產(chǎn)前診斷-中文版

產(chǎn)前

:進(jìn)展Guo Luo,

M.D.,

Ph.D.Director,

Center

for

Perinatal

MedicineDanbury

Hospital,

Danbury,

CTAssociate

Professor,

University

of

Vermont

&

Yale

UniversitySchool

of

Medicines

ofGuo Luo,

M.D.,

Ph.D.

has

nointerest

to

declare

in

regards

to

this

topic.Director,

Maternal-fetal

Medicine,

AssociateProfessor,

Department

of

Obstetrics

&Gynecology,

University

of

Connecticut,School

of

Medicine.2目的回顧產(chǎn)前關(guān)于產(chǎn)前的歷史的影像學(xué)的關(guān)于非整倍體的篩查及的3產(chǎn)前影像學(xué):超聲MRI鏡妊娠篩查:孕早期及孕中期篩查孕婦

游離DNA遺傳

:絨毛活檢羊膜腔穿刺術(shù)核型分析o人類

組5產(chǎn)前

的歷史超聲:1950年被引進(jìn)20世紀(jì)90年代快速改進(jìn)并廣泛使用羊膜腔穿刺術(shù)1877年首次開展（因?yàn)檠蛩^(guò)多)研究1966年首次應(yīng)用于70年代后普遍使用絨毛活檢(CVS)–第一例1968–在1980年-1990年被廣為接受1990年至今，

篩查、人類

組

及分子

學(xué)快速發(fā)展產(chǎn)前主要結(jié)構(gòu)異常次要結(jié)構(gòu)異常7超聲軟標(biāo)記8孕中期超聲標(biāo)記非整倍體（似然比（LR）常見(jiàn)的非整倍體鼻骨發(fā)育不全(缺失或≤2.5

mm)51~60%

DS頸褶增厚>6

mm17~35%

DS股骨短(<第三百分位數(shù))3DS肱骨短(<第三百分位數(shù))8DS腎盂擴(kuò)張1腸管強(qiáng)回聲6DS單臍動(dòng)脈1第五指中指骨發(fā)育不全/缺失2DS脈絡(luò)叢囊腫7T

18心臟的強(qiáng)回聲灶2DS10血流動(dòng)力學(xué)評(píng)價(jià)11MCA

DopplerMari

G,

et

al.

N

Eng

J

Med

2000;

342:9-1412Mari

G,

et

al.

N

Eng

J

Med

2000;

342:9-14MCA評(píng)估

貧血Oepkes

et

al.

NEJM,

2006.前瞻性多中心研究165例

因?yàn)樵袐D紅細(xì)胞同種免疫有貧血風(fēng)險(xiǎn).MCA-PSV

doppler:敏感性88%，特異性82%羊水delta-OD450:敏感性76%，特異性77%縱向發(fā)展14差異<平均孕齡第五百分位數(shù)或<平均孕齡2個(gè)標(biāo)準(zhǔn)差大多數(shù)孤立的短股骨是正常的或是性的在18到24周

為短股骨的，有13%在隨訪后為正常FGR非整倍體骨骼發(fā)育不良15種族變異16技術(shù)變化17技術(shù)變化8技術(shù)變化19腦發(fā)育的磁成像掃描20正常小腦發(fā)育不全葉外型肺癥2223非整倍體的篩選10

11

12

13

1415

16

17

18

19

2020…40

weeks1st

trimester

blood

draw2nd

trimester

blood

drawNuchal

TranslucencyTrimester

(11-14

weeks)Combined

test

(NT,PAPP-A,

-hCG)Second

Trimester

(15-20

weeks)Triple

test

(AFP,

uE3,

-hCG)

Quad

test

(AFP,

uE3,

-hCG,

InhA)Both

1st

and

2nd

trimesters

(10-14

+

15-20

weeks)Full

integrated

test

(NT,

PAPP-A,

-hCG

,

Quad)Serum

integrated

test

(PAPP-A,

-hCG

,

Quad)Sequential

integrated

test

(combination

of

both)Canick

J,

Palomaki

GE,

AA

resentation

2008.

Washington,

DC.ed

Ultrasound24CRL=

45

mm25Median:

中位數(shù)1.2mm2.1mm95th

percentile:CRL=

84

mmMedian:95th

percentile:1.9mm2.7mmThe

99th

percentile:

3.5

mm.96,127

pregnancies.

Lancet

351

(1998),

pp.

343–346頸項(xiàng)透明層NT(mm)異常核型DemiseAnomaly畸形Alive

&well<95%<1%<2%<2%97%95-99%4%<2%3%93%3.5-4.421%3%10%70%4.5-5.433%4%19%50%5.5-6.451%10%24%30%>

6.565%19%46%15%Souka

et

al.

AJOG

2005;192:1005-21.26Trimesters

Biochemical

Screen27孕早期篩查除了篩查非整倍體異常NT：結(jié)構(gòu)畸形低PAPP-A(<第五百分位數(shù)):生長(zhǎng)受限，先兆子癇核實(shí)孕周確定絨毛膜性檢測(cè)

重大畸形，Second

Trimesters

Biochemical

Screen29Malone

FD,

Canick

JA,

Ball

RH,

Nyberg

DA,

et

al..

N

Engl

J

Med.

2005

Nov10;353(19):2001-20

1.30雙向終生攜帶細(xì)胞可能

在某些有些是干細(xì)胞，在遇到壓力或是損傷時(shí)可

員微嵌合體是普遍的Lo

YM,

et

al.

AJHG

1999;

64:218-24Bianchi

DW,et

al.

AJMG

2000;

91:22-8O’Donoghue

K.

Lancet

2004;

364:179(male

stem

cell

inthe

bone

marrow

of

a

woman50

years

after

the

birth

of

her

only

son)細(xì)胞交換History

of

NIPT（無(wú)創(chuàng)產(chǎn)前檢查）105:16266-71Blood

drawat

9-20

weeksHigh-throughput

approachesSophisticated從ècfDNA中分離

cfDNA是不可行的中3-10%的cfDNA來(lái)自于è

更確切的說(shuō)è中的cfDNA來(lái)自于胎盤cfDNA量很少(1

μg

in

20

mL)Lo

YM,

et

al.

AJHG

1998;

62:768-75Ariga

H,

et

al.

Transfusion

2001;

41:1524-30NIPT的步驟**

OO

ll

titi

tt

dd

hh

bb

bblili

hh

dd

((BBii

hhii

tt

ll

OObb

tt

tt

GG

ll

20122012

119119

889900

990011

ffVV

ii

tt

HH

lthlth?)?)Commercial

NIPT

in

US**

Three

prospective

studies

have

been

published

(Palomaki

GE,

et

al.Genet

Med

2011

for

Sequonom

CMM?;

Bianchi

DW,et

al.

Obstet

Gynecol

2012

for

Verinata

Health?;

Nicolaides

KH,

et

al.

Prenat

Diagn

2013

for

Natera?)Comparison

of

Techniques

for

Prenatal

Diagnosis

using

Cell-Free

DNACompanies

inUnited

States

*Technical

approachAccuracy

of

detection

**Failed(‘no

call’)SequencingBioinformaticsAneuploidySensitivitySpecificitySequonom

CMM?MPSSZ-score+T21T1898.6%100%99.8%99.7%3-8%GC

correctionT1391.7%99.0%45,X----47,XXY----Verinata

Health?MPSSZ-score+NCV+T21T18100%97.2%100%99.8%3-5%T1378.6%99.4%45,X93.8%99.8%47,XXY----Ariosa

Diagnostics?ed(chromosomes21

and18)FDOARNTSERT21T18100%98%100%100%3%T13----45,X47,XXY--------1-7%Natera?ed(SNPs)esoperate

outside

ofSNPs

from

Hapmap+Parentalthe

U.SupportS.T21T18100%100%100%100%1-20%T13100%100%*

Two

additional

compani45,X47,XXY100%100%100%100%ACOG

Committee

Opinion

No.

545.

Obstet

Gynecol

2012;

120:1532-4NIPT適應(yīng)癥NIPT檢測(cè)

非整倍體適用于高危的單胎妊娠，如：高齡孕婦篩查異常史非整倍體孕婦或有非整倍體超聲異常NIPT局限性cfDNA為胎盤來(lái)源（而非來(lái)自于

）所有NIPT方法分析的是總量cfDNA，而不是提取或搜集

cfDNAcfDNA已經(jīng)是片段(~150-200

bp)半衰期短,排除前次妊娠的干擾測(cè)量的區(qū)別是定量的而不是定性的通常2%的cfDNA

來(lái)自于21號(hào)21三體

因?yàn)榫哂腥龡l21號(hào) ，從而增加了50%的循環(huán)遺傳物質(zhì)，

NIPT正想檢測(cè)出這種差異。36NIPT

是