Efficacy of Propranolol to Reduce Cesarean Delivery in Prolonged Labor: A Randomized Controlled Trial.

OBJECTIVE: To evaluate the rates of cesarean delivery in patients with prolonged labor randomized to receive intravenous (IV) propranolol compared with placebo. METHODS: A double-blind, placebo-controlled, randomized trial was conducted at two hospitals within a large academic health system. Eligible patients were at 36 weeks or more with a singleton gestation and prolonged labor , defined as: 1) prolonged latent phase of labor (dilation less than 6 cm after 8 hours or more with ruptured membranes and receiving oxytocin infusion) or 2) prolonged active phase of labor (dilation 6 cm or greater and less than 1-cm cervical dilation change over 2 hours or more with ruptured membranes and receiving oxytocin infusion). Patients were excluded for severe preeclampsia, maternal heart rate less than 70 beats per minute, maternal blood pressure less than 90/50 mm Hg, asthma, diabetes requiring insulin during labor, or a cardiac contraindication to ß-blockade. Patients were randomized to propranolol (2 mg IV) compared with placebo (2 mL normal saline IV), with one possible repeat dose. The primary outcome was cesarean delivery; secondary outcomes included labor duration, shoulder dystocia, and maternal and neonatal morbidity. With an estimated cesarean delivery rate of 45%, α 0.05, and 80% power, we required 163 patients per group to detect a 15% absolute reduction in cesarean delivery rate. A planned interim analysis was performed, and the trial was stopped for futility. RESULTS: From July 2020 to June 2022, 349 patients were eligible and approached; 164 were enrolled and randomized, with 84 in the propranolol group and 80 in the placebo group. The rate of cesarean delivery was not different between groups (57.1% propranolol vs 57.5% placebo, relative risk [RR] 0.99, 95% CI 0.76-1.29). Results were similar by subgroup of prolonged latent (n=123) and active (n=41) phases of labor and nulliparous (n=137) and multiparous (n=27) patients. Though not statistically significant, the frequency of postpartum hemorrhage was higher in the propranolol group (20% vs 10%, RR 2.02, 95% CI 0.93-4.43). CONCLUSION: In this multisite, double-blind, placebo-controlled randomized trial, there was no difference in cesarean delivery rate for patients who received propranolol compared with those who received placebo for management of prolonged labor. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov , NCT04299438.

Electronic Reminder to Transition Care After Hypertensive Disorders of Pregnancy: A Randomized Controlled Trial.

OBJECTIVE: Scalable interventions are needed to improve preventive care for those with increased cardiovascular disease (CVD) risk identified during pregnancy. We hypothesized that an automated reminder message for clinicians (nudge) would increase counseling at the postpartum visit on patient transitions of care. METHODS: We conducted a single-center, randomized controlled trial including birthing people with a hypertensive disorder of pregnancy evaluating a nudge compared with usual care. The nudge, including counseling phrases and patient-specific information on hypertensive diagnosis, was sent to the obstetric clinician through the electronic medical record up to 7 days before the postpartum visit. The primary outcome was documentation of counseling on transitions of care to primary care or cardiology. Secondary outcomes were documentation of CVD risk, use of counseling phrases, and preventive care visit within 6 months. A sample size of 94 per group (n=188) was planned to compare the nudge intervention with usual care; given the anticipated loss to follow-up, the sample size was increased to 222. Intention-to-treat analyses were performed, with P <.05 considered significant. RESULTS: From February to June 2021, 392 patients were screened, and 222 were randomized and analyzed. Of these, 205 (92.3%) attended a postpartum visit. Groups were similar, but more women in the usual care group had diabetes (16.1% vs 6.7%, P =.03). After adjustment for diabetes, patients in the nudge group were more likely to have documented counseling on transitions of care (38.8% vs 26.2%, adjusted relative risk [aRR] 1.53, 95% CI 1.02-2.31), CVD risk (21.4% vs 8.4%, aRR 2.57, 95% CI 1.20-5.49), and use of aspirin in a future pregnancy (14.3% vs 1.9%, aRR 7.49, 95% CI 1.66-33.93). Counseling phrases were used more often in the nudge group (11.2% vs 0.9%, aRR 12.27, 95% CI 1.50-100.28). Preventive care visit attendance did not differ by group (22.1% vs 24.6%, aRR 0.91, 95% CI 0.57-1.47). CONCLUSION: A timely electronic reminder to obstetric clinicians improved counseling about transitions of care after hypertensive disorders of pregnancy but did not result in increased preventive care visit attendance. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov , NCT04660032.

Racial Disparities in Sterilization Procedure Performed at Time of Cesarean Section.

OBJECTIVES: While bilateral tubal ligation has historically been performed for sterilization at cesarean delivery (CD), recent data supports the use and safety of opportunistic bilateral salpingectomy during CD to decrease lifetime ovarian cancer risk. Prior studies have described racial disparities in sterilization rates, but there is a paucity of data regarding racial disparities in type of sterilization procedure. Our objective was to determine differences in sterilization procedure type performed at CD by race (Black vs. non-Black) to evaluate for equity in bilateral salpingectomy utilization. STUDY DESIGN: We performed a retrospective cohort study of patients included in the American College of Surgeons National Surgical Quality Improvement Program database who underwent sterilization at time of CD from January 2019, to December 2020, identified using Current Procedural Terminology codes. Patients without documented race were excluded. Multivariable logistic regression was used to determine odds of undergoing bilateral salpingectomy compared with bilateral tubal ligation by race while controlling for confounders. RESULTS: Of 28,147 patients who underwent CD, 3,087 underwent concurrent sterilization procedure, and 2,161 met inclusion criteria (Black: n = 279; non-Black: n = 1,882). Black patients were significantly more likely to have hypertension (10.8% vs. 5.3%, p < 0.01), bleeding disorders (3.9% vs. 1.3%, p < 0.01), preoperative anemia (hemoglobin < 11 g/dL; 36.9% vs. 21.3%, p < 0.01), and be of American Society of Anesthesiologist class 3 or higher (29.4% vs. 22.5%, p = 0.01) than non-Black patients. After adjusting for differences, Black patients were almost 50% less likely than non-Black patients to undergo bilateral salpingectomy compared with bilateral tubal ligation for sterilization at CD (adjusted odds ratio = 0.52, 95% confidence interval: 0.36-0.75). CONCLUSION: Despite evidence that bilateral salpingectomy decreases ovarian cancer risk and is safe at CD, there is a racial disparity in bilateral salpingectomy utilization. While the cause of this disparity is unclear, further research is warranted to determine root causes and equitable solutions. KEY POINTS: · Opportunistic salpingectomy is recommended for primary prevention of ovarian cancer in patients undergoing pelvic surgery who have completed childbearing.. · Black patients were almost 50% less likely to undergo bilateral salpingectomy compared with bilateral tubal ligation than non-Black patients even after controlling for possible confounders.. · Further research is needed to determine root cause of the racial disparity in bilateral salpingectomy utilization rate..

Impact of type of maternal cardiovascular disease on pregnancy outcomes among women managed in a multidisciplinary cardio-obstetrics program.

BACKGROUND: Maternal cardiovascular disease complicates up to 4% of pregnancies in the United States. Knowledge regarding the impact of the cardiovascular disease category is limited. OBJECTIVE: The purpose of this study was to compare the maternal and neonatal outcomes among women with different types of cardiovascular diseases managed in a multidisciplinary program. STUDY DESIGN: This was a retrospective cohort study of patients with documented structural or functional cardiovascular disease who received care in a multidisciplinary program with maternal-fetal medicine and cardiology specialists at a single institution between March 2010 and November 2019. Women were categorized as having congenital heart disease, acquired heart disease, arrhythmias and channelopathies, or aortopathies. Women were excluded from the pregnancy outcome analysis if they never became pregnant or delivered at a different institution. The outcomes were analyzed according to the disease category using univariate techniques. RESULTS: A total of 232 women with 253 pregnancies met the inclusion criteria for pregnancy outcome analysis. Of these, 77 (30.4%) had congenital heart disease, 63 (24.9%) had acquired heart disease, 94 (37.2%) had arrhythmias or channelopathies, and 19 (7.5%) had aortopathies. Obesity and hypertension were more common among women with acquired heart disease, and women with acquired heart disease and arrhythmias had higher Cardiac Disease in Pregnancy II scores. Most of the pregnancies had good maternal and neonatal outcomes. Preeclampsia occurred more commonly in women with acquired heart disease (27% among those with acquired heart disease vs 10.4% among those with congenital heart disease, 13.8% among those with arrhythmias or channelopathies, and 0% among those with aortopathies; P=.009). Indicated preterm birth was highest among women with acquired heart disease (15.9%). Significant postpartum arrhythmias occurred in 2.4% of women. Preconception counseling was underutilized. CONCLUSION: Most women with preexisting cardiovascular disease experienced good pregnancy and neonatal outcomes when managed in a specialized, multidisciplinary program. Women with acquired heart disease were at highest risk for pregnancy complications such as preeclampsia and preterm birth.

IGF1R constitutive activation expands luminal progenitors and influences lineage differentiation during breast tumorigenesis.

Breast tumors display tremendous heterogeneity in part due to varying molecular alterations, divergent cells of origin, and differentiation. Understanding where and how this heterogeneity develops is likely important for effective breast cancer eradication. Insulin-like growth factor (IGF) signaling is critical for normal mammary gland development and function, and has an established role in tumor development and resistance to therapy. Here we demonstrate that constitutive activation of the IGF1 receptor (IGF1R) influences lineage differentiation during mammary tumorigenesis. Transgenic IGF1R constitutive activation promotes tumors with mixed histologies, multiple cell lineages and an expanded bi-progenitor population. In these tumors, IGF1R expands the luminal-progenitor population while influencing myoepithelial differentiation. Mammary gland transplantation with IGF1R-infected mammary epithelial cells (MECs) resulted in hyperplastic, highly differentiated outgrowths and attenuated reconstitution. Restricting IGF1R constitutive activation to luminal versus myoepithelial lineage-sorted MECs resulted in ductal reconstitutions co-expressing high IGF1R levels in the opposite lineage of origin. Using in vitro models, IGF1R constitutively activated MCF10A cells showed increased mammosphere formation and CD44+/CD24-population, which was dependent upon Snail and NFκB signaling. These results suggest that IGF1R expands luminal progenitor populations while also stimulating myoepithelial cell differentiation. This ability to influence lineage differentiation may promote heterogeneous mammary tumors, and have implications for clinical treatment.