Publications by Year: 2019

The immune complement system protects against pathogens; however, excess activation results in disease like hemolytic uremic syndrome, a clinical imitator of preeclampsia. Vascular endothelial factor (VEGF) protects against aberrant complement activation and is inhibited by soluble fms-like tyrosine kinase-1 (sFLT1) in other organs. We hypothesize that sFLT1 promotes complement-mediated placental damage through VEGF inhibition in preeclampsia. Objective: Quantify placental complement activity and sFLT1 expression in preeclampsia, and the subgroup of preeclampsia with hemolysis elevated liver enzymes low platelets (HELLP) syndrome. Methods: Placental complement activation marker C4d, membrane attack complex (MAC), and sFLT1 expression was quantified using immunofluores cence microscopy. Results: Placentas from 18 controls, 25 preeclampsia, including 6 cases of HELLP syndrome were identified. Placental C4d expression was greater in PE (median 6.4 [IQR: 5.1, 8.3]) compared to controls (4.4 [3.6, 5.5]; p = 0.003). MAC expression was also increased in preeclampsia compared to controls (6.5 [5.8, 8.7]; 5.4 [2.9, 5.9], p = 0.001). Placental sFLT1 expression was also higher in preeclampsia (p <0.0001). C4d and MAC were strongly correlated with sFLT1 levels in the placenta (R = 0.72; p < 0.0001 and R = 0.59; p = 0.01, respectively). Complement and sFLT1 expression was elevated in HELLP compared to preeclampsia without laboratory abnormalities, but this difference did not reach statistical significance. Conclusion: Increased placental complement activation and damage was seen in preeclampsia and correlates with sFLT1 expression. Our findings support the importance of the complement pathway in preeclampsia.

The rising trend in pregnancy-related deaths during the past 2 decades in the United States stands out among other high-income countries where pregnancy-related deaths are declining. Cardiomyopathy and other cardiovascular conditions, hemorrhage, and other chronic medical conditions are all important causes of death. Unintentional death from violence, overdose, and self-harm are emerging causes that require medical and public health attention. Significant racial/ethnic inequities exist in pregnancy care with non-Hispanic black women incurring 3 to 4 times higher rates of pregnancy-related death than non-Hispanic white women. Varied terminology and lack of standardized methods for identifying maternal deaths in the United States have resulted in nuanced data collection and interpretation challenges. State maternal mortality review committees are important mechanisms for capturing and interpreting data on cause, timing, and preventability of maternal deaths. Importantly, a thorough standardized review of each maternal death leads to recommendations to prevent future pregnancy-associated deaths. Key interventions to improve maternal health outcomes include 1) integrating multidisciplinary care for women with high-risk comorbidities during preconception care, pregnancy, postpartum, and beyond; 2) addressing structural racism and the social determinants of health; 3) implementing hospital-wide safety bundles with team training and simulation; 4) providing patient education on early warning signs for medical complications of pregnancy; and 5) regionalizing maternal levels of care so that women with risk factors are supported when delivering at facilities with specialized care teams.