Objectives: Chronic obstructive pulmonary disease (COPD) disproportionately affects low- and middle-income countries. Health systems are ill prepared to manage the increase in COPD cases. Methods: We performed a pilot effectiveness-implementation randomized field trial of a community health worker (CHW)-supported, 1-year self-management intervention in individuals with COPD grades B–D. The study took place in low-resource settings of Nepal, Peru, and Uganda. The primary outcome was the St. George’s Respiratory Questionnaire (SGRQ) score at 1 year. We evaluated differences in moderate to severe exacerbations, all-cause hospitalizations, and the EuroQol score (EQ-5D-3 L) at 12 months. Measurements and Main Results: We randomly assigned 239 participants (119 control arm, 120 intervention arm) with grades B–D COPD to a multicomponent, CHW-supported intervention or standard of care and COPD education. Twenty-five participants (21%) died or were lost to follow-up in the control arm compared with 11 (9%) in the intervention arm. At 12 months, there was no difference in mean total SGRQ score between the intervention and control arms (34.7 vs. 34.0 points; adjusted mean difference, 1.0; 95% confidence interval, −4.2, 6.1; P = 0.71). The intervention arm had a higher proportion of hospitalizations than the control arm (10% vs. 5.2%; adjusted odds ratio, 2.2; 95% confidence interval, 0.8, 7.5; P = 0.15) at 12 months. Conclusions: A CHW-based intervention to support self-management of acute exacerbations of COPD in three resource-poor settings did not result in differences in SGRQ scores at 1 year. Fidelity was high, and intervention engagement was moderate. Although these results cannot differentiate between a failed intervention or implementation, they nonetheless suggest that we need to revisit our strategy. Clinical trial registered with www.clinicaltrials.gov (NCT03359915).

Background: Biomass fuels are still in use for cooking by many households in resource poor countries such as Nepal and is a major source of household air pollution (HAP). Chronic exposure to HAP has been shown to be associated with shorter telomere length in adults. Objectives: To measure the association between exposure related to household biomass fuel in infancy and leukocyte telomere length (LTL) at 18–23 months of age among 497 children from Bhaktapur, Nepal. Methods: In a prospective cohort study design, we have collected information on household cooking fuel use and several clinical, anthropometric, demographic, and socioeconomic variables. We estimated the association between biomass fuel use and the relative LTL in multiple linear regression models. Results: Most of the families (78%) reported liquified petroleum gas (LPG) as the primary cooking fuel, and 18.7% used biomass. The mean relative (SD) LTL was 1.03 (0.19). Children living in households using biomass fuel had on average 0.09 (95% CI: 0.05 to 0.13) units shorter LTL than children in households with no biomass fuel use. The observed association was unaltered after adjusting for relevant confounders. The association between LTL and biomass use was strongest among children from households with ≤2 rooms and without separate kitchen. Significance: Exposure to biomass fuel use in early life might have consequences for longevity, and risk of chronic illnesses reflected in shortening of the telomeres. Our findings support the ongoing effort to reduce exposure to biomass fuel in low-resource settings. Impact statements: Biomass for cooking is a leading source of household air pollution in low and middle-income countries, contributing to many chronic diseases and premature deaths. Chronic exposure to biomass fuel through oxidative stress and inflammation has been associated with a shortening of the telomeres, a “biological marker” of longevity. This prospective cohort study describes the association between household biomass fuel use and leukocyte telomere length among 497 toddlers. Leukocyte telomere length was significantly shorter among children living in households with biomass fuel than in children from homes where mainly LPG was used for cooking. Clinical Trial registration: Clinicaltrials.gov: NCT02272842, registered October 21, 2014, Universal Trial Number: U1111-1161-5187 (September 8, 2014)

Background: Negative early-life exposures, particularly during the first 1000 days of life, may disrupt organ development and lead to lifelong negative health consequences. Objective: Using an exposome and deep phenotyping framework, this study aims to characterize established early-life risk factors, including environmental pollutants and nutritional status during pregnancy and infancy, and identify associated short- and long-term health and developmental outcomes. Methods: We leverage a pregnancy cohort of 800 mother-infant pairs in Bhaktapur, Nepal, nested within a randomized controlled trial (ClinicalTrials.gov: NCT03071666) that evaluated daily vitamin B12 supplementation from before 15 weeks of gestation until 6 months post partum. The primary outcomes of the original trial were linear growth and neurodevelopment at 12 months. In this follow-up, children will be evaluated up to school age to obtain more robust estimates of long-term health outcomes. Exposures include clinical, dietary, cognitive, demographic, and anthropometric variables during pregnancy and infancy, as well as analyses of environmental pollutants, inflammation, micronutrient status, and hormonal status. Outcomes comprise neurodevelopment, morbidity, mental health, vaccine responses, thyroid function, growth, body composition, lung function, and biomarkers of health and development. Our main research questions for this phase of the project are: (1) what are the most common environmental pollutants among Nepalese women and children? (2) Is there a social gradient in exposure to these pollutants? (3) To what extent are these exposures associated with nutritional status, growth, neurodevelopment, and clinical outcomes? Associations will be examined using cross-sectional, case-control, and cohort designs applying advanced statistical methods to address confounding and complex exposure patterns. Results: Enrollment began in March 2017, and the first child was born in August of the same year. More than 90% of the original cohort (734/800, 91.8%) have provided data up to the children’s fourth birthday. By December 2025, the project will have funding until July 2027, and the papers addressing the main research questions will be submitted for publication before the end of 2026. Conclusions: This study draws on a well-characterized mother-child cohort in a South Asian setting with repeated biological samples from blood, breast milk, and urine and extensive high-quality longitudinal data on health, growth, and neurodevelopment. By integrating data on environmental exposures, nutrition, inflammation, and biological responses, the project aims to improve understanding of early-life determinants of health and inform policies and potential interventions to protect vulnerable women and children in marginalized settings. While the exploratory nature of exposome analyses entails a risk of spurious associations, careful interpretation and transparent communication of uncertainty will be prioritized. International Registered Report Identifier (IRRID): DERR1-10.2196/78593

Background: Vitamin B12 is required for normal growth and development, but low and marginal status is endemic in low- and middle-income countries. We aimed to measure the effect of vitamin B12 supplementation from early pregnancy until 6 months postpartum on infant growth and neurodevelopment. Methods: We randomised (1:1) 800 pregnant women within 15 weeks of gestation in a community-based, double-blind, placebo-controlled trial in Nepal to daily supplementation with 50 μg oral vitamin B12 or placebo until 6 months postpartum. The randomisation list was generated by scientists not involved in the study. Treatment allocation was linked to the participants unique study ID. The primary outcomes were length-for-age z-scores (LAZ) at 12 months, and the cognitive composite score of the Bayley Scales of Infant and Toddler Development, 3rd edition (Bayley-III), measured at 6 and 12 months. All participants with outcomes were included in the analyses. The trial was registered at ClinicalTrials.gov: NCT03071666. Findings: Women were enrolled between March 28, 2017, and October 15, 2020, and follow up was completed May 18, 2022. At baseline, 71·5% of the women had plasma cobalamin indicating low or marginal status (<221 pmol/L). Vitamin B12supplementation substantially improved status in mothers and infants. We found no effect of vitamin B12 on the primary outcomes. The mean (±SD) LAZ-score at 12 months was -0·6 (1·0) in both study arms (366 and 363 infants). The mean difference (95% CI) in cognitive composite scores was 0·5 (-0·6, 1·7) (measured in 364 and 361 infants). Stillbirths or infant deaths occurred in 3 (0·8%) of 374 women in the vitamin B12 group and 9 (2·3%) of 379 women in the placebo group. Interpretation: Although poor status was prevalent and vitamin B12 supplementation from early pregnancy substantially improved vitamin B12 status, supplementation did not improve infant growth or neurodevelopment. Funding: This work was supported by the Research Council of Norway through its Centres of Excellence scheme (project number 223269) and the University of Bergen (UiB), Norway, to the Centre for Intervention Science in Maternal and Child Health (CISMAC) and the Innlandet Hospital Trust, Lillehammer, Norway. Declaration of Interests: The authors declare they have no actual or potential competing conflict interests. Ethics Approval: The ethical review boards in Nepal (NHRC 253/2016) and Norway (2016/1620/REK vest) approved the study Trial Registration: The trial was registered at ClinicalTrials. gov, NCT03071666