To identify distinguishing characteristics of neonates with persistent pulmonary hypertension of the newborn (PPHN) unresponsive to inhaled nitric oxide (iNO) and evaluate the use of milrinone in this cohort. STUDY DESIGN: Retrospective chart review of 99 neonates with PPHN treated with iNO over a five-year period at a quaternary neonatal intensive care unit. RESULTS: Neonates with iNO-unresponsive PPHN had an increased number of ventilator days (10 vs 7 days, p = 0.02), greater length of hospital stay (30 vs 22 days, p = 0.02), and increased risk of death or ECMO than iNO-responsive neonates (p = 0.03). Inhaled NO non-responders treated with milrinone had improved oxygenation (p < 0.03) and no change in systemic hemodynamics. CONCLUSION: Neonates with iNO-unresponsive PPHN had worse clinical outcomes than iNO responders. Milrinone may be a safe and effective adjuvant therapy, although large-scale studies are lacking. Identifying early predictors of iNO response and novel strategies to enhance iNO responsiveness should be prioritized.

Cases of high-risk pregnancies continue to rise throughout the United States and globally, increasing rates of maternal and neonatal morbidity. Common pregnancy complications and morbidities include preterm birth, hypertensive disorders, fetal growth restriction, diabetes mellitus, and chorioamnionitis. Exposure to these perinatal conditions contributes to cardiac morbidities in the fetus and neonate, including altered cardiac growth, congenital heart disease, and cardiac dysfunction. Significant research has demonstrated lasting effects of these pregnancy complications, with increased rates of cardiac morbidities seen in children and adults after these perinatal exposures. The link between the perinatal environment and long-term outcomes has not been fully elucidated. The aim of this review is to discuss the current understanding of the implications of a high-risk pregnancy on fetal and neonatal cardiac development.