A randomized controlled trial on the use of magnesium sulfate and melatonin in neonatal hypoxic ischemic encephalopathy

Farargy, Mohamed S El; Soliman, Nema A.

doi:10.3233/npm-181830

Cited by 16 publications

(14 citation statements)

References 28 publications

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“…Therefore, exogenous melatonin administration appears a promising strategy in the treatment of neonatal morbidities in which OS has a leading role. Moreover, as it shows neuroprotective properties, it was present as a joint therapy in addition to hypothermia after hypoxic-ischemic encephalopathy [5][6][7][8]. Several studies tested the efficacy of melatonin to counteract oxidative damage in diseases of newborns such as chronic lung disease, perinatal brain injury, necrotizing enterocolitis, retinopathy of prematurity, and sepsis, giving promising results [9][10][11].…”

Section: Introductionmentioning

confidence: 99%

Antioxidant Effect of Melatonin in Preterm Newborns

Marseglia

Gitto

Laschi

et al. 2021

Oxidative Medicine and Cellular Longevity

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Introduction. Preterm infants are at risk of free radical-mediated diseases from oxidative stress (OS) injury. Increased free radical generation has been demonstrated in preterm infants during the first seven days of life. Melatonin (MEL) is a powerful antioxidant and scavenger of free radicals. In preterm neonates, melatonin deficiency has been reported. Exogenous melatonin administration appears a promising strategy in the treatment of neonatal morbidities in which OS has a leading role. Objective. The aim was to evaluate plasma MEL concentrations and OS biomarkers in preterm newborns after early administration of melatonin. Methods. A prospective, randomized double-blind placebo-controlled pilot study was conducted from January 2019 to September 2020. Thirty-six preterm newborns were enrolled. Starting from the first day of life, 21 received a single dose of oral melatonin 0.5 mg/kg once a day, in the morning (MEL group); 15 newborns received an equivalent dose of placebo (placebo group). Samples of 0.2 mL of plasma were collected at 24 and 48 hours after MEL administration. Plasma concentrations of melatonin, non-protein-bound iron (NPBI), advanced oxidation protein products (AOPP), and F2-isoprostanes (F2-Isopr) were measured. Babies were clinically followed until discharge. Results. At 24 and 48 hours after MEL administration, the MEL concentrations were significantly higher in the MEL group than in the placebo group ( 52759.30 ± 63529.09 vs. 28.57 ± 46.24 pg/mL and 279397.6 ± 516344.2 vs. 38.50 ± 44.01 pg/mL, respectively). NPBI and AOPP did not show any statistically significant differences between the groups both at 24 and 48 hours. At 48 hours, the mean blood concentrations of F2-Isopr were significantly lower in the MEL group than in the placebo group ( 36.48 ± 33.85 pg/mL vs. 89.97 ± 52.01 pg/mL). Conclusions. Early melatonin administration in preterm newborns reduces lipid peroxidation in the first days of life showing a potential role to protect high-risk newborns. Trial Registration. This trial is registered with NCT04785183, Early Supplementation of Melatonin in Preterm Newborns: the Effects on Oxidative Stress.

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Section: Introductionmentioning

confidence: 99%

Antioxidant Effect of Melatonin in Preterm Newborns

Marseglia

Gitto

Laschi

et al. 2021

Oxidative Medicine and Cellular Longevity

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“…Melatonin has shown neuroprotective properties against different neurological disorders such as Alzheimer’s disease [ 242 , 243 ], amyotrophic lateral sclerosis [ 244 , 245 , 246 ], and stroke [ 247 , 248 ]. With regards to neonatal HI, numerous studies have investigated melatonin as a post-treatment using animal models [ 249 , 250 , 251 , 252 , 253 ], in addition to several randomized clinical trials in humans, which support its neuroprotective role as adjuvant therapy for the treatment of HI [ 254 , 255 , 256 ] (see [ 257 , 258 ] for a review). The focus of this review is those studies that evaluated the neuroprotection with melatonin as a pretreatment for neonatal HI damage, either as a maternal supplementation regime [ 77 , 78 ] or when administered to the pups prior to HI induction [ 36 , 79 , 80 ].…”

Section: Other Neuroprotective Natural Compoundsmentioning

confidence: 99%

“…Overall, melatonin is one of the most extensively studied nutraceuticals in regard to neonatal HI. There is robust literature on its neuroprotective properties (reviewed in [ 258 ]), including several clinical trials supporting its benefits as adjuvant therapy in newborns affected by HI [ 254 , 255 , 256 ]. Preclinical studies had shown promising results when administered as prophylactic dietary supplementation during pregnancy [ 77 , 78 ], warranting future pilot studies to study this gestational dietary intervention in humans.…”

Section: Other Neuroprotective Natural Compoundsmentioning

confidence: 99%

Nutraceuticals in the Prevention of Neonatal Hypoxia–Ischemia: A Comprehensive Review of their Neuroprotective Properties, Mechanisms of Action and Future Directions

Reyes-Corral

Sola-Idígora

Puerta

et al. 2021

IJMS

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Neonatal hypoxia–ischemia (HI) is a brain injury caused by oxygen deprivation to the brain due to birth asphyxia or reduced cerebral blood perfusion, and it often leads to lifelong limiting sequelae such as cerebral palsy, seizures, or mental retardation. HI remains one of the leading causes of neonatal mortality and morbidity worldwide, and current therapies are limited. Hypothermia has been successful in reducing mortality and some disabilities, but it is only applied to a subset of newborns that meet strict inclusion criteria. Given the unpredictable nature of the obstetric complications that contribute to neonatal HI, prophylactic treatments that prevent, rather than rescue, HI brain injury are emerging as a therapeutic alternative. Nutraceuticals are natural compounds present in the diet or used as dietary supplements that have antioxidant, anti-inflammatory, or antiapoptotic properties. This review summarizes the preclinical in vivo studies, mostly conducted on rodent models, that have investigated the neuroprotective properties of nutraceuticals in preventing and reducing HI-induced brain damage and cognitive impairments. The natural products reviewed include polyphenols, omega-3 fatty acids, vitamins, plant-derived compounds (tanshinones, sulforaphane, and capsaicin), and endogenous compounds (melatonin, carnitine, creatine, and lactate). These nutraceuticals were administered before the damage occurred, either to the mothers as a dietary supplement during pregnancy and/or lactation or to the pups prior to HI induction. To date, very few of these nutritional interventions have been investigated in humans, but we refer to those that have been successful in reducing ischemic stroke in adults. Overall, there is a robust body of preclinical evidence that supports the neuroprotective properties of nutraceuticals, and these may represent a safe and inexpensive nutritional strategy for the prevention of neonatal HI encephalopathy.

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“…To date, four of the five clinical trials [ 154 , 155 , 156 , 157 ] used the oral route of administration with variable doses of: 10 mg once only [ 156 ], every 2 h for 4 doses [ 154 ], or 10 mg/kg daily for 5 days [ 155 , 157 ] but the pharmacokinetic profiles in all studies were not reported. The oral bioavailability is less certain in newborns due to higher gastric pH, lower superior mesenteric arterial blood flow and delayed gastric emptying [ 158 ].…”

Section: Translating From Bench To Bedsidementioning

confidence: 99%

Melatonin for Neonatal Encephalopathy: From Bench to Bedside

Pang

Advic-Belltheus

Meehan

et al. 2021

IJMS

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Neonatal encephalopathy is a leading cause of morbidity and mortality worldwide. Although therapeutic hypothermia (HT) is now standard practice in most neonatal intensive care units in high resource settings, some infants still develop long-term adverse neurological sequelae. In low resource settings, HT may not be safe or efficacious. Therefore, additional neuroprotective interventions are urgently needed. Melatonin’s diverse neuroprotective properties include antioxidant, anti-inflammatory, and anti-apoptotic effects. Its strong safety profile and compelling preclinical data suggests that melatonin is a promising agent to improve the outcomes of infants with NE. Over the past decade, the safety and efficacy of melatonin to augment HT has been studied in the neonatal piglet model of perinatal asphyxia. From this model, we have observed that the neuroprotective effects of melatonin are time-critical and dose dependent. Therapeutic melatonin levels are likely to be 15–30 mg/L and for optimal effect, these need to be achieved within the first 2–3 h after birth. This review summarises the neuroprotective properties of melatonin, the key findings from the piglet and other animal studies to date, and the challenges we face to translate melatonin from bench to bedside.

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A randomized controlled trial on the use of magnesium sulfate and melatonin in neonatal hypoxic ischemic encephalopathy

Cited by 16 publications

References 28 publications

Antioxidant Effect of Melatonin in Preterm Newborns

Antioxidant Effect of Melatonin in Preterm Newborns

Nutraceuticals in the Prevention of Neonatal Hypoxia–Ischemia: A Comprehensive Review of their Neuroprotective Properties, Mechanisms of Action and Future Directions

Melatonin for Neonatal Encephalopathy: From Bench to Bedside

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