Transcript ASSESSMENT OF RISK FOR MATERNAL AGE AND FETAL …

FIRST TRIMESTER SCREENING FOR TRISOMY 21 BY
MATERNAL AGE, FETAL NUCHAL TRANSLUCENCY AND
NASAL BONE IN 13.049 UNSELECTED PREGNANCIES IN
SLOVENIA
DARIJA STRAH
Diagnostic Centre Strah, Domžale
MAJA POHAR - PERME
Institute for Biostatistics and Medical
Informatics, Faculty of Medicine,
University of Ljubljana
KSENIJA GERŠAK
Department of Obstetrics and Gynecology,
University Medical Centre Ljubljana
VI. Hrvatski kongres o ginekološkoj endokrinologiji, humanoj reprodukciji i menopavzi s međunarodnim sudjelovanjem 13.-16-9-2007, Brijuni
Definition
Prenatal screening programs
provide information with
which couples can make
appropriate decisions, rather
than focusing on disabilities
and their eradications.
(Royal College of Obstetricians
and Gynaecologists, 1977)
VIII. Hrvatski kongres o ginekološkoj endokrinologiji, humanoj reprodukciji i menopavzi s međunarodnim sudjelovanjem 8.-11.-9.-2011, Brijuni
Incidence I
The natural frequency of chromosomal
abnormalities at birth in the absence of any prenatal
diagnosis is 6 / 1.000 births.
Aneuploidies are the most frequent:
T 21: 1 IN 800 (Hook, 1992)
T 18: 1 IN 6.500
T 13: 1 IN 12.500.
Sex aneuplodies:
Turner sy (45, x0), Klinefelter sy (47, xxy),
triploidy type I (diandry) and type II (digyny).
VIII. Hrvatski kongres o ginekološkoj endokrinologiji, humanoj reprodukciji i menopavzi s međunarodnim sudjelovanjem 8.-11.-9.-2011, Brijuni
Incidence II
Age dependent - due to shift to women having babies at an
older age the general prevalence for T 21  from 1 in 740
(1974) to 1 in 504 (1997) (Egan et al., 2000).
The actual frequency changes with gestational age and
intrauterine lethality of various aneuploidies.
T 21:
40 % fetal loss  12. W
30 % fetal loss  16. W
T 18,13: 80 % fetal loss  12. W
40 % fetal loss  16. W
al.,1995)
term
term
term
term (Snijders et
VIII. Hrvatski kongres o ginekološkoj endokrinologiji, humanoj reprodukciji i menopavzi s međunarodnim sudjelovanjem 8.-11.-9.-2011, Brijuni
Second trimester screening
Screening for T21 has become an established part of
obstetric practise over last 20 years by second trimester
maternal serum biochemical markers. (Spencer, 1999;
Cuckle, 2000; Muller et al., 2002; Wald, 2003)
AFP, free -hCG, unconjugated ESTRIOL, inhibin A;
DR: 60 – 70 % at 5 % FPR (Nicolaides KH, 2004)
First trimester combined prospective screening:
DR: 88 % at 5 % FPR
(Nicolaides KH, 2005, Malone, 2005, O'Leary et al., 2006,
Wright at al, 2008, Kagan KO et al, 2008)
VIII. Hrvatski kongres o ginekološkoj endokrinologiji, humanoj reprodukciji i menopavzi s međunarodnim sudjelovanjem 8.-11.-9.-2011, Brijuni
First trimester screening
Earlier reassurance:
- Higher detection rate (Nicolaides, 2005,
2011, Malone, 2005, O'Leary et al., 2006)
- Lower invasive testing rate (Tabor, 2008)
- Termination is safer earlier (Lawson et al.,
1994)
VIII. Hrvatski kongres o ginekološkoj endokrinologiji, humanoj reprodukciji i menopavzi s međunarodnim sudjelovanjem 8.-11.-9.-2011, Brijuni
First trimester screening modes
OSCAR Clinic: contemporaneous approach - one stop Clinic
(Bindra et al., 2002, Avgidou et al., 2005, Nicolaides et al.,
2005, Tabor 2007)
Concurrent testing: biochemistry available after US, counselling
delayed (Czech Republic, Germany, Italy, Finland, Slovenia,
Stenhouse et al., 2004)
Sequential testing: biochemistry taken before, counselling on
the day of US (Borell et al., 2004),  DR blood at 9 -10 w
Two stage testing: biochemistry taken if risk > 1/1.000 (Kagan
KO, 2010)
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Nuchal translucency - NT
NT is the single most effective marker for fetal aneuploidy evaluated by
Mahalanobis distance – relative clinical effectiveness.
Mahalanobis distance =
 mean ( unaffected )  mean ( affected ) 


SD ( unaffected )


2
Markers in discriminating normal pregnancies and T 21 in the first
trimester:
NT
11,00
PAPP-A
2,48
Free -hCG 1,74
VIII. Hrvatski kongres o ginekološkoj endokrinologiji, humanoj reprodukciji i menopavzi s međunarodnim sudjelovanjem 8.-11.-9.-2011, Brijuni
First trimester screening
-Additional sonographic markers:
- Nasal bone – NB,
- Tricuspid flow –TR,
- Ductus venosus flow,
- Frontomaxilary angle – FMF,
- Intracranial Translucency – IT (Spina bifida)
DR: about 95 % at 2,5 % FPR (Nicolaides KH,
2011)
VIII. Hrvatski kongres o ginekološkoj endokrinologiji, humanoj reprodukciji i menopavzi s međunarodnim sudjelovanjem 8.-11.-9.-2011, Brijuni
Fetal Nasal bone - NB
The nasal root depth is abnormally short in 50 % of
T21 cases (Cicero et al., 2003) in the first trimester.
- Mid saggital view of the fetal profile
- Three lines: skin, tip of the nose, NB (thicker and
more echogenic)
Second trimester: 65 % of T21 has an absent or
short NB (charts)
VIII. Hrvatski kongres o ginekološkoj endokrinologiji, humanoj reprodukciji i menopavzi s međunarodnim sudjelovanjem 8.-11.-9.-2011, Brijuni
Sonographic screening by
maternal age, NT and NB
First – stage policy of screening without biochemistry has
advantages:
- Detailed examination of fetal anatomy – early diagnosis
in all pregnancies,
- Reduction in the cost of screening (Nicolaides KH, 2011)
Biochemistry in subgroup with positive first – stage
screening results
VIII. Hrvatski kongres o ginekološkoj endokrinologiji, humanoj reprodukciji i menopavzi s međunarodnim sudjelovanjem 8.-11.-9.-2011, Brijuni
Objectives
To examine the effectiveness of first stage screening using maternal age, NT
and NB in the detection of T 21 at 11-14
weeks in a low risk obstetric population.
VIII. Hrvatski kongres o ginekološkoj endokrinologiji, humanoj reprodukciji i menopavzi s međunarodnim sudjelovanjem 8.-11.-9.-2011, Brijuni
Methods
Period:
January 2005 – April 2010
13.535 women:
singleton pregnancies
12 4/7 (11 1/7 – 14 0/7)
CRL: 63 mm (45 – 83)
NT: 1,7 mm (0,9 – 13,4)
Excluded:
twin pregnancies (3,6 %)
fetal deaths
no follow up
Final analysis: 13.049 women, 29 median maternal age (28,9 in pop)
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Results 1:
45 chromosomal abnormalities
34 detected (17 T 21, 17 other)
NB present in 98,5 %,
absent in 25 % of abnormalities
DR: 85 % at 2,8 FPR for T 21
DR: 75,6 % at 2,8 FPR for all
DR: 68 % at 2,8 FPR for other
NT >95 c in 75 % T 21 (15/20)
NT >95 c in 64 % other (16/25)
VIII. Hrvatski kongres o ginekološkoj endokrinologiji, humanoj reprodukciji i menopavzi s međunarodnim sudjelovanjem 8.-11.-9.-2011, Brijuni
Results 2:
Risk  1 : 300
3 % normal pregnancies
85 % T 21
68 % other chromosomal abnormalities
PPV T 21: 4,3 % (17/394)
NPV T 21: 99,9 % (12.652/12.655)
PPV other: 4,3 % (17/394)
NPV other: 99,9 % (12.647/12.655)
DR T 21: 85 % (17/20)
VIII. Hrvatski kongres o ginekološkoj endokrinologiji, humanoj reprodukciji i menopavzi s međunarodnim sudjelovanjem 8.-11.-9.-2011, Brijuni
Results 3:
The change (lowering)
of risk treshold  DR of
other chromosomal
abnormalities.
Change would result in
 pregnancy loss due to
 FPR and  invasive
testing rate.
VIII. Hrvatski kongres o ginekološkoj endokrinologiji, humanoj reprodukciji i menopavzi s međunarodnim sudjelovanjem 8.-11.-9.-2011, Brijuni
Results 4:
Trend of ageing of
population of pregnant
women results in  FPR at
risk cut - off 1: 300.
DR at 2,8 % FPR adequate
according to FMF
standards,
no change of lowering the
risk limit need.
VIII. Hrvatski kongres o ginekološkoj endokrinologiji, humanoj reprodukciji i menopavzi s međunarodnim sudjelovanjem 8.-11.-9.-2011, Brijuni
Conclusions 1
DR
for all chromosomal aneuploidies 75,6 %;
for T 21 85 %
for other chromosomal aneuploidies 68 %.
One of twelve women defined as high risk pregnancy
carried a child with chromosomal aneuploidy.
NB  DR from 75 % (age, NT) to 85 % at low FPR.
VIII. Hrvatski kongres o ginekološkoj endokrinologiji, humanoj reprodukciji i menopavzi s međunarodnim sudjelovanjem 8.-11.-9.-2011, Brijuni
Conclusions 2
Our first – stage screening results:
DR for T 21 compared to reference centre Fetal
Medicine Foundation (FMF), London:
85 % (at 2,8 % FPR) Slovenia
85 % (at 2,7 % FPR) FMF
VIII. Hrvatski kongres o ginekološkoj endokrinologiji, humanoj reprodukciji i menopavzi s međunarodnim sudjelovanjem 8.-11.-9.-2011, Brijuni
References
• Genetics and Etiology of Down Syndrome,
2011, ISBN 978-953-307-631-7
• http://www.intechopen.com/articles/show/title/firsttrimester-screening-for-tris
• omy-21-by-maternal-age-nuchal-translucency-and-fetalnasal-bone-in
VIII. Hrvatski kongres o ginekološkoj endokrinologiji, humanoj reprodukciji i menopavzi s međunarodnim sudjelovanjem 8.-11.-9.-2011, Brijuni