Background: Although developmental supportive care is an effective approach to improve the long-term psychomotor and/or neurobehavioral function of preterm infants, very limited studies have focused on the impact of after-discharge developmental support. The underlying epigenetic changes are unclear. Purpose: This study aimed to explore the preliminary effect of an evidence-based Postdischarge Developmental Support Program (PDSP) on preterm infant neurodevelopment and underlying epigenetic changes, including brain-derived neurotrophic factor (BDNF) gene-related DNA methylation and expression. Methods: In this randomized controlled pilot trial, the preterm infant-parent dyads were randomized into either the intervention group/PDSP group (n = 22) or the control group/usual care group (n = 22). The neurodevelopmental outcomes of preterm infants were measured by Ages & Stages Questionnaires. Urine BDNF concentration level was tested by the enzyme-linked immunosorbent assay. Infant saliva specimens were collected to analyze the methylation level of BDNF gene promoter I at pre- and postintervention test. Results: After PDSP intervention, the total neurodevelopmental and the 5 domain scores of the PDSP group were all significantly higher than those of the control group (P < .05). The BDNF levels decreased significantly only within control group (P = .01). The difference in BDNF concentration and methylation levels between groups was not statistically significant. Implications for Practice and Research: Postdischarge Developmental Support Program may promote the neurodevelopment of preterm infants but has no effect on BDNF's expression and gene methylation level at 3 months of corrected age. The epigenetic mechanism of PDSP needs further study using a larger sample and longer follow-up.

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