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) 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

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 14-20 weeks gestation (ideally 15-17 weeks gestation) Biochemical analysis of; 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 DR for 5% 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 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