Transient Neonatal Cyanosis Exacerbated by Inhaled Nitric Oxide

Abstract Methemoglobinemia in newborns presents with cyanosis and hypoxemia, which can be mistaken for congenital heart disease or pulmonary hypertension. A term infant presented with cyanosis and low SpO2 (70s) immediately after birth, despite continuous positive airway pressure (CPAP) and 100% inspired oxygen. The patient was intubated and started on inhaled nitric oxide (iNO) and prostaglandin E1 infusion. Chest X-ray showed bilateral pneumothoraces; the echocardiogram was normal. Arterial blood gases demonstrated normal pH and elevated PaO2. iNO and prostaglandin E1 (PGE1) were discontinued. Attempts to obtain methemoglobin levels via a co-oximeter panel were unsuccessful, presumably due to out-of-range values. The infant's father revealed that he also had transient cyanosis as an infant. The infant was treated with ascorbic acid. A blood sample sent to a reference laboratory a day after discontinuation of inhaled NO showed a methemoglobin level of 10.2%. Targeted gamma globin gene sequencing found a heterozygous likely pathogenic variant in hemoglobin subunit gamma 2 (HBG2) (p.His63Tyr). He was discharged home at 1 week of age on room air. Hereditary causes of methemoglobinemia should be considered for newborns with persistent cyanosis with low SpO2 and elevated PaO2. Detailed family history and avoiding triggers of methemoglobinemia, such as iNO, are the cornerstones of management.