Exploring and Genetic Variants as a Risk Factor for Neonatal Respiratory Distress Syndrome and Its Outcome.

Neonatal respiratory distress syndrome (RDS) is a leading cause of morbidity and mortality in preterm infants. Interleukin-10 (IL-10) and endothelial nitric oxide synthase (eNOS, also known as ) regulate inflammation and vascular tone, and genetic variants may influence the risk of RDS. To investigate the association between rs1800872 (c.-149+1984T>G), rs1800896 (c.-149+2474T>C), and rs2070744 (c.-149+1691C>T), rs1799983 (c.894T>G) variants and the risk of RDS in a Romanian cohort of preterm neonates. This case-control study included 340 preterm neonates (113 with RDS, 227 controls) born at <36 weeks of gestation. Genotyping was performed using TaqMan SNP assays. Logistic regression adjusted for gestational age and sex estimated odds ratios (ORs) and 95% confidence intervals (CIs). ROC analyses evaluated predictive performance. No significant differences in genotype or allele distributions were observed between RDS and control groups for any variant. Haplotype analysis also revealed no association with RDS susceptibility or severity. :c.894T>G variant was associated with reduced risk of severe RDS after correction (adjusted = 0.009), though survival analysis showed no significant genotype-specific effects. Epistatic genotype interaction was observed for the T/G + T/C, present only in RDS ( = 0.0026). ROC analysis revealed a clinical prediction of RDS (AUC = 0.996), while the addition of genetic variants improved discrimination for severity (AUC = 0.865; 95% CI: 0.773-0.957) and mortality (AUC = 0.913; 95% CI: 0.791-1.000). and variants were not individually associated with overall RDS susceptibility. The observed epistatic interactions and the potential protective effect of :c.894T>G against severe forms can suggest modulatory roles in disease progression. Larger, ethnically homogeneous cohorts are needed to confirm these findings and assess their potential for informing personalized care for neonates.