1 Magnesium sulfate tocolysis and risk of neonatal death Judith K. Grether, PhD, a Jennifer Hoogstrate, MFA, a Steve Selvin, PhD, b and Karin B. Nelson, MD c Emeryville and Berkeley, California, and Bethesda, Maryland OBJECTIVE: Our purpose was to evaluate the association between in utero exposure to magnesium sulfate and neonatal death. STUDY DESIGN: Case-control comparison was performed of singleton infants who died at 0 to 28 days and control infants who survived to age 3 years and did not have disabling cerebral palsy. All subjects were born between 1983 and 1985 to mothers resident in one of four northern California counties. RESULTS: Magnesium sulfate tocolysis was associated with a decreased risk of neonatal mortality (odds ratio 0.25, 95% confidence interval 0.6 to 1.1). Adjustment for birth weight and gestational age increased the inverse association (odds ratio 0.09, 95% confidence interval 0.01 to 0.93). The association between neona- tal mortality and magnesium sulfate was not altered by maternal infection, gender, maternal race or ethnicity, maternal age, level of care, breech presentation, surgical delivery, corticosteroids, abruptio placentae, pla- centa previa, or bleeding on admission. CONCLUSIONS: Magnesium sulfate tocolysis was not associated with increased neonatal mortality in pre- mature infants. Thus any association of magnesium with reduced long-term neurologic morbidity is unlikely to be the result of selective mortality of vulnerable infants. (Am J Obstet Gynecol 1998;178:1-6.) Key words: Magnesium and neonatal death, magnesium sulfate tocolysis Antenatal treatment with magnesium sulfate for preterm labor or preeclampsia has been associated with decreased risk of congenital cerebral palsy in very-low- birth-weight (VLBW) infants in several observational studies. 1-4 The possibility must be considered that expo- sure to magnesium might increase the risk of death in in- fants who would otherwise survive with neurologic dam- age; the apparent protective effect might thus be a result of selective mortality. A range of studies with differing methods are inconclu- sive with regard to an association between in utero expo- sure to magnesium sulfate and subsequent perinatal mortality. Both decreased 5-8 and increased 9 risk of death have been reported; other studies have found no associa- tion between magnesium sulfate exposure and perinatal mortality. 2, 6, 10-14 Limitations common to many of these studies include small numbers of subjects, failure to ex- clude deaths resulting from major malformations, and lack of adjustment for confounding factors such as gesta- tional age, birth weight, and maternal medical condi- tions. We report here a population-based case-control inves- tigation of the association of neonatal mortality with magnesium sulfate exposure, focusing on deaths during the first 28 days of life when any effect of magnesium is most likely to be present and excluding deaths resulting from major malformations or traumatic events. We re- stricted major analyses to mother-baby pairs with expo- sure to one or more tocolytic agents, thus limiting con- sideration to a relatively homogeneous subgroup with no From the California Birth Defects Monitoring Program, California Department of Health Services, a the Division of Biostatistics and Information Science, School of Public Health, University of California, Berkeley, b and the Neuroepidemiology Branch, National Institute of Neurological Disorders and Stroke. c Supported by the authors’ institutions. Received for publication March 21, 1997; accepted July 17, 1997. Reprint requests: Judith K. Grether, PhD, California Birth Defects Monitoring Program, 1900 Powell St., Suite 1050, Emeryville, CA 94608-1811. 6/1/84757 American Journal of Obstetrics and Gynecology Founded in 1920 volume 178 number 1 part 1JANUARY 1998 GENERAL OBSTETRICS AND GYNECOLOGY Fetus-Placenta-Newborn