Neurological Outcome in Children Post–Sildenafil Therapy for Persistent Pulmonary Hypertension of the Newborn

Abstract Purpose: Evaluation of neurological outcome post sildenafil and inhaled nitric oxide (iNO) therapy in the first 72-months of life. Material and Methods: Prospective linear study of 84-neonates with severe persistent pulmonary hypertension of the newborn (PPHN). All neonates were on high frequency oscillatory ventilation (HFOV), surfactant, and inotropic support. In 40-neonates iNO was utilized, and intragastric sildenafil in 44-newborns. Bayley IIIUK was used at 38-months of age for developmental assessment. Intellectual ability was evaluated at 72-months of age by Wechsler Intelligence Scale for Children-Fourth EditionUK. Results: iNO monotherapy had a mortality rate of 4% versus 0% on sildenafil, p = 0.001. Resolution of PPHN without sequelae occurred in 81%, iNO 68% versus 93% sildenafil, p = 0.0001. Resolution with neurological impairment ensued in 19%, iNO 32% versus 7% on sildenafil, p = 0.0001. Resolution with chronic lung disease was observed in 5%, iNO 8% versus 2% sildenafil, p = 0.020. Intragastric sildenafil monotherapy failure rate was 14%. Sildenafil was the predominant variable that reduced mortality, p = 0.02, CI: 0.010 – 0.080. At 38-months, Bayley IIIUK scores were normal ≥85 in 81%. Neurologically normal children at 72-months of age scored either average or high average, qualitatively, on the Wechsler Intelligence Scale for Children-Fourth EditionUK. Effect of sildenafil in the neonatal period was global leading to preserved intellectual, cognitive, and neurological outcome, in later childhood. Conclusions: Intragastric sildenafil can be safely and effectively used in neonates with severe PPHN on HFOV and exogenous surfactant. Effect of sildenafil on neurodevelopment was positive.