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.

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.

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.

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.

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.

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.

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.

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.

Population Pharmacokinetic Modeling to Evaluate Standard Magnesium Sulfate Treatments and Alternative Dosing Regimens for Women With Preeclampsia.

Magnesium sulfate is the standard therapy for prevention and treatment of eclampsia. Two standard dosing regimens require either continuous intravenous infusion or frequent, large-volume intramuscular injections, which may preclude patients from receiving optimal care. This project sought to identify alternative, potentially more convenient, but similarly effective dosing regimens that could be used in restrictive clinical settings. A 2-compartment population pharmacokinetic (PK) model was developed to characterize serial PK data from 92 pregnant women with preeclampsia who received magnesium sulfate. Body weight and serum creatinine concentration had a significant impact on magnesium PK. The final PK model was used to simulate magnesium concentration profiles for the 2 standard regimens and several simplified alternative dosing regimens. The simulations suggest that intravenous regimens with loading doses of 8 g over 60 minutes followed by 2 g/h for 10 hours and 12 g over 120 minutes followed by 2 g/h for 8 hours (same total dose as the standard intravenous regimen but shorter treatment duration) would result in magnesium concentrations below the toxic range. For the intramuscular regimens, higher maintenance doses given less frequently (4 g intravenously + 10-g intramuscular loading doses with maintenance doses of 8 g every 6 hours or 10 g every 8 hours for 24 hours) or removal of the intravenous loading dose (eg, 10 g intramusculary every 8 hours for 24 hours) may be reasonable alternatives. In addition, individualized dose adjustments based on body weight and serum creatinine were proposed for the standard regimens.

Optimization of Maternal Magnesium Sulfate Administration for Fetal Neuroprotection: Application of a Prospectively Constructed Pharmacokinetic Model to the BEAM Cohort.

The aim of the study was to identify the optimal therapeutic maternal magnesium drug exposure and maternal serum concentration to prevent cerebral palsy in the extremely preterm fetus. We applied a previously constructed pharmacokinetic model adjusted for indication to a large cohort of pregnant women receiving magnesium sulfate to prevent cerebral palsy in their preterm offspring at 20 different US academic centers between December 1997 and May 2004. We simulated the population-based individual maternal serum magnesium concentration at the time of delivery and the total magnesium dose for each woman who received magnesium sulfate to determine the relationship between maternal serum magnesium level at the time of delivery and the development of cerebral palsy. Among 1905 women who met inclusion criteria, the incidence of cerebral palsy in the cohort was 3.6% for women who had received magnesium sulfate and 6.4% for controls. The simulated maternal serum concentration at delivery associated with the lowest probability of delivering an infant with cerebral palsy was 4.1 mg/dL (95%CI 3.7 to 4.4). Our population-based estimates of magnesium disposition suggest that to optimize fetal neuroprotection and prevent cerebral palsy, magnesium sulfate administration should target a maternal serum magnesium level between 3.7 and 4.4 mg/dL at delivery.

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.

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.

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.

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.

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.

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.

Conjugated bisphenol A in maternal serum in relation to miscarriage risk.

OBJECTIVE: To examine the relationship between the maternal serum bisphenol A (BPA) concentration at the time of the missed menstrual cycle and miscarriage risk. DESIGN: Retrospective cohort of prospectively collected serum samples. SETTING: Academic fertility center. PATIENT(S): Women presenting for early pregnancy monitoring with singleton pregnancies. INTERVENTION(S): Stored serum samples from 4 to 5 weeks' gestation analyzed for conjugated serum BPA concentrations. MAIN OUTCOME MEASURE(S): Live birth, miscarriage, and chromosome content of miscarriage. RESULT(S): With the 115 women included in the study, there were 47 live births and 68 clinical miscarriages (46 aneuploid and 22 euploid). Median conjugated BPA concentrations were higher in the women who had miscarriages than in those who had live births (0.101 vs. 0.075 ng/mL). Women with the highest quartile of conjugated BPA had an increased relative risk of miscarriage (1.83; 95% CI, 1.14-2.96) compared with the women in the lowest quartile. We found a similar increase risk for both euploid and aneuploid miscarriages. CONCLUSION(S): Maternal conjugated BPA was associated with a higher risk of aneuploid and euploid miscarriage in this cohort. The impact of reducing individual exposure on future pregnancy outcomes deserves further study.

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.