Previous epidemiological studies of cryptorchidism have led to the hypothesis that the risk of undescended testis is associated with excess oestrogen exposure during pregnancy. A case-control study was undertaken to test this hypothesis, comparing mothers of affected boys (244) and normal male births (488) born within six months of a case selected randomly from the British Columbia population. Information was collected on the mother's reproductive history, family history, and past medical history, and events surrounding all pregnancies ending in a birth. The results were analysed using both the population-based sample of male births and the male sibs of cases as control groups. Neither exogenous oestrogen exposure, nor any of the pregnancy-related variables hypothesized to be indirect indicators of endogenous oestrogen exposure, including bleeding and nausea and/or vomiting, were found to be significantly associated with risk of undescended testes in either comparison. More mothers with later index births reported menstrual irregularity greater than half the time, and smoking, thought to have a protective effect, was more prevalent among case mothers than control mothers. No other variables were significantly different between case and control mothers. The results of this study do not support the hypothesis that elevated exogenous or endogenous oestrogen exposure during pregnancy increases the risk of undescended testis in male children.

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A part from an increase in dental fluorosis, recent reviews of water fluoridation found little evidence of adverse effects. 1 2 Several studies looked at congenital abnormalities, two of which found a negative effect of water fluoridation, although overall the evidence was inconclusive. The reviews also raised the issue of the paucity of published data on congenital abnormalities, the possibility of publication bias, and the need for more data; and the age of existing research, the poor quality, and the failure to control for confounding factors. METHODS AND RESULTSOur study was based on residence within the boundaries of the former Northern health region in the north east of England, with a population of 3 million and about 35 000 deliveries per year. Artificially fluoridated and non-fluoridated areas were chosen with similar populations, sociodemographic characteristics, termination rates, and fluoride supplement regimens. Cases were identified from two population based registers, the Northern Perinatal Mortality Survey (PMS) and the Northern Congenital Abnormality Survey (NorCAS). 3All stillbirths occurring between 1 January 1989 and 31 December 1998 were identified from the PMS. All cases of a congenital abnormality with a final postnatal diagnosis of a trisomy (trisomy 21, 13, and 18 only, ICD-9 codes 758.0, 758.1, 758.2), a neural tube defect (as defined by the EUROCAT system of classification, ICD-9 codes 740.0, 740.1, 740.2, 741.0, 741.9, and 742.0) or facial cleft (cleft palate, cleft lip with or without cleft palate, Pierre Robin syndrome, ICD-9 codes 749.0, 749.1,749.2, 756.03) were identified from the NorCAS. Cases resulting in a miscarriage were excluded from the analysis as it is not possible to ascertain the total number of miscarriages for the denominator.Denominator birth data were obtained from the Office for National Statistics (ONS, formerly the Office of Population Census and Surveys) (OPCS Birth Statistics). Cases were grouped by year of delivery The number of defects was analysed using generalised linear modelling with a Poisson error structure and log link function. To take into account the different size of each geographical area, the natural logarithm of the total number of births was declared as an offset. The package MLwiN was used to model variation between areas and variation between occasions as random effects with occasions nested within areas.The analysis was under taken in two stages. Firstly, we hypothesised that if fluoridation influenced the risk of congenital abnormality then the largest difference would be between areas with no fluoridation (<0.3 parts fluoride per million water) and areas with full fluoridation (>0.9 parts fluoride per million water). We considered each type of abnormality separately and the difference between non-fluoridated and fully fluoridated areas was fitted as a fixed effect in the multilevel model. Results are given in the form of odds ratios-the relative odds of defects in a fluoridated area compared with those in a non-fluoridated area. The secon...