To explore the changes of serum hypoxia-inducible factor (HIF)-1α, vascular endothelial growth factor (VEGF) and endothelin-1 (ET-1) in neonatal hypoxic pulmonary hypertension (HPH) and the relationship with pulmonary systolic blood pressure (PASP).

From January 12, 2014 to December 19, 2017, a total of 50 HPH neonates hospitalized in the Department of Neonatology, Huadu Hospital Affiliated to Southern Medical University were selected as research subjects and included into HPH group. According to PASP of HPH neonates, 50 HPH neonates were further divided into moderate/severe HPH subgroup (n=22, PASP was > 50 mmHg) and mild HPH subgroup (n=28, PASP was 35-50 mmHg), 1 mmHg=0.133 kPa. Meanwhile, another 25 non-HPH neonates (dynamic PASP was < 35 mmHg) hospitalized in the Department of Neonatology during the same period in the same hospital were selected as control group. Their gestational age at birth, day age, gender, mode of delivery and serum sample retention time were matched to those in HPH group . The levels of serum HIF-1α, VEGF and ET-1 were detected by enzyme linked immunosorbent assay (ELISA) method, and their PASP were estimated by echocardiography. Independent-samples t test was used for the comparison of serum HIF-1α, VEGF and ET-1 levels between HPH group and control group, while one-way ANOVA was used for the comparison among moderate/severe HPH subgroup, mild HPH subgroup and control group, and further pairwise comparison were analyzed by LSD method. Pearson correlation analysis was applied for the correlation between serum HIF-1α, VEGF, ET-1 levels and PASP, as well as between these three factors. This study was approved by the Ethics Committee of Human Beings in Huadu Hospital Affiliated to Southern Medical University (Approval Number: 14-HDWS-001). There were no statistically significant differences between HPH group and control group in gestational age, day age, and constituent ratios of gender, delivery mode and basic diseases (P>0.05).

①The levels of serum HIF-1α, VEGF and ET-1 were (686.3 ± 235.9) g/mL, (154.7 ± 63.0) g/mL and (164.3 ± 115.3) pg/mL, respectively in HPH group. Those in control group were (260.9 ±132.0) g/mL, (96.2 ± 30.3) g/mL, (41.9 ± 3.7) pg/mL, respectively. The levels of serum HIF-1α, VEGF and ET-1 in HPH group were significantly higher than those in control group, and all the differences were statistically significant (t=8.336, 4.388, 5.288; P<0.001). There were statistically significant differences among moderate/severe HPH subgroup, mild HPH subgroup and control group in levels of serum HIF-1α, VEGF and ET-1 (F=156.362, 36.956, 67.464; P<0.001). For further pairwise comparison among those three groups, there were statistically significant differences between each groups in the aspects of levels of serum HIF-1α, VEGF and ET-1 (P<0.001). Furthermore, the higher the severity of HPH, the higher the serum levels of these three factors. ②Among all the subjects, the levels of serum HIF-1α, VEGF and ET-1 were positively correlated with PASP (r=0.941, 0.780, 0.864; P<0.001). ③The levels of serum VEGF and ET-1 were positively correlated with the level of serum HIF-1α among all the subjects (r=0.806, 0.850; P<0.001).

Hypoxia environment can induce increased expression of HIF-1α and upregulate the expression of VEGF and ET-1 through HIF-1α, which may play an important role in the development of neonatal HPH.