Early-Life Origins of Child Growth: Maternal Pre-Pregnancy BMI, Gestational Exposures, and Neonatal Microbiome Signatures

Childhood obesity represents a major global public health challenge, with increasing evidence identifying the prenatal period as a critical window for metabolic programming. This PhD thesis investigates early-life determinants relevant to childhood obesity risk, focusing on maternal pre-pregnancy body mass index (BMI), gestational weight gain (GWG), lifestyle factors during pregnancy, and neonatal gut microbiota signatures at birth. This thesis is structured as a publication-based doctoral work and is embedded within the LIMIT (LIfestyle and Microbiome InTeraction Early Adiposity Rebound in Children) prospective cohort study. It primarily addresses baseline (T0) assessments conducted at delivery. Framed within the Developmental Origins of Health and Disease (DOHaD) paradigm and the first 1,000 days framework, the thesis integrates evidence synthesis with original empirical analyses to examine how prenatal exposures may shape early metabolic and microbial profiles. The publication-based structure comprises a series of peer-reviewed and under-submission studies. First, a literature synthesis includes narrative and systematic reviews examining maternal lifestyle and nutritional exposures, early microbial environments, and the offspring exposome as determinants of obesity risk. Second, an original empirical study evaluates associations between maternal lifestyle behaviors during pregnancy and the adequacy of gestational weight gain. Third, a cross-sectional analysis investigates relationships between maternal pre-pregnancy BMI, GWG, lifestyle factors, and neonatal meconium microbiota composition at birth using 16S rRNA gene sequencing. Overall, this thesis characterizes key maternal and neonatal factors present at delivery that are biologically and behaviorally relevant to later obesity susceptibility. By focusing on early-life exposures rather than downstream obesity outcomes, this publication-based work contributes to advancing understanding of early metabolic programming and informs future preventive strategies beginning before and during pregnancy.