Background <p>In contrast to the extensive research on the effects of high-altitude exposure on adult neurological function, fetal and pediatric neurodevelopment in high-altitude environments has received relatively little attention. This study aimed to determine whether exposure to high-altitude exposure during gestation and infancy could influence neurodevelopmental outcomes compared with low-altitude infants.</p> Methods <p>A total of 50 high-altitude-born and 100 low-altitude-born infants were studied. Parents were followed longitudinally and instructed to complete the Ages and Stages Questionnaire, 3rd edition (ASQ-3), when their infants reached 6, 12, and 18 months of age. The primary outcome measures included neurodevelopmental scores and the proportion of infants classified as failing in the five ASQ-3 domains.</p> Results <p>High-altitude infants had lower gross motor scores and higher failure rates. Subgroup analysis revealed no significant differences attributable to confounding factors. Regression analysis identified high-altitude exposure as the only significant predictor of gross motor delay.</p> Conclusions <p>Prenatal and postnatal exposure to high-altitude exposure was found to be associated with an increased risk of gross motor neurodevelopmental delay in infants.</p> Impact <p><UnorderedList Mark="Bullet"> <ItemContent> <p>This is the first prospective cohort study to compare the neurodevelopmental outcomes of high-altitude born/raised infants with those of low-altitude controls.</p> </ItemContent> <ItemContent> <p>Infants born and raised at high-altitude exhibited lower neurodevelopmental scores and a higher likelihood of failing in the gross motor domain of ASQ-3.</p> </ItemContent> <ItemContent> <p>High-altitude exposure had no negative influence on infants’ physical growth and other neurodevelopmental domains assessed by the ASQ-3.</p> </ItemContent> </UnorderedList></p>