A More Selective vs a Standard Risk-Stratified, Heparin-Based, Obstetric Thromboprophylaxis Protocol.

Importance: In 2016, our institution adopted a pregnancy-related venous thromboembolism (VTE) prophylaxis protocol based on American College of Obstetricians and Gynecologists guidelines that recommended postpartum heparin-based chemoprophylaxis (enoxaparin) based on a risk-stratified algorithm. In response to increased wound hematomas without significant reduction in VTE using this protocol, a more selective risk-stratified approach was adopted in 2021. Objective: To evaluate outcomes of the more selective risk-stratified approach to heparin-based obstetric thromboprophylaxis (enoxaparin) protocol. Design, Setting, and Participants: Retrospective observational study of 17 489 patients who delivered at a single tertiary care center in the southeast US between January 1, 2016, and December 31, 2018 (original protocol), and between December 1, 2021, and May 31, 2023 (more selective protocol). Patients receiving outpatient anticoagulation for active VTE or high VTE risk during pregnancy were excluded. Exposure: Standard risk-stratified and more selective postpartum VTE chemoprophylaxis protocols. Main Outcomes and Measures: The primary outcome was clinical diagnosis of wound hematoma up to 6 weeks pos tpartum. The secondary outcome was new diagnosis of VTE up to 6 weeks post partum. We compared baseline characteristics and outcomes between groups and estimated adjusted odds ratios with 95% CIs of primary and secondary outcomes using the original protocol group as reference. Results: Of 17 489 patients included in the analysis, 12 430 (71%) were in the original protocol group and 5029 (29%) were in the more selective group. Rates of chemoprophylaxis decreased from 16% (original protocol) to 8% (more selective protocol). Patients in the more selective group were more likely to be older, be married, and have obesity or other comorbidities (hypertension, diabetes, cardiac disease). Compared with the original protocol, the more selective protocol was associated with a decrease in any wound hematoma (0.7% vs 0.3%; adjusted odds ratio [aOR], 0.38; 95% CI, 0.21-0.67), specifically due to a lower rate of superficial wound hematomas (0.6% vs 0.3%; aOR, 0.43; 95% CI, 0.24-0.75). There was no significant increase in VTE or individual types of VTE (0.1% vs 0.1%; aOR, 0.40; 95% CI, 0.12-1.36). Conclusions and Relevance: A more selective risk-stratified approach to an enoxaparin thromboprophylaxis protocol for VTE was associated with decreased rates of wound hematomas without increased rates of postpartum VTE.

Contemporary Trends in Cesarean Delivery Rates and Indications.

OBJECTIVE: This study aimed to describe cesarean delivery rates and indications at a single center in order to assess the impact of the guidelines published by the American College of Obstetricians and Gynecologists and the Society for Maternal-Fetal Medicine on trends in labor management. STUDY DESIGN: This is a retrospective cohort study of patients ≥23 weeks' gestation delivering at a single tertiary care referral center from 2013 to 2018. Demographic characteristics, mode of delivery, and main indication for cesarean delivery were ascertained by individual chart review. Cesarean delivery indications (mutually exclusive) were the following: repeat cesarean delivery, nonreassuring fetal status, malpresentation, maternal indications (e.g., placenta previa or genital herpes simplex virus), failed labor (any stage labor arrest), or other (i.e., fetal anomaly and elective). Polynomial (cubic) regression models were used to model rates of cesarean delivery and indications over time. Subgroup analyses further examined trends in nulliparous women. RESULTS: Of the 24,637 patients delivered during the study period, 24,050 were included in the analysis; 7,835 (32.6%) had a cesarean delivery. The rates of overall cesarean delivery were significantly different over time (p < 0.001), declining to a minimum of 30.9% in 2014 and peaking at 34.6% in 2018. With regard to the overall cesarean delivery indications, there were no significant differences over time. When limited to nulliparous patients, the rates of cesarean delivery were also noted to be significantly different over time (p = 0.02) nadiring at 30% in 2015 from 35.4% in 2013 and then rising up to 33.9% in 2018. As for nulliparous patients, there was no significant difference in primary cesarean delivery indications over time except for nonreassuring fetal status (p = 0.049). CONCLUSION: Despite changes in labor management definitions and guidelines encouraging vaginal birth, the rates of overall cesarean delivery did not decrease over time. The indications for delivery, particularly failed labor, repeat cesarean delivery, and malpresentation have not significantly changed over time. KEY POINTS: · The rates of overall cesarean deliveries did not decrease despite the 2014 published recommendations for the reduction in cesarean deliveries.. · There were no significant differences in the indications of cesarean deliveries among nulliparous or multiparous women.. · Despite the adoption of strategies to reduce the overall and primary cesarean delivery rates, these trends remain unchanged.. · Indications for delivery, particularly failed labor, repeat cesarean delivery, and malpresentation have also not significantly changed over time.. · Additional strategies to encourage and increase vaginal delivery rates must be adopted..

Synthesis and patterning of tunable multiscale materials with engineered cells.

Many natural biological systems--such as biofilms, shells and skeletal tissues--are able to assemble multifunctional and environmentally responsive multiscale assemblies of living and non-living components. Here, by using inducible genetic circuits and cellular communication circuits to regulate Escherichia coli curli amyloid production, we show that E. coli cells can organize self-assembling amyloid fibrils across multiple length scales, producing amyloid-based materials that are either externally controllable or undergo autonomous patterning. We also interfaced curli fibrils with inorganic materials, such as gold nanoparticles (AuNPs) and quantum dots (QDs), and used these capabilities to create an environmentally responsive biofilm-based electrical switch, produce gold nanowires and nanorods, co-localize AuNPs with CdTe/CdS QDs to modulate QD fluorescence lifetimes, and nucleate the formation of fluorescent ZnS QDs. This work lays a foundation for synthesizing, patterning, and controlling functional composite materials with engineered cells.

Operative vaginal delivery as an independent risk factor for maternal postpartum infectious morbidity.

BACKGROUND: A recent study from the United Kingdom suggested that a single dosage of adjunctive amoxicillin/clavulanic acid with operative vaginal delivery reduces maternal infectious morbidity by 40% (from 19% to 11%). However, 89% of their study population received an episiotomy. OBJECTIVE: This study aimed to evaluate whether operative vaginal delivery is an independent risk factor for composite maternal postpartum infectious morbidity in a population with a low episiotomy rate. STUDY DESIGN: This was a retrospective cohort study of patients with viable singleton vaginal deliveries after ≥34 weeks gestation at a single perinatal center (2013-2018). The patients were categorized by the mode of delivery: spontaneous vaginal delivery or operative vaginal delivery (forceps or vacuum-assisted). The primary outcome was a composite of maternal infectious morbidity up to 6 weeks after delivery, defined as (1) endometritis, (2) perineal wound morbidity (infection, breakdown, or dehiscence), or (3) culture-proven urinary tract infection. The patient characteristics and outcomes were compared between the groups using appropriate tests. Multivariable models were used to estimate the association between operative vaginal delivery and study outcomes compared with spontaneous vaginal delivery, with adjustment for selected confounders. RESULTS: Of 14,647 deliveries meeting the inclusion criteria, 732 (5.0%) were operative vaginal deliveries: 354 (48%) forceps and 378 (52%) vacuums. Overall, 210 (1.4%) patients developed the morbidity composite. Patients having an operative vaginal delivery were more likely to be nulliparous, have labor inductions, develop intrapartum chorioamnionitis, receive an episiotomy, and sustain a third- or fourth-degree laceration. After adjusting for confounding factors, no significant association was observed between operative vaginal delivery and composite morbidity (adjusted odds ratio, 1.4 [0.8-2.4]) or any of its individual components. Administration of postpartum antibiotics and documented fever were also similar between groups. There was also no significant association between instrument (forceps vs vacuum) and the maternal infection composite. CONCLUSION: In this single-center US cohort, operative vaginal delivery was not an independent risk factor for maternal composite postpartum infectious morbidity.

Venous thromboembolism and adverse outcomes in highest thromboembolism risk patients compared with those at lower risk.

BACKGROUND: A risk-based institutional protocol for inpatient heparin-based venous thromboembolism prophylaxis in a general obstetrical population previously demonstrated a greater than 2-fold increase in wound hematomas with no change in the frequency of thromboembolism. OBJECTIVE: We sought to compare the rates of thromboembolism and bleeding outcomes in patients at the highest risk for thromboembolism (eg, those with a history of thromboembolism or thrombophilia who require anticoagulation prophylaxis or therapy throughout pregnancy) than low-risk patients. STUDY DESIGN: We performed a retrospective cohort study of all deliveries >20 weeks at a single center from 2013-2018. Patients were categorized as high-risk (received outpatient heparin-based prophylaxis or treatment) or low-risk (no outpatient anticoagulation). The primary outcome was newly diagnosed postpartum thromboembolism; the main secondary outcome was wound/perineal hematoma. The outcomes were compared between the high- and low-risk cohorts. Adjusted odds ratios (with 95% confidence intervals) were calculated with the low-risk group as reference. RESULTS: Of 24,303 total deliveries, 395 (1.7%) were high-risk and 23,905 (98.3%) were low-risk. Among the low-risk patients, 8.6% received anticoagulation prophylaxis in accordance with our risk-based inpatient thromboembolism prophylaxis protocol. High-risk patients were more likely to be older and have a higher body mass index, earlier delivery gestational age, medical comorbidities, and pregnancy complications, eg, preeclampsia. Despite outpatient antepartum anticoagulation, high-risk patients had an 11-fold increased risk of thromboembolism (adjusted odds ratio, 11.1 [4.7-26.2]) than low-risk patients. High-risk patients also had significantly more wound/perineal hematomas (adjusted odds ratio, 4.8 [2.7-8.4]), overall wound complications (adjusted odds ratio, 3.0 [2.0-4.4]), blood transfusions, intensive care unit admissions, maternal deaths, and longer maternal lengths of stay. CONCLUSION: Patients at the highest risk of obstetrical thromboembolism had an 11-fold increased risk of thromboembolism with a more moderate increase (∼5-fold) in postpartum wound and bleeding complications than low-risk patients. This more favorable risk or benefit profile supports current anticoagulation recommendations in high-risk patients.

Evaluation of a Risk-Stratified, Heparin-Based, Obstetric Thromboprophylaxis Protocol.

OBJECTIVE: To evaluate outcomes before and after implementation of a risk-stratified heparin-based obstetric thromboprophylaxis protocol. METHODS: We performed a retrospective cohort study of all patients who delivered at our tertiary care center from 2013 to 2018. Deliveries were categorized as preprotocol (2013-2015; no standardized heparin-based thromboprophylaxis) and postprotocol (2016-2018). Patients receiving outpatient anticoagulation for active venous thromboembolism (VTE) or high VTE risk were excluded. Coprimary effectiveness and safety outcomes were postpartum VTEs and wound hematomas, respectively, newly diagnosed after delivery and up to 6 weeks postpartum. Secondary outcomes were other wound or bleeding complications, including unplanned surgical procedures (eg, hysterectomies, wound explorations) and blood transfusions. Outcomes were compared between groups, and adjusted odds ratios (aORs) and 95% CIs were calculated using the preprotocol group as reference. RESULTS: Of 24,229 deliveries, 11,799 (49%) occurred preprotocol. Although patients were more likely to receive heparin-based prophylaxis postprotocol (15.6% vs 1.2%, P<.001), there was no difference in VTE frequency between groups (0.1% vs 0.1%, odds ratio 1.0, 95% CI 0.5-2.1). However, patients postprotocol experienced significantly more wound hematomas (0.7% vs 0.4%, aOR 2.34, 95% CI 1.54-3.57), unplanned surgical procedures (aOR 1.29, 95% CI 1.06-1.57), and blood transfusions (aOR 1.34, 95% CI 1.16-1.55). CONCLUSION: Risk-stratified heparin-based thromboprophylaxis in a general obstetric population was associated with increased wound and bleeding complications without a complementary decrease in postpartum VTE. Guidelines recommending this strategy should be reconsidered.

A high-throughput method for quantification of glycoprotein sialylation.

Sialic acid can improve qualities of therapeutic glycoproteins such as circulatory half-life, biological activity, and solubility. In production of therapeutic glycoproteins, a high-throughput method is required for process monitoring and optimization to ensure consistent and optimal sialic acid content. Current methods for quantifying sialic acid, however, require chromatographic separation that is time-consuming and cannot rapidly analyze many samples in parallel. Here we present a novel high-throughput method for quantifying glycoprotein sialylation. Using chemical reduction, enzymatic release of sialic acid, and chemical derivatization of the sialic acid, the method can accurately, rapidly (15 min), and specifically analyze many samples in parallel. It requires only 45 µl of sample and has a quantitation limit of 2 µM sialic acid. It has also been validated for monitoring sialylation of recombinant interferon gamma (IFN-γ) produced in Chinese hamster ovary (CHO) cell culture. This method is useful for various applications in upstream and downstream bioprocesses.