Association of Neuregulin Levels and Neuregulin-1 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 NRG1 which acts as an endogenous protector in fetal development. Decreased levels of NRG1 affect several organs. The relationship between NRG1 polymorphism and the outcome of neonatal development has been widely studied. There are no studies that have assessed NRG1 levels and NRG1 rs35753505 C/T polymorphism in preterm neonates, as well as its association with shortterm morbidities in Indonesia. Methods: This crosssectional study was conducted on preterm neonates with the gestational age of 3236 weeks in Medan, North Sumatera, Indonesia, from December 2017 to December 2018. It aimed to evaluate the association of NRG1 levels and NRG1 polymorphism with shortterm morbidities. Samples were obtained from cord blood specimens. Enzymelinked immunosorbent assay (ELISA) was used to determine NRG1 levels, and NRG1 polymorphism was sequenced by polymerase chain reaction (PCR). Observations in preterm neonates were made during the first 72 h to assess shortterm morbidities. Results: During the study period, 48 cord blood specimens from preterm neonates were found eligible for analysis. Preterm neonates with low NRG1 levels had a 10times higher risk of developing shortterm morbidities. The presence of CC and CT genotypes increased the risk of developing shortterm morbidities 13.33 times (P=0.003) and 6.19 times (P=0.019), respectively. The presence of the C allele in subjects’ genotype increased the risk of shortterm morbidities 4.04 times (P=0.001), compared to those with T allele. Conclusion: As evidenced by the obtained results, preterm neonates with low NRG1 levels had a higher risk of developing shortterm morbidities. Furthermore, there was a significant association between NRG1 rs35753505 C/T polymorphism and shortterm morbidities.