Serum ionized magnesium during magnesium sulfate administration for preterm labor and preeclampsia

OBJECTIVE: The purpose of this study is to estimate the relations between ionized and total Mg levels during MgSO4 administration in patients with preterm labor and preeclampsia. METHODS: Forty-three pregnant patients who were candidates for MgSO4 were studied (preterm labor, 27; preeclampsia, 16). The administration method was intravenous injection of MgSO4 4 g over 30 min followed by 1-2 g/h. Ionized Mg was measured by the selective ion electrode method at bedside, and compared it with total Mg levels. RESULTS: Significant correlation was existed between levels of ionized and total Mg throughout therapy for both preterm labor (ionized Mg=0.19 x total Mg+0.19; r=0.61, p<0.001) and preeclampsia (ionized Mg=0.20 x total Mg+0.14; r=0.60, p<0.001). CONCLUSION: There are correlations between ionized and total Mg levels during administration of MgSO4 for both preterm labor and preeclampsia.     

Breast engorgement and galactorrhea during magnesium sulfate treatment of preterm labor

Breast engorgement and galactorrhea occasionally occur during tocolysis with ritodrine. We are not aware of breast engorgement and galactorrhea associated with other tocolytics. We report the first case of breast engorgement and galactorrhea during tocolysis with intravenous magnesium sulfate in a generally healthy 24-year-old woman admitted for tocolysis at 30 weeks' gestation. Breast engorgement and galactorrhea gradually subsided after magnesium sulfate was discontinued. The rapid disappearance of both the galactorrhea and the breast engorgement after discontinuation of magnesium sulfate treatment suggests a cause-effect relationship, the mechanism of which remains unclear.     

Celecoxib versus magnesium sulfate to arrest preterm labor: randomized trial

AIM: The effectiveness of the management of preterm birth remains an important health care issue, especially when considering that more than two thirds of singleton neonatal death occurs in preterm labor. The purpose of this study was to compare oral celecoxib with intravenous magnesium sulfate as tocolytic. METHODS: This was a randomized study of patients who were between 24 and 34 weeks of gestation with preterm labor. One hundred and four pregnant women with preterm labor were randomly assigned to receive celecoxib 100 mg b.i.d. for 48 h or intravenous magnesium sulfate (MgSO4) for maximum of 48 h. Outcome variables included delay of delivery for 48 h and the incidence of side-effects. Data was analyzed using the Student t-test and the chi(2) test. RESULTS: There was no difference between the groups over the course of the study in demographic characteristics, cervical examination and amniotic fluid index. Labor was arrested for 48 h was in 42 (81%) and 45 (87%) of the patients in the celecoxib and magnesium sulfate groups, respectively (p-0.298). There were no severe maternal or neonatal complications in either group. CONCLUSION: Celecoxib is as effective as magnesium sulfate for primary tocolysis.     

硫酸镁在保胎治疗中的有效性与安全性

早产作为引起新生儿疾病和死亡的主要原因,已成为产科领域内具有挑战性的问题之一.世界卫生组织将早产明确定义为在孕37周前或259 d前终止的妊娠.全球早产的发病率,特别是孕34周之前的早产发生率明显升高,病死率为75%～80%,占围产儿死亡构成比的第一位,且存活者近半数存在合并症和后遗症,其生存质量的改善远不尽人意[1].     

Calcium homeostasis in pregnant women receiving long-term magnesium sulfate therapy for preterm labor.

OBJECTIVES: The hypothesis of this study is that calcium homeostasis and bone mineralization are altered in pregnant women receiving long-term therapy with magnesium sulfate as compared with similar women not receiving magnesium sulfate to control preterm labor. STUDY DESIGN: Thirty-nine women between 24 and 32 weeks' gestation, matched for age, race, and duration of bed rest, were enrolled. Indices of calcium homeostasis in serum and urine were measured serially, and bone mineralization of the distal radius was measured at 1 and 11 weeks post partum. RESULTS: Magnesium therapy was administered for a mean duration of 26 +/- 14 days and a cumulative dose of 1405 +/- 963 gm. Serum concentrations of magnesium, phosphorus, and parathyroid hormone increased and those of calcium decreased from baseline values in the magnesium sulfate group and remained uniform throughout the 3-week investigation. The serum magnesium, phosphorus, parathyroid hormone, and calcium concentrations in the control group were unchanged during the study and differed significantly from those in the magnesium sulfate group (p < 0.001). Urinary output of magnesium, calcium, and copper was significantly greater in the magnesium sulfate group than in the control group throughout the study. Urinary losses of calcium in the magnesium sulfate group, approximately 800 to 900 mg/day, were substantial. Although radius bone density 1 week post partum did not differ between groups, the change in bone density from 1 to 11 weeks post partum was significantly lower in the magnesium sulfate group than in controls. CONCLUSIONS: These data suggest that calcium homeostasis is altered during and after long-term magnesium sulfate therapy. The marked, prolonged urinary calcium losses may affect maternal bone mineralization.     

Adjunctive use of magnesium sulfate with ritodrine for preterm labor tocolysis

The purpose of the study was to determine if the adjunctive administration of magnesium sulfate with ritodrine would result in decreased dosage requirements of ritodrine, and, therefore, decrease the incidence of ritodrine-associated side effects. Candidates for tocolysis were prospectively randomized so that some received a uniform tocolytic dose of magnesium sulfate in a blinded protocol. All patients received a ritodrine infusion which was titrated in the standard manner to achieve cessation of labor. Evaluations included interval cumulative ritodrine dose, maximal ritodrine infusion rate, fluid balance, and blood chemistry studies. Contrary to our hypothesis, there were significantly more cardiovascular effects in the group that received ritodrine plus magnesium sulfate (11/24) than in the group that received ritodrine alone (1/17) (p less than or equal to 0.02). The predominant side effect was chest pain, frequently associated with electrocardiogram changes indicative of myocardial ischemia. These results are consistent with the current understanding of the regulatory mechanisms of these tocolytic agents. We conclude from the results of our prospective, randomized, blinded study that the adjunctive use of magnesium sulfate with ritodrine is associated with an unacceptable increase in serious side effects and probably does not improve efficacy.     

Oral nicardipine versus intravenous magnesium sulfate for the treatment of preterm labor

OBJECTIVE: The aim of this study was to compare the efficacy and safety of oral nicardipine in acute therapy for preterm labor with those of parenteral magnesium sulfate. STUDY DESIGN: Patients between 24 and 34 weeks' gestation with documented preterm labor were randomly assigned to receive oral nicardipine (n = 57) or intravenous magnesium sulfate (n = 65) as initial tocolytic therapy. Patients in the nicardipine group received a 40-mg loading dose and then 20 mg every 2 hours as needed to stop contractions (total 80 mg). Patients in the magnesium sulfate group received a 6-g bolus followed by 2 to 4 g/h to provide uterine quiescence. Patients could be switched to another tocolytic regimen if they continued to have contractions after 6 hours of therapy. The main outcome variables examined were time to uterine quiescence, time gained in utero, recurrence of preterm labor, failure of tocolysis, and pertinent maternal and neonatal outcomes. RESULTS: There were no significant differences in maternal demographic characteristics between the groups. Among patients who responded with uterine quiescence within 6 hours, there was a significant decrease in the time to uterine quiescence in the nicardipine group (P <.01). Patients in the magnesium sulfate group were more likely to have recurrence of preterm labor necessitating further tocolytic attempts (P =.048). The patients in the magnesium sulfate group had more adverse side effects, mainly nausea and vomiting (P =.004). There were no differences in birth weight, estimated gestational age at delivery, or neonatal complications between the 2 groups. CONCLUSIONS: Oral nicardipine is an effective, safe, and well-tolerated tocolytic agent. In this prospective clinical trial patients randomly assigned to receive oral nicardipine had arrest of preterm labor more rapidly than did those randomly assigned to receive parenteral magnesium sulfate. Patients who received magnesium sulfate were more likely to have adverse medication effects and recurrent preterm labor.     

Randomized comparison of intravenous nitroglycerin and magnesium sulfate for treatment of preterm labor

Objective: To compare the safety and efficacy of high-dose intravenous (IV) nitroglycerin with those of IV magnesium sulfate for acute tocolysis of preterm labor.Methods: Thirty-one women with preterm labor before 35 weeks’ gestation were assigned randomly to IV magnesium sulfate or IV nitroglycerin for tocolysis. Preterm labor was defined as the occurrence of at least two contractions in 10 minutes, with cervical change or ruptured membranes. Acute tocolysis was defined as tocolysis for up to 48 hours. Magnesium sulfate was administered as a 4-g bolus, then at a rate of 2–4 g/h. Nitroglycerin was administered as a 100-μg bolus, then at a rate of 1- to 10-μg/kg/min. The primary outcome measure was achievement of at least 12 hours of successful tocolysis.Results: Thirty patients were available for analysis. There were no significant differences in gestational age, cervical dilation, or incidence of ruptured membranes between groups at the initiation of tocolysis. Successful tocolysis was achieved in six of 16 patients receiving nitroglycerin, compared with 11 of 14 receiving magnesium sulfate (37.5 versus 78.6%, P = .033). Tocolytic failures (nitroglycerin versus magnesium sulfate) were due to persistent contractions with cervical change or rupture of previously intact membranes (five of 16 versus two of 14), persistent hypotension (four of 16 versus none of 14), and other severe side effects (one of 16 versus one of 14). Maternal hemodynamic alterations were more pronounced in patients who received nitroglycerin, and 25% of patients assigned to nitroglycerin treatment had hypotension requiring discontinuation of therapy.Conclusion: Tocolytic failures were more common with nitroglycerin than with magnesium sulfate. The hemodynamic alterations noted in patients receiving nitroglycerin, including a 25% incidence of persistent hypotension, might limit the usefulness of IV nitroglycerin for the acute tocolysis of preterm labor.     

Use of magnesium sulfate to treat hyperstimulation in term labor

Magnesium sulfate has been shown in vivo and in vitro to decrease the frequency of uterine contractions while maintaining the amplitude; we therefore decided to assess the use of magnesium sulfate infusion in cases of uterine hyperstimulation. The medical records were reviewed retrospectively for 37 term pregnant patients diagnosed as having uterine hyperstimulation during labor. None of them had medical or obstetric complications. Twenty-two of them received oxytocin augmentation for abnormal labor. Although the vast majority of these patients had a decrease of the hyperstimulation while being given the magnesium, 31.8% in the group receiving oxytocin alone (P less than .05). Fifteen additional patients received magnesium sulfate for uterine hyperstimulation although they were not receiving oxytocin; of these, 16.7% required cesarean delivery. This rate was no different from that of the patients who required labor augmentation, but was double the overall primary cesarean rate at our hospital. There appears to be a group of patients with abnormal uterine activity (either spontaneous or associated with oxytocin augmentation) that responds to treatment with magnesium sulfate.     

Antenatal exposure to magnesium sulfate and neuroprotection in preterm infants

Cerebral palsy is a leading cause of childhood neuromotor disability and is strongly associated with preterm delivery. Basic science research and some observational studies have suggested a neuroprotective benefit from antenatal exposure to magnesium sulfate. Recent randomized controlled studies and meta-analyses suggest that antenatal exposure to magnesium sulfate before anticipated preterm birth is associated with reduction in the risk of developing cerebral palsy or its associated neurologic disabilities in surviving infants. More importantly. this benefit has been achieved without increasing the risk of perinatal mortality.     

Serum magnesium levels in pregnancy and preterm labor

Pregnancy is marked by a state of hypomagnesemia. The serum magnesium level shows no gestational dependence (mean, 1.79 +/- 0.44 mg/dl) until 33 weeks, at which point it continuously declines. Serum magnesium is not depressed further with the onset of labor at term. Patients in preterm labor have a significantly depressed serum magnesium level (mean, 1.60 +/- 0.46 mg/dl; 21 to 33 weeks; p less than 0.0005). This level was not dependent on whether the etiology for the preterm labor was premature rupture of the membranes (PROM), twin gestation, abruption, placenta previa with bleeding, or chorioamnionitis. With PROM, the serum magnesium level was not depressed prior to the initiation of preterm labor. However, observation of hypomagnesemia for this and other etiologies just prior to the initiation of preterm labor were not available. Possible mechanisms by which hypomagnesemia induces uterine irritability are explored, including inhibition of adenyl cyclase with resultant increase in cytoplasmic calcium levels. Patients with diabetes mellitus appeared to have slightly reduced serum magnesium levels, but the results were not statistically significant. Magnesium levels in patients with preeclampsia were not significantly different from controls. Hypomagnesemia (magnesium 1.4 mg/dl or less) may be a marker for true preterm labor.     

Association between the use of antenatal magnesium sulfate in preterm labor and adverse health outcomes in infants

OBJECTIVE: The purpose of this study was to determine whether the use of antenatal magnesium sulfate prevents adverse outcomes (neonatal intraventricular hemorrhage, periventricular leucomalacia, death, and cerebral palsy). STUDY DESIGN: In a controlled trial, we randomized mothers in preterm labor to magnesium sulfate, "other" tocolytic, or placebo. At delivery, umbilical cord blood was collected for the later determination of serum ionized magnesium levels. Neonatal cranial ultrasound scans were obtained periodically for the diagnosis of intraventricular hemorrhage and periventricular leucomalacia. Among survivors, the diagnosis of cerebral palsy was made at age 18 months. RESULTS: Children with adverse outcomes had higher umbilical cord magnesium levels at delivery. In regression models that controlled for confounders, which included very low birth weight, magnesium remained a significant risk factor (adjusted odds ratio, 3.7; 95% CI, 1.1-11.9; P =.03). CONCLUSION: Contrary to original hypotheses, this randomized trial found that the use of antenatal magnesium sulfate was associated with worse, not better, perinatal outcome in a dose-response fashion.