Objective
The purpose of this study was to estimate neonatal intensive care unit and special care unit (NICU) admission rates and care needs among term and late-preterm neonates who are exposed to antenatal magnesium sulfate.
Study Design
We conducted a retrospective cohort study of all singleton neonates of ≥35 weeks’ gestation who were exposed immediately antenatally to magnesium sulfate for maternal eclampsia prophylaxis (August 2006 through July 2008).
Results
Fifty-one of 242 neonates (21.1%) who, at ≥35 weeks’ gestation, had been exposed to antenatal magnesium sulfate were admitted to the NICU. NICU admission was associated in a dose-dependent fashion with total hours and mean dose of magnesium: >12 hours exposure, odds ratio, 2.81 (95% confidence interval, 1.31–6.03); >30 g exposure, odds ratio, 2.59 (95% confidence interval, 1.22–5.51). Infants in NICU who were diagnosed with hypermagnesemia required fluid or nutritional support more frequently (91.3% vs 39.3%; P < .001) than those without hypermagnesemia.
Conclusion
Antenatal magnesium sulfate exposure is associated with NICU admission among term and late-preterm neonates in a dose-dependent fashion. Fluid and nutritional assistance commonly are needed in this cohort.
Magnesium sulfate is one of the most commonly prescribed intravenous medications in obstetric medicine today. Magnesium sulfate has been shown to be superior to other agents for eclampsia prophylaxis and is the most frequently used medication for this purpose in the United States. Magnesium sulfate is also the first choice tocolytic for many obstetricians who care for hundreds of thousands of women who experience preterm labor each year. Additionally, the long-term risks and benefits of in utero magnesium exposure for the purposes of neuroprotection have been studied widely by large-scale prospective studies.
Despite the wealth of publications regarding the potential long-term neonatal effects of magnesium sulfate exposure, little has been studied about the short-term impact of magnesium sulfate on neonatal adaptation and well-being. A recent prospective investigation by Lyell et al that compared magnesium sulfate to nifedipine for tocolysis in the setting of preterm labor demonstrated that, although there were no differences in the primary outcome of delay in delivery between the 2 groups, preterm neonates who were exposed to magnesium had twice the length of stay in the neonatal intensive care unit, compared with those exposed to nifedipine. Differences between groups in acute care included an increase in respiratory assistance and feeding difficulties in the magnesium-exposed neonates, compared with those neonates who were exposed to nifedipine.
Our aim was to estimate the neonatal intensive care (level III) and special care (level II) unit admission rates among a population of term and late-preterm neonates who had been exposed acutely to magnesium sulfate in utero for maternal eclampsia prophylaxis in the setting of preeclampsia and to describe factors that are associated with neonatal intensive care unit (NICU) admission in this cohort.
Materials and Methods
We conducted a retrospective cohort study of newborn infants who were born at ≥35 weeks’ gestation at the Lucile Packard Children’s Hospital at Stanford University, Stanford, CA. All singleton deliveries between August 2006 and July 2008 with an admission or discharge diagnosis that was related to preeclampsia were identified. All maternal charts were reviewed to identify all women who received magnesium sulfate for eclampsia prophylaxis in the period immediately preceding delivery. Women who did not receive magnesium sulfate before delivery were excluded; the reasons that a woman might not receive magnesium sulfate before delivery included failure to confirm an antepartum diagnosis of preeclampsia by the treating physician, physician discretion, or contraindication to magnesium sulfate. The charts of all neonates in the magnesium-exposed cohort were then reviewed to determine admission to the neonatal intensive care nursery and special care nursery (hereafter referred to as NICU). Neonates were considered to have been admitted to the NICU if they were admitted either at birth or at any time before discharge from the hospital. In our institution, the special care nursery provides a high level of transitional care that includes respiratory support. Neonates were considered to have been admitted to the well-baby nursery (WBN) if the neonate remained in the care of the WBN throughout the hospital stay. Multiple gestations were excluded from analysis, as were neonates who met any antenatal criteria for automatic NICU admission, including maternal clinical chorioamnionitis before delivery and major fetal anomalies requiring immediate evaluation. Once the cohort was identified, all maternal and neonatal charts were abstracted.
The primary outcome was NICU admission. Maternal, labor and delivery, and neonatal variables were analyzed to determine associations with NICU admission. Gestational age of ≥35 weeks was determined by best obstetric estimate, which included ultrasound scanning. Total maternal magnesium sulfate exposure included only medication that had been administered in the period preceding delivery. A standard magnesium sulfate infusion protocol was used by providers throughout the study period and consisted of a 4-g bolus of intravenous magnesium sulfate over 20-30 minutes, followed by 1-2 g per hour. The total dose of magnesium sulfate that had been administered before delivery was determined by a review of medication infusion records for each patient.
During the study period, standard definitions of preeclampsia were used by the treating physicians according to the following criteria, and chart review was conducted to ensure consistency with these definitions. Mild preeclampsia was defined as new onset hypertension with systolic blood pressure of ≥140 mm Hg and/or diastolic blood pressure of ≥90 mm Hg with proteinuria ≥1+ on dipstick, urine protein–to–creatinine ratio of ≥0.3, or total protein of ≥300 mg on a 24-hour urine collection. Severe preeclampsia was defined as meeting the criteria for mild preeclampsia plus at least one of the following criteria: systolic blood pressure of ≥160 mm Hg or diastolic blood pressure ≥105 mm Hg, urine protein–to–creatinine ratio of ≥5, or ≥5 g of protein on 24-hour urine collection or evidence of end organ damage that was the result of persistent neurologic symptoms, pulmonary edema, elevated hepatic aminotransferases that were ≥2 times normal values, oliguria ≤30-mL urine output per hour or serum creatinine level of ≥1.0 mg/dL, platelet count <100,000, or evidence of fetal/placental involvement that included intrauterine growth restriction of ≤10th percentile by the Hadlock nomogram, oligohydramnios with an amniotic fluid index of ≤5, or placental abruption. Preeclampsia was considered to be superimposed if preexisting hypertension was complicated by new onset or suddenly worsening proteinuria, a sudden increase in blood pressure, or other associated features in accordance with definitions from the American College of Obstetricians and Gynecologists. Large for gestational age was defined as a birthweight at >90th percentile for gestational age; small for gestational age was defined as a birthweight of <10th percentile for gestational age.
Among the NICU group, data were abstracted that included the admission and discharge diagnoses, length of stay in the NICU, and type of treatment required. Neonatal admission and discharge diagnoses were abstracted as they were entered into the medical record by the treating physicians, who included resident physicians, neonatology fellows, and supervising neonatal faculty members. Suspected neonatal hypermagnesemia was defined clinically by the NICU treating physicians, based on evidence of hypotonia, respiratory depression, and poor gastrointestinal motility. Serum magnesium levels were checked in all neonates who had clinical signs of hypermagnesemia that were based on these criteria. Neonatal requirement for respiratory support was defined as a need for oxygen supplementation by any means, which included nasal cannula, continuous positive airway pressure, or intubation. Requirement for fluid/nutritional support was defined as a need for any intravenous fluids or nutritional supplementation.
Data were tested for normality by the Shapiro-Wilk test and analyzed by χ 2 and Fisher’s exact tests for categoric data, Kruskal-Wallis for nonparametric analysis, and multivariable logistic regression analysis to control for potential confounding variables. Predicted dose-response curves were generated from the logistic regression models. STATA software (version 7; StataCorp, College Station, TX) was used for all analyses. An alpha value of < .05 was considered significant. This study was approved by the Institutional Review Board at Stanford University Medical Center.
Results
Four hundred ninety-eight neonates at ≥35 weeks’ gestation were identified. Two hundred fourteen neonates were excluded for not having been exposed to magnesium sulfate during labor, either because their mothers received magnesium sulfate in the postpartum period only or did not receive it at all during the hospitalization. Twenty-nine neonates were excluded because of maternal chorioamnionitis. Three neonates were excluded because of major fetal anomalies. Ten neonates were excluded because of twin gestation. Two hundred forty-two neonates were included in the final analysis. Of the 242 neonates, 51 babies (21.1%) were admitted to the NICU.
Maternal demographics were similar between groups ( Table 1 ). Gestational age was significantly lower in the NICU group ( Table 1 ). Most labors were induced ( Table 2 ); preeclampsia was the indication for nearly 80% of inductions. Cesarean delivery was more frequent in the NICU group than in the WBN group. Indications for cesarean delivery are shown in Table 2 . Severe preeclampsia was a more frequent maternal diagnosis in the NICU group than in the WBN group. Birthweight and 1-minute Apgar scores were significantly lower in the NICU group. There were no differences between groups with regard to rates of meconium-stained amniotic fluid, shoulder dystocia, large for gestational age, or intrauterine growth restriction ( Table 2 ). Umbilical cord blood gases were available for 89 neonates; of those data that were available, no differences were seen between groups (data not shown).
