Objective: To determine whether there is a significant association between perinatal mortality and exposure to total doses of tocolytic magnesium sulfate larger than 48 g.
Methods: We did a case-control study in which cases were defined as neonates or fetuses who died after being exposed to tocolytic magnesium sulfate and controls were those who survived exposure. The study included fetuses and neonates who weighed between 700 and 1249 g and whose mothers had received tocolytic magnesium sulfate at Chicago Lying-in Hospital between January 1, 1986, and March 31, 1999. We excluded women who received prophylactic magnesium sulfate for preeclampsia or preeclampsia superimposed on chronic hypertension, and fetuses or neonates with major congenital anomalies. Data were analyzed by Fisher exact test, chi(2) test, Student t test, Mann-Whitney U test, multivariable logistic regression, and Cochrane-Armitage trend test.
Results: Controlling for birth weight or gestational age, year of delivery, receipt of betamethasone, acute maternal disease, and maternal race in a multivariable model, we found that exposure to total doses of tocolytic magnesium sulfate exceeding 48 g was significantly associated with increased perinatal mortality (adjusted odds ratio 4. 7; 95% confidence interval 1.1, 20.0; P =.035). Using the Cochrane-Armitage trend test, we found that a significant dose response was present (P =.03), but one that was most consistent with a threshold effect.
Conclusion: Our findings support the hypothesis that high doses of tocolytic magnesium sulfate are associated with increased perinatal mortality among fetuses and neonates weighing 700-1249 g.