Pro-inflammatory biomarkers and long term neurological outcomes in hypothermia plus melatonin treated asphyxiated newborns. A preliminary approach

• Published in: Pediatric research 2024-11
• Main Authors: Jerez Calero, Antonio, Contreras Chova, Francisco, Benítez Feliponi, Ángela, Azaryah, Hatim, Hurtado Suazo, Jose Antonio, Moreno Galdó, M Fernanda, Molina Carballo, Antonio
• Format: Article
• Language: English
• ISSN: 0031-3998; 1530-0447; 1530-0447
• DOI: 10.1038/s41390-024-03742-y

To evaluate serum neuronal and inflammatory biomarkers in asphyxiated newborns treated with hypothermia alone or hypothermia plus melatonin, and whether biomarkers correlate with neurodevelopmental outcomes. A pilot multicentre, randomized, controlled, double blind clinical trial. 25 newborns were recruited. Neonatal neural biomarkers were measured in serum samples at hospital admission (T0), 24 h (T1), 72 hours (T2) and 7-10 days of age (T3). Neurodevelopmental scales were performed at 6 and 18 months. Treated patients received a daily dose of intravenous melatonin, for 3 days. In melatonin-treated group, lower plasma levels of GM-CSF, IL-2 and IL-13 at T1 were measured vs placebo-group. We also corroborated, at T2, lower concentrations of GM-CSF, as well as IL-7 and IL-13 at T3. Throughout the study period, we found a significant decrease in GM-CSF concentrations in the treatment group. We have also observed sustained decrease over time of GM-CSF and inflammatory cytokines IL-2, IL-7 and IL-13 correlates with better neurodevelopmental outcomes at 6 and 18 months. In neonates affected by hypoxic-ischemic encephalopathy, the addition of iv melatonin to hypothermia therapy affects plasma biomarker concentration in the first week of life, with a high correlation with long-term neurological prognosis. Several plasma cytokines act as inflammatory mediators and biomarkers of hypoxia-ischemia-acquired neonatal brain damage. In animal research, melatonin has been shown to be a safe substance with proven anti-inflammatory and neuroprotective effects. Findings from our clinical trial show that melatonin affects plasma inflammatory biomarker concentration within the first week of life. This effect may be related to long-term neurological prognosis. To date, this is the only clinical trial in human infants including asphyxiated neonates treated with hypothermia and intravenous melatonin. Our study could help design future larger, well-designed clinical trials to clarify its effects in asphyxiated neonates.