IntroductionEarly parent–child relationships shape children’s future. Child development and parent–child interactions are multidetermined, and the combination of biological risks and social disadvantages can further compromise both outcomes. Interventions that promote responsive parenting may mitigate the risks for child development. We examined the effectiveness of a longitudinal psychosocial intervention to strengthen maternal interactive skills and the moderative role of biological and contextual variables. MethodsThe present study is part of a large study designed as a pragmatic quasi-experimental trial. The intervention was implemented in a public mother–child healthcare service, which is a reference for high-risk deliveries. The sample was a convenience subsample of the large project, comprised 67 mother–child dyads. The Intervention Group (IG) and Comparison Group (CG) included 33 and 34 dyads, respectively. The intervention consisted of two individual Newborn Behavioral Observation (NBO) sessions and six group sessions with the mothers. It was delivered at childbirth and 2, 4, 6, 9, and 12 months of child age. CG received usual care at the same age. IG and CG mothers were video recorded playing with their 12-month-old children; maternal interactive skills were assessed using the Parenting Interactions with Children: Checklist of Observations Linked to Outcomes (PICCOLO). PICCOLO captures mothers’ skills across four domains: affection, responsiveness, encouragement, and teaching. We performed a multiple linear regression to identify the moderative effect of the intervention on maternal interactive skills; the initial model included biological and contextual variables, the group, and the interaction between potential moderators and the group. ResultsIn general, most infants were boys, born preterm, and with low birth weight. On average, the mothers studied for 10 years, and most families were classified as having low or very low socioeconomic status. In general, IG mothers’ mean scores were higher than CG mothers’ in all PICCOLO domains, although without statistical significance. Lower maternal schooling moderated the effect of the intervention on mothers’ overall interaction and encouragement skills. Lower gestational age moderated the effect on PICCOLO total scores. Final regression models explained 22% and 14% of the variability of PICCOLO total and encouragement scores, respectively; no intervention’s effect was observed in other domains. ConclusionThe effects of our longitudinal psychosocial intervention on maternal interactive skills were moderated by infants’ gestational age and maternal years of schooling. These findings suggest that the intervention was more effective for vulnerable groups, specifically for mothers with less schooling and whose infants were born extremely preterm, confirming our hypothesis of the differential effect of the intervention.