 (0.11%)

Positive n=275

No result n=12

Positive n=10

Result n=276

Detection rate 285 / 294 (96.9%)

4% 4%

0.1% 99.5%

87.0%

97.9%

8.6%

24.3%

Combined test

risk ≥ 1:100

Fetal Medicine Foundation, 2004

Linee guida ISUOG Primo trimestre

Ultrasound Obstet Gynecol 2013; 41: 102–113

Organ/anatomical area

Present and/or normal ?

Head Present; Cranial bones; Midline falx; Choroid-

plexus-filled ventricles

Neck Normal appearance; Nuchal translucency

thickness (if accepted after informed consent and

trained/certified operator available)*

Face Eyes with lens* Nasal bone*

Normal profile/mandible* Intact lips*

Spine Vertebrae (longitudinal and axial)* Intact overlying

skin*

Chest Symmetrical lung fields; No effusions or masses

Heart Cardiac regular activity; Four symmetrical

chambers*

Abdomen Stomach present in left upper quadrant; Bladder*

Kidneys*

Abdominal wall Normal cord insertion

No umbilical defects

Extremities Four limbs each with three segments; Hands and

feet with normal orientation*

Placenta Size and texture

Cord Three-vessel cord*

The role of NIPT as an alternative to standard invasive testing

in women considered to be at very high risk (>1:10) after

combined screening but with no ultrasound anomaly should

be evaluated in prospective studies. Expert opinion currently

suggests that NIPT should not replace invasive testing in this

group. This is based on the fact that only 70% of

chromosomal abnormalities in this population are trisomy 21,

18 or 13.

In the presence of a fetal structural anomaly, the indications

for fetal karyotyping and/or microarray testing should not be

modified by a normal NIPT result obtained previously.

Results

Clinical implementation of cfDNA testing MM Gil et al., UOG 2016

• 12 134 women offered combined screening, 11 921 accepted (98.2%)

• 229 (1.9%) excluded from analysis due to pregnancy loss with no known karyotype (n=169)

or lost to follow-up (n=60)

• Mean maternal age in study population: 31 years

• Based on results of the combined screening, the 11 692 pregnancies were classified as

– High risk: 460 women (3.9%)

– Intermediate risk: 3552 women (30.4%)

– Low risk: 7680 women (65.7%)

• Diagnosis of trisomies in the study population of 11 692 pregnancies was

– Trisomy 21: 47 cases



– No trisomies: 11 617 pregnancies

Results: parental decision regarding further investigations


• In the high-risk group, 38% opted for CVS, 60% for cfDNA and 2% for no further investigation

• In the intermediate-risk group 92% opted for cfDNA and 9% for no further investigation

Results: pregnancy outcome in trisomies


• Among 43 prenatally detected cases of trisomy 21

– 74% (32/43) opted for pregnancy termination

– 26% (11/43) chose to continue with pregnancy

• 32% (15/47) of trisomy 21 fetuses were live born

• Among 28 prenatally detected cases of trisomy 18 or 13

– 82% (23/28) opted for termination of pregnancy

– 18% (5/28) chose to continue with pregnancy (resulting in 3 miscarriages or fetal deaths and 2

neonatal deaths)

Scelta informata

Lewis C et al. Prenatal Diagnosis 2017, doi: 10.1002/pd.5154

Scelta informata

Lewis C et al. Prenatal Diagnosis 2017, doi: 10.1002/pd.5154

RAPID Evaluation Study

Routine prenatal care

Informed choice

93.5% 76.5%

Good knowledge

96.7% 88.8%

Primi anni 2010


Test invasivi

2018


Test invasivi

cffDNA

Array

2018


Test invasivi

cffDNA

Array

13,18,21,X,Y 13,18,21,X,Y Altre aneuploidie

Sindromi Malformazioni

Aneuploidie ≥10MB

Aneuploidie ≅250 kB

2018


Test invasivi

cffDNA

Array



Aneuploidie ≥10MB


Tasso

perdita

fetale 1%

2018


Test invasivi

cffDNA

Array



Aneuploidie ≥10MB


Tasso

perdita

fetale <1%

www.ecm.aogoi.it

Punti chiave

• Differenza tra test di screening e test diagnostici

• Accuratezza e limitazioni dei diversi test di screening

• Rischio dei test diagnostici

• Test di screening a rischio ≠ feto malato

• Test di screening a rischio possibilità di eseguire test diagnostico

• Test diagnostico non è automatico in caso di screening a rischio

• Test diagnostico patologico possibilità di proseguire o meno con la gravidanza, percorso perinatale dedicato

• Accessibilità in regime di SSN e costi

www.sieog.it

Grazie

Test di screening per le anomalie cromosomiche nel 2018 ... fileTest di screening per le anomalie...

Documents

Transcript of Test di screening per le anomalie cromosomiche nel 2018 ... fileTest di screening per le anomalie...