Antenatal magnesium sulphate neuroprotection in the preterm infant

Discipline of Obstetrics and Gynaecology, University of Adelaide, Tarndarnya, South Australia, Australia
Seminars in Fetal and Neonatal Medicine (Impact Factor: 3.03). 09/2007; 12(4):311-7. DOI: 10.1016/j.siny.2007.04.001
Source: PubMed


Very preterm infants have high rates of neurological impairments and disabilities. These rates have not diminished as the survival rates have improved. Basic science research suggests that magnesium sulphate before birth can be neuroprotective for the preterm fetus. Some, but not all, observational studies in humans also suggest a protective effect of antenatal magnesium sulphate on cerebral palsy. Four randomised controlled trials of antenatal magnesium sulphate have reported long-term neurological effects in surviving infants, but only one of these was designed specifically to evaluate the long-term effects of treatment. These studies found that, overall, antenatal magnesium sulphate therapy had no significant effect on paediatric mortality or neurological outcomes in the first few years of life, including cerebral palsy, but it was found to lower the rate of motor problems at 2 years of age in one study. The role for antenatal magnesium sulphate therapy as a neuroprotective agent for the preterm fetus is not yet established.

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    ABSTRACT: With improving neonatal survival for very premature babies, the challenge for neonatalogists is to ameliorate outcome of surviving babies. Several pharmacological molecules have been shown to have protective effects in different types of in vitro or in vivo animal models of acquired cerebral brain damages. However translational research and conduction of therapeutic trials in human remain difficult due to failure to recognize start of deleterious cascade leading to cerebral damage and additional toxic effect of potential protective molecules. This review concentrates on best evidence emerging in recent years on prevention on brain damage by early drug administration. It has been shown in two randomised trials that prenatal low-dose of magnesium sulphate does not increase paediatric mortality in very-preterm infants and has non significant neuroprotective effects on occurrence of motor dysfunction (with a 0.62 odds ratio in the French trial Premag and 0.71 relative risk in the Australian trial ACTOMgSO4), justifying that magnesium sulphate should be discussed as a stand-alone treatment or as part of a combination treatment, at least in the context of clinical trials. Antenatal corticosteroid therapy increases the survival of very-preterm infants, including the most immature. Moreover in an observational recent study of the Epipage cohort, it has been observed a significant decrease in white matter injury in the 28-32 weeks’ gestation group but no effect on long term outcome and behaviour. Conversely in the most immature of the 24-27 weeks’ gestation group, no effect has been detected either in white matter injury incidence or in long term outcome rates. Caffeine has a protective effect since a decrease in cerebral palsy has been noted in the caffeine group in a randomised trial studying caffeine versus placebo. For what concern other widely used potential protective molecules during the perinatal period, there is no evidence of cerebral protection with indometacine, nitric oxide, eythropoietin, phenobarbital, and etamsylate. Due to their specific properties, a careful evaluation of aspirin, anaesthetic drugs and tocolytics should be done in the next months.
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    ABSTRACT: Cerebral palsy (CP) affects 2/1000 live-born children. Multiple antenatal factors, including preterm delivery, low birth weight, infection/inflammation, multiple gestation, and other pregnancy complications, are mostly associated with CP in both the preterm and term infant, with birth asphyxia playing a minor role. Owing to the increasing survival of the very preterm and very low birth weight infant secondary to improvements in neonatal and obstetric care, the incidence of CP may be increasing. The focus of this paper is to explore antenatal antecedents as etiologies of CP and the impact of obstetric care on the prevention of CP.
    No preview · Article · Jan 2009 · Clinical obstetrics and gynecology
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    ABSTRACT: Magnesium sulfate (MgSO4) is often used as a treatment for pre-eclampsia/eclampsia and preterm labor, resulting in the exposure of a significant number of neonates to this drug despite a lack of evidence suggesting that it is safe, or effective as a tocolytic. While there is evidence that MgSO4 may be neuroprotective in perinatal brain injury, recent reviews have suggested that the effects are dependent upon dose, and that higher doses may actually increase neonatal morbidity and mortality. There is a lack of evidence investigating the neurotoxic effects of neonatal magnesium (Mg) exposure on the developing brain, specifically in terms of neurodevelopmental apoptosis, a cell-killing phenomenon known to be potentiated by other drugs with mechanisms of action at Mg-binding sites (i.e. NMDA receptor antagonists such as MK-801, ketamine, and PCP). To investigate the effects of Mg exposure on the neonatal mouse brain at different postnatal ages to determine whether MgSO4 treatment causes significant cell death in the developing mouse brain. C57Bl/6 mice were treated with four doses of MgSO4 (250 mg/kg) on postnatal days 3 (P3), 7 (P7) or 14 (P14). Caspase-3 immunohistochemistry, cupric silver staining, and electron microscopy techniques were used to examine Mg-treated brains for neurotoxic effects. Qualitative evaluation using cupric silver staining revealed widespread damage throughout the brain in P7 animals. Results of electron microscopy confirmed that the cell death process was apoptotic in nature. Quantitative evaluation of damage to the cortex, caudate-putamen, hippocampus, thalamus, and cerebellum showed that Mg treatment caused significant brain damage in animals treated on P3 and P7, but not P14. Administration of high doses of Mg may be detrimental to the fetal brain, particularly if exposure occurs during critical periods of neurodevelopment.
    Full-text · Article · Mar 2009 · Neonatology
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