Early Life Origins of Neurodevelopmental Disabilities in the Boston Birth Cohort: Research findings and future directions.

Neurodevelopmental disabilities (NDD) are a group of conditions with onset in early development period and is characterized by limitations in several functional domains. Autism spectrum disorder (ASD) and Attention-Deficit Hyperactivity Disorders (ADHD), the most common NDDs, have complex etiologies and possibly multiple pathways leading up to the manifestation of these disorders. Boston Birth Cohort (BBC) is a preterm enriched birth cohort, and over the years, researchers have used the BBC dataset to study a broad spectrum of early life protective and risk factors in the context of NDDs. Broadly, some of them include: 1) nutrition (e.g. maternal folate, vitamin B12, cord folate species, selenium), 2) metabolic factors (e.g. role of maternal diabetes, obesity, branched chain amino acids and other essential amino acids), 3) lipid metabolism (e.g. maternal cholesterol), 4) immune activation and/or systematic inflammation (including maternal immune activation, inflammation of the placenta, inflammatory markers, maternal antibiotic use and acetaminophen use), and 5) other factors associated with NDDs (e.g. maternal stress, sickle cell disease). The findings from these studies are discussed in this review. BBC studies have advanced the field of NDD in the following important ways: 1) generating evidence that sheds light on new exposures, 2) furthering the existing knowledge using better methodological approaches, 3) analyzing novel mechanistic pathways on already proven relationship, and 4) advancing knowledge on the under-studied minority population in the U.S. BBC researchers are involved in ongoing efforts to characterize NDD developmental trajectories across the life stages by integrating multi-omics data (genome, epigenome, and metabolome) to gain a deeper understanding of the molecular pathways by which early life factors drive or shape the developmental trajectories of NDDs.