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Chronic arsenic exposure is known to affect the immune system. We aimed to evaluate the association between arsenic exposure and immune cell profile in 15 years old adolescents (n=389) in rural Bangladesh, with chronic exposure to groundwater arsenic. Single blood and urine were collected. Urinary arsenic (U-As) concentration was measured using atomic absorption spectrometry. Peripheral blood mononuclear cells (PBMC) were analyzed by flow cytometry. Non-linear association was found between U-As (median, 24.9 µg/L) and immune cells with a cut-off at U-As 20 µg/L. U-As (<20 µg/L) were significantly associated with increases in CD8 + T (21 %), na ï ve CD8 + T (42 %) and early B cells (40 %), and classical monocytes (55 %), but reduction in CD3 + T cells (37 % ) and intermediate-monocytes (56 %). U-As (>20 µg/L) were associated with a 3 % reduction in memory B cells. Arsenic exposure was associated with altered immune cell profile in adolescents likely rendering them vulnerable to adverse health effects in later life., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: This study investigates how lifestyle factors and westernization contribute to obesity and examines the influence of body mass index (BMI) changes and lifestyle factors on "lipitension," a significant risk factor for heart disease and metabolic syndrome. Methods: This prospective study focused on women aged 20-64 without pre-existing hypertension and dyslipidemia who underwent regular medical checkups between April 2016 and March 2022. Anthropometric measurements and blood pressure, along with low-density lipoprotein, high-density lipoprotein, and triglycerides levels, were assessed. Results: Over an average 46.5-month follow-up, 11.5% of initially healthy young and middle-aged women developed lipitension. Categorizing participants based on BMI changes revealed stable (63.8%), decreased (12.5%), and increased (23.8%) groups within this 11.5%. Increased BMI is linked with a heightened hazard risk for lipitension. Women with increased BMI who refrained from snacking (aHR [95% confidence interval (CI)] = 2.750 [1.433-5.279]), avoided late-night eating (aHR [95% CI] = 1.346 [1.032-1.754]), and engaged in alcohol consumption (aHR [95% CI] = 2.037 [1.138-3.646]) showed an elevated risk. Conversely, within the decreased BMI group, behaviors like skipping breakfast (aHR [95% CI] = 0.190 [0.047-0.764]), eating quickly (aHR [95% CI] = 0.457 [0.215-0.972]), and not eating late (aHR [95% CI] = 0.665 [0.467-0.948]) were associated to a reduced lipitension. Subgroup analysis for women with BMI <23 revealed specific behaviors influencing lipitension risk in both BMI-increased and BMI-stable groups. Conclusion: Customized interventions, including for women with BMI <23, enhance heart health, mitigating global lifestyle diseases and obesity.

Background Handgrip strength is an indicator of muscle function and a predictor of health outcomes. However, only a few studies have examined the association between handgrip strength and the development of kidney damage. This study aimed to investigate the longitudinal association of handgrip strength with kidney damage in a general Japanese population. Methods This prospective cohort study enrolled participants with normal kidney function who attended annual health check-ups in Ibaraki Prefecture, Japan, between April 2016 and March 2020. Clinical information, including data from blood and urine tests, physiological examinations, and handgrip strength tests, was collected at enrollment. Lifestyle information was also collected via a self-administered questionnaire. The study participants were followed up for the progression of kidney damage until March 2023. Relative handgrip strength was calculated by dividing the handgrip strength by the body mass index to adjust for differences in body mass. A Cox proportional hazards model was used to examine the relationship between relative handgrip strength and the progression of kidney damage. Results A total of 4304 participants with normal kidney function were enrolled in this study. During the mean follow-up period of approximately 4 years (SD 1.8 years), 15.4% of the participants developed kidney damage. After adjusting for covariates, higher relative handgrip strength was associated with a lower risk of kidney damage in men (HR = 0.63, 95% CI: 0.43 - 0.90; p = 0.012), but no significant association was observed in women. Conclusions Higher relative handgrip strength is associated with a lower risk of kidney damage in men. This finding highlights the importance of muscle strength in preventing kidney damage., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Research Ethics Committee of the Faculty of Medicine at the University of Tsukuba issued approval 1000. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: This work was supported by JST COI Grant Number JPMJCE1301, JST SPRING Grant Number JPMJSP2124. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Deng et al.)

Background: Diabetes is more apparent in adulthood but may be dormant in childhood and originates during early fetal development. In fetal biometry, femur length (FL) is crucial for assessing fetal growth and development. This study aimed to assess potential associations between fetal femur growth and prediabetic biomarkers in Bangladeshi children., Methods: A cohort study embedded in a population-based maternal food and micronutrient supplementation (MINIMat) trial was conducted in Matlab, Bangladesh. The children in the cohort were followed up until 15 years of age. In the original trial, pregnancy was confirmed by ultrasound before 13 gestational weeks (GWs). Afterward, ultrasound assessments were performed at 14, 19, and 30 GWs. FL was measured from one end to the other, capturing a complete femoral image. The FL was standardized by GW, and a z-score was calculated. FBG and HbA1c levels were determined in plasma and whole blood, and the triglyceride-glucose index, a biomarker of insulin resistance, was calculated as Ln [fasting triglycerides (mg/dl) × fasting glucose (mg/dl)/2]. Multivariable linear regression analysis using a generalized linear model was performed to estimate the effects of FL at 14, 19 and 30 GWs on prediabetic biomarkers at 9 and 15 years of age. Maternal micronutrient and food supplementation group, parity, child sex, and BMI at 9 years or 15 years were included as covariates., Results: A total of 1.2% (6/515) of the participants had impaired fasting glucose during preadolescence, which increased to 3.5% (15/433) during adolescence. At 9 years, 6.3% (32/508) of the participants had elevated HbA1c%, which increased to 28% (120/431) at 15 years. Additionally, the TyG index increased from 9.5% (49/515) (during preadolescence) to 13% (56/433) (during adolescence). A one standard deviation decrease in FL at 14 and 19 GWs was associated with increased FBG (β = - 0.44 [- 0.88, - 0.004], P = 0.048; β = - 0.59 [- 1.12, - 0.05], P = 0.031) and HbA1c (β = - 0.01; [- 0.03, -0.005], P = 0.007; β = - 0.01 [- 0.03, - 0.003], P = 0.018) levels at 15 years. FL was not associated with diabetic biomarkers at 9 years., Conclusion: Mid-trimester impaired femur growth may be associated with elevated prediabetic biomarkers in Bangladeshi adolescents., (© 2024. The Author(s).)

Introduction Several studies have reported the usefulness of measuring lower limb muscle strength through the motion of standing up using a reaction force measuring device positioned on the ground. There is inadequate information on the association between cardiovascular disease risk factors and ground reaction force (GRF) during standing up. Therefore, this study estimated the association between GRF by sit-to-stand movements and cardiovascular disease risk factors in a health check-up population. Methods This cross-sectional study included 1,182 healthy participants without chronic diseases who underwent periodic health check-ups from August 2019 to December 2020. The study included individuals aged ≥20 years who underwent a standing test from an initial seated position in a chair. A sit-to-stand force analyzer was used to measure GRF, and health status information was collected at enrollment. The relationships between blood test data and each measurement obtained from GRF measurements (forth/body mass (F/M), rate of forth development/body mass (RFD/M), and stable time) were parsed according to sex using linear regression analysis coordinated by age. GRF measurements and their relationships with cardiovascular disease risk factors were assessed using logistic regression analysis, adjusted for age and sex. Results A total of 1,182 participants was included in this study, with male participants accounting for 61.5%. The study participants had a median age of 57.0 years (IQR: 47.0-63.0). After adjusting for age, F/M was positively associated with high-density lipoprotein cholesterol in male (β=22.59, p<0.001) and female participants (β=20.35, p=0.011) and negatively associated with plasma glucose in male (β=-16.25, p=0.008) and female participants (β=-18.78, p=0.028). Stable time (time required to be stabilize after standing up movement) was positively associated with hemoglobin A1c levels in male (β=0.55, p=0.001) and female participants (β=0.56, p=0.036). Logistic regression analysis adjusted by age and sex showed that a lower F/M ratio was associated with hypertension, hyperlipidemia, and diabetes mellitus (adjusted odds ratio (aOR) =1.60, p=0.01; aOR=1.75, p=0.001; and aOR=2.23, p=0.002, respectively). Lower RFD/M was associated with hyperlipidemia and diabetes mellitus (aOR=1.46, p=0.013 and aOR=1.63, p=0.045, respectively). A shorter stable time was associated with diabetes mellitus (aOR=0.39, p<0.001). Conclusions These findings suggest that lower limb function impairment, as assessed via standing-up movements using a GRF-measuring device, may relate to cardiovascular disease. Further research is needed to confirm this association., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Hokimoto et al.)

Slum environment may pose risk to child health and nutrition. This study assessed the risks of anemia among under five-year-old children, five years after implementing a nutrition education and counseling intervention in two urban slums in Nairobi, Kenya. A cross-sectional study was conducted in May 2018 as a follow-up of a randomized controlled study carried out between 2012-2015. A trained nurse measured hemoglobin levels of 438 children from households which participated in the initial study. Multivariate logistic regression was conducted to identify risks of anemia. The mean (+ SD ) age of the children was 55.9 (5.3) months and mean (+ SD ) hemoglobin was 10.7 (1.5) g/dL. Anemia prevalence was 59.8%, 33.9% had mild, 24.7% moderate, and 1.2% severe anemia. Absence of home toilet (AOR = 3.31; 95% CI, 1.20-9.09), household which paid to use a toilet facility (AOR = 1.86; 95% CI, 1.12-3.08), child's frequency of eating colored fruits and vegetables (AOR = 0.28; 95% CI, 0.08-0.96), meat and meat products (AOR = 0.31; 95% CI, 0.23-6.01), number of meals a child aged <15years ate a day preceding the study (AOR = 1.49; 95% CI, 1.14-1.98), and a mother who had a history of anemia (AOR = 2.89; 95% CI, 1.22-12.01), were factors significantly associated with child's anemia status. The environment of urban informal settings influences child anemia status. Further studies with interventions are therefore required in order to improve sanitation facilities and access to meats, fruits, and vegetables in urban slums through innovative kitchen gardens and small animal husbandry.

Diabetic overweight patients are more likely to show the progression of kidney damage than the general population. The majority of people in the early stages of kidney damage do not recognize the importance of risk modification, mainly due to the asymptomatic nature of the disease. This study aimed to examine specific risk combinations of lifestyle and BMI regarding the deterioration of kidney function and to explore whether there are gender-based differences among the prediabetic population. Prediabetic participants with normal kidney function were identified via annual health examination from April 2016 to March 2019. The information on health status and lifestyle was collected at enrollment. The study subjects were followed until March 2021 to observe the progression of kidney damage. There were 2241 participants enrolled in this study. Smoking (HR = 3.5, p < 0.001), eating snacks (HR = 3.2, p < 0.001), not engaging in regular exercise (HR = 2.9, p < 0.001), and not having adequate sleep (HR = 3.0, p < 0.001) showed accelerated risks for kidney damage progression among the prediabetic population in males. These lifestyle effects were not observed in females. In conclusion, risk-based modification of lifestyle behavior is important to prevent kidney function damage among the overweight prediabetic population in males.

Background: Being underweight, overweight, or obese can lead to adverse health effects. Hence, it is important to understand the specific factors that change the burden of underweight and overweight to target appropriate disease control strategies. This study was designed to examine the prevalence and factors associated with underweight and overweight among young and middle-aged women in Japan., Materials and Methods: A cross-sectional study was conducted among women aged 20-59 years who participated in health checkups at a regional health care center in 2018 and 2019 ( N  = 1722). The assessments included anthropometric, blood pressure measurements, and a standardized self-administered questionnaire. Multivariable logistic regression analysis assessed lifestyle factors associated with body mass index for underweight <18.5 kg/m 2 ) and overweight/obesity (25.0 kg/m 2 and above)., Results: The prevalence of underweight and overweight/obesity were 12.3%, and 22.5%, respectively. No lifestyle factors were found to be significantly associated with being underweight. Having dinner within 2 hours before bed was positively associated with being overweight/obese [adjusted odds ratio (AOR): 1.448, 95% confidence interval (CI): 1.014-2.068]. Women who gained 10 kg since their 20s were more likely to fall into overweight/obesity category (AOR: 9.674, 95% CI: 1.014-2.068). Women who were using a lipid-lowering medication (AOR: 3.150, CI: 1.892-5.246) were associated with three times higher risk of being overweight/obese. Hypertension and dyslipidemia were significantly associated with overweight/obesity (AOR: 3.094, 95% CI: 2.201-4.351 and AOR: 2.498, 95% CI: 1.831-3.409, respectively)., Conclusion: One in five middle-aged women was overweight or obese, whereas one in eight was underweight. In relation to the prevention of overweight/obesity, specific health promotion messages regarding eating timing should be developed., Competing Interests: No competing financial interests exist., (© Rupa Singh et al., 2022; Published by Mary Ann Liebert, Inc.)

Objective: Hearing loss is a major public health concern. Higher physical function may be related to the maintenance of hearing acuity. Therefore, this study examined the association between hearing loss and physical function in the general population., Methods: This cross-sectional study was conducted with health checkup participants who underwent pure-tone audiometry at a regional health care center in Japan. Information for physical function included handgrip strength, vital capacity (VC), and forced expiratory volume in one second (FEV1). A hearing threshold of >30 dB at 1 kHz and/or >40 dB at 4 kHz in either ear was identified as hearing loss. The characteristics of the subjects were examined with stratification by sex and age group. Multivariable logistic regression analysis was performed to examine the association between hearing loss and physical function with adjustments for age, body mass index and current smoking., Results: Among the 4766 study subjects, 56.5% were male. The mean age was 47.7 years (SD: 13.8 years; range: 20-86 years), and the prevalence of hearing loss was 12.8% based on the definition stated above. For females, handgrip strength, VC, and FEV1 showed significant negative associations with hearing loss (multivariable-adjusted OR [95% CI] = 0.691 [0.560-0.852], 0.542 [0.307-0.959], and 0.370 [0.183-0.747], respectively). These associations were not found in males., Conclusions: Higher physical function was associated with a lower prevalence of hearing loss among females. This study suggests that it is important to maintain physical function for hearing loss in females. Further studies are required to investigate sex differences in the relationship between physical function and hearing loss in the general population., Competing Interests: The authors have declared that no competing interests exist.

Objective: Hearing loss is an important public health problem. Its causes vary, including infections, noise, and aging. The first wave of the COVID-19 pandemic occurred in April 2020 in Japan. During the pandemic, people were urged to stay at home and drastically changed their lifestyles. This study aimed to examine hearing loss before and during the pandemic. The prevalence during the pandemic after April 2020 was compared for the period in 2019. Study subjects were those who received health checkups in both periods. Hearing loss was defined as a hearing threshold of > 30 dB at 1 kHz and > 40 dB at 4 kHz in either ear using pure-tone audiometry., Results: A total of 2367 persons presented in both 2019 and 2020. The overall rates of hearing loss were 9.5% and 13.2% before and after the pandemic, respectively. After controlling for age, sex, current smoking, regular exercise and alcohol consumption, the rate of hearing loss showed a significant increase in 2020 (p =  < 0.0001). With age stratification, an increase was observed in the participants aged < 40 years (1.3% vs. 3.1%, p < 0.001) and 40-59 years (7.2% vs. 12.6%, p < 0.001). Further studies are needed to confirm the impact of the COVID-19 pandemic on hearing loss., (© 2022. The Author(s).)

Little is known about the usefulness of biomarkers to study the influence of prenatal nutrition supplementation in improving child growth. Anthropometry is not always straightforward to understand how nutrition might impact growth, especially in settings with high rates of malnutrition and infections. We examined the effects of prenatal supplementation on growth and growth biomarkers and the relationship between anthropometric measures and growth biomarkers of children at 4.5 and 9 years of age. Children were enrolled from a longitudinal cohort, where mothers were randomized into daily supplementation with either early-food (≤9 gestation week [GW]) or usual-food (~20 GW) (608 kcal 6 days/week); they were further randomized to receive 30-mg or 60-mg iron with 400-μg folic acid, or multiple micronutrients (MM) in rural Bangladesh. Anthropometric data were collected from mothers at GW8 and children at 4.5 (n = 640) and 9 years (n = 536). Fasting blood was collected from children at each age. Early-food supplementation showed reduced stunting and underweight at 4.5 and 9 years age respectively compared to usual-food. Prenatal supplementations did not have any effect on growth biomarkers except for STAT5b expression which was lower in the early-food compared to the usual-food group (β = -0.21; 95 CI% = -0.36, -0.07). Plasma concentrations of 25-hydroxy vitamin D and calcium were both inversely associated with weight-for-age and body mass index-for-age Z-scores at 9 years, particularly in early-food and MM groups. Although there was minimal effect on child growth by prenatal supplementations, the associations of biomarkers with anthropometric indices were predominantly driven by timing of food or MM supplementations., (© 2021 The Authors. Maternal & Child Nutrition published by John Wiley & Sons Ltd.)

Objective: Handgrip strength, a simple measure of muscle strength, has been reported as a predictor of both prediabetes and type 2 diabetes mellitus (T2DM) and has been suggested for screening prediabetes and T2DM risk. This study examined the relationship of handgrip strength with prediabetes and T2DM among rural- and urban-dwelling adults in Malawi., Methods: This was a cross-sectional study nested in a follow-up study of prediabetic and prehypertensive individuals identified during an extensive noncommunicable disease survey in Malawi. A total of 261 participants (women: 64%) were recruited. Univariate and multivariate binary logistic regression analyses were performed to examine the association of prediabetes and T2DM with relative handgrip strength., Results: The mean (SD) age of the participants was 49.7 (13.6) years, and 54.0% were between the ages of 40 and 59 years. The mean (SD) absolute handgrip strength and relative handgrip strength were 28.8 (7.3) kg and 1.16 (0.40) kg/BMI, respectively, and the mean relative handgrip strength differed significantly (p < 0.001) by T2DM status. In unadjusted model, the odds ratio (OR) of prediabetes and T2DM per unit increase in relative handgrip strength was 0.12 [95% CI; 0.04-0.33]. The result remained significant after adjusting for age (continuous), sex, place of study, hypertension, dyslipidaemia and level of education (aOR [95% CI]; 0.19 [0.03-0.95])., Conclusions: The findings suggest that handgrip strength could be a relatively inexpensive, noninvasive measure for contributing to risk scores to identify high-risk individuals for screening diabetes in SSA., (© 2021 John Wiley & Sons Ltd.)

Objective: Previous studies have shown that relative handgrip strength, handgrip measure divided by body mass index (BMI), affects the future onset of diabetes and prediabetes. However, fat free mass (FFM) has been suggested to adjust for this effect better than BMI. In this study, we examined applicability of models that adjusted handgrip-diabetes relationship with either BMI or FFM., Results: Of 1940 participants (56.2% male, average (SD) age, 57.2 [11.2] years), 267 (13.8%) had diabetes (DM) and 912 (47.0%) had prediabetes (pre-DM). The average handgrip measure for men was 40.0 kg (tertile measures, 37.4 kg and 42.5 kg) and for women 24.2 kg (tertile measures, 22.6 kg and 25.7 kg). Among both sexes, the percentage of people unaffected by DM or pre-DM was highest in the strong handgrip group and lowest in the weak handgrip group. Analysis using binary logistic models showed that an increase in handgrip measure was associated with a decrease in the chance of having either pre-DM or DM. This effect was detected by both BMI models and FFM models, even after adjustment for medical and lifestyle factors. Either or both should be used depending on the research aims, setting and methods., (© 2021. The Author(s).)

Objective: Chronic undernutrition is a common phenomenon in Bangladesh. However, information is grossly lacking to report the correlation between chronic undernutrition trajectory and lung function in children. The aim of the current study was to understand the association between early-childhood chronic undernutrition trajectory and lung function at preadolescence., Design: The current study is a part of the 9-year follow-up of a large-scale cohort study called the Maternal and Infant Nutrition Interventions in Matlab., Settings: The current study was conducted in Matlab, a sub-district area of Bangladesh that is located 53 km south of the capital, Dhaka., Participants: A total of 517 children participated in lung function measured with a spirometer at the age of 9 years. Weight and height were measured at five intervals from birth till the age of 9 years., Results: Over half of the cohort have experienced a stunting undernutrition phenomenon up to 9 years of age. Children who were persistently or intermittently stunted showed lower forced expiratory volume (ml/s) than normal-stature children (P < 0·05). Children who exhibited catch-up growth throughout 4·5 years from the stunted group showed similar lung function with normal counterparts, and a better lung function than in children with the same growth velocity or who had faltering growth. In the multivariable models, similar associations were observed in children who experienced catch-up growth than their counterparts after adjusting for covariates., Conclusion: Our data suggest that catch-up growth in height during early childhood is associated with a better lung function at preadolescence.

INTRODUCTION: Exposure to microgravity reduces muscle mass, volume, and performance. The ingestion of protein, especially combined with carbohydrate intake and exercise after ingestion, improves net muscle protein synthesis and increases muscle mass. However, there are few studies on this relationship during and after a long-term spaceflight. The objective of this study was to investigate the influence of protein and the combined effects of carbohydrate intake on muscle performance following long-term spaceflight. METHODS: This study is a retrospective cohort study involving secondary analysis of data stored in the NASA Lifetime Surveillance of Astronaut Health Repository. Multivariable analysis was performed to evaluate the impact of protein intake on physical performance by considering covariates potentially associated with each model. RESULTS: After adjusting for sex, age, flight week, energy intake, and preflight physical performance, protein intake was found to be significantly associated with concentric measurements for knee extension ( 51.66), ankle plantar flexion ( 32.86), and eccentric measurements for ankle plantar flexion ( 79.85) at 5 d after landing. Significant associations remained after controlling for exercise effect. No significant interaction between protein and carbohydrate intake was observed in either model. DISCUSSION: Protein intake during spaceflight was related to physical performance for knee extension and ankle plantar flexion, even after taking exercise effect into consideration. However, protein and carbohydrate intake provided no synergetic benefit. This suggests that high protein intake, about twice the current average intake, may serve as a countermeasure to offset the negative effects of long-duration spaceflights. Nozawa Y, Wagatsuma Y. Protein intake and physical performance following long-term stay on the International Space Station . Aerosp Med Hum Perform. 2021; 92(3):153159.

There is growing interest in understanding the contribution of environmental toxicant exposure in early life to development of cardiometabolic diseases (CMD) in adulthood. We aimed to assess associations of early life exposure to arsenic and cadmium with biomarkers of CMD in children in rural Bangladesh. From a longitudinal mother-child cohort in Matlab, Bangladesh, we followed up 540 pairs. Exposure to arsenic (U-As) and cadmium (U-Cd) was assessed by concentrations in urine from mothers at gestational week 8 (GW8) and children at ages 4.5 and 9 years. Blood pressure and anthropometric indices were measured at 4.5 and 9 years. Metabolic markers (lipids, glucose, hemoglobin A1c, adipokines, estimated glomerular filtration rate (eGFR) were determined in plasma/blood of 9 years old children. In linear regression models, adjusted for child sex, age, height-for-age z score (HAZ), BMI-for-age z score (BAZ), socioeconomic status (SES) and maternal education, each doubling of maternal and early childhood U-Cd was associated with 0.73 and 0.82 mmHg increase in systolic blood pressure (SBP) respectively. Both early and concurrent childhood U-Cd was associated with diastolic (D)BP (β = 0.80 at 4.5 years; β = 0.75 at 9 years). Each doubling of U-Cd at 9 years was associated with decrements of 4.98 mg/dL of total cholesterol (TC), 1.75 mg/dL high-density lipoprotein (HDL), 3.85 mg/dL low-density lipoprotein (LDL), 0.43 mg/dL glucose and 4.29 units eGFR. Each doubling of maternal U-Cd was associated with a decrement of 1.23 mg/dL HDL. Both maternal and childhood U-As were associated with decrement in TC and HDL. Multiple comparisons were checked with family-wise error rate Bonferroni-type-approach. The negative associations of arsenic and cadmium with biomarkers of CMD in preadolescent children indicated influence of both metal(loid)s on fat and carbohydrate metabolism, while cadmium additionally influenced kidney function and BP. Thus, fewer outcomes were associated with U-As compared to U-Cd at preadolescence., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: Pelvic organ prolapse (POP) is one of the main contributors to reproductive health problems that affect women's quality of life. Previous studies have reported the risk factors and prevalence of POP. The aim of this study is to examine the association between POP and short birth intervals in a rural area of Nepal., Methods: A cross-sectional study was conducted in Panchapuri municipality, located in Surkhet District of Karnali Province in Nepal. A questionnaire was used to collect information on POP, birth intervals, and other known confounding factors, such as age and parity. Multiple logistic regression analysis was used to examine the association between minimum birth intervals and POP., Results: The study recruited 131 women. The prevalence of POP was 29.8%. The mean (SD) of maternal age was 32.3 (0.7) years. The median parity was 2, with a range of 2-6 children. More than half (64.9%) of the women reported a minimum birth interval of less than 2 years. Maternal age at birth, minimum birth interval, parity, and latest birth interval were significantly associated with POP in univariate analyses. After adjusting for the potential confounding factors such as age and occupation, the minimum birth interval was significantly associated with POP [AOR = 3.08, 95% CI 1.04-9.19]., Conclusion: The prevalence of POP was high in this rural area of Nepal. Age, parity, occupation, and minimum birth interval were significantly associated with POP.

Conventional risk factors for prediabetes and type 2 diabetes such as obesity do not completely explain the higher prevalence of prediabetes; therefore, research to investigate the role of other independent risk factors is required. A few cross-sectional studies have reported an association between muscle strength and prediabetes among normal-weight adults, but the longitudinal relationship of muscle strength with incident prediabetes among adults has not been reported. This prospective cohort study was conducted to investigate whether relative handgrip strength in adults predicted prediabetes incidence after 2 years of follow-up. The study was conducted in Ibaraki prefecture, Japan and recruited individuals without prediabetes and diabetes attending lifestyle related medical examinations between April 2016 and March 2017 (n = 2054). Individuals who came for the follow-up medical examinations between April 2018 and March 2019 were included in the analysis (n = 1075). One hundred sixty-nine individuals (15.7%) developed prediabetes after a mean follow-up of 24.2 months (SD = 1.9 months). Multivariable adjusted hazard ratios (aHR) of new prediabetes cases were calculated using Cox regression. Higher baseline relative handgrip strength predicted a lower risk (aHR [95% CI] = 0.38 [0.21-0.71] of prediabetes incidence among adults. Importantly, relative handgrip strength predicted new prediabetes cases among normal weight individuals (aHR [95% CI] = 0.39 [0.16-0.96]). The findings suggest that handgrip strength measurement is useful to identify individuals at high risk of newly diagnosed prediabetes, importantly, among normal weight individuals. The identified individuals may benefit from early intervention to reduce the risk of prediabetes., (© 2020 The Authors.)

Background: Vitamin A deficiency (VAD) impairs T-cell-mediated immunity. In regions where VAD is prevalent, vitamin A supplementation (VAS) reduces child mortality, perhaps by improving immune function., Objective: Our objective was to determine if neonatal VAS would improve thymic function in Bangladeshi infants, and to determine if such effects differed by sex or nutritional status (i.e., birth weight above/below the median)., Methods: Three hundred and six infants were randomly assigned to 50,000 IU vitamin A (VA) or placebo (PL) within 48 h of birth. Primary outcomes were measured at multiple ages and included 1) thymic index (TI) at 1, 6, 10, and 15 wk; 2) T-cell receptor excision circles (TREC), an index of thymic output of naïve T cells; and 3) total/naïve T cells in peripheral blood at 6 wk, 15 wk, and 2 y. A mixed linear model for repeated measures was used to assess group differences at each age and identify interactions with sex and birth weight., Results: VAS did not significantly (P = 0.21) affect TI overall (i.e., at all ages) but decreased TI by 7.8% (P = 0.029) at 6 wk: adjusted TI means for the PL and VA groups at 1, 6, 10, and 15 wk were 4.09 compared with 3.80 cm2, 7.78 compared with 7.18 cm2, 8.11 compared with 7.84 cm2, and 7.91 compared with 7.97 cm2, respectively. VAS did not significantly (P = 0.25) affect TREC overall but decreased TREC by 19% (P = 0.029) at 15 wk: adjusted TREC means for the PL and VA groups at 6 wk, 15 wk, and 2 y were 13.6 compared with 16.1 copies/pg DNA, 19.4 compared with 15.7 copies/pg DNA, and 11.8 compared with 10.0 copies/pg DNA, respectively. VAS did not significantly affect overall total (P = 0.10) or naïve (P = 0.092) T cells: adjusted naïve T-cell means for the PL and VA groups at 6 wk, 15 wk, and 2 y were 3259 compared with 3109 cells/µL, 3771 compared with 3487 cells/µL, and 1976 compared with 1898 cells/µL, respectively., Conclusion: In contrast to our hypothesis, VAS decreased thymic function early in infancy but health effects are presumably negligible owing to the transience and small magnitude of this effect. This trial was registered at clinicaltrials.gov as NCT01583972 and NCT02027610., (Published by Oxford University Press on behalf of the American Society for Nutrition 2019.)

Objective: Pneumonia is a common but serious illness that continues to present significant morbidity and mortality. Although the effect of severity at admission on outcome has been well reported, the role of comorbidity is still not widely understood. The Charlson Comorbidity Index measures comorbidity with a well-established history of predicting long-term outcome but its utility in pneumonia prognosis is still limited. Here, we use the Charlson Comorbidity Index and hospital surveillance data to investigate associations between comorbidities and in-hospital mortality due to community-acquired pneumonia., Results: Among the 535 eligible adult patients (69.0% male, median [IQR] age, 79 [70-84] years), 100 (18.7%) acquired severe to extremely severe pneumonia. The median [IQR] CCI was 1 [1-3]. Malignancy (129 of 535, 24.1%), chronic pulmonary diseases (113 of 535, 21.1%) and congestive heart failure (103 of 535, 19.3%) were frequent. Higher Charlson Comorbidity Index scores were associated with higher risk of in-hospital mortality (OR 1.28; 95% CI 1.07-1.53). These results support the inclusion of comorbid burden in predicting community-acquired pneumonia outcome.

Objectives: To evaluate the prophylactic effect of sulfasalazine against Pneumocystis jirovecii pneumonia (PJP) among rheumatoid arthritis (RA) patients., Methods: We used a nationwide Japanese multicenter RA database to extract data from 2005 and 2014. To identify PJP cases, we selected patients hospitalized for PJP and verified their diagnosis. Two control groups, one unmatched and the other matched for age, sex, glucocorticoid, methotrexate, and tacrolimus dosage, and the use (and type, if used) of biological disease-modifying antirheumatic drug were selected by incidence-density sampling. The odds ratios for PJP associated with sulfasalazine use and other clinical factors were estimated by exact and standard conditional logistic regression., Results: From 18,668 participants, 60 cases, 356 unmatched controls, and 337 matched controls were selected. None of the cases received sulfasalazine before PJP onset. A comparison of the cases with the unmatched controls showed that sulfasalazine use carried a decreased risk of PJP (adjusted odds ratio 0.18, 95% confidence interval 0.00-0.92). A comparison of the cases and matched controls also showed that sulfasalazine use had a decreased risk of PJP (0.08, 0.00-0.36). In an analysis of the cases and unmatched controls who did not receive sulfasalazine, an increased risk of PJP was associated with lung disease (3.88, 1.89-7.95) and the use of glucocorticoid (5.71, 2.68-12.19), methotrexate (5.25, 2.01-13.74), and tumor necrosis factor inhibitors (2.32, 1.10-4.93)., Conclusions: The results of this nested case-control study demonstrated the preventive effect of sulfasalazine against PJP. The results await confirmation by future prospective studies., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Stress can impair T cell-mediated immunity. To determine if infants with high stress responses had deficits in T-cell mediated immunity, we examined the association of pain-induced cortisol responsiveness with thymic function and vaccine responses in infants. This study was performed among 306 (male = 153 and female = 153) participants of a randomized, controlled trial examining the effect of neonatal vitamin A supplementation on immune function in Bangladesh (NCT01583972). Salivary cortisol was measured before and 20 min after a needle stick (vaccination) at 6 weeks of age. The thymic index (TI) was determined by ultrasonography at 1, 6, 10 and 15 weeks. T-cell receptor excision circle and blood T-cell concentrations were measured at 6 and 15 weeks. Responses to Bacillus Calmette-Guérin (BCG), tetanus toxoid, hepatitis B virus and oral poliovirus vaccination were assayed at 6 and 15 weeks. Cortisol responsiveness was negatively associated with TI at all ages (p < .01) in boys only, was negatively associated with naïve helper T-cell concentrations in both sexes at both 6 (p = .0035) and 15 weeks (p = .0083), and was negatively associated with the delayed-type hypersensitivity (DTH) skin test response to BCG vaccination at 15 weeks (p = .034) in both sexes. Infants with a higher cortisol response to pain have differences in the T-cell compartment and a lower DTH response to vaccination. Sex differences in the immune system were seen as early as 6 weeks of age in these healthy infants.

Background: Guidelines recommend morphine as the first-line pharmacological treatment for cancer dyspnoea. However, trials with other opioids have not been performed. Our aim was to demonstrate the non-inferiority of oxycodone to morphine for relieving dyspnoea in cancer patients., Methods: We conducted a multicentre, open-label, parallel-group, randomized control trial. We randomly and equally assigned cancer patients on regular oxycodone who developed dyspnoea to get a single dose of oral immediate-release oxycodone or morphine. We evaluated the change in dyspnoea intensity (numeric rating scale: 0-10) and adverse events after the medication administration., Results: This study was preconfidence interval -maturely terminated. All 17 enroled patients (8 using oxycodone, 9 using morphine) completed evaluations. In the oxycodone group, dyspnoea intensity decreased 1.75 points [95% confidence interval, 0.72-2.78] at 60 min and 1.50 points (95% confidence interval, -0.11 to 3.11) at 120 min. In the morphine group, dyspnoea decreased 1.33 points (95% confidence interval, 0.41-2.25) at 60 min and 1.00 point (95% confidence interval, -0.08 to 2.08) at 120 min. The differences did not fulfil the non-inferiority requirement. Although two and four patients in morphine group developed drowsiness at 60 and 120 min, no patient in oxycodone group developed significant adverse events., Conclusions: Although we did not show the non-inferiority of oxycodone, oxycodone may have some effectiveness for cancer dyspnoea without significant safety concern., Clinical Trial Registration: UMIN-CTR: UMIN 000005760.

Background: The present study aimed to examine the risk factors for death due to pneumonia in young children and healthcare behaviors of the guardians for children in rural Bangladesh. A prospective autopsy study was conducted among guardians of children aged 4 weeks to 59 months in Mirzapur, Bangladesh, from 2008 to 2012., Results: Pneumonia was the primary cause of death, accounting for 26.4% ( n  = 81) of all 307 deaths. Of the pneumonia deaths, 58% ( n  = 47) deaths occurred in younger infants (aged 4 weeks to < 6 months) and 24.7% ( n  = 20) in older infants (aged 6-11 months). The median duration of illness before pneumonia death was 8 days (interquartile range [IQR] 3-20 days). Prior to death, 91.4% ( n  = 74) children with pneumonia sought treatment, and of those who sought treatment, 52.7% ( n  = 39) sought treatment ≥ 2 days after the onset of disease. Younger infants of 4 weeks to < 6 months old were at 5.5-time (95% confidence interval [CI] 2.5, 12.0) and older infants aged 6-11 months were at 3-time (1.2, 7.5) greater risk of dying from pneumonia than older children aged 12-59 months. Children with a prolonged duration of illness (2-10 days) prior to death were at more risk for death by pneumonia than those who died from other causes (5.8 [2.1, 16.1]). Children who died from pneumonia sought treatment 3.4-time more than children who died from other causes. Delayed treatment seeking (≥ 2 days) behavior was 4.9-time more common in children who died from pneumonia than those who died from other causes. Children who died from pneumonia more often had access to care from multiple sources (5.7-time) than children who died from other causes., Conclusions: Delay in seeking appropriate care and access to multiple sources for treatment are the underlying risk factors for pneumonia death in young children in Bangladesh. These results indicate the perplexity in guardians' decisions to secure appropriate treatment for children with pneumonia. Therefore, it further underscores the importance of focusing on mass media coverage that can outline the benefits of seeking care early in the progression of pneumonia and the potential negative consequences of seeking care late., Competing Interests: The GEMS was approved by the Institutional Review Board (IRB) of the University of Maryland (UMB) and the Research Review Committee (RRC) and Ethical Review Committee (ERC) of the International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b). The post-mortem verbal autopsy was part of GEMS which was also approved by the IRB of UMB and RRC and ERC of icddr,b. Verbal consent was obtained from parents, and the ERC was satisfied with the voluntary participation, maintenance of the rights of the participants, and confidential handling of personal information by the research personnel and approved this consenting procedure.The authors declare that they have no competing interests.Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Background: Spine injury epidemiology in Japan has not been studied since the 1990s when its incidence was 39.4-40.2 per million and the major cause of injury was motor vehicle crashes. We elucidate the current epidemiological state of spinal injury and spinal injury patients in Japan for the clinicians and public health prevention programs., Methods: Spine injury patients were retrospectively selected from the Japan Trauma Data Bank (JTDB) from 2004 to 2013 for all ages and all spinal injuries. The Abbreviated Injury Scale codes (AIS98) were translated into injuries. The dataset was contributed by 241 hospitals nationwide. The data was analysed for the causes of spinal injury, injury severity, age, gender differences, injury types, survival, anatomic location, circumstances of injury and medical history., Results: A total of 25,792 (M, 70.1%, F, 29.9%, mean age: 53.4 years) spinal injury patients were recorded in the JTDB from 2004 to 2013, when multiple injuries were included the number of cases swelled to 33,892 (M, 70.4%, F, 29.6%). The number of patients with spinal injuries as a percentage of all traumatic patients in the JTDB was observed to increase from 2004 (15.4%) to 2013 (17.6%). The aetiology of the injuries was mostly falls (52.4%) and motor vehicle crashes (39.8%). Most injuries occurred at the cervical spine level (49.7%). Medical histories of cardiovascular diseases were found, due mostly to hypertension (19.6%). In total, most of the injuries were associated with fractures (64.8%) and others (30.7%) involved the spinal cord. Suicides (12.0%) and industrial accidents (9.0%) caused spine injury were uniquely prevalent in the population., Conclusion: The number of spine injuries has increased in the JTDB between 2004 and 2013. Motor vehicle crashes have been replaced by falls due to various causes as the leading cause of spine injury. Suicides and industrial accidents are becoming a burden. More studies are needed to verify the actual incidence., (Copyright © 2017 The Japanese Orthopaedic Association. Published by Elsevier B.V. All rights reserved.)

Background: Fetal growth restriction (FGR) and low birth weight(LBW) are serious public health problems. In developing countries, the incidence of low birth weight is predominantly the result of FGR, and both low birth weight and FGR are associated with neonatal death and later growth and development. Fetal growth charts are important for assessing the size of the fetus during pregnancy. The aims of this study were to describe the fetal growth pattern of a population in rural Bangladesh where maternal undernutrition is prevalent and to compare the timing of FGR in that population with WHO and INTERGROWTH- 21st international reference values., Methods: From November 2001 to October 2003, pregnant women were recruited in Matlab, a sub district of Bangladesh, and underwent three follow-up ultrasound examinations during pregnancy for measurement of the parameters of the fetal head, abdomen, and femur. The data were fitted to a linear-cubic model, and the derived values were compared with international reference values., Results: A total of 2678 singleton pregnancies were included in the analyses. The mean (SD) maternal age was 25.9 (5.8) years (range, 14-47 years). The mean (SD) early pregnancy BMI was 20.1 (2.6) kg/m 2 , and 27.6% of the women were underweight (BMI < 18.5 kg/m 2 ). The growth of the biparietal diameter and abdominal circumference was significantly smaller throughout the pregnancy than the reference values ( P  ≤ 0.05). Moreover, a larger deviation in the growth of Bangladeshi fetuses was observed after 28 weeks of gestation when compared with the WHO and INTERGROWTH-21st reference fetal growth charts ( P  ≤ 0.05). After 28 weeks of gestation, the average Bangladesh estimated fetal weight gain per week of gestational age was significantly lower than the WHO estimated fetal weight by as much as 67.4 g ( P  ≤ 0.001)., Conclusions: The present population-based study showed that fetuses were smaller in the third trimester when compared with the reference charts. Growth faltering started in the second trimester for all the biometric parameters for the head, abdomen, and femur. This finding provides more challenges concerning nutritional interventions., Competing Interests: The study was conducted according to the guidelines laid down in the Declaration of Helsinki, and the MINIMat study was approval by the Research Review and Ethical Review Committees of icddr,b. Written informed consent was obtained from each participant or from her legal guardian before the start of the study.Not applicableThe authors declare that they have no competing interests.Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Purpose: Maintaining independence after hip fracture repair is important for geriatric patients and general welfare. We investigated the effects of anesthetic methods on postoperative activities of daily living (ADLs) following hip fracture surgery in elderly patients., Methods: The medical records of 12,342 patients aged ≥65 years who underwent typical surgeries for hip fracture using either general anesthesia or spinal anesthesia were reviewed. To adjust for baseline differences and minimize selection bias for the chosen method of anesthesia, patients were matched by propensity scores. Factors affecting the deterioration in ADLs during hospital stay were also investigated in all subjects using a multivariate logistic regression analysis. Eating, grooming, toileting, bathing, and walking were selected as the ADL parameters, as they are considered important for an independent life., Results: Of the 12,342 patients, 6918 (56.1%) received general anesthesia and 5424 (43.9%) received spinal anesthesia. After the propensity score matching, the anesthesia types were not associated with ADL scores except toileting at discharge. Results from the multivariate logistic regression analysis showed that the types of anesthesia were not associated with deterioration in ADL scores. Advanced age, male sex, high Charlson Comorbidity Index scores, psychiatric disease, no administration of nonsteroidal anti-inflammatory drugs, and short length of hospital stay were associated with deterioration in ADL scores., Conclusion: The anesthesia types were not associated with ADL dependency except toileting at discharge. Spinal anesthesia adversely affected toilet use at hospital discharge. However, anesthesia types were not factors that affected deterioration in ADL during hospital stay in elderly patients who underwent hip fracture surgery.

Fetal growth restriction in early pregnancy increases the risk of adverse pregnancy outcome, which has a significant social and psychological impact on women. There is limited information related to community-based study to evaluate early indicators related to miscarriage. The aim of this study is to examine the relationship between fetal growth restriction, measured by ultrasound crown-rump length (CRL), and subsequent occurrence of miscarriage in pregnant women in rural Bangladesh. The study was conducted within the Maternal and Infant Nutrition Interventions Trial in Matlab (MINIMat study), Bangladesh. A total of 4436 pregnant women were enrolled in the study when they were at less than 14 gestational weeks. The expected CRL was determined based on an established growth curve of gestational age and CRL, and deviation from this curve of CRL was expressed as a z-score. After identifying related covariates, the multiple Poisson regression model was used to determine the independent contribution from the CRL to miscarriage. A total of 3058 singleton pregnant women were included in analyses, with 92 miscarriages and 2966 continued pregnancies. The occurrence of miscarriages was significantly higher in the smaller categories of CRL z-score after adjustments for maternal age, parity, early pregnancy BMI, gestational age at CRL measurement and socioeconomic status (adjusted relative risk [95% confidence interval]: 1.03 [1.02-1.05] for less than -2 z-score). In a rural Bangladesh population, smaller than expected CRL for the gestational age was related to subsequent miscarriage. Ultrasound biometry information together with careful clinical assessment should provide much needed attention and care for pregnant women.

Background: Early-life arsenic exposure has been associated with reduced cell-mediated immunity, but little is known about its effects on humoral immunity., Objective: We evaluated whether prenatal and childhood arsenic exposure was associated with humoral immune function in school-aged children., Methods: Children born in a prospective mother–child cohort in rural Bangladesh were immunized with measles, mumps, and rubella (MMR) vaccines at 9 years of age (n=525). Arsenic exposure was assessed in urine (U-As), from mothers during pregnancy and their children at 4.5 and 9 years of age. Total IgG (tIgG), tIgE, tIgA, and MMR-specific IgG concentrations were measured in plasma using immunoassays., Results: Arsenic exposure was positively associated with child tIgG and tIgE, but not tIgA. The association with tIgG was mainly apparent in boys ( p for interaction=0.055), in whom each doubling of maternal U-As was related to an increase in tIgG by 28 mg/dL. The associations of U-As at 9 years with tIgG and tIgE were evident in underweight children ( p for interaction <0.032). Childhood arsenic exposure tended to impair mumps-specific vaccine response, although the evaluation was complicated by high preimmunization titers. Postimmunization mumps–specific IgG titers tended to decrease with increasing U-As at 4.5 and 9 years of age [regression coefficient (β)=−0.16; 95% confidence interval (CI): −0.33, 0.01; p=0.064 and β=−0.12; 95% CI: −0.27, −0.029; p=0.113, respectively) in 25% children with the lowest preexisting mumps-specific IgG titers., Conclusions: Arsenic exposure increased tIgG and tIgE in plasma, and tended to decrease mumps-specific IgG in children at 9 years of age. https://doi.org/10.1289/EHP318.

Exposure to arsenic has been associated with increased risk of reduced lung function in adults, but the adverse impacts in early life are unclear. We aim to examine whether prenatal and childhood arsenic exposure is associated with reduced lung function and increased airway inflammation in school-aged children. Children born in the MINIMat cohort in rural Bangladesh were evaluated at 9years of age (n=540). Arsenic exposure was assessed in urine (U-As) that was collected from mothers during early pregnancy and their children aged 4.5 and 9years. In the 9-year-old children, lung function was assessed using spirometry and airway inflammation was assessed by the NIOX MINO system. C-reactive protein (CRP) and Clara cell secretory protein (CC16) concentrations were measured in plasma by immunoassays. The U-As concentrations in 9-year-old children were lower (median 53μg/l) compared to their mothers (median 76μg/l). Maternal U-As (log 2 transformed) was inversely associated with forced vital capacity (FVC) and forced expiratory volume at 1s (FEV1) (β=-12; 95% CI: -22, -1.5; p=0.031 and β=-12; 95% CI: -22, -1.9; p=0.023, respectively) in all children, and the associations were stronger in boys and among children with adequate height and weight, as well as among those whose mothers had higher percentages of methylarsonic acid (MMA) and lower percentages of dimethylarsinic acid (DMA). U-As (log 2 transformed) at 4.5 and 9years was positively associated with fractional exhaled nitric oxide (FE NO ) concentrations in boys (β=0.89; 95% CI: 0.13, 1.66; p=0.022 and β=0.88; 95% CI: 0.16, 1.61; p=0.017, respectively) but not in girls. Increased CC16 concentrations were associated with higher lung function indices. In conclusion, our findings suggest that prenatal arsenic exposure is related to impaired lung function, while childhood exposure may increase airway inflammation, particularly in boys., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Septic shock-associated mortality in intensive care units (ICUs) remains high, with reported rates ranging 30-50%. In particular, Gram-negative bacilli (GNB), which induce significant inflammation and consequent multiple organ failure, are the etiological bacterial agent in 40% of severe sepsis cases. Hemoperfusion using polymyxin B-immobilized fiber (PMX), which adsorbs endotoxin, is expected to reduce the inflammatory sepsis cascade due to GNB. However, the clinical efficacy of this treatment has not yet been demonstrated. Here, we aimed to verify the efficacy of endotoxin adsorption therapy using PMX through a retrospective analysis of 413 patients who received broad spectrum antimicrobial treatment for GNB-related septic shock between January 2009 and December 2012 in 11 ICUs of Japanese tertiary hospitals. After aligning the patients' treatment time phases, we classified patients in two groups depending on whether PMX hemoperfusion (PMXHP) therapy was administered or not within 24 hours after ICU admission (PMXHP group: n = 134, conventional group: n = 279). The primary study endpoint was the mortality rate at 28 days after ICU admission. The mean age was 72.4 (standard deviation: 12.6) years, and the mean Sequential Organ Failure Assessment score at ICU admission was 9.9 (3.4). The infection sites included intra-abdominal (38.0%), pulmonary (18.9%), and urinary tract (32.2%), and two thirds of all patients had GNB-related bacteremia. Notably, the mortality at 28 days after ICU admission did not differ between the groups (PMXHP: 29.1% vs. conventional: 29.0%, P = 0.98), and PMXHP therapy was not found to improve this outcome in a Cox regression analysis (hazard ratio = 1.16; 95% confidence interval, 0.81-1.64, P = 0.407). We conclude that PMX-based endotoxin adsorption within 24 hours from ICU admission was not associated with mortality among patients with septic shock due to GNB., Trial Registration: University Hospital Medical Information Network Clinical Trial Registry (UMIN-CTR ID: UMIN000012748).

Background: Birth weight and length have seasonal fluctuations. However, it is uncertain which meteorological element has an effect on birth outcomes and which timing of pregnancy would explain such effect. Therefore, the purpose of this study was to examine temperature effects during pregnancy and which timing of pregnancy has effects on size at birth., Methods: A large, randomized, controlled trial of food and micronutrient supplementation for pregnant women was conducted in Matlab, Bangladesh (MINIMat Study), where women were enrolled from November 2001 to October 2003. The fetal growth data which included the size at birth and information of their mothers were obtained ( n  = 3267). Meteorological data such as temperature, precipitation, relative humidity, and daily sunshine hours during pregnancy were observed at the nearest observatory site of Bangladesh Meteorological Department., Results: Infants born in colder months (November-January) were shorter than those born in hot and dry, and monsoon months (mean (SD) of birth length was 47.5 cm (2.2) vs. 47.8 cm (2.1) vs. 47.9 cm (2.1) respectively; P  < 0.001). Increased temperature during the last month of pregnancy was significantly related with increased birth length with adjustment for gestational weeks and the season at birth, and remained significant with further adjustments for precipitation, sex of infants, maternal early-pregnancy BMI, parity, and education status of the mother ( P  < 0.01). On the other hand, increased temperature at mid-gestation was associated with increased birth weight ( P  < 0.05)., Conclusions: These findings suggest that temperature affects both birth weight and length. The more temperature increased at the last month of pregnancy, birth length became longer. For birth weight, the temperature at mid-pregnancy affected in a positive way.

Background: Exposure to lead, a common environmental pollutant, is known to cause cardiovascular and nephrotoxic effects in adults. Potential effects of early-life lead exposure on these functions are, however, less well characterized., Objectives: To assess blood pressure and kidney function in preschool-aged children in relation to prenatal lead exposure., Methods: This prospective study in rural Bangladesh measured children's systolic and diastolic blood pressure in triplicate at the follow-up at 4.5±0.11 years. Their kidney function was assessed by the estimated glomerular filtration rate (eGFR), calculated based on serum cystatin C concentrations, and by kidney volume, measured by sonography. Exposure to lead was assessed by concentrations in the mothers' blood (erythrocyte fraction; Ery-Pb) in gestational weeks (GW) 14 and 30, the effects of which were evaluated separately in multivariable-adjusted linear regression analyses., Results: We found no associations between maternal exposure to lead [n~1500 for GW14 and 700 for GW30] and children's blood pressure or eGFR. However, we found an inverse association between late gestation lead and kidney volume, although the sample size was limited (n=117), but not with early gestation lead (n=573). An increase of 85µg/kg in Ery-Pb (median concentration at GW30) was associated with a 6.0cm 3 /m 2 decrease in kidney volume (=0.4SD; p=0.041). After stratifying on gender, there seemed to be a somewhat stronger association in girls., Conclusions: Prenatal lead exposure may cause long-lasting effects on the kidney. This warrants follow-up studies in older children, as well as additional studies in other populations., (Copyright © 2016. Published by Elsevier Inc.)

Objective: The present analysis aimed to observe nutritional impacts among children <5 years of age by mother's engagement in paid employment., Design: Between 1996 and 2012, 21 443 children <5 years of age with diarrhoea attended the International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b), Dhaka Hospital. They were enrolled in the hospital-based Diarrhoeal Disease Surveillance System and their relevant information was extracted from the electronic database., Setting: The icddr,b, Bangladesh., Subjects: The analytic sample was 19 597 children aged <5 years who had a mother aged ≤35 years with or without engagement in paid employment., Results: Eleven per cent of the mothers (n 2051) were currently engaged in paid employment on behalf of the family. Univariate analysis showed that children with mothers engaged in paid employment had a 1·14 times higher risk of being undernourished, a 1·20 times of higher risk of being stunted, a 1·21 times higher risk of being wasted and a 1·31 times higher risk of being underweight (risk ratios) than were children with mothers not likewise engaged. Multivariate analysis showed that such associations remained significant for stunting (1·08; 95 % CI 1·00, 1·16), wasting (1·15; 95 % CI 1·06, 1·25) and underweight (1·09; 95 % CI 1·02, 1·17) after controlling for covariates., Conclusions: Mothers' engagement in income-generating employment was associated with undernutrition in children <5 years of age in urban Bangladesh.

Background: Limited data is available on the role of prenatal nutritional status on the health of school-age children. We aimed to determine the impact of maternal micronutrient supplementation on the health status of Bangladeshi children., Methods: Children (8.6-9.6 years; n = 540) were enrolled from a longitudinal mother-child cohort, where mothers were supplemented daily with either 30mg iron and 400μg folic acid (Fe30F), or 60mg iron and 400μg folic acid (Fe60F), or Fe30F including 15 micronutrients (MM), in rural Matlab. Blood was collected from children to determine the concentration of hemoglobin (Hb) and several micronutrients. Anthropometric and Hb data from these children were also available at 4.5 years of age and mothers at gestational week (GW) 14 and 30., Results: MM supplementation significantly improved (p≤0.05) body mass index-for-age z-score (BAZ), but not Hb levels, in 9 years old children compared to the Fe30F group. MM supplementation also reduced markers of inflammation (p≤0.05). About 28%, 35% and 23% of the women were found to be anemic at GW14, GW30 and both time points, respectively. The prevalence of anemia was 5% and 15% in 4.5 and 9 years old children, respectively. The adjusted odds of having anemia in 9 year old children was 3-fold higher if their mothers were anemic at both GW14 and GW30 [Odds Ratio (OR) = 3.05; 95% Confidence Interval (CI) 1.42, 6.14, P = 0.002] or even higher if they were also anemic at 4.5 years of age [OR = 5.92; 95% CI 2.64, 13.25; P<0.001]., Conclusion: Maternal micronutrient supplementation imparted beneficial effects on child health. Anemia during pregnancy and early childhood are important risk factors for the occurrence of anemia in school-age children.

Acute graft-versus-host disease (aGVHD) is a major complication of allogeneic hematopoietic stem cell transplantation (allo-HSCT). Because diagnosis of aGVHD is exclusively based on clinical symptoms and pathological findings, reliable and noninvasive laboratory tests for accurate diagnosis are required. An activating immunoreceptor, DNAM-1 (CD226), is expressed on T cells and natural killer cells and is involved in the development of aGVHD. Here, we identified a soluble form of DNAM-1 (sDNAM-1) in human sera. In retrospective univariate and multivariate analyses of allo-HSCT patients (n = 71) at a single center, cumulative incidences of all grade (grade I-IV) and sgrade II-IV aGVHD in patients with high maximal serum levels of sDNAM-1 (≥30 pM) in the 7 days before allo-HSCT were significantly higher than those in patients with low maximal serum levels of sDNAM-1 (<30 pM) in the same period. However, sDNAM-1 was not associated with other known allo-HSCT complications. Our data suggest that sDNAM-1 is potentially a unique candidate as a predictive biomarker for the development of aGVHD.

Background: Studies have addressed the immunomodulatory effects of helminths and their protective effects upon asthma. However, anti-Ascaris IgE has been reported to be associated with an increased risk of asthma symptoms. We examined the association between serum levels of anti-Ascaris IgE and bronchial hyper-responsiveness (BHR) in children living in rural Bangladesh., Methods: Serum anti-Ascaris IgE level was measured and the BHR test done in 158 children aged 9 years selected randomly from a general population of 1705 in the Matlab Health and Demographic Surveillance Area of the International Centre for Diarrhoeal Disease Research, Bangladesh. We investigated wheezing symptoms using a questionnaire from the International Study of Asthma and Allergies in Childhood. BHR tests were successfully done on 152 children (108 'current wheezers'; 44 'never-wheezers'). We examined the association between anti-Ascaris IgE level and wheezing and BHR using multiple logistic regression analyses., Results: Of 108 current-wheezers, 59 were BHR-positive; of 44 never-wheezers, 32 were BHR-negative. Mean anti-Ascaris IgE levels were significantly higher (12.51 UA/ml; 95% confidence interval (CI), 9.21-17.00) in children with current wheezing with BHR-positive than in those of never-wheezers with BHR-negative (3.89; 2.65-5.70; t test, p < 0.001). A BHR-positive test was independently associated with anti-Ascaris IgE levels with an odds ratio (OR) = 7.30 [95% CI, 2.28-23.33], p = 0.001 when adjusted for total IgE, anti-Dermatophagoides pteronyssinus IgE, pneumonia history, parental asthma, Trichuris infection, forced expiratory volume in one second, eosinophilic leukocyte count, and sex., Conclusions: Anti-Ascaris IgE level is associated with an increased risk of BHR among 9-year-old rural Bangladeshi children., (Copyright © 2015 Japanese Society of Allergology. Production and hosting by Elsevier B.V. All rights reserved.)

Background: Although sepsis is often associated with high mortality in severely malnourished children, data are very limited on appropriate diagnostic tools to predict mortality. We examined the role of urinary liver-type fatty acid-binding protein (L-FABP) in children <5 years old with sepsis who died., Methods: This prospective observational study was conducted at the Dhaka Hospital of the International Centre for Diarrhoeal Disease Research, Bangladesh. Children aged 6-59 months admitted with sepsis from April 2010 to December 2011 were enrolled. Comparison of clinical and laboratory characteristics was made between children who survived (n = 83) and those who did not survive (n = 22)., Results: On multiple Poisson regression analysis, after adjusting for potential confounders such as mid-upper arm circumference < 115 mm, plasma albumin < 2.5 g/dL, potassium > 5.0 mmol/L, and blood urea nitrogen > 20 mg/dL on admission, first urine L-FABP ≥ 370 ng/mL (relative risk [RR], 2.76; 95%CI: 1.22-6.25), weight-for-length/height z score < -3 (RR, 2.54; 95%CI: 1.26-5.09), capillary refilling time > 2.0 s (RR, 5.16; 95%CI: 1.46-18.3), and sodium > 160 mmol/L (RR, 2.72; 95%CI: 1.07-6.90) were identified as significant risk factors of mortality in children with sepsis. Diagnostic performance of first urine L-FABP was analyzed using receiver operating characteristic curve, and the area under the curve was 0.647 (95%CI: 0.500-0.795)., Conclusion: Urinary L-FABP may be a useful predictor of mortality in septic children. Urinary examination is non-invasive and easy to apply at the bedside., (© 2015 Japan Pediatric Society.)

Dengue fever (DF), one of the most important emerging arboviral diseases, is transmitted through the bite of container breeding mosquitoes Aedes aegypti and Aedes albopictus. A household entomological survey was conducted in Dhaka from August through October 2000 to inspect water-holding containers in indoor, outdoor, and rooftop locations for Aedes larvae. The objective of this study was to determine mosquito productivity of each container type and to identify some risk factors of households infested with Aedes larvae. Of 9,222 households inspected, 1,306 (14.2%) were positive for Aedes larvae. Of 38,777 wet containers examined, 2,272 (5.8%) were infested with Aedes larvae. Containers used to hold water, such as earthen jars, tanks, and drums were the most common containers for larval breeding. Tires in outdoor and rooftop locations of the households were also important for larval breeding. Although present in abundance, buckets were of less importance. Factors such as independent household, presence of a water storage system in the house, and fully/partly shaded outdoors were found to be significantly associated with household infestation of Aedes larvae. Identification and subsequent elimination of the most productive containers in a given area may potentially reduce mosquito density to below a level at which dengue transmission may be halted.

Background: Early-life exposure to toxic compounds may cause long-lasting health effects, but few studies have investigated effects of childhood exposure to nephrotoxic metals on kidney and cardiovascular function., Objectives: To assess effects of exposure to arsenic and cadmium on kidney function and blood pressure in pre-school-aged children, and potential protection by selenium., Methods: This cross-sectional study was part of the 4.5 years of age (range: 4.4-5.4 years) follow-up of the children from a supplementation trial in pregnancy (MINIMat) in rural Bangladesh, and nested studies on early-life metal exposures. Exposure to arsenic, cadmium and selenium from food and drinking water was assessed by concentrations in children's urine, measured by ICP-MS. Kidney function was assessed by the estimated glomerular filtration rate (eGFR, n=1106), calculated from serum cystatin C, and by kidney volume, measured by ultrasound (n=375). Systolic and diastolic blood pressure was measured (n=1356) after five minutes rest., Results: Multivariable-adjusted regression analyzes showed that exposure to cadmium, but not arsenic, was inversely associated with eGFR, particularly in girls. A 0.5 µg/L increase in urinary cadmium among the girls (above spline knot at 0.12) was associated with a decrease in eGFR of 2.6 ml/min/1.73 m(2), corresponding to 0.2SD (p=0.022). A slightly weaker inverse association with cadmium was also indicated for kidney volume, but no significant associations were found with blood pressure. Stratifying on children's urinary selenium (below or above median of 12.6 µg/L) showed a three times stronger inverse association of U-Cd with eGFR (all children) in the lower selenium stratum (B=-2.8; 95% CI: -5.5, -0.20; p=0.035), compared to those with higher selenium (B=-0.79; 95% CI: -3.0, 1.4; p=0.49)., Conclusions: Childhood cadmium exposure seems to adversely affect kidney function, but not blood pressure, in this population of young children in rural Bangladesh. Better selenium status appears to be protective. However, it is important to follow up these children to assess potential long-term consequences of these findings., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: Resuscitative endovascular balloon occlusion of the aorta (REBOA) is one of the ultimately invasive procedures for managing a noncompressive torso injury. Since it is less invasive than resuscitative open aortic cross-clamping, its clinical application is expected., Methods: We retrospectively evaluated the safety and clinical feasibility of REBOA (intra-aortic occlusion balloon, MERA, Tokyo, Japan) using the Seldinger technique to control severe hemorrhage. Of 5,230 patients admitted to our trauma center in Japan from 2007 to 2013, we included 24 who underwent REBOA primarily. The indications for REBOA were a pelvic ring fracture or hemoperitoneum with hemodynamically instability and impending cardiac arrest. Emergency hemostasis was performed during REBOA in all patients., Results: All 24 patients had a blunt injury, the median age was 59 (interquartile range, 41-71 years), the median Injury Severity Score (ISS) was 47 (interquartile range, 37-52), the 30-day survival rate was 29.2% (n = 7), and the median probability survival rate was 12.5%. Indications for REBOA were hemoperitoneum and pelvic ring fracture in 15 cases and overlap in 8 cases. In 10 cases of death, the balloon could not be deflated in 5 cases. In 19 cases in which the balloon was deflated, the median duration of aortic occlusion was shorter in survivors than in deaths (21 minutes vs. 35 minutes, p = 0.05). The mean systolic blood pressure was significantly increased by REBOA (from 53.1 [21] mm Hg to 98.0 [26.6] mm Hg, p < 0.01). There were three cases with complications (12.5%), one external iliac artery injury and two lower limb ischemias in which lower limb amputation was necessary in all cases. Acute kidney injury developed in all three cases, but failure was not persistent., Conclusion: REBOA seems to be feasible for trauma resuscitation and may improve survivorship. However, the serious complication of lower limb ischemia warrants more research on its safety., Level of Evidence: Therapeutic/care management, level V.

Background: The aim of this study is to evaluate the awareness status, attitudes, and care-seeking behaviors concerning tuberculosis (TB) and associated factors among the public in Inner Mongolia, China., Methods: A five-stage sampling was conducted, in which counties as the primary survey units and towns, villages, and households as sub-survey units were selected progressively. A standardized questionnaire was used to collect TB information. Complex survey analysis methods, including the procedures of survey frequency and survey logistic regression, were applied for analysis of TB knowledge and associated factors. The sample was weighted by survey design, non-respondent, and post-stratification adjustment., Results: Among 10 581 respondents, awareness that TB is an infectious disease was 86.7%. Knowing that a cough lasting ≥3 weeks is suggestive of TB was 26.9%. Knowledge about TB dispensaries in county administrative areas was reported by 68.3% of respondents, and knowledge about the free TB detection/treatment policy was reported by 57.5% of respondents. About 52.5% of participants would stigmatize TB patients. Compared with the majority Han ethnic group, Mongolians and other minorities were 1.52-2.18 times more likely to know about TB curability, TB symptoms, the free detection/treatment policy, and TB dispensaries' locations, but were less likely to know about the TB transmission mode (odds ratio, 0.74; 95% confidence interval, 0.65-0.84). The main sources of TB information were TV (65.6%) and other persons (47.2%). In the past year, 19.7% of TB knowledge was from acquaintances, and 16.1% was from TB institutes., Conclusions: Improvement in knowledge about TB risk (symptoms and transmission), the free treatment policy, and facilities is necessary and should be provided through effective multimedia for different target populations.

Prenatal arsenic exposure has been associated with reduced thymic index and increased morbidity in infants, indicating arsenic-related impaired immune function. We aimed at elucidating potential effects of pre- and postnatal arsenic exposure on cell-mediated immune function in pre-school aged children. Children born in a prospective mother-child cohort in rural Bangladesh were followed up at 4.5 years of age (n = 577). Arsenic exposure was assessed by concentrations of arsenic metabolites (U-As) in child urine and maternal urine during pregnancy, using high-performance liquid chromatography online with inductively coupled plasma mass spectrometry. For assessment of delayed type hypersensitivity response, an intradermal injection of purified protein derivative (PPD) was given to Bacillus Calmette-Guerin vaccinated children. The diameter (mm) of induration was measured after 48-72 h. Plasma concentrations of 27 cytokines were analyzed by a multiplex cytokine assay. Children's concurrent, but not prenatal, arsenic exposure was associated with a weaker response to the injected PPD. The risk ratio (RR) of not responding to PPD (induration <5 mm) was 1.37 (95% confidence interval (CI): 1.07, 1.74) in children in the highest quartile of U-As (range 126-1228 μg/l), compared with the lowest (range 12-34 μg/l). The p for trend across the quartiles was 0.003. The association was stronger in undernourished children. Children's U-As in tertiles was inversely associated with two out of 27 cytokines only, i.e., IL-2 and TNF-α, both Th1 cytokines (in the highest tertile, regression coefficients (95% CI): -1.57 (-2.56, -0.57) and -4.53 (-8.62, -0.42), respectively), but not with Th2 cytokines. These associations were particularly strong in children with recent infections. In conclusion, elevated childhood arsenic exposure appeared to reduce cell-mediated immunity, possibly linked to reduced concentrations of Th1 cytokines., (© The Author 2014. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Objective: To investigate the association between current childhood nutritional status and current wheezing among pre-school children in rural Bangladesh., Design: Cross-sectional study., Setting: Matlab region, rural Bangladesh., Subjects: Children (n 912) aged 4·5 years. Anthropometric measurements of the mothers and their children were taken during a 1-year period from December 2007 to November 2008. Current wheezing was identified using the International Study of Asthma and Allergies in Childhood questionnaire. Serum total IgE was measured by human IgE quantitative ELISA. IgE specific antibody to dust mites (Dermatophagoides pteronyssinus) was measured by the CAP-FEIA system (Phadia AB, Uppsala, Sweden)., Results: Wheezing at 4·5 years old was significantly associated with stunting (OR = 1·58; 95 % CI 1·13, 2·22) and underweight (OR = 1·39; 95 % CI 1·00, 1·94). The association with stunting remained significant after adjustment for sex, birth weight, birth length, gestational age at birth, mother's parity, maternal BMI, family history of asthma, socio-economic status, season of birth and intervention trial arm (OR = 1·74; 95 % CI 1·19, 2·56)., Conclusions: Stunting was a significant risk factor for wheezing among rural Bangladeshi children. Further studies will be required to confirm the relationship between nutritional status and allergic illnesses in developing countries.

Controversy persists as to whether helminth infections cause or protect against asthma and atopy. The aim of this study was to investigate the effects of helminth infection on asthma and atopy among Bangladeshi children. A total of 912 children aged 4.5 years (mean = 54.4, range = 53.5-60.8 months) participated in a cross-sectional study nested into a randomized controlled trial in Bangladesh. Ever-asthma, ever-wheezing and current wheezing were identified using the International Study of Asthma and Allergies in Childhood questionnaire. Current helminth infection was defined by the presence of helminth eggs in stools, measured by routine microscopic examination. Repeated Ascaris infection was defined by the presence of anti-Ascaris IgE ≥ 0.70 UA/ml in serum measured by the CAP-FEIA method. Atopy was defined by specific IgE to house dust mite (anti-DP IgE) ≥ 0.70 UA/ml measured by the CAP-FEIA method and/or positive skin prick test (≥ 5 mm). Anti-Ascaris IgE was significantly associated with ever asthma (odds ratio (OR) = 1.86, 95% CI: 1.14-3.04, highest vs. lowest quartile; P for trend 0.016). Anti-Ascaris IgE was also significantly associated with positive anti-DP IgE (OR = 9.89, 95% CI: 6.52-15.00, highest vs. lowest; P for trend < 0.001) and positive skin prick test (OR = 1.69, 95% CI: 1.01-2.81, highest vs. lowest, P for trend 0.076). These findings suggest that repeated Ascaris infection is a risk factor for asthma and atopy in rural Bangladeshi children. Further analysis is required to examine the mechanism of developing asthma and atopy in relation to helminth infection.

Background: Data from West Africa indicate that a small thymus at birth and at 6 months of age is a strong and independent risk factor for infection-related mortality up to 24 and 36 months of age, respectively. We investigated the association between thymus size (thymic index, TI) in infancy and subsequent infant and child survival in a contemporary South Asian population., Methods: The study focused on the follow-up of a randomized trial of prenatal nutritional interventions in rural Bangladesh (ISRCTN16581394), with TI measured longitudinally in infancy (at birth and weeks 8, 24 and 52 of age) and accurate recording of mortality up to 5 years of age., Results: A total of 3267 infants were born into the Maternal and Infant Nutrition Interventions, Matlab study; data on TI were available for 1168 infants at birth, increasing to 2094 infants by 52 weeks of age. TI in relation to body size was largest at birth, decreasing through infancy. For infants with at least one measure of TI available, there were a total of 99 deaths up to the age of 5 years. No association was observed between TI and subsequent mortality when TI was measured at birth. However, an association with mortality was observed with TI at 8 weeks of age [odds ratio (OR) for change in mortality risk associated with 1 standard deviation change in TI: all deaths: OR = 0.64, 95% confidence interval (CI) 0.41, 0.98; P = 0.038; and infection-related deaths only: OR = 0.32, 95% CI 0.14, 0.74; P = 0.008]. For TI when measured at 24 and 52 weeks of age, the numbers of infection-related deaths were too few (3 and 1, respectively) for any meaningful association to be observed., Conclusion: These results confirm that thymus size in early infancy predicts subsequent survival in a lower mortality setting than West Africa. The absence of an effect at birth and its appearance at 8 weeks of age suggests early postnatal influences such as breast milk trophic factors.

Background: Exposure to inorganic arsenic (As) through drinking water during pregnancy is associated with lower birth size and child growth. The aim of the study was to assess the effects of As exposure on child growth parameters to evaluate causal associations., Methodology/findings: Children born in a longitudinal mother-child cohort in rural Bangladesh were studied at 4.5 years (n=640) as well as at birth (n=134). Exposure to arsenic was assessed by concurrent and prenatal (maternal) urinary concentrations of arsenic metabolites (U-As). Associations with plasma concentrations of insulin-like growth factor 1 (IGF-1), calcium (Ca), vitamin D (Vit-D), bone-specific alkaline phosphatase (B-ALP), intact parathyroid hormone (iPTH), and phosphate (PO4) were evaluated by linear regression analysis, adjusted for socioeconomic factor, parity and child sex. Child U-As (per 10 µg/L) was significantly inversely associated with concurrent plasma IGF-1 (β=-0.27; 95% confidence interval: -0.50, -0.0042) at 4.5 years. The effect was more obvious in girls (β=-0.29; -0.59, 0.021) than in boys, and particularly in girls with adequate height (β=-0.491; -0.97, -0.02) or weight (β=-0.47; 0.97, 0.01). Maternal U-As was inversely associated with child IGF-1 at birth (r=-0.254, P=0.003), but not at 4.5 years. There was a tendency of positive association between U-As and plasma PO4 in stunted boys (β=0.27; 0.089, 0.46). When stratified by % monomethylarsonic acid (MMA, arsenic metabolite) (median split at 9.7%), a much stronger inverse association between U-As and IGF-1 in the girls (β=-0.41; -0.77, -0.03) was obtained above the median split., Conclusion: The results suggest that As-related growth impairment in children is mediated, at least partly, through suppressed IGF-1 levels.

Observational evidence suggests nutritional exposures during in utero development may have long-lasting consequences for health; data from interventions are scarce. Here, we present a trial follow-up study to assess the association between prenatal food and micronutrient supplementation and childhood blood pressure and kidney function. During the MINIMat Trial in rural Bangladesh, women were randomly assigned early in pregnancy to receive an early or later invitation to attend a food supplementation program and additionally to receive either iron and folate or multiple micronutrient tablets daily. The 3267 singleton birth individuals with measured anthropometry born during the trial were eligible for a follow-up study at 4.5 y old. A total of 77% of eligible individuals were recruited and blood pressure, kidney size by ultrasound, and glomerular filtration rate (GFR; calculated from plasma cystatin c) were assessed. In adjusted analysis, early invitation to food supplementation was associated with a 0.72-mm Hg [(95% CI: 0.16, 1.28); P = 0.01] lower childhood diastolic blood pressure and maternal MMS supplementation was associated with a marginally higher [0.87 mm Hg (95% CI: 0.18, 1.56); P = 0.01] childhood diastolic blood pressure. There was also some evidence that a supplement higher in iron was associated with a higher offspring GFR. No other effects of the food or micronutrient interventions were observed and there was no interaction between the interventions on the outcomes studied. These marginal associations and small effect sizes suggest limited public health importance in early childhood.