The Association between Sickle Cell Disease and Postpartum Severe Maternal Morbidity.

OBJECTIVE: To compare the risk of severe maternal morbidity (SMM) from the delivery admission to 42 days' postdischarge among persons with sickle cell disease (SCD) to those without SCD. STUDY DESIGN: This retrospective cohort study included deliveries ≥20 weeks' gestation at an urban safety net hospital in Atlanta, GA from 2011 to 2019. The exposure was SCD diagnosis. The outcome was a composite of SMM from the delivery admission to 42 days' postdischarge. SMM indicators as defined by the Centers for Disease Control and Prevention were identified using the International Classification of Diseases, Ninth and Tenth Revisions (ICD-9/10) codes; transfusion of blood products and sickle cell crisis were excluded. RESULTS: Of N = 17,354 delivery admissions, n = 92 (0.53%) had SCD. Persons with SCD versus without SCD had an increased risk of composite SMM (15.22 vs. 2.29%, p < 0.001), acute renal failure (6.52 vs. 0.71%, p < 0.001), acute respiratory distress syndrome (4.35 vs. 0.17%, p < 0.001), puerperal cerebrovascular disorders (3.26 vs. 0.10%, p < 0.001), sepsis (4.35 vs. 0.42%, p < 0.01), air and thrombotic embolism (5.43 vs. 0.10%, p < 0.001), and ventilation (2.17 vs. 0.09%, p < 0.01). Ultimately, those with SCD had an approximately 6-fold higher incidence risk ratio of SMM, which remained after adjustment for confounders (adjusted incidence risk ratio [aIRR]: 5.96, 95% confidence interval [CI]: 3.4-9.19, p < 0.001). Persons with SCD in active vaso-occlusive crisis at the delivery admission had an approximately 9-fold higher risk of SMM up to 42 days' postdischarge compared with those with SCD not in crisis at the delivery admission (incidence: 25.71 vs. 8.77%, p < 0.05; aIRR: 8.92, 95% CI: 4.5-10.04, p < 0.05). Among those with SCD, SMM at the delivery admission was primarily related to renal and cerebrovascular events, whereas most postpartum SMM was related to respiratory events or sepsis. CONCLUSION: SCD is significantly associated with an increased risk of SMM during the delivery admission and through 42 days' postdischarge. Active crisis at delivery further increases the risk of SMM. KEY POINTS: · Sickle cell disease was associated with an approximately 6-fold increased risk of SMM.. · Active vaso-occlusive crisis at delivery was associated with an approximately 9-fold increased risk of SMM.. · 48% of SMM events in persons with SCD occurred postpartum and were respiratory- or sepsis-related..

Protease-Activated Receptor 2 Controls Vascular Smooth Muscle Cell Proliferation in Cyclic AMP-Dependent Protein Kinase/Mitogen-Activated Protein Kinase Kinase 1/2-Dependent Manner.

INTRODUCTION: Cardiovascular disorders are characterized by vascular smooth muscle (VSM) transition from a contractile to proliferative state. Protease-activated receptor 2 (PAR2) involvement in this phenotypic conversion remains unclear. We hypothesized that PAR2 controls VSM cell proliferation in phenotype-dependent manner and through specific protein kinases. METHODS: Rat clonal low (PLo; P3-P6) and high passage (PHi; P10-P15) VSM cells were established as respective models of quiescent and proliferative cells, based on reduced PKG-1 and VASP. Western blotting determined expression of cytoskeletal/contractile proteins, PAR2, and select protein kinases. DNA synthesis and cell proliferation were measured 24-72 h following PAR2 agonism (SLIGRL; 100 nM-10 µm) with/without PKA (PKI; 10 µm), MEK1/2 (PD98059; 10 µm), and PI3K (LY294002; 1 µm) blockade. RESULTS: PKG-1, VASP, SM22α, calponin, cofilin, and PAR2 were reduced in PHi versus PLo cells. Following PAR2 agonism, DNA synthesis and cell proliferation increased in PLo cells but decreased in PHi cells. Western analyses showed reduced PKA, MEK1/2, and PI3K in PHi versus PLo cells, and kinase blockade revealed PAR2 controls VSM cell proliferation through PKA/MEK1/2. DISCUSSION: Findings highlight PAR2 and PAR2-driven PKA/MEK1/2 in control of VSM cell growth and provide evidence for continued investigation of PAR2 in VSM pathology.

Timely treatment of severe hypertension and risk of severe maternal morbidity at an urban hospital.

BACKGROUND: Hypertensive disorders of pregnancy have been identified as a leading contributor to severe maternal morbidity and mortality. Pregnant persons with hypertensive disorders who develop severe hypertension at delivery admission have been shown to experience higher rates of severe maternal morbidity relative to those without severe hypertension. Current guidelines recommend prompt treatment of severe hypertension given known associated maternal and fetal risks; however, only 1 previous study has described an association between timeliness of antihypertensive therapy and risk of severe maternal morbidity. OBJECTIVE: This study aimed to characterize how development of severe intrapartum hypertension and its timely treatment affect the risk of severe maternal morbidity. STUDY DESIGN: We conducted a population cohort study of deliveries with and without hypertensive disorders of pregnancy at a single urban hospital between 2016 and 2018. Among deliveries of persons with hypertensive disorders of pregnancy, we identified those with persistent severe hypertension (defined as blood pressure ≥160/105 mm Hg sustained over ≥15 minutes) and further classified individuals with severe hypertension as having received timely (within 60 minutes) or delayed treatment. Severe maternal morbidity was identified using a composite measure developed by the Centers for Disease Control and Prevention. We calculated overall and indicator-specific rates of severe maternal morbidity for 4 categories of deliveries: without hypertensive disorder of pregnancy, with hypertensive disorder of pregnancy without severe hypertension, with severe hypertension and timely treatment, and with severe hypertension and delayed treatment. We assessed the association between hypertensive disorder of pregnancy, severe hypertension, timeliness of treatment, and severe maternal morbidity using multivariable robust Poisson regression, adjusting for demographic and clinical characteristics. RESULTS: Of 3723 delivery hospitalizations within the study time frame, 32.3% (1204/3723) were complicated by presence of a hypertensive disorder without severe hypertension and 5.7% (211/3723) by presence of a hypertensive disorder with severe hypertension. Among those with severe hypertension, 48.8% (103/211) received timely treatment. Compared with deliveries not complicated by a hypertensive disorder, severe maternal morbidity risk was increased for hypertensive disorder of pregnancy without severe hypertension (124.4/1000 vs 52.0/1000; adjusted risk ratio, 1.84; 95% confidence interval, 1.41-2.40), severe hypertension with timely treatment (233.0/1000; adjusted risk ratio, 3.81; 95% confidence interval, 2.45-5.92), and severe hypertension with delayed treatment (305.6/1000; adjusted risk ratio, 5.38; 95% confidence interval, 3.75-7.73). CONCLUSION: Patients with hypertensive disorders of pregnancy are at an elevated risk of severe maternal morbidity, and development of severe hypertension further increases this risk. Timely antihypertensive treatment is associated with lower risk of severe maternal morbidity among those with severe hypertension. These findings emphasize the importance of provider education and quality improvement efforts aimed at expediting treatment of severe hypertension.

Fibrodysplasia Ossificans Progressiva and Pregnancy: A Case Series and Review of the Literature.

Objective: To evaluate maternal and fetal outcomes in pregnant patients with fibrodysplasia ossificans progressiva (FOP; OMIM#135100), an ultrarare genetic disorder characterized by progressive heterotopic ossification of soft tissues and cumulative disability. Methods: This is a retrospective case series of three patients with FOP who were admitted to Grady Memorial Hospital in Atlanta, Georgia, from to February 2011 to July 2021. Results: Three women delivered preterm infants at our institution. These cases posed unique anesthetic and obstetric technical challenges, particularly when securing the airway and performing cesarean delivery. Importantly, each patient received perioperative glucocorticoids for prevention of further heterotopic ossification. Conclusion: FOP is a unique clinical diagnosis encountered by obstetricians and requires multidisciplinary management for optimal outcomes.