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Epidemiological studies of congenital heart defects in the Southeast region of Sweden
Linköping University, Department of Molecular and Clinical Medicine, Obstetrics and gynecology. Linköping University, Faculty of Health Sciences.
2002 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

In the most recent analysis of Swedish data on congenital malformations, it appeared that in the county of Östergötland, the prevalence of infants with a diagnosed congenital malformation was higher than in the rest of the country. This observation initiated an effort to make a more complete identification of all infants born with a congenital malformation in that county and to compare it with the other two counties in the Southeast region of Sweden (Jönköping and Kalmar), utilising all the relevant Swedish medical health registers available. A total of 10,171 infants with a congenital malformation of any type were identified in the region: 4,698 infants in Östergötland county (6.2%), and 5,473 in the reference counties (5.4%). A 15% excess malformation risk in Östergötland compared with the two reference counties. Various validations of the register data were undertaken and different types of error were detected. Limb reduction defects seemed to occur more often in Östergötland county and there was an increased risk of cardiovascular malformations in Östergötland county (22%).

The next step comprised an exploration of putative risk factors for cardiac defects in the area. Maternal body mass index (BMI) >29 was found to be a significant risk factor for cardiac defects. Maternal diabetes mellitus and maternal use of antiepileptics were associated with an increased risk of cardiac defects in the offspring.

To explore if the pregnant women in Östergötland county differed from the women in the reference counties, a comparative analysis of potential risk factors was performed. The only single putative risk factor that could contribute to the excess risk of cardiac defects in Östergötland county was matemal residency in a rural district. Notably, nearly all the potential risk factors studied i.e. spontaneous abortions, involuntary childlessness, maternal disease, high maternal body mass index, matemal medical during use and alcohol use in early pregnancy, parental employment and paternal age were stronger in Östergötland county compared to the reference area. A conceivable explantation is that one or more unidentified factors could activate prevalent and weak teratogenic risk factors for cardiac defects.

Drinking water could be such a factor. By using a geographical infmmation system (GIS) it was possible to obtain individual data on drinking water characteristics. An increased tisk of a congenital cardiac defect seemed to be associated with the chlorination procedure, in particular the use of chlorine dioxide, and with increasing total trihalomethane concentration.

Place, publisher, year, edition, pages
Linköping: Linköpings universitet , 2002. , 63 p.
Series
Linköping University Medical Dissertations, ISSN 0345-0082 ; 733
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:liu:diva-26647Local ID: 11212ISBN: 91-7373-174-9 (print)OAI: oai:DiVA.org:liu-26647DiVA: diva2:247196
Public defence
2002-05-24, Berzeliussalen, Universitetssjukhuset, Linköping, 13:00 (Swedish)
Opponent
Available from: 2009-10-08 Created: 2009-10-08 Last updated: 2012-09-13Bibliographically approved
List of papers
1. Congenital malformations in the southeast of Sweden: a registry study with validation
Open this publication in new window or tab >>Congenital malformations in the southeast of Sweden: a registry study with validation
2000 (English)In: Acta Paediatrica, ISSN 0803-5253, E-ISSN 1651-2227, Vol. 89, no 10, 1238-1243 p.Article in journal (Refereed) Published
Abstract [en]

A study was made of the occurrence of congenital malformations in the southeast region of Sweden, utilizing all available relevant health registries. Östergötland county had been pinpointed in a routine surveillance as having an increased malformation risk. Various validations of the register data were undertaken and different types of errors were detected. An increased risk was seen, in Östergötland county compared to the reference counties, for specific types of malformations: preauricular appendices, pylorostenosis, uterine/vaginal malformations, foot deformities, limb reduction defects and cardiovascular malformations. Variable classification or registration artefacts explained the excess among the first four conditions. Limb reduction defects were also mis-coded, but the increased risk in Östergötland county may persist.

Conclusion: There is an increased risk of major cardiovascular malformations in Östergötland county compared to the reference counties that also shows an uneven distribution within the county.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-25854 (URN)10.1111/j.1651-2227.2000.tb00742.x (DOI)10291 (Local ID)10291 (Archive number)10291 (OAI)
Available from: 2009-10-08 Created: 2009-10-08 Last updated: 2012-09-13Bibliographically approved
2. Risk factors for cardiovascular malformation: a study based on prospectively collected data
Open this publication in new window or tab >>Risk factors for cardiovascular malformation: a study based on prospectively collected data
2002 (English)In: Scandinavian Journal of Work, Environment and Health, ISSN 0355-3140, Vol. 28, no 1, 12-17 p.Article in journal (Refereed) Published
Abstract [en]

Objectives The aim of this study was to identify risk factors for cardiovascular malformation.

Methods In a case-referent study prospectively collected data were obtained from original medical records. The study included 277 woman who had infants with a severe cardiac defect, and for each case two referents (medical records study) were included. Data on parental age, maternal reproductive history, disease in early pregnancy, reported maternal use of drugs and alcohol, smoking habits, parental occupation, and maternal body mass index (BMI) were extracted. When data were available from Swedish medical health registers, a comparison was made (register study) between all infants with cardiovascular defects (2208) and all infants born (175 768).

Results Maternal diabetes mellitus was associated with an increased risk for cardiovascular malformation [odds ratio (OR) 2.38, 95% confidence interval (95% CI) 1.36-4.15], as was a high BMI (>29) (OR 1.46, 95%CI 1.12-1.90). A tendency towards an increased risk was found for involuntary childlessness, spontaneous abortion, thyroid drugs, and nonsteroid anti-inflammatory drugs.

Conclusions Some known risk factors for cardiac defects (eg, maternal diabetes mellitus and the use of antiepileptics) could be identified. Other postulated risk factors could not be verified, for example, paternal age and parental occupation. The use of medicinal drugs seems not to be a major factor in the etiology of cardiac defects. It is possible, however, that there is an association with the use of nonsteroid anti-inflammatory drugs or drugs for thyroid disease. The relationship between a high BMI and cardiovascular malformation observed in this study may be explained by impaired maternal glucose tolerance.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-26405 (URN)10.5271/sjweh.641 (DOI)10945 (Local ID)10945 (Archive number)10945 (OAI)
Available from: 2009-10-08 Created: 2009-10-08 Last updated: 2012-09-13Bibliographically approved
3. Geographic variations in possible risk factors for severe cardiac malformations
Open this publication in new window or tab >>Geographic variations in possible risk factors for severe cardiac malformations
2002 (English)In: Acta Paediatrica, ISSN 0803-5253, E-ISSN 1651-2227, Vol. 91, no 2, 222-228 p.Article in journal (Refereed) Published
Abstract [en]

The aim of this study was to investigate various putative risk factors in a county in Sweden, described as having a 28% increased prevalence of cardiovascular malformations, and to compare them with the risk factors in two reference counties. Women giving birth in the studied counties differed in age and parity distribution, smoking, and educational level but these differences could not explain the increased risk of cardiovascular malformations in the county, since after stratification for these variables, the risk estimate did not change substantially. A number of potential risk factors were studied in a case/control design: spontaneous abortions, involuntary childlessness, maternal disease, body mass index, medical drug use, alcohol use, parental employment, paternal age, and urban/rural residency. No single factor could be attributed to the increased rate, with the exception of living in a rural district. Nearly all risk factors, however, were stronger in the county studied than those in the reference counties (0.02 > p > 0.01).

Conclusion: The only single putative risk factor that could have contributed to the increased risk for cardiac defects described in the county studied was maternal residency in a rural district. Notably, nearly all potential risk factors studied were stronger in the county studied compared with those in the reference area. A conceivable explanation is that one or more unidentified factors related to rural residency could potentiate prevalent and weak teratogenic risk factors for cardiac defects.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-26404 (URN)10.1111/j.1651-2227.2002.tb01699.x (DOI)10944 (Local ID)10944 (Archive number)10944 (OAI)
Available from: 2009-10-08 Created: 2009-10-08 Last updated: 2012-09-13Bibliographically approved
4. Chlorination Byproducts and Nitrate in Drinking Water and Risk for Congenital Cardiac Defects
Open this publication in new window or tab >>Chlorination Byproducts and Nitrate in Drinking Water and Risk for Congenital Cardiac Defects
2002 (English)In: Environmental Research, ISSN 0013-9351, E-ISSN 1096-0953, Vol. 89, no 2, 124-130 p.Article in journal (Refereed) Published
Abstract [en]

Drinking water disinfection byproducts have been associated with an increased risk for congenital defects including cardiac defects. Using Swedish health registers linked to information on municipal drinking water composition, individual data on drinking water characteristics were obtained for 58,669 women. Among the infants born, 753 had a cardiac defect. The risk for a cardiac defect was determined for ground water versus surface water, for different chlorination procedures, and for trihalomethane and nitrate concentrations. Ground water was associated with an increased risk for cardiac defect when crude rates were analyzed but after suitable adjustments this excess rate was found to be determined by chlorination procedures including chlorine dioxide. Chlorine dioxide appears itself as an independent risk factor for cardiac defects (adjusted odds ratio 1.61 (95%CI 1.00–2.59)). The risk for cardiac defects increased with increasing trihalomethane concentrations (P=0.0005). There was an indicated but statistically nonsignificant excess risk associated with nitrate concentration. The individual risk for congenital cardiac defect caused by chlorine dioxide and trihalomethanes is small but as a large population is exposed to public drinking water, the attributable risk for cardiac defects may not be negligible.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-26406 (URN)10.1006/enrs.2001.4362 (DOI)10946 (Local ID)10946 (Archive number)10946 (OAI)
Available from: 2009-10-08 Created: 2009-10-08 Last updated: 2012-09-13Bibliographically approved

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