Surfactant Protein A and B Gene Polymorphisms and Risk of Respiratory Distress Syndrome in Late-Preterm Neonates

BACKGROUND AND OBJECTIVES Newborns delivered late-preterm (between 340/7 and 366/7 weeks of gestation) are at increased risk of respiratory distress syndrome (RDS). Polymorphisms within the surfactant protein (SP) A and B gene have been shown to predispose to RDS in preterm neonates. The aim of this study was to investigate whether specific SP-A and/or SP-B genetic variants are also associated with RDS in infants born late-preterm. METHODS This prospective cross-sectional study included 56 late-preterm infants with and 60 without RDS. Specific SP-A1/SP-A2 haplotypes and SP-B Ile131Thr polymorphic alleles were determined in blood specimens using polymerase-chain-reaction and DNA sequencing. RESULTS The SP-A1 6A4 and the SP-A2 1A5 haplotypes were significantly overrepresented in newborns with RDS compared to controls (OR 2.86, 95%CI 1.20-6.83 and OR 4.68, 95%CI 1.28-17.1, respectively). The distribution of the SP-B Ile131Thr genotypes was similar between the two late-preterm groups. Overall, the SP-A1 6A4 or/and SP-A2 1A5 haplotype was present in 20 newborns with RDS (35.7%), resulting in a 4.2-fold (1.60-11.0) higher probability of RDS in carriers. Multivariable regression analysis revealed that the effect of SP-A1 6A4 and SP-A2 1A5 haplotypes was preserved when adjusting for known risk or protective factors, such as male gender, smaller gestational age, smaller weight, complications of pregnancy, and administration of antenatal corticosteroids. CONCLUSIONS Specific SP-A genetic variants may influence the susceptibility to RDS in late-preterm infants, independently of the effect of other perinatal factors.