Magnesium Sulfate Tocolysis Research Articles

Risk factors for intraventricular haemorrhage in very low birth weight infants.

In a prospective study at Uludag University Hospital, 120 premature infants with birthweights of 1500 g or less were screened for intraventricular hemorrhage (IVH) using cranial ultrasound. With the purpose of studying the incidence of IVH, the associated risk factors for these neonates were considered. We studied all the very low birth weight infants admitted in our neonatal unit. We examined the following variables as risk factors for IVH: sex, birth weight, gestational age, Apgar score, mechanichal ventilation, hypercapnia, use of antenatal steroids, tocolytic drugs, vaginal versus cesarean section delivery, and inborn versus outborn status, vasopressor infusion (any vasoactive drug such as dopamine, dobutamine, or epinephrine) not associated with resuscitation, and surfactant administration. The incidence of IVH was 15% (18/120), 50% grade I (9/18), 17% grade II (3/18), 11% grade III (2/18), and 22% grade IV (4/18). IVH occurred mainly in the first week of life (78%; 14/18). The significant risk factors for IVH were found to be prematurity, outborn status, low 5 minute Apgar score, vaginal delivery, hypercapnia, mechanical ventilation, hypotension, and use of vasopressors on the day of admission. Significant protective factors against IVH included antenatal steroid therapy, cesarean section, magnesium sulfate tocolysis, increasing gestational age, and increasing birth weight. Our results concur with the notion that a tertiary center is the optimal location for delivery of the high risk neonate. Transportation of infants in utero to a perinatal center specializing in high risk-deliveries results in a decreased incidence of IVH when compared to infants transported postnatally. Aggressive resuscitation, with avoidance of hypercarbia, and rapid restoration of hypovolemia could potentially reduce the incidence of PVH/IVH.

Pancreatitis secondary to hyperparathyroidism during pregnancy

Background: It has been suggested that magnesium can be used to reduce serum calcium levels seen with hyperparathyroidism during pregnancy, thus reducing maternal and fetal risk. Case: A young woman presented at 32 weeks’ gestation with abdominal pain from pancreatitis caused by hyperparathyroidism from a parathyroid adenoma. She was started on magnesium sulfate tocolysis for preterm labor. During treatment, serum parathyroid hormone was undetectable, but serum calcium and vitamin D-1,25 were elevated. When magnesium was discontinued, her vitamin D-1,25 was suppressed and the parathyroid hormone was elevated. Conclusion: For some patients, because of persistent hypercalcemia, magnesium sulfate might not be a viable treatment option for hyperparathyroidism during pregnancy.

Tocolytic Magnesium Sulfate Exposure and Risk of Cerebral Palsy Among Children With Birth Weights Less than 1,750 Grams

The authors examined the relation between intrapartum magnesium sulfate exposure and risk of cerebral palsy in a case-control study of low birth weight children designed to control for confounding by the clinical indications for magnesium in pregnancy. Case children (n = 97) included all singleton children with cerebral palsy who were born in 1985-1989 in Atlanta, Georgia with a birth weight less than 1,750 g and whose mothers had not had a hypertension-related disease during pregnancy. Control children (n = 110) were randomly selected from the infant survivors using identical selection criteria. Data on magnesium sulfate exposure, labor and delivery, and infant characteristics were abstracted from hospital records. The authors found no association between exposure to magnesium sulfate and cerebral palsy risk (odds ratio = 0.9; 95% confidence interval: 0.3, 2.6) either in all children or in subgroups with varying likelihoods for exposure to magnesium. However, the association did vary by birth weight, with a protective effect being seen in children born weighing less than 1,500 g and an elevated risk in children with birth weights of 1,500 g or more; all confidence intervals included 1.0 except for the combined <1,500 g group. Several ongoing randomized clinical trials of magnesium and cerebral palsy may shed more definitive light on this relation.

Magnesium sulfate tocolysis prolongs QT interval

Objective: Magnesium sulfate (MgSO 4) tocolysis causes maternal ionized calcium (Ca ++) to fall precipitously. Changes in Ca ++ levels are known to alter electrical conduction in the heart, possibly resulting in arrhythmias. The goal of this study was to determine the effects on maternal QT interval when intravenous MgSO 4 is used for tocolysis in preterm labor. Methods: All patients admitted for MgSO 4 tocolysis were considered for the study. Patients with any underlying medical conditions were excluded. Levels of ionized calcium, calcium, potassium, phosphate, magnesium (Mg ++), and albumin, and an electrocardiogram (ECG) were obtained before initiation of MgSO 4. These labs and ECG were repeated after 12 hours of tocolysis and again after 24 hours. Magnesium sulfate was given as a 4-g bolus and continued as a 2–3 g/hour infusion. Results: In the initial six patients, the QTc was prolonged in all patients by 12 hours. At 24 hours, the QTc further lengthened in two out of six patients. In the other four women, the QTc remained longer than the initial measurement but did not continue to be prolonged. During the initial 12 hours, the average Mg ++ level was 6.2 mg/dL and the Ca ++ had declined an average of 19 % for five of the six patients. Conclusion: In this preliminary study, intravenous MgSO 4 tocolysis had an effect on the level of ionized calcium and the length of the QTc. This effect occurred within 12 hours of tocolysis. Whether this results in an adverse effect in certain individuals remains to be determined.

Magnesium sulfate therapy affects attention and working memory in patients undergoing preterm labor

Objective: Patients commonly consent to undergoing invasive procedures while receiving magnesium sulfate therapy. This study evaluated the effects of magnesium sulfate on attention, comprehension, and memory in patients undergoing preterm labor. Study Design: Consenting patients were studied while receiving(study) and not receiving (control) intravenous magnesium sulfate tocolysis for preterm labor. Excluded were patients with possible preeclampsia, imminent delivery, sedative administration, or prior mental illness. Patient comprehension was assessed with the Boston Diagnostic Aphasia Examination. Level of attention and working memory were evaluated with the Paced Auditory Serial Addition Test. Verbal learning, short-term memory, and recognition were determined with the Hopkins Verbal Learning Test. Gross mental-neurologic deficits were evaluated with the Mini-Mental Status Examination. The tests were administered by the same examiner. Control testing was performed >24 hours after intravenous magnesium sulfate was discontinued. Magnesium levels were obtained at the time of testing. The primary outcome measure was the Paced Auditory Serial Addition Test score because of its ability to elicit subtle differences in attention capacity. Statistical analysis included the paired t test and the McNemar test. Results: Fifteen patients completed the study. Paced Auditory Serial Addition Test scores were significantly higher (ie, more errors were made) during magnesium sulfate therapy than periods without therapy (14 ± 8 vs 7 ± 7; P < .05). Comprehension (Boston Diagnostic Aphasia Examination score) was not different between the groups ( P = .7). There was no difference in short-term memory (Hopkins Verbal Learning Test) or gross mental-neurologic deficits between the 2 groups (all P > .1). Conclusions: Magnesium sulfate therapy appears to have an effect on attention and working memory but not on long-term memory or comprehension. The significant differences in Paced Auditory Serial Addition Test scores reveal deficits in information-processing ability in patients on a regimen of magnesium sulfate therapy. (Am J Obstet Gynecol 2000;183:940-4.)

Magnesium sulfate for tocolysis and risk of spastic cerebral palsy in premature children born to women without preeclampsia

Objective: Our aim was to examine magnesium sulfate tocolysis and cerebral palsy in infants born prematurely to women without preeclampsia. Study Design: We conducted a retrospective case-control study of infants with birth weights <1500 g and of infants with birth weights from 1500 to 1999 g who were born at <33 weeks’ gestation. The study infants were born in level 2 or level 3 hospitals from 1988 through 1994 to women without preeclampsia, were delivered >3 hours after admission, and had survived to age 2 years. Results: Among 170 children with cerebral palsy and 288 control subjects, similar proportions of case mothers (58%) and control mothers (62%) had received magnesium sulfate tocolysis. In women with some tocolytic treatment, these proportions were 78% and 76%, respectively. The duration of treatment with magnesium was comparable for case and control women, as were the intervals from beginning and termination of treatment to delivery. Adjustment for gestational age, birth weight, and other variables did not alter this result. Conclusion: Magnesium exposure was not associated with a lower risk of cerebral palsy in infants born prematurely to women without preeclampsia. The difference between this finding and that in our previous study showing an apparent neuroprotective effect of magnesium is not explained by the more restrictive selection criteria used here and may be related to a number of changes in medical practice between the 2 periods. (Am J Obstet Gynecol 2000;183:717-25.)

Perinatal Death and Tocolytic Magnesium Sulfate

In Brief Objective To determine whether there is a significant association between perinatal mortality and exposure en route for 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, χ2 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. Higher total doses of tocolytic magnesium sulfate are associated with an increased risk of perinatal death among infants with birth weights of 700–1249 g.

Perinatal death and tocolytic magnesium sulfate

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, χ 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.

Tocolytic magnesium sulfate exposure and risk of cerebral palsy among children with birth weights less than 1,750 grams.

The authors examined the relation between intrapartum magnesium sulfate exposure and risk of cerebral palsy in a case-control study of low birth weight children designed to control for confounding by the clinical indications for magnesium in pregnancy. Case children (n = 97) included all singleton children with cerebral palsy who were born in 1985-1989 in Atlanta, Georgia with a birth weight less than 1,750 g and whose mothers had not had a hypertension-related disease during pregnancy. Control children (n = 110) were randomly selected from the infant survivors using identical selection criteria. Data on magnesium sulfate exposure, labor and delivery, and infant characteristics were abstracted from hospital records. The authors found no association between exposure to magnesium sulfate and cerebral palsy risk (odds ratio = 0.9; 95% confidence interval: 0.3, 2.6) either in all children or in subgroups with varying likelihoods for exposure to magnesium. However, the association did vary by birth weight, with a protective effect being seen in children born weighing less than 1,500 g and an elevated risk in children with birth weights of 1,500 g or more; all confidence intervals included 1.0 except for the combined <1,500 g group. Several ongoing randomized clinical trials of magnesium and cerebral palsy may shed more definitive light on this relation.

Fetal cardiovascular function during prolonged magnesium sulfate tocolysis.

The purpose of this study was to evaluate the fetal cardiovascular function during prolonged magnesium sulfate tocolysis. We performed a fetal ultrasonographic examination in 15 patients (Mg group) during magnesium sulfate tocolysis for the treatment of preterm labor. The maternal serum magnesium concentration was 5.7 +/- 0.5 mg/dl at the time of the examination. Sixteen fetuses in normal pregnancies at similar gestational ages were used as the control group. The fetal heart rate and the middle cerebral artery pulsatility index in the Mg group were lower than in the control group (p < 0.01). Fractional shortening (FS) of the right ventricle in the Mg group was lower (p < 0.01), while FS of the left ventricle was higher (p < 0.01) than in the controls. The calculated blood flow through the tricuspid orifice in the Mg group was lower than in the control group (p < 0.01). In contrast, the blood flow through the mitral orifice in the Mg group was higher than in the control group (p < 0.01). In conclusion, in spite of the fact that the right ventricular function is depressed, the fetus maintains its cardiac output during prolonged hypermagnesemia by increasing its left ventricular function. These results indicate the different fetal intracardiac and peripheral circulation, especially in the brain, from normal fetuses.

The Effect of Maternal Magnesium Sulfate Treatment on Neonatal Morbidity in ≤1000-Gram Infants

Data from retrospective observational studies suggest that fetal exposure to magnesium sulfate may correlate with a lower risk of both intraventricular hemorrhage and cerebral palsy in live-born infants. The present study, also retrospective, was done to learn whether extremely low birth weight (1000 gm or less) infants who live at least 2 days after being born to a woman given magnesium for uterine tocolysis had neonatal outcomes differing from those of unexposed infants. Only potentially viable singleton infants with a gestational age of at least 20 weeks were included. None had major congenital anomalies. The final study group of 308 infants, seen in a 12-month period, included 124 exposed in utero to magnesium sulfate and 184 who were not so exposed. Mortality from day 3 to 4 months of life was similar in the two groups. Women given magnesium sulfate for tocolysis were less often black, were more often in active labor at the time of delivery, and received more steroids, but in other respects, the groups were comparable. The infants were similar in birth weight and gestational age at delivery, and there were no significant differences in neonatal morbidity. Multivariate analysis affirmed the lack of any significant association between neonatal disorders and exposure to magnesium sulfate. This included measures of neurological morbidity such as seizure activity and intraventricular bleeding. A prospective randomized trial is needed before concluding that intrapartum magnesium sulfate does not improve the neurological outcome in very premature infants.

Predicting Delivery Within 48 Hours in Women Treated With Parenteral Tocolysis

In Brief Objective To develop a prediction rule using clinical admission characteristics for women treated with parenteral tocolysis for preterm labor who are at highest risk of delivery within 48 hours. Methods We performed a case-control study of patients treated with magnesium sulfate for idiopathic preterm labor. A case was defined as a patient who received magnesium sulfate tocolysis and delivered within 48 hours of admission. We selected a 48-hour delay to delivery as a clinically relevant endpoint for the maximization of steroid benefit. Controls were patients who received magnesium sulfate tocolysis and remained undelivered 48 hours after admission. Cases and controls were identified by merging a pharmacy billing database with International Classification of Disease codes for premature labor. Medical records were reviewed and risk factor information was obtained. We focused on risk factors within the first hour of admission, because our goal was to identify patients at high risk of delivery early in their hospital course. Backward stepwise logistic regression was used to develop explanatory and predictive models. The focus of the predictive model was to maximize the test's sensitivity and negative predictive value. Results We identified 50 cases and 150 controls. The following six variables were included in the initial multivariable models based on bivariate analyses: white blood cell count at least 14.0 (1000/μL), cervical dilation at least 2 cm, bleeding, substance abuse, parity, and previous abortion. A two-variable model containing cervical dilation and bleeding had an overall accuracy of 73%, sensitivity of 62%, and specificity of 76%, and it was as sensitive and specific as more complex models. Conclusion Cervical dilation of at least 2 cm and bleeding on admission had an overall accuracy of 73% in predicting the likelihood of delivery within 48 hours in women receiving magnesium sulfate. Cervical dilation of 2 cm or more and bleeding on admission predict likelihood of delivery within 48 hours in women receiving magnesium sulfate.

Predicting delivery within 48 hours in women treated with parenteral tocolysis

Objective: To develop a prediction rule using clinical admission characteristics for women treated with parenteral tocolysis for preterm labor who are at highest risk of delivery within 48 hours. Methods: We performed a case-control study of patients treated with magnesium sulfate for idiopathic preterm labor. A case was defined as a patient who received magnesium sulfate tocolysis and delivered within 48 hours of admission. We selected a 48-hour delay to delivery as a clinically relevant endpoint for the maximization of steroid benefit. Controls were patients who received magnesium sulfate tocolysis and remained undelivered 48 hours after admission. Cases and controls were identified by merging a pharmacy billing database with International Classification of Disease codes for premature labor. Medical records were reviewed and risk factor information was obtained. We focused on risk factors within the first hour of admission, because our goal was to identify patients at high risk of delivery early in their hospital course. Backward stepwise logistic regression was used to develop explanatory and predictive models. The focus of the predictive model was to maximize the test’s sensitivity and negative predictive value. Results: We identified 50 cases and 150 controls. The following six variables were included in the initial multivariable models based on bivariate analyses: white blood cell count at least 14.0 (1000/μL), cervical dilation at least 2 cm, bleeding, substance abuse, parity, and previous abortion. A two-variable model containing cervical dilation and bleeding had an overall accuracy of 73%, sensitivity of 62%, and specificity of 76%, and it was as sensitive and specific as more complex models. Conclusion: Cervical dilation of at least 2 cm and bleeding on admission had an overall accuracy of 73% in predicting the likelihood of delivery within 48 hours in women receiving magnesium sulfate.

Is adverse pregnancy outcome predictable after blunt abdominal trauma?

Objective: The aim of the study was to evaluate the following: (1) pregnancy outcome after blunt abdominal trauma and (2) factors that may predict preterm birth and adverse peripartum outcomes. Study Design: All women who had noncatastrophic abdominal trauma and came to the labor and delivery suite July 1994-August 1997 were prospectively evaluated and admitted for continuous uterine and fetal monitoring. A complete blood cell count, coagulation profile, and Kleihauer-Betke stain were performed. Ultrasonographic examination was performed to rule out hematoma. Tocolytic agents were administrated in cases with persistent contractions. Pregnancy outcomes and risk factors were compared between those with preterm birth before 37 weeks’ gestation and those who were delivered after 37 weeks’ gestation. Results: Delivery information was available for 85 women with blunt abdominal trauma from motor vehicle accident (28), falls (27), and direct assault (30, which included 17 cases of domestic abuse). Four women, 3 of whom were exposed to domestic abuse, were hospitalized twice. Thirteen patients had preterm birth and 72 patients were delivered at term. In all cases the results of Kleihauer-Betke stains, maternal vital signs, blood cell count, coagulation profile, and placental ultrasonographic examinations were normal. The differences between the 2 groups with respect to gestational age at the time of trauma, length of hospital stay, subjective reports of abdominal pain, objective findings of abdominal tenderness, patterns of uterine contractions, interval between trauma and delivery, and Apgar scores were not statistically significant. However, the preterm birth group received magnesium sulfate tocolysis more frequently (31% vs 7%) and had a significantly greater rate of peripartum complications, such as rupture of membranes and abruptio placentae, than the group of patients who delivered at term (46.2% vs 12.5%, P < .05). Women with domestic abuse had increased uterine contractions at the time of abdominal trauma (52.9% vs 19.1%, P = .01) but did not require increased use of tocolysis. Women with domestic abuse had more peripartum complications (41.8% vs 11.8%, P < .01). Conclusions: Women with noncatastrophic blunt abdominal trauma in pregnancy tend to have favorable neonatal outcomes. Findings or reports of abdominal tenderness and uterine contractions are not predictive of preterm birth. Preterm birth was associated with increased peripartum complications. However, domestic abuse was associated with repeated trauma in the index pregnancy and increased peripartum complications. (Am J Obstet Gynecol 1998;179:1140-4.)

Terbutaline pump maintenance therapy for prevention of preterm delivery: A double-blind trial

Objective: This study’s aim was to determine whether maintenance therapy with terbutaline administered by pump prolongs gestation in women after treatment with intravenous magnesium sulfate tocolysis for suspected preterm labor. Study Design: Consenting women with a singleton gestation and intact membranes who had uterine contractions and >1 cm cervical dilation, 80% effacement, or progressive cervical change and whose contractions were successfully arrested with intravenous magnesium were randomly assigned to receive either terbutaline or normal saline solution placebo by subcutaneous infusion pump. Pump therapy was administered with a standardized protocol. Pump therapy was discontinued and parenteral magnesium was resumed if recurrent preterm labor developed while women were on the therapeutic regimen at <34 weeks’ gestation and no contraindication for tocolysis existed. If recurrent labor was arrested, pump therapy was restarted according to the original treatment group. A sample size of 48 women was required to detect a 2-week intergroup difference in mean time to delivery. Analyses were based on intent to treat. Results: Fifty-two women received terbutaline (n = 24) or placebo (n = 28). At random assignment the groups were similar with respect to age, race, parity, previous preterm delivery, gestational age, and cervical examination. Overall there was a 1-day difference in mean time to delivery between the groups (terbutaline 29 ± 22 days and placebo 28 ± 23 days, P = .78). There were no differences in the rates of preterm delivery at <34 and <37 weeks’ gestation. Neonatal outcomes were similar. Conclusions: Maintenance terbutaline therapy administered by pump does not prolong gestation in women successfully treated for suspected preterm labor. (Am J Obstet Gynecol 1998;179:874-8.)

If tocolytic magnesium sulfate is associated with excess total pediatric mortality, what is its impact?

The Magnesium and Neurologic Endpoints Trial was a randomized controlled trial (RCT) done to learn whether or not receiving magnesium sulfate during preterm labor could prevent cerebral palsy. Unexpectedly, in the tocolytic arms of the trial, seven (including one set of twins) of 46 cases assigned to receive magnesium ended in total pediatric mortality (fetal + neonatal + postneonatal), compared to none of 47 cases assigned to other tocolytics ending in death. The difference between the two treatment arms is highly statistically significant (risk difference 15.2%; 95% confidence interval 4.8, 25.6; P = .006). If this relationship is confirmed by experimentation with animals or through the conduct of a large RCT at other institutions, it is possible that tocolytic magnesium will be found to be associated with the deaths of several thousand newborns in the United States annually. If the true excess total pediatric mortality is 10%, and if magnesium accounts for 40% of all tocolytics used, then tocolytic magnesium increases the absolute number of infant deaths by about 4800 every year.

Magnesium sulfate tocolysis and risk of neonatal death

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 neonatal 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, placenta previa, or bleeding on admission. CONCLUSIONS: Magnesium sulfate tocolysis was not associated with increased neonatal mortality in premature 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.)

Successful magnesium sulfate tocolysis: Is “weaning” the drug necessary?

OBJECTIVE: Magnesium sulfate is the most commonly used tocolytic agent for preterm labor. A common clinical practice is to slowly discontinue the drug (wean) after successful tocolysis. Our objective was to determine the necessity of this practice. STUDY DESIGN: A prospective, randomized clinical trial was performed from June 1993 to July 1996. After successful magnesium sulfate tocolysis, patients with preterm labor were randomized to two groups: stopping the drug abruptly (no weaning) or gradually weaning the drug (approximately 1 gm every 4 hours). Preterm labor was defined as documented cervical change with regular uterine contractions or regular uterine contractions with a cervix of 2 cm and 75% effacement. The primary outcome variable was the necessity to reinstitute magnesium sulfate therapy within 24 hours of discontinuation of successful tocolysis. RESULTS: One hundred forty-one patients completed the study. No patient in the no-wean group required retocolysis within 24 hours of magnesium discontinuation. However, eight patients in the wean group required retocolysis within 24 hours of magnesium discontinuation ( p = 0.01). Significantly more patients in the wean group had retocolysis during pregnancy (3 vs 12, p = 0.03). Patients in the wean group were also in the labor and delivery unit longer and, as would be anticipated, received magnesium sulfate significantly longer. No differences in the neonatal outcomes were noted between the two groups. Seventy-seven percent of the patients in the study were delivered prematurely. CONCLUSION: This study demonstrated an increased need for retocolysis in the group weaned from magnesium sulfate. We also found that patients in the wean group had an increased labor and delivery time and a longer administration time of magnesium sulfate. Thus weaning magnesium sulfate increases health care cost. The practice of weaning magnesium sulfate does not appear beneficial. (Am J Obstet Gynecol 1997;177:742-5.)

Magnesium tocolysis as the cause of urinary calculus during pregnancy

Twenty-one days of magnesium sulfate tocolysis were performed on a 28-year-old woman because of preterm labor at 31 weeks gestation. In association with this tocolysis, urinary calculus of magnesium ammonium phosphate occurred at 34 weeks gestation. J. Matern.–Fetal Med. 6:296–297, 1997. © 1997 Wiley-Liss, Inc.

Lack of effect of antenatal indomethacin on fetal cerebral blood flow

OBJECTIVE: Our purpose was to investigate fetal cerebral blood flow and the incidence of intraventricular hemorrhage in patients undergoing tocolysis with either indomethacin or magnesium sulfate at <30 weeks' gestation. STUDY DESIGN: Consenting patients at <30 weeks' gestation with preterm labor were randomized to receive indomethacin or magnesium sulfate tocolysis. Magnesium sulfate was administered intravenously with an 8 gm loading dose given over the first hour, 4 gm over the second hour, and then a maintenance infusion of 2.5 gm per hour. The infusion was continued for approximately 12 hours after the cessation of uterine contractions. Patients randomized to receive indomethacin were given an initial dose of 50 to 100 mg orally or per rectum, followed by 25 to 50 mg orally every 4 to 6 hours for 24 to 48 hours. Oral tocolytic agents were not used after successful tocolysis. Betamethasone was administered to all patients. Patients underwent fetal cerebral Doppler studies during tocolytic therapy and at least 24 hours after completion of the treatment. RESULTS: Twelve patients were randomized to receive indomethacin and twelve patients were randomized to receive magnesium sulfate. Twenty-one fetuses underwent cerebral Doppler studies in triplicate during and after therapy. The mean gestational age at tocolysis was 27.5 ± 1.9 weeks for the indomethacin group and 26.4 ± 1.6 weeks for the magnesium sulfate group ( p = 0.14). The middle cerebral artery resistance index for fetuses during indomethacin treatment was 0.73 ± 0.09, whereas the resistance index after therapy was 0.75 ± 0.05 ( p = 0.49). The resistance index during magnesium sulfate tocolysis was 0.79 ± 0.04 and after therapy it was 0.76 ± 0.04 ( p = 0.18). There was no significant difference in the resistance index between the groups on or off therapy. In addition, the incidence of intraventricular hemorrhage was similar in both groups. CONCLUSION: These results suggest that indomethacin does not significantly affect fetal cerebral blood flow. If antenatal indomethacin in the preterm fetus increases the risk of intraventricular hemorrhage, it would appear to be by another mechanism. (Am J Obstet Gynecol 1997;176:1166-71.)