Early-Life Exposures, Neurodevelopment, and Health Outcomes: Protocol for a Birth Cohort Study

Negative early-life exposures, particularly during the first 1000 days of life, may disrupt organ development and lead to lifelong negative health consequences.

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.

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.

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.

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.

DERR1-10.2196/78593.