Association of Neuregulin Levels and Neuregulin-1 Polymorphism with Short-term Morbidities in Preterm Neonates

Document Type : Original Article


1 Department of Pediatrics, Faculty of Medicine, Universitas Sumatera Utara, Medan, Indonesia

2 Department of Clinical Pathology, Faculty of Medicine, Universitas Sumatera Utara, Medan, Indonesia

3 Department of Pediatrics, Faculty of Medicine, Universitas Padjajaran, Bandung, Indonesia


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-1 which acts as an endogenous protector in fetal development. Decreased levels of NRG-1 affect several organs. The relationship between NRG-1 polymorphism and the outcome of neonatal development has been widely studied. There are no studies that have assessed NRG-1 levels and NRG-1 rs35753505 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 32-36 weeks in Medan, North Sumatera, Indonesia, from December 2017 to December 2018. It aimed to evaluate the association of NRG-1 levels and NRG1 polymorphism with short-term morbidities. Samples were obtained from cord blood specimens. Enzyme-linked immunosorbent assay (ELISA) was used to determine NRG-1 levels, and NRG-1 polymorphism was sequenced by polymerase chain reaction (PCR). Observations in preterm neonates were made during the first 72 h to assess short-term morbidities.
Results: During the study period, 48 cord blood specimens from preterm neonates were found eligible for analysis. Preterm neonates with low NRG-1 levels had a 10-times higher risk of developing short-term morbidities. The presence of CC and CT genotypes increased the risk of developing short-term 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 short-term morbidities 4.04 times (P=0.001), compared to those with T allele.
Conclusion: As evidenced by the obtained results, preterm neonates with low NRG-1 levels had a higher risk of developing short-term morbidities. Furthermore, there was a significant association between NRG-1 rs35753505 C/T polymorphism and short-term morbidities.


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