Echocardiographic changes and impact on clinical management in pregnant women with heart disease.

BACKGROUND: While guidelines recommend echocardiography for pregnant women with heart disease, there are limited data on its effect on clinical practice. In this study, we investigated pregnancy-associated echocardiographic changes and their impact on management. METHODS: This was a retrospective study of pregnant women with heart disease followed at an academic medical centre from 2016 to 2020. Data on maternal intrapartum and postpartum echocardiograms were collected and the impact on management analysed. RESULTS: 421 echocardiograms in 232 pregnancies were included in the study. The most common cardiac diagnosis was CHD (60.8% of pregnancies), followed by cardiomyopathy (9.9%). The frequency of baseline echocardiographic abnormalities varied by diagnosis, with abnormal right ventricular systolic pressure being the most common (15.0% of pregnancies in CHD and 23.1% of pregnancies with cardiomyopathy). 39.2% of the 189 follow-up echocardiograms had a significant change from the prior study, with the most common changes being declines in right ventricular function (4.2%) or left ventricular function (3.7%), and increases in right ventricular systolic pressure (5.3%) and aortic size (21.2%). 17.8% of echocardiograms resulted in a clinical management change, with the most common change being shorter interval follow-up. CONCLUSIONS: Echocardiographic changes in pregnant women with heart disease are common, in particular increases in aortic size. Echocardiography results in changes in management in a small but significant proportion of patients. Further studies are needed to determine how other factors, including patient access and resource allocation, factor into the use of echocardiography during pregnancy.

Pharmacokinetics and Tolerability of Intraperitoneal Chloroprocaine After Fetal Extraction in Women Undergoing Cesarean Delivery.

BACKGROUND: Intraperitoneal chloroprocaine has been used during cesarean delivery to supplement suboptimal neuraxial anesthesia for decades. The short in vitro half-life of chloroprocaine (11-21 seconds) has been cited to support the safety of this approach. However, there are no data regarding the rate of absorption, representing patient drug exposure, through this route of administration. Accordingly, we designed a study to determine the in vivo half-life of intraperitoneal chloroprocaine and assess clinical tolerability. METHODS: We designed a single-center, prospective, cohort, multiple-dose escalation study of women 18 to 50 years of age undergoing cesarean delivery with spinal anesthesia. Chloroprocaine (40 mL) was administered after delivery of the newborn and before uterine closure. The first cohort (n = 5) received 1%, the second cohort (n = 5) received 2%, and the third cohort (n = 5) received 3% chloroprocaine solution. Maternal blood samples were obtained before administration and 1, 5, 10, 20, and 30 minutes after dosing. The primary objective was to define the pharmacokinetic profile of intraperitoneal chloroprocaine, including in vivo half-life. The secondary objective was to evaluate tolerability through determination of peak plasma concentration and prospective assessment for local anesthetic systemic toxicity. RESULTS: The peak plasma concentration occurred 5 minutes after intraperitoneal administration in all 3 cohorts: 64.8 ng/mL (6.5 µg/kg), 28.7 ng/mL (2.9 µg/kg), and 799.2 ng/mL (79.9 µg/kg) for 1%, 2%, and 3% chloroprocaine, respectively. The in vivo half-life of chloroprocaine after intraperitoneal administration was estimated to be 5.3 minutes (95% confidence interval, 4.0-6.6). We did not detect clinical signs of local anesthetic systemic toxicity in any of the 3 cohorts. CONCLUSIONS: The in vivo half-life of intraperitoneal chloroprocaine (5.3 minutes) is more than an order of magnitude greater than the in vitro half-life (11-21 seconds). However, maximum plasma concentrations of chloroprocaine (C max range, 0.05-79.9 µg/kg) were not associated with local anesthetic systemic toxicity and remain well below our predefined safe level of exposure (970 µg/kg) and levels associated with clinical symptoms (2.6-2.9 mg/kg). Therefore, our study suggests that intraperitoneal chloroprocaine, in a dosage ≤1200 mg, administered after fetal extraction, is well tolerated during cesarean delivery.

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.

Aneuploidy rates and blastocyst formation after biopsy of morulae and early blastocysts on day 5.

PURPOSE: Studies have demonstrated high implantation rates after trophectoderm biopsy of day 5 expanded blastocysts. However, biopsy of cleavage stage embryos may adversely affect embryo development and implantation. No studies have assessed the utility of day 5 morulae and early blastocyst biopsy. This study sought to better understand these slower embryos' aneuploidy rates and implantation potential. METHODS: This was a retrospective review of all autologous IVF cycles utilizing PGS at a single academic infertility center. RESULTS: The biopsy of day 5 morulae and early blastocysts provided 22 % additional euploid blastocysts available for fresh day 6 transfer compared to day 5 biopsy of only expanded blastocysts. Aneuploidy did correlate with embryo stage on day 5, even after controlling for maternal age, with 16 % of morulae and 35 % of blastocysts being euploid. The majority (83 %) of euploid morulae progressed to the blastocyst stage by day 6. Experience transferring slower developing embryos is limited, but preliminary pregnancy and implantation rates appear similar to euploid embryos biopsied as expanded blastocysts. CONCLUSIONS: The biopsy of all non-arrested embryos on day 5 provides genetic information for all blastocysts on day 6, increasing the pool of euploid blastocysts available for fresh transfer and avoiding the need to cryopreserve developmentally competent embryos without genetic information.

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.

The use of selexipag, a prostacyclin receptor analog, for treatment of severe pulmonary artery hypertension during pregnancy, a case report.

Pregnancy in patients with pulmonary artery hypertension (PAH) is associated with high mortality and morbidity. Despite the risks, more patients with PAH are becoming pregnant. Case reports and case series have described the use of IV epoprostenol in these patients with some success. However, there are no published reports regarding the use of oral prostacyclins and prostacyclin receptor agonists in pregnancy. We describe the use of selexipag, an oral prostacyclin receptor agonist, for treating severe PAH during pregnancy in a patient who refused IV prostacyclin therapy. She remained stable throughout pregnancy and delivered a healthy baby girl; however, she died 13 days after her delivery by cesarean section due to developing worsening heart failure. While there is data and support for IV prostacyclins in pregnancy, patients may opt for oral formulations, like in our case. Registry data on the use of oral prostacyclins and prostacyclin receptor agonists in pregnancy may help improve patient outcomes.

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.

Magnesium sulfate pharmacokinetics after intramuscular dosing in women with preeclampsia.

BACKGROUND: Current intramuscular magnesium dosing regimens in low and middle-income countries are based on indirect absorption parameters to inform pharmacokinetic and pharmacodynamic response. OBJECTIVE: To determine if therapeutic serum magnesium levels are obtained in women with severe preeclampsia receiving intramuscular administration of magnesium sulfate using the Pritchard regimen and to compare the key pharmacokinetic variables to those previously published. STUDY DESIGN: Serum magnesium levels were obtained at multiple time points at baseline and after magnesium sulfate administration from women with severe preeclampsia receiving the standard Pritchard regimen for seizure prophylaxis at Bayero University, Kano, Nigeria. The pharmacokinetic profiles were constructed for the study cohort and the updated pharmacokinetic model was compared with the one that was previously published. RESULTS: A total of 80 blood samples were collected from 20 women with severe preeclampsia (45 collected before childbirth and 35 collected after childbirth). After 11.5 hours of magnesium sulfate administration, 63% of women in the cohort had serum magnesium levels of ≥2.0 mmol/L. Data from women receiving the Pritchard regimen combined with data from women previously modeled after the receipt of intravenous magnesium sulfate were adequately described using a 2-compartment model with first-order absorption and linear elimination from the central compartment. All structural pharmacokinetic parameters including clearance, central volume of distribution, peripheral volume of distribution, and intercompartment clearance were adjusted for maternal weight, and the clearance was further adjusted for serum creatinine level and antepartum or postpartum status. The simulated pharmacokinetic profiles of the updated pharmacokinetic model and the previously published pharmacokinetic model are similar. In previously published pharmacokinetic modeling, absorption rate constant=0.32 and absolute bioavailability=0.86. In the updated pharmacokinetic model, absorption rate constant=0.45 and absolute bioavailability=0.91. CONCLUSION: These data support the use of the Pritchard regimen as acceptable to achieve therapeutic serum magnesium levels and support the reported simulation of serum magnesium levels and eclampsia response associated with different intramuscular regimens.

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.