Early childhood weight gain and alanine aminotransferase at age 8: an adjunct study of the Japan Environment and Children’s Study

BACKGROUND: The critical age window during which early-life adiposity impacts liver health remains unclear. This study aimed to identify the timing of adiposity gain associated with elevated alanine aminotransferase (ALT) levels in 8-year-old children. METHODS: This prospective cohort study included 1322 children (665 boys; mean age 96.2 ± 3.4 months) from a subset of the Japan Environment and Children's Study. Anthropometric data were collected at birth and at 1, 2, 3, 4, 5, 6, and 8 years. Adiposity gain was assessed using conditional weight, a residual-based metric adjusted for prior weight and current height. Excess adiposity was defined as conditional weight above the 90th percentile. ALT was measured at age 8, with elevation defined as > 26 IU/L in boys and > 22 IU/L in girls. Multivariable regression models were adjusted for maternal, perinatal, and early-life factors. RESULTS: ALT elevation was observed in 3.3% of the children. Adiposity gain was significantly associated with higher ALT concentrations, beginning at age 3 in girls (adjusted coefficient: 0.11, p < 0.01) and at age 4 in boys (adjusted coefficient: 0.10, p < 0.05). The 4-5-year interval marked the earliest period of notable risk, with adjusted risk ratios (95% CI) of 4.18 (1.77-9.87) in boys and 3.29 (1.04-10.40) in girls. Birth weight and adiposity during infancy were not consistently associated with ALT concentrations. CONCLUSIONS: Early childhood-particularly between ages 3 and 5 years-may represent a period during which associations between excess adiposity gain and later liver health become detectable. Because liver enzymes were assessed at a single time point, the temporal onset of these associations cannot be established. These findings should be interpreted cautiously and warrant confirmation using longitudinal assessments of liver health.