Objective To clarify the causes of deaths among patients with Itai-itai disease and severe cadmium (Cd) poisoning. Design Nested case–control analysis of a population-based cohort study. Setting Database of patients with Itai-itai disease and residents of Cd-polluted areas, maintained by the Ministry of Environment, Japan. Participants Subjects included 142 women with Itai-itai disease, 111 women with Cd-induced renal tubular dysfunction and 253 controls matched for sex, age and occupation. All subjects participated in a health impact survey between 1979 and 1984 and were followed until 30 November 2005. Main outcomes and measures Adjusted HRs with 95% CIs for cause of death in women with Itai-itai disease and screened female cases with tubular dysfunction were compared with matched pair controls, using Cox’s proportional hazard model. Vital statistics data were used to determine cause of death. Direct causes of death from autopsy records were used in 29 patients who died from Cd poisoning. Results The most common cause of death among patients with Itai-itai disease was pneumonia, with a significantly increased adjusted HR of 4.54 (95% CI 2.65 to 7.76). Renal diseases were the most common cause of death in renal tubular dysfunction cases, with an increased HR of 12.0 (95% CI 3.92 to 36.8). The adjusted HR for renal diseases was also significantly increased in patients with Itai-itai disease (19.49 (95% CI 6.43 to 59.09)), with a greater impact on mortality of patients with Itai-itai disease than screened cases. The HR for gastrointestinal (GI) diseases was significantly increased (13.79 (95% CI 3.87 to 49.10)) in patients, especially in the first 10 years (37.1 (4.81 to 286.0)). Conclusions Among patients with Itai-itai disease, pneumonia and GI diseases contributed to increased mortality risk. Renal disease is also a significant mortality risk in patients with Itai-itai disease and women with renal tubular dysfunction.

Objective:The effects of cadmium (Cd) on birth weight have been discussed in the scientific literature. However, investigations on the effects of maternal body burden of Cd on the next generation during pregnancy and lactation have been limited. The relation between maternal exposure to Cd and pregnancy outcome or Cd in breast milk in Japanese mothers was investigated.Methods:Cd concentrations in urine and colostrum milk samples of 57 mothers were measured by atomic absorption spectrophotometery. The relations between maternal urinary Cd and infant growth, gestational age at birth, and Cd in breast milk were investigated.Results:The rate of perterm deliveries of mothers with higher urinary Cd (≥2 nmol/mmol creatinine (Cr)) was higher than that of mothers with lower urinary Cd (<2 nmol/mmol Cr). The gestational age was significantly correlated with urinary Cd even after adjustment for maternal age. The height and weight of newborn infants of mothers with higher urinary Cd were significantly lower than those of the newborn infants of mothers with lower urinary Cd, but these decreases were ascribed to early delivery induced by Cd. The Cd in breast milk of mothers with higher urinary Cd was significantly higher than that of mothers with lower urinary Cd. A significant positive correlation was found between maternal urinary Cd and Cd in breast milk.Conclusion:Maternal exposure to Cd seems to increase early delivery, which leads to a lower birth weight. Also, the Cd is transferred in part to the next generation through breast milk after birth.

Objectives:To clarify the causes of death of residents with renal tubular dysfunction induced by cadmium (Cd) in the environment.Methods:A 15 year follow up study was performed with the inhabitants living in the Cd polluted Kakehashi River basin in Japan. Standardised mortality ratios (SMRs) for causes of death, classified by ICD-9, were computed using the person-years method to investigate the excess mortality of subjects with urinary β2-MG (microglobulin) ⩾1000 μg/gCr. Mortality risk analysis was performed using Cox’s proportional model to compare mortality between subjects with urinary β2-MG ⩾1000 and <1000 μg/gCr, and to investigate the relationship between the degree of urinary β2-MG and mortality.Results:Excess mortality due to heart failure and cerebral infarction in both sexes, and nephritis and nephrosis in men, was observed among subjects with urinary β2-MG ⩾1000 μg/gCr. Significant increases in mortality risk for cerebral infarction in men and for malignant neoplasms in women with urinary β2-MG ⩾1000 μg/gCr were observed during the first five year observation period. For nephritis and nephrosis, the mortality risks for men and women with urinary β2-MG ⩾1000 μg/gCr significantly increased over the 15 year observation period. The mortality risks for heart failure and cerebral infarction increased in proportion to the increased urinary β2-MG in both sexes. Increased mortality risks for nephritis and nephrosis were identified in the subjects with urinary β2-MG ⩾10000 μg/gCr in both sexes.Conclusion:Renal tubular dysfunction induced by Cd affected the causes of death, and mortality for heart failure, cerebral infarction, and nephritis and nephrosis was increased among inhabitants living in a Cd polluted area in Japan. In women, cancer mortality may have been increased while Cd pollution was ongoing.

Dioxin levels in the breast milk of mothers residing near a contaminated former airbase in Vietnam remain much higher than in unsprayed areas, suggesting high perinatal dioxin exposure for their infants. The present study investigated the association of perinatal dioxin exposure with autistic traits in 153 3-year-old children living in a contaminated area in Vietnam. The children were followed up from birth using the neurodevelopmental battery Bayley-III. The high-2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) exposed groups (3.5 pg per g fat) showed significantly higher Autism Spectrum Rating Scale (ASRS) scores for both boys and girls than the mild-TCDD exposed groups, without differences in neurodevelopmental scores. In contrast, the high total dioxin-exposed group, indicated by polychlorinated dibenzo-p-dioxins/furans (PCDDs/Fs)—the toxic equivalents (TEQ) levels17.9 pg-TEQ per g fat, had significantly lower neurodevelopmental scores than the mild-exposed group in boys, but there was no difference in the ASRS scores. The present study demonstrates a specific impact of perinatal TCDD on autistic traits in childhood, which is different from the neurotoxicity of total dioxins (PCDDs/Fs).