Magnesium sulphate for the prevention of cerebral palsy in Australia and New Zealand.

• Jurisdiction: Australia
• Date: 01 July 2013
• Author: Bain, Emily

Introduction

In 2010, the Australian National Health and Medical Research Council (NHMRC) endorsed Australian and New Zealand clinical practice guidelines that recommend magnesium sulphate to be given to women at risk of imminent, very early preterm birth (at less than 30 weeks gestation) for the prevention of death and cerebral palsy in their infants (The Antenatal Magnesium Sulphate for Neuroprotection Guideline Development Panel 2010). Now, the WISH Project (Working to Improve Survival and Health of babies born preterm), supported by the Cerebral Palsy Alliance, is working to bring Australian and New Zealand clinical practice in line with the recommendations from these guidelines (ARCH 2013).

Preterm birth and cerebral palsy: the burden of disease

Cerebral palsy is an umbrella term which "describes a group of disorders of the development of movement and posture, causing activity limitations, which are attributed to nonprogressive disturbances that occurred in the developing fetal or infant brain" (Bax et al 2005). It is the most common physical disability in childhood, and the most severe physical disability within the spectrum of developmental delay. Cerebral palsy is a complex neurological condition, with the motor and/or postural dysfunction often found alongside cognitive, communication, sight and hearing impairments, or epilepsy, pain, behaviour and sleep disorders (Novak et al 2012). Understandably cerebral palsy has considerable emotional, social and economic costs to individuals, their families and communities. In 2007, the cost of cerebral palsy to the Australian community was estimated at $A3.87 billion (including financial cost and lost wellbeing) (Access Economics 2008). The overall incidence of cerebral palsy in developing countries remains static at 2.1 per 1,000 live births (Oskoui et al 2013).

In Australia, over 600 children are diagnosed with cerebral palsy each year; and it has been estimated that approximately 40% of these cases are related to preterm birth (ACPR Group 2013). The prevalence of cerebral palsy increases significantly with decreasing gestational age; infants born very preterm are at a substantially higher risk than infants born at term (Saigal and Doyle 2008). The most recent Australian Cerebral Palsy Register report suggests that while the rate of cerebral palsy in infants born most preterm is starting to decrease, survival (with associated morbidities) is continuing to increase (ACPR Group 2013). The identification of primary preventive measures has therefore been identified as a key priority by consumers, clinicians and researchers (McIntyre et al 2010); prevention for infants born very preterm is of high interest, due to their increased risk of developing cerebral palsy, and also their apparent ability to respond to interventions.

Magnesium sulphate and prevention of cerebral palsy: the evidence base

Nearly 20 years ago, a case control study first described the association between antenatal magnesium and a reduction in cerebral palsy. Nelson and colleagues observed that in infants born with a birthweight of less than 1,500 grams, their risk of cerebral palsy was reduced if their mother had received magnesium sulphate in labour (whether received as a tocolytic to suppress preterm labour, or for severe pre-eclampsia) (Nelson and Grether 1995). In order to establish more reliable evidence, a number of randomised controlled trials were undertaken to assess the effects of in utero exposure to magnesium for preventing cerebral palsy. Of the five trials conducted, the primary aim of four (two from the United States (Mittendorf et al 2002; Rouse et al 2008), one from France (Marret et al 2007) and one from Australia and New Zealand (Crowther et al 2003)) was to assess the use of magnesium sulphate for neuroprotection of the fetus. The primary aim of the fifth (conducted worldwide (Magpie Trial Follow-Up Collaborative Group 2007)) was assessing use for the prevention of eclampsia, however longer term outcomes were reported for the infants.

These five trials were included in a Cochrane systematic review meta-analysis (Doyle et al 2009) and a number of other systematic reviews, which each supported a neuroprotective role for antenatal magnesium sulphate. Specifically in the Cochrane review, magnesium sulphate given to the mother prior to preterm birth was shown to reduce the risk of cerebral palsy or death for the infant (risk ratio (RR) 0.85; 95% confidence interval (CI) 0.74 to 0.94; four trials...