Magnesium Sulphate for Preterm Birth (MASP Study)

• Moderate or severe cerebral palsy [ Time Frame: At 18 months of age ] [ Designated as safety issue: No ]
  The difference in the number of children with moderate or severe cerebral palsy at 18 months of age, whose mothers had magnesium sulphate before birth compared to the group of children whose mothers received placebo before birth.
  
  

• Perinatal death [ Time Frame: From date of randomization until the date of death from any cause, assessed up to 18 months ] [ Designated as safety issue: No ]
  The difference in the number of children with perinatal death, whose mothers had magnesium sulphate before birth compared to the group of children whose mothers received placebo before birth.
  
  
• Blindness [ Time Frame: At 18 months of age ] [ Designated as safety issue: No ]
  The difference in the number of children with blindness at 18 months of age, whose mothers had magnesium sulphate before birth compared to the group of children whose mothers received placebo before birth.
  
  
• Apgar scores [ Time Frame: At 1 minute and 5 minutes after birth ] [ Designated as safety issue: No ]
  The difference in apgar scores in the group of children, whose mothers had magnesium sulphate before birth compared to the group of children whose mothers received placebo before birth.
  
  

Cerebral palsy consists of chronic and non-progressive clinical syndromes that are characterized by motor and postural dysfunction. In affected infants, voluntary movements become difficult and limited, and although clinical expression may change with time, this disability is accompanied with major personal and socioeconomic burdens. Preterm infants have increased risk of cerebral palsy, which is inversely correlated with gestational age at birth. Previous studies have indicated that magnesium sulphate may be neuroprotective for the preterm infant, when the drug is given to women prior to preterm birth. However, this benefit of antenatal magnesium sulphate was recently questioned by Trial Sequential Analysis (TSA), a statistical method that adjusts for risk of random error on published meta-analyses. TSA demonstrates that additional data are needed before accepting magnesium sulphate as evidence based therapy for women in preterm labour. Therefore we will close the gap by performing a new randomised clinical trial (RCT), which aims to assess whether magnesium sulphate for women prior to preterm birth can protect their children against cerebral palsy. The RCT will not individually have the power to detect a significant difference between magnesium and placebo. Instead, when the trial is completed, the results will be added to the previous meta-analysis to obtain firm evidence for magnesium sulphate as a neuroprotector, and determine whether it should be used as standard therapy for women in preterm birth.

From Denmark, Sweden, Norway and Iceland 1,240 eligible women, who are at risk of preterm birth at 24 to 32 weeks of gestation, will be randomised to receive either intravenous magnesium sulphate or placebo. Randomisation will be performed blinded by computer generated random numbers.The children are followed up after 18 months of age by forwarding a standardized developmental questionnaire to the parents. If signs of cerebral palsy are suspected from the questionnaire, the children will be examined neurologically.