Chromosomal congenital anomalies and residence near hazardous waste landfill sites

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The Lancet, Volume 359, Issue 9303, Pages 320 – 322, 26 January 2002

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Chromosomal congenital anomalies and residence near hazardous waste landfill sites

Original Text

Dr M Vrijheid PhD a , Prof H Dolk PhD b, B Armstrong PhD a, L Abramsky BA c, F Bianchi PhD d, I Fazarinc MD e, E Garne MD f, R Ide MinstAM g, V Nelen MD h, E Robert MD i, JES Scott FRCS j, D Stone MD k, Prof R Tenconi MD l

Previous findings of the EUROHAZCON study showed a 33% increase in risk of non-chromosomal anomalies near hazardous waste landfill sites. Here, we studied 245 cases of chromosomal anomalies and 2412 controls who lived near 23 such sites in Europe. After adjustment for confounding by maternal age and socioeconomic status, we noted a higher risk of chromosomal anomalies in people who lived close to sites (0—3 km) than in those who lived further away (3—7 km; odds ratio 1·41, 95% CI 1·00—1·99). Our results suggest an increase in risk of chromosomal anomalies similar to that found for non-chromosomal anomalies.

EUROHAZCON study findings1 have shown a 33% increase in the risk of non-chromosomal anomalies for residents living within 3 km of 21 European hazardous waste landfill sites. We report findings from the EUROHAZCON study on chromosomal anomalies. EUROHAZCON study methods have been described in detail.1 We obtained data from regional population-based registers of congenital malformations in five European countries. In addition to the regions included previously (table 1), we included data from the England and Wales Down’s Syndrome register, selecting only two regions (Essex 1989—92, and Mersey 1989—93) because resources were insufficient to provide case data with full postcodes for all regions. These two regions were selected because of good collaboration with local environment agencies and presence of hazardous waste landfill sites which conformed to our criteria for inclusion.1 In total, we included 23 landfill sites in 17 study areas (table 1). Details of site characteristics have been published.2 One landfill site included in the non-chromosomal part of the study was excluded because geographical site co-ordinates proved incorrect. Exclusion of this site (study area 14) did not change findings published for non-chromosomal anomalies: the odds ratio for living within 3 km of a landfill site including site 14 was 1·33 (95% CI 1·11—1·59) for non-chromosomal anomalies.1 After exclusion of site 14 this estimate was 1·34 (1·12—1·60).

Table 1Table image

Odds ratios for chromosomal anomaly in residents within 3 km of a hazardous waste landfill site

On a-priori advice of landfill specialists, we defined a 0—3 km proximate zone around each site to represent the zone of most likely exposure.1 This zone was compared with a 3—7 km distant zone. We defined cases as livebirths, stillbirths, and terminations of pregnancy with chromosomal anomalies (International Classification of Disease [ICD] 9 codes 7580—89) registered on malformation registers. Controls were normal live births, around two per case, selected from the same year of birth and 7 km study area as the case.1 In the Essex Region (study areas 16 and 17), controls were selected by random selection of two neonates from all normal births on the day after the birth of the case, within the same 7 km study area. In the Mersey region (study area 18), controls were a random sample of all live births in the same year of birth and study area as the case. These different methods were used in order to obtain complete maternal age information for controls. In analyses we used the total pool of controls selected for non-chromosomal and chromosomal cases in each 7 km study area, giving about 10 controls per hromosomal case. We included a total of 245 cases and 2412 controls. The geographical locations of cases and controls were determined with an accuracy of 100 m or less by use of the mother’s address or postcode of residence at time of birth. The association between distance of residence from the nearest waste site and risk of chromosomal anomalies was analysed with logistic and related binomial regression models. Terms for study area and year of birth, were included in all models, and analyses were adjusted for maternal age and socioeconomic status.1 Distance of residence was fitted as a dichotomous measure (0—3 km and 3—7 km zones) and as a continuous measure only in analyses pooling data over all study areas. We fitted the same continuous distance models as in the non-chromosomal part of the study, including one model in which risk declines exponentially with distance.1, 3

The adjusted odds ratio for living near a site, for all chromosomal anomalies combined, was 1·41 (95% CI 1·00—1·99, table 2). Adjustment for confounding factors increased the crude odds ratio slightly (from an unadjusted odds ratio of 1·32, 0·96—1·81), almost entirely because of adjustment for maternal age. Odds ratios did not vary significantly between study areas (p=0·79). A similiar odds ratio was found for the fifteen study areas on which previous non-chromosomal analyses had been based (table 2). Point estimates of odds ratios for Down’s syndrome and non-Down’s syndrome separately were greater than 1, but were not significant (table 2). Risk did not decline consistently with increasing distance from sites: various models fitting distance as a continuous measure and six distance zones showed no significant trends (p>0·10). Odds ratios were highest in the 0—1 km (1·68, 0·72—3·89) and 2—3 km (1·74, 1·12—2·70) distance zones, and lowest in the 1—2 km (1·08, 0·61—1·93) and 3—4 km (1·05, 0·69—1·60) zones compared with a 5—7 km baseline. In most individual study areas, odds ratios were not significant before or after adjustment for maternal age (table 1). However, numbers of cases were small and 95% CI wide.

Table 2Table image

Odds ratios for chromosomal anomaly in residents within 3 km of a hazardous waste landfill site

Risk estimates for chromosomal anomalies were similar to those noted for non-chromosomal anomalies,1 in pooled analyses and in individual study areas. This similarity can be interpreted in two main ways. Either landfill exposures are causally related to risk of congenital anomaly and have both teratogenic and mutagenic effects, or the relation is not causal and findings indicate a common bias, or a chance effect in the selection of a common pool of control births. Potential sources of bias, including misclassification of exposure, ascertainment bias, migration bias, and occupational and industrial exposure have been discussed in detail1 and apply to the present findings. The similar increase in risk of chromosomal and non-chromosomal anomalies renders residual socioeconomic confounding unlikely as an explanation for findings as socioeconomic status affects risks of chromosomal and non-chromosomal anomalies differently. We noted higher risks of non-chromosomal anomalies and lower risks of chromosomal anomalies in groups with lower compared with higher socioeconomic status, mainly because of differences in maternal age distribution.4 Maternal age is a confounding factor in analysis of chromosomal anomalies, but adjustment for maternal age shifted odds ratios away from unity. A previous study reported on chromosomal anomalies near waste sites and showed an increased risk (1·46, 1·01—2·01) near sites containing plastic chemicals, following an a-priori hypothesis that plastic chemicals such as styrene might induce chromosomal anomalies.5 More study into the chemical causes of chromosomal anomalies and exposure of residents to landfill sites is needed to interpret our findings.

Contributors

M Vrijheid and H Dolk wrote the paper and coordinated the study. M Vrijheid did analyses of chromosomal congenital anomaly risk near landfill sites and reviewed the literature. B Armstrong supervised statistical analyses. The other authors took part in protocol design of the study (including advice on data collection, classification of cases, &c), and supplied data from participating registries. All authors contributed to revision of the paper.

Conflict of interest statement

None declared.

Acknowledgments

We thank colleagues from the participating registries and laboratories contributing data to the Down Syndrome Register. The main study was funded by the EC DGXII BIOMED programme, this work was carried out specifically under a Research Fellowship for M Vrijheid from the Colt Foundation. The sponsors of the study had no role in study design, data collection, data analysis, data interpretation, or writing of the report.

1 Dolk H, Vrijheid M, Armstrong B, et al. Risk of congenital anomalies near hazardous-waste landfill sites in Europe: the EUROHAZCON study. Lancet 1998; 352: 423-427. Summary | Full Text | PDF(72KB) | CrossRef | PubMed

2 Vrijheid M. Risk of congenital anomalies in the vicinity of hazardous waste landfill sites. (thesis). London: University of London, 2000.

3 Dolk H, Vrijheid M, Armstrong BEUROHAZCON collaborative group. Congenital anomalies near hazardous waste landfill sites in Europe. In: Lawson AB, Biggeri A, Bohning D, Lesaffre E, Viel JF, Bertollini R, et al, eds. Disease Mapping and Risk Assessment for Public Health. Chichester: Wiley, 1999.

4 Vrijheid M, Dolk H, Stone D, Abramsky L, Alberman E, Scott J. Socioeconomic inequalities in risk of congenital anomaly. Arch Dis Child 2000; 82: 349-352. CrossRef | PubMed

5 Geschwind SA, Stolwijk JAJ, Bracken M, et al. Risk of congenital malformations associated with proximity to hazardous waste sites. Am J Epidemiol 1992; 135: 1197-1207. PubMed

a EUROCAT Central Registry, Environmental Epidemiology Unit, Department of Public Health and Policy, London School of Hygiene and Tropical Medicine, London, UK

b EUROCAT Central Registry, Faculty of Life and Health Sciences, University of Ulster at Jordanstown, Belfast, UK

c North Thames (West) Congenital Malformation Register, North Thames Perinatal Public Health Unit, Northwick Park Hospital, London

d Tuscany EUROCAT Register, Unit of Epidemiology, CNR Institute of Clinical Physiology, Pisa, Italy

e Institute of Public Health, Ljubljana, Slovenia

f Funen County Eurocat Register, Institute of Public Health, University of Southern Denmark, Odense, Denmark

g National Down Syndrome Cytogenetic Register, The Wolfson Institute of Preventive Medicine, St Bartholomew’s and the London School of Medicine and Dentistry, London

h Antwerp Eurocat Register, Provincial Institute for Hygiene, Antwerp, Belgium

i France Central East Register of Congenital Malformations, Institut Européen des Génomutations, Lyon, France

j Northern Congenital Abnormality Survey (NorCAS), Maternity Survey Office, University of Newcastle-upon-Tyne, Newcastle, UK

k Glasgow EUROCAT Register, Paediatric Epidemiology and Community Health (PEACH) Unit, Department of Child Health, University of Glasgow, Glasgow, UK

l North-East Italy Registry of Congenital Malformations, Genetica Medica, University of Padova, Padova, Italy

Correspondence to: Dr M Vrijheid, Environmental Epidemiology Unit, Department of Public Health and Policy, London School of Hygiene and Tropical Medicine, Keppel St, London WC1E 7HT, UK