Magnesium Sulfate in Labor and Risk of Neonatal Brain Lesions and Cerebral Palsy in Low Birth Weight Infants

Objectives. We tested the hypothesis that administration of magnesium sulfate in labor protects against the development of neonatal brain lesions and cerebral palsy (CP) in low birth weight infants. Methods. Magnesium exposure was ascertained in a population-based cohort of 1105 infants weighing 2000 g or less through review of medical records of maternal magnesium sulfate administration and, where available, elevated maternal serum magnesium levels. Neonatal germinal matrix/intraventricular hemorrhage and parenchymal brain lesions were ascertained by a prospective, timed ultrasound scanning protocol in the first week of life. CP was ascertained at 2 years of age by clinical examination in 80% of survivors and by interview and medical record review in another 6% and was classified as disabling or nondisabling. Results. No significant reduction in risk of nondisabling CP (adjusted odds ratio [OR], 1.00; 95% confidence interval [CI], 0.53 to 1.88) or disabling CP [DCP] (adjusted OR, 0.63; 95% CI, 0.32 to 1.24) CP with magnesium exposure was found in a logistic regression model that controlled for gestational age, fetal growth, gender, multiple birth status, mode of delivery, amnionitis, and hypertensive disorders. In a small subset of infants, those with onset of parenchymal lesions at 7 days of age or later (n 5 29), magnesium exposure was associated with a significantly reduced risk of DCP (OR, 0.10; 95% CI, 0.02 to 0.65). Magnesium sulfate exposure was not associated with germinal matrix/intraventricular hemorrhage (adjusted OR, 0.89; 95% CI, 0.64 to 1.25) or with parenchymal brain lesions (adjusted OR, 0.83; 95% CI, 0.53 to 1.30). Conclusions. The hypothesis that magnesium sulfate use reduces the risk of neonatal brain lesions or CP in low birth weight infants was not statistically supported in this study, although a modest reduction in risk of DCP cannot be excluded. The data further suggest that magnesium exposure may be associated with reduction in risk of CP in low birth weight infants who have lateonset brain lesions, but this unpredicted observation requires confirmation in another data set. Pediatrics 1997; 99(5). URL: http://www.pediatrics.org/cgi/content/full/99/ 5/e1; cerebral palsy; magnesium sulfate; infant, low birth weight; preeclampsia; cerebral hemorrhage, infant. ABBREVIATIONS. PE, preeclampsia; CP, cerebral palsy; NBH, Neonatal Brain Hemorrhage (cohort); DCP, disabling CP; GM/ IVH, germinal matrix or intraventricular hemorrhage; PEL/VE, parenchymal lesion/ventricular enlargement; HYP, hypertension; OR, odds ratio; CI, confidence interval. Magnesium sulfate is widely used in obstetric practice both to treat preeclampsia (PE) and to attempt to arrest the progress of premature labor. A recent case-control study in infants weighing less than 1500 g at birth demonstrated a substantial reduction in cerebral palsy (CP) in children whose mothers received magnesium sulfate in labor.1 This observation is coherent with the multiple catalytic roles of magnesium in cellular enzyme systems and neuronal functioning2 and particularly with evidence that magnesium can block the N-methyl-daspartate receptor and thus prevent excitatory amino acids, commonly released during episodes of hypoxia and ischemia, from producing neuronal damage.3 We set out to test the hypothesis suggested by this case-control study, namely, that magnesium exposure is associated with a decreased risk of CP in the Central New Jersey Neonatal Brain Hemorrhage (NBH) cohort. In the NBH cohort, low birth weight infants were assessed prospectively with cranial ultrasound scanning in the neonatal period and examined at 2 years of age for the presence or absence of CP. Included in this cohort of 1105 infants are 362 infants whose mothers received magnesium sulfate, 280 infants with ultrasonographically diagnosed neonatal brain lesions, and 113 children with the diagnosis of either disabling CP (DCP) or nondisabling CP. This study thus provides considerable power to assess the relationships of magnesium sulfate exposure to important neurologic outcomes in the neonatal and early childhood periods.