Background: The prevalence of liver disorders and metabolic syndrome has increased among youth. Glyphosate, the most widely used herbicide worldwide, could contribute to the development of these conditions.

Objective: We aimed to assess whether lifetime exposure to glyphosate and its degradation product, aminomethylphosphonic acid (AMPA), is associated with elevated liver transaminases and metabolic syndrome among young adults.

Methods: We conducted a prospective cohort study ($n=480$ mother-child dyads) and a nested case-control study ($n=60$ cases with elevated liver transaminases and 91 controls) using data from the Center for the Health Assessment of Mothers and Children of Salinas (CHAMACOS). We measured glyphosate and AMPA concentrations in urine samples collected during pregnancy and at child ages 5, 14, and 18 y from cases and controls. We calculated glyphosate residue concentrations: [$\text{glyphosate}+\left(1.5\times \text{AMPA}\right)$]. We estimated the amount of agricultural-use glyphosate applied within a $1-\mathrm{km}$ radius of every residence from pregnancy to age 5 y for the full cohort using California Pesticide Use Reporting data. We assessed liver transaminases and metabolic syndrome at 18 y of age.

Results: Urinary AMPA at age 5 y was associated with elevated transaminases [relative risk (RR) per $2-\text{fold increase}=1.27$, 95% confidence interval (CI): 1.06, 1.53] and metabolic syndrome ($\text{RR}=2.07$, 95% CI: 1.38, 3.11). Urinary AMPA and glyphosate residues at age 14 y were associated with metabolic syndrome [$\text{RR}=1.80$ (95% CI: 1.10, 2.93) and $\text{RR}=1.88$ (95% CI: 1.03, 3.42), respectively]. Overall, a 2-fold increase in urinary AMPA during childhood was associated with a 14% and a 55% increased risk of elevated liver transaminases and metabolic syndrome, respectively. Living near agricultural glyphosate applications during early childhood (birth to 5 y of age) was also associated with metabolic syndrome at age 18 y in the case-control group ($\text{RR}=1.53$, 95% CI: 1.16, 2.02).

Discussion: Childhood exposure to glyphosate and AMPA may increase risk of liver and cardiometabolic disorders in early adulthood, which could lead to more serious diseases later in life. https://doi.org/10.1289/EHP11721.