Prenatal and Early Postnatal Lead Exposure, Sensitive Periods, and Later Adult Mental Health.

Importance: Early lead exposure is associated with psychological concerns in childhood, but less is known about sensitive periods of exposure or persistence into later adulthood. Objective: To examine the association between prenatal and early postnatal lead exposure and risk of anxiety and depression in later adulthood. Design, Setting, and Participants: This cohort study included participants from the Saint Louis Baby Tooth-Later Life Health Study (SLBT), who donated deciduous (baby) teeth in childhood during the 1950s through 1970s. SLBT participants were recontacted beginning in 2021 to complete health surveys and were masked to lead status. These data were analyzed from February 2025 through May 2025. Exposure: Lead exposure was measured in baby teeth across prenatal (approximately second trimester to birth, also split into second and approximately third trimesters), and early postnatal (birth to approximately 6 months old) periods. Main Outcomes and Measures: Self-reported depressive and anxiety symptoms were assessed via the Patient Health Questionnaire-9 (PHQ-9) and Generalized Anxiety Disorder Screener-7 (GAD-7) at a mean age of 62 (SD, 3.6) years. Outcomes were dichotomized using clinical cutoffs for major depressive disorder and generalized anxiety disorder. Secondary analyses treated outcomes as continuous symptom scores. Results: Of 5131 SLBT participants, 718 (13.3%) had their baby teeth analyzed for lead (381 female [53%] and 334 male [47%]). In total, 695 and 697 participants responded to the PHQ-9 and GAD-7, respectively. The median (25th-75th percentile) combined tooth lead concentration was 1.34 (95% CI, 1.02-1.82) ppm. After adjusting for covariates, an IQR increase in combined tooth lead was associated with nearly 2 times the odds of later adulthood depression (odds ratio, 1.90; 95% CI, 1.20-2.99). The late prenatal period (approximately third trimester) appeared to be the most sensitive window (odds ratio, 1.55; 95% CI, 1.23-1.97). There was no association between early lead exposure and major later adulthood generalized anxiety disorder, but late prenatal and postnatal lead were associated with greater later adulthood anxiety symptoms. Conclusions and Relevance: Third-trimester lead exposure was associated with higher risk of major depressive disorder and anxiety symptoms in later adulthood. These findings emphasize the importance of factoring in later life health outcomes when considering the benefits of lead exposure interventions in childhood and suggest investment in screening and mental health services may be needed to address the long-term burden of historical lead exposure.