Association of Neuregulin Levels and Neuregulin-۱ Polymorphism with Short-term Morbidities in Preterm Neonates

Background: Premature birth is linked to neonatal morbidity and mortality worldwide. Neuregulin (NRG) is a trophic factor from the growth factor (GF) of a transmembrane polypeptide, encoded by four different genes, including NRG-۱ which acts as an endogenous protector in fetal development. Decreased levels of NRG-۱ affect several organs. The relationship between NRG-۱ polymorphism and the outcome of neonatal development has been widely studied. There are no studies that have assessed NRG-۱ levels and NRG-۱ rs۳۵۷۵۳۵۰۵ C/T polymorphism in preterm neonates, as well as its association with short-term morbidities in Indonesia. Methods: This cross-sectional study was conducted on preterm neonates with the gestational age of ۳۲-۳۶ weeks in Medan, North Sumatera, Indonesia, from December ۲۰۱۷ to December ۲۰۱۸. It aimed to evaluate the association of NRG-۱ levels and NRG۱ polymorphism with short-term morbidities. Samples were obtained from cord blood specimens. Enzyme-linked immunosorbent assay (ELISA) was used to determine NRG-۱ levels, and NRG-۱ polymorphism was sequenced by polymerase chain reaction (PCR). Observations in preterm neonates were made during the first ۷۲ h to assess short-term morbidities. Results: During the study period, ۴۸ cord blood specimens from preterm neonates were found eligible for analysis. Preterm neonates with low NRG-۱ levels had a ۱۰-times higher risk of developing short-term morbidities. The presence of CC and CT genotypes increased the risk of developing short-term morbidities ۱۳.۳۳ times (P=۰.۰۰۳) and ۶.۱۹ times (P=۰.۰۱۹), respectively. The presence of the C allele in subjects' genotype increased the risk of short-term morbidities ۴.۰۴ times (P=۰.۰۰۱), compared to those with T allele. Conclusion: As evidenced by the obtained results, preterm neonates with low NRG-۱ levels had a higher risk of developing short-term morbidities. Furthermore, there was a significant association between NRG-۱ rs۳۵۷۵۳۵۰۵ C/T polymorphism and short-term morbidities.    

Keywords:

Neuregulinlevels , Neuregulin-۱ polymorphism , Pretermneonates , short-term morbidities