G Model IJHEH-12772; No. of Pages 6
ARTICLE IN PRESS International Journal of Hygiene and Environmental Health xxx (2014) xxx–xxx
Contents lists available at ScienceDirect
International Journal of Hygiene and Environmental Health journal homepage: www.elsevier.com/locate/ijheh
Arsenic in drinking water and congenital heart anomalies in Hungary Tamás Rudnai a,∗ , János Sándor b , Mihály Kádár a , Mátyás Borsányi a , Judit Béres c , Júlia Métneki c , Gabriella Maráczi d , Péter Rudnai a a
National Institute of Environmental Health, Budapest, Hungary University of Debrecen, Institute of Preventive Medicine, Debrecen, Hungary National Institute for Health Development, Budapest, Hungary d Békés County Public Health Institute, Békéscsaba, Hungary b c
a r t i c l e
i n f o
Article history: Received 7 December 2013 Received in revised form 13 May 2014 Accepted 15 May 2014 Keywords: Arsenic Birth defects Congenital heart anomalies Drinking water Teratogenicity
a b s t r a c t Inorganic arsenic can get easily through the placenta however there are very few human data on congenital anomalies related to arsenic exposure. Objective of our study was to explore the associations between arsenic content of drinking water and prevalence of some congenital anomalies. Four anomalies reported to the Hungarian Congenital Anomalies Registry between 1987 and 2003 were chosen to be analysed in relation to arsenic exposure: congenital anomalies of the circulatory system (n = 9734) were considered as cases, while Down syndrome, club foot and multiple congenital malformations were used as controls (n = 5880). Arsenic exposure of the mothers during pregnancy was estimated by using archive measurement data for each year and for each settlement where the mothers lived. Analysis of the associations between the prevalence of congenital heart anomalies and arsenic exposure during pregnancy was performed by logistic regression. The child’s gender and age of the mother were adjusted for. The associations were evaluated by using the present EU health limit value of 10.0 g/L arsenic concentration as a cut-off point. Regular consumption of drinking water with arsenic concentration above 10 g/L during pregnancy was associated with an increased risk of congenital heart anomalies in general (adjusted OR = 1.41; 95% C.I.: 1.28–1.56), and especially that of ductus Botalli persistens (adjusted OR = 1.81, 95%C.I.: 1.54–2.11) and atrial septal defect (adjusted OR = 1.79; 95%C.I.: 1.59–2.01). The presented results showed an increased risk of congenital heart anomalies among infants whose mothers were exposed to drinking water with arsenic content above 10 g/L during pregnancy. Further studies of possible similar effects of concentrations below 10 g/L are warranted. © 2014 Elsevier GmbH. All rights reserved.
Introduction More than one hundred million people worldwide are at risk of elevated arsenic exposure (Vahter, 2009). Hungary has also been struggling with the health risks of high arsenic level in the drinking water for the last decades. (Csanády et al., 1985; Leonardi et al., 2012; Rudnai et al., 2013) It has been widely accepted that arsenic exposure via drinking water is associated with excess risk of skin, lung, bladder and kidney cancer. According to data from animal experiments inorganic arsenic can easily get through the placenta and cause serious teratogenic effects.
∗ Corresponding author at: National Institute of Environmental Health, Albert Flórián út 2-6, Budapest H-1097, Hungary. Tel.: +36 1 476 1282; fax: +36 1 215 2046. E-mail address: [email protected] (T. Rudnai).
Inorganic arsenic proved to be teratogenic in mice (Baxley et al., 1981; Morrissey and Mottet, 1983; Nagymajtényi et al., 1985; Wlodarczyk et al., 1996), rats (Beaudoin, 1974) and hamsters (Carpenter, 1987; Ferm and Hanlon, 1985; Hood and Harrison, 1982; Willhite, 1981) following oral, parenteral or inhalational exposure. Congenital disorders varied depending on the arsenic dosage and gestation period. The major teratogenic effects induced by inorganic arsenic observed in animal experiments were neural tube defects and similar disorders of the cephalic neural folds. The minor disorders that could be observed due to arsenic exposure were fused ribs, renal agenesis, micromelia, facial malformations, twisted hindlimb, anophthalmia and microphthalmia (WHO, 2001) Human placental transfer of arsenic was indicated by increased frequency of spontaneous abortion, still birth and perinatal death among those exposed to drinking water with high arsenic level during pregnancy (Ahmad et al., 2001; ATSDR, 2007; Bloom et al., 2010; Börzsönyi et al., 1992; Hopenhayn-Rich et al., 1999; Milton et al.,
http://dx.doi.org/10.1016/j.ijheh.2014.05.002 1438-4639/© 2014 Elsevier GmbH. All rights reserved.
Please cite this article in press as: Rudnai, T., et al., Arsenic in drinking water and congenital heart anomalies in Hungary. Int. J. Hyg. Environ. Health (2014), http://dx.doi.org/10.1016/j.ijheh.2014.05.002
G Model IJHEH-12772; No. of Pages 6
ARTICLE IN PRESS T. Rudnai et al. / International Journal of Hygiene and Environmental Health xxx (2014) xxx–xxx
1082 26,9 (± 5.6)
n 1272 1039
458 26.9 (± 6.0)
% 48.1 51.9 803 27.2 (± 5.6) 1784 27.1 (± 5.7) 2560 26.6 (± 5.6)
Pulmonary artery anomalies
n 426 460 % 48.3 51.7
Ductus Botalli persistens
n 665 713 % 45.7 54.3
More than one anomaly per child is possible.
4180 27.7 (± 6.6)
n 3271 2328
Gender Male Female Mother’s age n Mean (± s.d.)
a
5531 26.8 (± 5.6)
n 4744 4942
Controls Variables
In the frame of the National Database of Drinking Water Quality, arsenic measurements were started from 1981 first by a semi-quantitative screening method and later by systematic measurement programmes using samples taken simultaneously by the local public health institutions at several points of the settlements and determined in 12 centrally controlled laboratories (Csanády et al., 1985). Step by step, more and more settlements were covered by arsenic measurement results. Some waterworks using deep well waters with high arsenic content started to implement drinking water quality improvement programmes from 1986 on, therefore water quality in settlements of their distribution system changed in the course of time and was repeatedly sampled. However, these results were stored in several locations, mostly on paper files.
Table 1 Characteristics of the study population.
Exposure estimation
% 58.4 41.6
Casesa
% 49.0 51.0
Ventricular septal defect
Atrial septal defect
The Hungarian Congenital Abnormality Registry was established as the first country-wide registry in the world in 1962. (Métneki et al., 2013). Since then it has been collecting and evaluating the data and reports in the whole country on congenital anomalies of newborn babies and infants observed during the first year of life either by the obstetricians or the paediatricians. We used a part of this database covering a period of 17 years between 1987 and 2003. Out of the registered congenital disorders we chose four anomalies to be analysed in relation to arsenic exposure: congenital anomalies of the circulatory system (International Classification of Diseases, ICD-10 codes: Q20.0–Q28.9) were considered as cases (n = 9734), while Down syndrome (trisomia, Q90.0–Q90.9), club foot (talipes equinovarus, Q66.0) and multiple congenital malformations (Q89.7) were used as controls (n = 5880). As most of the congenital disorders of the circulatory system relate to the heart, for practical reasons we use “congenital heart anomalies (CHA)” in this sense. In order to eliminate any disturbing “noise”, data of children with overlapping both case and control diagnoses (especially Down syndrome and multiple congenital malformations) were transformed to “missing”. The following pieces of information were also taken into consideration: the child’s gender, year of birth, the mother’s year of birth, place of living, postal code and further diagnoses (up to 10). Unfortunately, information on gender of the child was missing in 48 cases (0.5%) and 281 controls (4.8%) and age of the mother in 42.9% of the cases and 25.3% of the controls (Table 1).
n 1245 1480
Studied health outcomes
% 46.6 53.4
Methods
n 1959 2249
Other anomalies
% 55.0 45.0
2005; Rahman et al., 2007; Rudnai et al., 2006, 2013; von Ehrenstein et al., 2006). Very few studies have been published, however, with findings on possible associations between arsenic content of drinking water and congenital anomalies in humans (Dorsch et al., 1984; Engel and Smith, 1994; Kwok et al., 2006; Nordström et al., 1979; Orr et al., 2002; Wu et al., 2011; Zierler et al., 1988). Out of the mentioned ones only two papers reported about increased risk of congenital heart anomalies (Engel and Smith, 1994; Zierler et al., 1988) in areas supplied with drinking water with high arsenic content though the reported levels of arsenic were not unequivocal. Heart anomalies are the second most frequent congenital defects in Hungary (Susánszky and Czeizel, 1989). The database of the Hungarian Congenital Abnormality Registry (HCAR) and the archive measurement results of arsenic concentrations of drinking water in settlements all over Hungary provided a unique opportunity to study the associations between the prevalence of congenital heart anomalies (CHA) and the arsenic level of drinking water supplied to the settlements where the mothers lived during pregnancy.
Total
2
Please cite this article in press as: Rudnai, T., et al., Arsenic in drinking water and congenital heart anomalies in Hungary. Int. J. Hyg. Environ. Health (2014), http://dx.doi.org/10.1016/j.ijheh.2014.05.002
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3
Fig. 1. Arsenic levels of dinking water in the settlements of hungary, 1997–1999.
We collected all available information from different sources in order to estimate the arsenic content of the drinking water of the relevant settlements, mainly individual measurement results and data collected by the Water Hygiene Department of the National Institute of Environmental Health throughout the years and also a country-wide survey conducted in the frame of the National Environmental Health Action Programme (NEHAP) between 1997–99. (Fig. 1.) As measured arsenic concentrations were not available for each year for each settlement, missing values were replaced by values extrapolated based on the closest previous measurement data. We hypothesised that in case the drinking water supply was constant and no change in the supplying wells or any intervention occurred, no change was expected in the arsenic concentration, at least as far as the arsenic categories are concerned. This way, we set up a priori a working table with all the examined 2412 settlements (76.5% of all settlements in Hungary) characterised by categories of arsenic content of the drinking water for each year between 1987 and 2003. We used the following exposure categories: 0–10.0 g/L, 10.1–20.0 g/L, 20.1–30.0 g/L, 30.1–40.0 g/L, 40.1–50.0 g/L and >50.0 g/L. Distribution of the studied congenital anomalies by arsenic categories is illustrated in Fig. 2.
Fig. 2. Distribution of the studied congenital anomalies by arsenic categories.
Statistical analysis Analysis of the associations between the prevalence of CHA and the exposure by arsenic categories during pregnancy was performed by logistic regression using STATA/SE 10.0 statistical programme. The child’s gender and age of the mother at the time of birth (by categories of 38 years) were adjusted for. Taking also the present EU health limit value of 10 g/L into consideration, the associations were evaluated by using a cutoff point of 10.0 g/L arsenic concentration. Results Table 1 presents the characteristics of the study population. As far as overall congenital anomalies of the circulatory system are concerned there was no significant difference between the genders but in the two most frequent types of CHA female dominance could be observed. In the control group there was a male dominance reflecting the gender distribution of both club foot and multiple congenital malformations. Table 2 shows the raw and the adjusted associations between arsenic concentrations of drinking water and the prevalence of CHA by exposure categories. Compared to the lowest level of exposure (0–10 g/L) all unadjusted categories up to 50 g/L showed increased risks of congenital heart malformations. After adjustment to the child’s gender and the mother’s age the Odds Ratios kept on indicating increased risk of congenital heart anomalies up to 50 g/L arsenic concentration, in most cases in a statistically significant way. Above 50 g/L no increased risk was observed. Table 3 shows the associations between prevalence of congenital anomalies and the variables used for adjustment. The unadjusted odds ratios are the results of a simple and the adjusted ones a multiple logistic regression analysis. Compared to the controls, girls were found at significantly higher risk of CHA than boys and mothers of age between 22 and 38 years were more likely to have babies born with CHA than those in the younger or older age groups.
Please cite this article in press as: Rudnai, T., et al., Arsenic in drinking water and congenital heart anomalies in Hungary. Int. J. Hyg. Environ. Health (2014), http://dx.doi.org/10.1016/j.ijheh.2014.05.002
G Model
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T. Rudnai et al. / International Journal of Hygiene and Environmental Health xxx (2014) xxx–xxx
4
Table 2 Associations between arsenic concentrations of the supplied drinking water during pregnancy and prevalence of congenital heart anomalies. As conc. (g/L)
0–10.0 10.1–20.0 20.1–30.0 30.1–40.0 40.1–50.0 >50 a
Adjusteda
Unadjusted Cases
Controls
OR (95% C.I.)
7605 1308 367 202 121 131
4845 602 178 109 57 89
1.00 1.38 (1.25–1.53) 1.31 (1.09–1.58) 1.18 (0.93–1.49) 1.35 (0.99–1.86) 0.94 (0.72–1.23)
P value
Cases
Controls
OR (95% C.I.)
P value
10 g/L
Adjusted
OR (95% C.I.)
P value
OR (95% C.I.)
P value
1.46 (1.37–1.56) 0.91 (0.82–1.01) 0.41 (0.34–0.49) 1.31 (1.21–1.42)
ARTICLE IN PRESS International Journal of Hygiene and Environmental Health xxx (2014) xxx–xxx
Contents lists available at ScienceDirect
International Journal of Hygiene and Environmental Health journal homepage: www.elsevier.com/locate/ijheh
Arsenic in drinking water and congenital heart anomalies in Hungary Tamás Rudnai a,∗ , János Sándor b , Mihály Kádár a , Mátyás Borsányi a , Judit Béres c , Júlia Métneki c , Gabriella Maráczi d , Péter Rudnai a a
National Institute of Environmental Health, Budapest, Hungary University of Debrecen, Institute of Preventive Medicine, Debrecen, Hungary National Institute for Health Development, Budapest, Hungary d Békés County Public Health Institute, Békéscsaba, Hungary b c
a r t i c l e
i n f o
Article history: Received 7 December 2013 Received in revised form 13 May 2014 Accepted 15 May 2014 Keywords: Arsenic Birth defects Congenital heart anomalies Drinking water Teratogenicity
a b s t r a c t Inorganic arsenic can get easily through the placenta however there are very few human data on congenital anomalies related to arsenic exposure. Objective of our study was to explore the associations between arsenic content of drinking water and prevalence of some congenital anomalies. Four anomalies reported to the Hungarian Congenital Anomalies Registry between 1987 and 2003 were chosen to be analysed in relation to arsenic exposure: congenital anomalies of the circulatory system (n = 9734) were considered as cases, while Down syndrome, club foot and multiple congenital malformations were used as controls (n = 5880). Arsenic exposure of the mothers during pregnancy was estimated by using archive measurement data for each year and for each settlement where the mothers lived. Analysis of the associations between the prevalence of congenital heart anomalies and arsenic exposure during pregnancy was performed by logistic regression. The child’s gender and age of the mother were adjusted for. The associations were evaluated by using the present EU health limit value of 10.0 g/L arsenic concentration as a cut-off point. Regular consumption of drinking water with arsenic concentration above 10 g/L during pregnancy was associated with an increased risk of congenital heart anomalies in general (adjusted OR = 1.41; 95% C.I.: 1.28–1.56), and especially that of ductus Botalli persistens (adjusted OR = 1.81, 95%C.I.: 1.54–2.11) and atrial septal defect (adjusted OR = 1.79; 95%C.I.: 1.59–2.01). The presented results showed an increased risk of congenital heart anomalies among infants whose mothers were exposed to drinking water with arsenic content above 10 g/L during pregnancy. Further studies of possible similar effects of concentrations below 10 g/L are warranted. © 2014 Elsevier GmbH. All rights reserved.
Introduction More than one hundred million people worldwide are at risk of elevated arsenic exposure (Vahter, 2009). Hungary has also been struggling with the health risks of high arsenic level in the drinking water for the last decades. (Csanády et al., 1985; Leonardi et al., 2012; Rudnai et al., 2013) It has been widely accepted that arsenic exposure via drinking water is associated with excess risk of skin, lung, bladder and kidney cancer. According to data from animal experiments inorganic arsenic can easily get through the placenta and cause serious teratogenic effects.
∗ Corresponding author at: National Institute of Environmental Health, Albert Flórián út 2-6, Budapest H-1097, Hungary. Tel.: +36 1 476 1282; fax: +36 1 215 2046. E-mail address: [email protected] (T. Rudnai).
Inorganic arsenic proved to be teratogenic in mice (Baxley et al., 1981; Morrissey and Mottet, 1983; Nagymajtényi et al., 1985; Wlodarczyk et al., 1996), rats (Beaudoin, 1974) and hamsters (Carpenter, 1987; Ferm and Hanlon, 1985; Hood and Harrison, 1982; Willhite, 1981) following oral, parenteral or inhalational exposure. Congenital disorders varied depending on the arsenic dosage and gestation period. The major teratogenic effects induced by inorganic arsenic observed in animal experiments were neural tube defects and similar disorders of the cephalic neural folds. The minor disorders that could be observed due to arsenic exposure were fused ribs, renal agenesis, micromelia, facial malformations, twisted hindlimb, anophthalmia and microphthalmia (WHO, 2001) Human placental transfer of arsenic was indicated by increased frequency of spontaneous abortion, still birth and perinatal death among those exposed to drinking water with high arsenic level during pregnancy (Ahmad et al., 2001; ATSDR, 2007; Bloom et al., 2010; Börzsönyi et al., 1992; Hopenhayn-Rich et al., 1999; Milton et al.,
http://dx.doi.org/10.1016/j.ijheh.2014.05.002 1438-4639/© 2014 Elsevier GmbH. All rights reserved.
Please cite this article in press as: Rudnai, T., et al., Arsenic in drinking water and congenital heart anomalies in Hungary. Int. J. Hyg. Environ. Health (2014), http://dx.doi.org/10.1016/j.ijheh.2014.05.002
G Model IJHEH-12772; No. of Pages 6
ARTICLE IN PRESS T. Rudnai et al. / International Journal of Hygiene and Environmental Health xxx (2014) xxx–xxx
1082 26,9 (± 5.6)
n 1272 1039
458 26.9 (± 6.0)
% 48.1 51.9 803 27.2 (± 5.6) 1784 27.1 (± 5.7) 2560 26.6 (± 5.6)
Pulmonary artery anomalies
n 426 460 % 48.3 51.7
Ductus Botalli persistens
n 665 713 % 45.7 54.3
More than one anomaly per child is possible.
4180 27.7 (± 6.6)
n 3271 2328
Gender Male Female Mother’s age n Mean (± s.d.)
a
5531 26.8 (± 5.6)
n 4744 4942
Controls Variables
In the frame of the National Database of Drinking Water Quality, arsenic measurements were started from 1981 first by a semi-quantitative screening method and later by systematic measurement programmes using samples taken simultaneously by the local public health institutions at several points of the settlements and determined in 12 centrally controlled laboratories (Csanády et al., 1985). Step by step, more and more settlements were covered by arsenic measurement results. Some waterworks using deep well waters with high arsenic content started to implement drinking water quality improvement programmes from 1986 on, therefore water quality in settlements of their distribution system changed in the course of time and was repeatedly sampled. However, these results were stored in several locations, mostly on paper files.
Table 1 Characteristics of the study population.
Exposure estimation
% 58.4 41.6
Casesa
% 49.0 51.0
Ventricular septal defect
Atrial septal defect
The Hungarian Congenital Abnormality Registry was established as the first country-wide registry in the world in 1962. (Métneki et al., 2013). Since then it has been collecting and evaluating the data and reports in the whole country on congenital anomalies of newborn babies and infants observed during the first year of life either by the obstetricians or the paediatricians. We used a part of this database covering a period of 17 years between 1987 and 2003. Out of the registered congenital disorders we chose four anomalies to be analysed in relation to arsenic exposure: congenital anomalies of the circulatory system (International Classification of Diseases, ICD-10 codes: Q20.0–Q28.9) were considered as cases (n = 9734), while Down syndrome (trisomia, Q90.0–Q90.9), club foot (talipes equinovarus, Q66.0) and multiple congenital malformations (Q89.7) were used as controls (n = 5880). As most of the congenital disorders of the circulatory system relate to the heart, for practical reasons we use “congenital heart anomalies (CHA)” in this sense. In order to eliminate any disturbing “noise”, data of children with overlapping both case and control diagnoses (especially Down syndrome and multiple congenital malformations) were transformed to “missing”. The following pieces of information were also taken into consideration: the child’s gender, year of birth, the mother’s year of birth, place of living, postal code and further diagnoses (up to 10). Unfortunately, information on gender of the child was missing in 48 cases (0.5%) and 281 controls (4.8%) and age of the mother in 42.9% of the cases and 25.3% of the controls (Table 1).
n 1245 1480
Studied health outcomes
% 46.6 53.4
Methods
n 1959 2249
Other anomalies
% 55.0 45.0
2005; Rahman et al., 2007; Rudnai et al., 2006, 2013; von Ehrenstein et al., 2006). Very few studies have been published, however, with findings on possible associations between arsenic content of drinking water and congenital anomalies in humans (Dorsch et al., 1984; Engel and Smith, 1994; Kwok et al., 2006; Nordström et al., 1979; Orr et al., 2002; Wu et al., 2011; Zierler et al., 1988). Out of the mentioned ones only two papers reported about increased risk of congenital heart anomalies (Engel and Smith, 1994; Zierler et al., 1988) in areas supplied with drinking water with high arsenic content though the reported levels of arsenic were not unequivocal. Heart anomalies are the second most frequent congenital defects in Hungary (Susánszky and Czeizel, 1989). The database of the Hungarian Congenital Abnormality Registry (HCAR) and the archive measurement results of arsenic concentrations of drinking water in settlements all over Hungary provided a unique opportunity to study the associations between the prevalence of congenital heart anomalies (CHA) and the arsenic level of drinking water supplied to the settlements where the mothers lived during pregnancy.
Total
2
Please cite this article in press as: Rudnai, T., et al., Arsenic in drinking water and congenital heart anomalies in Hungary. Int. J. Hyg. Environ. Health (2014), http://dx.doi.org/10.1016/j.ijheh.2014.05.002
G Model IJHEH-12772; No. of Pages 6
ARTICLE IN PRESS T. Rudnai et al. / International Journal of Hygiene and Environmental Health xxx (2014) xxx–xxx
3
Fig. 1. Arsenic levels of dinking water in the settlements of hungary, 1997–1999.
We collected all available information from different sources in order to estimate the arsenic content of the drinking water of the relevant settlements, mainly individual measurement results and data collected by the Water Hygiene Department of the National Institute of Environmental Health throughout the years and also a country-wide survey conducted in the frame of the National Environmental Health Action Programme (NEHAP) between 1997–99. (Fig. 1.) As measured arsenic concentrations were not available for each year for each settlement, missing values were replaced by values extrapolated based on the closest previous measurement data. We hypothesised that in case the drinking water supply was constant and no change in the supplying wells or any intervention occurred, no change was expected in the arsenic concentration, at least as far as the arsenic categories are concerned. This way, we set up a priori a working table with all the examined 2412 settlements (76.5% of all settlements in Hungary) characterised by categories of arsenic content of the drinking water for each year between 1987 and 2003. We used the following exposure categories: 0–10.0 g/L, 10.1–20.0 g/L, 20.1–30.0 g/L, 30.1–40.0 g/L, 40.1–50.0 g/L and >50.0 g/L. Distribution of the studied congenital anomalies by arsenic categories is illustrated in Fig. 2.
Fig. 2. Distribution of the studied congenital anomalies by arsenic categories.
Statistical analysis Analysis of the associations between the prevalence of CHA and the exposure by arsenic categories during pregnancy was performed by logistic regression using STATA/SE 10.0 statistical programme. The child’s gender and age of the mother at the time of birth (by categories of 38 years) were adjusted for. Taking also the present EU health limit value of 10 g/L into consideration, the associations were evaluated by using a cutoff point of 10.0 g/L arsenic concentration. Results Table 1 presents the characteristics of the study population. As far as overall congenital anomalies of the circulatory system are concerned there was no significant difference between the genders but in the two most frequent types of CHA female dominance could be observed. In the control group there was a male dominance reflecting the gender distribution of both club foot and multiple congenital malformations. Table 2 shows the raw and the adjusted associations between arsenic concentrations of drinking water and the prevalence of CHA by exposure categories. Compared to the lowest level of exposure (0–10 g/L) all unadjusted categories up to 50 g/L showed increased risks of congenital heart malformations. After adjustment to the child’s gender and the mother’s age the Odds Ratios kept on indicating increased risk of congenital heart anomalies up to 50 g/L arsenic concentration, in most cases in a statistically significant way. Above 50 g/L no increased risk was observed. Table 3 shows the associations between prevalence of congenital anomalies and the variables used for adjustment. The unadjusted odds ratios are the results of a simple and the adjusted ones a multiple logistic regression analysis. Compared to the controls, girls were found at significantly higher risk of CHA than boys and mothers of age between 22 and 38 years were more likely to have babies born with CHA than those in the younger or older age groups.
Please cite this article in press as: Rudnai, T., et al., Arsenic in drinking water and congenital heart anomalies in Hungary. Int. J. Hyg. Environ. Health (2014), http://dx.doi.org/10.1016/j.ijheh.2014.05.002
G Model
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IJHEH-12772; No. of Pages 6
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4
Table 2 Associations between arsenic concentrations of the supplied drinking water during pregnancy and prevalence of congenital heart anomalies. As conc. (g/L)
0–10.0 10.1–20.0 20.1–30.0 30.1–40.0 40.1–50.0 >50 a
Adjusteda
Unadjusted Cases
Controls
OR (95% C.I.)
7605 1308 367 202 121 131
4845 602 178 109 57 89
1.00 1.38 (1.25–1.53) 1.31 (1.09–1.58) 1.18 (0.93–1.49) 1.35 (0.99–1.86) 0.94 (0.72–1.23)
P value
Cases
Controls
OR (95% C.I.)
P value
10 g/L
Adjusted
OR (95% C.I.)
P value
OR (95% C.I.)
P value
1.46 (1.37–1.56) 0.91 (0.82–1.01) 0.41 (0.34–0.49) 1.31 (1.21–1.42)
