Int Arch Occup Environ Health (1992) 64: 59-64
internationalArchivesof
Oceupionlad
Environmental © Springer-Verlag 1992
Occupational risk factors for congenital heart disease Jorma Tikkanenl and Olli P Heinonen 2 'National Public Health Institute, Kalliolinnantie 4, SF-00140 Helsinki, Finland University of Helsinki and National Public Health Institute, Helsinki, Finland
2
Received November 4, 1991 / Accepted February 5, 1992
Summary To investigate possible associations between cardiovascular malformations and maternal occupational exposure to various factors during the first trimester of pregnancy, 406 cases and 756 controls were studied retrospectively The cases were taken from all infants diagnosed with cardiovascular malformations born in Finland during 1982 and 1983 The controls were randomly selected from all normal births in the country during the same period All mothers were interviewed approximately 3 months after delivery by a midwife, using a structured questionnaire Maternal overall exposure to chemicals at work was more prevalent among the case group ( 35 8%) than the control group ( 26 2%, P < 0 01) Among the specific chemical groups, maternal exposure to dyes, lacquers, or paints was significantly associated with the risk of congenital heart disease. Exposure to organic solvents during the first trimester seemed to increase to risk of ventricular septal defect (P < 0 05) Work at video display terminals was slightly more prevalent among the case group (6 3 %) than among the control group ( 5 0%) The mothers' education level, regular exposure to passive smoking at work, or temperature at the workplace were not risk factors for congenital heart disease in the offspring, neither was maternal exposure to microwave ovens, disinfectants, pesticides, or anesthetic gases It is concluded that many maternal exposures at work seem not to have a teratogenic effect on the fetal heart, although the limited power of this investigation needs to be borne in mind. OccupaKey words: Cardiovascular malformations tional exposure Chemical and physical factors
Introduction The birth prevalence of congenital heart disease is approximately 8-10 cases per 1000 births (Kenna et al. 1975 ; Bound and Logan 1977 ; Tikkanen 1986; Spooner et al 1988 ; Stoll et al 1989), so that about 1 3 million babies with congenital heart disease are born each year worldwide. Offprint requests to: J Tikkanen
In spite of intense research over recent years, the etiology of this common form of congenital anomaly remains almost unknown (Congenital Malformations Worldwide 1991) It has been estimated that known risk factors for congenital heart disease, such as chromosomal anomalies, maternal rubella infection, and alcohol consumption during the first trimester, explain only 10 % of cases (Tikkanen 1986). There is little reliable information on associations between the incidence of congenital heart disease and various occupational exposures, although many physical and chemical factors in the working environment have been suspected of damaging the fetal heart (Stoll et al 1989 ; Tikkanen 1986) According to a Finnish case-control study, maternal exposure to organic solvents at work during early pregnancy seemed to increase the risk of congenital heart disease in the offspring (Tikkanen and Heinonen 1988) Other case-control studies, which investigated the possible influence of maternal work exposure during early pregnancy to noise (Kurppa et al. 1989), video display terminals (Kurppa et al 1985), pesticides, disinfectants, and woodstains (Kurppa et al. 1983), failed to indicate any risk between these exposures and cardiovascular malformations Neither was maternal shift work or physical workload during pregnancy associated with a risk for congenital heart disease in the offspring (Nurminen 1989 ; Nurminen et al 1989). At present, many mothers are exposed at work to several chemical and physical factors (Schardein 1985) which, according to animal studies, may have a teratogenic effect on the developing fetal heart (Hemminki and Vineis 1985) For this reason, the Finnish National Board of Health decided in 1981 to investigate all possible causes of cardivascular malformation (Tikkanen 1986) The present report is part of this large project and deals with maternal exposures to occupational factors as possible risks for congenital heart disease in the offspring. Methods Cardiovascularmalformations Congenital heart disease was defined in this material as a structural abnormality of the heart or major intrathoracic vessels Ductus arteriosus was considered a
60 heart defect if still patent after the neonatal period (Tikkanen and Heinonen 1990). The infants included in the study were selected from 133000 offspring born in Finland during 1982-1983 Infants with cardiovascular malformation were identified independently from the Finnish Register of Congenital Malformations or the Children's Cardiac Register One-third (31 %) of the malformations were reported only to the former registry, one-third (34 %) only to the latter, and one-third (35 %) to both. In both registers, the cardiovascular anomaly, detected during the first year of life was diagnosed by echocardiography, cardiac catheterization, surgery, or autopsy Some 26 of the children were stillborn, and their diagnosis was based on the autopsy findings. Between 1 January 1982 and 31 December 1983, 492 infants with congenital heart disease were reported Twenty-three case children were excluded because the diagnosis of cardiovascular malformation was made solely on the basis of a clinical examination which had not been confirmed by cardiac catheterization, echocardiography, cardiac surgery, or autopsy. Sixty-three cases with a chromosomal anomaly (e g , Down's syndrome, trisomy 18, trisomy 13) or a known genetic or specific malformation syndrome, as well as cases with extracardiac anomalies, were also deleted from the study The exclusion of these children thus reduced the numbers from 492 to 406 cases, giving a total of 583 cardiovascular malformations Every cardiovascular anomaly was checked and coded by a pediatric cardiologist. Common cardiovascular malformations in these data were ventricular septal defect (VSD, N = 150), patent ductus arteriosus (PDA, N = 90), coarctation of the aorta (COA, N = 50), atrial septal defect (ASD, N = 50), transposition of the great arteries (TGA, N= 36), hypoplastic left ventricle (LHHS, N = 34), tetralogy of Fallot (TOF, N = 23), endocardial cushion defect (ECD, N= 22), and truncus arteriosus (TAC, N = 14). Rarer cardiovascular malformations included pulmonary atresia (n = 11), total anomalous pulmonary venous drainage (n = 9), pulmonary stenosis (valvular) (n = 5), aortic stenosis (n = 3), and tricuspid atresia (n = 2). These cardiovascular malformations were classified ontogenetically as follows: ventricular septal defect (VSD), conus arteriosus syndrome (CAS), atrial septal defect (ASD), hypoplastic left ventricle (LHHS), endocardial cushion defect (ECD), and other defects ( 0) CAS includes the following cardiac anomalies: TOF, TGA, TAC, double outlet right ventricle, aortopulmonic window, and pulmonic valve atresia The LHHS group consists of aortic and mitral valve atresia, mitral valve stenosis, and hypoplastic left heart The ECD group includes atrial septal defect (primum) and atrioventricular canal (Heinonen 1976; Tikkanen and Heinonen 1990). In 58 3% of these babies (n = 406), the diagnosis had been made during the first month of life, in 14 5% during the second month, and later in 27 2 % The mean age of the case group at the time of diagnosis was 62 5 days, with a range of 1-360 days (Tikkanen and Heinonen 1990). Controls Almost every birth (99 7%) in Finland takes place in 1 of the 52 hospitals The controls were randomly selected from all deliveries in Finland during 1982-1983 (approximately 133000) For each year, 400 nonmalformed infants were selected from the 52 hospitals on the basis of their frequency of deliveries in 1981 (Tikkanen and Heinonen 1990). Dates were chosen at random, and the first infant born on each date and free of anomaly in every organ was included in the study. Forty-four ( 5 5 %) of the mothers could not be contacted or refused to participate Thus, the final group consisted of 756 infants. Interview of the mother All the mothers were interviewed by midwives at maternity welfare centers using a structured and pretested questionnaire The mothers of affected infants were interviewed approximately 92 days (range 14 147), and those of normal infants 96 days (range 21-154), after delivery The interview lasted approximately 1 h.
In the first part of the interview, the mothers were asked about drug consumption during the first trimester of pregnancy First came general questions on their drug consumption, medications used in some common diseases, and those most frequently used during pregnancy in Finland General background variables, maternal occupational education, working conditions, and environmental exposures at work formed the second part of the interview. First, the mother was asked to describe her work during the first trimester of pregnancy Following a structured plan, the interviewer sought details of exposures to chemicals or physical factors at work. The following exposures were noted: organic solvents, dyes, lacquers or paints, mineral oil products, glues, plastic raw materials, wood preservatives, pesticides, anesthetic gases, disinfectants, dusts, microwave ovens, and video display terminals Data on the temperature at the workplace and the prevalence of passive smoking were also collected If the mother reported any exposure to specific physical or chemical factors, the interviewer noted the frequency of exposure (regular, occasional) Regular exposure was defined as one which occurred approximately every day Occasional exposure meant less frequently than that. The third part of the interview contained questions on some symptoms, illnesses, and selected habits of the mothers during the first trimester of pregnancy In this section, the mothers were asked details about maternal smoking, and coffee, tea, and alcohol consumption, etc , as well as use of deodorants and other chemicals in their leisure time. Statistical methods In cross-tabulation of the data, the X2 -test was used to test the hypothesis that maternal characteristics or exposures of affected infants somehow differed from those of normal ones (Armitage 1985).
Results Table 1 lists some maternal characteristics and exposure at work during the first trimester No marked differences were found between case and control mothers in residential area or education level Working during preg-
Table 1 Some maternal occupational characteristics and exposures at work during the first trimester Maternal chracteristic or exposure
Cases
Controls
(n = 406)
(n = 755)
(%)
(%)
43 3 25 5 31 2
41 2 24 3 34 5
17 33 0 39 6 59
15 32 3 37 1 73
13 9 59
16 3 55
73 8
67 0
Regular exposure to passive smoking at work 14 0 Temperature at workplace > 20 °C 25 0
14 1 23 0
Residential area Rural area Town, < 50000 inhabitants Town, > 50000 inhabitants Level of education No basic school Basic school Occupational school High school graduate High school graduate plus another qualification Academic grade Employed during pregnancy
No significant differences between cases and controls, except proportion employed during pregnancy, where P < 0 05 ( 2-test)
61 Table 2 Maternal overall exposure to chemicals at work during the first trimester of pregnancy Exposure
Yes No Not at work
VSD (n = 150)
CAS (n = 90)
ASD (n = 50)
LHHS (n = 34)
ECD (n = 22)
Other (n = 237)
Controls (n = 756)
(%)
(%)
(%)
(%)
(%)
(%)
(%)
34 7 42 0 23 3
43 3 32 3 24 4
40 0 32 0 28 0
47 1 35 3 17 6
40 9 31 8 27 3
34 6 35 4 30 0
26 2 40 8 33 0
Statistical significance between cases and controls: (P, X2 -test)
internationalArchivesof
Oceupionlad
Environmental © Springer-Verlag 1992
Occupational risk factors for congenital heart disease Jorma Tikkanenl and Olli P Heinonen 2 'National Public Health Institute, Kalliolinnantie 4, SF-00140 Helsinki, Finland University of Helsinki and National Public Health Institute, Helsinki, Finland
2
Received November 4, 1991 / Accepted February 5, 1992
Summary To investigate possible associations between cardiovascular malformations and maternal occupational exposure to various factors during the first trimester of pregnancy, 406 cases and 756 controls were studied retrospectively The cases were taken from all infants diagnosed with cardiovascular malformations born in Finland during 1982 and 1983 The controls were randomly selected from all normal births in the country during the same period All mothers were interviewed approximately 3 months after delivery by a midwife, using a structured questionnaire Maternal overall exposure to chemicals at work was more prevalent among the case group ( 35 8%) than the control group ( 26 2%, P < 0 01) Among the specific chemical groups, maternal exposure to dyes, lacquers, or paints was significantly associated with the risk of congenital heart disease. Exposure to organic solvents during the first trimester seemed to increase to risk of ventricular septal defect (P < 0 05) Work at video display terminals was slightly more prevalent among the case group (6 3 %) than among the control group ( 5 0%) The mothers' education level, regular exposure to passive smoking at work, or temperature at the workplace were not risk factors for congenital heart disease in the offspring, neither was maternal exposure to microwave ovens, disinfectants, pesticides, or anesthetic gases It is concluded that many maternal exposures at work seem not to have a teratogenic effect on the fetal heart, although the limited power of this investigation needs to be borne in mind. OccupaKey words: Cardiovascular malformations tional exposure Chemical and physical factors
Introduction The birth prevalence of congenital heart disease is approximately 8-10 cases per 1000 births (Kenna et al. 1975 ; Bound and Logan 1977 ; Tikkanen 1986; Spooner et al 1988 ; Stoll et al 1989), so that about 1 3 million babies with congenital heart disease are born each year worldwide. Offprint requests to: J Tikkanen
In spite of intense research over recent years, the etiology of this common form of congenital anomaly remains almost unknown (Congenital Malformations Worldwide 1991) It has been estimated that known risk factors for congenital heart disease, such as chromosomal anomalies, maternal rubella infection, and alcohol consumption during the first trimester, explain only 10 % of cases (Tikkanen 1986). There is little reliable information on associations between the incidence of congenital heart disease and various occupational exposures, although many physical and chemical factors in the working environment have been suspected of damaging the fetal heart (Stoll et al 1989 ; Tikkanen 1986) According to a Finnish case-control study, maternal exposure to organic solvents at work during early pregnancy seemed to increase the risk of congenital heart disease in the offspring (Tikkanen and Heinonen 1988) Other case-control studies, which investigated the possible influence of maternal work exposure during early pregnancy to noise (Kurppa et al. 1989), video display terminals (Kurppa et al 1985), pesticides, disinfectants, and woodstains (Kurppa et al. 1983), failed to indicate any risk between these exposures and cardiovascular malformations Neither was maternal shift work or physical workload during pregnancy associated with a risk for congenital heart disease in the offspring (Nurminen 1989 ; Nurminen et al 1989). At present, many mothers are exposed at work to several chemical and physical factors (Schardein 1985) which, according to animal studies, may have a teratogenic effect on the developing fetal heart (Hemminki and Vineis 1985) For this reason, the Finnish National Board of Health decided in 1981 to investigate all possible causes of cardivascular malformation (Tikkanen 1986) The present report is part of this large project and deals with maternal exposures to occupational factors as possible risks for congenital heart disease in the offspring. Methods Cardiovascularmalformations Congenital heart disease was defined in this material as a structural abnormality of the heart or major intrathoracic vessels Ductus arteriosus was considered a
60 heart defect if still patent after the neonatal period (Tikkanen and Heinonen 1990). The infants included in the study were selected from 133000 offspring born in Finland during 1982-1983 Infants with cardiovascular malformation were identified independently from the Finnish Register of Congenital Malformations or the Children's Cardiac Register One-third (31 %) of the malformations were reported only to the former registry, one-third (34 %) only to the latter, and one-third (35 %) to both. In both registers, the cardiovascular anomaly, detected during the first year of life was diagnosed by echocardiography, cardiac catheterization, surgery, or autopsy Some 26 of the children were stillborn, and their diagnosis was based on the autopsy findings. Between 1 January 1982 and 31 December 1983, 492 infants with congenital heart disease were reported Twenty-three case children were excluded because the diagnosis of cardiovascular malformation was made solely on the basis of a clinical examination which had not been confirmed by cardiac catheterization, echocardiography, cardiac surgery, or autopsy. Sixty-three cases with a chromosomal anomaly (e g , Down's syndrome, trisomy 18, trisomy 13) or a known genetic or specific malformation syndrome, as well as cases with extracardiac anomalies, were also deleted from the study The exclusion of these children thus reduced the numbers from 492 to 406 cases, giving a total of 583 cardiovascular malformations Every cardiovascular anomaly was checked and coded by a pediatric cardiologist. Common cardiovascular malformations in these data were ventricular septal defect (VSD, N = 150), patent ductus arteriosus (PDA, N = 90), coarctation of the aorta (COA, N = 50), atrial septal defect (ASD, N = 50), transposition of the great arteries (TGA, N= 36), hypoplastic left ventricle (LHHS, N = 34), tetralogy of Fallot (TOF, N = 23), endocardial cushion defect (ECD, N= 22), and truncus arteriosus (TAC, N = 14). Rarer cardiovascular malformations included pulmonary atresia (n = 11), total anomalous pulmonary venous drainage (n = 9), pulmonary stenosis (valvular) (n = 5), aortic stenosis (n = 3), and tricuspid atresia (n = 2). These cardiovascular malformations were classified ontogenetically as follows: ventricular septal defect (VSD), conus arteriosus syndrome (CAS), atrial septal defect (ASD), hypoplastic left ventricle (LHHS), endocardial cushion defect (ECD), and other defects ( 0) CAS includes the following cardiac anomalies: TOF, TGA, TAC, double outlet right ventricle, aortopulmonic window, and pulmonic valve atresia The LHHS group consists of aortic and mitral valve atresia, mitral valve stenosis, and hypoplastic left heart The ECD group includes atrial septal defect (primum) and atrioventricular canal (Heinonen 1976; Tikkanen and Heinonen 1990). In 58 3% of these babies (n = 406), the diagnosis had been made during the first month of life, in 14 5% during the second month, and later in 27 2 % The mean age of the case group at the time of diagnosis was 62 5 days, with a range of 1-360 days (Tikkanen and Heinonen 1990). Controls Almost every birth (99 7%) in Finland takes place in 1 of the 52 hospitals The controls were randomly selected from all deliveries in Finland during 1982-1983 (approximately 133000) For each year, 400 nonmalformed infants were selected from the 52 hospitals on the basis of their frequency of deliveries in 1981 (Tikkanen and Heinonen 1990). Dates were chosen at random, and the first infant born on each date and free of anomaly in every organ was included in the study. Forty-four ( 5 5 %) of the mothers could not be contacted or refused to participate Thus, the final group consisted of 756 infants. Interview of the mother All the mothers were interviewed by midwives at maternity welfare centers using a structured and pretested questionnaire The mothers of affected infants were interviewed approximately 92 days (range 14 147), and those of normal infants 96 days (range 21-154), after delivery The interview lasted approximately 1 h.
In the first part of the interview, the mothers were asked about drug consumption during the first trimester of pregnancy First came general questions on their drug consumption, medications used in some common diseases, and those most frequently used during pregnancy in Finland General background variables, maternal occupational education, working conditions, and environmental exposures at work formed the second part of the interview. First, the mother was asked to describe her work during the first trimester of pregnancy Following a structured plan, the interviewer sought details of exposures to chemicals or physical factors at work. The following exposures were noted: organic solvents, dyes, lacquers or paints, mineral oil products, glues, plastic raw materials, wood preservatives, pesticides, anesthetic gases, disinfectants, dusts, microwave ovens, and video display terminals Data on the temperature at the workplace and the prevalence of passive smoking were also collected If the mother reported any exposure to specific physical or chemical factors, the interviewer noted the frequency of exposure (regular, occasional) Regular exposure was defined as one which occurred approximately every day Occasional exposure meant less frequently than that. The third part of the interview contained questions on some symptoms, illnesses, and selected habits of the mothers during the first trimester of pregnancy In this section, the mothers were asked details about maternal smoking, and coffee, tea, and alcohol consumption, etc , as well as use of deodorants and other chemicals in their leisure time. Statistical methods In cross-tabulation of the data, the X2 -test was used to test the hypothesis that maternal characteristics or exposures of affected infants somehow differed from those of normal ones (Armitage 1985).
Results Table 1 lists some maternal characteristics and exposure at work during the first trimester No marked differences were found between case and control mothers in residential area or education level Working during preg-
Table 1 Some maternal occupational characteristics and exposures at work during the first trimester Maternal chracteristic or exposure
Cases
Controls
(n = 406)
(n = 755)
(%)
(%)
43 3 25 5 31 2
41 2 24 3 34 5
17 33 0 39 6 59
15 32 3 37 1 73
13 9 59
16 3 55
73 8
67 0
Regular exposure to passive smoking at work 14 0 Temperature at workplace > 20 °C 25 0
14 1 23 0
Residential area Rural area Town, < 50000 inhabitants Town, > 50000 inhabitants Level of education No basic school Basic school Occupational school High school graduate High school graduate plus another qualification Academic grade Employed during pregnancy
No significant differences between cases and controls, except proportion employed during pregnancy, where P < 0 05 ( 2-test)
61 Table 2 Maternal overall exposure to chemicals at work during the first trimester of pregnancy Exposure
Yes No Not at work
VSD (n = 150)
CAS (n = 90)
ASD (n = 50)
LHHS (n = 34)
ECD (n = 22)
Other (n = 237)
Controls (n = 756)
(%)
(%)
(%)
(%)
(%)
(%)
(%)
34 7 42 0 23 3
43 3 32 3 24 4
40 0 32 0 28 0
47 1 35 3 17 6
40 9 31 8 27 3
34 6 35 4 30 0
26 2 40 8 33 0
Statistical significance between cases and controls: (P, X2 -test)
