Perinatal and Lifestyle Factors Associated with Childhood Alanine Aminotransferase Levels as an Early Indicator of Metabolic Dysfunction-Associated Steatotic Liver Disease: A Population-Based Study.

Abstract

To investigate associations of perinatal and lifestyle factors with alanine aminotransferase (ALT) levels as an early indicator of metabolic dysfunction-associated steatotic liver disease (MASLD). Data from the population-representative longitudinal physical activity and nutrition in children study, conducted among Finnish schoolchildren (n = 736), were utilized. Three visits during childhood included comprehensive assessments of metabolic biomarkers, body composition, and lifestyle factors. Perinatal data were obtained from registries and questionnaires. Altogether, 488 children were included in midchildhood (ages 7-8), 421 in late childhood (9-11), and 255 in adolescence (15-17). The predefined primary outcome was plasma ALT level, used as a biomarker of early-stage MASLD. In midchildhood and adolescence, significant associations (P < .05) between the children's ALT were detected for prepregnancy hypertension (β = 0.155-0.157). In late childhood, higher waist-to-height ratio and visceral adiposity by dual-energy X-ray absorptiometry became positively associated with ALT independent of body mass index SDS (β = 0.246-0.377). In adolescence, higher insulin levels and dyslipidemia (0.184-0.378) were positively associated with ALT. In late childhood, intake of protein and animal and dairy products (β = 0.121-0.184), and in adolescence, intake of protein and fish (β = 0.154-0.280), were positively associated with ALT, and intake of vegetables, fruit and berries, and fructose (β = -0.135 to -0.141) showed a negative association. In mid- and late childhood, levels of phenylalanine and branched-chain amino acids (β = 0.131-0.248), and in adolescence, those of omega-3/6 (β = -0.103 to 0.198) and all fatty acids (β = 0.197-0.228), were all positively associated with ALT. Sleep or measured physical activity were not associated with ALT. Several associations attenuated after multiple-testing correction for false discovery rate. Maternal hypertension, offspring intake of protein, animal and dairy products, levels of phenylalanine, branched-chain amino acids and fatty acids, and offspring cardiometabolic risk factors were associated with elevated ALT as an indicator of MASLD. The findings underscore the importance of pre- and postnatal influences and support early prevention, although caution is warranted as associations were modest and reduced after adjustment for false discovery rate. ClinicalTrials.gov (ID number, NCT01803776; https://clinicaltrials.gov/study/NCT01803776).