Brain health Begins Before Birth (B4): A “learning” pregnancy and birth cohort study

Abstract Mental health disorders affect over 1 billion people worldwide, profoundly impacting individuals, families, and the global economy. Risk for psychopathology begins early in life, with the perinatal period representing a critical window of vulnerability. The Brain health Begins Before Birth (B4) Study at Massachusetts General Hospital (MGH) is a prospective birth cohort designed to identify modifiable risk and resilience factors influencing early brain development and child- and adult-onset psychopathology. This study aims to deeply phenotype prenatal exposures through maternal surveys administered at multiple time points during and after pregnancy; assess early neurodevelopmental outcomes through the first two years of life; and triangulate exposure and outcome data with underlying biological mechanisms. The B4 Study consists of structured, remote surveys covering psychosocial, environmental, and health-related factors throughout pregnancy and the first two years of life, supplemented by medical record review. By integrating risk and resilience factors into a dynamic learning cohort model, the B4 Study aims to advance the field of preventive psychiatry by identifying actionable pathways for early intervention, testing strategies in real-time, and ultimately shaping policies that promote lifelong mental health and wellbeing from the earliest stages of development. Competing Interest Statement The authors have declared no competing interest. Funding Statement This study was funded by the Massachusetts General Hospital (MGH) Early Brain Development Initiative (J.L.R.). Victoria Grunberg is supported by a K23 award from the Eunice Kennedy Shriver National Institute of Child Health and Human Development (K23HD110597). Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Ethics committee/IRB of Mass General Brigham gave ethical approval for this work. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes Data Availability Data that has been and will be generated by the present study may be made available upon reasonable request to the authors.