Download Role of Prenatal screening

The Role of Prenatal screening
as part of Routine Obstetric Care
Dr Sarah Pixton
O & G Registrar
4th June 2014
Current Practise in providing
antenatal support and care
• A large part of the now routine antenatal care we
provide is to identify potential risks to the
pregnancy- affecting the wellbeing of both
mother and fetus.
– We look for infections and offer treatment or
vaccinations
– We check the blood group and look for any antibodies
– We screen for gestational diabetes
…As providers of maternal healthcare We watch on
vigilantly, keeping the pregnant woman under close
surveillance so we can act promptly and appropriately
if a problem arises in an aim to help them have a
happy healthy baby
Pre-test counselling and information
(RANZCOG)
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Offer prenatal screening as early as possible in pregnancy to allow women
to make an informed choices
Information should be provided so that it is easily understood and culturally
appropriate
Describe the difference between a screening test and a diagnostic test
Emphasise that screening is entirely voluntary and antenatal care will be
provided the same regardless
Provide details on screening options including advantages and
disadvantages
Explain potential psychological implications and burden of disease
Explain logistics of testing and availability of results
Women with high risk results will be timely informed and offered diagnostic
testing
Explain option of TOP if the event of a fetal abnormality
Offer referral to paediatrician, social work, genetic counsellor
Prenatal Screening in Australia
• First trimester combined NT and serum
screening test for aneuploidy
• Second trimester serum quadruple test
screening for those who missed the first
trimester tests
• Morphology ultrasound at 18-20weeks
– Diagnostic testing (amniocentesis/CVS) if
screening comes back high risk or inheritable
condition is to be excluded
• 1st trimester:
• Blood is collected from 9-13 weeks gestation (ideally 912/40)
• Biochemical analysis of PAPP-A
• 2nd trimester:
• Blood is collected from 14-20 weeks gestation (ideally
15-17 weeks gestation)
• Biochemical analysis of;
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Alpha fetoprotein (AFP)
Free BhCG (or total hCG)
Unconjugated estriol (uE3)
Inhibin A
Different types serum screening
tests
• Triple test: Based on measurement of maternal
AFP, uE3, & BhCG +maternal age
• Quadruple test: Based on measurement of
maternal AFP, uE3, BhCG, & inhibin A +
maternal age
• Serum integrated test: single test result with
integration of PAPP-A measurement in 1st
trimester with quadruple test markers in the 2nd
trimester, + maternal age
FASTER (2005):
Test
FPR for 85% DR for 5%
DR
FPR
Triple test
14
70
Quadruple
test
7.3
80
Serum
integrated
test
4.4
88
Current Gold Standard
• Down Syndrome screen= combined first trimester
screening.
• Performed between 11 weeks and 13+6 weeks
• Based on:
– Maternal age
– US measurement of Nuchal transluency thickness
– Maternal serum analytes ( PAPP-A Free BHCG)
85- 93% sensitivity and 95% specificity for Down
Syndrome
Nuchal translucency
fetal crown-rump length should be between
45 and 84mm.
NT depends on
weeks < 3mm
Other benefits of the 12 week
ultrasound
• Accurate dating of the pregnancy
• Identification of multiple pregnancies
• Structural rather than chromosomal
anomalies identified. Other causes of
increased NT:
• Cystic hygroma
• Cardiac anomalies
• Other adverse pregnancy outcomes such as PET
or IUGR can be identified ( uterine artery dopplers)
Diagnostic Testing
amniocentesis and CVS
Cell free Fetal DNA
…Way of the future??
Timeline of cell free fetal DNA
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1969 Discovery of fetal cells in maternal bloodstream
1997 Discovery of cell-free fetal DNA (cffDNA) in maternal bloodstream;
demonstration of sex determination using PCR of cffDNA
1998 Demonstration of RhD blood typing using PCR of cffDNA
2000 Demonstration of detection of first dominant mutation myotonic dystrophy
2001 Testing using PCR of cffDNA becomes commercially available for sex detection and RhD
typing
2002 Demonstration of detection or exclusion of first recessive mutation congenital adrenal
hyperplasia and cystic fibrosis
2002 Demonstration of paternally-inherited fetal HLA haplotyping
2004 Demonstration of fetal polymorphism detection by parental haplotype analysis using PCR
and mass spectrometry of cffDNA
2006 Demonstration of Trisomy 18 detection using methylation-specific PCR of cell-free fetal
mRNA
2007 Demonstration of Trisomy 21 detection using digital PCR of cell-free fetal mRNA
2007 Demonstration of RhC, RhE, and Kell blood typing using PCR of cffDNA
2008 Demonstration of Trisomy 13, 18, and 21 detection using sequencing of cffDNA
2010 Demonstration of whole fetal genome mapping by parental haplotype analysis using
sequencing of cffDNA
2011 3 large clinical studies demonstrate high sensitivity and specificity
for Trisomy 18 and 21 detection
Suggested model to integrate it into
obstetric screening