1. Effectiveness of prenatal screening for Down-syndrome on the basis of the Hungarian Congenital Abnormality Registry Effectiveness of prenatal screening for Down-syndrome on the basis of the Hungarian Congenital Abnormality Registry Judit Beres, Andrea Valek, Janos Sandor and Julia Metneki Department of Hungarian Congenital Abnormality Registry (HCAR), National Institute for Health Development, Budapest, Hungary 38th Annual Meeting of ICBDSR 38th Annual Meeting of ICBDSR Geneva 27-30 September 2011 Geneva 27-30 September 2011 National Institute for Health Development

2. Preliminaries 1970 – establishing of Hungarian Congenital Abnormality Registry (HCAR) 1974 - ICBD founder member: prof. Andrew Czeizel - monitoring of all congenital malformations and chromosomal aberrations (ICD-10 codes: Q00-Q99) including Down syndrome = DS 1985 - effectiveness of the prenatal screening (PS) for DS had become the compulsory part of the prenatal care Ratio of notification of HCAR, 1990-2009 2007 - without minor anomalies: hernias, haemangioma, etc. 2009 – on-line notification

3. Objectives to map the time and spatial patterns of DS and PS to map the time and spatial patterns of DS and PS to describe the quality indicators of prenatal screening to describe the quality indicators of prenatal screening of DS in Hungary to plan and start clinical audit of prenatal screening of DS to plan and start clinical audit of prenatal screening of DS to support the exploration of the non-utilized opportunities to support the exploration of the non-utilized opportunities to improve the screening effectiveness to improve the screening effectiveness

4. Materials and methods Compulsory and whole-country-covering reporting in the study period, 2001-2009. Compulsory and whole-country-covering reporting in the study period, 2001-2009. Active search of unrecorded cases significantly expanded the HCARS database. Active search of unrecorded cases significantly expanded the HCARS database. All the records contain data on age and residence of the mother, outcome of the pregnancy, prenatal diagnoses, and gestation age of detection. All the records contain data on age and residence of the mother, outcome of the pregnancy, prenatal diagnoses, and gestation age of detection. The prevalence of DS has been calculated for all pregnancies and for livebirths separately. The prevalence of DS has been calculated for all pregnancies and for livebirths separately. The data on deliveries and the age-specific fertility rates of mothers had been determined by the National Center for Statistics. The data on deliveries and the age-specific fertility rates of mothers had been determined by the National Center for Statistics.

5. Prevalence of DS in Hungary, 1970-2009 2005: 1,9‰ 2009: 1,6‰ 2009: 0,86‰ % Prevalence 2001-2009: 1,78 ‰ (1 : 563 total births) Number of total births: 877.744 Registered number of DS: 1.558

6. Changes of age-group of mothers in the Hungarian population between 1990-2009 49,4 8,4 5 15 25 35 45 55 1990-19941995-19992000-20042005-2006200720082009 - 2425-2930-34?35 15,0 20,7 The age of mothers shows remarkable time-trend change. The age-specific fertility rate of younger mothers decreased, while this rate of older mothers increased %

7. Live births by age-group of mother per 1000 females of corresponding age, 1970-2009 There is a significant demographic change in the maternal age in the Hungarian population. A drastic decline can be observed in proportion of women under 25, while a significant increasing tendency in the proportion of women over 30 or more.

8. The distribution of mothers 35 years or above in the Hungarian population, 2001-2009 The proportion of mothers 35 years or above increased from 8% to 15% (this value is almost the double). 2009 – number of mothers over 35: 14.471 (over 45 or more: 81, over 50 or more: 3)

9. Ratio of prenatally diagnosed fetus with DS by region, 2009 Significantly lower No significant difference difference Significantly higher 13/2162% 7/1258% 11/2446% 15/2560% 54/7572% 16/2857% 6/1735% Ratio of detection - national average: 123/203 60,6% Significant variability was observed in the efficiency of prenatal screening of cases with DS by region (minimum value 35% maximum value 72%)

10. Prenatal diagnosis of DS 2005 – 2009 (EUROCAT) HCAR: 2005-2009: 57,9% EUROCAT: 2005-2009: 60,4% www.urocat.ulster.ac.uk

11. The ratio of prenatally detected fetus with DS, 2001-2009 The ratio of prenatally detected fetus with DS has been increased year by year

12. Age of mother and efficacity of prenatal screening The older the mother, the higher the probability of prenatally detected fetus with DS

13. Number of cases and prevalence for DS by age-group of mothers More than half of cases with DS (108/202) arise from mothers 35 years or above. The risk having a baby with DS increases exponentially with the maternal age and slightly higher among mothers under 20 comparing to mother aged 20-24. In the group of mothers 40-44 the ratio of cases with DS is 20/1000

14. Conclusions The increasing prevalence of DS can be primarily attributed to the increasing ratio of advanced age of mothers 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 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 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 Hungary The decreasing ratio of livebirths has indicated the improving effectiveness of prenatal DS screening practice in Hungary The increasing geographical inequalities in screening effectiveness demonstrated the existence of non-exploited opportunities in certain (non-properly managed) areas of Hungary The increasing geographical inequalities in screening effectiveness demonstrated the existence of non-exploited opportunities in certain (non-properly managed) areas of Hungary

15. Effectiveness of prenatal screening Bases of score: age of mother, NT (nuchal translucency), beta-hCG and PAPP-A Contradiction in effectiveness of PS – theoretically: ≅ 80-90% – on the basis of HCAR60%

16. Clinical audit of prenatal screening for DS I. Prenatal diagnosis and prenatal screening (PS) of DS Aims: to increase the effectiveness of PS to increase the effectiveness of PS to improve the quality of PS to improve the quality of PS to spread the application of the valid professional guideline to spread the application of the valid professional guideline to identify of weak points of practice (min) to identify of weak points of practice (min) to describe the priority order of treatments (max) to describe the priority order of treatments (max) to increase the number of audited experts in ultrasonic examination to increase the number of audited experts in ultrasonic examination to establish ultrasonic centers to establish ultrasonic centers to prepare united proposal for biochemical screening to prepare united proposal for biochemical screening to map the financial problems to map the financial problems to prepare the revision of protocol to prepare the revision of protocol the improve the quality of data reporting the improve the quality of data reporting

17. Clinical audit of prenatal screening for DS II. Cases included in the study Birth data: 01.01.2008.-31.12.2010. All cases born with DS + all prenatally diagnosed terminated fetus with DS Content of data: Equipment and skilled of institutions doing PS Documentation of the process of PS (ultrasonic or biochemical) and diagnosis Determination of results of examinations Method of clinical audit: Paper-based questionnaire (min) On-line data sheet (max) Collecting data through the network of HCARSR representatives Institutions filling out the questionnaire (or data-sheet) All Hungarian institutions taking care of PS Data-sheet of institutions Data sheet of prenatal detected and not-detected cases with DS Starting of research: 01.09.2011.

18. Expected results of clinical audit to identify the weak points of screeningto identify the weak points of screening to establish necessary interventionto establish necessary intervention to increase the prenatal detection rate of DSto increase the prenatal detection rate of DS to decrease the number of unnecessary invasive interventionsto decrease the number of unnecessary invasive interventions to prepare new guideline for PSto prepare new guideline for PS to improve the professional skill of sonographersto improve the professional skill of sonographers to establish correct ultrasonic diagnostic machinesto establish correct ultrasonic diagnostic machines

19. Thank you for your attention ! Team of HCAR Dr. Julia Métneki Dr. János Sándor Vanessza Vigmann Márta Vadász Dr. Andrea Valek Maternity leave:Melinda Szunyogh and Erzsébet Puhó Maternity leave: Melinda Szunyogh and Erzsébet Puhó Eszter Balku Magdolna Vámos