Impact of altered heme oxygenase-1 in caring for preterm neonates: navigating the unknown

Heme-oxygenase-1 (HO-1) is a key regulatory factor in organ development, organ function, cellular metabolism, heme processing, and bilirubin production. HO-1 homeostasis is crucial for healthy pregnancy and fetus. Dysregulation of HO-1 adversely affects placentation, yolk sac development, cardiovascular development, immune function, angiogenesis, microcirculation, alters the oxidoreductive balance, and is associated with adverse respiratory outcomes and necrotizing enterocolitis. The impact of HO-1 on neonatal neurodevelopment is unknown and is currently being investigated by our laboratory. In this review, we will discuss the morbidities associated with HO-1 dysregulation and importantly, we will navigate the unknown. We will highlight how infection or inflammation affect HO-1 homeostasis, its implications on neonatal morbidities at the limits of viability, summarize the relevant basic, translational, clinical and epidemiologic studies. We will conclude with proposing new approaches for the future, filling the gap between what is currently known and unknown. IMPACT: What does this article add to the existing literature? HO-1 pathway is relevant to pregnancy, fetus, neonatal, and later life outcomes. Provides comprehensive organ systems-based evaluation of Heme-oxygenase-1 in pregnancy, fetus, extreme preterm, and periviable neonates. Highlights how environmental factors, including infection, inflammation resulting in systemic dysregulation of HO-1 affects major neonatal morbidities. Underscores that novel investigations to close the knowledge gap are forthcoming to transform the HO-1 field.