Association of Maternal Medical Comorbidities with Duration of Expectant Management in Patients with Severe Preeclampsia.

OBJECTIVE: This study aimed to estimate the association between number of maternal comorbidities and duration of expectant management and perinatal outcomes in patients with preeclampsia with severe features. STUDY DESIGN: Retrospective cohort of patients with preeclampsia with severe features delivering live, nonanomalous singletons at 23 to 342/7 weeks' gestation at a single center from 2016 to 2018. Patients delivered for an indication other than severe preeclampsia were excluded. Patients were categorized based on the number (0, 1, or ≥2) of comorbidities present: chronic hypertension, pregestational diabetes, chronic kidney disease, and systemic lupus erythematosus. The primary outcome was proportion of potential expectant management time achieved, that is, days of expectant management achieved divided by total potential expectant management time (days from severe preeclampsia diagnosis to 340/7 weeks). Secondary outcomes included delivery gestational age, days of expectant management, and perinatal outcomes. Outcomes were compared in bivariable and multivariable analyses. RESULTS: Of 337 patients included, 167 (50%) had 0, 151 (45%) had 1, and 19 (5%) had ≥2 comorbidities. Groups differed with respect to age, body mass index, race/ethnicity, insurance, and parity. The median proportion of potential expectant management achieved in this cohort was 1.8% (interquartile range: 0-15.4), and did not differ by number of comorbidities (adjusted ß: 5.3 [95% confidence interval [CI]: -2.1 to 12.9] for 1 comorbidity vs. 0 and adjusted ß: -2.9 [95% CI: -18.0 to 12.2] for ≥2 comorbidities vs. 0). There was no difference in delivery gestational age or duration of expectant management in days. Patients with ≥2 (vs. 0) comorbidities had higher odds of composite maternal morbidity (adjusted odds ratio: 3.0 [95% CI: 1.1-8.2]). There was no association between number of comorbidities and composite neonatal morbidity. CONCLUSION: Among patients with preeclampsia with severe features, the number of comorbidities was not associated with duration of expectant management; however, patients with ≥2 comorbidities had higher odds of adverse maternal outcomes. KEY POINTS: · Greater number of medical comorbidities were not associated with expectant management duration.. · Two or more medical comorbidities were associated with higher odds of adverse maternal outcomes.. · Expectant management should be undertaken cautiously in medically complicated patients..

Defining a Strategy for Laboratory Evaluation with Expectant Management of Preeclampsia.

OBJECTIVE: The objective of this study was to compare the frequency and timing of laboratory abnormalities and evaluate optimal laboratory testing strategies in women with preeclampsia (PE) undergoing expectant management. STUDY DESIGN: Retrospective cohort study of women with inpatient expectant management of PE at ≥23 weeks at a tertiary center from 2015 to 2018 was conducted. Women ineligible for expectant management or with less than two laboratory sets (platelets, aspartate aminotransferase, and serum creatinine) before the decision to deliver were excluded. Women were categorized as per the American College of Obstetricians and Gynecologists' definitions by initial diagnosis: PE without severe features, superimposed preeclampsia (SiPE) without severe features, and their forms with severe features. The frequency and timing of laboratory abnormalities were compared across the four PE categories. Kaplan-Meier curves modeled time to a laboratory abnormality (event) with censoring for delivery and were compared using log-rank tests. Logistic regression analysis modeled the development of a laboratory abnormality as a function of testing time intervals (days) for each PE type. Receiver operating characteristic curves and areas under the curve (AUC) were calculated; optimal cut points were determined using the Liu method. RESULTS: Among 636 women who met inclusion criteria, laboratory abnormalities were uncommon (6.3%). The median time to a laboratory abnormality among all women was ≤10 days, time being shortest in women with PE with severe features. Time to laboratory abnormality development did not differ significantly between the four PE groups (p = 0.36). Laboratory assessment intervals were most predictive for PE and SiPE with severe features (AUC = 0.87, AUC = 0.72). Optimal cutoffs were every 4 days for PE without severe features, 2 days for PE with severe features, 8 days for SiPE without severe features, and 3 days for SiPE with severe features. CONCLUSION: Most laboratory abnormalities in PE occur earlier and more frequently in those with severe features. Individual phenotypes should undergo serial evaluation based on this risk stratification. KEY POINTS: · Most laboratory abnormalities occur within 10 days of diagnosis.. · Laboratory abnormalities occur more often with severe features.. · Laboratory testing should occur according to disease severity..

Amount of Proteinuria and Duration of Expectant Management in Severe Preeclampsia.

OBJECTIVE: The aim of the study is to evaluate the association between the amount of proteinuria at the time of diagnosis of preeclampsia with severe features (severe preeclampsia [SPE]) and duration of expectant management (EM) and other perinatal outcomes. STUDY DESIGN: This is a retrospective cohort study of patients with SPE delivering live, non-anomalous singletons at 230/7 to 342/7 weeks' estimated gestational age (EGA) at a single tertiary center 2016 to 2018. Patients with proteinuria assessment (24-hour total urine protein or urine protein-to-creatinine ratio extrapolation) within 3 days of SPE diagnosis were included. Patients delivered for an indication other than SPE were excluded. Patients were categorized by amount of proteinuria (mg): none (≤300), mild (301-1,000), moderate (1,001-3,000), and massive (≥3,001). The primary outcome was the proportion of potential EM time achieved (%EM), i.e., days of EM divided by days from SPE diagnosis to 34 weeks. Secondary outcomes included delivery EGA, days of EM, and perinatal outcomes. Bivariable and multivariable analyses compared outcomes across groups. RESULTS: Of 295 patients included, 21% had no proteinuria, 33% mild, 19% moderate, and 27% massive. Groups differed by EGA at diagnosis, age, parity, chronic hypertension, and renal disease. %EM was not significantly different between groups (adjusted ß coefficient 4.1 [95% CI -5.3, 13.5] for mild proteinuria vs. none, -4.1 [95% CI -14.9, 6.6] for moderate proteinuria vs. none, and -5.6 [95% CI -16.0, 4.7] for massive proteinuria vs. none). Increasing proteinuria was associated with earlier delivery EGA but only days of EM in the mild versus no proteinuria groups. There was no significant association between proteinuria and maternal composite morbidity, but patients with mild and massive proteinuria had higher odds of neonatal composite morbidities compared with no proteinuria. CONCLUSION: Among patients with SPE, proteinuria level was not consistently associated with duration of EM. However, patients with the greatest amounts of proteinuria may have worse neonatal and selected maternal outcomes. KEY POINTS: · Amount of proteinuria was not associated with the duration of expectant management.. · Greater proteinuria was associated with earlier delivery in severe preeclampsia.. · Massive proteinuria in preeclampsia was associated with select adverse maternal and neonatal outcomes..

Feasibility, Safety, and Provider Perspectives of Bipolar Electrosurgical Cautery Device for (Opportunistic or Complete) Salpingectomy at the Time of Cesarean Delivery.

OBJECTIVES: The aim of the study is to evaluate the use of a bipolar electrocautery device for complete salpingectomy at cesarean to improve procedure completion rates, operative time, and surgeon reported satisfaction as compared with standard bilateral tubal ligation (BTL) and suture-cut-tie salpingectomy. STUDY DESIGN: This is a prospective cohort study of women undergoing planned, non-emergent cesarean with desired sterilization with complete salpingectomy utilizing a bipolar electrocautery device. Study patients were compared with historic controls from a randomized controlled trial (RCT) of complete salpingectomy via suture-cut-tie method versus BTL conducted at our institution (SCORE trial, NCT02374827). Outcomes were compared with groups from the original RCT. RESULTS: Thirty-nine women were consecutively enrolled (12/2018-11/2019) into the device arm of the study and compared with the original SCORE cohort (n = 40 BTL, n = 40 salpingectomy without a device). Salpingectomy performance with the bipolar electrocautery device was successfully completed in 100% (39/39) of enrolled women, with one device failure requiring the use of a second device, as compared with 95% (38/40) in the BTL (p = 0.49) and 67.5% (27/40) in salpingectomies without a device (p < 0.001). Mean operative time of sterilization procedure alone demonstrated device use as having the shortest operative time of all (device salpingectomy 5.0 ± 3.6 vs. no device 18.5 ± 8.3 minutes, p < 0.001; and vs. BTL 6.9 ± 5.0, p = 0.032). Mean sterilization procedure endoscopic band ligation (EBL) was demonstrated to be significantly different between each group, least amongst BTL followed by device (6.3 ± 4.8 vs. 8.4 ± 24.8, p < 0.001), and most by suture-cut-tie method (17.7 ± 14.3, p < 0.001 compared with device). Surgeon reported attitudes of complete salpingectomy performance in general practice outside an academic setting was greater with a device than without (79.5 vs. 35.3%; p < 0.001). CONCLUSION: Use of a bipolar electrocautery device improved operative times and surgeon satisfaction for salpingectomy at cesarean over standard suture ligation. Device use improved surgeon reported outcomes and may improve incorporation of complete salpingectomy at cesarean. KEY POINTS: · Electrocautery bipolar device use was safe at the time of salpingectomy during cesarean.. · Greater surgeon satisfaction occurs using a device than without.. · Decreased surgical time with device use is seen making the procedure equal to BTL..

Outcomes before and after Adopting Guidelines for Expectant Management of Severe Preeclampsia.

OBJECTIVE: This study aimed to compare maternal and neonatal outcomes in women with severe preeclampsia before and after implementation of the American College of Obstetricians and Gynecologists (ACOG) taskforce hypertensive guidelines. STUDY DESIGN: Single-center retrospective cohort study of women with severe preeclampsia delivering live nonanomalous singletons 23 to 342/7 weeks from 2013 to 2017. In 2015, the ACOG guidelines for expectant management of severe preeclampsia were implemented at our institution. Based on this, patients were categorized as preguideline (January 2013-December 2015) or postguideline adoption (January 2016-December 2017). Primary outcomes included composite maternal morbidity and composite neonatal morbidity; secondary outcomes included composite components, length of stay, birth weight, and delivery gestational age. Groups were compared with Student's t-test, Chi-square, and Wilcoxon's rank-sum tests; adjusted odds ratios (aOR; 95% confidence intervals [CIs]) were calculated. Yearly composite outcomes were compared using the Cochran-Armitage trend test. We estimated a sample size of 250 per group would provide 80% power at α = 0.05 to detect a 50% reduction in neonatal morbidity from a baseline rate of 21.5%. RESULTS: From 2013 to 2017, a total of 543 women with severe preeclampsia were identified: 278 (51%) preguideline and 265 (49%) postguideline. Baseline characteristics were overall similar between groups. There were no significant differences in maternal (aOR = 0.96, 95% CI: 0.6-1.41) or neonatal (aOR = 0.88, 95% CI: 0.61-1.28) composite morbidity between groups. Furthermore, there were no differences in composite maternal or neonatal morbidity over time. CONCLUSION: Perinatal outcomes were similar before and after implementation of severe preeclampsia management guidelines at our institution. Studies to evaluate if benefits are limited to subsets of this population, such as earlier gestational ages, are needed. KEY POINTS: · Expectant management of severe preeclampsia has yet to be fully evaluated outside of trial conditions.. · We did not see a significant improvement in neonatal composite morbidity/mortality.. · We also did not see a worsened composite maternal morbidity/mortality..

Aldosterone-stimulating somatic gene mutations are common in normal adrenal glands.

Primary aldosteronism (PA) represents the most common cause of secondary hypertension, but little is known regarding its adrenal cellular origins. Recently, aldosterone-producing cell clusters (APCCs) with high expression of aldosterone synthase (CYP11B2) were found in both normal and PA adrenal tissue. PA-causing aldosterone-producing adenomas (APAs) harbor mutations in genes encoding ion channels/pumps that alter intracellular calcium homeostasis and cause renin-independent aldosterone production through increased CYP11B2 expression. Herein, we hypothesized that APCCs have APA-related aldosterone-stimulating somatic gene mutations. APCCs were studied in 42 normal adrenals from kidney donors. To clarify APCC molecular characteristics, we used microarrays to compare the APCC transcriptome with conventional adrenocortical zones [zona glomerulosa (ZG), zona fasciculata, and zona reticularis]. The APCC transcriptome was most similar to ZG but with an enhanced capacity to produce aldosterone. To determine if APCCs harbored APA-related mutations, we performed targeted next generation sequencing of DNA from 23 APCCs and adjacent normal adrenal tissue isolated from both formalin-fixed, paraffin-embedded, and frozen tissues. Known aldosterone driver mutations were identified in 8 of 23 (35%) APCCs, including mutations in calcium channel, voltage-dependent, L-type, α1D-subunit (CACNA1D; 6 of 23 APCCs) and ATPase, Na(+)/(K+) transporting, α1-polypeptide (ATP1A1; 2 of 23 APCCs), which were not observed in the adjacent normal adrenal tissue. Overall, we show three major findings: (i) APCCs are common in normal adrenals, (ii) APCCs harbor somatic mutations known to cause excess aldosterone production, and (iii) the mutation spectrum of aldosterone-driving mutations is different in APCCs from that seen in APA. These results provide molecular support for APCC as a precursor of PA.

Opioids and Opioid Use Disorder in Pregnancy.

Overdose is a leading cause of pregnancy-associated morbidity and mortality in the United States. As such, all obstetric providers have a responsibility to provide evidence-based care for patients with opioid use disorder to mitigate adverse outcomes associated with substance use during pregnancy.

Quantifying the additional maternal morbidity in women with preeclampsia with severe features in whom immediate delivery is recommended.

BACKGROUND: Preeclampsia with severe features when diagnosed at less than 34 weeks is associated with maternal morbidity and is managed by immediate delivery or inpatient expectant management. OBJECTIVE: This study aimed to compare maternal morbidity in women with preeclampsia with severe features in whom the American College of Obstetricians and Gynecologists recommends immediate delivery versus those eligible for expectant management. STUDY DESIGN: This was a retrospective cohort study of women with preeclampsia with severe features delivered between 23 to 34 weeks of gestation from 2013 to 2017 at a single tertiary center. Women were categorized into 2 groups: (1) those recommended by the American College of Obstetricians and Gynecologists for immediate delivery, that is, ineligible for expectant management, and (2) those eligible for expectant management. The primary outcome was composite postpartum maternal morbidity, which included maternal intensive care unit admission, stroke, death, and other severe morbidities. The secondary outcomes included select adverse perinatal outcomes. Groups were compared and adjusted odds ratios (95% confidence intervals) calculated. RESULTS: Of the 1172 women with preeclampsia identified during the study period, 543 with preeclampsia with severe features were included for analysis: 211 (39%) were ineligible for expectant management and 332 (61%) were eligible for expectant management. Baseline characteristics, including age, body mass index, race and ethnicity, parity, marital status, and gestational age at preeclampsia diagnosis, were similar between the 2 groups. Women ineligible for expectant management had significantly higher composite postpartum maternal morbidity (adjusted odds ratio, 5.02 [95% confidence interval, 1.35-18.69]). In addition, those ineligible for expectant management were more likely to have postpartum intensive care unit admission (adjusted odds ratio, 4.19 [95% confidence interval, 1.09-16.16]) and postpartum hemoglobin level of <7 g/dL (adjusted odds ratio, 5.07 [95% confidence interval, 1.35-19.08]). There was no demonstrable difference in neonatal outcomes between the 2 groups. CONCLUSION: Women with preeclampsia with severe features who were ineligible for expectant management per the American College of Obstetricians and Gynecologists guidelines had a 5-fold increased risk of maternal morbidity, confirming the need for escalation of care and delivery without delay.

Synthetic High-Density Lipoprotein (sHDL) Inhibits Steroid Production in HAC15 Adrenal Cells.

High density lipoprotein (HDL) transported cholesterol represents one of the sources of substrate for adrenal steroid production. Synthetic HDL (sHDL) particles represent a new therapeutic option to reduce atherosclerotic plaque burden by increasing cholesterol efflux from macrophage cells. The effects of the sHDL particles on steroidogenic cells have not been explored. sHDL, specifically ETC-642, was studied in HAC15 adrenocortical cells. Cells were treated with sHDL, forskolin, 22R-hydroxycholesterol, or pregnenolone. Experiments included time and concentration response curves, followed by steroid assay. Quantitative real-time RT-PCR was used to study mRNA of 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase, lanosterol 14-α-methylase, cholesterol side-chain cleavage enzyme, and steroid acute regulatory protein. Cholesterol assay was performed using cell culture media and cell lipid extracts from a dose response experiment. sHDL significantly inhibited production of cortisol. Inhibition occurred in a concentration- and time-dependent manner and in a concentration range of 3µM-50µM. Forskolin (10µM) stimulated cortisol production was also inhibited. Incubation with 22R-hydroxycholesterol (10µM) and pregnenolone (10µM) increased cortisol production, which was unaffected by sHDL treatment. sHDL increased transcript levels for the rate-limiting cholesterol biosynthetic enzyme, 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase. Extracellular cholesterol assayed in culture media showed a positive correlation with increasing concentration of sHDL, whereas intracellular cholesterol decreased after treatment with sHDL. The current study suggests that sHDL inhibits HAC15 adrenal cell steroid production by efflux of cholesterol, leading to an overall decrease in steroid production and an adaptive rise in adrenal cholesterol biosynthesis.