Background
Observational studies on the effect of antenatal magnesium sulphate on neurodevelopment
Biological plausibility for use of magnesium sulphate for fetal and infant neuroprotection
Maternal and neonatal adverse effects and side effects of magnesium sulphate
How antenatal magnesium sulphate can reduce the burden of being born preterm
Systematic review of randomized trials of magnesium sulphate for neonatal neuroprotection
Results of the meta-analysis of the Cochrane systematic review
Primary outcomes | RR, 95% CI | Number of trials; participants |
---|---|---|
Death or cerebral palsy
| 0.85, 0.74 to 0.98* | four trials; 4446 infants |
Death (fetal and later)
| 0.95, 0.80 to 1.12 | four trials; 4446 infants |
Cerebral palsy
| 0.71, 0.55 to 0.91* | four trials; 4446 infants |
Any neurological impairment
| 1.03, 0.87 to 1.21 | one trial; 1255 infants |
Death or substantial gross motor dysfunction
| 0.84, 0.71 to 1.00 | three trials; 4387 infants |
Is there clinical evidence for the role of antenatal magnesium sulphate for neuroprotection of the fetus, infant and child prior to preterm birth at 30 to 34 weeks gestation?
Trial | N | Eligible (GA wks) | DEATH or CP | CP | DEATH |
---|---|---|---|---|---|
RR, 95% CI | RR, 95% CI | RR, 95% CI | |||
MagNetǂ [43] | 59 | >24 to <34 | 4.83, 0.60 to 38.90 | 6.77, 0.37 to 125.65 | 1.93, 0.19 to 20.18 |
Marret[46] | 688 | viable to <33 | 0.80, 0.58 to 1.10 | 0.70, 0.41 to 1.19 | 0.85, 0.55 to 1.32 |
Rouse[44] | 2444 | 24 to <32 | 0.90, 0.73 to 1.10 | 0.59, 0.40 to 0.85* | 1.13, 0.87 to 1.48 |
Crowther[45] | 1255 | <30 | 0.82, 0.66 to 1.02 | 0.85, 0.55 to 1.31 | 0.81, 0.62 to 1.05 |
Overall | 4446 | viable to <34 | 0.85, 0.75 to 0.98* | 0.71, 0.55 to 0.91* | 0.95, 0.80 to 1.12 |
Summary of CPG evidence statement judgements for gestational age subgroup
Recommendations made by the Australian and New Zealand Bi-National CPG panel for use of antenatal magnesium sulphate
Aims and objectives of this trial
Hypotheses
Methods/design
Ethics statement
Study design
Inclusion criteria
Exclusion criteria
Trial entry
Study groups
Magnesium sulphate study group
Placebo study group
Both study groups
Follow up after birth until the time of primary discharge for both groups
Longer term follow up
Two years assessments
Categorisation of neurosensory disability
Severe Disability
| Any severe cerebral palsy (child non-ambulant and likely to remain so; GMFCS level 4 or 5), severe developmental delay (standardised score <−3 SD) or blindness. |
Moderate Disability
| Moderate cerebral palsy (child non-ambulant at 2 years of age but who is likely to ambulate subsequently; GMFCS level 2 or 3), or deafness, or moderate developmental delay (standardised score from −3 SD to <−2 SD). |
Mild Disability
| Mild cerebral palsy (child walking at 2 years of age with only minimal limitation of movement (GMFCS level 1), or suspect developmental delay (standardised score from −2 SD to <−1 SD). |
No Neurosensory Disability
| Children without any neurosensory impairment. |
Primary study endpoints
Secondary study endpoints
For the infant
-
Health outcomes considered to be important measures of mortality and morbidity prior to primary hospital discharge; (defined as stillbirth and death of liveborn infant before hospital discharge; IVH, severe IVH, cystic PVL, neonatal encephalopathy, neonatal convulsions, proven necrotising enterocolitis, retinopathy of prematurity needing treatment, patent ductus arteriosus needing treatment, respiratory distress syndrome, severity of any neonatal lung disease, chronic lung disease (oxygen dependent at 36 weeks post-menstrual age or 28 days of life if born after 32 weeks gestation), use of respiratory support, airleak requiring drainage, confirmed infection within the first 48 hours, infection after the first 48 hours, body size at birth (weight, length, head circumference) and at discharge home).
-
Composite serious health outcome (defined as stillbirth and death of liveborn infant before hospital discharge severe respiratory disease, severe intraventricular haemorrhage (grade 3 & 4); chronic lung disease (oxygen dependent at 36 weeks post-menstrual age or 28 days of life if born after 32 weeks gestation); proven necrotising enterocolitis; severe retinopathy of prematurity (Stage 3 or worse in the better eye); cystic periventricular leukomalacia).
For the child
-
Individual components of the primary outcome including severity of cerebral palsy (defined as death; cerebral palsy).
-
Death or any neurosensory disability (death defined as stillbirth, death of live born infant before hospital discharge or death after hospital discharge; and any neurosensory disabilities that includes the neurosensory impairments of cerebral palsy, [GMFCS level 1 to 5], blindness [corrected visual acuity worse than 6/60 in the better eye], deafness [hearing loss requiring amplification or worse], and any developmental delay defined as standardised score more than 1 SD below the mean (< −1SD).
-
Death or major neurosensory disability. Major neurosensory disability includes severe and moderate disability (defined as any of: legal blindness, sensorineural deafness requiring hearing aids; moderate or severe cerebral palsy [GMFCS level 2 to 5] or developmental delay/intellectual impairment [standardised score more than two SD below the mean].
-
General health of the child (including use of health services since primary hospitalisation), childhood respiratory morbidity, blood pressure (Z scores and proportions in hypertensive ranges), behaviour as assessed by the Child Behaviour Checklist [54] and body size.
For the mother
-
Maternal serious adverse cardiovascular and/or respiratory outcome of the infusion (defined as maternal death, cardiac arrest, respiratory arrest).
-
Maternal side effects of the infusion (including nausea; vomiting; flushing, infusion arm discomfort; mouth dryness; sweating; dizziness; blurred vision; respiratory rate decreased > four breaths per minute below baseline or <12 breaths per minute; blood pressure decreased > 15 mmHg below baseline level; whether the infusion is discontinued because of side effects).
-
Incidence of postpartum haemorrhage, estimated blood loss at birth 500 ml or more; and major postpartum haemorrhage, estimated blood loss 1500 ml or more; mode of birth.