The Italian Screening Programme for Fetal Aneuploidies Pietro Cignini, MD Department of Prenatal Diagnosis ARTEMISIA Fetal Maternal Medical Centre Rome, Italy e-Health and Info Biomedical Technologies Budapest, 30 May 2013 Summary • • • • • Artemisia Fetal Maternal Medical Centre Italian College of Fetal Maternal Medicine SCA-Test (Computerized Programme for Fetal Aneuploidies) ERA (Early Risk Assesment) OSCAR (One-Stop Clinic Assessment of Risk) • Research Interest: – Over 10 Years of Experience in Prenatal US – Over 10 Years of experience in Prenatal Screening www.pietrocignini.it ARTEMISIA SPA (Rome, ITALY) 1. Private centre 2. Dpt of prenatal Diagnosis 3. Dpt of Molecular Biology 4. Dpt of day Surgery 5. Dpt of Reproductive Medicine Number of amniocentesis per/year 2012 Ministry of Halth Report APGA Trial • 2791 obs/gyn • Largest Scientific Society for Prenatal Care in Italy • Recognized by the Italian Ministry of Helath • Journal of Prenatal Medicine (indexed in PubMed) • Member of the International Federation of Prenatal Diagnosis 1970 –EmiliaRomagna (IMER) registry , Registry of Tuscany (RTDC) North East Registry (NEI). 1990 – Campania Region - monitoring of all congenital malformations and chromosomal aberrations (ICD-10 codes: Q00-Q99) including Down syndrome = DS 1992 - effectiveness of the prenatal screening (PS) for DS had become the compulsory part of the prenatal care Prenatal diagnosis of DS 2005 – 2009 (EUROCAT) Age of mother and efficacy of prenatal screening 70 72,3% Diagnosed 60 No. of cases 57,1% Not diagnosed 50 74,4% 40 30 50,0% 20 10 16,7% 20,0% 28,6% 0 16-19 20-24 25-29 30-34 35-39 40- Unknow n Age-group of m other The older the mother, the higher the probability of prenatally detected fetus with DS Facts • The increasing prevalence of DS can be primarily attributed to the increasing ratio of advanced age of mothers • PS showed a significant improvement year by year • The prevalence of DS and the efficiency of PS was slightly lower than the values observed in other European countries • The decreasing ratio of livebirths has indicated the improving effectiveness of prenatal DS screening practice in Italy • The increasing geographical inequalities in screening effectiveness demonstrated the existence of non-exploited opportunities in certain (non-properly managed) areas of Italy 11. By 2008, screening programs should aim to provide a screen that, as a minimum, offers women who present in the first trimester a detection rate of 75% for Down syndrome, with no more than a 3% false positive rate. (III-B) Principles of Screening Characteristics of Screening Test Sensitivity (Detection rate): Abn screen, abn result False Positive Rate*: Abn screen, normal result False Negative Rate: Normal screen, abn result Specificity: Normal screen, normal result = 100-FPR Likelihood Ratio: Proportn Abn / Proportn Normal * Also called initial positive rate, is used interchangeably with amniocentesis rate The SCA-TEST is an ultrasound screening and / or biochemical Multiple Computerized Calculation of Risk for Fetal Aneuploidies in the First and Second Trimester of Pregnancy, recognized and published on the National Guidelines of Italian Ministry of Health • Prospective Study April-October 2007 • Sca-Test II trimester Before Amniocentesis • Sacco A. et al. Journal of Prenatal Medicine 2007; 1 (4): 47-56 Meta-analysis of second trimester markers for trisomy 21 Agathokleous et al., UOG 2013 Marker DR FPR LR + ve LR – ve Isolated marker Cardiac echogenic focus 24.4 3.9 5.8 0.80 0.95 Ventriculomegaly 7.5 0.2 27.5 0.94 3.81 Increased nuchal fold 26.0 1.0 23.3 0.80 3.79 Echogenic bowel 16.7 1.1 11.4 0.90 1.65 Mild hydronephrosis 13.9 1.7 7.6 0.92 1.08 Short humerus 30.3 4.6 4.8 0.74 0.78 Short femur 27.7 6.4 3.7 0.80 0.61 ARSA 30.7 1.5 21.5 0.71 3.94 Absent or hypoplastic NB 59.8 2.8 23.3 0.46 6.58 No markers LR 0.13 = 7.7 fold reduction Meta-analysis 47 studies 1995–2012 Trachea ARSA Spine The Early Risk Assessment (ERA) Program: First Trimester Screening and Early Detection of Pregnancy Complications GOAL “To promote the health and well-being of pregnant women through a collaborative and multidisciplinary prenatal risk assessment program that would enable early, more accurate identification and management of pregnancies at increased risk for adverse perinatal health outcomes”. Early Risk Assessment Program : Prenatal Screening for Chromosome Disorders Purpose: •To introduce FTS •To develop patient and physician educational materials •To evaluate program performance and patient satisfaction First Trimester Combined Screening • Maternal age • NT • Free-bHCG • PAPP-A Early Risk Assessment Program: Early detection of Pregnancies at risk of Adverse Outcome 1. To examine the predictive value of certain biochemical/US markers (11 -20 w) in detection of women at increased risk of poor pregnancy outcome (pre-eclampsia, IUGR, preterm labor), 2. To identify risk factors and interventions that may improve pregnancy outcome in this group MSS FTS 10 12 14 16 Genetic sonogram 18 Why “Point of Care?” One Stop Clinics • One stop clinics have developed in several clinical areas – breast cancer screening, menopausal clinics, oncology assessment, cardiovascular risk clinics, one-stop surgical clinics • Benefits: – integration of clinical and diagnostic services – better use of clinical time, improved diagnostic efficiency OSCAR: “One-Stop Clinic Assessment of Risk” Patient advantages: •Maximizes patient satisfaction •Reduced number of patient visits •Decreased patient travel costs, (missing work, babysitting, parking), anxiety, and stress especially that associated with waiting for results •Allows for timely, qualified interpretation of results Evidence and Innovations leading to OSCAR • Ultrasound markers of chromosomal anomalies - fetal nuchal translucency thickness at 11-14 weeks. • Maternal serum Biochemical markers of chromosomal anomalies - free b-hCG & PAPP-A at 10-14 weeks. • Development of new rapid assay technology for biochemical marker measurement leading to Point of Care testing. OSCAR in ARTEMISIA One Stop Clinic for Assessment of Risk Woman departs Woman arrives Post-test counselling Pre-test counselling* Free b HCG NT SCAN PAPP-A Blood sample Risk Assessment U/S data Ultrasound Examination (11-13+6 weeks scan) www.earlyriskassessment.com * Mean T/O time 92 minutes *1-1 Counselling, video, pamphlets Invasive testing usually not same day OSCAR in ARTEMISIA FTS Uptake March 2012-2013 600 500 400 300 200 100 0 MarAprMayJunJulAugSepOctNovDecJanFeb FTS Performance March 13 2012- March 13 2013 Screening for Trisomy 21 • DR Trisomy 21 93% (29/32), FPR 6.5% (1/300) • 2 “false negative” cases: •1 negative screen for T21, +ve T13,18 (had invasive) • Other case: no blood obtained, NTS alone. Characteristics of the T21 cases •27/ 31 Trisomy 21 (87%) detected prenatally •CVS 17/27 (63%), amnio 10/26 (38.4%) • 3 LB T21 in screen +ve group (declined invasive) •1 had no invasive (FN result) • Risk assessment on NT alone due to unsuccessful phlebotomy OSCAR Satisfaction Study •Uptake of invasive testing in women attending the OSCAR clinic: • Positive screen (T21): 49.1% • Negative screen: 15% Invasive uptake related to level of risk 80 60 40 20 0 1/100 1/100-1/1000 >1/1000 *DR of T21 87% at 5% FPR Clinical audit of prenatal screening for DS I. Prenatal diagnosis and prenatal screening (PS) of DS Aims: • • • • • • • • • • • to increase the effectiveness of PS to improve the quality of PS to spread the application of the valid professional guideline to identify of weak points of practice (min) to describe the priority order of treatments (max) to increase the number of audited experts in ultrasonic examination to establish ultrasonic centers to prepare united proposal for biochemical screening to map the financial problems to prepare the revision of protocol the improve the quality of data reporting Expected results of clinical audit • • • • • • • to identify the weak points of screening to establish necessary intervention to increase the prenatal detection rate of DS to decrease the number of unnecessary invasive interventions to prepare new guideline for PS to improve the professional skill of sonographers to establish correct ultrasonic diagnostic machines Early Prenatal Risk Assessment: More Than an Aneuploidy Screen 11-14 WEEK SCAN NT, NB Fetal anatomy UA Doppler Placental morphology 1st TM Volume (3D) Maternal Serum PAPP-A Free beta hCG Store sample PHASE 1: FTS PHASE 2: Pregnancy complications DETAILED ANATOMY Fetal echo Uterine artery Doppler Placental morphology Timing of scan Maternal Serum AFP,uE3,hCG DIA? Contingent screening Store sample TV cervix clinic U/A Doppler Cervical length (c/w 18-20 week) PS Program Key Points •One-stop multidisciplinary approach associated with high patient satisfaction •Operationally efficient (few call backs, demographic and ultrasound information available, collaborative atmosphere between disciplines (MFM, genetics, ultrasound, lab, nursing). •Established infrastructure for efficient high quality ultrasound as well as audit and research •Ability to introduce new markers/ protocols •Performance excellent and within expected range A child can always teachs an adult three things: to be happy for no reason, to always be busy with something, and to pretend with all his power what he wants. Paulo Coelho, Monte Cinque, 1996 Questions?