Persistent Pulmonary Hypertension of the Newborn in Very Low Birth Weight Infants: Risk Factors and Clinical Outcomes from a Matched Case–Control Study

<b>Background/Objectives</b>: To identify the risk factors and clinical outcomes of persistent pulmonary hypertension of the newborn (PPHN) in very low birth weight (VLBW) infants in a resource-limited setting. <b>Methods</b>: We conducted a 1:4 matched case-control study in a Thai neonatal unit between 2014 and 2023. Neonates born at a gestational age (GA) < 32 weeks and with a birth weight (BW) < 1500 g were included. Neonates who died in the delivery room or had major congenital anomalies were excluded. Matching was based on GA, BW, year of birth, and endotracheal intubation at birth. Conditional logistic regression analysis was performed. <b>Results</b>: Over the 10-year study period, the incidence of PPHN among VLBW neonates was 4.6% (31/667). After matching, there were 31 cases and 124 controls. In univariable analysis, PPHN was significantly associated with lower 1 min and 5 min Apgar scores; however, no significant association remained in multivariable analysis. PPHN was significantly associated with composite adverse outcomes-including mortality and major morbidities (adjusted odds ratio [aOR] = 7.51, 95% confidence interval [CI]: 2.41-23.40), mortality alone (aOR = 2.88, 95% CI: 1.06-7.63), major morbidities (aOR = 2.99; 95% CI: 1.29-6.95), and severe neurological injury (aOR = 4.44, 95% CI: 1.56-12.59). Daily hospital costs were also higher in PPHN cases, with an average increase of 97.1 USD. <b>Conclusions</b>: In VLBW infants, PPHN was associated with a lower Apgar score and surfactant administration. PPHN was significantly linked to adverse outcomes, particularly mortality, major morbidities, and severe neurological injury.