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Professor of Obstetrics and Gynaecology’

Aneuploidy screening

2Owk markers đỀ12WNT TLUS markers
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Karyotype FSH qỨŒ W

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Baseline: combined first trimester screening

Dotocton rato

[at FPR]

Risk! 20° Euplold
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What does the normal range for NT look like?

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4 99" centile 3.2-3.5mm Wright et of Mixture Model UOG 2008

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NTin common aneuploidies

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Local Hath

Implications of increased NT

ABNORMAL ffM MANOR Healthy lve birth
KARYOTYPE DEATH DEFECTS
807
80)

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Nuchal translucency (mm)
Nuchal translucency (mm)

10 10

Frrrrrrr o rrro rrrrn oot 4 50 55 6 6 7 75 8 8
45 55 6S 75 85-45 55 65 75 8505 55 65 15 8
Crown-rump length (mm)
Crown-tump length (mi)
WESTERN SYDNEY
ails |Heth ww UNIVERSITY

NSW South Western Sydney incham instbute

oven Local Heath Distt ee

Genomic innovation:

isolation of cel free fetal DNA

LÍ DNA extraction fom plasma

\\ Multiplex PCR to ‘enrich’ SNPs of interest

senSouth Western Sydney Inaham In WESTERN SYDNEY
UNIVERSITY
NSW Local Health District m a

NIPT for common trisomies:

higher sensitivity with improved specificity

WATE a

Trisomy 21 99.7% (Cl:99.4-99.9) 0%

Trisomy 18 | 98.2% (C.95.5-99.2) | 0.05%

Trisomy 13 | 99.0% (Cl: 658-999) 0.04%

ASX 95.8% (Cl:703-995) | 0.14%

Giletol. Meta-analysUiOsG 2017

ils Heath wwian hat WESTERN SYDNEY
waite
cá South Ween Schey UNIVERSITY

NS cast

Incremental Cost Effectiveness Ratio:
MIPT for al

CATS21 EAVOSIDED

Total Cost Case2s1 ICER//T21

avoided avoided

Routine care 150000000 1800 83,333

4JÚM ÿWM ⁄] ĐUM #ÚM NPT cost $50,000,000 MU 750M
Difference
d0 costs 400,000,000 MỤ 167

34

ii Health Ww WESTERN SYDNEY
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UNIVERSITY

NIPT for 721:

cADNA- including the n0 results’

/ 192(1.2%) low \ 100% 38)
83 (05H) nf th
19134)4Mitiatt 1%

488 (3.0%) not reported tt 1%

13((in3, 27|aneuplil Norton et a/. NEJM 2015

Including: 3721 0W

1718/2113

4 triploldy ,

1716 mosaic M

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Astruc.rearrange | 2 1W 1W

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fr CDNA reporte d

all cases Oh Detection rate FPR PPV

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South Western Sy incham instute UNIVERSITY

NSW Local Health Distt sl.

The ‘mechanics’ of NIPT

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Compan Chromorom2e1 |
‘Chromovome fragments
Fan eta, 2011
‘gents

Muscle o,2011

a |Heath & Porrecoet al A10G 2014

South Western Sychey hgh WESTERN SYDNEY
UNWERSIY
NSW clan

Ifwe expand the range of screening,

what should we screen for?

S s

n / 100K livebirths=

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Tụ! (nat)belts

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aneuploidy screening — (tri "m WESTERN SYDNEY

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Implications of del 22q41

Aortic arch anomalies vp to 75% haavcarediac abnormality:

Absent pulmonavralyve
Whim
Truncus arteriosus
(IN
Tetralogy of Fallot HUY, Ws (Tremonton (TotaolFylt

\SD with pulmonary atresia ‘rtwrd ch

Cleft lp / palate M0000.

Vertebral anomalies + Pulmonary atresia we vrticle IV:
Holoprosencephaly 11.0% © Unapectiod contralto
Renal anomalies
Hypoplastic thymus Povelpa ene rppa

IUGR *napbeet ot

Polyhydramnios US tots
wi 4WN Veni“Rpt at
senSouth Western Sydney
úN ÏIW0df0 MS
NSW Local Health District
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, Besseau-Ayasse et ol, OPND 2014

Ingham instute WESTERN SYDNEY

UNIVERSITY

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Panorama Al validated to detect most 22q11.2 deletions , SMART
Wwr
incsmlalleur, dnestied ndelegtions

2q11.2 region of chromosome 22 (not to scale) Incidence of small deletions in SMART

| Focofumsost much higthahn eexpercted

Full AD dlt2o6+ni) NPT tude 42%
—
— PanoramaAl Smal, |
Smaller, nested deletions
I6 Mb) ised nested

_— deletions
(6/12)
sale eis
58%

Ful

tin

[|

Wratera

Panorama 22q11.2 Performance

Sensitivity + Inciof 2d29e112ndecleteions
was fin 1,524 (12/12980)
Spectity WA
4h + Sensiintchasevs wiitthtyhe
1701100) fll AD deletion was9999 (17

oy W0 ‹- 8IfUlt00ttilUlly

nested deletions (10/12

(ee Parra (ocr version) Panorama A

(ed nr pet ato Pa cht nn ec eck of Me i ro 0 AD Ral
tha 50

Wratera

Clinical impact of RATs identified by CVS
The majority of RATs are mosaic and confined to the placenta

0,180 The majoroif tRAyTS dentedin

1 Prevalence of TFM involving cytotrophoblast Cytotrophoblast (CVS specimensar)e
0.160 Prevalence of CPM involving cytotrophoblast
confintoetdhe placenta (CPM)!
0140
True fetal mosaicism (TFM) occurs ina
010 small percentage of cases and has highly

0,100 variable outcome’?

0,080 CPM for trisom1y6 has been associated
with fetal abnormalities and pregnancy
060 complications?
(W0
Risk of adverse outcome associatweitdh
0,020 CPM for other trisomies has not been
0 established and appropriate management

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Slide from Max Schmid

cFTS in twin pregnancies

Spencer: Prospective one-stop clinic (n= 224 twin alts)

ORT752% L(3/4)

FPR 9% pregnancies (19/206) | 6.9% of individual fetuses (28/412)

Madsen: 4843 unaffected twins | 47 T2L-affected twins

Add chorioni-specifc biochemical medians to NT measurements

DRTDADC twins 4 from 78%-> 90% Ÿ FPR from 8.0~5.9%

Cleary-Goldman: Addition of nasal bone assessment to cFTS (n = 2094 twin pais)

DRT2L 4 from 79-80% at 5% SPR

Accuracy improved for DCtwins | DR W and FPR in MC twins

Spencer BOG 2003; Madsen U0G 2011; Cleary-Goldman AIOG 2008

NSW cada ae Ị

cFTS in twin pregnancies: problems

Certainty of chorionicity?
Nuchal translucency;

MC Increased NT? TTTS or cardiac abnormality

Ductus venosus:

Rev i’ - wave 2 TTTS or cardiac abnormality

\ tạn Ẳœraha tite ESTENSYDAEY

NSW | Sut est ie UNIVERSIsm TY

coven | LOCal Health District

NIPT in twin pregnancies

Detection Rate au

Trisom2y1 2582-98 412

IiwmllÐ 889⁄(04-972) 401%

Trisomy 13 (6754722?) 02%

Gi et a Meta-analysis (twins) UOG 2019

als _| < WESTER STONEY
UNIVERSITY

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