The Impact of OXTR, COMT, and GRIN2B Polymorphisms on Brain Development in Preterm Infants

<b>Background/Objectives</b>: Preterm infants are at risk for developmental delays due to immature brain development and increased sensitivity to environmental stress. Genetic factors, such as polymorphisms in *<i>OXTR</i>* rs2268490, *<i>COMT</i>* rs4818, and *<i>GRIN2B</i>*, may influence these vulnerabilities and affect neurodevelopment. <b>Methods</b>: We recruited 91 preterm infants (<35 weeks gestation) admitted to the NICU at Hanyang University Seoul Hospital between January 2020 and December 2022. Brain MRIs were conducted at term-equivalent age, and DNA samples were analyzed for SNPs. Neurodevelopmental assessments were performed at 18 months corrected age using the Korean Developmental Screening Test (K-DST) and Bayley Scales of Infant Development, Third Edition (BSID-III). <b>Results</b>: Carriers of the minor alleles in *<i>OXTR</i>* rs2268490 showed significantly lower language and adaptive behavior, and *<i>COMT</i>* rs4818, rs740603 showed significantly lower social-emotional scores on BSID-III. *<i>OXTR</i>* rs2268490 was also associated with altered brain network metrics, including decreased small-worldness (<i>p</i> = 0.012) and increased global (<i>p</i> = 0.038) and local efficiency (<i>p</i> = 0.042). <b>Conclusions</b>: Polymorphisms in the *<i>OXTR</i>* genes are associated with differences in brain network organization and neurodevelopmental outcomes in preterm infants. These variants may influence how environmental factors affect early brain development, highlighting the importance of genetic screening and early intervention.