The feasibility of a randomized clinical perinatal trial: maternal magnesium sulfate for the prevention of cerebral palsy.
OBJECTIVE
Because recent epidemiologic data suggest an association between maternal magnesium sulfate use and a decreased risk of cerebral palsy in infants who survive preterm birth, we investigated the feasibility of a randomized trial of intrapartum maternally administered magnesium sulfate to prevent cerebral palsy in children who were born before term.


METHODS
On the basis of a literature review, we calculated cumulative rates of delivery, neonatal survival, and cerebral palsy for progressively longer gestational age intervals beginning at 24 weeks' gestation. Sample size estimates with two-tailed chi 2 tests without Yates' correction (alpha = 0.05, beta = 0.2, 50% effect size) for a clinical trial were calculated for these rates.


RESULTS
In the 4-week interval from 24 weeks 0 days to 27 weeks 6 days the minimum number of neonates required to conduct a randomized trial would be 1189. Loss to follow-up of neonates, maternal ineligibility, and failure of enrollment would substantially increase the number of necessary gravid women delivered in the 4-week interval to complete such a trial, such that 1 million pregnancies would be required to generate the necessary number of eligible gravid women. Shorter gestational age intervals (e.g., 24 weeks 0 days to 25 weeks 6 days) required fewer neonates (n = 729) but more pregnancies (n = 1.5 million). Because of the decreasing prevalence of cerebral palsy at higher gestational ages, extending the gestational age interval (e.g., to 29 weeks 6 days) markedly increased the minimum number of neonates to 1982 but only slightly decreased the necessary number of pregnancies, to 900,000.


CONCLUSIONS
A randomized trial of maternally administered intrapartum magnesium sulfate to reduce the rate of cerebral palsy in surviving preterm neonates would be a formidable undertaking, requiring a concerted multicentered effort.
Rouse
D J
DJ
Department of Obstetrics and Gynecology, University of Alabama at Birmingham, USA.
Hauth
J C
JC
Nelson
K G
KG
Goldenberg
R L
RL
D002547:Cerebral Palsy / Q000453:epidemiology / Q000517:prevention & control*; D005240:Feasibility Studies; D005260:Female; D005865:Gestational Age; D006801:Humans; D007226:Infant Mortality; D007231:Infant, Newborn; D008278:Magnesium Sulfate / Q000008:administration & dosage / Q000627:therapeutic use*; D007752:Obstetric Labor, Premature; D011247:Pregnancy; D016032:Randomized Controlled Trials as Topic; D012107:Research Design; D018401:Sample Size
D008278:Magnesium Sulfate