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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 filiation 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% Cl: 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% Cl: 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. [ABSTRACT FROM AUTHOR]

Abstract: Prenatal exposures to arsenic (As) and cadmium (Cd) have been associated with decreased size at birth. We here studied associations of prenatal As and Cd exposures with multiple fetal size parameters measured by ultrasound in gestational week (GW) 14 and 30 in a population-based mother–child cohort in rural Bangladesh. We measured As (n =1929) and Cd (n =1616) in urine during pregnancy. In the longitudinal evaluation of combined exposure, urinary Cd (UCd) showed an inverted U-shaped association (turning-point 1.5μg Cd/L) with all fetal size parameters, while UAs showed no significant association. Cross-sectional analyses indicated that associations with UCd were somewhat stronger in early gestation. Stratification indicated stronger associations between UCd and fetal size in girls than in boys, and in poorer than in richer families, while UAs was weakly associated with fetal size in boys. In conclusion, particularly Cd, but also As, appeared to influence fetal development in a sex-dependent manner. [Copyright &y& Elsevier]

Diagnosis of visceral leishmaniasis (VL) by demonstration of parasites in tissue smears obtained from bone marrow, spleen or lymph nodes is risky, painful, and difficult. The rK-39 strip test is widely used for the diagnosis of VL using blood/serum samples in endemic countries. The aim of the study was to evaluate the rK-39 strip test using urine sample as a non-invasive means for the diagnosis of VL. The rk-39 strip test was performed using urine from 100 suspected VL cases along with 25 disease control (malarial febrile cases) and 50 healthy control (from endemic and non-endemic areas). All the VL suspected cases were positive with the rK-39 strip test using serum. The sensitivity and specificity of the rK-39 strip test using urine samples was 95% and 93.3%, respectively, compared to serum based rK-39 test. The findings suggest that the urine based rK-39 test could be a practical and efficient tool for the diagnosis of VL patients in rural areas, particularly where resources are limited. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. Image 1 • Early signs of detrimental influence of metal(loid)s on fat metabolism in children. • Early life cadmium exposure was associated with increased preadolescent blood pressure. • Early life arsenic or cadmium exposure was associated with decreased plasma lipoproteins. • Childhood cadmium exposure was inversely associated with kidney function (eGFR). I n utero through early childhood exposure to arsenic and cadmium is linked with impaired fat and carbohydrate metabolism, while cadmium is additionally associated with reduced kidney function and increased blood pressure in preadolescent children in rural Bangladesh. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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 %), naïve 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. • Urinary arsenic level was non-linearly associated with immune cell numbers in 15 years old chronically exposed children. • Urinary As level below 20 µg/L was associated with increased CD8+ cytotoxic T cells, early B cells and classical monocytes. • Urinary-As concentration below 20 µg/L was associated with reduced CD3+ T cells and intermediate-monocytes. • Urinary-As concentration above 20 µg/L, was inversely associated with memory B cells in adolescents. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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 9 years 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 9 years. 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 53 μg/l) compared to their mothers (median 76 μg/l). Maternal U-As (log 2 transformed) was inversely associated with forced vital capacity (FVC) and forced expiratory volume at 1 s (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 9 years 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. [ABSTRACT FROM AUTHOR]

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 85 µg/kg in Ery-Pb (median concentration at GW30) was associated with a 6.0 cm 3 /m 2 decrease in kidney volume (=0.4 SD; 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. [ABSTRACT FROM AUTHOR]