Rates of Preeclampsia and Post-preeclamptic Cardiovascular Disease Among US Military Servicewomen: A Retrospective Case-cohort Study.

INTRODUCTION: Preeclampsia (PE), a hypertensive-inflammatory disorder of pregnancy, poses acute risks of seizures, stroke, and heart attack during pregnancy and up to 6 weeks post-delivery. Recent data suggest that residual increased risks for cardiovascular disease (CVD) linger for much longer, possibly decades, after PE pregnancies. In civilian studies, PE and the major vascular events resulting from it disproportionately affect women from minority groups, especially African American women. The Military Health System (MHS) provides equal access to care for all active-duty servicewomen (ADSW), thus theoretically mitigating disparities. Racial/ethnic breakdown for PE and post PE CVD has not been studied in the MHS. MATERIALS AND METHODS: We identified healthy pregnancies in the MHS electronic health records of ADSW in the years 2009/2010 and those with a PE diagnosis. Patients with preexisting conditions of PE or CVD based on a look-back period of two calendar years were excluded. Cases were matched to controls based on age at pregnancy within 5 years and race/ethnicity. Cohort was assessed for diagnosed CVDs, race, age, and service during 2011-2017. Time to first CVD event was assessed with Cox proportional hazards model, results reported as relative risks (95% CI). All variables were summarized using mean (SD) for normally distributed continuous variables; non-normal continuous variables were characterized by median [IQR] and categorical variables were summarized by counts and frequencies. All statistical testings were two-sided with a significance level of 5% and were completed using SAS-EG version 9.2 or R version 3.5.2. RESULTS: From an analysis of 106,808 inpatient ADSW records, PE incidence by race is 11.8% for White, 12% for African American, 11.4% for Asian/Pacific Islander, 11.2% for Native American, 9.5% for Other, and 7.6% for unknown (not documented) race. Thus, in the US Military, African American women have comparable (0.2% higher) PE rate than White women in contrast with civilian studies that often report much higher incidence in the African American population. Using Asians as referent group, PE increases the risk of CVD. White women have a hazard ratio (HR) of 1.47 95%CI (1.15-1.88), African Americans a HR of 1.51 95% CI (1.18-1.93), and Other a HR of 1.39 95% CI (1.01-1.91). CONCLUSION: In this study, we report overall higher incidence of PE in military women than what is published for civilian women in all races and across all services. Importantly, we do not find significantly higher numbers of PE and post-PE CVD for African American, compared to White women in the military. Our study is not designed to address differences between military and civilian PE epidemiology, but these results deserve further exploration. This study shines light on a health risk unique to women, which we found to be more prevalent in the US Military than published civilian population. Further study to determine the details of long-term morbidity, disability, and death attributable to PE (CVD, stroke, and kidney diseases) are needed to design optimal medical management protocols, ensure readiness for duty, and protect our Women Warfighters.

The association of regional perinatal risk factors and neonatal intensive care capacity for Military Health System-insured newborns.

OBJECTIVE: To characterize hospitals where military-insured newborns received care and test the association of regional perinatal risk with neonatal intensive care unit (NICU) capacity. STUDY DESIGN: We identified birth hospitals for live newborns October 2015-December 2018 (n = 296,568) and assigned newborns to health service areas (HSAs). Perinatal risk factors and the number of neonatal special care beds and neonatologists were calculated at HSA levels. Cross-sectional correlation analyses assessed perinatal risk factors and capacity across HSAs. RESULTS: 27.0% (n = 10) of military birth hospitals had special care beds (intermediate and intensive) compared with 44.3% of civilian hospitals (n = 1224; p < 0.05). The number of special care beds and neonatologists per newborn varied more than twofold across regions and were only weakly associated with the proportion of higher risk newborns (R2 < 0.05). CONCLUSIONS: The lack of meaningful association of regional perinatal risk with NICU capacity poses challenges for effective specialized care among military-associated newborns.

Umbilical Cord Blood Use for Admission Blood Tests of VLBW Preterm Neonates: A Randomized Control Trial.

OBJECTIVE: Umbilical cord blood (UCB) for admission laboratories is an approach to decrease anemia risk in very low birth weight (VLBW) neonates. We hypothesized that UCB use results in higher hemoglobin concentration [HgB] around 24 hours of life. STUDY DESIGN: A randomized control trial among VLBW infants whose admission laboratories were drawn from UCB (n = 39) or the infant (n = 41) in three U.S. military NICUs (clinicaltrials.gov#NCT02103296). RESULTS: No demographic differences were observed between groups. UCB infants had higher [HgB] at 12 to 24 hours of life (15.5 vs. 14.0 g/dL, p = 0.02). The median time to first transfusion was 17 days longer in the experimental group (p = 0.04), and at discharge, their number of donor exposures was lower (1.1 vs. 1.8, p = 0.04). CONCLUSION: In the first 24 hours of life that is a period of higher risk for hemodynamic instability, UCB utilization for admission bloodwork in VLBW infants results in higher [HgB]. KEY POINTS: · Umbilical cord blood laboratory work in preterm infants is feasible.. · Cord blood use for admission laboratories results in increased hemoglobin in the first 24 hours of life.. · Cord blood use for admission laboratories delays time to first transfusion in preterm infants..

The Novel Use of Umbilical Cord Blood to Obtain Complete Blood Counts for Critical Neonatal Assessment.

BACKGROUND: Neonates undergoing clinical evaluations are often subjected to potentially painful phlebotomy for laboratory tests. The use of cord blood laboratory values for admission has been suggested as a means to decrease the risk of painful venipuncture and anemia. METHODS: Peripheral and umbilical cord blood complete blood count (CBC) results were obtained from infants who required a CBC. Results were compared using the Sysmex XN heme analyzer (Sysmex, Kobe, Japan). RESULTS:  White blood cell (WBC) and hemoglobin (HgB) values were significantly higher in peripheral samples than in cord samples. The mean cord WBC count was 14.1 × 103/mm3 versus 15.6 × 103/mm3 peripherally (p < 0.001). The mean cord HgB was 15.8 g/dL versus 16.8 g/dL peripherally (p < 0.001). Cord platelet (Plt) counts were, conversely, lower in peripheral samples than in cord samples (264.8 × 103/mm3 versus 242.3 × 103/mm3, respectively; p < 0.001). Although statistically different, the mean CBC values from both samples were within the reference ranges. Delayed cord clamping (DCC) increased peripheral versus cord HgB difference nearly threefold (0.6-1.7 g/dL; p = 0.01). CONCLUSIONS: Cord blood is an acceptable source for CBC blood sampling in newborn infants and can be used for clinical decisions. CBC laboratory values for cord blood remained within the peripheral blood reference range, with slight variability between the two samples.

The Impact of Graduate Medical Education on Scholarly Activity at a Military Medical Treatment Facility.

INTRODUCTION: Graduate medical education (GME) faculty and trainees have required scholarly activities to meet accreditation requirements. The impact of this contribution to the Military Health System, especially regarding innovations in military medicine, has not been previously examined. This study measured the contribution of GME in published manuscripts from a tertiary military medical center. MATERIALS AND METHODS: Utilizing the Scopus database, published manuscripts from the primary military GME institutions for the San Antonio Uniformed Services Health Education Consortium were identified from 2008 to 2018. Manuscripts were sorted based on the number of citations in Scopus and analyzed for their overall impact in medicine to include military unique topics. RESULTS: A total of 3,700 manuscripts were identified through Scopus and based on a 10 citation minimum, 1,365 manuscripts were further analyzed; 1,152 (84.4%) included authors with GME affiliation and 554 (40.6%) had direct applicability to unique aspects of military medicine. The mean number of citations per manuscript was 39.2 ± 63.6; Mean Cite Score was 2.97 ± 2.14 and Field Weighted Citation Index of 2.22 ± 3.27. Analysis of number of citations (10-19; 20-39; or >40) did not show any significant differences in Cite Score or military relevance, whereas the percentage of military relevant articles remained consistent yearly. CONCLUSIONS: These findings highlight the importance of military medical research and addressing specific medical needs of the warfighter. Graduate medical education in a tertiary Military Health System facility has enormous impact in scholarly activity, in particular the importance related to military medicine topics that emphasize combat casualty care and military readiness.

ECMO with vasopressor use during early endotoxic shock: Can it improve circulatory support and regional microcirculatory blood flow?

INTRODUCTION: While extracorporeal membrane oxygenation (ECMO) is effective in preventing further hypoxemia and maintains blood flow in endotoxin-induced shock, ECMO alone does not reverse the hypotension. In this study, we tested whether concurrent vasopressor use with ECMO would provide increased circulatory support and blood flow, and characterized regional blood flow distribution to vital organs. METHODS: Endotoxic shock was induced in piglets to achieve a 30% decrease in mean arterial pressure (MAP). Measurements of untreated pigs were compared to pigs treated with ECMO alone or ECMO and vasopressors. RESULTS: ECMO provided cardiac support during vasodilatory endotoxic shock and improved oxygen delivery, but vasopressor therapy was required to return MAP to normotensive levels. Increased blood pressure with vasopressors did not alter oxygen consumption or extraction compared to ECMO alone. Regional microcirculatory blood flow (RBF) to the brain, kidney, and liver were maintained or increased during ECMO with and without vasopressors. CONCLUSION: ECMO support and concurrent vasopressor use improve regional blood flow and oxygen delivery even in the absence of full blood pressure restoration. Vasopressor-induced selective distribution of blood flow to vital organs is retained when vasopressors are administered with ECMO.

Dysnatremia in extremely low birth weight infants is associated with multiple adverse outcomes.

OBJECTIVE: The objective of this study is to discern patterns of serum sodium in a broad cohort of extremely low birth weight (ELBW) infants and associate those patterns with hospital outcomes. STUDY DESIGN: Retrospective cohort study of ELBW infants from 323 neonatal intensive care units (NICUs) discharged from 2004 to 2014. We included patients who survived at least 7 days and had daily sodium levels available, and categorized infants by their minimum and maximum sodium levels. RESULTS: We identified 26,871 infants of whom 12,428 met inclusion criteria. Only 1964 (15.8%) maintained eunatremia for the first week. We found most dysnatremias to be associated with increased overall mortality compared with eunatremic patients including moderate hyponatremia (12.9% vs. 8.6%, p < 0.05) and severe hypernatremia (34.8% vs. 8.6%, p < 0.001). Most of these associations were maintained after regression modeling for mortality. CONCLUSION: Sodium fluctuations occurring within the first week of life are associated with increased mortality.

ECMO Maintains Cerebral Blood Flow During Endotoxic Shock in Piglets.

Cerebrovascular injury while on extracorporeal membrane oxygenation (ECMO) may be caused by excessive brain perfusion during hypoxemic reperfusion. Previous studies have postulated that the most vulnerable period of time for cerebrovascular injury is during the transfer period to ECMO. Therefore, our objective was to compare brain perfusion and hemodynamics in a piglet endotoxic shock ECMO model. The effect of ECMO flow on microcirculation of different brain regions was compared between 10 control pigs and six pigs (7-10 kg) administered IV endotoxin to achieve a drop in mean arterial blood pressure (MAP) of at least 30%. Cardiac output (CO), brain oxygen utilization, and microcirculatory blood flow (BF) were compared at baseline and 2 hours after ECMO stabilization. Matching ECMO delivery with baseline CO in control animals increased perfusion (p < 0.05) in all areas of the brain. In contrast, with endotoxin, ECMO returned perfusion closer to baseline levels in all regions of the brain and maintained brain tissue oxygen consumption. Both control and endotoxic pigs showed no evidence of acute neuronal necrosis in histologic cerebral cortical sections examined after 2 hours of ECMO. Results show that during endotoxic shock, transition to ECMO can maintain brain BF equally to all brain regions without causing overperfusion, and does not appear to cause brain tissue histopathologic changes (hemorrhage or necrosis) during the acute stabilization period after ECMO induction.

Continuous renal replacement therapy to reduce inflammation in a piglet hemorrhage-reperfusion extracorporeal membrane oxygenation model.

BACKGROUND: During extracorporeal membrane oxygenation (ECMO), circulation of blood across synthetic surfaces triggers an inflammatory response. Therefore, we evaluated the ability of continuous renal replacement therapy (CRRT) to remove cytokines and reduce the inflammatory response in a piglet hemorrhage-reperfusion ECMO model. METHODS: Three groups were studied: (i) uninjured controls (n = 11); (ii) hemorrhage-reperfusion while on venoarterial ECMO (30% hemorrhage with subsequent blood volume replacement within 60 min) (n = 8); (iii) treatment with CRRT after hemorrhage-reperfusion while on ECMO (n = 7). Hemodynamic parameters, oxygen utilization, and plasma and broncho-alveolar lavage (BAL) cytokine levels were recorded and lung tissue samples collected for histologic comparison. RESULTS: Whereas mean arterial pressures decreased among hemorrhage-reperfusion piglets, ECMO with CRRT did not significantly alter mean arterial pressures or systemic vascular resistance and was able to maintain blood flow as well as oxygen delivery after hemorrhage-reperfusion. Plasma interleukin (IL)-6 and IL-10, and BAL tumor necrosis factor (TNF)-α, IL-1ß, IL-6, IL-8, and IL-10 increased as a result of hemorrhage-reperfusion while on ECMO. After a 6-h period of CRRT, plasma IL-6 and BAL TNF-α, IL-6, and IL-8 levels decreased. CONCLUSION: Data suggest CRRT may decrease inflammatory cytokine levels during the initial phase of ECMO therapy following hemorrhage-reperfusion while maintaining cardiac output and oxygen utilization.