This document discusses Down syndrome screening and diagnostic tests. It begins by explaining what Down syndrome is and its relationship to maternal age. It then describes various first and second trimester screening tests like the integrated screen, quad screen, cell-free DNA screening, chorionic villus sampling, and amniocentesis. Key markers like nuchal translucency, nasal bone, and maternal serum markers are also explained. The document concludes with some facts about Down syndrome and references.

1. Menna Allah Mohammed Fatma Ghoneim
Yassmin Nasser Maram
Khaled
Eman Mohammed Rania Farid
Mohammed Ibrahim Sohib Khairy
Under Supervision of Dr. Mohammed Elfar
Cairo University
Faculty of medicine
Gynecology & Obstetrics Department
Dr. Mamdouh Sheba‘s Unit
February 2019

2. WHAT IS DOWN SYNDROME?
 Nondisjunction is an error in meiosis that results in a gamete with
one extra chromosome, fertilization of this gamete results in a
conception with 47 chromosomes.
 Down syndrome known as trisomy 21 is a genetic disorder. It is
associated with physical growth delay, health problems, mild to
moderate intellectual disability & characteristic facial features.

3. RELATION WITH MATERNAL AGE
Incidence in term live
births
Maternal Age
(Years)
1 in 150015-29
1 in 80030-34
1 in 27035-39
1 in 10040-44
1 in 50>45

4. FIRST
TRIMESTER
SECOND
TRIMESTER
Integrated screen
1st Trimester
combined screen
BloodTests
9 - 13 weeks
Ultrasound (NT)
11 - 13 weeks
Quad Screen
15 - 20 weeks
Cell-free DNA (cfDNA) screen
ChorionicVillus
Sampling (CVS)
10 – 13 weeks
Amniocentesis
15 – 20 weeks
ScreeningTestsDiagnosticTests

5. MATERNAL SERUM SCREENING
 1stTrimester screening tests:
 Maternal serum markers:
 Preg. Asso. Placental proteinA (PAPP-A)
 free B-hCG
 Fetal marker: Nuchal translucency
 2ndTrimester screening tests:
 AFP
 E3
 hCG
 Inhibin A
85 %
Quadruple test
76 %
Triple test
70 %
94 %
The values ofThese
serum markers are
converted into patient
specific risk, 1:250 is
taken as cut off

6. CELL-FREE FETAL DNA

7. CELL-FREE FETAL DNA
Advantages:
 Sensitivity 98.58∼100% and specificity 97.95∼100%
 Can be evaluated as early as 8 gestational weeks.
 There is no procedure related fetal loss.
 Drawbacks:
 Difficulty of separating free fetal DNA completely.
 Not all health facilities have the equipment and laboratory for the cell-
free fetal DNA analysis.
 The cost is much higher than other down syndrome screening tests.

8. 2
2
1
1
1

9. NUCHALTRANSLUCENCY
 Subcutaneous fluid-filled space located between back of fetal neck and
skin
 Measured on U/S between 11–13+ 6/7 weeks, measurement is not valid
outside of this time period
 NT increases with gestational age
 NT >3.0 or 3.5mm (depending on the centre) is considered elevated
Diagnostic testing indicated
Fetal echocardiogram indicated ~20 weeks (if NT>3mm)
Detailed anatomy scan at 18-20 weeks
Genetic counselling

10. Increased NT associated
with:
 Trisomies 21, 18, 13, triploidy and
Turner syndrome
 Spontaneous fetal loss
 With normal chromosomes:
cardiac defects, diaphragmatic
hernia, pulmonary defects, skeletal
dysplasias, congenital infection,
metabolic disorders, rare single
gene disorders
 Normal pregnancy – chance of a
normal birth varies with size of NT
measurement
Chance of normal
birth
NT measurement
95%≤ 3.4mm
70-86%3.5 – 4.4mm
50-77%4.5 – 5.4mm
67%5.5 – 6.4mm
31%≥ 6.5mm
NUCHALTRANSLUCENCY

12. NASAL BONE
Absent nasal bone on US done at 11 to 13 weeks is another
marker of Down Syndrome.
Detection rate of Down Syndrome is 67%
When combined with NT detection rate is 90%

14. CHORIONICVILLUS SAMPLING (CVS)
 Performed at 10-14 weeks.
 Highly accurate for
chromosome disorders.
 Done either by
transabdominal or
transvaginal methods
under local anasthesia.
 Risk of fetal loss 1-2%

15. AMNIOCENTESIS
 Performed from 15-20
weeks (15-17 ideal)
 Results available 1-3
weeks later
 Highly accurate
 Complications:
• Risk of fetal loss 0.5-1%
• Infection
• Insufficient sample

16. FACTS ABOUT DOWN
SYNDROME
 Children with Down Syndrome can & do learn, and are capable of
developing skills throughout their lives.They simply reach their
goals at a different pace.
 Lots of people with down syndrome are able to leave home , have
relationships , work & lead largely independent lives.
The learning potential of an individual with Down Syndrome can
be maximized through early intervention, good education and
higher expectations.
There is a support available to help these children leading to
healthy full filling lives,This include:
Regular health care check up, Speech language therapy, Physiotherapy,
Home teaching, Support groups.

17. FAMOUS PEOPLEWITH
DOWN SYNDROME

19. REFERENCES
 Spencer K, Nicolaides KH, Falcon O, Gerovassili a., Auer M. Screening for
trisomy 21 by fetal tricuspid regurgitation, nuchal translucency and
maternal serum free β-hCG and PAPP-A at 11 + 0 to 13 + 6 weeks.
Ultrasound Obstet Gynecol. 2005;27(2):151–5.
 Spencer K, Nicolaides KH. Screening for trisomy 21 in twins using first
trimester ultrasound and maternal serum biochemistry in a one-stop clinic:
A review of three years experience. BJOG An Int J Obstet Gynaecol.
2003;110(3):276–80.
 Baker a., Nicolaides KH, Kagan KO, Wright D, Sahota D. Screening for
trisomy 21 by maternal age, fetal nuchal translucency thickness, free beta-
human chorionic gonadotropin and pregnancy-associated plasma protein-
A. Ultrasound Obstet Gynecol. 2008;31(6):618–24.
 Koster MPH, Wortelboer EJ, Stoutenbeek P,Visser GH a., Schielen PCJI.
Modeling Down syndrome screening performance using first-trimester
serum markers. Ultrasound Obstet Gynecol. 2011;38(2):134–9.
 Meta-analysis of second-trimester markers for trisomy 21M.
Agathokleous, P. Chaveeva, L. C.Y. Poon, P. Kosinski, K. H.
NicolaidesUltrasound in Obstetrics & Gynecology 24 Jan 2013; DOI:
10.1002/uog.12364

20. REFERENCES
 Rafi I, Chitty L. Cell-free fetal DNA and non-invasive prenatal
diagnosis. Br J Gen Pract. 2009;59(562):320–1.
 Patil M, PanchanadikarTM,Wagh G.Variation of Papp-A level in the
first trimester of pregnancy and its clinical outcome. J Obstet Gynecol
India. 2014;64(2):116–9.
 Bhupendra J, Moulali S,Amargandhi M, KristineT, Shiefa S. First
Trimester Maternal Serum Screening Using Biochemical Markers
PAPP-A and Free β-hCG for Down Syndrome, Patau Syndrome and
Edward Syndrome. Indian J Clin Biochem. 2012;28(1):3–12.
 Lee FK, Chen LC, Cheong ML, Chou CY,Tsai MS. First trimester
combined test for Down syndrome screening in unselected
pregnancies - A report of a 13-year experience.Taiwan J Obstet
Gynecol [Internet]. 2013;52(4):523–6. Available from:
http://dx.doi.org/10.1016/j.tjog.2013.10.012