1. CONGENITAL DISEASES IN BULGARIA E. Terlemesian, S. Stoyanov University of Chemical Technology and Metallurgy Centre of Ecology Sofia, Bulgaria

2. CONGENITAL DISEASES IN BULGARIA Introduction Introduction Congenital diseases in Bulgaria Congenital diseases in Bulgaria Infant mortality rates Infant mortality rates Discussion Discussion Conclusion Conclusion

3. OBJECTIVES To present statistical data on To present statistical data on -the incidence rates, -the incidence rates, -types and -types and -trends in the congenital diseases and -trends in the congenital diseases and -infant mortality rates -infant mortality rates in Bulgaria during the last years and to discuss the causal factors.

4. Sofia Register of Congenital Anomalies (SORCA) emerged in 1996 in response to a growing need for current scientific information about the effects of drugs and other environmental agents on developing human embryo and fetus. 40 isolated congenital anomalies (CA) and congenital diseases, detectable at birth or to the end of the first year of live have been detected out of 34124 pregnancies, registered in the period 1996 – 1999 almost one third of the registered families have contacted personally

5. EUROCAT has 41 members in 20 countries has 41 members in 20 countries more than one million births per year are surveyed more than one million births per year are surveyed in EU member states and non-EU countries in EU member states and non-EU countries the central database helds a total of more than 250 000 cases of congenital anomalies since 1980 including live births, stillbirths and termination of pregnancy following prenatal diagnosis the central database helds a total of more than 250 000 cases of congenital anomalies since 1980 including live births, stillbirths and termination of pregnancy following prenatal diagnosis

6. Sofia register database, 1996 – 1999 Type of registrations Total number PercentagePercentage of CA Pregnancies39124100- Congenital anomalies, incl. 7781,9100 * Live births668-89,3 * Fetal deaths38-5,1 * Induced abortions 42-5,6 Source: Euroworkshop on reproductive and developmental toxicity of pesticides, Sofia, 2000

7. Sofia register data base for congenital anomalies, 1996 - 1999 Source: Euroworkshop on reproductive and developmental toxicity of pesticides, Sofia, 2000

8. Registered congenital anomalies by type, 1996 - 1999 Type of congenital anomalies Live births, (no) Fetal deaths (No) Induced abortions (No) Total (No) Incidents rate per 10000 pregnancies EUROCAT Register (Rate) Total number6683842748191,49215,47 Nervous system83353114837,8921,75 Neutral tube defects3518237619,4610,03 Spina bifida34584712,035,11 Hearth diseases2453225064,0060,84 Cleft lip with or without cleft palate 3221358,969,11 Cleft palate90092,305,84 Digestive system anomalies, excluding pyloric stenosis 65226917,6616,06 Intern.urogenital system2702297,4227,86 External genital organs3900 9,9813,11 Limb anomalies54526115,6236,62 Muskoskeletal and connective tissue anomalies 62447017,7222,17 Down syndrome44034712,0318,85 Other chromosomal anomalies, incl. 1618194,8613,29 Trisomy 1321030,771,53 Trisomy 1810120,513,61 Eye anomalies (total)40114411,264,44 Ear anomalies (total)59236416,383,89 Source: Sofia Register Database, 1996 – 1999; EUROCAT, 1996 - 2001

9. Registered congenital anomalies in Sofia and EUROCAT by type, 1996 1999

10. Registered congenital anomalies in Sofia and EUROCAT by type, 1996 - 1999

11. SORCAWORLDWIDE Spina bifida0.89 babies per 1000 live births about one in every 1000 - 2000 births (USA) Neural tube defects 0.92 babies per 1000 newborns 2.6 babies per 1000 newborns (worldwide) about 2 children per 1000 newborns (in W. Australia). – until 1996; 1.3 children per 1000 births (in W. Australia) after 1996 Congenital facial clefting 1.12 per 1000 live births 1.71 per 1000 live births (in the US) 1.49 per 1000 live births (EUROCAT) Source: http://encyclopedia.thefreedictionary.comhttp://encyclopedia.thefreedictionary.com

12. Total number of live births in Bulgaria

13. Percentage of total live births in Bulgaria according to the mother’s age

14. Mortality rates – all ages, per 1000 198019851990199520002005 8 10 12 14 16 18 20 Total In the town In the country side Year

15. Infant mortality rate per 1000 live births

16. During the last years an increased trend of delivery at home is registered in Bulgaria. This is a reason for the high mother mortality In the rural areas mother mortality is 25,5 per 100 000 births In Kazakhstan – 40 per 100 000 births Source: UN Population Fund Report, 2004 Delivery at home

17. Infant mortality rates per 100 000 live births (2003)

18. Trends in the mortality rates in the period 1990 – 2003 according to different reasons

19. Infant mortality rates Source: National Statistical Institute Yearbook: Health, 2002, 2003 Reasons for deathDeath rate per 100 000 live births 19901995200020022003 Congenital anomalies (total) including: 401,2418,2320,3282,7259,8 Spina bifida20,922,213,616,510,4 Other nervous system anomalies38,066,743,451,120,8 Anomalies of bulbus cordis30,426,419,033,138,6 Other congenital heart anomalies136,9105,6103,266,275,7 Congenital respiratory system anomalies 37,159,716,312,013,4 Congenital digestive system anomalies 37,137,528,525,632,7 Certain conditions, originating in the prenatal period, including: 393,6464,1438,4398,5386,0 Disorders related to a preterm delivery and low birth weight 130,384,862,4120,3154,4 Difficult breathing syndrome (sudden infant death syndrome) 42,862,569,249,644,5

20. Infant mortality rate due to congenital anomalies Infant mortality rate due to congenital anomalies

21. Infant mortality rates due to congenital anomalies

22. Infant mortality rates due to certain conditions, originating in the prenatal period

23. Territorial distribution of infant’s mortality in 2003 caused by congenital anomalies and due to reasons originating in the prenatal period Live births rate per Still births rate per Infant mortality per 1000 live birth Infant mortality rate per 1000 live births due to District 1000 people 100000 people In the townsIn the country- side Congenital anomalies Reasons from the prenatal period Average for the country8,67,010,716,52,63,9 Vratzsa8,16,412,315,62,84,0 Montana7,78,012,322,41,56,0 Dobrich8,88,612,513,93,84,9 Varna9,96,79,419,23,93,7 Silistra8,79,412,318,15,84,7 Targovishte9,46,414,323,65,36,6 Shumen9,520,913,323,93,14,7 Burgas9,68,612,716,61,2 Sliven11,915,926,238,33,113,7 Yambol8,24,612 044,94,94,1 Kardjali9,64,913,217,91,95,2 Plovdiv8,86,514,318,42,95,9 Kyustendil7,25,115,517,93,50,9 Sofia-capital./district.*8,9/7,5*4,7/7,3*6,920,1*1,6/4,0*2,0/3,5*

24. SORCA data: About 60 per cent of the registered fetus/children cases have been identified as isolated, probably multifactorial congenital anomalies About 60 per cent of the registered fetus/children cases have been identified as isolated, probably multifactorial congenital anomalies 40 per cent – with multiple congenital anomalies distributed as follows: 40 per cent – with multiple congenital anomalies distributed as follows: * chromosomal aberrations – 8 per cent * single gene disorders – 10 per cent, * purely environmental – 2 per cent and * multiple congenital anomalies of unknown etiology – 20 per cent The experience of the TIS in Jerusalem - reported 38000 calls for twelve years. Of them 75 per cent – due to exposure to drugs, 75 per cent – due to exposure to drugs, 9 per cent – to exposure to diagnostic irradiation, 9 per cent – to exposure to diagnostic irradiation, 6 per cent – suspected to have intrauterine infection, 6 per cent – suspected to have intrauterine infection, 5 per cent – due to vaccination and 5 per cent – due to vaccination and only 2 per cent following exposure to environmental pollutants only 2 per cent following exposure to environmental pollutants

25. OTIS fact sheets of the effects of environmental agents Summarize six categories of exposure: Summarize six categories of exposure: medications medications infections infections illicit substances illicit substances herbal products herbal products maternal medical conditions maternal medical conditions others others

26. Risk assessment of prenatal exposures requires knowledge about chemical structure chemical structure dosage dosage developmental stage at exposure developmental stage at exposure duration of exposure duration of exposure

27. Types of exposures Type of exposureDistribution, % Mental illness4 Environmental agent8 Radiation3 Occupational agents17 Herbal products4 Drugs of abuse6 Medications58 Source: www.otispregnancy.org

28. Distribution of the reproductive status Reproductive statusDistribution, % Pregnancy74 Paternal3 Preconception9 Breast feeding8 Not specified6 Source: www.otispregnancy.org www.otispregnancy.org

29. Epidemiological work in cities with high level of environmental pollution with dioxins (Chapaevsk) – higher frequency of newborn with congenital hydrocephaly with dioxins (Chapaevsk) – higher frequency of newborn with congenital hydrocephaly with PCBs (Serpukov) – 4.5 newborn with CA per 100 newborn with PCBs (Serpukov) – 4.5 newborn with CA per 100 newborn 2.2 newborn with CA per 100 newborn in the majority of other Russian cities 2.2 newborn with CA per 100 newborn in the majority of other Russian cities Source: Revich at al, 2000

30. Pesticides used in Bulgaria (in tons) in the period 2002 - 2004 Source: Annual Report, National office for Plant Defence, 2004, p. 45

31. The area of wine yards treated with herbicides (thousands ha) Source: Annual Report, National office for Plant Defence, 2004, p. 44

32. Expenses spent for permanent disposal of the pesticides unfit for use Source: Annual Report, National office for Plant Defence, 2004, p. 45

33. Systematic control of the appearance, dissemination, density and degree of invasion of the plant diseases, insects and weeds and their natural regulators. Systematic control of the appearance, dissemination, density and degree of invasion of the plant diseases, insects and weeds and their natural regulators. Localization of pests in the unplantet areas (locusts) Localization of pests in the unplantet areas (locusts) Determination the exact time of the pesticides application Determination the exact time of the pesticides application Use of more effective chemicals Use of more effective chemicals Control of their content in soil, water, plants and food Control of their content in soil, water, plants and food Strategy for reduction the hazardous impact of pesticides in Bulgaria

34. Executive Body – National Office for Plant Defense Responsibilities: Responsibilities: Biological testing of the Plant Defense Products (PDP) according Directive 91/414/EEC and Annex I for PDP and their active substances Biological testing of the Plant Defense Products (PDP) according Directive 91/414/EEC and Annex I for PDP and their active substances Official registration of PDP and their active substances Official registration of PDP and their active substances 54 of the included in Annex I 91 active substances are components of PDP, permitted in Bulgaria 54 of the included in Annex I 91 active substances are components of PDP, permitted in Bulgaria Control of the import of PDP Control of the import of PDP Control of PDP in the market network Control of PDP in the market network

35. Shortages Problems with the pesticides unfit for use Problems with the pesticides unfit for use * Deposited in ruined, unprotected stores * Deposited in ruined, unprotected stores * Illegal use of forbidden pesticides * Illegal use of forbidden pesticides * Trans-boundary pollution with pesticides * Trans-boundary pollution with pesticides Control is increasing but not regular and not enough Control is increasing but not regular and not enough It does not cover all regions of the country It does not cover all regions of the country

36. Measures Inventory in correspondence with Directive 67/548/EEC and Annex 5 for the recent available chemicals Inventory in correspondence with Directive 67/548/EEC and Annex 5 for the recent available chemicals 35 tons DDT from 6 stores are exterminated in the Netherlands 35 tons DDT from 6 stores are exterminated in the Netherlands Permanent disposal of the pesticides forbidden for use Permanent disposal of the pesticides forbidden for use

37. Conclusion Sofia Register of Congenital Anomalies (SORCA) emerged in 1996 in response to a growing need for current scientific information about the effects of drugs and other environmental agents on developing human embryo and fetus. Sofia Register of Congenital Anomalies (SORCA) emerged in 1996 in response to a growing need for current scientific information about the effects of drugs and other environmental agents on developing human embryo and fetus. 40 isolated congenital anomalies (CA) and congenital diseases have been detected out of 34124 pregnancies, registered in the period 1996 – 1999 in Sofia. 40 isolated congenital anomalies (CA) and congenital diseases have been detected out of 34124 pregnancies, registered in the period 1996 – 1999 in Sofia. In general, the incidence rates of CA in Sofia do not differ significantly from the average figures of EUROCAT (1996 – 2001). Prevalence of non-chromosomal congenital anomalies has been registered. In general, the incidence rates of CA in Sofia do not differ significantly from the average figures of EUROCAT (1996 – 2001). Prevalence of non-chromosomal congenital anomalies has been registered.

38. Conclusion Total chromosomal anomalies, registered in Sofia per 10000 pregnancies, are almost twice less than the registered by EUROCAT diseases. At the same time the age-specific fertility of Bulgarian women in 1998 – 2002 shows that the average age of mothers has increased. Total chromosomal anomalies, registered in Sofia per 10000 pregnancies, are almost twice less than the registered by EUROCAT diseases. At the same time the age-specific fertility of Bulgarian women in 1998 – 2002 shows that the average age of mothers has increased. In 2003 certain conditions, originating in the prenatal period (386/1000 live births) and congenital anomalies (259,8/1000 live births) could be ranked at the first two places between the causes of the infant deaths. In the period 1990 – 2003 trends of reduction are noticed for the both leading reasons for the infant mortality. In 2003 certain conditions, originating in the prenatal period (386/1000 live births) and congenital anomalies (259,8/1000 live births) could be ranked at the first two places between the causes of the infant deaths. In the period 1990 – 2003 trends of reduction are noticed for the both leading reasons for the infant mortality.

39. Conclusion About 2 per cent of the registered fetus/children cases have been identified to be with purely environmental etiology. About 2 per cent of the registered fetus/children cases have been identified to be with purely environmental etiology. In the well developed agricultural areas and highly industrialized regions in Bulgaria with production of big amount of energy the proportion of congenital anomalies and conditions, originating in the prenatal period as reasons for infant mortality exceed the averages for the country. In the well developed agricultural areas and highly industrialized regions in Bulgaria with production of big amount of energy the proportion of congenital anomalies and conditions, originating in the prenatal period as reasons for infant mortality exceed the averages for the country. Strategy for reduction the amount of the pesticides used for plant defence in Bulgaria is elaborated, which includes systematic control of the appearance, dissemination, density and the degree of invasion of the plant diseases, insects and weeds and their natural regulators and control on the PDP. Strategy for reduction the amount of the pesticides used for plant defence in Bulgaria is elaborated, which includes systematic control of the appearance, dissemination, density and the degree of invasion of the plant diseases, insects and weeds and their natural regulators and control on the PDP.