1. The Role of Prenatal screening as part of Routine Obstetric Care
Dr Sarah Pixton
O & G Registrar
4th June 2014

2. 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

3. Pre-test counselling and information (RANZCOG)
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

4. 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

5. Blood is collected from 9-13 weeks gestation (ideally 9-12/40)
1st trimester:
Blood is collected from 9-13 weeks gestation (ideally 9-12/40)
Biochemical analysis of PAPP-A
2nd trimester:
Blood is collected from weeks gestation (ideally weeks gestation)
Biochemical analysis of;
Alpha fetoprotein (AFP)
Free BhCG (or total hCG)
Unconjugated estriol (uE3)
Inhibin A

6. 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

7. FASTER (2005): Test FPR for 85% DR DR for 5% FPR Triple test 14 70
Quadruple test
7.3 80
Serum integrated test
4.4 88

8. 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

9. Nuchal translucency
fetal crown-rump length should be between 45 and 84mm.
NT depends on weeks < 3mm

10. 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)

11. Diagnostic Testing
amniocentesis and CVS

12. Cell free Fetal DNA …Way of the future??

13. Timeline of cell free fetal DNA
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
large clinical studies demonstrate high sensitivity and specificity
for Trisomy 18 and 21 detection

14. Suggested model to integrate it into obstetric screening