DARIJA STRAH

1
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

2
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)?

3
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).

4
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 term
• 30 fetal loss ? 16. W term
• T 18,13 80 fetal loss ? 12. W term
• 40 fetal loss ? 16. W term
  (Snijders et al.,1995)?

5
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)?

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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)?
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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 gt
  1/1.000 (Kagan KO, 2010)

8
Nuchal translucency - NT

• NT is the single most effective marker for fetal
  aneuploidy evaluated by Mahalanobis distance
  relative clinical effectiveness.
• Mahalanobis distance
• Markers in discriminating normal pregnancies and
  T 21 in the first trimester
• NT 11,00
• PAPP-A 2,48
• Free ?-hCG 1,74

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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)?
10
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)

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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

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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.
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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 gt95 c in 75 T 21 (15/20) NT
gt95 c in 64 other (16/25)
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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)?
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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.
17
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.
18
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.
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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
20
References

• Genetics and Etiology of Down Syndrome, 2011,
  ISBN 978-953-307-631-7
• http//www.intechopen.com/articles/show/title/firs
  t-trimester-screening-for-tris
• omy-21-by-maternal-age-nuchal-translucency-and-fet
  al-nasal-bone-in