Neurodevelopmental outcome at 5 to 6 years of age of an early intervention program in preterm infants.

Preterm birth presents long-term neurodevelopmental complications imposing substantial burdens on affected children and families. Early intervention (EI) programs have shown promise in mitigating these challenges, but their long-term efficacy remains unclear. The aim of the study was to assess the long-term neurodevelopmental outcomes of preterm infants following participation in a parent-based EI program during NICU stay. Additionally, the study investigates the modulation of LINE1 promoter methylation at early school age. We conducted a secondary analysis of a larger RCT that included preterm infants (25-29 weeks gestational age) randomized to receive Standard Care (SC) or Early Intervention (EI), including parental training and multisensory experiences. At 5-6 years, neurodevelopmental assessments were conducted and LINE1 promoter methylation levels were analyzed in buccal swab samples. 36 infants (21 EI, 15 SC) completed the long-term follow-up and were included in the present analysis. EI children exhibited significantly higher Griffiths scores compared to the SC group (mean General Developmental Quotient: EI = 90.4 SC = 82.3, p = 0.003). Longitudinal analysis performed with a mixed model revealed sustained benefits of EI, with increasing divergence in developmental outcomes over time. LINE1 methylation analysis did not reveal significant variations between groups. This study demonstrates the potential of EI programs in improving long-term neurodevelopmental outcomes for preterm infants. These findings underscore the need for continued research into effective intervention strategies to optimize outcomes for preterm-born children.Trial registration: ClinicalTrial.gov (NCT02983513).