Y HOC VlgT NAM THANG 6 - s 6 1/2013
CHAN DOAN TRUttC SINH THAI MANG NHliM SAC THE CHUYEN DOAN
Hoang Thj Ngoc L a n \ P h a m Thj Hong Thuy^
T O M T A T
Phat hien sdm thai mang nhiem sac the chuyen doan se giiip cho tU van di truyen de cd the cho ra ddt nhu'ng dya tre khde manh, Muc tieu Oanh gia gia tn cda cac test sang loc trUdc sinh trong viec phat hien cac thai mang nhiem sac the chuyen doan, tim hieu moi lien quan gida nhi^m sac the bat thudng cua thai vdi nhi§m sac the bo, me, Doi tUong' 15 thai c6 nhi^m sac the chuyen doan tUOng ho va 2 thai c6 nhiem sac the chuyen khong tuang ho trong tong sd 4014 thai dupc phan ti'ch nhilm sac the ty 2006-2012, Ket qua. 11/17 thai chuyen doan thuan (7 tyong ho, 2 khong tUOng ho, 2 chuyen doan lUOng hd va trisomy 21), co 9/11 thai nhi§m sac the bat thudng lay ti/ bd, me, 6/11 thai chuyen doan kham (1 dong te bao chuyen doan tuong hd va 1 dong te bao binh thudng) khong tim thay nhiem sac the bat thudng do tu' bo, me. Trong 6/11 thai nhiem sac the chuyen doan tUOng hd, 5 thai lam sang loc huyet thanh me, thi 4/5 thai cd ket qua sang loc huyet thanh me thuoc nhdm nguy co cao, 1/11 thai mang chuyen doan tUong ho kep sang Ipc huyet thanh me va sieu am thai thuoc nhdm nguy co thap. 2/11 thai NST chuyen doan khong tUdng hd cd sieu am thai bat thudng va sang loc huyet thanh me. 6/17 thai nhiem sac the kham deu phat hien do sang Ipc huyet thanh me thuoc nhom nguy cd cao.
Tdkhoa: Chuyen doan nhilm sac the, sang loc, chan doan trUdc sinh.
SUMMARY
PRENATAL DIAGNOSIS OF FETAL CHROMOSOME RECIPROCAL
TRANSLOCATION
Reciprocal translocation is a structure mutation of chromosomes, whom carry the chromosome reciprocal translocation is usually normal, but may be unusual for the next generation, so the early detection of fetuses with chromosome translocation will help genetic counseling in order to give birth to healthy children. Objectives To assess the value of prenatal screening tests for the detection of fetal chromosome translocation, explore the relationship between chromosomal abnormalities of fetuses with their parents. Subjects 15 fetuses with chromosome reciprocal translocation and 2 fetuses with chromosome no reciprocal translocation of 4014 fetuses were analyzed chromosomes from
' Dai hgc Y Ha Noi ^ Dai hoc Y Hai Phong Phan bien khoa hoc: PGS.TS. Phan Thi Hoan 142
2006 lo 2012. Results: 11/17 chromosome translocation with only cell line (7 reciprocal translocations, 2 no reciprocal translocations , 2 reciprocal translocations and trisomy 21), in wich 9 fetal chromosomal abnormalities from their parents, 6/17 fetuses chromosome mosaics (1 cell line reciprocal translocation and one normal cell line) did not find abnormal chromosomes from their parents.
Of 6 fetetes carry chromosomal reciprocal translocation, 5 fetuses maternal serum were screened there are 4 fetuses results in high-risk groups, 1/11 fetus with double chromosome reciprocal translocations result aternal serum screening and fetus ultrasound in low-risk groups.
2/11 fetuses chromosomal translocation is not mutual abnormal fetus ultrasound and maternal serum screening. 6/17 fetuses with chromosome translocation mosaics detected by screening maternal serum are in high-risk group.
Key w/ord: chromosome reciprocal translocations, screening, diagnosis
I. OAT V A N O E
Chuyen doan t y d n g ho (Reciprocal translocations) la mpt trong nhirng dang dot bien cau true nhiem sac the (NST) do cac NST bj dui va trao doi d o a n dui cho nhau, thifdng vat lieu di truyen khdng bi mat di.dang chuyen doan nay con dypc gpi chuyen doan can bang, tan suat 1/625 tre sP sinh. Cac ca the mang bat t h y d n g chuyen d o a n can bang thydng co kieu hinh hoan toan binh t h y d n g bd NST gom 46 chiec NST, trong d o cd 2 chie'c NST bat thydng nhyng lai di truyen cho cac the' he sau nhdng NST cau true bat t h y d n g dd va cd the bieu hien benh. Nhieu nghien cdu 6 cac cap vd chong bat thydng sinh san da phat hien difdc nguyen nhan gay say thai lien tiep la do dot bien NST va chCi yeu do dot bien cau true gay nen.
Viec sang Ipc va chan doan tsddc sinh se giup lam giam ty le cac tre mang dj tat bam sinh va ti!f vong chu sinh, nang cao chat lu'png dan so.
Viec phat hien thai bat t h y d n g cau true NST cd y nghTa rat quan trpng trong t y van cho the he hien tai cijng n h y nhu'ng the he tiep sau do. Vi vay, chung toi tien hanh thyc hien de tai vdi hai muc tieu:
1. Danh gia gia trt cOa cac test sang IQC
Y HOC VIET NAM THAHG 6 - 50 1/2013
trddc sinh trong viec phat hien cac thai mang
NST chuyin doan (ngoai trd trudng hop chuyen doan hoa nhap tini).
2. Tim hiSu moi Hen quan giCfa NST bat thddng cOa thai vdi NST bo, me.
II. 061 TUONG VA PHl/ONG PHAP NGHIEN CCfU
2.1. Doi tUdng nghien curu: 17 thai co bat thudng cau true NST chuyen doan tuong hd va
khdng tUPng hd, dypc phat hien trong 4014 thai phu dypc xet nghiem dl de chan doan trudc sinh tai bo mon Y sinh hpc - Di truyen trudng Oai hpc Y Ha Ndi.
2.2. PhUdng phap nghien cUu: md ta Nudi cay te bao di, phan tich NST thai dupe thuc hien tai Bd mon Y Sinh hpc - Di truyen Trudng Dai hpc Y Ha Ndi dam bao dung tieu chuan quoc te ISCN 2009.
III. KET QUA NGHIEN CQU
17 tRidng hpp thai mang NST chuyen doan trong sd 41 tiudng hdp thai bat thudng cau tnJc NST dupe phat hien trong 4014tnJdnghap xet nghiem NST td tebao di nudi cay tU nam 2006 den 2012, Ty lethal bd't thudng cau tme ndi chung la 1,02%.
1. Cac dang bat thudng NST kieu chuyen doan khdng hoa nhap tam Bang 1. Bat thudng NST kieu chuyen doan
Cac dang BTCT
CD tirong h6
CD khong tirong ho CD tLfdnq ho kep CD ti/dng h6+ roi loan so iLTdng NST Dang kham (dong te bao CD tliong h5/ dong te bao binh thi/dng)
Ket qua phan tich NST thai 46.XX.t(12.13)(g13.q33)
46.XY.t(4.8){p15-3.d21 1) 46.XY,t(1.17){p32.2.c|22) 46.XX.l(9:20)(q21 ,pl2) 46.XY.t(2:5Kq32 :q33) 46.XY,t(2,21)(p11 2 ;q22) 46,XX,-5.+t(5;15)(p15.1,q25) 46,XY,-6.+t(6.11)(q22.1.q22,3) 45,XY,t(1q.17q)(q24.q25).t(13q.21q) 47,XX.+21,t(2.18){q23,q21) 47,XX.+21,t(1;3:21)(p22.q11 2,p13) 46.XY.t(1:3)(q42,p13)|40%|/46,XY[60%]
45.XX.t(1,3)(q32,p23)[29%l/46,XX|71%1 45.XY,t( 1,19)(q21 ,p13 2)f20%i; 46,XY|80%1 46,XY,t(7,20)(q11.2,p12)(6.6%l/46.XY|93,4%l 46,XY,t(l.10)(p22.p13)[10%l/46.XY|90%l 46,XY.t(4;12)(q31.1.q22)[13%]/46,XY|87%]
Tong
n
117
%
06 (35.3%)
02(11,76%) 5,88%
02 (1.76%)
06 (35.3%)
100,0%
Nhan xet: Trong 17 cac bat thudng cau true NST dang chuyen doan co:
- Chuyen doan tUPng ho chiem 52.94% (9/17), dang khdng tUPng hd (2/17 = 11,76%).
- Dang kham (gom 2 ddng TB: dong te bao chuyen doan tUPng ho/ dong te bao binh thudng) chiem 35,3% (6/17).
2. Doi chieu ket qua NST ttiai vdi cac piiirong piiap sang ioc Banq 2. Doi chieu ket qua NST thai vdi cac phUdns phap sang loc
Cac dangBTCT NST
Chuyen doan ti/dng h5
CD tUdng h6 kep
— — K e t q u a sang loc Kai^otype cualHal—•—-^_, 46.XX.t(12.13)(q13;q33) 46,XY.t(4;8)(p15.3;q21.1) 46.XY,t(1;17)(p32.2;q22) 46.XX,l(9;20)(q21.p12) 46,XY,t(2,6)(q32;q33) 46.XY.t(2;21)(p11.2.q22) 45,XY,t(1;17)(q24;q25), t(13o;21q)
Tien sur san khoa
bl thai liaj 3 lan
bt bl thai luu 1 lan
bt smh con Down
Tuoi me 31 39 38 30 22 42 28
Sieu am KSSG 3.3mm
bt bt Di tat tim langKSSG. di lat lim
bt bt
XN HTme
(+) (•) (+) Ko lam
(-)
(+) {-)
N 06
01
Y HOC VlgT HAM THANG 6 - SO 1/2013 CD tUdng h6
+ RL soli/dng CO khong
tUdng ho
47,XX.+21.1(2;18)(q23.q21) 47,XX.+21,t(1.3;21) (P22,q11.2:p13) 46,XX.-5.
+t(5;15)(p15-1;q25) 46,XY.-6, +I(6;11)(q22 1.q22.3)
thai luu 3 ISn thai luu 1 lan
bt smh 2 con dj tat
27 33 25 31
KSSG 6,9mm bt Phij thai nao thcit ben
Smm ko lam
(*)
kolam
(*)
02
02
NC Ihap {-), NC cao slnh con HC Down (+), binh thUdng (bt)Nhan xet:
- 6 thai mang NST chuyen doan tUPng hd cd 5 thai lam sang Ipc thi c6 4/5 thai co sang Ipc HTM thuoc nhdm nguy cP cao sinh con hpi chdng Down, 2 trUdng hPp con lai co ket qua cda sieu am bat thudng hoSe eo lien sCr say thai, thai luu cua thai phu.
- Vdi tnjdng hc^ ttiai mang chuyen doan tutJng hd kep. ca sieu am va huyet thanh me deu thupc nhdm nguy CP thap. san phu ctToc oi vi tien su'sinh con mac ha diung Down.
- 2 thai chuyen doan khong tutsigh6;1 thai dupe lam sang be dHTlVl tfiicd nguy cd cao sinh con hdi (Mig Dcwn, Ca 2 tnjong hpp nay deu cd hinh anh sieu am thai batthuiftig.
- Vdi 2 thai c6 phdi hpp giua chuyen doan va trisomy 21 thi ca 2 trUdng hpp nay thai phu dupe chi dinh chpc hut di do hp cd tien sir thai luu va sieu am bat thudng hoac xet nghiem sang Ipc d HTM ed nguy cp cao cho thai hpi chUng Down.
- 6/11 trUdng hpp cd tien sCr thai san bat IhUPng,
- 3/11 trudng hpp cd nguy cP cao cho bat thudng NST theo yeu to tuoi me.
Sang 3. Ddi chie'u ket qua NST thai bat thudng cau true kieu chuyen doan tUPng hd dang kham vdi cac phUdng phap sang loc
^'^"'^.---^^^^^^ Ket qua sang loc Karyotyp cua tliai —^^
46,XY.t(1;3)(q42;p13)[40%]/
46.XY[60%]
46,XX,t(1:3)(q32;p23)[29%]/
46,XX|71%1
46,XY.t(1:19)(q21;p13.2)[20%]/
46.XY[80%]
46.XY.t(7:20)(q11.2,p12)[6,6%]
/46.XY|93.4%]
46.XY.t(1;10)(p22.p13)(10%]/
46.XY[90%I
46,XY,t(4;12)(q31 1,q22)(13%]/
46.XYI87%1
Tien SLf gia dint) sinh 7 lan, 6 con to vong
bt thai luu 2 lan thai li/u 1 lan say thai 1 lan. thai luu 1
lan bt
Tuoi me 39 40 36 39 40 25
Sieu am da oi
bt bt bt bt bt
HTIM khong lam
(+) (+)
M
{*)
M
n
06
NC Ihap (-).NC cao smh con HC Down (+). binh thudng (bt)
Nlian xet: - Vdi 6 trudng hop thai mang 2 ddng te bao (5 thai lam sang loc HTM) ca 5/5 trudng hdp ket qua deu thuoc nhdm nguy cd cao cho thai Down va deu cd sieu am thai binh thudng.
- 4/6 trudng hop c6 tien sil thai san bat thudng.
- 5/6 trudng hdp c6 nguy cd cao cho bat thudng NST theo yeu to tuoi me 4. Boi chieu NST thai bat thifdng cau
trtjc vdi karyotype cua bo' me
-_ Vdi 11 thai c6 bat thudng cau true chuyen doan dang thuan thi 9/11 thai cd NST
bat thudng gio'ng bo, me trong dd 5 trudng help
thai mang NST bat thudng giong me, 3 trUdng
hdp thai mang NST bat thUdng giong bo, 1 thai
ctiuyen doan kep thi cd 1 NST chuyen doan
144Y HOC VlgT NAM THANG 6 - s 6 1/2013 giong b d va 1 NST chuyen doan giong me.
- Vdi 6 thai mang 2 ddng te bao (1 ddng te bao binh thudng va 1 ddng te bao bat thudng) thi khdng phat hien 6dac bat thudng NST d bd me. 100% bo me co karyotype binh thudng.
IV. BAN LUAN
Trong thdi gian tU thang 8 nam 2006 den thang 8 nam 2012, chung tdi da tien hanh nudi cay 4014 m&u di cda nhijfng thai phy nguy eo cao sinh con di tat va da phat hien 41 trUdng hpp bat UiUdng cau true NST chiem ty le 1.02%. Trong dd cd 17 thai mang NST chuyen doan.
Sang Ipc dUa vao tuoi me la mdt trong nhijmg phuong phap dPn gian va de thUe hien nhat. Trong tong sd 17 thai phu cd thai mang NST chuyen doan, gap d tat cac Ida tudi. 8/17 thai phu_> 35 tudi va 9/17 thai phu < 35 tuoi.
Thai phy nhd tudi nhat la 22 tud'i, Idn nhat la 42 tudi va do tudi trung binh la 31,53 ± 6,3 tuoi. Tuoi trung binh cua cac thai phu trong nghien cUu cua chung loi cao hon nghien cdu cCia Phan Thi Hoan (28,5 ± 6,3 tudi) [1], ed le do chung tdi lay p cac ddi tUPng dupe chan doan trUde sinh.
Mpt s d nude tren the gidi, ngUdi ta khuyen cao nen chpc hut dich di d nhung thai phu s 35 tudi, Tuy nhien trong nghien cdu cua chung tdi.
bat thudng cau true NST cd the gap d cae nhdm tudi sinh cJe. Chung tdi chua gap d thai phu nao cd thai bat thudng NST ma chi djnh chpc di vi ly do Idn tuoi ma cac thai dUpc xet nghiem chan doan dua vao cac xet nghiem sang Ipc khac (HTM, sieu a m thai hay tien s d san khoa...). Theo Rozenberg P [5] va Rouquet Y [6] tinh nguy co dua vao ket hpp tudi me. s d do K S S G va xet nghiem sang Ipc cho dp nhay 9 1 . 7 % vdi ty le dUPng tinh gia khoang 5%.
Vdi thai c6 bat thudng cau true yeu t d tien SLf rat quan trpng, trong nghien cdn nay cd 6/11 thai cd tien sir thai san bat thudng. Thai mang NST loai chuyen doan tUPng ho cd 5/9 thai tien sCf thai san bat thudng. De phat hien cac thai chuyen doan NST khdng phai luc nao thai phu den vdi chung ta deu cd van de thai san bat thudng (vi cd the day la lan mang thai dau tien cda hp hoac ho da sinh nhung dUa con binh thudng ve kieu hinh) vi vay can ket hpp vdi cac yeu t d sang Ipc khac nhu sieu am thai va
sang Ipc HTM d ^ tranh Ipt sang cac thai mang NST chuyen doan.
Trong nghien cdu cda chung tdi cd 2 trudng hpp thai nhi mang bat thudng cau true NST kieu chuyen doan tUPng ho phdi hpp vdi roi loan so lUpng NST (trisomi 21). Vdi bat thudng cau true nay, thai nhi mang dac diem eua thai chuyen doan tUPng ho va trisomi 2 1 . Ca 2 trudng hpp nay thai phu dupe chi dinh choc hut oi do cd tien s d say thai, thai luu (100%), 1 trudng hpp sang Ipc HTM nguy co cao cho thai hoi chdng Down va 1 trudng hop khdng lam sang loc HTM nhUng sieu am cd hinh anh tang KSSG 6,9mm,
Cac thai bat thudng cau true NST kieu chuye'n doan khdng can bSng thudng cd bat thudng hinh thai thai nen sieu am thudng phat hien dupe, vi vay trong nghien cdu cda chung tdi thi ea 2 trudng hpp thai cd NST chuyen doan khdng can bang deu cd hinh anh sieu am bat thudng (phu thai, gian nao tha't ben Smm).
Vdi bat thudng ve sd lUOng NST, nhung bat thudng hinh thai rat die'n hinh cho mdt kieu bat thudng ve NST, vi du: nang bach huyet vung cd' vdi HC Turner, tSng KSSG, tac ta trang vdi HC Down, nang DRMM vdi HC Edwards, Tuy nhien, vdi thai cd bat thudng cau true NST, sieu am thai cd the' chUa phat hien thay bat thydng hinh thai. Vi vay, ddng trudc mdt thai phu cd mdt trong ba yeu td nguy co cao sinh eon dj tat: tien s d thai san, sieu am thai bat thUdng hoac sang Ipc HTM cd nguy ea cao sinh con dj tat, thai phu can dUpc tU van lam chan doan trUdc sinh de' loai trd kha nang thai nhi bi bat thudng NST,
Phat hien cae thai bat thudng cau true NST kieu chuyen doan tUong ho dang kham, chij yeu dUa vao ket qua sang Ipc HTM nguy CO cao sinh eon dj tat, 6 thai mang NST chuye'n doan tuong ho dang kham (trU 1 thai khdng lam sang loc HTM) edn lai 5/5 thai (100%) ed sang loc HTM nguy co cao cho thai hpi chdng Down, ca 5 trudng hpp nay sieu am thai deu chya phat hien dupe bat thudng, 1 trudng hpp khdng lam sang loc d huyet thanh me nhung thai phu cd tien s d san khoa nang ne (smh 7 eon, t d v o n g 6 do cac benh ve nao) va sieu am thai cd hinh anh bat thudng (da di).
Thuc te' cho thay nhirng ngudi mang NST chuyen doan can bSng thi hau nhU khdng phat hien thai cd bat thudng ve mat hinh thai. Vi vay
Y HOC VlgT NAM THANG 6 • SO' 1/2013 khi ket qua sieu am thai binh thudng nhUng kdt
qua sang Ipc HTM nguy co cao sinh con dj tat hoac thai phu eo tien s d san khoa nang ne (say thai, thai luu hoac da slnh con dj tat) c^n t u van cho thai phu chpc di lam NST thai nhi. Nhdn xet nay eung tuong t u nhu nhan xet cCia lac gia Phung N h u T o a n [3] va Hoang t h i ngpc Lan [2]
Tat ca cac thai cd bat thudng cau true NST deu dupe phan tich NST b d me de xac dmh nguyen nhan bat thudng NST cua thai.
Dieu nay rat quan trpng trong t u van di truyen.
Vdi 11 thai mang NST chuyen doan dang Ihuan thi ed 9/11 thai ed NST bat thUPng cd nguon gdc tU bd hoSc me (5 trudng hpp thai mang NST bat thudng cau true di truyen lU me, 3 thai cd NST bat thudng di truyen t d bd va 1 trudng hpp chuye'n doan tUOng ho kep; 1 NST bat thudng nhan t d b d va 1 NST bat thudng kia nhan tUme).
Xet nghiem NST bd me la rat quan trong trong nhung trudng hpp bat thudng cau true NST, ngoai viec xae dinh nguyen nhan bat thydng NST ciJa thai nhi, edn giup t u van cho gia dinh thai phu ve kha nang sinh eon dj tat d nhUng lan mang thai tiep theo. Theo mpt so nghien eUu, kha nang di truydn NST cau true bat thudng cho thai nhi khong phu thudc vao kieu bat thudng cau true ma chu yeu phu thude vao viec bd hoac me mang NST bat thudng cau true do.
Stoll C, thay r i n g thUc te nguy eP di truyen cho eon NST cau true bat thudng la 16% neu me la ngudi mang NST chuye'n doan can bang va dudi 8% neu la ngudi bd mang NST chuye'n doan can bang dd [4], Dieu nay cang the dUOc hien ro trong tien s d san khoa, gia dinh cd me la ngudi mang NST cau true bat thudng thi ty le say thai, thai luu va smh eon dj tat cao hdn trudng hop bo mang,
Neu bd hoac me la ngydi mang NST cau true bat thudng can dUdc lam ehan doan trUde sinh mac dii ket qua sang Ipc thudc nhdm nguy CO Ihap cho thai bat thudng NST. Trudng hpp bd me binh thudng thi thai bat thudng cau true la do dot bien mdi phat smh, thai phu se lam sarig loc va chi chan doan trUdc smh khi ket qua cua sang loc thudc nhdm nguy co cao eho bat thudng NST
Trong trudng hpp thai mang chuyen doan khdng tuong hd (la dang trisomy tdng phan va monosomy tUng phdn) ed the gay ra nhUng bat
thudng hinh thai cho thai. Trong nghidn cijfu cua Chung tdi thi ca 2 trudng hpp chuyen doan khong tuong ho d ^ u co hinh anh sieu a m thai bat thudng.
6 trudng hpp bat thudng thudng e§'u trtic dang kham (mpt d d n g t ^ bao binh thudng va mdt ddng td' bao chuyen doan tUPng ho), chung tdi khdng tim thay NST bat thudng dd d bd me, 1 0 0 % b d m e co karyotyp binh thudng, V. KET LUAN
1. Ty le bS't thudng cau true NST thai qua phan tich NST te bao di la 1,02%.
2. Gia trj ci!ia cac phUPng phap sang Ipc trudc sinh trong vide phat hidn cac thai bat thudng cau true NST.
- Thai mang NST loai chuyen doan tuong ho cd 5/9 thai tien sCr thai san t}d't thudng dong thdi 5/7 (2 thai khong lam sang Ipc HTM) cd sang Ipc HTM nguy cP cao cho HC Down
Thai mang NST loai chuyen doan khdng tuong ho dupc phat hien chu ydu dUa vao sieu am hinh thai thai phdi hpp tien sCf thai san bat thudng va sang Ipc huyet thanh me nguy cP cao.
3. Thai m a n g NST chuyen doan dang thuan thudng di truyen t U b d , me (9/11 thai).
4. Tat ea cac trudng hpp thai bat thudng cau true NST dang kham deu khdng phat hien thay bat thudng NST do tU b d me.
TAI LIEU T H A M KHAO
1. Phan Thj Hoan {2007}. "Tuoi bd me sinh con bj dj tat bam sinh". Hoi nghi quoc te vS di truyen - sang loc va chan iloan Irudc sinh. Ir. 138-140
i , Hoang thi Ngpc Lan, Tran Thi Thanh HuOng [2010]:
"Chan Irutitc smh hpi chung Down, Tap chi Nghien cuU Y hoc Volume 69. N" 4, August, tr 3&43.
3. Phung NhU Toan (2003). Khao sat kaiyotyp Iha nhi qua nuoi ca'y te bao a trong chan doan Ben san^ Wai'san S ^ / ^ khoa. sd dac bet 2003, tr, 27&-282
4. Stoll C, Alembik Y., Dott B., Roth M.P (1998).
"Study of Down syndrome in 238942 consecutive births". Ann, Genef 41 N" 1 44-51 5. Rozenberg P, Senat MV (2007). "Depistage de la
tnsomie 21 en France le consensus du pire", J Gynecol Obstet Biol Reponj (Paris) 2007; 36: 95-103, 6 Rouquet Y. (2006). "Depistage des anomalies
chromosomiques: actualites, conseils pour le depistage de la trisomie". College national des gynecologues et obstetnciens frani^ais Trentiemes pumees nationales Pans,2006. Gynecologie- obstetrique pour le medecins generalistes. Paris:
Vigot 2006 5- 20
