Low dose acetyl salicylic acid (LDA) mediates epigenetic changes in preeclampsia placental mesenchymal stem cells similar to cells from healthy pregnancy.

INTRODUCTION: Preeclampsia (PE) affects 2-8% of all pregnancies, and is the leading cause of maternal and fetal morbidity and mortality. We reported on pathophysiological changes in placenta mesenchymal stem cells (P-MSCs) in PE. P-MSCs can be isolated from different layers of the placenta at the interface between the fetus and mother. The ability of MSCs from other sources to be immune licensed as immune suppressor cells indicated that P-MSCs could mitigate fetal rejection. Acetylsalicylic acid (aspirin) is indicated for treating PE. Indeed, low-dose aspirin is recommended to prevent PE in high risk patients. METHODS: We conducted robust computational analyses to study changes in gene expression in P-MSCs from PE and healthy term pregnancies as compared with PE-MSCs treated with low dose acetyl salicylic acid (LDA). Confocal microscopy studied phospho-H2AX levels in P-MSCs. RESULTS: We identified changes in >400 genes with LDA, similar to levels of healthy pregnancy. The top canonical pathways that incorporate these genes were linked to DNA repair damage - Basic excision repair (BER), Nucleotide excision repair (NER) and DNA replication. A role for the sumoylation (SUMO) pathway, which could regulate gene expression and protein stabilization was significant although reduced as compared to BER and NER pathways. Labeling for phopho-H2AX indicated no evidence of double strand break in PE P-MSCs. DISCUSSION: The overlapping of key genes within each pathway suggested a major role for LDA in the epigenetic landscape of PE P-MSCs. Overall, this study showed a new insight into how LDA reset the P-MSCs in PE subjects around the DNA.

Aspirin-Mediated Reset of Preeclamptic Placental Stem Cell Transcriptome - Implication for Stabilized Placental Function.

Preeclampsia (PE) is a pregnancy-specific disease, occurring in ~ 2-10% of all pregnancies. PE is associated with increased maternal and perinatal morbidity and mortality, hypertension, proteinuria, disrupted artery remodeling, placental ischemia and reperfusion, and inflammation. The mechanism of PE pathogenesis remains unresolved explaining limited treatment. Aspirin is used to reduce the risk of developing PE. This study investigated aspirin's effect on PE-derived placenta mesenchymal stem cells (P-MSCs). P-MSCs from chorionic membrane (CM), chorionic villi, membranes from the maternal and amniotic regions, and umbilical cord were similar in morphology, phenotype and multipotency. Since CM-derived P-MSCs could undergo long-term passages, the experimental studies were conducted with this source of P-MSCs. Aspirin (1 mM) induced significant functional and transcriptomic changes in PE-derived P-MSCs, similar to healthy P-MSCs. These include cell cycle quiescence, improved angiogenic pathways, and immune suppressor potential. The latter indicated that aspirin could induce an indirect program to mitigate PE-associated inflammation. As a mediator of activating the DNA repair program, aspirin increased p53, and upregulated genes within the basic excision repair pathway. The robust ability for P-MSCs to maintain its function with high dose aspirin contrasted bone marrow (M) MSCs, which differentiated with eventual senescence/aging with 100 fold less aspirin. This difference cautions how data from other MSC sources are extrapolated to evaluate PE pathogenesis. Dysfunction among P-MSCs in PE involves a network of multiple pathways that can be restored to an almost healthy functional P-MSC. The findings could lead to targeted treatment for PE.

Maternal antepartum antibiotic administration and patterns of bacterial resistance in early preterm neonates.

OBJECTIVE: The objective of this study was to determine the relationship between maternal antepartum antibiotic administration and antibiotic resistance patterns in preterm neonates admitted to the neonatal intensive care unit (NICU). METHODS: This was a retrospective cohort study of women and their preterm neonates delivered at a single tertiary care center over a 5-year period. Women and neonates were included if they delivered between 23 weeks 0 days and 28 weeks 6 days of gestation and neonates were admitted to the NICU. Subjects were excluded if there was incomplete antibiotic administration data or incomplete laboratory or bacterial culture data for either mothers or neonates. Data collected from maternal and neonatal charts included the type, duration, and total number of antibiotics administered to subjects, neonatal culture results within the first 7 days of life, and bacterial antibiotic resistance information. Women with neonates that cultured positive for bacteria demonstrating antibiotic resistance were compared to those whose neonates did not have antibiotic-resistant bacteria. RESULTS: 79 women with 90 neonates met inclusion criteria. Of the 79 women, 71 (89.9%) received at least 1 antibiotic antepartum. 14 neonatal bacterial isolates were resistant to at least 1 antibiotic. Antibiotic-resistant bacteria were present in 11 neonates; 3 neonates had more than 1 resistant bacteria cultured. The most common resistant bacteria cultured were Coagulase-negative Staphylococcus (6/14, 42.9%), S. aureus (3/14, 21.4%), and E. coli (2/14, 14.3%). Enterobacter spp (2) and Klebsiella pneumoniae (1) made up the remainder. Of the 11 neonates with resistant bacteria isolated, 10 of their mothers received antibiotics antepartum. Neonates with antibiotic-resistant bacterial isolates were more likely to be born at lower gestational ages (24.6 vs 25.9 weeks, p = .013) and have lower mean birth weights (679.5 vs 849.3 g, p = .009) than those without resistant bacteria. In 8 of 11 (73%) neonates with resistant bacteria, the mother received an antibiotic to which the bacteria cultured were resistant: 6 coagulase-negative Staphylococcus, 1 MRSA, and 1 S. aureus. CONCLUSIONS: Although preterm neonates are often treated for presumed sepsis, they infrequently have positive bacterial cultures. In this study, those that had positive bacterial cultures for resistant bacteria were born at earlier gestational ages and had lower birth weights. These bacteria cultured in neonates are likely to be resistant to antibiotics received by mothers in the antepartum period. Careful selection of maternal and neonatal antibiotics in the preterm setting with consideration for local antibiotic resistance patterns is suggested.

Novel collaborative cardiology and maternal fetal medicine practice - experience at the heart and pregnancy program.

PURPOSE: The Heart and Pregnancy Program (HPP) was created to evaluate and manage pregnant women with cardiac conditions simultaneously by cardiology and maternal-fetal medicine (MFM). The objective of our study was to describe the experience at this multidisciplinary program. METHODS: This is a retrospective review of women managed at HPP for over 4.5 years. Subjects were compared based on indication for referral. RESULTS: One hundred and seventy-three women were seen during the time period. Referral indications included cardiac complaints without history of cardiac disease (n = 49, 28.3%), known cardiac disease (n = 96, 55.5%), and other high-risk conditions (n = 28, 16.2%). Those with a known history of cardiac disease were significantly more likely to be nulliparous, and those referred for other high-risk conditions were significantly more likely to be obese. Most women underwent echocardiography (n = 137, 79.2%). For the 140 women who delivered at our hospital, the average gestational age at delivery was 38.8 weeks and the Cesarean rate was 41.4% (n = 58). No significant adverse perinatal outcomes were noted. CONCLUSIONS: In our collaborative cardiology/MFM practice, most pregnant women had known cardiac disease. No significant adverse outcomes were noted. Our experience provides support for creating a joint model of care for pregnant women with cardiac disease.

Maternal morbidity after early preterm delivery (23-28 weeks).

BACKGROUND: Previous research has focused mainly on neonatal outcomes associated with preterm and periviable delivery, but maternal outcomes with preterm delivery are less well described. OBJECTIVE: This study aimed to determine if early preterm delivery results in an increase in maternal morbidity. STUDY DESIGN: This is a retrospective cohort study conducted at a tertiary care center over a 5-year time period. Subjects were women identified by review of neonatal intensive care unit admission logs. Women were included if they delivered between 23 0/7 and 28 6/7 weeks' gestation and their neonate was admitted to the neonatal intensive care unit. The prevalence of maternal morbidities was assessed, including blood transfusion, maternal infection, placental abruption, postpartum depression or positive depression screen, hemorrhage, and prolonged maternal postpartum hospitalization. A composite outcome comprising blood transfusion, maternal infectious morbidity, placental abruption, and postpartum depression was developed. Outcomes for women who delivered between 23 0/7 and 25 6/7 weeks' gestation (early group) and 26 0/7 and 28 6/7 weeks' gestation (late group) were compared. Multivariate logistic regression analysis was performed to evaluate contributors to the composite morbidity, controlling for confounding. RESULTS: A total of 82 women met the inclusion criteria: 38 in the early group and 44 in the late group. Maternal demographics were similar between the groups. The early group was significantly more likely to experience composite maternal morbidity (60.5% vs 27.3%; P=.004) and infection (42.1% vs 13.6%; P=.006). Regression analysis determined that delivery at a later gestational age was associated with lower rates of composite morbidity (odds ratio, 0.6; 95% confidence interval, 0.41-0.83). CONCLUSION: In this study, data suggest that maternal morbidity is higher with delivery at periviable gestational ages. Composite morbidity and maternal infection were more frequent in women who delivered at less than 26 weeks' gestation. The management of women at risk for delivery at early gestational ages should include a discussion of increased maternal complications.

Factors associated with attendance at the postpartum blood pressure visit in pregnancies complicated by hypertension.

OBJECTIVES: Women with hypertensive disorders of pregnancy should have a blood pressure evaluation no later than 7-10 days after delivery. The objective of this study was to identify the factors associated with patient attendance at the postpartum blood pressure follow-up visit. STUDY DESIGN: This was a retrospective cohort study of postpartum women who had a hypertensive disorder of pregnancy. Postpartum follow-up rates were recorded, and characteristics of women who attended a postpartum visit for blood pressure evaluation were compared to women who did not return for the visit. Multiple logistic regression was performed. MAIN OUTCOME MEASURES: Characteristics of women who returned for a blood pressure visit. RESULTS: There were 378 women who met inclusion criteria; 193(51.1%) attended the blood pressure visit. Women who returned were older and more likely to have preeclampsia, severe features, magnesium sulfate use, or severe hypertension during hospitalization. They were less likely to have gestational hypertension. Adjusted analysis demonstrated that black/non-Hispanic women (OR 0.53, 95% CI 0.34-0.83), the presence of any preeclampsia diagnosis (OR 2.19, 95% CI 1.03-4.81), and whether the woman underwent a cesarean delivery (OR 3.06, 95% CI 1.85-5.14) remained significant factors in predicting adherence. CONCLUSIONS: Women who returned for a blood pressure visit were more likely to have had significant hypertensive disease or a cesarean delivery. Non-Hispanic black women had the lowest rate of follow-up. Given black women have the highest rates of maternal morbidity and mortality nationwide, effective interventions to increase follow-up for them are needed.

Evaluation and Treatment of Cardiac Tamponade in a Pregnant Patient.

Cardiac tamponade is an uncommon but life-threatening emergency that may occur in pregnant women. There is a plethora of causes, but prompt diagnosis and intervention is imperative to optimize both maternal and fetal outcomes. We report on a case of a large pericardial effusion leading to cardiac tamponade occurring in the 32nd week of gestation in a previously healthy woman. Rapid recognition and a multidisciplinary team meeting resulted in a therapeutic pericardial window and drainage and relief of symptoms. The woman underwent an uncomplicated repeat cesarean delivery at term with a positive neonatal outcome. This case highlights the importance of a rapid diagnosis and a team-based approach to managing a complex medical condition like cardiac tamponade in pregnancy.

Mesenchymal stem cell therapies in brain disease.

As treatments for diseases throughout the body progress, treatment for many brain diseases has been at a standstill due to difficulties in drug delivery. While new drugs are being discovered in vitro, these therapies are often hindered by inefficient tissue distribution and, more commonly, an inability to cross the blood brain barrier. Mesenchymal stem cells are thus being investigated as a delivery tool to directly target therapies to the brain to treat wide array of brain diseases. This review discusses the use of mesenchymal stem cells in hypoxic disease (hypoxic ischemic encephalopathy), an inflammatory neurodegenerative disease (multiple sclerosis), and a malignant condition (glioma).

Treatment of a Pregnant Patient in a Persistent Vegetative State.

BACKGROUND: Brain injury leading to a persistent vegetative state during pregnancy involves difficult medical and ethical decisions. CASE: A 21-year-old multigravid woman entered a persistent vegetative state at 20 1/7 weeks of gestation after cardiac arrest with postanoxic brain injury from a suspected drug overdose. The clinical disciplines responsible for her case formed a collaborative care plan involving ventilator, nutrition, and medication support of the mother and regular fetal monitoring and ultrasound testing. A planned delivery by cesarean at term resulted in a good neonatal outcome. CONCLUSION: There is no standardized management plan for obstetric care in a persistent vegetative state. This case illustrates a successful multidisciplinary approach that may be useful as a template in similar situations.

Catecholaminergic Polymorphic Ventricular Tachycardia in Pregnancy.

BACKGROUND: Catecholaminergic polymorphic ventricular tachycardia is a genetic disorder in which ventricular tachycardia occurs in the absence of structural heart disease or a prolonged QT interval. If untreated, there is a high incidence of sudden cardiac death. Management of this cardiac condition during pregnancy merits a multidisciplinary approach. CASE: A nulliparous woman with catecholaminergic polymorphic ventricular tachycardia presented at 15 weeks of gestation. Her care involved a multidisciplinary team including cardiology, maternal-fetal medicine, obstetric nursing, cardiac nursing, and anesthesia. A simulation scenario was designed to prepare for cardiac events during labor. A term intrapartum cesarean delivery was performed for fetal indications. CONCLUSION: A multidisciplinary approach to the antepartum, intrapartum, and postpartum care of women with catecholaminergic polymorphic ventricular tachycardia is critical to a team-based successful pregnancy outcome.