Fetal Neuroprotection by Magnesium Sulfate: From Translational Research to Clinical Application

Abstract

Despite improvements in perinatal care, preterm birth still occurs regularly and the associated brain injury and adverse neurological outcomes remain a persistent challenge. Antenatal magnesium sulfate administration is an intervention with demonstrated neuroprotective effects for preterm births before 32 weeks of gestation (WG). Owing to its biological properties, including its action as an N-methyl-d-aspartate receptor blocker and its anti-inflammatory effects, magnesium is a good candidate for neuroprotection. In hypoxia models, including hypoxia-ischemia, inflammation, and excitotoxicity in various species (mice, rats, pigs), magnesium sulfate preconditioning decreased the induced lesions’ sizes and inflammatory cytokine levels, prevented cell death, and improved long-term behavior. In humans, some observational studies have demonstrated reduced risks of cerebral palsy after antenatal magnesium sulfate therapy. Meta-analyses of five randomized controlled trials using magnesium sulfate as a neuroprotectant showed amelioration of cerebral palsy at 2 years. A meta-analysis of individual participant data from these trials showed an equally strong decrease in cerebral palsy and the combined risk of fetal/infant death and cerebral palsy at 2 years. The benefit remained similar regardless of gestational age, cause of prematurity, and total dose received. These data support the use of a minimal dose (e.g., 4 g loading dose ± 1 g/h maintenance dose over 12 h) to avoid potential deleterious effects. Antenatal magnesium sulfate is now recommended by the World Health Organization and many pediatric and obstetrical societies, and it is requisite to maximize its administration among women at risk of preterm delivery before 32 WG.

The Effect of Antenatal Neuroprotective Magnesium Sulfate Treatment on Cerebral Oxygenation in Preterm Infants

“…There is still a lack of evidence, and conflicting results about the effect of antenatal MgSO 4 on both cerebral oxygenation and the incidence of severe IVH, and the reports suggest that outcomes may depend on the antenatal maternal magnesium dose/serum concentrations and neonatal serum magnesium concentrations. [21][22][23][24][25][26][27][28] Despite the uncertainty about the exact mechanism of fetal MgSO 4 neuroprotection, some factors have been asserted to have a role in lowering CP risk. MgSO 4 was shown to have multiple direct effects on the nervous tissue, such as blockade of NMDA (N-Methyl-d-aspartate) receptors and increasing angiogenesis.…”

Role of magnesium sulfate in the treatment of acute postoperative pain

“…Takođe, korist od magnezijuma moguća je i u prevenciji/lečenju pretkomorskih i komorskih aritmija (18) i astme (19), hipertenzije (20), dijabetesa, dispepsije, opstipacije, kao i mnogih drugih oboljenja (16). Pored toga, magnezijum može da ispolji analgetičko, anestetičko, kao i neuroprotektivno dejstvo (21,22,23,24,25). Velika raznolikost kliničkih efekata može se objasniti značajnom ulogom magnezijuma u fiziologiji različitih organa i sistema.…”

“…Cochrane-ski pregled upotrebe magnezijuma u preeklampsiji podržava bezbednost primene magnezijum-sulfata u dozama do 1 g/h (79). Slične doze magnezijum-sulfata preporučuje Svetske zdravstvena organizacija kod sve prevremeno rođene dece (pre 32 nedelje gestacije) u cilju prevencije cerebralne paralize (80).…”

The effect of antenatal magnesium sulphate administration on patent ductus arteriozus in very low birth weight preterms

“…Magnezyum sülfatın doğumdan sonra prematüre morbidite ve mortalitesi üzerine etkisi olabileceği tartışılmaktadır (6)(7)(8)(9). Son yıllarda yapılan çalışmalarda, MgSO4'ün uzun dönemde nöroprotektif ve serebral palsiden koruyucu etkisi olduğu rapor edilmiştir (10)(11)(12)(13)(14)(15). Magnezyum, vasküler tonun düzenlenmesinde önemli bir rol oynar.…”

“…Ayrıca, yenidoğanda hipotansiyon, apne, gastrointestinal sistem motilitesinde azalma gibi yan etkilere neden olabilir (11,30). Bu etkilerine rağmen nöroprotektif etkisi ve serebral palsi riskini azalması gibi olumlu etkileri de vardır (10)(11)(12)(13)15). Antenatal MgSO4 hem tokolitik hem de nöroprotektif olarak uygulanmasında rağmen PDA sıklığını artırabilmektedir.…”