Hormonal, liver, and renal function associated with electronic waste (e-waste) exposure in Dhaka, Bangladesh.

Electronic waste (e-waste) contains numerous metals and organic pollutants that have detrimental impacts on human health. We studied 199 e-waste recycling workers and 104 non-exposed workers; analyzed blood, urine, and hair samples to measure heavy metals, hormonal, liver, and renal function. We used quantile regression models to evaluate the impact of Pb, Cd, and Hg on hormonal, liver and renal function, and the role of DNA oxidative damage in mediating the relationship between exposures and outcomes. Exposed workers had higher blood lead (Pb) (median 11.89 vs 3.63µg/dL), similar blood cadmium (Cd) (1.04 vs 0.99µg/L) and lower total mercury (Hg) in hair (0.38 vs 0.57 ppm) than non-exposed group. Exposed workers also had elevated median concentrations of total triiodothyronine (TT3), aspartate aminotransferase (AST), alanine aminotransferase (ALT), urinary albumin, albumin creatinine ratio (ACR) and estimated glomerular filtration rate (eGFR) were significantly higher than non-exposed group (p≤0.05). Sex hormones including luteinizing hormone, follicle stimulating hormone, estrogen, progesterone and testosterone concentrations were not significantly different between exposed and non-exposed (all p≥0.05). The median concentration of ALT was 4.00 (95% CI: 0.23, 7.77), urinary albumin was 0.09 (95% CI: 0.06, 0.12) and ACR was 1.31 (95% CI: 0.57, 2.05) units higher in the exposed group compared to non-exposed group. Pb was associated with a 3.67 unit increase in the ALP (95% CI: 1.53, 5.80), 0.01 unit increase in urinary albumin (95% CI: 0.00, 0.01), and 0.07 unit increase in ACR (95% CI: 0.01, 0.13). However, no hormonal, renal, and hepatic parameters were associated with Cd or Hg. Oxidative DNA damage did not mediate exposure-outcome relationships (p≥0.05). Our data indicate e-waste exposure impairs liver and renal functions secondary to elevated Pb levels. Continuous monitoring, longitudinal studies to evaluate the dose-response relationship and effective control measure are required to protect workers from e-waste exposure.

High Rates of Placental Inflammation Among Samples Collected by the MOMI Consortium.

BACKGROUND: The Multi-Omics for Mothers and Infants (MOMI) consortium aims to improve birth outcomes. Preterm birth is a major obstetric complication globally causing significant infant and childhood morbidity and mortality. OBJECTIVES: We analyzed placental samples (basal plate, placenta/chorionic villi and/or the chorionic plate) collected by the 5 MOMI sites: The Alliance for Maternal and Newborn Health Improvement (AMANHI) Bangladesh, AMANHI Pakistan, AMANHI Tanzania, The Global Alliance to Prevent Prematurity and Stillbirth (GAPPS) Bangladesh and GAPPS Zambia. The goal was to analyze the morphology and gene expression of samples collected from preterm and uncomplicated term births. STUDY DESIGN: The teams provided biopsies from 166 singleton preterm (<37 weeks) and 175 term (≥37 weeks) deliveries. They were formalin-fixed and paraffin embedded. Tissue sections from these samples were stained with hematoxylin and eosin and subjected to morphological analyses. Other placental biopsies (n = 35 preterm, 21 term) were flash frozen, which enabled RNA purification for bulk transcriptomics. RESULTS: The morphological analyses revealed a surprisingly high rate of inflammation involving the basal plate, placenta/chorionic villi and/or the chorionic plate. The rate in chorionic villus samples, likely attributable to chronic villitis, ranged from 25% (Pakistan site) to 60% (Zambia site) of cases. Leukocyte infiltration in this location vs. the basal plate or chorionic plate correlated with preterm birth. Our transcriptomic analyses identified 267 genes as differentially expressed (DE) between placentas from preterm vs. term births (123 upregulated, 144 downregulated). Mapping the DE genes onto single cell RNA-seq data from human placentas suggested that all the component cell types, either singly or in subsets, contributed to the observed dysregulation. Consistent with the histopathological findings, GO (Gene Ontology) analyses highlighted leukocyte infiltration/activation and inflammatory responses in both the fetal and maternal compartments. CONCLUSION: The relationship between placental inflammation and preterm birth is appreciated in developed countries. Here, we show that this link also exists in developing geographies. Also, among the participating sites, we found geographic- and/or population-based differences in placental inflammation and preterm birth, suggesting the importance of local factors.

Antibody longevity and waning following COVID-19 vaccination in a 1-year longitudinal cohort in Bangladesh.

COVID-19 vaccines have been effective in preventing severe illness, hospitalization and death, however, the effectiveness diminishes with time. Here, we evaluated the longevity of antibodies generated by COIVD-19 vaccines and the risk of (re)infection in Bangladeshi population. Adults receiving two doses of AstraZeneca, Pfizer, Moderna or Sinopharm vaccines were enrolled at 2-4 weeks after second dosing and followed-up at 4-monthly interval for 1 year. Data on COVID-like symptoms, confirmed COVID-19 infection, co-morbidities, and receipt of booster dose were collected; blood was collected for measuring spike (S)- and nucleocapsid (N)-specific antibodies. S-specific antibody titers reduced by ~ 50% at 1st follow-up visit and continued to decline unless re-stimulated by booster vaccine dose or (re)infection. Individuals infected between follow-up visits showed significantly lower S-antibody titers at preceding visits compared to the uninfected individuals. Pre-enrolment infection between primary vaccination dosing exhibited 60% and 50% protection against reinfection at 5 and 9 months, respectively. mRNA vaccines provided highest odds of protection from (re)infection up to 5 months (Odds Ratio (OR) = 0.08), however, protection persisted for 9 months in AstraZeneca vaccine recipients (OR = 0.06). In conclusion, vaccine-mediated protection from (re)infection is partially linked to elevated levels of S-specific antibodies. AstraZeneca vaccine provided the longest protection.

Blood lead, cadmium and hair mercury concentrations and association with soil, dust and occupational factors in e-waste recycling workers in Bangladesh.

BACKGROUND: Electronic waste (e-waste) recycling activities release toxic metals, which pose substantial hazard to the environment and human health. We evaluated metal concentrations in biological and environmental samples, and examined the associations between biological lead (Pb), cadmium (Cd), and mercury (Hg) with soil and dust metals, and other possible determinants, among populations exposed and non-exposed to e-waste in Bangladesh. METHODS: A total of 199 e-waste workers and 104 non-exposed individuals were recruited. We measured blood Pb (BPb) and Cd (BCd) concentrations and total Hg (THg) from hair samples. Data were collected on occupational, and behavioral factors. We fitted an elastic net regression (ENET) to model the relationship between a set of influencing factors and metals as outcome variables while controlling for potential covariates. RESULTS: The median concentrations of BPb (11.89 µg/dL) and BCd (1.04 µg/L) among exposed workers were higher than those of non-exposed workers (BPb: 3.63 µg/dL and BCd: 0.83 µg/L respectively). A 100 ppm increment in soil Pb level was associated with an increase in ln-Pb (transformed) in blood (ß = 0.002; 95% CI = 0.00, 0.02). Similarly, ln-BCd level increased (ß = 0.02; 95% CI = 0.001, 0.07) with every ppm increase in dust Cd level. The number of years worked in e-waste activities was associated with elevated ln-BPb (ß = 0.01; 95% CI = 0.01, 0.02) and ln-BCd levels (ß = 0.003; 95% CI = 0.00, 0.05). Smoking significantly contributed to elevated levels of ln-BCd (ß = 0.46; 95% CI = 0.43, 0.73). An increment of 100 kg of e-waste handling per week led to an increase in ln-BPb levels (ß = 0.002; 95% CI = 0.00, 0.01), while respondents knowledge about adverse impact on e-waste reduced the ln-BPb level (ß = -0.14; 95% CI = -0.31, -0.03). Fish consumption frequency had a positive association with THg in hair. CONCLUSIONS: Our data show the need for workplace controls to reduce exposure to Pb and Cd with a broader view of exposure source taken.

Pivotal relationship between heavy metal, PM2.5 exposures and tuberculosis in Bangladeshi children: protocol paper of a case-control study.

INTRODUCTION: Air pollution is a global issue that poses a significant threat to public health. Children, due to their developing physiology, are particularly susceptible to the inhalation of environmental pollutants. Exposure can trigger immune modulation and organ damage, increasing susceptibility to respiratory diseases. Therefore, we aim to examine the association between heavy metal and particulate matter exposure with tuberculosis in children. METHODS AND ANALYSIS: As a case-control study, we will include children diagnosed with pulmonary tuberculosis (n=60) and matched healthy controls (n=80) recruited from the same communities in Dhaka, Bangladesh. Exposure data for both cases and controls will be collected by a trained field team conducting home visits. They will administer an exposure questionnaire, measure child anthropometry, collect blood and household dust samples and instal 48-hour air quality monitors. The blood samples will be analysed by inductively coupled plasma mass spectrometry for serum heavy metal concentrations (lead, cadmium, arsenic, mercury and chromium), as a representative marker of exposure, and the presence of inflammatory biomarkers. Descriptive and inferential statistics, including independent samples t-tests, analysis of variance and conditional regression analysis, will be used to quantify heavy metal and particulate matter exposure status in tuberculosis cases compared with healthy controls, while accounting for potential confounders. Dust samples and air quality results will be analysed to understand household sources of heavy metal and particulate matter exposure. To test the study hypothesis, there is a positive association between exposure and tuberculosis diseases, we will also measure the accumulated effect of simultaneous exposures using Bayesian statistical modelling. ETHICS AND DISSEMINATION: This study has been approved by International Centre for Diarrhoeal Disease Research, Bangladesh's Institutional Review Board (PR-22030). The study findings will be disseminated at conferences and published in peer-reviewed journals.

Effects of vitamin B12 supplementation on oxidative stress markers and pro-inflammatory cytokines during pregnancy and postpartum among Bangladeshi mother-child pairs.

BACKGROUND: There is limited research to determine whether vitamin B12 (B12) supplementation during pregnancy and lactation is protective against oxidative stress and pro-inflammatory cytokines and whether this effect is transferred to breastfed infants via milk. In addition, associations among maternal plasma/ milk and infant B12 status and immune function markers are poorly characterized. OBJECTIVES: To evaluate effects of oral B12 supplementation during pregnancy and postpartum on maternal and infant 8-hydroxy-2'-deoxyguanosine (8-OH-dG, an oxidative stress marker) and proinflammatory cytokine levels, and examine associations between maternal plasma, breastmilk and infant B12 status as well as immune function markers. METHOD: In a blinded, placebo-controlled trial, Bangladeshi women (n = 68, 18-35 years, hemoglobin < 11 g/dL, gestational weeks 11-14) received either 250 µg/day B12 or placebo throughout pregnancy up to 3-months postpartum. Samples were collected from mothers at baseline and 3-months postpartum and from infants at 3-months to measure B12 status indicators, 8-OH-dG and proinflammatory cytokines. RESULTS: Maternal postpartum B12 was positively associated with infant plasma B12. Higher milk B12 concentrations were associated with increased infant B12 (beta (ß) = 277, 95% confidence interval (CI) = (132, 423), p<0.001) and lower total homocysteine (ß = -7.63, 95% CI = (-12.40, -2.86), p = 0.002) levels. Maternal B12 supplementation reduced plasma 8-OH-dG concentrations among postpartum mothers and infants compared to the placebo group. Supplementation increased plasma TNF-α and IL-6 levels among mothers and IL-10 and IFN-γ levels among infants. CONCLUSION: Milk and maternal plasma B12 at 3 months were associated with infant B12. Maternal B12 supplementation modulates 8-OH-dG and several cytokines which may protect against immune response-induced oxidative stress. TRIAL REGISTRATION: (clinicaltrials.gov: NCT01795131- 1st posted on 20/02/2013).

Serosurveillance among urban slum and non-slum populations immunized with COVID-19 vaccines in Bangladesh.

Using two rounds of serosurveillance, we aimed to observe the COVID-19 vaccination status and the dynamics of antibody responses to different vaccines among urban slum and non-slum populations of Bangladesh. Adults (>18 years) and children (10-17 years) were enrolled in March and October 2022. Data including COVID-19 vaccine types and dosage uptake were collected. SARS-CoV-2 spike (S)-specific antibodies were measured in blood. The proportion of vaccinated children was significantly lower among slum than non-slum populations. Two doses of vaccines showed an increase in the level of anti-S-antibodies up to 2 months, followed by reduced levels at 2-6 months and a resurgence at 6-12 months. Children showed significantly higher anti-S-antibodies after two doses of the Pfizer-BioNTech vaccine than adults; however, after 6 months, the level of antibodies declined in younger children (10 - < 12 years). In a mixed vaccine approach, mRNA vaccines contributed to the highest antibody response whether given as the first two doses or as the third dose. Our findings emphasized the need for increasing the coverage of COVID-19 vaccination among slum children and booster dosing among all children. The use of mRNA vaccines in the mixed vaccination approach was found to be useful in boosting the antibody response to SARS-CoV-2.

Standardised quantitative assays for anti-SARS-CoV-2 immune response used in vaccine clinical trials by the CEPI Centralized Laboratory Network: a qualification analysis.

BACKGROUND: Accurate quantitation of immune markers is crucial for ensuring reliable assessment of vaccine efficacy against infectious diseases. This study was designed to confirm standardised performance of SARS-CoV-2 assays used to evaluate COVID-19 vaccine candidates at the initial seven laboratories (in North America, Europe, and Asia) of the Coalition for Epidemic Preparedness Innovations (CEPI) Centralized Laboratory Network (CLN). METHODS: Three ELISAs (pre-spike protein, receptor binding domain, and nucleocapsid), a microneutralisation assay (MNA), a pseudotyped virus-based neutralisation assay (PNA), and an IFN-γ T-cell ELISpot assay were developed, validated or qualified, and transferred to participating laboratories. Immune responses were measured in ELISA laboratory units (ELU) for ELISA, 50% neuralisation dilution (ND50) for MNA, 50% neutralisation titre (NT50) for PNA, and spot-forming units for the ELISpot assay. Replicate assay results of well characterised panels and controls of blood samples from individuals with or without SARS-CoV-2 infection were evaluated by geometric mean ratios, standard deviation, linear regression, and Spearman correlation analysis for consistency, accuracy, and linearity of quantitative measurements across all laboratories. FINDINGS: High reproducibility of results across all laboratories was demonstrated, with interlaboratory precision of 4·1-7·7% coefficient of variation for all three ELISAs, 3·8-19·5% for PNA, and 17·1-24·1% for MNA, over a linear range of 11-30 760 ELU per mL for the three ELISAs, 14-7876 NT50 per mL for PNA, and 21-25 587 ND50 per mL for MNA. The MNA was also adapted for detection of neutralising antibodies against the major SARS-CoV-2 variants of concern. The results of PNA and MNA (r=0·864) and of ELISA and PNA (r=0·928) were highly correlated. The IFN-γ ELISpot interlaboratory variability was 15·9-49·9% coefficient of variation. Sensitivity and specificity were close to 100% for all assays. INTERPRETATION: The CEPI CLN provides accurate quantitation of anti-SARS-CoV-2 immune response across laboratories to allow direct comparisons of different vaccine formulations in different geographical areas. Lessons learned from this programme will serve as a model for faster responses to future pandemic threats and roll-out of effective vaccines. FUNDING: CEPI.

Early to mid-pregnancy HbA1c levels and its association with adverse pregnancy outcomes in three low middle-income countries in Asia and Sub-Saharan Africa.

BACKGROUND: Hyperglycemia during pregnancy leads to adverse maternal and fetal outcomes. Thus, strict monitoring of blood glucose levels is warranted. This study aims to determine the association of early to mid-pregnancy HbA1c levels with the development of pregnancy complications in women from three countries in South Asia and Sub-Saharan Africa. METHODS: We performed a secondary analysis of the AMANHI (Alliance for Maternal and Newborn Health Improvement) cohort, which enrolled 10,001 pregnant women between May 2014 and June 2018 across Sylhet-Bangladesh, Karachi-Pakistan, and Pemba Island-Tanzania. HbA1c assays were performed at enrollment (8 to < 20 gestational weeks), and epidemiological data were collected during 2-3 monthly household visits. The women were followed-up till the postpartum period to determine the pregnancy outcomes. Multivariable logistic regression models assessed the association between elevated HbA1c levels and adverse events while controlling for potential confounders. RESULTS: A total of 9,510 pregnant women were included in the analysis. The mean HbA1c level at enrollment was found to be the highest in Bangladesh (5.31 ± 0.37), followed by Tanzania (5.22 ± 0.49) and then Pakistan (5.07 ± 0.58). We report 339 stillbirths and 9,039 live births. Among the live births were 892 preterm births, 892 deliveries via cesarean section, and 532 LGA babies. In the multivariate pooled analysis, maternal HbA1c levels of ≥ 6.5 were associated with increased risks of stillbirths (aRR = 6.3, 95% CI = 3.4,11.6); preterm births (aRR = 3.5, 95% CI = 1.8-6.7); and Large for Gestational Age (aRR = 5.5, 95% CI = 2.9-10.6). CONCLUSION: Maternal HbA1c level is an independent risk factor for predicting adverse pregnancy outcomes such as stillbirth, preterm birth, and LGA among women in South Asia and Sub-Saharan Africa. These groups may benefit from early interventional strategies.

Arsenic exposure and increased C-reactive protein are independently associated with lower erythrocyte glutathione peroxidase activity in Bangladeshi children.

Toxic metal contaminants present in food and water have widespread effects on health and disease. Chalcophiles, such as arsenic, cadmium, and mercury, show a high affinity to selenium and exposure to these metals could have a modulating effect on enzymes dependent on selenocysteine in their active sites. The aim of this study was to assess the influence of these metals on the activity of the selenoprotein glutathione peroxidase 1 (GPX1) in erythrocytes of 100 children residing in rural Bangladesh, where drinking water often contains arsenic. GPX1 expression, as measured using high-throughput immunoblotting, showed little correlation with GPX activity (rs = 0.02, p = 0.87) in blood samples. Toxic metals and selenium measured in erythrocytes using inductively coupled plasma mass spectrometry (ICP-MS) and C-reactive protein (CRP) measured in plasma, were all considered as effectors of this divergence in GPX enzymatic activity. Arsenic concentrations in erythrocytes were most influential for GPX1 activity (rs = -0.395, p < 0.0001), and CRP levels also negatively impacted GPX1 activity (rs = -0.443, p < 0.0001). These effects appear independent of each other as arsenic concentrations and CRP showed no correlation (rs = 0.124, p = 0.2204). Erythrocyte selenium, cadmium, and mercury did not show any correlation with GPX1 activity, nor with CRP or arsenic. Our findings suggest that childhood exposure to inorganic arsenic, as well as inflammation triggering the release of CRP, may negatively affect GPX1 activity in erythrocytes.

Optimizing SARS-CoV-2 Immunoassays for Specificity in Dengue-Co-Endemic Areas.

Introduction The overlap in clinical presentation between COVID-19 and dengue poses challenges for diagnosis in co-endemic regions. Furthermore, there have been reports of antibody cross-reactivity between SARS-CoV-2 and dengue. Our research aims to evaluate SARS-CoV-2 antigens for serological testing while reducing the possibility of cross-reactivity with anti-dengue antibodies. Method Two hundred and ten serum samples were collected from 179 patients and divided into four panels. Panels 1 and 2 consisted of COVID-19-negative healthy donors (n=81) and pre-pandemic dengue patients (n=50), respectively. Alternatively, Panel 3 (n=19) was composed of reverse transcription-quantitative polymerase chain reaction (RT-qPCR)-positive samples collected within two weeks of COVID-19 symptom onset, while Panel 4 (n=60) was composed of positive samples collected after two weeks of symptom onset. Previously developed and characterized in-house SARS-CoV-2 spike-1 (S1), receptor binding domain (RBD), and nucleocapsid (N) immunoglobin G (IgG)-enzyme-linked immunosorbent assay (ELISA) assays were used for the study. Results Six dengue-positive sera cross-reacted with the RBD of SARS-CoV-2. However, only one dengue-positive sera cross-reacted with the S1 and N proteins of SARS-CoV-2. Co-immobilization of S1 and RBD in different ratios revealed an 80:20 (S1:RBD) ratio as optimal for achieving an overall 96.2% sensitivity with the least cross-reaction to anti-dengue antibodies. Conclusion Our findings indicated that SARS-CoV-2 RBD-based immunoassays present more cross-reactivity with anti-dengue antibodies than S1 and N proteins. Furthermore, co-immobilization of S1 and RBD reduces the cross-reactivity with anti-dengue antibodies compared to RBD, thereby increasing the immunoassay specificity without affecting overall sensitivity for the dengue-endemic areas.

Micronutrient status during pregnancy is associated with child immune status in rural Bangladesh.

Background: Poor immune function increases children's risk of infection and mortality. Several maternal factors during pregnancy may affect infant immune function during the postnatal period. Objectives: We aimed to evaluate whether maternal micronutrients, stress, estriol, and immune status during the first or second trimester of pregnancy were associated with child immune status in the first two years after birth. Methods: We conducted observational analyses within the water, sanitation, and hygiene (WASH) Benefits Bangladesh randomized controlled trial. We measured biomarkers in 575 pregnant women and postnatally in their children. Maternal biomarkers measured during the first and second trimester of pregnancy included nutrition status via vitamin D (25-hydroxy-D [25(OH)D]), ferritin, soluble transferrin receptor (sTfR), and retinol-binding protein (RBP); cortisol; estriol. Immune markers were assessed in pregnant women at enrollment and their children at ages 14 and 28 mo, including C-reactive protein (CRP), alpha-1-acid glycoprotein (AGP), and 13 cytokines (including IFN-γ). We generated a standardized sum score of log-transformed cytokines. We analyzed IFN-γ individually because it is a critical immunoregulatory cytokine. All outcomes were prespecified. We used generalized additive models and reported the mean difference and 95% confidence intervals at the 25th and 75th percentiles of exposure distribution. Results: At child age 14 mo, concentrations of maternal RBP were inversely associated with the cytokine sum score in children (-0.34 adjusted difference between the 25th and 75th percentile [95% confidence interval -0.61, -0.07]), and maternal vitamin A deficiency was positively associated with the cytokine sum score in children (1.02 [0.13, 1.91]). At child age of 28 mo, maternal RBP was positively associated with IFN-γ in children (0.07 [0.01, 0.14]), whereas maternal vitamin A deficiency was negatively associated with child AGP (-0.07 [-0.13, -0.02]). Maternal iron deficiency was associated with higher AGP concentrations in children at age 14 mo (0.13 [0.04, 0.23]), and maternal sTfR concentrations were positively associated with child CRP concentrations at age 28 mo (0.18 [0, 0.36]). Conclusion: Maternal deficiencies in vitamin A or iron during the first 2 trimesters of pregnancy may shape the trajectory of a child's immune status.

Reduction of household air pollution through clean fuel intervention and recovery of cellular immune balance.

BACKGROUND: We conducted a clean fuel intervention trial (Bangladesh Global Environmental and Occupational Health (GEOHealth) (NCT02824237) with liquefied petroleum gas (LPG) for 26 months among rural Bangladeshi women chronically exposed to household air pollution (HAP) from biomass fuel (BMF) use. We aimed to evaluate the effect of HAP reduction following LPG intervention on immune response outcome. METHODS: We supplied LPG cook stove and refills in cylinder in 200 households for 26 months. We measured personal exposure to HAP [particulate matter 2.5 (PM2·5), black carbon (BC) and carbon monoxide (CO)] in 200 women (main cook) by personal monitors at pre- and post-intervention. Immune function was assessed before and after intervention, in blood collected within 2 weeks of HAP measurements. Primary endpoints included reduction in HAP, lymphocyte proliferation and oxidative stress response, and alterations in T and B cell proportions. FINDINGS: Exclusive LPG use for 26 months resulted in significant reduction in PM2·5 (43.5%), BC (13%) and CO (48%) exposure in the women. For one unit decrease in BC, Treg cells and memory B cells increased by 7% and 34% respectively, in the peripheral circulation. One unit decrease in CO was significantly associated with increase in early B cells and plasmablasts by 66% and 5% respectively. For one unit decrease in BC, percent-dividing cells, proliferation and expansion indices increased by 2%, 0.4%, and 1%, respectively. INTERPRETATION: Reduced personal exposure to HAP through clean fuel intervention was related to a return towards cellular immune balance.

Comparative predictive power of serum vs plasma proteomic signatures in feto-maternal medicine.

BACKGROUND: Blood proteins are frequently measured in serum or plasma, because they provide a wealth of information. Differences in the ex vivo processing of serum and plasma raise concerns that proteomic health and disease signatures derived from serum or plasma differ in content and quality. However, little is known about their respective power to predict feto-maternal health outcomes. Predictive power is a sentinel characteristic to determine the clinical use of biosignatures. OBJECTIVE: This study aimed to compare the power of serum and plasma proteomic signatures to predict a physiological pregnancy outcome. STUDY DESIGN: Paired serum and plasma samples from 73 women were obtained from biorepositories of a multinational prospective cohort study on pregnancy outcomes. Gestational age at the time of sampling was the predicted outcome, because the proteomic signatures have been validated for such a prediction. Multivariate and cross-validated models were independently derived for serum and plasma proteins. RESULTS: A total of 1116 proteins were measured in 88 paired samples from 73 women with a highly multiplexed platform using proximity extension technology (Olink Proteomics Inc, Watertown, MA). The plasma proteomic signature showed a higher predictive power (R=0.64; confidence interval, 0.42-0.79; P=3.5×10-6) than the serum signature (R=0.45; confidence interval, 0.18-0.66; P=2.2×10-3). The serum signature was validated in plasma with a similar predictive power (R=0.58; confidence interval, 0.34-0.75; P=4.8×10-5), whereas the plasma signature was validated in serum with reduced predictive power (R=0.53; confidence interval, 0.27-0.72; P=2.6×10-4). Signature proteins largely overlapped in the serum and plasma, but the strength of association with gestational age was weaker for serum proteins. CONCLUSION: Findings suggest that serum proteomics are less informative than plasma proteomics. They are compatible with the view that the partial ex-vivo degradation and modification of serum proteins during sample processing are an underlying reason. The rationale for collecting and analyzing serum and plasma samples should be carefully considered when deriving proteomic biosignatures to ascertain that specimens of the highest scientific and clinical yield are processed. Findings suggest that plasma is the preferred matrix.

Betel quid use is associated with anemia among both men and women in Matlab, Bangladesh.

Anemia accounts for 8.8% of total disability burden worldwide. Betel quid use among pregnant women has been found to increase anemia risk. Betel quid is prepared by wrapping the betel (or areca) nut, with spices and other additions, in betel or tobacco leaf and it is chewed or placed in the mouth. We explored the association between betel quid use and anemia among men and non-pregnant women. We collected data from a random sample of women and their husbands in Matlab, Bangladesh. Participants reported their current betel quid use and individual characteristics. We assessed hemoglobin (a biomarker of anemia) with a hemoglobinometer and soluble transferrin receptor (a biomarker of iron deficiency) and C-reactive protein (a biomarker of inflammation) in dried blood spots via enzyme immunoassay. We estimated logistic regression models to evaluate the association between betel quid use and anemia and structural equation models (SEM) to evaluate mediating roles of iron deficiency and elevated inflammation. A total of 1133 participants (390 men and 743 non-pregnant women) were included. After controlling for important confounders, any betel quid use was positively associated with anemia among men (OR: 1.80; 95% CI: 1.12, 2.89). Among women, betel quid use was associated with anemia only among the most frequent users (OR: 1.62; 95% CI: 1.03, 2.53). SEM did not reveal indirect paths through inflammation or iron deficiency. Betel quid use may contribute to the burden of anemia among adults in Bangladesh. Our findings suggest the burden of disease attributed to betel quid use has been underestimated.

Vitamin D deficiency in pregnancy and the risk of preterm birth: a nested case-control study.

BACKGROUND: Each year, an estimated 15 million babies are born preterm. Micronutrient deficiencies, including vitamin D deficiency (VDD), are common in many low- and middle-income countries (LMICs), and these conditions are often associated with adverse pregnancy outcomes. Bangladesh experiences a high prevalence of VDD. The country also has a high preterm birth (PTB) rate. Using data from a population-based pregnancy cohort, we estimated the burden of VDD during pregnancy and its association with PTB. METHODS: Pregnant women (N = 3,000) were enrolled after ultrasound confirmation of gestational age at 8-19 weeks of gestation. Trained health workers prospectively collected phenotypic and epidemiological data at scheduled home visits. Trained phlebotomists collected maternal blood samples at enrollment and 24 -28 weeks of gestation. Aliquots of serum were stored at -800 C. We conducted a nested case-control study with all PTB (n = 262) and a random sample of term births (n = 668). The outcome, PTB, was defined as live births < 37 weeks of gestation, based on ultrasound. The main exposure was vitamin D concentrations of 24-28 weeks maternal blood samples. The analysis was adjusted for other PTB risk factors. Women were categorized as VDD (lowest quartile of 25(OH)D; < = 30.25 nmol/L) or not deficient (upper-three quartiles of 25(OH)D; > 30.25 nmol/L). We used logistic regression to determine the association of VDD with PTB, adjusting for potential confounders. RESULTS: The median and interquartile range of serum 25(OH)D was 38.0 nmol/L; 30.18 to 48.52 (nmol/L). After adjusting for co-variates, VDD was significantly associated with PTB [adjusted odds ratio (aOR) = 1.53, 95% confidence interval (CI) = 1.10 - 2.12]. The risk of PTB was also higher among women who were shorter (aOR = 1.81, 95% CI: 1.27-2.57), primiparous (aOR = 1.55, 95% CI = 1.12 - 2.12), passive smokers (aOR = 1.60, 95% CI = 1.09 - 2.34), and those who received iron supplementation during pregnancy (aOR = 1.66, 95% CI: 1.17, 2.37). CONCLUSION: VDD is common in Bangladeshi pregnant women and is associated with an increased risk of PTB.

Factors Associated with Reported COVID-like Symptoms and Seroprevalence Data Matched with COVID-like Symptoms in Slums and Non-Slums of Two Major Cities in Bangladesh.

OBJECTIVES: To examine the levels and socio-demographic differentials of: (a) reported COVID-like symptoms; and (b) seroprevalence data matched with COVID-like symptoms. METHODS: Survey data of reported COVID-like symptoms and seroprevalence were assessed by Roche Elecsys® Anti-SARS-CoV-2 immunoassay. Survey data of 10,050 individuals for COVID-like symptoms and seroprevalence data of 3205 individuals matched with COVID-like symptoms were analyzed using bivariate and multivariate logistic analysis. RESULTS: The odds of COVID-like symptoms were significantly higher for Chattogram city, for non-slum, people having longer years of schooling, working class, income-affected households, while for households with higher income had lower odd. The odds of matched seroprevalence and COVID-like symptoms were higher for non-slum, people having longer years of schooling, and for working class. Out of the seropositive cases, 37.77% were symptomatic-seropositive, and 62.23% were asymptomatic, while out of seronegative cases, 68.96% had no COVID-like symptoms. CONCLUSIONS: Collecting community-based seroprevalence data is important to assess the extent of exposure and to initiate mitigation and awareness programs to reduce COVID-19 burden.

Multiomic signals associated with maternal epidemiological factors contributing to preterm birth in low- and middle-income countries.

Preterm birth (PTB) is the leading cause of death in children under five, yet comprehensive studies are hindered by its multiple complex etiologies. Epidemiological associations between PTB and maternal characteristics have been previously described. This work used multiomic profiling and multivariate modeling to investigate the biological signatures of these characteristics. Maternal covariates were collected during pregnancy from 13,841 pregnant women across five sites. Plasma samples from 231 participants were analyzed to generate proteomic, metabolomic, and lipidomic datasets. Machine learning models showed robust performance for the prediction of PTB (AUROC = 0.70), time-to-delivery (r = 0.65), maternal age (r = 0.59), gravidity (r = 0.56), and BMI (r = 0.81). Time-to-delivery biological correlates included fetal-associated proteins (e.g., ALPP, AFP, and PGF) and immune proteins (e.g., PD-L1, CCL28, and LIFR). Maternal age negatively correlated with collagen COL9A1, gravidity with endothelial NOS and inflammatory chemokine CXCL13, and BMI with leptin and structural protein FABP4. These results provide an integrated view of epidemiological factors associated with PTB and identify biological signatures of clinical covariates affecting this disease.