The Fetus Can Teach Us: Oxygen and the Pulmonary Vasculature

Abstract

Neonates suffering from pulmonary hypertension of the newborn (PPHN) continue to represent an important proportion of patients requiring intensive neonatal care, and have an increased risk of morbidity and mortality. The human fetus has evolved to maintain a high pulmonary vascular resistance (PVR) in utero to allow the majority of the fetal circulation to bypass the lungs, which do not participate in gas exchange, towards the low resistance placenta. At birth, oxygen plays a major role in decreasing PVR to enhance pulmonary blood flow and establish the lungs as the organ of gas exchange. The failure of PVR to fall following birth results in PPHN, and oxygen remains the mainstay therapeutic intervention in the management of PPHN. Knowledge gaps on what constitutes the optimal oxygenation target leads to a wide variation in practices, and often leads to excessive oxygen use. Owing to the risk of oxygen toxicity, avoiding hyperoxemia is as important as avoiding hypoxemia in the management of PPHN. Current evidence supports maintaining arterial oxygen tension in the range of 50–80 mm Hg, and oxygen saturation between 90–97% in term infants with hypoxemic respiratory failure. Clinical studies evaluating the optimal oxygenation in the treatment of PPHN will be enthusiastically awaited.

Genetic Predisposition to High-Altitude Pulmonary Edema

“…This either implies a reduced penetrance of the missense mutation, or possible epigenetic reprogramming in the two HAPE-S children during a crucial phase of pulmonary artery remodeling. At birth children display muscular pulmonary arteries to divert blood flow as a fetus redirects blood to the placenta away from the nonoxygen perfused lung (Vali and Lakshminrusimha, 2017). Directly after birth, a remodeling process sets in to lower the PVR and to optimize lung perfusion (Vali and Lakshminrusimha, 2017).…”

“…At birth children display muscular pulmonary arteries to divert blood flow as a fetus redirects blood to the placenta away from the nonoxygen perfused lung (Vali and Lakshminrusimha, 2017). Directly after birth, a remodeling process sets in to lower the PVR and to optimize lung perfusion (Vali and Lakshminrusimha, 2017). Thus, the different oxygen levels and saturation of oxyhemoglobin at birth and in the subsequent weeks in the two older siblings could have altered epigenetic regulations predisposing pathogenic variant carriers to excessive HPV and HAPE.…”

Perinatal Management of Bart's Hemoglobinopathy: Paradoxical Effects of Intrauterine, Transplacental, and Partial Exchange Transfusions

“…Fetal hypoxemia has been demonstrated to cause pulmonary vasoconstriction and increase pulmonary vascular resistance. 5 In fact, vascular beds of multiple organ systems can be affected. Fetuses with prolonged in utero hypoxemia exhibit cardiovascular adaptations that redistribute blood flow to the brain, myocardium, and adrenal glands.…”

The CoDiNOS trial protocol: an international randomised controlled trial of intravenous sildenafil versus inhaled nitric oxide for the treatment of pulmonary hypertension in neonates with congenital diaphragmatic hernia

“…During fetal life, there is high resistance in the pulmonary circulation which results in most of the blood flow to bypass the lungs through the ductus arteriosus and oval foramen. Immediately after birth, the pulmonary vascular resistance drops and the blood flow to the lungs significantly increases 4. In contrast, the pulmonary vascular resistance often does not drop adequately in children with CDH due to a decreased vascular bed associated with lung hypoplasia, and an altered development of the pulmonary vasculature with excessive muscularisation of the arterioles, with increased thickness of the arterial media and adventitia.…”