Syed Moshfiqur Rahman

Elevated childhood exposure to arsenic despite reduced drinking water concentrations--A longitudinal cohort study in rural Bangladesh.

OBJECTIVESnThe aim of this study was to evaluate the massive efforts to lower water arsenic concentrations in Bangladesh.nnnMETHODSnIn our large mother-child cohort in rural Matlab, we measured the arsenic concentrations (and other elements) in drinking water and evaluated the actual exposure (urinary arsenic), from early gestation to 10 years of age (n=1017).nnnRESULTSnMedian drinking water arsenic decreased from 23 (2002-2003) to <2 μg/L (2013), and the fraction of wells exceeding the national standard (50 μg/L) decreased from 58 to 27%. Still, some children had higher water arsenic at 10 years than earlier. Installation of deeper wells (>50 m) explained much of the lower water arsenic concentrations, but increased the manganese concentrations. The highest manganese concentrations (~900 μg/L) appeared in 50-100 m wells. Low arsenic and manganese concentrations (17% of the children) occurred mainly in >100 m wells. The decrease in urinary arsenic concentrations over time was less apparent, from 82 to 58 μg/L, indicating remaining sources of exposure, probably through food (mean 133 μg/kg in rice).nnnCONCLUSIONnDespite decreased water arsenic concentrations in rural Bangladesh, the children still have elevated exposure, largely from food. Considering the known risks of severe health effects in children, additional mitigation strategies are needed.

Manganese in drinking water and cognitive abilities and behavior at 10 years of age: a prospective cohort study

Background: Cross-sectional studies have indicated impaired neurodevelopment with elevated drinking water manganese concentrations (W-Mn), but potential susceptible exposure windows are unknown. Objectives: We prospectively evaluated the effects of W-Mn, from fetal life to school age, on children’s cognitive abilities and behavior. Methods: We assessed cognitive abilities and behavior in 1,265 ten-year-old children in rural Bangladesh using the Wechsler Intelligence Scale for Children (WISC-IV) and the Strengths and Difficulties Questionnaire (SDQ), respectively. Manganese in drinking water used during pregnancy and by the children at 5 y and 10 y was measured using inductively coupled plasma mass spectrometry. Results: The median W-Mn was 0.20mg/L (range 0.001–6.6) during pregnancy and 0.34mg/L (<0.001–8.7) at 10 y. In multivariable-adjusted linear regression analyses, restricted to children with low arsenic (As) exposure, none of the W-Mn exposures was associated with the children’s cognitive abilities. Stratifying by gender (p for interaction in general <0.081) showed that prenatal W-Mn (<3mg/L) was positively associated with cognitive ability measures in girls but not in boys. W-Mn at all time points was associated with an increased risk of conduct problems, particularly in boys (range 24–43% per mg/L). At the same time, the prenatal W-Mn was associated with a decreased risk of emotional problems [odds ratio (OR)=0.39 (95% CI: 0.19, 0.82)] in boys. In girls, W-Mn was mainly associated with low prosocial scores [prenatal W-Mn: OR=1.48 (95% CI: 1.06, 1.88)]. Conclusions: Elevated prenatal W-Mn exposure was positively associated with cognitive function in girls, whereas boys appeared to be unaffected. Early life W-Mn exposure appeared to adversely affect children’s behavior. https://doi.org/10.1289/EHP631

Elevated Manganese Concentrations in Drinking Water May Be Beneficial for Fetal Survival

Background Elevated exposure to the essential element manganese (Mn) can be toxic. Manganese concentrations in ground water vary considerably, and reported associations between Mn and early-life mortality and impaired development have raised concern. We assessed the effects of drinking water Mn exposure during pregnancy upon fetal and infant survival. Methods In this population-based cohort study, we identified the outcomes of pregnancies registered between February 2002 and April 2003 in Matlab, Bangladesh. Using inductively coupled plasma mass spectrometry, we measured the concentrations of Mn and other elements in the pregnant women’s drinking water. Results A total of 1,875 women were included in the analysis of spontaneous abortions (n=158) and 1,887 women in the perinatal mortality analysis (n=70). Water Mn ranged from 3.0–6,550 µg/L (median=217 µg/L). The adjusted odds ratio (OR) for spontaneous abortion was 0.65 (95% CI 0.43–0.99) in the highest water Mn tertile (median=1,292 µg/L) as compared to the lowest tertile (median=56 µg/L). The corresponding OR for perinatal mortality was 0.69 (95% CI 0.28–1.71), which increased to 0.78 (95% CI 0.29–2.08) after adjustment for BMI and place of delivery (home/health facility; n=1,648). Conclusions Elevated water Mn concentrations during pregnancy appear protective for the fetus, particularly in undernourished women. This effect may be due to the element’s role in antioxidant defense.

Common Polymorphisms in the Solute Carrier SLC30A10 are Associated With Blood Manganese and Neurological Function

Manganese (Mn) is an essential nutrient in humans, but excessive exposure to Mn may cause neurotoxicity. Despite homeostatic regulation, Mn concentrations in blood vary considerably among individuals. We evaluated if common single-nucleotide polymorphisms (SNPs) in SLC30A10, which likely encodes an Mn transporter, influence blood Mn concentrations and neurological function. We measured blood Mn concentrations by ICP-MS or atomic absorption spectroscopy and genotyped 2 SLC30A10 non-coding SNPs (rs2275707 and rs12064812) by TaqMan PCR in cohorts from Bangladesh (Nu2009=u2009406), the Argentinean Andes (Nu2009=u2009198), and Italy (Nu2009=u2009238). We also measured SLC30A10 expression in whole blood by TaqMan PCR in a sub-group (Nu2009=u2009101) from the Andean cohort, and neurological parameters (sway velocity and finger-tapping speed) in the Italian cohort. The rs2275707 variant allele was associated with increased Mn concentrations in the Andes (8%, Pu2009=u2009.027) and Italy (10.6%, Pu2009=u2009.012), but not as clear in Bangladesh (3.4%, Pu2009=u2009.21; linear regression analysis adjusted for age, gender, and plasma ferritin). This allele was also associated with increased sway velocity (15%, Pu2009=u2009.033; adjusted for age and sex) and reduced SLC30A10 expression (−24.6%, Pu2009=u2009.029). In contrast, the rs12064812 variant homozygous genotype was associated with reduced Mn concentrations, particularly in the Italian cohort (−18.4%, Pu2009=u2009.04), and increased finger-tapping speed (8.7%, Pu2009=u2009.025). We show that common SNPs in SLC30A10 are associated with blood Mn concentrations in 3 unrelated cohorts and that their influence may be mediated by altered SLC30A10 expression. Moreover, the SNPs appeared to influence neurological functions independent of blood Mn concentrations, suggesting that SLC30A10 could regulate brain Mn levels.

Risk factors for suicidal behaviour in individuals on disability pension due to common mental disorders : a nationwide register-based prospective cohort study in Sweden

Background Common mental disorders (CMD) have become one of the leading causes for disability pension (DP). Studies on predictors of adverse health outcome following DP are sparse. This study aimed to examine the association of different socio-demographic factors and health care consumption with subsequent suicidal behaviour among individuals on DP due to CMD. Method This is a population-based prospective cohort study based on register data. All individuals aged 18–64 years, living in Sweden on 31-Dec-2004 who in 2005 were on DP due to CMD (Nu200a=u200a46 745) were followed regarding suicide attempt and suicide (2006–10). Univariate and multivariate hazard ratios (HR) and 95% confidence intervals (CI) for suicidal behaviour were estimated by Cox regression. Results During the five-year follow-up, 1 046 (2.2%) and 210 (0.4%) individuals attempted and committed suicide, respectively. Multivariate analyses showed that young age (18–24 years) and low education predicted suicide attempt, while living alone was associated with both higher suicide attempt and suicide (range of HRs 1.23 to 1.68). Combined prescription of antidepressants with anxiolytics during 2005 and inpatient care due to mental diagnoses or suicide attempt (2001–05) were strongly associated with suicide attempt and suicide (range of HRs 1.3 to 4.9), while inpatient care due to somatic diagnoses and specialized outpatient care due to mental diagnoses during 2001–05 only predicted suicide attempt (HR 1.45; 95% CI: 1.3–1.7; HR 1.30; 95% CI: 1.1–1.7). Conclusions Along with socio-demographic factors, it is very important to consider type of previous healthcare use and medication history when designing further research or intervention aiming at individuals on DP due to CMD. Further research is warranted to investigate both characteristics of disability pension due to CMD, like duration, diagnoses and grade as well as mechanisms to subsequent suicidal behavior, taking potential gender differences into consideration.

Manganese exposure through drinking water during pregnancy and size at birth: A prospective cohort study.

The essential element manganese (Mn) might be toxic at excess exposure. We assessed the impact of elevated Mn exposure through drinking water during pregnancy on birth size in a population-based cohort(n = 1695) in rural Bangladesh. Concentrations of water Mn (median = 236 μg/L, range = 7.1-6336; n = 1177) and erythrocyte Mn (median = 30 μg/kg, range = 6.3-114; n = 758) were measured using ICP-MS. In regression analyses, newborns of women in the highest tertile of water Mn (median = 1495 μg/L) were 0.49 cm (0.20 SD) shorter (B = -0.42; 95% CI: -0.77, -0.08) than those in the lowest tertile (56μg/L). The inverse association was significant in girls and also in boys of mothers with lowest hemoglobin values, likely due to higher absorption of Mn. Manganese concentrations in water and erythrocytes did not correlate, and the associations of the latter with birth size were less obvious. This study suggests that consumption of water with highly elevated Mn levels during pregnancy may impair fetal growth.

Disability pension due to common mental disorders and healthcare use before and after policy changes; a nationwide study

Background: Despite common mental disorders (CMDs) being a main reason for preterm exit from the labour market, there is limited knowledge regarding healthcare use around the time of being granted disability pension (DP) due to CMD. The aim was to study specialized healthcare use before and after being granted DP due to CMD and whether these trajectories differed before and after changes in DP granting criteria in Sweden in 2008. Methods: Included individuals lived in Sweden, aged 19–64 years with incident DP due to CMD before (wave 1, 2005–06, n = 24 298) or after (wave 2, 2009–10, n = 4056) the changes in 2008. Healthcare trajectories during a 7-year window were assessed by generalized estimating equations. Between- and within-wave differences were examined by interaction models. Results: Psychiatric healthcare increased until the year preceding DP and declined thereafter, with one exception; such outpatient care kept increasing in wave 1 following DP. In the year preceding DP, 4.6 and 19.2% of the individuals in wave 1 had psychiatric in- and specialized outpatient care, respectively, compared with 7.9 and 46.6% in wave 2. No clear pattern was observed regarding somatic healthcare. The slopes of the different DP waves differed mainly during DP granting years (1 year prior to 1 year after), showing a sharper decline in wave 2. Conclusion: Transition to DP due to CMD seems to be associated with changes in psychiatric healthcare use, with higher rates in the year preceding DP. Outpatient healthcare patterns somewhat differed among those granted DP after stricter rules were introduced.

Burden for Parents of Patients With Schizophrenia—A Nationwide Comparative Study of Parents of Offspring With Rheumatoid Arthritis, Multiple Sclerosis, Epilepsy, and Healthy Controls

BACKGROUNDnThe study aimed to (1) compare the risk of health care use, adverse health status, and work productivity loss of parents of patients with schizophrenia to parents of patients with multiple sclerosis (MS), rheumatoid arthritis (RA), epilepsy, and healthy controls; and (2) evaluate such outcome measures while considering disease severity of schizophrenia.nnnMETHODSnBased on linkage of Swedish registers, at least one parent was included (n = 18215) of patients with schizophrenia (information 2006-2013, n = 10883). Similarly, parental information was linked to patients with MS, RA, epilepsy, and matched healthy controls, comprising 11292, 15516, 34715, and 18408 parents, respectively. Disease severity of schizophrenia was analyzed. Different regression models yielding odds ratios (OR), hazard ratios (HR), or relative risks (RR) with 95% confidence intervals (CI) were run.nnnRESULTSnPsychiatric health care use, mainly due to anxiety and affective disorders, showed a strongly increasing trend for parents of patients with schizophrenia throughout the observation period. During the follow-up, these parents had an up to 2.7 times higher risk of specialized psychiatric health care and receipt of social welfare benefits than other parents. Parents of the moderately severely ill patients with schizophrenia had higher risk estimates for psychiatric health care (RR: 1.12; 95% CI: 1.07-1.17) compared with parents of least severely ill patients.nnnCONCLUSIONSnParents of patients with schizophrenia have a considerably higher risk of psychiatric health care and social welfare benefit receipt than other parents. Psychiatric health care use worsens over time and with increasing disease severity of the offspring.

Trajectories of antidepressant medication use in individuals before and after being granted disability pension due to common mental disorders : a nationwide register-based study

BackgroundEarly retirement caused by disability pension (DP) due to common mental disorders (CMDs) is frequent in European countries. Inadequate treatment, e.g., suboptimal antidepressant (AD) medication before DP can be crucial in such DP. This explorative study aimed to disentangle trajectories of AD based on defined daily dose (DDD) before and after granted DP, and to characterize the trajectories by socio-demographics and medical factors.MethodsAll 4642 individuals in Sweden aged 19–64 with incident DP due to CMD in 2009–2010 were included. Trajectories of annual DDDs of AD were analysed over a 6-year period by a group-based trajectory method. Associations between socio-demographic or medical factors and different trajectories were estimated by chi2-test and multinomial logistic regression.ResultsFive trajectories of ADs were identified. Three groups, comprising 34%, 34%, and 21% of the cohort, had constant AD levels before and after DP with mean annual DDDs of 29, 234, and 580, respectively. Two groups, each including 6% of the cohort, had increasing levels of DDDs, levelling off at around 1150 and 785 DDDs after DP. Particularly age, outpatient care due to mental diagnoses and DP diagnoses were significantly associated with different trajectories (pu2009<u20090.05). All the groups had a larger proportion of older individuals (>u200950%, 45–64xa0years), except for the ‘increasing low’ group, where younger individuals were in majority (>u200960%, 18–44xa0years), who more frequently exited labour market due to ‘anxiety disorders’, with lower education and more specialised healthcare before DP than the other groups.ConclusionThe heterogeneity among the five trajectory groups was partly explained by age, the severity of the mental disorder and the DP diagnoses. DDDs of ADs, though on different levels, varied marginally before and after granted DP in the majority. Moreover, AD levels were very low in one third of the individuals. Early identification and focus on the ‘increasing low’ group might be important in order to identify individuals at risk for further increase in annual DDDs of ADs even after granted DP, and might also contribute in prevention of DP. Further detailed research regarding different groups is warranted.

Trajectories and characteristics of functional impairment before and after suicide attempt in young adults – a nationwide register-based cohort study

BackgroundDespite high rates of youth suicide attempt, little is known about patterns of functional impairment in terms of sickness absence and disability pension (SA/DP) before and after an attempt. The aim was to identify SA/DP trajectories among young adults with or without suicide attempt and to describe associations of socio-demographic and clinical factors with such trajectories.MethodsThis is a population-based cohort study of 5385 individuals aged 25–40xa0years with a first suicide attempt during 2007–2009. One control for each case without suicide attempt was matched by socio-demographic factors. Trajectories of annual SA/DP months over an eight-year period were analysed by group-based trajectory modelling. Associations between socio-demographic and clinical factors with trajectory groups were estimated by chi2-test and multinomial logistic regression.ResultsTwo groups of suicide attempters had low SA/DP levels over time (62%). One group had constantly high SA/DP levels (16%). The remaining two groups had increased SA/DP initially, which then decreased at different time points. Socio-demographic and clinical factors were associated with different trajectories (R2xa0=xa00.44). Suicide attempters with low levels of SA/DP were likely to be unemployed whereas a larger proportion of those with high levels of SA/DP had psychiatric health care before the suicide attempt, particularly due to schizophrenia and non-affective psychoses or personality disorders.ConclusionsYoung suicide attempters even with no/low levels of SA/DP were likely to be marginalised at the labour market. Schizophrenia/non-affective psychoses and personality disorders were important clinical factors for differentiating the levels of SA/DP among young suicide attempters.