Magnesium sulfate use for fetal neuroprotection.

PURPOSE OF REVIEW: The aim of this review is to describe the proposed mechanisms of action of magnesium sulfate for fetal neuroprotection, different dosing regimens of the drug that have shown benefit, and to review recent pharmacokinetic studies of the drug to better inform clinicians regarding expected benefits and remaining research questions. RECENT FINDINGS: Retrospective secondary analysis of the beneficial effects of antenatal magnesium sulfate trial database and prospective pharmacokinetic/pharmacodynamic modeling indicate magnesium sulfate administration for duration longer than 18 h, given within 12 h of delivery, and maintaining a maternal serum level of 4.1 mg/dl may maximize the neuroprotective benefits of the drug. SUMMARY: Magnesium sulfate in some dosage given before very preterm pregnancy delivery is beneficial for fetal neuroprotection. The exact dose, duration, and timing of administration to maximize this benefit may be more precisely studied using pharmacokinetic/pharmacodynamic modeling techniques before conducting larger randomized trials.

Does Infection During Pregnancy Outside of the Time of Delivery Increase the Risk of Cerebral Palsy?

Objective We sought to evaluate whether maternal antepartum infection (excluding chorioamnionitis) is associated with cerebral palsy (CP). Study Design This is a secondary analysis from a multicenter trial in women at risk of preterm delivery who received antenatal magnesium sulfate versus placebo. We compared the risk of CP in the children of women who had evidence of antepartum infection over the course of pregnancy to those women who had no evidence of antepartum infection during pregnancy. Results Within a cohort of 2,251 women who met our inclusion criteria, 1,350 women had no history of infection in pregnancy and 801 women had a history of some type of antepartum infection during pregnancy. The incidence of CP was similar between the two groups (4.9 vs 5.0%; p = 0.917). After adjustment for maternal and obstetric confounders, we observed no significantly increased risk of CP among infants born to women with evidence of antepartum infection; (adjusted relative risk [aRR], 1.09 (0.72, 1.66); p = 0.68). Conclusion Compared with women with no evidence of antepartum infection during pregnancy, those women with infections excluding chorioamnionitis may not be at an increased risk of delivering an infant with CP.

Pharmacokinetics and placental transfer of magnesium sulfate in pregnant women.

BACKGROUND: Magnesium sulfate is one of the most commonly prescribed intravenous medications in obstetrics. Despite its widespread use, there are limited data about magnesium pharmacokinetics, and magnesium is prescribed empirically without dose adjustment for different indications. OBJECTIVE: The aim of this study was to characterize the pharmacokinetics and placental transfer of magnesium sulfate in pregnant women and to determine key covariates that impact the pharmacokinetics. STUDY DESIGN: This is a prospective pharmacokinetic cohort study of pregnant women who were prescribed magnesium sulfate for preeclampsia, preterm labor, or extreme prematurity. Women received a 4-g loading dose and 2 g/h maintenance dose as clinically indicated. Maternal blood samples were obtained before and at multiple time points during and after magnesium administration. Cord blood also was sampled at delivery. A population pharmacokinetic approach that used a nonlinear mixed-effects modeling was used to characterize magnesium disposition. RESULTS: Pharmacokinetic profiles of 111 pregnant women were analyzed. Magnesium clearance was 3.98 L/h in preeclamptic women and 5.88 L/h non-preeclamptic women. Steady-state concentration of magnesium was 7.2 mg/dL in preeclamptic women compared with 5.1 mg/dL in non-preeclamptic women. Maternal weight significantly impacted time to steady state. The ratio of the mean umbilical vein magnesium level to the mean maternal serum magnesium level at the time of delivery was 0.94 ± 0.15. CONCLUSIONS: The study accurately characterizes the pharmacokinetics of magnesium administered to pregnant women. Preeclamptic status and maternal weight significantly impact serum magnesium levels. This pharmacokinetic model could be applied to larger cohorts to help tailor magnesium treatment and account for these covariates.

Racial and Ethnic Disparities in Mode of Anesthesia for Cesarean Delivery.

BACKGROUND: Racial and ethnic disparities have been identified in the provision of neuraxial labor analgesia. These disparities may exist in other key aspects of obstetric anesthesia care. We sought to determine whether racial/ethnic disparities exist in mode of anesthesia for cesarean delivery (CD). METHODS: Women who underwent CD between 1999 and 2002 at 19 different obstetric centers in the United States were identified from the Maternal-Fetal Medicine Units Network Cesarean Registry. Race/ethnicity was categorized as: Caucasian, African American, Hispanic, and Non-Hispanic Others (NHOs). Mode of anesthesia was classified as neuraxial anesthesia (spinal, epidural, or combined spinal-epidural anesthesia) or general anesthesia. To account for obstetric and non-obstetric covariates that may have influenced mode of anesthesia, multiple logistic regression analyses were performed by using sequential sets of covariates. RESULTS: The study cohort comprised 50,974 women who underwent CD. Rates of general anesthesia among racial/ethnic groups were as follows: 5.2% for Caucasians, 11.3% for African Americans, 5.8% for Hispanics, and 6.6% for NHOs. After adjustment for obstetric and non-obstetric covariates, African Americans had the highest odds of receiving general anesthesia compared with Caucasians (adjusted odds ratio [aOR] = 1.7; 95% confidence interval [CI], 1.5-1.8; P < 0.001). The odds of receiving general anesthesia were also higher among Hispanics (aOR = 1.1; 95% CI, 1.0-1.3; P = 0.02) and NHOs (aOR = 1.2; 95% CI, 1.0-1.4; P = 0.03) compared with Caucasians, respectively. In our sensitivity analysis, we reconstructed the models after excluding women who underwent neuraxial anesthesia before general anesthesia. The adjusted odds of receiving general anesthesia were similar to those in the main analysis: African Americans (aOR = 1.7; 95% CI, 1.5-1.9; P < 0.001); Hispanics (aOR = 1.2; 95% CI, 1.1-1.4; P = 0.006); and NHOs (aOR = 1.2; 95% CI, 1.0-1.5; P = 0.05). CONCLUSIONS: Based on data from the Cesarean Registry, African American women had the highest odds of undergoing general anesthesia for CD compared with Caucasian women. It is uncertain whether this disparity exists in current obstetric practice.

Does Time of Delivery Influence the Risk of Neonatal Morbidity?

OBJECTIVE: To examine whether time of delivery influences the risk of neonatal morbidity among women with singleton pregnancies. STUDY DESIGN: Secondary analysis of data from the Maternal Fetal Medicine Units Network Factor V Leiden Mutation study. We categorized time of delivery as day (07:00-16:59), evening (17:00-23:59), and overnight (midnight-06:59). Severe neonatal morbidity was defined by at least one of the following: respiratory distress syndrome, transient tachypnea of the newborn, sepsis, seizures, neonatal intensive care admission, or a 5-minute APGAR ≤3. We calculated frequencies of severe neonatal morbidity by time of delivery. Multivariate analysis was performed to determine whether time of delivery was independently associated with severe neonatal morbidity. RESULTS: Among 4,087 women, 1,917 (46.9%) delivered during the day, 1,140 (27.9%) delivered in the evening, and 1,030 (25.2%) delivered overnight. We observed no significant differences in the rates of neonatal morbidity between delivery time periods (day: 12.3%; evening: 12.8%; overnight: 12.6%; p = 0.9). No significant association was observed between time of delivery and neonatal morbidity after adjustment for maternal, obstetric, and peripartum factors. CONCLUSION: Our findings suggest that time of delivery is not associated with severe neonatal morbidity.

Antenatal corticosteroids for preterm premature rupture of membranes: single or repeat course?

OBJECTIVE: The aim of this article is to determine the risk of maternal chorioamnionitis and neonatal morbidity in women with preterm premature rupture of membranes (PPROM) exposed to one corticosteroid course versus a single repeat corticosteroid steroid course. STUDY DESIGN: Secondary analysis of a cohort of women with singleton pregnancies and PPROM. The primary outcome was a clinical diagnosis of maternal chorioamnionitis. Using multivariate logistic regression, we controlled for maternal age, race, body mass index, diabetes, gestational age at membrane rupture, preterm labor, and antibiotic administration. Neonatal morbidities were compared between groups controlling for gestational age at delivery. RESULTS: Of 1,652 women with PPROM, 1,507 women received one corticosteroid course and 145 women received a repeat corticosteroid course. The incidence of chorioamnionitis was similar between groups (single course = 12.3% vs. repeat course = 11.0%; p = 0.8). Women receiving a repeat corticosteroid course were not at increased risk of chorioamnionitis (adjusted odds ratio, 1.28; 95% confidence interval, 0.69-2.14). A repeat course of steroids was not associated with an increased risk of any neonatal morbidity. CONCLUSION: Compared with a single steroid course, our findings suggest that the risk of maternal chorioamnionitis or neonatal morbidity may not be increased for women with PPROM receiving a repeat corticosteroid course.

Perioperative and transfusion outcomes in women undergoing cesarean hysterectomy for abnormal placentation.

BACKGROUND: Women with placenta increta (PI) and placenta percreta (PP) are at high risk of obstetric hemorrhage; however, the severity of hemorrhage and perioperative morbidity may differ according to the degree of placental invasion. We sought to compare blood component usage and perioperative morbidity between women with PI versus PP undergoing cesarean hysterectomy (CH). STUDY DESIGN AND METHODS: We identified 77 women who underwent CH for PI or PP from the NICHD MFMU Network Cesarean Registry, which sourced data from 19 centers from 1999 to 2002. We examined demographic, obstetric, and surgical data and rates of transfusion and perioperative morbidity. We performed statistical tests for between-group analyses; p values less than 0.05 were significant. RESULTS: Rates of intraoperative or postoperative red blood cell (RBC) transfusion were similar between groups (PI 84% vs. PP 88%; p=0.7). We observed no between-group differences in rates of fresh-frozen plasma (FFP) transfusion (intraoperative FFP-PI 30% vs. PP 41%; p=0.3; postoperative FFP-PI 28% vs. PP 18%; p=0.4) or platelet (PLT) transfusion (intraoperative PLTs-PI 14% vs. PP 29%; p=0.2; postoperative PLTs-PI 9% vs. PP 9%; p=1.0). Among the morbidities, a higher proportion of PP women underwent cystotomy (PI 14% vs. PP 38%; p=0.02) and postoperative mechanical ventilation (PI 14% vs. PP 35%; p=0.03). CONCLUSION: Rates of intraoperative RBC, FFP, and PLT transfusion are similar for PI and PP women, and perioperative outcomes are worse for PP women. We suggest the same mobilization transfusion medicine support for both groups, including blood ordering (type and cross-match for CH) and availability of emergency blood protocols including fibrinogen-containing preparations.

Maternal death in the emergency department from trauma.

PURPOSE: Trauma during pregnancy is among leading causes of non-pregnancy-related maternal death (MD). This study describes risk factors for MD from trauma during pregnancy in a large urban population. METHODS: We queried an urban Level One Trauma Center registry for the medical records of pregnant women suffering trauma from 1990 to 2007. Associations were examined between maternal demographics, injury mode details, injury characteristics, and risk of maternal death upon arrival to the emergency room. RESULTS: Overall, 351 patients were identified. Most traumas was caused by motor vehicle collision (71.8 %), accounting for 78.9 % of MD, followed by gun shot wound (10.3 %), stabbing (8.5 %), falls (4.3 %), and assaults (4 %). Abdominal and head injuries were more frequent in cases of MD compared with patients admitted to the hospital (33.3 vs. 25.1 % abdominal, 55.6 vs. 29.4 % head; p < 0.001). A greater proportion of MDs were characterized by lack of restraint use (66.7 %) compared to women admitted to the hospital (47.7 %) and women discharged after observation (43.1 %); p = 0.014. ER deaths had more negative base excess scores than women who were admitted or discharged (-14 vs. -3 vs. -2; p < 0.001), lower blood pH values (6.96 vs. 7.40 vs. 7.44; p < 0.001), greater Injury Severity Scores (ISS) (44.4 vs. 11.49 vs. 2.66; p < 0.001), and lower Revised Trauma Scores (RTS) (0.5 vs. 7.49 vs. 7.83; p < 0.001). CONCLUSIONS: Lack of restraint use in the pregnant population is associated with increased MD. Although not validated in the pregnant population, the ISS and RTS were associated with maternal mortality outcomes.

Magnesium Sulfate Use in Pregnancy for Preeclampsia Prophylaxis and Fetal Neuroprotection: Regimens in High-Income and Low/Middle-Income Countries.

Magnesium sulfate is one of the most commonly used medications in obstetrics, most notably for the prevention of eclamptic seizures and fetal neuroprotection of the extremely preterm neonate. Pharmacokinetic and pharmacodynamic studies have demonstrated a variety of IV and IM regimens are effective for these indications. Existing models and data can be used to tailor treatment regimens to increase coverage in poor resource areas, maximize efficacy and minimize toxicity for patients of different weights and renal function.

Duration of membrane rupture and risk of perinatal transmission of HIV-1 in the era of combination antiretroviral therapy.

OBJECTIVE: The objective of the study was to determine whether the duration of membrane rupture of 4 or more hours is a significant risk factor for perinatal transmission of human immunodeficiency virus (HIV) in the era of combination antiretroviral therapy (ART). STUDY DESIGN: This was a prospective cohort study of 717 HIV-infected pregnant women-infant pairs with a delivery viral load available who received prenatal care and delivered at our institution during the interval 1996-2008. RESULTS: The cohort comprised 707 women receiving ART who delivered during this interval. The perinatal transmission rate was 1% in women with membranes ruptured for less than 4 hours and 1.9% when ruptured for 4 or more hours. For 493 women with a delivery viral load less than 1000 copies/mL receiving combination ART in pregnancy, there were no cases of perinatal transmission identified up to 25 hours of membrane rupture. Logistic regression demonstrated only a viral load above 10,000 copies/mL as an independent risk factor for perinatal transmission. CONCLUSION: Duration of membrane rupture of 4 or more hours is not a risk factor for perinatal transmission of HIV in women with a viral load less than 1000 copies/mL receiving combination ART.

Malnutrition as a predictor of poor postoperative outcomes in gynecologic cancer patients.

PURPOSE: Poor nutritional status has been associated with increased postoperative morbidity and mortality in surgical patients. The purpose of this study is to evaluate if decreased nutritional parameters correlate with increased postoperative complications regardless of other risk factors in the gynecologic cancer patient. METHODS: A retrospective chart review was performed among women who underwent surgical management for gynecologic malignancies from October 2006 to June 2008. Variables included age, race, medical comorbidities, cancer type/stage, preoperative albumin, absolute lymphocyte count (ALC), and body mass index (BMI), estimated blood loss (EBL), intraoperative blood transfusion (BT), intraoperative or postoperative complications, intensive care unit (ICU) admissions, hospital readmissions, reoperations, and cancer recurrence. RESULTS: Three hundred gynecologic oncology patients with preoperative nutritional parameters were included in the study. Decreased albumin was significantly associated with more postoperative complications (p < 0.001), hospital readmissions (p = 0.01), reoperations (p = 0.03), ICU admissions (p < 0.001), and cancer recurrence (p < 0.001). Decreased ALC and BMI preoperatively was also significantly associated with higher incidence of cancer recurrence (p = 0.01, p = 0.01). Surgical cases involving increased EBL (p = 0.01, p < 0.001) and more BT (p < 0.001, p < 0.001) had significantly more postoperative complications and more ICU admissions. Multivariable logistic regression found preoperative albumin to be an independent predictor of increased postoperative complications. CONCLUSIONS: Decreased albumin is significantly associated with more postoperative complications, hospital readmissions, reoperations, ICU admissions, and cancer recurrence. This nutritional parameter is an important predictor of postoperative morbidity and mortality. Thus, it is important to assess nutritional status preoperatively and offer nutritional support or alternate treatment options if necessary.

Vasopressin versus a combination of vasopressin and tourniquets: a comparison of blood loss in patients undergoing abdominal myomectomies.

OBJECTIVE: To compare blood loss and need for blood transfusions in women who underwent abdominal myomectomies after receiving vasopressin or combined vasopressin and tourniquet. METHODS: A retrospective chart review was performed reviewing abdominal myomectomies that took place at our institution. Subjects were divided into three groups: no intervention, vasopressin, or combined vasopressin and tourniquet. Blood loss, need for blood transfusion, and drop in hemoglobin and hematocrit were compared across all groups. RESULTS: One-hundred and thirty-two subjects were included in the study. No statistically significant difference was found between groups in blood loss, drop in hemoglobin or hematocrit, or blood transfusions. CONCLUSION: Combined vasopressin and tourniquets was not associated with a statistically significant decrease in blood loss or need for blood transfusion.

Impact of enhanced recovery after cesarean delivery on maternal outcomes: A systematic review and meta-analysis.

BACKGROUND: This meta-analysis explores the impact of enhanced recovery after cesarean delivery (ERAC) on maternal outcomes. METHODS: We searched 4 databases (Web of Science, Embase, PubMed and CINAHL) in October 2020 without date limiters, for studies quantitatively comparing ERAC implementation to a control group. The primary outcome was length of hospital stay and secondary outcomes included time to mobilization and time to urinary catheter removal, opioid consumption, readmission rates and cost savings. Mean differences and odds ratios (MD and OR with 95% confidence intervals) were calculated. Levels of evidence were assessed using GRADE. RESULTS: Twelve studies involving 17,607 patients (9693 without ERAC and 7914 with ERAC) were included. ERAC was associated with reduced: length of hospital stay (MD -0.51 days [-0.94, -0.09]; p = 0.018; I2 = 99%), time to first mobilization (MD -11.05 h [-18.64, -3.46]; p = 0.004; I2 = 98%), time to urinary catheter removal (MD -13.19 h [-17.59, -8.79]; p < 0.001; I2 = 97%) and opioid consumption (MD -21.85 mg morphine equivalents [-33.19, -10.50]; p = < 0.001; I2 = 91%), with no difference in maternal readmission rate (OR 1.23 [0.96, 1.57]; p = 0.10; I2 = 0%). Three studies reported cost savings associated with ERAC. The GRADE levels of evidence were rated as low or very low quality for all study outcomes. CONCLUSION: ERAC is associated with reduction in length of stay, times to first mobilization and urinary catheter removal and opioid consumption. ERAC does not significantly affect maternal hospital readmission rates following discharge. Further studies are required to determine which ERAC interventions to implement and which outcomes best determine ERAC efficacy.

Excessive weight gain among obese women and pregnancy outcomes.

We evaluated pregnancy outcomes in obese women with excessive weight gain during pregnancy. A retrospective study was performed on all obese women. Outcomes included rates of preeclampsia (PEC), gestational diabetes, cesarean delivery (CD), preterm delivery, low birth weight, very low birth weight, macrosomia, 5-minute Apgar score of <7, and neonatal intensive care unit (NICU) admission and were stratified by body mass index (BMI) groups class I (BMI 30 to 35.9 kg/m(2)), class II (36 to 39.9 kg/m(2)), and class III (>or=40 kg/m(2)). Gestational weight change was abstracted from the mother's medical chart and was divided into four categories: weight loss, weight gain of up to 14.9 pounds, weight gain of 15 to 24.9 pounds, and weight gain of more than 25 pounds. A total 20,823 obese women were eligible for the study. Univariate analysis revealed higher rates of preeclampsia, gestational diabetes, Cesarean deliveries, preterm deliveries, low birth weight, macrosomia, and NICU admission in class II and class III obese women when compared with class I women. When different patterns of weight gain were used as in the logistic regression model, rates of PEC and CD were increased. Excessive weight gain among obese women is associated with adverse outcomes with a higher risk as BMI increases.

Alternate Dosing Protocol for Magnesium Sulfate in Obese Women With Preeclampsia: A Randomized Controlled Trial.

OBJECTIVE: To evaluate whether obese women need greater doses of magnesium sulfate to obtain therapeutic serum concentrations for eclamptic seizure prevention. METHODS: Women with preeclampsia and a body mass index (BMI) of 35 or higher were randomly allocated to either the Zuspan regimen of magnesium sulfate (4-g intravenous [IV] loading dose, then a 1-g/h infusion) or to alternate dosing (6-g IV loading dose, then a 2-g/h infusion). Women had serum magnesium concentrations obtained at baseline, as well as after administration of magnesium sulfate at 1 hour, 4 hours, and delivery. The primary outcome was the proportion of women who had subtherapeutic serum magnesium concentrations (less than 4.8 mg/dL) 4 hours after administration. A sample size of 18 women per group was planned to compare the proportion of women with subtherapeutic serum magnesium concentrations in each group. RESULTS: From July 12, 2016, to March 14, 2019, 89 women with preeclampsia were screened and 37 were enrolled: 18 to the Zuspan regimen and 19 to the alternate regimen. A significantly greater proportion of women administered the Zuspan regimen had subtherapeutic serum magnesium concentrations at 4 hours (100% [95% CI 59-100] vs 63% [95% CI 41-81]; P=.01) compared with women administered the alternate higher dose regimen. At 4 hours, mean concentrations were significantly higher in the alternate regimen group (3.53 mg/dL±0.3 [Zuspan regimen] vs 4.41±0.5 [alternate regimen]; P<.01). CONCLUSION: The alternate dosing regimen of a 6-g IV loading dose followed by a 2-g/h IV maintenance dose more reliably achieves therapeutic serum magnesium concentrations (as defined by a concentration of at least 4.8 mg/dL) in obese women with preeclampsia. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT02835339.

A population-based analysis of 1037 malignant ovarian tumors in the pediatric population.

BACKGROUND: Concerns of malignant potential have impacted the utilization of ovarian salvage for treatment of ovarian masses in children. METHODS: The Surveillance, Epidemiology, and End Results (SEER) registry was analyzed for all females < or =19 y diagnosed with an ovarian tumor between 1973 and 2005. RESULTS: Overall, 1037 pediatric patients with ovarian tumors were identified. Approximately 61.7% of tumors occurred in patients 15 to 19 y old. The age-adjusted incidence of all malignant pediatric ovarian tumors in those < or =9 y was 0.102 versus 1.072 per 100,000 in those aged 10 to 19 y. The majority of cases (57.4%) present at an early localized stage. The predominant pathology was germ cell tumors in all age groups (77.4%). Overall 5- and 10-y survival rates are 91.7% and 91.4%, respectively. By multivariate analysis, advanced disease stage (HR 3.17, P<0.001), lack of surgery (HR 4.49, P =0.039), and poorly differentiated tumors (HR 3.40, P=0.011) were associated with worse outcomes. CONCLUSIONS: Malignant ovarian tumors are rare, particularly in patients under 5 y of age. Furthermore, the most common histologies are of low metastatic potential and carry high cure rates. Thus, the surgeon should implement ovarian-sparing strategies on the affected ovary unless a malignancy is clearly suspected and conserve the contralateral ovary in all children.

Should delivery timing for repeat cesarean be reconsidered based on dating criteria?

PURPOSE: We sought to examine if the method of pregnancy dating at five increasing term gestational ages is associated with increasing neonatal morbidity. MATERIALS AND METHODS: A cohort of women who underwent elective repeat cesarean delivery at ≥37 weeks' gestation were identified from the NICHD MFMU Network registry. We excluded women who were in labor, those carrying a fetus with a congenital anomaly, those with a non-reassuring fetal heart tracing, and those with preeclampsia, preexisting chronic hypertension or diabetes. Composite neonatal morbidity was defined for our study as any of the following: NICU admission, hypotonia, meconium aspiration, seizures, need for ventilator support, NEC, RDS, TTN, hypoglycemia, or neonatal death. We compared composite neonatal morbidity rates among infants born at five different gestational age cutoffs according to their method of pregnancy dating. RESULTS: At 39 and 40 weeks' gestation, the lowest rate of neonatal complications was seen in pregnancies dated by first trimester ultrasound (5.8% and 5.5%, respectively), while those with the highest neonatal morbidity rates were seen when dated by a second or third trimester ultrasound (8.1% and 6.0%, respectively); p < .001. Additionally within each pregnancy dating category, the neonatal morbidity rates declined from 37 to 40 weeks' gestation and then significantly increased at 41 + 0 weeks' gestation. CONCLUSION: Even with suboptimal dating methods, amongst women undergoing elective repeat cesarean delivery, neonatal morbidity was lowest when delivery occurred between 40 and 40 + 6 weeks gestation.

Alternative Magnesium Sulfate Dosing Regimens for Women With Preeclampsia: A Population Pharmacokinetic Exposure-Response Modeling and Simulation Study.

Magnesium sulfate is the anticonvulsant of choice for eclampsia prophylaxis and treatment; however, the recommended dosing regimens are costly and cumbersome and can be administered only by skilled health professionals. The objectives of this study were to develop a robust exposure-response model for the relationship between serum magnesium exposure and eclampsia using data from large studies of women with preeclampsia who received magnesium sulfate, and to predict eclampsia probabilities for standard and alternative (shorter treatment duration and/or fewer intramuscular injections) regimens. Exposure-response modeling and simulation were applied to existing data. A total of 10 280 women with preeclampsia who received magnesium sulfate or placebo were evaluated. An existing population pharmacokinetic model was used to estimate individual serum magnesium exposure. Logistic regression was applied to quantify the serum magnesium area under the curve-eclampsia rate relationship. Our exposure-response model-estimated eclampsia rates were comparable to observed rates. Several alternative regimens predicted magnesium peak concentration < 3.5 mmol/L (empiric safety threshold) and eclampsia rate ≤ 0.7% (observed response threshold), including 4 g intravenously plus 10 g intramuscularly followed by either 8 g intramuscularly every 6 hours × 3 doses or 10 g intramuscularly every 8 hours × 2 doses and 10 g intramuscularly every 8 hours × 3 doses. Several alternative magnesium sulfate regimens with comparable model-predicted efficacy and safety were identified that merit evaluation in confirmatory clinical trials.

How should pregnant women with spinal disease be managed?

This Practice Point commentary discusses a retrospective case series by Han et al. that investigated the management of spinal disease during pregnancy. On the basis of their experiences with 10 patients, Han et al. concluded that pregnant women who have progressive neurological deficit at 34-36 weeks' gestation or later should undergo induction of delivery or cesarean section before, or at the same time as, they undergo spinal surgery. As expressed by Han et al., MRI is the safest imaging modality with which to diagnose spinal disorders in pregnancy; however, it is our opinion that single exposure to any source of radiation from diagnostic imaging is unlikely to justify advising the pregnant patient to undergo therapeutic abortion. Spinal surgery has successfully relieved neurological symptoms in pregnant patients with spinal disorders and been followed by a successful delivery in a number of circumstances. In order to provide the optimum care for the pregnant woman and the fetus, however, a health-care team involving the spine surgeon, the obstetrician, and the anesthesiologist is necessary.