TABLE 1.
Study, year | Location | Inclusion/exclusion criteria | No of infants |
Magnesium sulfate |
Cerebral palsy |
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---|---|---|---|---|---|---|---|---|---|
Magnesium group |
No magnesium group |
Loading dose (g) |
Maintenance dose |
Median total dose (g) received by women in magnesium group |
Definition and/or diagnostic criteria |
Health professional who made the diagnosis and age at diagnosis |
|||
Mittendorf et al,29, 301997 | United States, Single center |
1. Neuroprotective arm Inclusion: women with single or twin pregnancy in preterm labor between 25 and 33 weeks of gestation with or without premature rupture of the membranes, reassuring fetal assessment, and cervical dilatation >4 cm. Exclusion: preeclampsia, infection |
30 | 29 | 4 | None | 4 | Not reported | Developmental pediatrician after 18 months of corrected age |
2. Tocolytic arm Inclusion: women with single or twin pregnancy in preterm labor between 25 and 33 weeks of gestation with or without premature rupture of the membranes, reassuring fetal assessment, and cervical dilatation ≤4 cm. Exclusion: preeclampsia, infection |
55 | 51 | 4 | 2–3 g/h; Duration not reported |
49.8 | Not reported | Developmental pediatrician after 18 months of corrected age |
||
Crowther et al,31 2003 | Australia and New Zealand, 16 centers |
Inclusion: women with single, twin, triplet or quadruplet fetuses at risk of preterm delivery before 30 weeks' gestation because of planned or expected birth within 24 hours. Exclusion: women in second stage of labor, if they had received magnesium sulfate in this pregnancy, and contraindications to magnesium sulfate |
629 | 626 | 4 | 1 g/h until birth (if occurred within 24 hours) or up to 24 hours |
≈10.5 | Abnormalities of muscle tone and loss of motor function. Mild cerebral palsy: disability in ambulant children that interfered only slightly with normal daily activities; moderate cerebral palsy: children attempting to walk at two years with or without appliances; Severe cerebral palsy: children permanently non ambulant |
Developmental pediatrician and psychologist at 24 months of corrected age |
Magpie32 2007a |
19 countries across five continents, 125 centers |
Inclusion: women with singleton or multiple pregnancy with preeclampsia who had not given birth or were 24 hours or less postpartum and uncertainty about whether to use magnesium sulfate to prevent eclampsia, irrespective of whether they had received previously magnesium sulfate or other anticonvulsant. Exclusion: hypersensitivity to magnesium, hepatic coma with a risk of renal failure, or myasthenia gravis. |
404 | 401 | 4 | Either 1 g/h intravenously for 24 hours or 5 g every four hours intramuscularly for 24 hours |
18.0b | Severe cerebral palsy: not walking or unlikely to walk unaided by 24 months; non severe cerebral palsy: not defined |
Pediatrician at 18 months of corrected age |
Marret etal, 33, 34 2007 | France, 13 centers |
Inclusion: Inclusion: women with single, twin or triplet fetuses at risk of preterm delivery before 33 weeks' gestation because of planned or expected birth within 24 hours. Exclusion: fetus with severe malformations or chromosomal abnormalities and women with pregnancy-associated vascular disease (preeclampsia, growth restriction, HELLP syndrome, retroplacental hematoma) or with at least one of the following criteria: hypotension, cardiac rhythm abnormalities, hydroelectrolyte abnormalities, renal insufficiency, ingestion during the last 24 hours of calcium channel blockers, digitalins or indomethacin, persistent signs of cardiovascular toxicity or tachycardia >1 hour after cessation of tocolytic intake, myasthenia, or indication for emergency cesarean section. |
352 | 336 | 4 | None | 4 | European Cerebral Palsy Network definition |
Pediatrician by clinical examination (77% of survivors) or parent telephone interview (22% of survivors) at 24 months of age |
Rouse et al,35 2008 | United States, 20 centers |
Inclusion: women carrying singletons or twins at 24 through 31 weeks of gestation and at high risk for spontaneous delivery because of premature rupture of the membranes, advanced preterm labor with dilatation of 4 to 8 cm and intact membranes, or indicated preterm delivery anticipated within 2 to 24 hours. Exclusion: delivery anticipated within less than 2 hours, cervical dilatation >8 cm, rupture of the membranes before 22 weeks, unwillingness of the obstetrician to intervene for the benefit of the fetus, major fetal anomalies or death, maternal hypertension or preeclampsia, maternal contraindications to magnesium sulfate, and receipt of intravenous magnesium sulfate within the previous 12 hours. |
1188 | 1256 | 6 | 2 g/hc | 31.5 | Presence of two or more of the following three features: (1) a delay of 30% or more in gross motor developmental milestones; (2) abnormality in muscle tone, 4+ or absent deep tendon reflexes, or movement abnormality; (3) persistence of primitive reflexes or absence of protective reflexes |
Pediatrician or pediatric neurologist at or beyond 24 months of corrected age |
Data for children whose mothers were less than 34 weeks of gestation and undelivered at randomization extracted from Doyle et al.’s review22
For women of all gestational ages and undelivered at randomization
If delivery had not occurred after 12 hours and was no longer considered imminent, the infusion was discontinued and resumed when delivery was deemed imminent again. If at least 6 hours had passed since the discontinuation of the study medication, another loading dose was given