Immediate postpartum management of patients with severe hypertensive disorders of pregnancy: pathophysiology guiding practice.

Developing clinically-focused evidence and experience-based approaches to improve maternity care is a national priority. Safety and quality collaborative initiatives related to management of hypertensive disorders of pregnancy are vital in the implementation of improved care. We reviewed the obstetric literature to construct a concise summary of the core pathophysiologic issues, practice principles and clinical interventions which are foundational for physicians providing immediate postpartum care for patients with severe pregnancy-related hypertension (including those with eclampsia, HELLP syndrome, and superimposed preeclampsia inclusive of those with gestational hypertension that develop severe range blood pressures). While based largely upon the American College of Obstetrics and Gynecology (ACOG) Hypertension Task Force Guidelines released in 2013 as well as updated 2018 guidelines set forth by ACOG for hypertensive disorders of pregnancy, this summary goes beyond the basic safety bundles for hypertension management and lays a pathophysiologic foundation for the immediate postpartum care of patients with severe hypertensive disorders of pregnancy.

Fas ligand neutralization attenuates hypertension, endothelin-1, and placental inflammation in an animal model of HELLP syndrome.

Neutralization of FasL is linked to suppression of hypertension, placental inflammation, and endothelin system activation in an animal model of hemolysis, elevated liver enzymes, low platelets (HELLP) syndrome. During HELLP syndrome the placenta has been reported to serve as the primary source of Fas ligand (FasL), which has an impact on inflammation and hypertension during pregnancy and is dysregulated in women with severe preeclampsia and HELLP syndrome. We hypothesize that neutralization of FasL during pregnancy in an animal model of HELLP syndrome decreases inflammation and placental apoptosis, improves endothelial damage, and improves hypertension. On gestational day (GD) 12, rats were chronically infused with placental antiangiogenic factors sFlt-1 and sEng to induce HELLP syndrome. To neutralize FasL, MFL4 or FasL antibody was infused into a subset of HELLP or normal pregnant rats on GD13. IgG infusion into another group of NP and HELLP rats on GD13 was used as a control for FasL antibody, and all rats were euthanized on GD19 after blood pressure measurement. Plasma and placentas were collected to assess inflammation, apoptosis, and the degree of placental debris activation of endothelial cells. Administration of MFL4 to HELLP rats significantly decreased blood pressure compared with untreated HELLP rats and HELLP rats infused with IgG and improved the biochemistry of HELLP syndrome. Both circulating and placental FasL were significantly attenuated in response to MFL4 infusion, as were levels of placental and circulating TNFα when compared with untreated HELLP rats and HELLP rats infused with IgG. Endothelial cells exposed to placental debris and media from HP + MFL4 rats secreted significantly less endothelin-1 compared with stimulated endothelial cells from HELLP placentas. Neutralization of FasL is associated with decreased MAP and improvement in placental inflammation and endothelial damage in an animal model of HELLP syndrome.

Placental Alpha-Microglobulin-1 Test in Resource-Limited Settings: A Cost-Effectiveness Analysis.

OBJECTIVE: To evaluate whether the use of placental alpha-microglobulin-1 (PAMG-1) for the diagnosis of preterm premature rupture of membranes is cost-effective in resource-limited settings. METHODS: We designed a decision-analytic model from a third-party payer's perspective to determine the cost-effectiveness of the PAMG-1 test compared with the traditional diagnostic test of pooling, Nitrazine, and ferning in diagnosing preterm premature rupture of membranes in a resource-limited setting. The primary health outcome of interest is the number of hospital transfers averted by each strategy per 1,000 patients screened. Baseline probabilities and cost assumptions were derived from published literature. We conducted sensitivity analyses using both deterministic and probabilistic models. Cost estimates reflect 2015 U.S. dollars. RESULTS: Under our baseline parameters, the use of a PAMG-1 test was the preferred cost-effective strategy. The PAMG-1 test averted hospital transfers of 447 true-negative patients per 1,000 tested at a cost of $143,407 ($320.82 per hospital transfer averted). The traditional test averted hospital transfers of 395 true-negative patients per 1,000 tested at a cost of $172,652 ($437.40 per hospital transfer averted). In a Monte Carlo simulation of 10 million trials, the PAMG-1 test was selected as the most cost-effective strategy with a frequency of 74%. The traditional test was only selected with a frequency of 26%. The "do-nothing" strategy was not selected throughout the trial. CONCLUSION: Among women presenting at resource-limited settings with a history suspicious of preterm premature rupture of membranes between 24 and 36 weeks of gestation, our analysis provides evidence suggesting that PAMG-1 is the most cost-effective testing strategy.