Plasma serotonergic biomarkers are associated with hypoxemia events in preterm neonates

Background Hypoxemia is a physiological manifestation of immature respiratory control in preterm neonates, which is likely impacted by neurotransmitter imbalances. We investigated relationships between plasma levels of the neurotransmitter serotonin (5-HT), metabolites of tryptophan (TRP), and parameters of hypoxemia in preterm neonates. Methods TRP, 5-HT, 5-hydroxyindoleacetic acid (5-HIAA), and kynurenic acid (KA) were analyzed in platelet-poor plasma at ~1 week and ~1 month of life from a prospective cohort of 168 preterm neonates <31 weeks gestational age (GA). Frequency of intermittent hypoxemia (IH) events and percent time hypoxemic (<80%) were analyzed in a 6 h window after the blood draw. Results At 1 week, infants with detectable plasma 5-HT had fewer IH events (OR (95% CI) = 0.52 (0.29, 0.31)) and less percent time <80% (OR (95% CI) = 0.54 (0.31, 0.95)) compared to infants with undetectable 5-HT. A similar relationship occurred at 1 month. At 1 week, infants with higher KA showed greater percent time <80% (OR (95% CI) = 1.90 (1.03, 3.50)). TRP, 5-HIAA or KA were not associated with IH frequency at either postnatal age. IH frequency and percent time <80% were positively associated with GA < 29 weeks. Conclusions Circulating neuromodulators 5-HT and KA might represent biomarkers of immature respiratory control contributing to hypoxemia in preterm neonates. Impact Hypoxemia events are frequent in preterm infants and are associated with poor outcomes. Mechanisms driving hypoxemia such as immature respiratory control may include central and peripheral imbalances in modulatory neurotransmitters. This study found associations between the plasma neuromodulators serotonin and kynurenic acid and parameters of hypoxemia in preterm neonates. Imbalances in plasma biomarkers affecting respiratory control may help identify neonates at risk of short- and long-term adverse outcomes.