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Highlights The kinematics of hand movements (spatial use, curvature, acceleration, and velocity) of infants with their mothers in an interactive setting are significantly associated with age in cohorts of typical and at-risk infantsdiffer significantly at 5–6 months of age, depending on the context: relating either with an object or a person.Environmental and developmental factors shape the developmental trajectories of hand movements in different cohorts: environment for infants with VIMs; stage of development for premature infants and those with West syndrome; and both factors for infants with orality disorders.The curvature of hand movements specifically reflects atypical development in infants with West syndrome when developmental age is considered.We aimed to discriminate between typical and atypical developmental trajectory patterns of at-risk infants in an interactive setting in this observational and longitudinal study, with the assumption that hand movements (HM) reflect preverbal communication and its disorders. We examined the developmental trajectories of HM in five cohorts of at-risk infants and one control cohort, followed from ages 2 to 10 months: 25 West syndrome (WS), 13 preterm birth (PB), 16 orality disorder (OD), 14 with visually impaired mothers (VIM), 7 early hospitalization (EH), and 19 typically developing infants (TD). Video-recorded data were collected in three different structured interactive contexts. Descriptors of the hand motion were used to examine the extent to which HM were associated with age and cohort. We obtained four principal results: (i) the kinematics of HM (spatial use, curvature, acceleration, and velocity) were significantly associated with age in all cohorts; (ii) HM significantly differed at 5–6 months of age in TD infants, depending on the context; (iii) environmental and developmental factors shaped the developmental trajectories of HM in different cohorts: environment for VIM, development for PB and WS, and both factors for OD and; (iv) the curvatures of HM showed atypical development in WS infants when developmental age was considered. These findings support the importance of using kinematics of HM to identify very early developmental disorders in an interactive context and would allow early prevention and intervention for at-risk infants.