Background <p>Annually, over 20 million newborns are affected by low-birth-weight, posing a global public health challenge. Interactions between mothers and low-birth-weight infants during the first year post-discharge from neonatal intensive care unit are crucial for developmental trajectories. However, longitudinal research to explore the experiences of mother-infant interactions within the corrected age of 12&#xa0;months and to analyze the factors influencing these interactions in low-birth-weight infants is limited.</p> Methods <p>A longitudinal qualitative study based on semi-structured interviews was conducted. From November 2021 to March 2023, twenty pairs of low-birth-weight infants and their mothers were recruited from two maternal and child health hospitals in Shanghai, China. Interviews were scheduled to be conducted three times within the corrected age of 12&#xa0;months. The longitudinal data were analyzed using a trajectory analysis approach.</p> Results <p>Mother-infant interactions were categorized into three stages: 3–6&#xa0;months (lack of interactive awareness and skill), 6–9&#xa0;months (interaction and work balance), and 9–12&#xa0;months (interactive effects and problems emergence). Based on inductive thematic analysis of maternal interview data, interaction-related influences were organized into two contrasting patterns- favorable and unfavorable- both derived from three common dimensions: the quality of the maternal-infant relationship, the nature of infant responsiveness, and the adequacy of external support. Within the unfavorable trajectory, parents described an alienated maternal-infant relationship, negative emotional response from infants, and a lack of external support (e.g., family conflict, unstable assistance, or limited environmental facilitation). Conversely, within the favorable trajectory, parents described a close maternal-infant relationship, moderate infant responses, and multidimensional support for stress relief (e.g., long-term support from family members, stable financial income and time). In addition, a sub-theme was identified at each time stage based on the theme.</p> Conclusions <p>This study highlights the importance of recognizing mother-infant interaction as a continuous process with evolving challenges. The varying interaction attitudes and experiences of mothers can result in diverse cognitive and developmental outcomes in low-birth-weight infants. The identified factors of interaction may inform the development of individualized nursing guidance aimed at supporting high-quality mother–infant interactions.</p>