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Abstract Background Antenatal Care (ANC) during pregnancy can play an important role in the uptake of evidence-based services vital to the health of women and their infants. Studies report positive effects of ANC on use of facility-based delivery and perinatal mortality. However, most existing studies are limited to cross-sectional surveys with long recall periods, and generally do not include population-based samples. Methods This study was conducted within the Health and Demographic Surveillance System (HDSS) of the International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b) in Matlab, Bangladesh. The HDSS area is divided into an icddr,b service area (SA) where women and children receive care from icddr,b health facilities, and a government SA where people receive care from government facilities. In 2007, a new Maternal, Neonatal, and Child Health (MNCH) program was initiated in the icddr,b SA that strengthened the ongoing maternal and child health services including ANC. We estimated the association of ANC with facility delivery and perinatal mortality using prospectively collected data from 2005 to 2009. Using a before-after study design, we also determined the role of ANC services on reduction of perinatal mortality between the periods before (2005 – 2006) and after (2008–2009) implementation of the MNCH program. Results Antenatal care visits were associated with increased facility-based delivery in the icddr,b and government SAs. In the icddr,b SA, the adjusted odds of perinatal mortality was about 2-times higher (odds ratio (OR) 1.91; 95% confidence intervals (CI): 1.50, 2.42) among women who received ≤1 ANC compared to women who received ≥3 ANC visits. No such association was observed in the government SA. Controlling for ANC visits substantially reduced the observed effect of the intervention on perinatal mortality (OR 0.64; 95% CI: 0.52, 0.78) to non-significance (OR 0.81; 95% CI: 0.65, 1.01), when comparing cohorts before and after the MNCH program initiation (Sobel test of mediation P < 0.001). Conclusions ANC visits are associated with increased uptake of facility-based delivery and improved perinatal survival in the icddr,b SA. Further testing of the icddr,b approach to simultaneously improving quality of ANC and facility delivery care is needed in the existing health system in Bangladesh and in other low-income countries to maximize health benefits to mothers and newborns.

Abstract Background Improving perinatal health is the key to achieving the Millennium Development Goal for child survival. Recently, several reviews suggest that scaling up available effective perinatal interventions in an integrated approach can substantially reduce the stillbirth and neonatal death rates worldwide. We evaluated the effect of packaged interventions given in pregnancy, delivery and post-partum periods through integration of community- and facility-based services on perinatal mortality. Methods This study took advantage of an ongoing health and demographic surveillance system (HDSS) and a new Maternal, Neonatal and Child Health (MNCH) Project initiated in 2007 in Matlab, Bangladesh in half (intervention area) of the HDSS area. In the other half, women received usual care through the government health system (comparison area). The MNCH Project strengthened ongoing maternal and child health services as well as added new services. The intervention followed a continuum of care model for pregnancy, intrapartum, and post-natal periods by improving established links between community- and facility-based services. With a separate pre-post samples design, we compared the perinatal mortality rates between two periods--before (2005-2006) and after (2008-2009) implementation of MNCH interventions. We also evaluated the difference-of-differences in perinatal mortality between intervention and comparison areas. Results Antenatal coverage, facility delivery and cesarean section rates were significantly higher in the post- intervention period in comparison with the period before intervention. In the intervention area, the odds of perinatal mortality decreased by 36% between the pre-intervention and post-intervention periods (odds ratio: 0.64; 95% confidence intervals: 0.52-0.78). The reduction in the intervention area was also significant relative to the reduction in the comparison area (OR 0.73, 95% CI: 0.56-0.95; P = 0.018). Conclusion The continuum of care approach provided through the integration of service delivery modes decreased the perinatal mortality rate within a short period of time. Further testing of this model is warranted within the government health system in Bangladesh and other low-income countries.

Introduction: Digital technology is increasingly used to support interventions targeting smoking cessation in people with severe mental illness (SMI). However, little is known about their implementation and effectiveness in this population. We aimed to determine their effectiveness, stakeholder experiences, factors influencing implementation, and quality of reporting of digital interventions for smoking cessation in adults living with SMI., Method: Five online bibliographic databases were searched for articles published between 31 December 2000 and 31 January 2023. Studies involving adults accessing treatment for alcohol and substance use disorders, neurocognitive disorders and terminal illnesses were excluded. Risk of bias was assessed using the Mixed Methods Appraisal Tool (MMAT). A Mantel-Haenszel random-effects meta-analysis of randomized controlled trials (RCTs) was conducted. Participant experience and intervention implementation were explored using a narrative synthesis. Quality of reporting of interventions was assessed using the Template for Intervention Description and Replication (TIDieR) checklist., Results: Thirty-one studies enrolling 3,794 participants were included. Meta-analysis of biochemically verified abstinence at longest follow-up (month-1 to month-6) did not find an overall effect in favour of intervention [risk ratio (RR) = 0.66, 95% confidence interval (CI) = -0.005 - 1.37]. Interventions tailored to people with SMI were perceived as acceptable. Implementation strategies concentrated on overcoming practical challenges at the participant/user level., Conclusion: No evidence of the effectiveness of digital interventions to support smoking cessation in people with SMI was found. The importance of tailoring interventions to the needs of people with SMI is highlighted. Robust reporting of implementation is required to enhance future efforts to support smoking cessation in adults with SMI., Implications: The findings of this review add to the emerging evidence on digital interventions to support smoking cessation among people with SMI. We highlight the importance of tailoring interventions to the population, particularly considering the role of mental illness and the side effects of psychotropic medication in the accessibility and usability of digital interventions., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco.)

Background: Chewing betel quid (BQ) - a preparation commonly containing areca nut and slaked lime wrapped in betel leaf - is entrenched in South Asia. Although BQ consumption during pregnancy has been linked to adverse birth outcomes, its effect on postnatal growth remains largely unexplored., Objective: We examined the associations of BQ use during pregnancy with children's height-for-age and body mass index-for-age z-scores (HAZ and BAZ, respectively) and fat and fat-free mass along with sex-based differences in association in rural Bangladesh., Methods: With a prospective cohort design, we assessed BQ use among mothers enrolled in the Preterm and Stillbirth Study, Matlab ( n  = 3140) with a structured questionnaire around early third trimester. Children born to a subset of 614 women (including 134 daily users) were invited to follow-up between October 2021 and January 2022. HAZ and BAZ were calculated from anthropometric assessment, and fat and fat-free mass were estimated using bioelectric impedance. Overall and sex-specific multiple linear regression models were fitted., Results: Growth data were available for 501 children (mean age 4.9 years): 43.3% of them were born to non-users, 35.3% to those using prior to or less-than-daily during the survey, and 21.3% to daily users. No statistically significant associations were observed after adjusting for sex, parity, maternal height and education, and household wealth., Conclusions: There was no effect of BQ use during pregnancy on postnatal growth in this study. Longitudinal studies following up those born to heavy users beyond childhood are warranted for capturing long-term implications of prenatal BQ exposure.

Background: The Multi-Omics for Mothers and Infants consortium aims to improve birth outcomes. Preterm birth is a major obstetrical complication globally and causes significant infant and childhood morbidity and mortality., Objective: We analyzed placental samples (basal plate, placenta or chorionic villi, and the chorionic plate) collected by the 5 Multi-Omics for Mothers and Infants sites, namely The Alliance for Maternal and Newborn Health Improvement Bangladesh, The Alliance for Maternal and Newborn Health Improvement Pakistan, The Alliance for Maternal and Newborn Health Improvement Tanzania, The Global Alliance to Prevent Prematurity and Stillbirth Bangladesh, and The Global Alliance to Prevent Prematurity and Stillbirth 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' gestation) and 175 term (≥37 weeks' gestation) deliveries. The samples were fixed in formalin and paraffin embedded. Tissue sections from these samples were stained with hematoxylin and eosin and subjected to morphologic analyses. Other placental biopsies (n=35 preterm, 21 term) were flash frozen, which enabled RNA purification for bulk transcriptomics., Results: The morphologic analyses revealed a surprisingly high rate of inflammation that involved the basal plate, placenta or chorionic villi, and the chorionic plate. The rate of inflammation 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 in the basal plate or chorionic plate correlated with preterm birth. Our transcriptomic analyses identified 267 genes that were differentially expressed between placentas from preterm vs those from term births (123 upregulated, 144 downregulated). Mapping the differentially expressed genes onto single-cell RNA sequencing data from human placentas suggested that all the component cell types, either singly or in subsets, contributed to the observed dysregulation. Consistent with the histopathologic findings, gene ontology analyses highlighted the presence of leukocyte infiltration or 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. In this study, we showed that this link also exists in developing geographies. In addition, among the participating sites, we found geographic- and population-based differences in placental inflammation and preterm birth, suggesting the importance of local factors., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Copper (Cu), an essential trace mineral regulating multiple actions of inflammation and oxidative stress, has been implicated in risk for preterm birth (PTB)., Objectives: This study aimed to determine the association of maternal Cu concentration during pregnancy with PTB risk and gestational duration in a large multicohort study including diverse populations., Methods: Maternal plasma or serum samples of 10,449 singleton live births were obtained from 18 geographically diverse study cohorts. Maternal Cu concentrations were determined using inductively coupled plasma mass spectrometry. The associations of maternal Cu with PTB and gestational duration were analyzed using logistic and linear regressions for each cohort. The estimates were then combined using meta-analysis. Associations between maternal Cu and acute-phase reactants (APRs) and infection status were analyzed in 1239 samples from the Malawi cohort., Results: The maternal prenatal Cu concentration in our study samples followed normal distribution with mean of 1.92 μg/mL and standard deviation of 0.43 μg/mL, and Cu concentrations increased with gestational age up to 20 wk. The random-effect meta-analysis across 18 cohorts revealed that 1 μg/mL increase in maternal Cu concentration was associated with higher risk of PTB with odds ratio of 1.30 (95% confidence interval [CI]: 1.08, 1.57) and shorter gestational duration of 1.64 d (95% CI: 0.56, 2.73). In the Malawi cohort, higher maternal Cu concentration, concentrations of multiple APRs, and infections (malaria and HIV) were correlated and associated with greater risk of PTB and shorter gestational duration., Conclusions: Our study supports robust negative association between maternal Cu and gestational duration and positive association with risk for PTB. Cu concentration was strongly correlated with APRs and infection status suggesting its potential role in inflammation, a pathway implicated in the mechanisms of PTB. Therefore, maternal Cu could be used as potential marker of integrated inflammatory pathways during pregnancy and risk for PTB., (Copyright © 2023. Published by Elsevier Inc.)

Introduction: A history of preterm birth reportedly increases the risk of subsequent preterm birth. This association has primarily been studied in high-income countries and not in low-income settings in transition with rapidly descending preterm birth figures. We evaluated the population-based trends of preterm births and recurrent preterm births and the risk of preterm birth recurrence in the second pregnancy based on prospectively studied pregnancy cohorts over three decades in Matlab, Bangladesh., Methods: A population-based cohort included 72 160 live births from 1990 to 2019. We calculated preterm birth and recurrent preterm birth trends. We assessed the odds of preterm birth recurrence based on a subsample of 14 567 women with live-born singletons in their first and second pregnancies. We used logistic regression and presented the associations by OR with a 95% CI., Results: The proportion of preterm births decreased from 25% in 1990 to 13% in 2019. The recurrent preterm births had a similar, falling pattern from 7.4% to 3.1% across the same period, contributing 27% of the total number of preterm births in the population. The odds of second pregnancy preterm birth were doubled (OR 2.18; 95% CI 1.96 to 2.43) in women with preterm birth compared with the women with term birth in their first pregnancies, remaining similar over the study period. The lower the gestational age at the first birth, the higher the odds of preterm birth in the subsequent pregnancy (test for trend p<0.001)., Conclusion: In this rural Bangladeshi setting, recurrent preterm births contributed a sizeable proportion of the total number of preterm births at the population level. The increased risk of recurrence remained similar across three decades when the total proportion of preterm births was reduced from 25% to 13%., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Pancreatic ductal adenocarcinoma (PDAC) is a lethal disease characterized by a diverse tumor microenvironment. The heterogeneous cellular composition of PDAC makes it challenging to study molecular features of tumor cells using extracts from bulk tumor. The metabolic features in tumor cells from clinical samples are poorly understood, and their impact on clinical outcomes are unknown. Our objective was to identify the metabolic features in the tumor compartment that are most clinically impactful. Methods: A computational deconvolution approach using the DeMixT algorithm was applied to bulk RNASeq data from The Cancer Genome Atlas to determine the proportion of each gene's expression that was attributable to the tumor compartment. A machine learning algorithm designed to identify features most closely associated with survival outcomes was used to identify the most clinically impactful metabolic genes. Results: Two metabolic subtypes (M1 and M2) were identified, based on the pattern of expression of the 26 most important metabolic genes. The M2 phenotype had a significantly worse survival, which was replicated in three external PDAC cohorts. This PDAC subtype was characterized by net glycogen catabolism, accelerated glycolysis, and increased proliferation and cellular migration. Single cell data demonstrated substantial intercellular heterogeneity in the metabolic features that typified this aggressive phenotype. Conclusion: By focusing on features within the tumor compartment, two novel and clinically impactful metabolic subtypes of PDAC were identified. Our study emphasizes the challenges of defining tumor phenotypes in the face of the significant intratumoral heterogeneity that typifies PDAC. Further studies are required to understand the microenvironmental factors that drive the appearance of the metabolic features characteristic of the aggressive M2 PDAC phenotype., Competing Interests: HighLifeR is owned by Qualisure Diagnostics Inc., and OB is director and shareholder of Qualisure Diagnostics Inc. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Pervin, Asad, Cao, Jang, Feizi, Haibe-Kains, Karasinska, O’Kane, Gallinger, Schaeffer, Renouf, Zogopoulos and Bathe.)

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., (© 2023 The Authors.)

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.

Introduction: Evidence suggests that smokers can successfully quit, remain abstinent or reduce smoking during a smoke-free mental health inpatient stay, provided behavioral/pharmacological support are offered. However, few evidence-based strategies to prevent the return to prehospital smoking behaviors post-discharge exist., Aims and Methods: We report the development of an intervention designed to support smoking-related behavior change following discharge from a smoke-free mental health stay. We followed the Behavior Change Wheel (BCW) intervention development process. The target behavior was supporting patients to change their smoking behaviors following discharge from a smoke-free mental health stay. Using systematic reviews, we identified the barriers and enablers, classified according to the Theoretical Domains Framework (TDF). Potential intervention functions to address key influences were identified by consulting the BCW and Behavior Change Technique (BCT) taxonomy. Another systematic review identified effectiveness of BCTs in this context. Stakeholder consultations were conducted to prioritize and refine intervention content., Results: Barriers and enablers to supporting smoking cessation were identified within the domains of environmental context and resources (lack of staff time); knowledge (ill-informed interactions about smoking); social influences, and intentions (lack of intention to deliver support). Potential strategies to address these influences included goal setting, problem-solving, feedback, social support, and information on health consequences. A strategy for operationalizing these techniques into intervention components was agreed upon: Pre-discharge evaluation sessions, a personalized resource folder, tailored behavioral and text message support post-discharge, and a peer interaction group, delivered by a trained mental health worker., Conclusions: The intervention includes targeted resources to support smoking-related behavior change in patients following discharge from a smoke-free mental health setting., Implications: Using the BCW and TDF supported a theoretically and empirically informed process to define and develop a tailored intervention that acknowledges barriers and enablers to supporting smoking cessation in mental health settings. The result is a novel complex theory- and evidence-based intervention that will be formally tested in a randomized controlled feasibility study., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco.)

Background: Accurate estimates of gestational age (GA) at birth are important for preterm birth surveillance but can be challenging to obtain in low income countries. Our objective was to develop machine learning models to accurately estimate GA shortly after birth using clinical and metabolomic data., Methods: We derived three GA estimation models using ELASTIC NET multivariable linear regression using metabolomic markers from heel-prick blood samples and clinical data from a retrospective cohort of newborns from Ontario, Canada. We conducted internal model validation in an independent cohort of Ontario newborns, and external validation in heel prick and cord blood sample data collected from newborns from prospective birth cohorts in Lusaka, Zambia and Matlab, Bangladesh. Model performance was measured by comparing model-derived estimates of GA to reference estimates from early pregnancy ultrasound., Results: Samples were collected from 311 newborns from Zambia and 1176 from Bangladesh. The best-performing model accurately estimated GA within about 6 days of ultrasound estimates in both cohorts when applied to heel prick data (MAE 0.79 weeks (95% CI 0.69, 0.90) for Zambia; 0.81 weeks (0.75, 0.86) for Bangladesh), and within about 7 days when applied to cord blood data (1.02 weeks (0.90, 1.15) for Zambia; 0.95 weeks (0.90, 0.99) for Bangladesh)., Conclusions: Algorithms developed in Canada provided accurate estimates of GA when applied to external cohorts from Zambia and Bangladesh. Model performance was superior in heel prick data as compared to cord blood data., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Hawken et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Several metals act as endocrine disruptors, but there are few large longitudinal studies about associations with puberty onset., Objectives: We evaluated whether early life cadmium, lead, and arsenic exposure was associated with timing of menarche., Methods: In a mother-child cohort in rural Bangladesh ( n = 935 ), the exposure was assessed by concentrations in maternal erythrocytes in early pregnancy and in girls' urine at 5 and 10 years of age using inductively coupled plasma mass spectrometry. The girls were interviewed twice, at average ages 13.3 [standard deviation ( SD ) = 0.43 ] and 13.8 ( SD = 0.43 ) y, and the date of menarche, if present, was recorded. Associations were assessed using Kaplan-Meier analysis and multivariable-adjusted Cox regression., Results: In total, 77% of the girls ( n = 717 ) had reached menarche by the second follow-up. The median age of menarche among all girls was 13.0 y (25th-75th percentiles: 12.4-13.7 y). At 10 years of age, median urinary cadmium was 0.25 μ g / L (5th-95th percentiles: 0.087 - 0.72 μ g / L ), lead 1.6 μ g / L ( 0.70 - 4.2 μ g / L ), and arsenic 54 μ g / L ( 19 - 395 μ g / L ). Given the same age, girls in the highest quartile of urinary cadmium at 5 and 10 years of age had a lower rate of menarche than girls in the lowest quartile, with an adjusted hazard ratio of (HR) 0.80 (95% CI: 0.62, 1.01) at 5 years of age, and 0.77 (95% CI: 0.60, 0.98) at 10 years of age. This implies that girls in the highest cadmium exposure quartile during childhood had a higher age at menarche. Comparing girls in the highest to the lowest quartile of urinary lead at 10 years of age, the former had a higher rate of menarche [adjusted HR = 1.23 (95% CI: 0.97, 1.56)], implying lower age at menarche, whereas there was no association with urinary lead at 5 years of age. Girls born to mothers in the highest quartile of erythrocyte arsenic during pregnancy were less likely to have attained menarche than girls born to mothers in the lowest quartile [adjusted HR = 0.79 (95% CI: 0.62, 0.99)]. No association was found with girls' urinary arsenic exposure., Discussion: Long-term childhood cadmium exposure was associated with later menarche, whereas the associations with child lead exposure were inconclusive. Maternal exposure to arsenic, but not cadmium or lead, was associated with later menarche. https://doi.org/10.1289/EHP11121.

Background: Diet being a modifiable factor, its relationship with cardiometabolic risk is of public health interest. The vast majority of studies on associations of dietary patterns with cardiometabolic risk indicators among adolescents are from high-income countries and urban settings. We sought to describe dietary patterns and examine their associations with selected cardiometabolic risk indicators-waist circumference (WC), systolic blood pressure, fasting lipid profile and insulin resistance-along with its gender stratification among adolescents in a low-income, rural setting., Methods: This cross-sectional study utilized data from the 15-year follow-up of the Maternal and Infant Nutrition Interventions in Matlab (MINIMat) cohort in southeast Bangladesh. The children who were born as singletons to the mothers randomized in the MINIMat trial and had valid birth anthropometrics were eligible for the follow-up. We employed a single, qualitative 24-hour recall to assess diet. Dietary patterns were derived from simple K -means cluster analysis, and calculation of dietary diversity score (DDS) using a validated instrument. Anthropometric parameters and systolic blood pressure were recorded. Fasting plasma triglyceride, total cholesterol, low- and high-density lipoproteins, insulin and glucose levels were measured. We calculated insulin resistance using the Homeostasis Model Assessment equation (HOMA-IR). Three right-skewed outcome variables were natural log (Ln) transformed: WC, triglyceride and HOMA-IR. Omnibus and gender-specific multiple linear regression models were fitted., Results: Among 2,253 adolescents (52.1% girls, 7.1% overweight/obese), we identified four diet clusters: Traditional, Fish-dominant, Meat-dominant, and High-variety. No significant associations were found between the clusters and indicators. On gender-stratification, triglyceride levels were lower among boys in the Fish-dominant (Ln-triglyceride β adjusted : -0.09; 95% confidence interval (CI): -0.15, -0.02) and Meat-dominant (Ln-triglyceride β adjusted : -0.08; 95% CI: -0.15, -0.004) clusters than among boys in the Traditional cluster. Compared to boys in the bottom quartile of DDS, boys in the top quartile had 2.1 mm of Hg (95% CI: 0.5, 3.6) higher systolic blood pressure and 1.9% (95% CI: 0.01-3.8%) higher WC., Conclusion: While statistically significant, the gender-specific differences in triglyceride, systolic blood pressure, and waist circumference across dietary patterns were small. Associations between dietary patterns and cardiometabolic risk indicators may require a time lag beyond mid-adolescence to manifest in a rural setting. Prospective studies are warranted to delineate the magnitude and direction of those associations., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Islam, Rahman, Selling, Näsänen-Gilmore, Kippler, Kajantie, Rahman, Pervin and Ekström.)

Background: Although consumption of ultra-processed and deep-fried foods among adolescents is a global health concern, little is known about its gender and socio-economic stratification in rural settings of low- and middle-income countries. We, thus, aimed to describe ultra-processed and deep-fried food consumption among rural adolescents by gender and socio-economic factors, and to explore their relative importance in shaping consumption., Methods: This cross-sectional study drew on data from a household survey in Matlab, a rural sub-district in Bangladesh. The analytic sample comprised 2463 adolescents. We assessed consumption of four ultra-processed food groups: ready-to-eat or "instant" foods; confectionery, sweets and similar packaged products; savory snacks; sugar-sweetened beverage; and of deep-fried foods with a 24-hour, qualitative recall. Asset scores were constructed. Proportion of consumption was calculated and compared by gender and household wealth. Logistic regression models were fitted to isolate socio-demographic variables associated with consumption., Results: Approximately 83% (81.5-84.4) adolescents consumed at least one ultra-processed or deep-fried item. Confectioneries were the most consumed (53.5%), whereas sugar-sweetened beverage was the least consumed (12%) group. Boys had greater odds of consumption than girls for all food groups. The association was strongest for sugar-sweetened beverage (adjusted odds ratio = 2.57; 95% CI: 1.97, 3.37), followed by deep-fried foods (adjusted odds ratio = 1.96; 95% CI: 1.66, 2.32) and ready-to-eat foods (adjusted odds ratio = 1.85; 95% CI: 1.45, 2.38). Belonging to the richest households was associated with ready-to-eat food consumption (adjusted odds ratio = 1.55; 95% CI: 1.12, 2.16). Adolescents with higher educational attainment had lower odds of consuming sugar-sweetened beverage (adjusted odds ratio = 0.73; 95% CI: 0.54, 0.98)., Conclusion: Consumption of packaged confectioneries, savory snacks, and deep-fried foods appeared common, while SSB consumption was relatively low. Role of gender was pre-eminent as consumption was more likely among boys across the food groups. This may disproportionately expose them to the risk of diet-related non-communicable diseases., Competing Interests: The authors have declared that no competing interests exist.

Introduction: Evidence-based smoking cessation and temporary abstinence interventions to address smoking in mental health settings are available, but the impact of these interventions is limited., Aims and Methods: We aimed to identify and synthesize the perceived barriers and enablers to supporting smoking cessation in mental health settings. Six databases were searched for articles reporting the investigation of perceived barriers and enablers to supporting smoking cessation in mental health settings. Data were extracted and coded using a mixed inductive/deductive method to the theoretical domains framework, key barriers and enablers were identified through the combining of coding frequency, elaboration, and expressed importance., Results: Of 31 included articles, 56 barriers/enablers were reported from the perspectives of mental healthcare professionals (MHPs), 48 from patient perspectives, 21 from mixed perspectives, and 0 from relatives/carers. Barriers to supporting smoking cessation or temporary abstinence in mental health settings mainly fell within the domains: environmental context and resources (eg, MHPs lack of time); knowledge (eg, interactions around smoking that did occur were ill informed); social influences (eg, smoking norms within social network); and intentions (eg, MHPs lack positive intentions to deliver support). Enablers mainly fell within the domains: environmental context and resources (eg, use of appropriate support materials) and social influences (eg, pro-quitting social norms)., Conclusions: The importance of overcoming competing demands on staff time and resources, the inclusion of tailored, personalized support, the exploitation of patients wider social support networks, and enhancing knowledge and awareness around the benefits smoking cessation is highlighted., Implications: Identified barriers and enablers represent targets for future interventions to improve the support of smoking cessation in mental health settings. Future research needs to examine the perceptions of the carers and family/friends of patients in relation to the smoking behavior change support delivered to patients., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco.)

Assessment of gestational age (GA) is key to provide optimal care during pregnancy. However, its accurate determination remains challenging in low- and middle-income countries, where access to obstetric ultrasound is limited. Hence, there is an urgent need to develop clinical approaches that allow accurate and inexpensive estimations of GA. We investigated the ability of urinary metabolites to predict GA at time of collection in a diverse multi-site cohort of healthy and pathological pregnancies (n = 99) using a broad-spectrum liquid chromatography coupled with mass spectrometry (LC-MS) platform. Our approach detected a myriad of steroid hormones and their derivatives including estrogens, progesterones, corticosteroids, and androgens which were associated with pregnancy progression. We developed a restricted model that predicted GA with high accuracy using three metabolites (rho = 0.87, RMSE = 1.58 weeks) that was validated in an independent cohort (n = 20). The predictions were more robust in pregnancies that went to term in comparison to pregnancies that ended prematurely. Overall, we demonstrated the feasibility of implementing urine metabolomics analysis in large-scale multi-site studies and report a predictive model of GA with a potential clinical value., (© 2022. The Author(s).)

Background: There has been a steady increase in the number of primary care patients receiving long-term maintenance antidepressant treatment, despite limited evidence of a benefit of this treatment beyond 8 months., Objective: The ANTidepressants to prevent reLapse in dEpRession (ANTLER) trial investigated the clinical effectiveness and cost-effectiveness of antidepressant medication in preventing relapse in UK primary care., Design: This was a Phase IV, double-blind, pragmatic, multisite, individually randomised parallel-group controlled trial, with follow-up at 6, 12, 26, 39 and 52 weeks. Participants were randomised using minimisation on centre, type of antidepressant and baseline depressive symptom score above or below the median using Clinical Interview Schedule - Revised (two categories). Statisticians were blind to allocation for the outcome analyses., Setting: General practices in London, Bristol, Southampton and York., Participants: Individuals aged 18-74 years who had experienced at least two episodes of depression and had been taking antidepressants for ≥ 9 months but felt well enough to consider stopping their medication. Those who met an International Statistical Classification of Diseases and Related Health Problems , Tenth Revision, diagnosis of depression or with other psychiatric conditions were excluded., Intervention: At baseline, participants were taking citalopram 20 mg, sertraline 100 mg, fluoxetine 20 mg or mirtazapine 30 mg. They were randomised to either remain on their current medication or discontinue medication after a tapering period., Main Outcome Measures: The primary outcome was the time, in weeks, to the beginning of the first depressive episode after randomisation. This was measured by a retrospective Clinical Interview Schedule - Revised that assessed the onset of a depressive episode in the previous 12 weeks, and was conducted at 12, 26, 39 and 52 weeks. The depression-related resource use was collected over 12 months from medical records and patient-completed questionnaires. Quality-adjusted life-years were calculated using the EuroQol-5 Dimensions, five-level version., Results: Between 9 March 2017 and 1 March 2019, we randomised 238 participants to antidepressant continuation (the maintenance group) and 240 participants to antidepressant discontinuation (the discontinuation group). The time to relapse of depression was shorter in the discontinuation group, with a hazard ratio of 2.06 (95% confidence interval 1.56 to 2.70; p  < 0.0001). By 52 weeks, relapse was experienced by 39% of those who continued antidepressants and 56% of those who discontinued antidepressants. The secondary analysis revealed that people who discontinued experienced more withdrawal symptoms than those who remained on medication, with the largest difference at 12 weeks. In the discontinuation group, 37% (95% confidence interval 28% to 45%) of participants remained on their randomised medication until the end of the trial. In total, 39% (95% confidence interval 32% to 45%) of participants in the discontinuation group returned to their original antidepressant compared with 20% (95% confidence interval 15% to 25%) of participants in maintenance group. The health economic evaluation demonstrated that participants randomised to discontinuation had worse utility scores at 3 months (-0.037, 95% confidence interval -0.059 to -0.015) and fewer quality-adjusted life-years over 12 months (-0.019, 95% confidence interval -0.035 to -0.003) than those randomised to continuation. The discontinuation pathway, besides giving worse outcomes, also cost more [extra £2.71 per patient over 12 months (95% confidence interval -£36.10 to £37.07)] than the continuation pathway, although the cost difference was not significant., Conclusions: Patients who discontinue long-term maintenance antidepressants in primary care are at increased risk of relapse and withdrawal symptoms. However, a substantial proportion of patients can discontinue antidepressants without relapse. Our findings will give patients and clinicians an estimate of the likely benefits and harms of stopping long-term maintenance antidepressants and improve shared decision-making. The participants may not have been representative of all people on long-term maintenance treatment and we could study only a restricted range of antidepressants and doses. Identifying patients who will not relapse if they discontinued antidepressants would be clinically important., Trial Registration: Current Controlled Trials ISRCTN15969819 and EudraCT 2015-004210-26., Funding: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment ; Vol. 25, No. 69. See the NIHR Journals Library website for further project information.

Mental health problems are associated with lower quality of life, increased unscheduled care, high economic and social cost, and increased mortality. Nature-based interventions (NBIs) that support people to engage with nature in a structured way are asset-based solutions to improve mental health for community based adults. However, it is unclear which NBIs are most effective, or what format and dose is most efficacious. We systematically reviewed the controlled and uncontrolled evidence for outdoor NBIs. The protocol was registered at PROSPERO (CRD42020163103). Studies that included adults (aged ≥18 years) in community-based settings with or without mental and/or physical health problems were eligible for inclusion. Eligible interventions were structured outdoor activities in green and/or blue space for health and wellbeing. We searched ASSIA, CENTRAL, Embase, Greenfile, MEDLINE, PsycINFO, and Web of Science in October 2019; the search was updated in September 2020. We screened 14,321 records and included 50 studies. Sixteen studies were randomised controlled trials (RCTs); 18 were controlled studies; and 16 were uncontrolled before and after studies. Risk of bias for RCTs was low to moderate; and moderate to high for controlled and uncontrolled studies. Random effects meta-analysis of RCTs showed that NBIs were effective for improving depressive mood -0.64 (95% CI: 1.05 to -0.23), reducing anxiety -0.94 (95% CI: 0.94 to -0.01), improving positive affect 0.95 (95% CI: 0.59 to 1.31), and reducing negative affect -0.52 (95% CI: 0.77 to -0.26). Results from controlled and uncontrolled studies largely reflected findings from RCTs. There was less evidence that NBIs improved physical health. The most effective interventions were offered for between 8 and 12 weeks, and the optimal dose ranged from 20 to 90 min. NBIs, specifically gardening, green exercise and nature-based therapy, are effective for improving mental health outcomes in adults, including those with pre-existing mental health problems., Competing Interests: We can confirm that no authors have any conflicts of interest to declare., (© 2021 The Authors. Published by Elsevier Ltd.)

Background: Patients with depression who are treated in primary care practices may receive antidepressants for prolonged periods. Data are limited on the effects of maintaining or discontinuing antidepressant therapy in this setting., Methods: We conducted a randomized, double-blind trial involving adults who were being treated in 150 general practices in the United Kingdom. All the patients had a history of at least two depressive episodes or had been taking antidepressants for 2 years or longer and felt well enough to consider stopping antidepressants. Patients who had received citalopram, fluoxetine, sertraline, or mirtazapine were randomly assigned in a 1:1 ratio to maintain their current antidepressant therapy (maintenance group) or to taper and discontinue such therapy with the use of matching placebo (discontinuation group). The primary outcome was the first relapse of depression during the 52-week trial period, as evaluated in a time-to-event analysis. Secondary outcomes were depressive and anxiety symptoms, physical and withdrawal symptoms, quality of life, time to stopping an antidepressant or placebo, and global mood ratings., Results: A total of 1466 patients underwent screening. Of these patients, 478 were enrolled in the trial (238 in the maintenance group and 240 in the discontinuation group). The average age of the patients was 54 years; 73% were women. Adherence to the trial assignment was 70% in the maintenance group and 52% in the discontinuation group. By 52 weeks, relapse occurred in 92 of 238 patients (39%) in the maintenance group and in 135 of 240 (56%) in the discontinuation group (hazard ratio, 2.06; 95% confidence interval, 1.56 to 2.70; P<0.001). Secondary outcomes were generally in the same direction as the primary outcome. Patients in the discontinuation group had more symptoms of depression, anxiety, and withdrawal than those in the maintenance group., Conclusions: Among patients in primary care practices who felt well enough to discontinue antidepressant therapy, those who were assigned to stop their medication had a higher risk of relapse of depression by 52 weeks than those who were assigned to maintain their current therapy. (Funded by the National Institute for Health Research; ANTLER ISRCTN number, ISRCTN15969819.)., (Copyright © 2021 Massachusetts Medical Society.)

Background: Timely utilization of antenatal care and delivery services supports the health of mothers and babies. Few studies exist on the utilization and determinants of timely ANC and use of different types of health facilities at the community level in Bangladesh. This study aims to assess the utilization, timeliness of, and socio-demographic determinants of antenatal and delivery care services in two sub-districts in Bangladesh., Methods: This cross-sectional study used data collected through a structured questionnaire in the eRegMat cluster-randomized controlled trial, which enrolled pregnant women between October 2018-June 2020. We undertook univariate and multivariate logistic regression analysis to determine the associations of socio-demographic variables with timely first ANC, four timely ANC visits, and facility delivery. We considered the associations in the multivariate logistic regression as statistically significant if the p-value was found to be <0.05. Results are presented as adjusted odds ratios (AOR) with 95% confidence intervals (CI)., Results: Data were available on 3293 pregnant women. Attendance at a timely first antenatal care visit was 59%. Uptake of four timely antenatal care visits was 4.2%. About three-fourths of the women delivered in a health facility. Women from all socio-economic groups gradually shifted from using public health facilities to private hospitals as the pregnancy advanced. Timely first antenatal care visit was associated with: women over 30 years of age (AOR: 1.52, 95% CI: 1.05-2.19); nulliparity (AOR: 1.30, 95% CI: 1.04-1.62); husbands with >10 years of education (AOR: 1.40, 95% CI: 1.09-1.81) and being in the highest wealth quintile (AOR: 1.49, 95% CI: 1.18-1.89). Facility deliveries were associated with woman's age; parity; education; the husband's education, and wealth index. None of the available socio-demographic factors were associated with four timely antenatal care visits., Conclusions: The study observed socio-demographic inequalities associated with increased utilization of timely first antenatal care visit and facility delivery. The pregnant women, irrespective of wealth shifted from public to private facilities for their antenatal care visits and delivery. To increase the health service utilization and promote good health, maternal health care programs should pay particular attention to young, multiparous women, of low socio-economic status, or with poorly educated husbands., Clinical Trial Registration: ISRCTN69491836; https://www.isrctn.com/. Registered on December 06, 2018. Retrospectively registered., Competing Interests: The authors have declared that no competing interests exist.

Background: Millions of individuals worldwide, particularly in Bangladesh, are exposed to arsenic, mainly through drinking water from tube wells. Arsenic is a reproductive toxicant, but there is limited knowledge of whether it influences pubertal development., Objectives: We evaluated the association between prenatal arsenic exposure and age at menarche., Methods: This prospective study was based on data from two studies conducted in Matlab, Bangladesh-the Maternal and Infant Nutrition Interventions in Matlab (MINIMat) trial and the Health Consequences of Arsenic in Matlab (AsMat) study. We included 809 MINIMat girls who participated in assessing age at menarche from July 2016 to June 2017 and had prenatal arsenic exposure data through the AsMat study via measurements in tube well water used by the mothers during pregnancy. The exposure was categorized into <10, 10-49, 50-99, 100-199, and ≥200 µg/L. We used Kaplan-Meier and Cox proportional hazards analyses with adjustment for potential confounders to evaluate the association between arsenic exposure and age at menarche. The results were presented by adjusted hazards ratio (aHR) with a 95% confidence interval (CI)., Results: The median arsenic concentration in tube well water consumed by pregnant women was 80 µg/L (interquartile range 2-262 µg/L), and 55% drank water with concentrations above Bangladesh's acceptable value of 50 µg/L. The median age at menarche was 13.0 years. The unadjusted analysis revealed 3.2 months delay in menarche for girls exposed to arsenic concentrations ≥200 µg/L compared with the girl exposed to arsenic concentrations <10 µg/L. Girls exposed to the same higher arsenic concentrations were 23% (aHR 0.77, 95% CI: 0.63-0.95) less likely to have reached menarche than girls exposed to low arsenic concentrations., Conclusions: Increased levels of prenatal arsenic exposure were associated with older age at menarche. This delay may indicate endocrine disruptions that could potentially result in adverse health consequences in later life. This finding, along with other severe adverse health reinforces the need for arsenic mitigation at the population level., (Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Selenium (Se), an essential trace mineral, has been implicated in preterm birth (PTB). We aimed to determine the association of maternal Se concentrations during pregnancy with PTB risk and gestational duration in a large number of samples collected from diverse populations., Methods: Gestational duration data and maternal plasma or serum samples of 9946 singleton live births were obtained from 17 geographically diverse study cohorts. Maternal Se concentrations were determined by inductively coupled plasma mass spectrometry analysis. The associations between maternal Se with PTB and gestational duration were analysed using logistic and linear regressions. The results were then combined using fixed-effect and random-effect meta-analysis., Findings: In all study samples, the Se concentrations followed a normal distribution with a mean of 93.8 ng/mL (SD: 28.5 ng/mL) but varied substantially across different sites. The fixed-effect meta-analysis across the 17 cohorts showed that Se was significantly associated with PTB and gestational duration with effect size estimates of an OR=0.95 (95% CI: 0.9 to 1.00) for PTB and 0.66 days (95% CI: 0.38 to 0.94) longer gestation per 15 ng/mL increase in Se concentration. However, there was a substantial heterogeneity among study cohorts and the random-effect meta-analysis did not achieve statistical significance. The largest effect sizes were observed in UK (Liverpool) cohort, and most significant associations were observed in samples from Malawi., Interpretation: While our study observed statistically significant associations between maternal Se concentration and PTB at some sites, this did not generalise across the entire cohort. Whether population-specific factors explain the heterogeneity of our findings warrants further investigation. Further evidence is needed to understand the biologic pathways, clinical efficacy and safety, before changes to antenatal nutritional recommendations for Se supplementation are considered., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY. Published by BMJ.)

Background: Digital health interventions (DHIs) can alleviate several barriers to achieving better maternal and child health. The World Health Organization's guideline recommendations for DHIs emphasize the need to integrate multiple DHIs for maximizing impact. The complex health system of Bangladesh provides a unique setting for evaluating and understanding the role of an electronic registry (eRegistry) for antenatal care, with multiple integrated DHIs for strengthening the health system as well as improving the quality and utilization of the public health care system., Objective: The aim of this study is to assess the effect of an eRegistry with DHIs compared with a simple digital data entry tool without DHIs in the community and frontline health facilities., Methods: The eRegMat is a cluster-randomized controlled trial conducted in the Matlab North and Matlab South subdistricts in the Chandpur district, Bangladesh, where health facilities are currently using the eRegistry for digital tracking of the health status of pregnant women longitudinally. The intervention arm received 3 superimposed data-driven DHIs: health worker clinical decision support, health worker feedback dashboards with action items, and targeted client communication to pregnant women. The primary outcomes are appropriate screening as well as management of hypertension during pregnancy and timely antenatal care attendance. The secondary outcomes include morbidity and mortality in the perinatal period as well as timely first antenatal care visit; successful referrals for anemia, diabetes, or hypertension during pregnancy; and facility delivery., Results: The eRegistry and DHIs were co-designed with end users between 2016 and 2018. The eRegistry was implemented in the study area in July 2018. Recruitment for the trial started in October 2018 and ended in June 2020, followed by an 8-month follow-up period to capture outcome data until February 2021. Trial results will be available for publication in June 2021., Conclusions: This trial allows the simultaneous assessment of multiple integrated DHIs for strengthening the health system and aims to provide evidence for its implementation. The study design and outcomes are geared toward informing the living review process of the guidelines for implementing DHIs., Trial Registration: ISRCTN Registry ISRCTN69491836; https://www.isrctn.com/ISRCTN69491836., International Registered Report Identifier (irrid): DERR1-10.2196/26918., (©Anisur Rahman, Ingrid K Friberg, Akuba Dolphyne, Ingvild Fjeldheim, Fatema Khatun, Brian O'Donnell, Jesmin Pervin, Monjur Rahman, A M Qaiyum Rahman, U Tin Nu, Bidhan Krishna Sarker, Mahima Venkateswaran, J Frederik Frøen. Originally published in JMIR Research Protocols (https://www.researchprotocols.org), 06.07.2021.)

Background: Timely and appropriate evidence-based practices during antenatal care improve maternal and neonatal health. There is a lack of information on how pregnant women and families perceive antenatal care in Bangladesh. The aim of our study was to develop targeted client communication via text messages for increasing antenatal care utilization, as part of an implementation of an electronic registry for maternal and child health., Methods: Using a phenomenological approach, we conducted this qualitative study from May to June 2017 in two sub-districts of Chandpur district, Bangladesh. We selected study participants by purposive sampling. A total of 24 in-depth interviews were conducted with pregnant women (n = 10), lactating women (n = 5), husbands (n = 5), and mothers-in-law (n = 4). The Health Belief Model (HBM) was used to guide the data collection. Thematic analysis was carried out manually according to the HBM constructs. We used behavior change techniques to inform the development of targeted client communication based on the thematic results., Results: Almost no respondents mentioned antenatal care as a preventive form of care, and only perceived it as necessary if any complications developed during pregnancy. Knowledge of the content of antenatal care (ANC) and pregnancy complications was low. Women reported a variety of reasons for not attending ANC, including the lack of information on the timing of ANC; lack of decision-making power; long-distance to access care; being busy with household chores, and not being satisfied with the treatment by health care providers. Study participants recommended phone calls as their preferred communication strategy when asked to choose between the phone call and text message, but saw text messages as a feasible option. Based on the findings, we developed a library of 43 automatically customizable text messages to increase ANC utilization., Conclusions: Pregnant women and family members had limited knowledge about antenatal care and pregnancy complications. Effective health information through text messages could increase awareness of antenatal care among the pregnant women in Bangladesh. This study presents an example of designing targeted client communication to increase antenatal care utilization within formal scientific frameworks, including a taxonomy of behavior change techniques., Trial Registration: ISRCTN69491836 . Registered on December 06, 2018. Retrospectively registered.

Background: Misfolded proteins in the urine of women with preeclampsia bind to Congo Red dye (urine congophilia). We evaluated a beta prototype of a point-of-care test for the identification of urine congophilia in preeclamptic women., Methods: Prospective diagnostic case-control study conducted in 409 pregnant women ( n  = 204 preeclampsia; n  = 205 uncomplicated pregnancies) presenting for delivery in two tertiary level hospitals located in Bangladesh and Mexico. The GV-005, a beta prototype of a point-of-care test for detecting congophilia, was performed on fresh and refrigerated urine samples. The primary outcome was the prevalence of urine congophilia in each of the two groups. Secondary outcome was the likelihood of the GV-005 (index test) to confirm and rule-out preeclampsia based on an adjudicated diagnosis (reference standard)., Findings: The GV-005 was positive in 85% of clinical cases (83/98) and negative in 81% of clinical controls (79/98) in the Bangladesh cohort. In the Mexico cohort, the GV-005 test was positive in 48% of clinical cases (51/106) and negative in 77% of clinical controls (82/107). Adjudication confirmed preeclampsia in 92% of Bangladesh clinical cases (90/98) and 61% of Mexico clinical cases (65/106). The odds ratio of a urine congophilia in adjudicated cases versus controls in the Bangladesh cohort was 34 . 5 (14 . 7 - 81 . 1) ( p <0 . 001) compared to 4 . 2 (2 . 1 - 8 . 4; p <0 . 001) in the Mexico cohort., Interpretation: The GV-005, a beta prototype of a point-of-care test for detection of urine congophilia, is a promising tool for rapid identification of preeclampsia., Funding: Saving Lives at Birth., Competing Interests: Dr. Irina Buhimschi reports grants from Saving Lives at Birth (SLaB) partners including USAID, Bill & Melinda Gates Foundation, Goverments of Canada, Norway and UK DFID, during the conduct of the study; other from GestVision Inc. In addition, Dr. Irina Buhimschi has a patent US Patent Number 8263,342 with royalties paid by GestVision Inc, a patent US Patent Number 9229,009 with royalties paid by GestVision Inc and by Shuwen Biotech, a patent U.S. Patent Number 10,324,094 with royalties paid by GestVision Inc, and a patent European patent No 3,129,779 with royalties paid by GestVision Inc. These royalties are paid to Yale University who disburses a percentage to inventors and co-inventors. The Congo Red devices used in this study were purchased from GestVision Inc who had no input in data interpretation or decision to submit for publication. Dr. Catalin Buhimschi reports grants from Saving Lives at Birth (SLaB) partners including USAID, Bill & Melinda Gates Foundation, Goverments of Canada, Norway and UK DFID, during the conduct of the study; other from GestVision Inc. In addition, Dr. Catalin Buhimschi has a patent US Patent Number 8263,342 with royalties paid by GestVision Inc, a patent US Patent Number 9229,009 with royalties paid by GestVision Inc and by Shuwen Biotech, a patent U.S. Patent Number 10,324,094 with royalties paid by GestVision Inc, and a patent European patent No 3,129,779 with royalties paid by GestVision Inc. These royalties are paid to Yale University who disburses a percentage to inventors and co-inventors. The Congo Red devices used in this study were purchased from GestVision Inc who had no input in data interpretation or decision to submit for publication. Dr. Easterling reports personal fees from DiabetOmics, Inc., outside the submitted work. The other authors have no conflicts to declare., (© 2020 The Authors.)

Importance: Worldwide, preterm birth (PTB) is the single largest cause of deaths in the perinatal and neonatal period and is associated with increased morbidity in young children. The cause of PTB is multifactorial, and the development of generalizable biological models may enable early detection and guide therapeutic studies., Objective: To investigate the ability of transcriptomics and proteomics profiling of plasma and metabolomics analysis of urine to identify early biological measurements associated with PTB., Design, Setting, and Participants: This diagnostic/prognostic study analyzed plasma and urine samples collected from May 2014 to June 2017 from pregnant women in 5 biorepository cohorts in low- and middle-income countries (LMICs; ie, Matlab, Bangladesh; Lusaka, Zambia; Sylhet, Bangladesh; Karachi, Pakistan; and Pemba, Tanzania). These cohorts were established to study maternal and fetal outcomes and were supported by the Alliance for Maternal and Newborn Health Improvement and the Global Alliance to Prevent Prematurity and Stillbirth biorepositories. Data were analyzed from December 2018 to July 2019., Exposures: Blood and urine specimens that were collected early during pregnancy (median sampling time of 13.6 weeks of gestation, according to ultrasonography) were processed, stored, and shipped to the laboratories under uniform protocols. Plasma samples were assayed for targeted measurement of proteins and untargeted cell-free ribonucleic acid profiling; urine samples were assayed for metabolites., Main Outcomes and Measures: The PTB phenotype was defined as the delivery of a live infant before completing 37 weeks of gestation., Results: Of the 81 pregnant women included in this study, 39 had PTBs (48.1%) and 42 had term pregnancies (51.9%) (mean [SD] age of 24.8 [5.3] years). Univariate analysis demonstrated functional biological differences across the 5 cohorts. A cohort-adjusted machine learning algorithm was applied to each biological data set, and then a higher-level machine learning modeling combined the results into a final integrative model. The integrated model was more accurate, with an area under the receiver operating characteristic curve (AUROC) of 0.83 (95% CI, 0.72-0.91) compared with the models derived for each independent biological modality (transcriptomics AUROC, 0.73 [95% CI, 0.61-0.83]; metabolomics AUROC, 0.59 [95% CI, 0.47-0.72]; and proteomics AUROC, 0.75 [95% CI, 0.64-0.85]). Primary features associated with PTB included an inflammatory module as well as a metabolomic module measured in urine associated with the glutamine and glutamate metabolism and valine, leucine, and isoleucine biosynthesis pathways., Conclusions and Relevance: This study found that, in LMICs and high PTB settings, major biological adaptations during term pregnancy follow a generalizable model and the predictive accuracy for PTB was augmented by combining various omics data sets, suggesting that PTB is a condition that manifests within multiple biological systems. These data sets, with machine learning partnerships, may be a key step in developing valuable predictive tests and intervention candidates for preventing PTB.

Background: Maternal nutrition is one of the most influential factors that affect the health of the mother and her offspring and remains a significant public health challenge globally. There is a lack of studies evaluating the trends of maternal nutrition and its impact on the burden of pregnancy complications from low-income countries, including Bangladesh. We aimed to determine the burden of early-pregnancy nutrition status based on body mass index (BMI), and the associations of nutritional status with pregnancy-induced hypertension (PIH), cesarean section (CS) delivery, perineal tear and postpartum hemorrhage (PPH) in a rural area in Bangladesh., Methods: This prospective study analyzed data from two cohorts: the Maternal, Neonatal, and Child Health (MNCH) project carried out from January 2008 to June 2010, and the Preterm and Stillbirth Study, Matlab (PreSSMat) conducted from October 2015 to March 2018. In total, information of 9287 women who gave birth from the two cohorts was available for analysis. Early-pregnancy BMI was categorized into underweight, normal-weight, and overweight groups. The change in the burden of malnutrition between two cohort periods and the associations between women's BMI and maternal health outcomes were presented in odds ratios (ORs) with their 95% confidence interval (CI)., Results: Between the two cohort periods, the prevalence of underweight decreased from 17.5% to 15.4%, and overweight increased from 10.8% to 20.9%. The risk of being overweight in pregnant women was about two times (OR = 2.19; 95% CI = 1.94-2.46) higher in the PreSSMat cohort than in the MNCH cohort. After multivariate-adjustment for socio-demographic factors, the pooled ORs of PIH, CS delivery, perineal tear, and PPH were 2.41 (95% CI = 1.95-2.99), 2.12 (95% CI = 1.86-2.41), 2.46 (95% CI = 1.54-3.92), and 1.68 (95% CI = 1.12-2.53), respectively, in women with overweight compared to the normal-weight group., Conclusions: The results confirmed the existence of a double burden of malnutrition in rural women in Bangladesh. Women with overweight had an increased risk of selected pregnancy complications. The findings call for the adoption of appropriate prenatal counseling and preparedness tailored to women's nutritional status to prevent possible adverse health outcomes., Competing Interests: Conflict of interest: The authors completed the ICMJE Unified Competing Interest form (available upon request from the corresponding author), and declare no conflicts of interest., (Copyright © 2020 by the Journal of Global Health. All rights reserved.)

Background: Proper utilization of skilled care services in neonatal illnesses is crucial to reduce neonatal morbidity and mortality. The study aimed to evaluate the level and factors associated with seeking care from skilled healthcare service providers for reported neonatal illnesses in rural Matlab, Bangladesh., Methods: This community based cross-sectional study was based on data from a randomly selected sample comprised of 2223 women who delivered live-born babies in 2014. Data were collected from June to October 2015 through a structured questionnaire. We used a multivariable logistic regression model and presented the results by adjusted odds ratios (AOR) with 95% confidence intervals (CI)., Results: Of the neonates, 1361 (61.2%) suffered from at least one complication, and among these, 479 (35.2%) sought care from skilled healthcare service providers. In the multivariable logistic regression analysis, the participants' husbands' educational level, number of antenatal care visits, and place of childbirth were significantly associated with seeking skilled care for reported neonatal illnesses. The care-seeking from skilled healthcare service providers for neonatal illness was more than two times higher (AOR = 2.26, 95% CI = 1.51-3.39) in the group in which the participants' husband had attended school for more than 10 years as compared to the group in which they had attended school for less than six years. The AORs of seeking skilled care were 1.93 (95% CI = 1.42-2.62) and 2.26 (95% CI = 1.51-3.39) with the mothers receiving two to three and four or more antenatal care services, respectively, compared to the mothers with no or one antenatal care visit. Women who gave birth at a health facility were three times (AOR = 3.24, 95% CI = 2.50-4.19) more likely to seek skilled care for sick neonates compared to those who gave birth at home., Conclusion: The utilization of skilled care for neonatal sicknesses was low in this rural setting in Bangladesh. The participants' husbands' higher school attendance, increased number of ANC visits, and facility delivery were positively associated with care-seeking from skilled healthcare providers for neonatal illness. The husbands with low school attendance should be targeted for intervention, and continue efforts to increase ANC coverage and facility delivery to improve neonatal health in this country's rural area., Competing Interests: The authors have declared that no competing interests exists.

Background: Strengthening the antenatal care programme is suggested as one of the public health strategies to reduce preterm birth burden at a population level. However, the evidence so far available is inconclusive., Objectives: To evaluate the association between antenatal care (ANC) visit and preterm birth; and also to explore to what extent the increased usage of ANC after the initiation of the Maternal, Neonatal and Child Health (MNCH) project in Matlab, Bangladesh, contributed to the reduction of preterm birth., Setting: This population-based cohort study was conducted in Matlab, a subdistrict under Chandpur. The analysis was based on data collected from 2005 to 2009. In 2007, an MNCH project was initiated in the area that strengthened the ongoing ANC services., Participants: In total, 12 980 live births with their mothers during the study period were included in the analysis., Analysis: We performed logistic regression with generalised estimating equation models to evaluate the associations., Outcome Measures: Preterm birth., Results: The number of ANC visits was associated with preterm birth in a dose-dependent way (p for linear trend <0.001). The adjusted odds of preterm birth were 2.4-times higher (OR 2.37, 95% CI 2.07 to 2.70) among women who received ≤1 ANC compared with women who received ≥3 ANC. We observed a significant reduction of preterm birth rates (OR 0.69, 95% CI 0.61 to 0.77) in the period after (2008 to 2009) MNCH project initiation in comparison to the period before (2005 to 2006). Controlling for ANC visits substantially attenuated this observed effect of the MNCH project on preterm birth (OR 0.88, 95% CI 0.77 to 0.99) (Sobel test of mediation p<0.001)., Conclusions: ANC visits are associated with decreased occurrences of preterm births. Strengthening the ANC services should be prioritised in countries with high preterm birth rates to reduce the preterm birth burden at the population level., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Aim: This paper aimed to analyse the association between small for size at birth, stunting, recovery from stunting and pubertal development in a rural Bangladeshi cohort., Methods: The participants were 994 girls and 987 boys whose mothers participated in the Maternal and Infant Nutrition Interventions in Matlab trial. The birth cohort was followed from birth to puberty 2001-2017. Pubertal development according to Tanner was self-assessed. Age at menarche was determined and in boys, consecutive height measurements were used to ascertain whether pubertal growth spurt had started. The exposures and outcomes were modelled by Cox's proportional hazards analyses and logistic regression., Results: There was no difference in age at menarche between girls that were small or appropriate for gestational age at birth. Boys born small for gestational age entered their pubertal growth spurt later than those with appropriate weight. Children who were stunted had later pubertal development, age at menarche and onset of growth spurt than non-stunted children. Children who recovered from infant or early childhood stunting had similar pubertal development as non-stunted children., Conclusion: Infant and childhood stunting was associated with a later pubertal development. Recovery from stunting was not associated with earlier puberty in comparison with non-stunted children., (© 2019 The Authors. Acta Paediatrica published by John Wiley & Sons Ltd on behalf of Foundation Acta Paediatrica.)

In the aftermath of nutrition transition and ever-increasing sedentarism, adolescents globally are exposed to negative health consequences. Diverse sociocultural influences play a critical role in their adoption of unhealthy dietary practices and suboptimal physical activity behaviors. Context-specific understandings of how these sociocultural influences shape adolescents' dietary and physical activity patterns in a rural, resource-limited setting remained elusive. Aiming to address the gap, this qualitative study explored adolescents' and mothers' perception of broader sociocultural aspects that sculpt the food choices, eating habits and physical activity behaviors of adolescents in Matlab, Bangladesh. Six digitally-recorded focus group discussions were transcribed verbatim, translated into English and analyzed thematically. Marked taste-driven dietary preference of adolescents and its prioritization within family by the mothers, popularity of street foods, better understanding of the importance of food hygiene and safety contrasting with narrow perception of balance and diversity in diet, peer influence along with deficient school and community food environment, internalization and rigidity of gender norms were found to be exerting major influence. The findings highlighted key targets for community-based nutrition interventions and endorsed thorough consideration of socio-cultural factors in formulating strategies to promote healthful eating and physical activity behaviors among the adolescents., Competing Interests: The authors declare no conflict of interest.

Background: Depression is usually managed in primary care, but most antidepressant trials are of patients from secondary care mental health services, with eligibility criteria based on diagnosis and severity of depressive symptoms. Antidepressants are now used in a much wider group of people than in previous regulatory trials. We investigated the clinical effectiveness of sertraline in patients in primary care with depressive symptoms ranging from mild to severe and tested the role of severity and duration in treatment response., Methods: The PANDA study was a pragmatic, multicentre, double-blind, placebo-controlled randomised trial of patients from 179 primary care surgeries in four UK cities (Bristol, Liverpool, London, and York). We included patients aged 18 to 74 years who had depressive symptoms of any severity or duration in the past 2 years, where there was clinical uncertainty about the benefit of an antidepressant. This strategy was designed to improve the generalisability of our sample to current use of antidepressants within primary care. Patients were randomly assigned (1:1) with a remote computer-generated code to sertraline or placebo, and were stratified by severity, duration, and site with random block length. Patients received one capsule (sertraline 50 mg or placebo orally) daily for one week then two capsules daily for up to 11 weeks, consistent with evidence on optimal dosages for efficacy and acceptability. The primary outcome was depressive symptoms 6 weeks after randomisation, measured by Patient Health Questionnaire, 9-item version (PHQ-9) scores. Secondary outcomes at 2, 6 and 12 weeks were depressive symptoms and remission (PHQ-9 and Beck Depression Inventory-II), generalised anxiety symptoms (Generalised Anxiety Disorder Assessment 7-item version), mental and physical health-related quality of life (12-item Short-Form Health Survey), and self-reported improvement. All analyses compared groups as randomised (intention-to-treat). The study is registered with EudraCT, 2013-003440-22 (protocol number 13/0413; version 6.1) and ISRCTN, ISRCTN84544741, and is closed to new participants., Findings: Between Jan 1, 2015, and Aug 31, 2017, we recruited and randomly assigned 655 patients-326 (50%) to sertraline and 329 (50%) to placebo. Two patients in the sertraline group did not complete a substantial proportion of the baseline assessment and were excluded, leaving 653 patients in total. Due to attrition, primary outcome analyses were of 550 patients (266 in the sertraline group and 284 in the placebo group; 85% follow-up that did not differ by treatment allocation). We found no evidence that sertraline led to a clinically meaningful reduction in depressive symptoms at 6 weeks. The mean 6-week PHQ-9 score was 7·98 (SD 5·63) in the sertraline group and 8·76 (5·86) in the placebo group (adjusted proportional difference 0·95, 95% CI 0·85-1·07; p=0·41). However, for secondary outcomes, we found evidence that sertraline led to reduced anxiety symptoms, better mental (but not physical) health-related quality of life, and self-reported improvements in mental health. We observed weak evidence that depressive symptoms were reduced by sertraline at 12 weeks. We recorded seven adverse events-four for sertraline and three for placebo, and adverse events did not differ by treatment allocation. Three adverse events were classified as serious-two in the sertraline group and one in the placebo group. One serious adverse event in the sertraline group was classified as possibly related to study medication., Interpretation: Sertraline is unlikely to reduce depressive symptoms within 6 weeks in primary care but we observed improvements in anxiety, quality of life, and self-rated mental health, which are likely to be clinically important. Our findings support the prescription of SSRI antidepressants in a wider group of participants than previously thought, including those with mild to moderate symptoms who do not meet diagnostic criteria for depression or generalised anxiety disorder., Funding: National Institute for Health Research., (Copyright © 2019 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Introduction: Preterm birth is the major cause of under-five mortality. Population-based data on determinants and proportions of children born preterm are limited, especially from low-income countries. This study aimed at assessing time trends and social, reproductive and environmental determinants of preterm births based on a population-based pregnancy cohort over 25 years in rural Bangladesh., Methods: In this cohort study in Matlab, a rural area in Bangladesh, we used data from the Health and Demographic Surveillance System from 1990 to 2014. Gestational age at birth was based on the reported last menstrual period and verified by ultrasound assessments. Preterm birth proportions were assessed within strata of social and reproductive characteristics, and time series analysis was performed with decomposition for trend and seasonality. We also determined the prevented fractions of preterm birth reduction associated with social and demographic changes during the follow-up period., Results: Analyses were based on 63 063 live births. Preterm birth decreased from 29% (95% CI 28.6 to 30.1) in 1990-1994 to 11% (95% CI 10.5 to 11.6) in 2010-2014. Low education, older age and multi-parity were associated with higher proportions of preterm births across the study period. Preterm births had a marked seasonal variation. A rapid increase in women's educational level and decrease in parity were associated with the decline in preterm births, and 27% of the reduction observed from 1990 to 2014 could be attributed to these educational and reproductive changes., Conclusion: The reduction in preterm birth was to a large extent associated with the sociodemographic transition, especially changes in maternal education and parity. The persistent seasonal variation in the proportion of preterm birth may reflect the environmental stressors for pregnant women across the study period. Continued investments in girls' education and family planning programmes may contribute to further reduction of preterm births in Bangladesh., Competing Interests: Competing interests: None declared.

This study sought to evaluate the performance of metabolic gestational age estimation models developed in Ontario, Canada in infants born in Bangladesh. Cord and heel prick blood spots were collected in Bangladesh and analyzed at a newborn screening facility in Ottawa, Canada. Algorithm-derived estimates of gestational age and preterm birth were compared to ultrasound-validated estimates. 1036 cord blood and 487 heel prick samples were collected from 1069 unique newborns. The majority of samples (93.2% of heel prick and 89.9% of cord blood) were collected from term infants. When applied to heel prick data, algorithms correctly estimated gestational age to within an average deviation of 1 week overall (root mean square error = 1.07 weeks). Metabolic gestational age estimation provides accurate population-level estimates of gestational age in this data set. Models were effective on data obtained from both heel prick and cord blood, the latter being a more feasible option in low-resource settings., Competing Interests: MM, SH, WC, LW, ML, MH, JP, AC, CG, EL, BP, MW, JL, AR, PC, KW No competing interests declared, (© 2019, Murphy et al.)

Background: Newborn screening programs are essential preventative public health initiatives but are not widely available in low-resource settings. The objective of this study was to describe the frequency and nature of screen positive determinations as made by a Canadian newborn screening program in a cohort of infants born in Matlab, Bangladesh. Dried newborn cord and heel-prick blood spot samples collected as part of a validation study nested within a preterm birth research cohort were collected between January 2017 and July 2018 and analyzed in a Canadian newborn screening laboratory where the laboratory's disease panel and screening thresholds were applied., Results: A total of 1661 newborn samples (520 heel-prick and 1141 cord blood samples) were available for analysis. Based on the applied screening thresholds, 61 samples (22 by heel-prick and 39 by cord blood) were screen positive for conditions included in the Canadian disease panel. Congenital hypothyroidism was the most common determination for heel-prick (n = 17) and cord blood (n = 12) samples. Carriers of hemoglobinopathy variants were identified in 6.9% of both tested heel-prick and cord blood samples., Conclusions: This study provides insight into the nature and frequency of treatable congenital conditions in a rural Bangladesh community where such data were previously unavailable. As comment to the feasibility of newborn screening in the region we confirm that screening based on cord blood sampling continues to be the most acceptable modality to parents in such settings. Acknowledged barriers include early infant discharge, which may affect the reliability of initial screening thresholds to determine disease risk. We further highlight the importance of continuing efforts in the country to identify infants with congenital hypothyroidism.

Background: Increasing the level of birth preparedness and complication readiness (BP/CR) is one of the key interventions to promote optimal utilization of skilled maternal health services. It is therefore essential to determine the women's ability to recognize the danger signs and the level of BP/CR. This information can be used to design more effective health interventions., Objectives: This study was conducted to determine the knowledge in recognition of maternal complications, and the level and factors associated with BP/CR in rural Matlab, Bangladesh., Methods: A community-based cross-sectional survey was conducted from June- October 2015 on a randomly selected 2262 women who delivered live or stillbirth during the year 2014. A pretested and structured questionnaire was used for data collection. Descriptive and analytical statistical methods were used., Results: The proportion of study participants with "good knowledge", measured by the ability to recognise three or more danger signs, in pregnancy and delivery were 26% and 23%, respectively. Out of four BP/CR components, about 15% women saved money, 12% women identified facility for delivery, 9.6% women planned to deliver by skilled birth attendant and 5.3% of women arranged transport. About 12% of women were "well prepared", measured by planning of at least two components, for skilled childbirth and emergency obstetric complications. In the multivariable logistic regression analysis, asset index, antenatal care (ANC) visits and knowledge of danger signs during pregnancy and delivery were associated with BP/CR. The adjusted odds ratio (OR) of "well prepared" was 4.09 (95% confidence interval [CI]: 2.45-6.82) among women with an asset index of five (richest), compared with women in the asset index of one (poorest). The odds of "well prepared" was six times (OR 5.98, 95% CI: 3.85-9.28) higher for women with four or more ANC visits, compared to women with none or one ANC visit. In comparison to women with "poor knowledge" on maternal danger signs during pregnancy and delivery, the odds ratio of "well prepared" among women with good knowledge during pregnancy and in delivery were 1.95 (95% CI: 1.44-2.63) and 1.74 (95% CI: 1.28-2.36), respectively., Conclusion: The study revealed a low level of maternal knowledge of danger signs and BP/CR among pregnant women. Further, low socioeconomic status, fewer ANC visits and poor knowledge in recognition of dangers signs on maternal health were associated with low BP/CR. More emphasis should be placed on the quality of information offered to the pregnant women during the prenatal contact and women from low socio-economic gradient should be prioritized to optimize the impact of future BP/CR interventions., Competing Interests: The authors have declared that no competing interests exists.

Objective: To evaluate the efficacy of care in the second stage of labour with a package of interventions that included (1) maintaining the birthing position according to the woman's choice, (2) adopting a spontaneous pushing technique and (3) using a support person, to reduce maternal and neonatal complications., Design: Used the data collected from two cohorts- before and after an initiative to improve care during the second stage of labour., Setting: A rural hospital in Bangladesh where 90-100 deliveries are conducted monthly and cesarean section provision is not available., Participants: One thousand and fifty-one singleton pregnancies who attended the hospital for giving birth in the first stage of labour before full dilatation of the cervix and with cephalic presentation., Measurements and Findings: Data were collected through a structured checklist and questionnaire completed by research assistants; and also retrieved from hospital case record files, and the ongoing demographic surveillance system database. Coverage of adopting the upright or lateral position in the post-intervention period increased to 76% from about 1% in the pre-intervention period, and the spontaneous pushing technique increased to 97% from 77% in the same period. The odds of combined maternal and neonatal complications decreased by 46% between pre- and post-intervention periods (odds ratio: 0.54, 95% confidence interval: 0.43-0.70). Frequency of episiotomy (from 43% to 29%, P < 0.001), cervical tear (3.8% to 1.5%, P = 0.02), and median blood loss (200 ml to 150 ml; P < 0.001) were reduced significantly in the same period. No significant associations were observed in perineal tear or birth asphyxia occurrences., Key Conclusions and Implications for Practice: The study suggests that there is a beneficial effect of care during the second stage of labour with a package of interventions in reducing maternal and neonatal complications, particularly in reducing the frequency of episiotomy, cervical tear, and blood loss during delivery. The preferred choice of posture during giving birth, adopting a spontaneous pushing technique and continuous presence of support person during the second stage of labour may be encouraged for better health outcomes., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Background: Depression in older adults is common and is associated with poor quality of life, increased morbidity and early mortality, and increased health and social care use. Collaborative care, a low-intensity intervention for depression that is shown to be effective in working-age adults, has not yet been evaluated in older people with depression who are managed in UK primary care. The CollAborative care for Screen-Positive EldeRs (CASPER) plus trial fills the evidence gap identified by the most recent guidelines on depression management., Objectives: To establish the clinical effectiveness and cost-effectiveness of collaborative care for older adults with major depressive disorder in primary care., Design: A pragmatic, multicentred, two-arm, parallel, individually randomised controlled trial with embedded qualitative study. Participants were automatically randomised by computer, by the York Trials Unit Randomisation Service, on a 1 : 1 basis using simple unstratified randomisation after informed consent and baseline measures were collected. Blinding was not possible., Setting: Sixty-nine general practices in the north of England., Participants: A total of 485 participants aged ≥ 65 years with major depressive disorder., Interventions: A low-intensity intervention of collaborative care, including behavioural activation, delivered by a case manager for an average of six sessions over 7-8 weeks, alongside usual general practitioner (GP) care. The control arm received only usual GP care., Main Outcome Measures: The primary outcome measure was Patient Health Questionnaire-9 items score at 4 months post randomisation. Secondary outcome measures included depression severity and caseness at 12 and 18 months, the EuroQol-5 Dimensions, Short Form questionnaire-12 items, Patient Health Questionnaire-15 items, Generalised Anxiety Disorder-7 items, Connor-Davidson Resilience Scale-2 items, a medication questionnaire, objective data and adverse events. Participants were followed up at 12 and 18 months., Results: In total, 485 participants were randomised (collaborative care, n  = 249; usual care, n  = 236), with 390 participants (80%: collaborative care, 75%; usual care, 86%) followed up at 4 months, 358 participants (74%: collaborative care, 70%; usual care, 78%) followed up at 12 months and 344 participants (71%: collaborative care, 67%; usual care, 75%) followed up at 18 months. A total of 415 participants were included in primary analysis (collaborative care, n  = 198; usual care, n  = 217), which revealed a statistically significant effect in favour of collaborative care at the primary end point at 4 months [8.98 vs. 10.90 score points, mean difference 1.92 score points, 95% confidence interval (CI) 0.85 to 2.99 score points; p   <  0.001], equivalent to a standard effect size of 0.34. However, treatment differences were not maintained in the longer term (at 12 months: 0.19 score points, 95% CI -0.92 to 1.29 score points; p  = 0.741; at 18 months: < 0.01 score points, 95% CI -1.12 to 1.12 score points; p  = 0.997). The study recorded details of all serious adverse events (SAEs), which consisted of 'unscheduled hospitalisation', 'other medically important condition' and 'death'. No SAEs were related to the intervention. Collaborative care showed a small but non-significant increase in quality-adjusted life-years (QALYs) over the 18-month period, with a higher cost. Overall, the mean cost per incremental QALY for collaborative care compared with usual care was £26,016; however, for participants attending six or more sessions, collaborative care appears to represent better value for money (£9876/QALY)., Limitations: Study limitations are identified at different stages: design (blinding unfeasible, potential contamination), process (relatively low overall consent rate, differential attrition/retention rates) and analysis (no baseline health-care resource cost or secondary/social care data)., Conclusion: Collaborative care was effective for older people with case-level depression across a range of outcomes in the short term though the reduction in depression severity was not maintained over the longer term of 12 or 18 months. Participants who received six or more sessions of collaborative care did benefit substantially more than those who received fewer treatment sessions but this difference was not statistically significant., Future Work Recommendations: Recommendations for future research include investigating the longer-term effect of the intervention. Depression is a recurrent disorder and it would be useful to assess its impact on relapse and the prevention of future case-level depression., Trial Registration: Current Controlled Trials ISRCTN45842879., Funding: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment ; Vol. 21, No. 67. See the NIHR Journals Library website for further project information.

Background: Knowledge of gestational age (GA) is critical for guiding neonatal care and quantifying regional burdens of preterm birth. In settings where access to ultrasound dating is limited, postnatal estimates are frequently used despite the issues of accuracy associated with postnatal approaches. Newborn metabolic profiles are known to vary by severity of preterm birth. Recent work by our group and others has highlighted the accuracy of postnatal GA estimation algorithms derived from routinely collected newborn screening profiles. This protocol outlines the validation of a GA model originally developed in a North American cohort among international newborn cohorts., Methods: Our primary objective is to use blood spot samples collected from infants born in Zambia and Bangladesh to evaluate our algorithm's capacity to correctly classify GA within 1, 2, 3 and 4 weeks. Secondary objectives are to 1) determine the algorithm's accuracy in small-for-gestational-age and large-for-gestational-age infants, 2) determine its ability to correctly discriminate GA of newborns across dichotomous thresholds of preterm birth (≤34 weeks, <37 weeks GA) and 3) compare the relative performance of algorithms derived from newborn screening panels including all available analytes and those restricted to analyte subsets. The study population will consist of infants born to mothers already enrolled in one of two preterm birth cohorts in Lusaka, Zambia, and Matlab, Bangladesh. Dried blood spot samples will be collected and sent for analysis in Ontario, Canada, for model validation., Discussion: This study will determine the validity of a GA estimation algorithm across ethnically diverse infant populations and assess population specific variations in newborn metabolic profiles., Competing Interests: Competing interests: None declared.

Importance: There is little evidence to guide management of depressive symptoms in older people., Objective: To evaluate whether a collaborative care intervention can reduce depressive symptoms and prevent more severe depression in older people., Design, Setting, and Participants: Randomized clinical trial conducted from May 24, 2011, to November 14, 2014, in 32 primary care centers in the United Kingdom among 705 participants aged 65 years or older with Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition) subthreshold depression; participants were followed up for 12 months., Interventions: Collaborative care (n=344) was coordinated by a case manager who assessed functional impairments relating to mood symptoms. Participants were offered behavioral activation and completed an average of 6 weekly sessions. The control group received usual primary care (n=361)., Main Outcomes and Measures: The primary outcome was self-reported depression severity at 4-month follow-up on the 9-item Patient Health Questionnaire (PHQ-9; score range, 0-27). Included among 10 prespecified secondary outcomes were the PHQ-9 score at 12-month follow-up and the proportion meeting criteria for depressive disorder (PHQ-9 score ≥10) at 4- and 12-month follow-up., Results: The 705 participants were 58% female with a mean age of 77 (SD, 7.1) years. Four-month retention was 83%, with higher loss to follow-up in collaborative care (82/344 [24%]) vs usual care (37/361 [10%]). Collaborative care resulted in lower PHQ-9 scores vs usual care at 4-month follow-up (mean score with collaborative care, 5.36 vs with usual care, 6.67; mean difference, -1.31; 95% CI, -1.95 to -0.67; P < .001). Treatment differences remained at 12 months (mean PHQ-9 score with collaborative care, 5.93 vs with usual care, 7.25; mean difference, -1.33; 95% CI, -2.10 to -0.55). The proportions of participants meeting criteria for depression at 4-month follow-up were 17.2% (45/262) vs 23.5% (76/324), respectively (difference, -6.3% [95% CI, -12.8% to 0.2%]; relative risk, 0.83 [95% CI, 0.61-1.27]; P = .25) and at 12-month follow-up were 15.7% (37/235) vs 27.8% (79/284) (difference, -12.1% [95% CI, -19.1% to -5.1%]; relative risk, 0.65 [95% CI, 0.46-0.91]; P = .01)., Conclusions and Relevance: Among older adults with subthreshold depression, collaborative care compared with usual care resulted in a statistically significant difference in depressive symptoms at 4-month follow-up, of uncertain clinical importance. Although differences persisted through 12 months, findings are limited by attrition, and further research is needed to assess longer-term efficacy., Trial Registration: isrctn.org Identifier: ISRCTN02202951.

Background: Computerised cognitive behaviour therapy (cCBT) is an efficient form of therapy potentially improving access to psychological care. Indirect evidence suggests that the uptake and effectiveness of cCBT can be increased if facilitated by telephone, but this is not routinely offered in the NHS., Objectives: To compare the clinical effectiveness and cost-effectiveness of telephone-facilitated free-to-use cCBT [e.g. MoodGYM (National Institute for Mental Health Research, Australian National University, Canberra, ACT, Australia)] with minimally supported cCBT., Design: This study was a multisite, pragmatic, open, two-arm, parallel-group randomised controlled trial with a concurrent economic evaluation., Setting: Participants were recruited from GP practices in Bristol, Manchester, Sheffield, Hull and the north-east of England., Participants: Potential participants were eligible to participate in the trial if they were adults with depression scoring ≥ 10 on the Patient Health Questionnaire-9 (PHQ-9)., Interventions: Participants were randomised using a computer-generated random number sequence to receive minimally supported cCBT or telephone-facilitated cCBT. Participants continued with usual general practitioner care., Main Outcome Measures: The primary outcome was self-reported symptoms of depression, as assessed by the PHQ-9 at 4 months post randomisation., Secondary Outcomes: Secondary outcomes were depression at 12 months and anxiety, somatoform complaints, health utility (as assessed by the European Quality of Life-5 Dimensions questionnaire) and resource use at 4 and 12 months., Results: Clinical effectiveness: 182 participants were randomised to minimally supported cCBT and 187 participants to telephone-facilitated cCBT. There was a difference in the severity of depression at 4 and 12 months, with lower levels in the telephone-facilitated group. The odds of no longer being depressed (defined as a PHQ-9 score of < 10) at 4 months were twice as high in the telephone-facilitated cCBT group [odds ratio (OR) 2.05, 95% confidence interval (CI) 1.23 to 3.42]. The benefit of telephone-facilitated cCBT was no longer significant at 12 months (OR 1.63, 95% CI 0.98 to 2.71). At 4 months the between-group difference in PHQ-9 scores was 1.9 (95% CI 0.5 to 3.3). At 12 months the results still favoured telephone-facilitated cCBT but were no longer statistically significant, with a difference in PHQ-9 score of 0.9 (95% CI -0.5 to 2.3). When considering the whole follow-up period, telephone-facilitated cCBT was asssociated with significantly lower PHQ-9 scores than minimally supported cCBT (mean difference -1.41, 95% CI -2.63 to -0.17; p  = 0.025). There was a significant improvement in anxiety scores over the trial period (between-group difference 1.1, 95% CI 0.1 to 2.3; p  = 0.037). In the case of somatic complaints (assessed using the Patient Health Questionnaire-15), there was a borderline statistically significant difference over the trial period (between-group difference 1.1, 95% CI 0.0 to 1.8; p  = 0.051). There were gains in quality-adjusted life-years at reduced cost when telephone facilitation was added to MoodGYM. However, the results were subject to uncertainty., Conclusions: The results showed short-term benefits from the addition of telephone facilitation to cCBT. The effect was small to moderate and comparable with that of other primary care psychological interventions. Telephone facilitation should be considered when offering cCBT for depression., Limitations: Participants' depression was assessed with the PHQ-9, cCBT use was quite low and there was a slightly greater than anticipated loss to follow-up., Future Research Recommendations: Improve the acceptability of cCBT and its capacity to address coexisting disorders. Large-scale pragmatic trials of cCBT with bibliotherapy and telephone-based interventions are required., Trial Registration: Current Controlled Trials ISRCTN55310481., Funding: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment ; Vol. 20, No. 89. See the NIHR Journals Library website for further project information.

Background: The gap between what is known and what is practiced results in health service users not benefitting from advances in healthcare, and in unnecessary costs. A supportive context is considered a key element for successful implementation of evidence-based practices (EBP). There were no tools available for the systematic mapping of aspects of organizational context influencing the implementation of EBPs in low- and middle-income countries (LMICs). Thus, this project aimed to develop and psychometrically validate a tool for this purpose., Methods: The development of the Context Assessment for Community Health (COACH) tool was premised on the context dimension in the Promoting Action on Research Implementation in Health Services framework, and is a derivative product of the Alberta Context Tool. Its development was undertaken in Bangladesh, Vietnam, Uganda, South Africa and Nicaragua in six phases: (1) defining dimensions and draft tool development, (2) content validity amongst in-country expert panels, (3) content validity amongst international experts, (4) response process validity, (5) translation and (6) evaluation of psychometric properties amongst 690 health workers in the five countries., Results: The tool was validated for use amongst physicians, nurse/midwives and community health workers. The six phases of development resulted in a good fit between the theoretical dimensions of the COACH tool and its psychometric properties. The tool has 49 items measuring eight aspects of context: Resources, Community engagement, Commitment to work, Informal payment, Leadership, Work culture, Monitoring services for action and Sources of knowledge., Conclusions: Aspects of organizational context that were identified as influencing the implementation of EBPs in high-income settings were also found to be relevant in LMICs. However, there were additional aspects of context of relevance in LMICs specifically Resources, Community engagement, Commitment to work and Informal payment. Use of the COACH tool will allow for systematic description of the local healthcare context prior implementing healthcare interventions to allow for tailoring implementation strategies or as part of the evaluation of implementing healthcare interventions and thus allow for deeper insights into the process of implementing EBPs in LMICs.

Aim: This study evaluated stable and unstable low birthweight infants admitted to a Kangaroo mother care (KMC) unit at a resource-limited rural hospital in Bangladesh., Methods: This was a descriptive consecutive patient series study of 423 low birthweight neonates <2500 g enrolled from July 2007 to December 2010. KMC was initiated as soon as possible after birth, regardless of health, and we monitored skin-to-skin contact, weight gain, exclusive breastfeeding, length of hospital stay and death rates., Results: Mean birthweight was 1796 g, and mean gestational age was 34.9 weeks. Mean (median, 90th percentile) time of skin-to-skin initiation for stable and unstable neonates was 1.1 h (0.3-2.5) and 1.7 h (0.3-3.0), respectively. Adjusted mean daily skin-to-skin contact duration was significantly higher for unstable infants. About 99% of neonates were exclusively breastfed. The death rate was 8.3% (stable 1.9%, unstable 19%) at discharge. Neonatal mortality rate was 90 per 1000 live births (stable: 23 per 1000; unstable: 203 per 1000)., Conclusion: Skin-to-skin duration was higher for unstable than stable low birthweight infants, and exclusive breastfeeding was almost universal at discharge. KMC was suitable for unstable infants and may be successfully implemented in resource-limited hospitals., (©2015 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.)

Objective: to conduct and describe results from a process evaluation of home-based life saving skills (HBLSS) one year post-implementation., Design: a non-experimental, descriptive design was utilised employing both qualitative and quantitative techniques for data collection including: (1) key informant interviews, (2) group discussions, (3) performance testing, and (4) review of programme data., Setting: rural Matlab, Bangladesh in the sub-district of Chandpur., Participants: 41 community health research workers (CHRW), five pregnant women, 14 support persons and four programme co-ordinators., Intervention: HBLSS is a family-centred approach to improving recognition of and referral for potentially life-threatening maternal and newborn complications. In June 2007, four HBLSS meetings were implemented in Matlab by 41 CHRW with all pregnant women in the study area., Measurements: (1) knowledge retention among CHRW, (2) programme coverage, and (3) strengths and challenges in HBLSS implementation., Findings: results revealed rapid integration of the programme into the Matlab community with nearly 4500 HBLSS contacts with 2409 pregnant women between 15 June 2007 and 31 March 2008. Over 51% of pregnant women attended all four HBLSS meetings. Knowledge testing of CHRW showed strong retention with an increase in mean scores between immediate post-training and one-year post-training (from 78.7% to 92.7% and from 77.8% to 97.7% for two different HBLSS modules). Strengths of the HBLSS programme include high satisfaction among pregnant women, dedication of CHRW to the community, and strong organisation and supervision by programme staff. Challenges include lack of involvement of men, loss of two master trainers, and limited access to comprehensive emergency obstetric care at some referral sites., Key Conclusions: the HBLSS programme was successfully implemented as a result of the high level of support and supervision by the maternal, newborn and child health staff at ICDDR,B. This evaluation highlights the value of community health workers in the fight against maternal and newborn mortality. Findings emphasise the strength of the HBLSS training approach in transferring knowledge from trainer to HBLSS guide., (Copyright © 2009 Elsevier Ltd. All rights reserved.)