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Background: The etiology of most cases of congenital hypothyroidism (CHT) due to thyroid dysgenesis (DG) is unknown. If transient environmental factors can impact on thyroid gland development, then clustering of cases in time and/or space may occur, and this would be more likely in thyroid DG than dyshormonogenesis (DHG). Methods: The newborn screening program for CHT in Scotland is linked to a central database that includes case details such as postcode. The etiology of CHT is investigated in many cases of CHT using scintigraphy and/or ultrasonography. We looked for evidence of a change in CHT incidence with year of birth and according to season of the year. We then undertook space–time clustering analysis (using a method based on K-functions, with nearest neighbor thresholds) of CHT in Scotland between 1979 and 2015. We also looked for evidence of overall changes associated with sex and area-based birth density. Results: Of 531 cases with CHT during the study period, 290 cases had been categorized as DG (n = 229) or DHG (n = 61) following more detailed investigation. The incidence of CHT increased with year of birth and was in part linked to changing methodology, but there was no seasonality. There was no evidence of overall space–time clustering (p = 0.06), but there was evidence of clustering in babies with DG (p = 0.007). This picture appeared to be most closely linked to underlying thyroid gland hypoplasia rather than thyroid gland agenesis or ectopia. There was significant space–time clustering for both males and females, but clustering was restricted to lesser birth density areas. There was also evidence of clustering for unknown cases (p < 0.001). Clustering of these cases was restricted to females but was present for cases from both greater and lesser birth density areas. There was no evidence of clustering in cases of DHG. Conclusions: These data suggest that an unidentified environmental factor or factors may be involved in the etiology of thyroid DG in Scotland. The variation in CHT incidence observed internationally may reflect environmental as well as genetic factors. [ABSTRACT FROM AUTHOR]

Various environmental factors have been proposed as triggers of primary biliary cirrhosis (PBC), a progressive autoimmune cholestatic liver disease which is characterised by the destruction of the small intrahepatic bile ducts. Support for their pathogenic role in PBC is provided by epidemiological studies reporting familial clustering and clusters of the disease within a given geographical area. The seminal study by Triger reporting that the great majority of PBC cases in the English city of Sheffield drank water from a specific water reservoir, has been followed by studies reporting disease 'hot spots' within a restricted geographic region of the former coal mining area of Newcastle. The New York study reporting an increased risk and significant clustering of PBC cases near toxic federal waste disposal sites has added strength to the notion that environmental factors, possibly in the form of infectious agents or toxic/chemical environmental factors in areas of contaminated land, water or polluted air may play a key role in the development of the disease. This review discusses the findings of reports investigating environmental factors which may contribute to the cause of primary biliary cirrhosis. [ABSTRACT FROM AUTHOR]

Purpose: The etiology of congenital cerebral palsy is unclear. Recent studies have suggested that maternal infection is involved. Indirect, but supportive, evidence for an infectious hypothesis would be provided by the finding of space-time clustering. Methods: We analyzed all 906 cases born during the period 1991–2003 using a population-based registry from Northern England. We applied the K-function method for testing global space-time clustering and used residential addresses at the time of birth. The Knox method was used to determine the spatio-temporal range over which global clustering occurred. Tests were repeated using nearest neighbor thresholds to allow for variable population density. Additionally, Kulldorff''s scan statistic identified specific space-time clusters. Results: There was statistically significant evidence of global space-time clustering (p ≤ 0.05). Clustering occurred over a range of close distances, but was most pronounced for cases born within 1–4 months of one another. A specific space-time cluster was identified during 1994. Conclusions: The application of spatial statistics for the study of cerebral palsy is novel. There is tentative evidence for the involvement of spatially and temporally varying environmental etiological factors. These findings may support a role for infections or similar agents. However, the role of chance cannot be excluded. [Copyright &y& Elsevier]

Abstract: We previously demonstrated significant space–time clustering amongst cases of childhood leukaemia (in particular acute lymphoblastic leukaemia (ALL)), central nervous system (CNS) tumour (especially astrocytoma), soft tissue sarcoma and Wilms’ tumour. We hypothesised that there may be common aetiological mechanisms between some of these diagnostic groups. To test this hypothesis we analysed for cross-space–time clustering between these diagnostic groups, using population-based data from north-west England. Data were examined by a second-order procedure based on K-functions. Reference points in time and space were dates and addresses at birth and diagnosis. The results showed statistically significant (P <0.05) cross-clustering between cases of leukaemia and CNS tumour and between cases of ALL and astrocytoma. There was no statistically significant cross-clustering of Wilms’ tumours and soft tissue sarcomas with any other malignancy. In conclusion, these findings are consistent with common, possibly infectious, aetiological mechanisms for childhood leukaemia (particularly ALL) and CNS tumours (particularly astrocytoma). [Copyright &y& Elsevier]

Abstract: Previously, we reported space–time clustering and seasonal variation in childhood central nervous system (CNS) tumours for the period 1954–1998. These previous studies provided evidence that infections may be involved in aetiology. To determine whether there were also localised spatial factors involved in aetiology we analysed the geographical distribution of CNS tumours in children aged 0–14 years using Manchester Children’s Tumour Registry (MCTR) data for the period 1976–2000. Specifically, the Potthoff–Whittinghill test for spatial clustering was applied and Poisson regression was used to analyse the relationship between incidence rates and small-area population density, ethnic composition and deprivation index. No relationships were seen for all CNS tumours together and only a few for the subgroups. The previous findings of space–time clustering and seasonal variation, involving astrocytoma and ependymoma, together with the lack of spatial clustering and ecological relationships for these tumours provide evidence that astrocytoma and ependymoma may be associated with a highly mobile transient aetiological agent. An example of such an agent is an infection that occurs in mini-epidemics. [Copyright &y& Elsevier]

The aim of this paper was to study the geographical distribution of Wilms’ tumours (WT) and soft-tissue sarcomas (STS) for 0–14 year olds included in a population-based registry from North West England during 1976–2000. Standardised morbidity ratios (SMRs) were calculated. Relationships between incidence rates and small area (ward) population density, ethnic composition, deprivation index and urban–rural status were examined using Poisson regression. There was a non-linear relationship between WT incidence and population density (P=0.008), with a higher incidence associated with wards with low deprivation scores (P=0.02); and which included a greater proportion of whites (P=0.01). For STS, a higher incidence was associated with wards with low deprivation scores (P=0.04); and which were ‘more rural/less urban’ (P=0.03). These results are consistent with a role for localised environmental exposures, in combination with lifestyle factors, in the aetiology of WT. For STS, there is some evidence for the involvement of environmental and/or lifestyle factors. [Copyright &y& Elsevier]