Background: Inflammation plays an important role in neonatal hypoxia-induced organ damage. Newborns with perinatal asphyxia often develop persistent pulmonary hypertension of the neonate.

Aim: Early detection of pulmonary arterial hypertension in newborn to improve patient morbidity and mortality by estimated serum HMGB1 by ELISA.

Patients and methods: This case control study was conducted in Zagazig University Hospital, Pediatric (NICU) and clinical pathology departments, during a period of eight months from March 2020 to January 2021. Following were the three groups into which patients were split: Group 1: fifteen apparently healthy neonates included 11 male and 4 females, group 2: fifteen congenital heart diseases without pulmonary hypertension neonates included 10 male and 5 female and group 3: Fifteen congenital heart diseases with pulmonary hypertension neonates included 10 male and 5 female.

Results: There is a statistically significant difference between the groups that were looked at for HMGB1 expression. When compared pairwise, CHD with pulmonary hypertension and the other groups show a significant difference (the greatest level was in CHD with pulmonary hypertension) hypertension then CHD without pulmonary hypertension then control group).

Conclusion: HMGB1 levels in newborns with pulmonary hypertension increased.