Magnesium Sulphate for Preterm Birth (MASP Study)
Condition: Cerebral Palsy
MeSH terms: Cerebral Palsy
Study type: Interventional
Phase: Phase 3

Summary: 
      The purpose of the study is to assess whether magnesium sulphate for women at risk of preterm
      birth can protect their children against cerebral palsy. The results from this randomised
      controlled trial 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.
    

Detailed description: 
      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 560 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 by medical records and by Ages and Stages Questionnaire (ASQ) in
      the age of 18 month or older. To screen for cerebral palsy, the domains gross motor skills
      and fine motor skills are together with the total score the most suitable measures.

        1. If the medical record is without any information on cerebral palsy and/or delayed motor
           development or if there is no medical record to be found and there is an ASQ score above
           the 20% percentile (in the domains of gross motor function, fine motor function or total
           score), the child is classified as not having cerebral palsy.

        2. If the child in the ASQ scores under the 20% percentile in the domains of gross motor
           function, fine motor function and/or total score and there is no diagnosis of cerebral
           palsy in the medical record, the parents are contacted. The parents are contacted as
           well, if there is no medical record to be found. If the parents explain that the child
           is developing normally and is not seen by doctors or physiotherapists, the child is
           classified as not having cerebral palsy. If the parents state that the child is not
           developing normally, the child is invited to further examination by a pediatric
           neurologist.

        3. If the child is diagnosed with cerebral palsy or delayed motor development, the medical
           journal is reviewed by a pediatric neurologist to verify the diagnosis. If there is any
           doubt about the correctness of the diagnosis, the child is invited to further
           examination by a pediatric neurologist.
    

Intervention name(s): Magnesium sulphate
Intervention type(s): Drug
Intervention description(s): Magnesium sulphate will be given as a loading dose of 5 g infused for 20-30 minutes, followed by a maintenance dose of 1 g per hour. Placebo will be given in identical appearing doses. The maintenance infusion will be continued until delivery appears, or for 24 hours if delivery does not occur or no longer is considered imminent. The infusion will be resumed when delivery is considered imminent again. Another loading dose of 5 g will be given if at least 6 hours has passed after infusion was stopped. The doses that are used in this project are similar to those used for prevention of eclampsia among women with severe preeclampsia.
Other intervention name(s): Magnesium sulfat
Intervention MeSH terms: Magnesium Sulfate
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Prevention
Keywords: magnesium sulphate; preterm birth; cerebral palsy