A. pek 1,2,3 , V. Gregor 1,2 , J. Horek 1,4 , A . pek Jr. 1,5 , P. - PowerPoint PPT Presentation

NATIONAL REGISTRY OF CONGENITAL ANOMALIES OF THE CZECH REPUBLIC: 50 YEARS OF SURVEILLANCE HISTORY AND CHALLENGES OF THE FUTURE A. Šípek 1,2,3 , V. Gregor 1,2 , J. Horáček 1,4 , A . Šípek Jr. 1,5 , P. Langhammer 6 1. Department of Medical Genetics, Thomayer Hospital, Prague, Czech Republic 2. Department of Medical Genetics, Pronatal Sanatorium, Prague, Czech Republic 3. Department of General Biology and Genetics, 3rd Faculty of Medicine of Charles University in Prague, Prague, Czech Republic 4. Gennet, Centre for Fetal Medicine and Reproductive Genetics, Prague, Czech Republic 5. Institute of Medical Biology and Genetics, 1st Faculty of Medicine of Charles University in Prague and General University Hospital, Prague, Czech Republic 6. National Institute of Health Information and Statistics of the Czech Republic, Prague, Czech Republic http://www.vrozene-vady.cz/

50 years anniversary National Registry of Congenital Anomalies of the Czech Republic Selected congenital anomalies surveillance programs in the world - Timeline  1962 – Hungary  1963 – Finland  1964 – Czechoslovakia  1966 – Canada (British Columbia since r. 1952), Israel  1967 – Georgia (USA), Norway, South Africa  1968 – Denmark  1970 – Northern Ireland (Belfast area since 1957)

Czech Republic - History National Registry of Congenital Anomalies of the Czech Republic (NRCA) • Unofficial monitoring in former Czechoslovakia started in 1961 • Official monitoring started on 1st of January 1964 • First stage (1964 – 1974) – only 36 selected diagnoses of congenital anomalies (CA) were registered • Second stage (1975 – 1993) – 60 diagnoses of CA registered • Present time: (1994 – now) – all cases in terminations of pregnancies (TOPs), stillbirths and live births are registered (age limit for reporting = 15 years ) • Near future: no age limit, additional diagnoses (rare diseases), electronic registration, OMIM and Orphanet codes etc.

Czech Republic - Present State Registry: population based (whole area of the Czech Republic) Law: The registration is compulsory, required by the Internal Law of Ministry of Health (nr. 14/2001). The database is run by the Institute of Health Information and Statistics of the Czech Republic. Additional data on prenatally diagnosed cases are collected thanks to the country-wide cooperation. Cases: all cases in TOPs, live births and stillbirths are reported Coding: ICD-10 (international), no verbal description Sources: Multiple sources, including departments of medical genetics, genetic laboratories, pediatric and neonatology departments, delivery units, ultrasound diagnostics departments etc. Termination of Pregnancy: Legal, up to the 24th week of gestation (from genetic reasons)

Czech Republic Population: 10 548 527 Area: 78,866 km 2 Regions: 13 regions and the capital Prague; 76 districts in total Population density: 133/km 2 Annual births: approx. 100 000 Capitol and largest city: Prague (1 241 000 inhabitants) Life expectancy (years): Males - 73.54; Females - 80.28 Language: Czech Ethnicity: Czech 90.4%, Moravian 3.7%, Slovak 1.9%, other 4% Religions : Roman Catholic 27%, Protestant 2%, unaffiliated 59%

International Cooperation Established in 1974 Established in 1979 World-Wide organization European organization CZE: Full membership CZE: Associate membership (1974) (2009) http://www.icbdsr.org http://www.eurocat-network.eu/

Anencephaly Anencephaly – All cases in live births and prenatal diagnosis

Anencephaly Anencephaly – All cases in live births and prenatal diagnosis

Down syndrome Down syndrome – All cases in live births and prenatal diagnosis

Down syndrome Births Prenatal diagnosis Per 10.000 of live births 25 20 15 10 5 0 1961 1963 1965 1967 1969 1971 1973 1975 1977 1979 1981 1983 1985 1987 1989 1991 1993 1995 1997 1999 2001 2003 2005 2007 2009 2011 2013 Down syndrome – All cases in live births and prenatal diagnosis

Invasive prenatal diagnosis 1140 1200 20000 CVS CC AMC 18655 18284 1056 18099 17954 17499 18000 15989 1000 15554 898 16000 14673 872 835 14000 12799 800 11866 12000 10831 10858 12526 11099 600 10000 642 497 10361 8000 400 376 400 8534 400 318 294 6000 268 250 250 234 231 216 212 203 4000 165 200 129 125 100 90 85 86 85 86 2000 62 53 20 0 0 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013

Prenatal diagnosis - Indications % 90 Maternal age Screening 80 70 Ultrasonography Other 60 50 40 30 20 10 0 1992 1994 1996 1998 2000 2002 2004 2006 2008 2010 Year

10 15 20 25 0 5 1985 1986 % 1987 1988 1989 Maternal age – Time trends 1990 1991 1992 Proportion of 35+ years old mothers 1993 1994 1995 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013

10 15 20 25 30 35 40 45 50 0 5 1987 % 1988 1989 1990 1991 Maternal age – Time trends 1992 1993 15-19 1994 1995 1996 1997 1998 20-24 1999 2000 2001 2002 25-29 2003 2004 2005 2006 30-34 2007 2008 2009 2010 35-39 2011 2012 2013

Conclusions 1. The number of prenatally diagnosed cases of Down syndrome is increasing 2. The number of Down syndrome cases in live births is decreasing 3. The indication criteria for the invasive prenatal diagnosis are changing during last years 4. The average maternal age is notably increasing during last years 5. The early prenatal diagnosis (during the first trimester of gravidity) is becoming much more important during last years

Screening 16 44 I. trimester II. trimester Integrated 143 Proportion of screening programs in prenatal diagnosis (2013)

Down syndrome Per 10.000 of live births Births Prenatal diagnosis 25 20 15 10 5 0 1994 1995 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 Down syndrome – All cases in live births and prenatal diagnosis

Down syndrome % 100 90 80 70 60 50 40 30 20 10 0 1994 1995 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 Down syndrome – relative number of prenatally diagnosed cases (%)

Edwards syndrome Per 10.000 of live births Births Prenatal diagnosis 8 7 6 5 4 3 2 1 0 1994 1995 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 Edwards syndrome – All cases in live births and prenatal diagnosis

Edwards syndrome % 100 90 80 70 60 50 40 30 20 10 0 1994 1995 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 Edwards syndrome – relative number of prenatally diagnosed cases (%)

Patau syndrome Per 10.000 of live births Births Prenatal diagnosis 4 3 2 1 0 1994 1995 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 Patau syndrome – All cases in live births and prenatal diagnosis

Patau syndrome % 100 90 80 70 60 50 40 30 20 10 0 1994 1995 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2012 2013 2011 Patau syndrome – relative number of prenatally diagnosed cases (%)

Spina bifida Spina bifida – All cases in live births and prenatal diagnosis

Spina bifida Spina bifida – All cases in live births and prenatal diagnosis

Effectiveness 160 35 146 145 140 29 140 131 128 30 123 122 118 116 114 120 125 25 102 21 89 100 AMC CVS 20 81 80 18 15 15 60 10 10 10 9 9 9 10 8 7 7 40 6 5 20 0 0 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 Number of invasive procedures needed for one diagnosis of Down syndrome

Time of diagnosis 22 21 20,92 20,33 20 19,98 19,60 19,20 19,24 18,97 19,57 19 19,17 19,23 18,12 18 17,44 17,52 17 17,39 16,58 16,56 16 15,78 15,55 15 15,08 14,98 14 13 12 1994 1995 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 Average week of gestation at diagnosis of Down syndrome