Melatonin is an endogenous indoleamine with well known antioxidant properties demonstrated in vitro, in animal and in human studies. Therefore, melatonin is an attractive agent in the treatment of “Oxidative stress related diseases” of the newborn. In newborn humans, melatonin has been used at doses ranging from 0.1 to 100 mg/Kg, however, due to the lack of pharmacokinetic data in neonates, it is difficult to establish a therapeutic effective dose. Recent investigations on the pharmacokinetic on newborns, reported that after administration of melatonin, in a single bolus of 0.5 mg/Kg, by intragastric administration, resulted in higher serum melatonin level than adults. Such findings suggest that is possible to obtain and mantain therapeutic concentrations with this dose. However, no data were available on the therapeutic efficacy of these specific doses. The aim of the present study is to investigate the effects of oral administration of melatonin on oxidative stress biomarkers in premature neonates. Therefore 0.5 mg/Kg/die of melatonin has been administrated orally to 35 preterms infants with gestational age <34 weeks, for the first week of life in comparison to placebo. Serum levels of oxidative stress (OS) biomarkers (F2 Isoprostanes, Advanced Oxidative Protein Products, Non-Protein Bound Iron) and serum melatonin were assessed at baseline T0 (0-2h of life), T1 (24h), T2 (72h). We found no significant reduction in serum levels of OS biomarkers except for F2 Isoprostanes at T1 which remains of unclear relevance. Analyzing serum melatonin levels, as expected, we found a significant increase from baseline T0 to T1 and T2 in the group receiving melatonin. However, endogenous melatonin levels increased also in the placebo group, and this result may be considered a response to counteract the elevated oxidative stress associated with the preterm birth. We also found that, despite the fact that melatonin was administered based on the weight of the newborn, serum melatonin levels were dependent on the total amount of melatonin administered rather than related to the ratio melatonin/weight. Clinical data concerning mechanical ventilation, occurrance of sepsis, Broncho Pulmonary Dysplasia, Necrotizing Enterocolitis, Retinopathy of Premature, Periventricular Leukomalacia and Intraventricular Hemorrage, were also recorded and, although the sample size was too small to make a proper statistical analysis, no difference were found between the two groups. The main limitation of this study is the small number of patients enrolled. The data obtained indicate that studies with more preterm infants are needed to verify the efficacy of the antioxidant effect of melatonin and a higher, fixed dose, instead of a weight based dosage, is required to have a clearer therapeutic efficacy.

Melatonin therapy in preterm infants

MARSEGLIA, LUCIA MARINA
2019-10-30

Abstract

Melatonin is an endogenous indoleamine with well known antioxidant properties demonstrated in vitro, in animal and in human studies. Therefore, melatonin is an attractive agent in the treatment of “Oxidative stress related diseases” of the newborn. In newborn humans, melatonin has been used at doses ranging from 0.1 to 100 mg/Kg, however, due to the lack of pharmacokinetic data in neonates, it is difficult to establish a therapeutic effective dose. Recent investigations on the pharmacokinetic on newborns, reported that after administration of melatonin, in a single bolus of 0.5 mg/Kg, by intragastric administration, resulted in higher serum melatonin level than adults. Such findings suggest that is possible to obtain and mantain therapeutic concentrations with this dose. However, no data were available on the therapeutic efficacy of these specific doses. The aim of the present study is to investigate the effects of oral administration of melatonin on oxidative stress biomarkers in premature neonates. Therefore 0.5 mg/Kg/die of melatonin has been administrated orally to 35 preterms infants with gestational age <34 weeks, for the first week of life in comparison to placebo. Serum levels of oxidative stress (OS) biomarkers (F2 Isoprostanes, Advanced Oxidative Protein Products, Non-Protein Bound Iron) and serum melatonin were assessed at baseline T0 (0-2h of life), T1 (24h), T2 (72h). We found no significant reduction in serum levels of OS biomarkers except for F2 Isoprostanes at T1 which remains of unclear relevance. Analyzing serum melatonin levels, as expected, we found a significant increase from baseline T0 to T1 and T2 in the group receiving melatonin. However, endogenous melatonin levels increased also in the placebo group, and this result may be considered a response to counteract the elevated oxidative stress associated with the preterm birth. We also found that, despite the fact that melatonin was administered based on the weight of the newborn, serum melatonin levels were dependent on the total amount of melatonin administered rather than related to the ratio melatonin/weight. Clinical data concerning mechanical ventilation, occurrance of sepsis, Broncho Pulmonary Dysplasia, Necrotizing Enterocolitis, Retinopathy of Premature, Periventricular Leukomalacia and Intraventricular Hemorrage, were also recorded and, although the sample size was too small to make a proper statistical analysis, no difference were found between the two groups. The main limitation of this study is the small number of patients enrolled. The data obtained indicate that studies with more preterm infants are needed to verify the efficacy of the antioxidant effect of melatonin and a higher, fixed dose, instead of a weight based dosage, is required to have a clearer therapeutic efficacy.
30-ott-2019
melatonin; oxidative stress; preterm infants
File in questo prodotto:
File Dimensione Formato  
TESI Dottorato Lucia Marseglia.pdf

accesso aperto

Descrizione: Tesi di Dottorato
Tipologia: Versione Editoriale (PDF)
Licenza: Tutti i diritti riservati (All rights reserved)
Dimensione 480.34 kB
Formato Adobe PDF
480.34 kB Adobe PDF Visualizza/Apri
Pubblicazioni consigliate

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11570/3146504
Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus ND
  • ???jsp.display-item.citation.isi??? ND
social impact