Oral Melatonin as Neuroprotectant in Preterm Infants
Condition: Malondialdehyde; Melatonin
MeSH terms: Premature Birth
Study type: Interventional

Summary: 
      Preterm newborns survival rates are improved, but long-term disabilities are still common.
      Major destructive focal lesions became less common, the most predominant lesion at present is
      diffuse white matter (WM damage). Melatonin (ME) serves as a neuroprotectant cerebral
      ischemia through its potent anti-oxidant/-inflammatory effect. Preclinical studies
      demonstrated that protects the developing brain by preventing abnormal myelination and
      inflammatory glial reaction. Clinical studies demonstrated ME ability in reducing brain
      damage after neonatal Hypoxic Ischemic Encephalopathy (HIE) or preventing neonatal
      impairments due to antenatal/ post-natal injuries: preeclampsia,
      IntraUterineGrowthRestriction (IUGR), ventilation, Bronchopulmonary Dysplasia (BPD). ME has a
      good safety profile with no known adverse effects. This study aims to highlight that ME can
      prevent brain impairment due to premature birth. ME will be administered orally (3 mg/kg/die
      for 15 days to neonates born before 29+6 week gestation, in a prospective double blind,
      randomized vs placebo study, 2 parallel arms. ME and malondialdehyde (MDA), a lipid
      peroxidation product) levels before and at the end of treatment will be measured . Other
      outcomes: Cerebral ultrasounds (cUS); cerebral magnetic resonance imaging (cMRI), " Fagan
      test " eye tracking, ophthalmological, auditory, neurological/cognitive child assessments.
      Monitoring parental distress, which can influence the neurodevelopmental outcome in preterms.
    

Detailed description: 
      About 552.000 infants are born in Italy each year, 1% of them with gestational age under 30
      weeks. Survival rates are improved, but long-term disabilities are still common. Major
      destructive focal lesions became less common, the most predominant lesion at present is
      diffuse white matter (WM damage). The prevention of neurodevelopmental impairment is a major
      public health challenge and efforts are needed to test neuroprotective strategies. Melatonin
      (ME) serves as a neuroprotectant cerebral ischemia through its potent
      anti-oxidant/-inflammatory effect. Preclinical studies demonstrated that protects the
      developing brain by preventing abnormal myelination and inflammatory glial reaction. Clinical
      studies demonstrated ME ability in reducing brain damage after neonatal Hypoxic Ischemic
      Encephalopathy (HIE) or preventing neonatal impairments due to antenatal/ post-natal
      injuries: preeclampsia, IntraUterineGrowthRestriction (IUGR), ventilation, Bronchopulmonary
      Dysplasia (BPD). Ongoing studies are testing in premature neonates and pregnant women its
      neuroprotective properties. ME has a good safety profile with no known adverse effects.

      This study aims to highlight that ME can prevent brain impairment due to premature birth. ME
      will be administered orally (3 mg/kg/die for 15 days within 96 hours from birth) to neonates
      born before 29+6 week gestation age (GA), in a prospective double blind, randomized vs
      placebo study, 2 parallel arms (30 preterm infants each). ME and malondialdehyde (MDA, a
      lipid peroxidation product) levels will be measured before and at the end of treatment. At
      birth, within 40 weeks of neonatal age, at 4-6 and at 24 months of age the following
      examinations are performed: Cerebral ultrasounds (cUS); cerebral magnetic resonance imaging
      (cMRI), during natural sleep (i.e. adopting sleep deprivation and/or feeding protocols);
      "Fagan test"eye tracking, ophthalmological, auditory brain stem evoked response (ABR),
      neurological/cognitive child assessments. Monitoring parental distress, which can influence
      the neurodevelopmental outcome in preterms.
    

Intervention name(s): melatonin; placebo
Intervention type(s): Dietary Supplement; Drug
Intervention description(s): orally administered drops; orally administered drops
Other intervention name(s): not reported; not reported
Intervention MeSH terms: Melatonin
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Supportive Care
Keywords: Preterm neonate; Neuroprotection; Malondialdehyde; Melatonin