Transient Neonatal Cyanosis Exacerbated by Inhaled Nitric Oxide

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 SpO ₂ (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 PaO ₂ . 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 SpO ₂ and elevated PaO ₂ . Detailed family history and avoiding triggers of methemoglobinemia, such as iNO, are the cornerstones of management.