Stephen K. Hunter

The maternal early warning criteria: a proposal from the national partnership for maternal safety.

Case reviews of maternal death have revealed a concerning pattern of delay in recognition of hemorrhage, hypertensive crisis, sepsis, venous thromboembolism, and heart failure. Early-warning systems have been proposed to facilitate timely recognition, diagnosis, and treatment for women developing critical illness. A multidisciplinary working group convened by the National Partnership for Maternal Safety used a consensus-based approach to define The Maternal Early Warning Criteria, a list of abnormal parameters that indicate the need for urgent bedside evaluation by a clinician with the capacity to escalate care as necessary in order to pursue diagnostic and therapeutic interventions. This commentary reviews the evidence supporting the use of early-warning systems and describes The Maternal Early Warning Criteria, along with considerations for local implementation.

The association between hospital obstetrical volume and maternal postpartum complications

OBJECTIVE The purpose of this study was to examine the relationship between delivery volume and maternal complications. STUDY DESIGN We used administrative data to identify women who had been admitted for childbirth in 2006. Hospitals were stratified into deciles that were based on delivery volume. We compared composite complication rates across deciles. RESULTS We evaluated 1,683,754 childbirths in 1045 hospitals. Decile 1 and 2 hospitals had significantly higher rates of composite complications than decile 10 (11.8% and 10.1% vs 8.5%, respectively; P < .0001). Decile 9 and 10 hospitals had modestly higher composite complications as compared with decile 6 (8.8% and 8.5% vs 7.6%, respectively; P < .0001). Sixty percent of decile 1 and 2 hospitals were located within 25 miles of the nearest greater volume hospital. CONCLUSION Women who deliver at very low-volume hospitals have higher complication rates, as do women who deliver at exceedingly high-volume hospitals. Most women who deliver in extremely low-volume hospitals have a higher volume hospital located within 25 miles.

Vasopressin in Preeclampsia A Novel Very Early Human Pregnancy Biomarker and Clinically Relevant Mouse Model

Preeclampsia, a cardiovascular disorder of late pregnancy, is characterized as a low-renin hypertensive state relative to normotensive pregnancy. Because other nonpregnant low-renin hypertensive disorders often exhibit and are occasionally dependent on elevated arginine vasopressin (AVP) secretion, we hypothesized a possible use for plasma AVP measurements in the prediction of preeclampsia. Copeptin is an inert prosegment of AVP that is secreted in a 1:1 molar ratio and exhibits a substantially longer biological half-life compared with AVP, rendering it a clinically useful biomarker of AVP secretion. Copeptin was measured throughout pregnancy in maternal plasma from preeclamptic and control women. Maternal plasma copeptin was significantly higher throughout preeclamptic pregnancies versus control pregnancies. While controlling for clinically significant confounders (age, body mass index, chronic essential hypertension, twin gestation, diabetes mellitus, and history of preeclampsia) using multivariate regression, the association of higher copeptin concentration and the development of preeclampsia remained significant. Receiver operating characteristic analyses reveal that as early as the sixth week of gestation, elevated maternal plasma copeptin concentration is a highly significant predictor of preeclampsia throughout pregnancy. Finally, chronic infusion of AVP during pregnancy (24 ng per hour) is sufficient to phenocopy preeclampsia in C57BL/6J mice, causing pregnancy-specific hypertension, renal glomerular endotheliosis, proteinuria, and intrauterine growth restriction. These data implicate AVP release as a novel predictive biomarker for preeclampsia very early in pregnancy, identify chronic AVP infusion as a novel and clinically relevant model of preeclampsia in mice, and are consistent with a potential causative role for AVP in preeclampsia in humans.Preeclampsia, a cardiovascular disorder of late pregnancy, is characterized as a low-renin hypertensive state relative to normotensive pregnancy. Because other nonpregnant low-renin hypertensive disorders often exhibit and are occasionally dependent on elevated arginine vasopressin (AVP) secretion, we hypothesized a possible use for plasma AVP measurements in the prediction of preeclampsia. Copeptin is an inert prosegment of AVP that is secreted in a 1:1 molar ratio and exhibits a substantially longer biological half-life compared with AVP, rendering it a clinically useful biomarker of AVP secretion. Copeptin was measured throughout pregnancy in maternal plasma from preeclamptic and control women. Maternal plasma copeptin was significantly higher throughout preeclamptic pregnancies versus control pregnancies. While controlling for clinically significant confounders (age, body mass index, chronic essential hypertension, twin gestation, diabetes mellitus, and history of preeclampsia) using multivariate regression, the association of higher copeptin concentration and the development of preeclampsia remained significant. Receiver operating characteristic analyses reveal that as early as the sixth week of gestation, elevated maternal plasma copeptin concentration is a highly significant predictor of preeclampsia throughout pregnancy. Finally, chronic infusion of AVP during pregnancy (24 ng per hour) is sufficient to phenocopy preeclampsia in C57BL/6J mice, causing pregnancy-specific hypertension, renal glomerular endotheliosis, proteinuria, and intrauterine growth restriction. These data implicate AVP release as a novel predictive biomarker for preeclampsia very early in pregnancy, identify chronic AVP infusion as a novel and clinically relevant model of preeclampsia in mice, and are consistent with a potential causative role for AVP in preeclampsia in humans. # Novelty and Significance {#article-title-45}

Rotary Culture Enhances Pre-osteoblast Aggregation and Mineralization

Three-dimensional environments have been shown to enhance cell aggregation and osteoblast differentiation. Thus, we hypothesized that three-dimensional (3D) growth environments would enhance the mineralization rate of human embryonic palatal mesenchymal (HEPM) pre-osteoblasts. The objective of this study was to investigate the potential use of rotary cell culture systems (RCCS) as a means to enhance the osteogenic potential of pre-osteoblast cells. HEPM cells were cultured in a RCCS to create 3D enviroments. Tissue culture plastic (2D) cultures served as our control. 3D environments promoted three-dimensional aggregate formations. Increased calcium and phosphorus deposition was significantly enhanced three- to 18-fold (P < 0.001) in 3D cultures as compared with 2D environments. 3D cultures mineralized in 1 wk as compared with the 2D cultures, which took 4 wks, a decrease in time of nearly 75%. In conclusion, our studies demonstrated that 3D environments enhanced osteoblast cell aggregation and mineralization.

Promotion of neovascularization around hollow fiber bioartificial organs using biologically active substances

A limiting factor of the long-term function of bioartificial organs is oxygen delivery to the encapsulated tissue. This study determined whether incorporation of endothelial cell growth factor (ECGF) into the alginate core of a hollow fiber bioartificial organ will induce neovascularization around the hollow fiber. Polyethersulfone (PES) and polyvinylidine difluoride (PVDF) hollow fibers were examined. Endothelial cell growth factor was incorporated into sodium alginate, extruded into the lumen of hollow fibers, and cured in calcium chloride. Samples without ECGF were fabricated and used as controls. Hollow fibers were implanted into 16 rats. For each rat, two implants were placed subcutaneously and two intraperitoneally, one with and one without ECGF at each site. Implants were placed on opposite sides of each animal. Implants were removed 65 days later and examined using immunohistochemical methods and light microscopy to determine the extent of neovascularization. A total of 64 implants were used. Most intraperitoneal implants were found free floating but were encased within a 100-microm thick avascular fibrotic reaction. This finding was independent from the presence of ECGF. Hollow fibers without ECGF, implanted subcutaneously, also had an avascular fibrotic reaction surrounding each implant. Subcutaneous implants with incorporation of ECGF within the alginate core had marked neovascularization within the fibrotic overgrowth that surrounded these implants. This was most prevalent in hollow fibers, with the thin separation layer facing the fiber lumen irrespective of limiting pore size. Potent angiogenic factors, such as ECGF, incorporated into diffusion chamber bioartificial organs can promote neovascularization around the subcutaneously implanted hollow fiber and may improve oxygen delivery to the tissue encapsulated within devices based on this technology.

Leukemia in pregnancy and fetal response to multiagent chemotherapy

Background Leukemia is rare in pregnancy and treatment with intensive, multiagent chemotherapy produces complete remission in most adults, but might have deleterious effects on fetuses. Case A 24-year-old gravida 3 para 2 presented at 24 weeks with pruritus, rash, pancytopenia, and hepatitis. A bone marrow biopsy found acute lymphocytic leukemia. She completed three cycles of intensive multiagent chemotherapy with transient oligohydramnios in each cycle. Although there was decreased fetal growth rate, umbilical artery Doppler scans were normal. She delivered a normal 2150-g male infant at 36 weeks. Conclusion Pregnant women with newly diagnosed leukemia should not delay treatment, but multiagent chemotherapy might have transient effects on fetuses, most notably oligohydramnios. However, if fetal testing is normal, delivery might not be indicated.

Perinatal management of women with immune thrombocytopenic purpura: survey of United States perinatologists.

OBJECTIVE The aim of the study was to determine how perinatologists in the United States manage the care of women with immune thrombocytopenic purpura with respect to mode of delivery. STUDY DESIGN US members of the Society of Perinatal Obstetricians were surveyed with a 4-question questionnaire. Two mailings were sent. Questions 1 and 2 asked for a response regarding the perinatal management of delivery for women with chronic immune thrombocytopenic purpura and new-onset disease. The options were cordocentesis or fetal scalp blood sampling and cesarean delivery if the platelet count was <50,000 cells/microL, cesarean delivery if the maternal platelet count was <50,000 cells/microL, cesarean delivery of all women with immune thrombocytopenic purpura, and trial of labor without determining fetal platelet count. The third question asked for an opinion on whether cesarean delivery was protective against intracranial hemorrhage in cases of immune thrombocytopenic purpura. The fourth question asked whether the practitioner was in academic or private practice or both. RESULTS Among the 1596 perinatologists surveyed, there were 940 informative responses (58.9%). Most would allow a trial of labor for women with chronic (59.0%) or new-onset (66.6%) immune thrombocytopenic purpura. In cases of chronic immune thrombocytopenic purpura, 31.0% of those responding would perform an invasive procedure to determine fetal platelet count, followed by cesarean delivery if this count was <50, 000 cells/microL. In cases of new-onset immune thrombocytopenic purpura, 25.4% would do so. Of the respondents, 11.8% reportedly considered cesarean delivery protective against intracranial hemorrhage, whereas 56.6% did not and 31.6% were unsure. CONCLUSIONS The management of women with immune thrombocytopenic purpura remains controversial in the United States. Approximately two thirds of perinatologists would allow a trial of labor without a procedure to determine fetal platelet count. Most physicians surveyed did not consider cesarean delivery to be protective against intracranial hemorrhage.

The gamete and embryo compatibility of various synthetic polymers.

Several popular and well-characterized polymeric materials were evaluated for their biocompatibility toward the cells unique to reproduction. To accomplish these studies, several in vitro tests were developed that evaluated biocompatibility between the polymers and spermatozoa, ova, and embryos. The data indicated significant differences between the materials with respect to their biocompatibility toward sperm motility, the sperms ability to penetrate zona-free hamster eggs, and the ability of two-cell mouse embryos to divide. Polytetrafluoroethylene (PTFE-Teflon; PTFE, Chemplast Inc., Wayne, NJ), polyethylene glycol (PEG), and polyhydroxyethyl methacrylate (PHEMA) appear to be the most inert of the materials studied. Polyvinyl chloride (PVC; Tygon-Norton, Akron, OH) was found to be the most detrimental material toward gametes and embryos, with gross physiologic and morphologic changes observed in the PVC-exposed cells.

The Maternal Early Warning Criteria: A Proposal from the National Partnership for Maternal Safety

Case reviews of maternal death have revealed a concerning pattern of delay in recognition of hemorrhage, hypertensive crisis, sepsis, venous thromboembolism, and heart failure. Early-warning systems have been proposed to facilitate timely recognition, diagnosis, and treatment for women developing critical illness. A multidisciplinary working group convened by the National Partnership for Maternal Safety used a consensus-based approach to define The Maternal Early Warning Criteria, a list of abnormal parameters that indicate the need for urgent bedside evaluation by a clinician with the capacity to escalate care as necessary in order to pursue diagnostic and therapeutic interventions. This commentary reviews the evidence supporting the use of early-warning systems, describes The Maternal Early Warning Criteria, and provides considerations for local implementation.

Efficacy of polymeric encapsulated C5a peptidase–based group B streptococcus vaccines in a murine model

OBJECTIVE The purpose was to examine in mice the efficacy of various polymeric-encapsulated C5a peptidase vaccine formulations in eliciting a long-term immune response and preventing group B streptococcus (GBS) infection. STUDY DESIGN C5a peptidase was encapsulated in semipermeable microspheres of poly(lactide-coglycolide) (PLGA). Female ICR mice were immunized with 0, 10, or 30 μg of encapsulated C5a peptidase within 2 different formulations of PLGA polymers. Booster doses were given at weeks 4 and 8. Antibody responses were measured by enzyme-linked immunosorbent assay at weeks 4, 8, 11, and 40. Vaginal challenges with GBS types 1a, III, and V were performed at week 12. RESULTS Thirty microgram doses of the 75:25 and 50:50 PLGA formulations generate the highest and most sustained C5a peptidase-specific immune responses. Mice that received encapsulated C5a peptidase were significantly protected from vaginal colonization compared with mice that received empty microspheres. CONCLUSION Encapsulated C5a peptidase elicited significant immune responses and protection against a GBS challenge. C5a peptidase microsphere encapsulation has potential as a GBS vaccine.