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The aim of this thesis was to analyse possible effects of prenatal arsenic exposure on foetal and infant health. The setting is Bangladesh, where two cohorts were studied, both part of a health and demographic surveillance system in Matlab. A historical cohort 1991-2000 included 29,134 pregnant women with information on drinking water sources and arsenic testing of tube well water. A prospective cohort study included pregnant women 2002 - 2003 where urinary arsenic concentrations were assessed twice during pregnancy; 2,924 women and their pregnancy outcomes were evaluated for foetal loss, perinatal and infant mortality; 1,578 mother-infant pairs were analysed for size at birth; and 1,552 were analysed for morbidity during infancy. Women exposed to arsenic levels ≥ 50 µg/L in water had an increased risk of foetal loss and infant death in comparison with women exposed to arsenic levels < 50 µg/L. These findings were confirmed in the prospective cohort study. Women with urine arsenic concentrations at the 5th quintile had 62% increased risk of spontaneous abortion (OR 1.62, 95% CI 1.04 - 2.55) in comparison with women who had arsenic concentrations at the 1st quintile level. Increased risks of perinatal morality (RR 3.01, 95% CI 1.07 - 8.45) and infant mortality (RR 5.01; 95% CI: 1.41 - 17.84) were also observed at the 5th quintile of exposure. Significant negative dose-effect associations were found between arsenic exposure and birth weight, head and chest circumferences at a relatively low level of exposure (<100 µg/L in urine). In this range of exposure birth weight decreased by 1.68 g (SE 0.62) for each 1 µg/L increase of arsenic in urine. In comparison with exposure at the 1st quintile level the risk of lower respiratory tract infection was significantly increased (RR 1.68, 95% CI 1.35-2.07) for women who had urinary arsenic concentrations at the 5th quintile level. The risk was also increased for diarrhoeal diseases. The study findings highlight the negative effects of arsenic exposures on pregnancy outcomes and infant health. Mitigation programs need to be strengthened and women of reproductive ages should be prioritized in arsenic affected regions worldwide.

The overall aim of this thesis is to evaluate the risk for increased morbidity and mortality due to long-term arsenic exposure via drinking water by use of epidemiological and spatial approaches in studies performed in Matlab, Bangladesh. A total of 166,934 individuals aged 4 years and above were screened for skin lesions in 2002-2003. Another sample of 115,903 adults aged 15 years or more and a third sample of 26,972 pregnancies in 1991-2000 were considered in a historical cohort and an ecological study, respectively, where risk of adult mortality and spatial clusters of foetal loss and infant death were analysed in relation to arsenic exposure. More than 70% of the tube-wells in the study area exceeded the threshold for arsenic contamination according to the WHO guideline (10 µg/L). The prevalence of arsenic-induced skin lesions was 3/1000 and men had significantly higher prevalence of skin lesions (SMR 158, 95% CI: 133-188) compared to women. There was an increased risk for death in adulthood due to all non-accidental causes (hazards ratio = 1.16, [95% CI 1.06-1.26]) even at a low level of arsenic contamination (10-49 µg/L). Slightly lower risks were observed for death in cancers (1.44 [1.06-1.95]) and infectious diseases (1.30 [1.13-1.49]) at 50-149 µg/L, but for cardiovascular diseases, it was evident (1.23 [1.01-1.51]) from the level 150-299 µg/L. A dose-response relationship was observed for each of these causes. We identified high and low risk clusters of foetal loss and infant death that coincided with identified high and low clusters of arsenic exposure. Water arsenic concentration of the reported main water source was significantly correlated with arsenic concentration in urine, which reflects current arsenic intake from all sources (R2=0.41, ρ< 0.0001), and the influence of neighbouring water sources was minimal. The study findings underlines that the ongoing arsenic exposure has resulted in a series of severe public health consequences in Bangladesh that call for reinforcement in the mitigation efforts. Knowledge about the spatial distribution of exposure and health effects may be of value in that process.

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