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.

Ornithine transcarbamylase deficiency and pregnancy: A case series and review of recommendations.

Background: Ornithine transcarbamylase deficiency (OTCD) is a rare disorder of the urea cycle that obstetricians should be aware of in order to guide management for pregnant carriers of the X-linked gene that causes the condition. Cases: We present the pregnancy management and outcomes of two women with OTCD. The particular manifestations of the disease drive antenatal, intrapartum and postpartum management. Conclusion: Preconception counseling, early prenatal diagnostics and multidisciplinary intrapartum and postpartum management plans contribute to improved outcomes for patients.

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.

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).

Procalcitonin in amniotic fluid at the time of genetic amniocentesis and preterm delivery.

PURPOSE: Procalcitonin (PCT) is an acute-phase protein that has been infrequently studied in amniotic fluid. We sought to determine if PCT levels measured in amniotic fluid samples at the time of genetic amniocentesis are predictive of preterm delivery. MATERIALS AND METHODS: A retrospective cohort study was performed on all women presenting for genetic amniocentesis between 15-23 weeks of pregnancy at our institution from 2011 to 2013 with stored amniotic fluid samples. PCT protein levels were measured in the samples by enzyme-linked immunosorbent assay (ELISA). PCT levels in women who delivered less than 37 weeks versus those who delivered at or after 37 week were compared. Mann-Whitney test was used. RESULTS: Eighty-seven samples were available for analysis and of these eight (9.2%) were from patients who delivered preterm. Sixty-two (70%) had PCT levels below the lower limit of quantification, which was 25 pg/mL. Median PCT levels did not differ between the preterm and term group [20.4 pg/mL (range 0-82.8) and 20.2 pg/mL (range 0-198.4), respectively, p = .95]. CONCLUSION: In asymptomatic women undergoing genetic amniocentesis in this cohort, procalcitonin levels were low to undetectable and did not correlate with risk of subsequent preterm birth.

Salmonella enterica Serotype Typhi Bacteremia Complicating Pregnancy in the Third Trimester.

Background. Salmonella enterica serotype Typhi (S. Typhi) is an anaerobic gram-negative enteric rod that causes infection when contaminated food or water is ingested and may cause illness in pregnancy. Case. This is a patient who presented at 31 weeks' gestation with abdominal pain and fever and was diagnosed with S. Typhi bacteremia. Conclusion. S. Typhi should be considered in febrile patients with recent travel presenting with abdominal discomfort with or without elevated liver enzymes.

Is preeclampsia an independent predictor of diastolic dysfunction? A retrospective cohort study.

OBJECTIVE: To determine if preeclampsia is an independent predictor of diastolic dysfunction and what factors among patients with preeclampsia are associated with diastolic dysfunction. METHODS: This is a retrospective cohort study of patients who delivered between 2008 and 2013 at a single institution who had a maternal echocardiogram during their pregnancy or within 5months of delivery. Patients with structural heart disease, ejection fraction less than 45%, pulmonary embolus, or age over 45years were excluded. Medical records were reviewed for medical and obstetric complications and echocardiogram findings. Demographic characteristics and rate of diastolic dysfunction were compared between patients with preeclampsia and without preeclampsia. Multivariate logistic regression was performed controlling for age, ethnicity, gestational age at delivery, diabetes, preeclampsia, intrauterine growth restriction (IUGR), antihypertensive use and magnesium sulfate administration. RESULTS: Sixty-six patients were identified, of which 39 (59%) had preeclampsia. Past history of preeclampsia, IUGR in the current pregnancy, antihypertensive use and magnesium sulfate use were higher in the preeclampsia group. Fifteen patients (39%) in the preeclampsia group were African-American compared to 2 (3%) in the control group (p<0.01). Seventeen (44%) of the patients with preeclampsia were found to have diastolic dysfunction compared to 3 (11%) controls (OR=6.18, 95% CI 1.59,24.02; p=0.006). Logistic regression analysis did not reveal other independent predictors of diastolic dysfunction. In the patients with preeclampsia, history of preeclampsia with severe features and IUGR were not associated with diastolic dysfunction. CONCLUSIONS: Our study supports previous findings that preeclampsia is associated with diastolic dysfunction.

Patient Awareness of Untoward Effects of Smoking on Fetal and Maternal Well-being During Pregnancy: A Pilot Study.

INTRODUCTION: To identify knowledge gaps regarding adverse effects of smoking during pregnancy that could be targeted through antenatal education. METHODS: This was a cross-sectional survey of patients who presented for initial prenatal care from April 6, 2011, through May 25, 2011. Inclusion criteria included fluency in English and completion of at least 75% of the questionnaire. Survey included demographic information and 4 sections that assessed (1) general knowledge about the effects of smoking, (2) cancer risks associated with smoking, (3) maternal and fetal complications resulting from smoking, and (4) long-term effects of smoking on offspring. Participants were grouped as nonsmokers, former smokers, and current smokers. Data from each group were compared using analysis of variance with Tukey-Kramer post-hoc tests. RESULTS: There were 82 participants (54 nonsmokers, 17 former smokers, and 11 smokers). Self-perceived knowledge about the adverse effects of smoking was significantly less in smokers than in nonsmokers (P < 0.05). There was no statistical difference between the knowledge base of smokers when compared with nonsmokers and former smokers. Smokers seemed to be less aware of the long-term respiratory morbidity associated with maternal smoking in their offspring. There was an overall deficit in knowledge among all 3 groups of cancer risks associated with smoking other than lung cancer. CONCLUSIONS: Obstetrician-gynecologists should employ more aggressive approaches in the education of pregnant parturients about the known deleterious maternal and fetal effects of smoking, especially those risks related to cancers other than lung and long-term respiratory morbidity in their children.

Labor outcomes of obese patients undergoing induction of labor with misoprostol compared to dinoprostone.

OBJECTIVE: The aim of the article is to evaluate and compare labor outcomes in obese patients undergoing induction of labor (IOL) with misoprostol and dinoprostone. STUDY DESIGN: This was a retrospective review of patients who delivered from February 1, 2008, to July 1, 2013 at our institution. All obese women who underwent IOL were identified. The rates of successful cervical ripening and cesarean delivery (CD) for patients who underwent IOL with misoprostol and dinoprostone were calculated and compared. RESULTS: A total of 564 women met inclusion criteria; 297 (52.7%) were induced with misoprostol, and 267 (47.3%) were induced with dinoprostone. The misoprostol group had a higher successful cervical ripening rate (78.1 vs. 66.7%; odds ratio [OR], 1.79; 95% confidence interval [CI], 1.23-2.6; p = 0.002) and a lower CD rate (39.1 vs. 51.3%; OR, 0.61; 95% CI, 0.44-0.85; p = 0.003) than the dinoprostone group. This significance persisted in a multivariate model adjusting for parity, gestational age, birth weight, and indication for IOL. The rates of tachysystole, terbutaline use, postpartum hemorrhage, and infectious morbidity were comparable in both groups, as were Apgar scores, rates of neonatal intensive care unit admission, and meconium passage. CONCLUSION: In obese women undergoing IOL, misoprostol leads to a higher successful cervical ripening rate and a lower CD rate than dinoprostone, with a similar rate of peripartum complications and neonatal outcomes.

Does genital tract GBS colonization affect the latency period in patients with preterm premature rupture of membranes not in labor prior to 34 weeks?

OBJECTIVE: To determine if genital tract colonization with GBS at the time of preterm premature rupture of membranes (PPROM) affects the latency period. STUDY DESIGN: A retrospective cohort study was performed of all gravidas admitted with PPROM between 23 and 34 weeks of gestation from 1 January 2003 to 29 February 2012. Vaginal/rectal specimens for GBS were performed on admission. The latency period and infectious complications were evaluated in GBS-positive and GBS-negative groups. RESULTS: Hundred and eighty-nine women were identified with PPROM, 177 meet the inclusion criteria. 60 patients were GBS positive on admission, 117 were GBS negative. Median latency period in GBS-positive and GBS-negative groups did not differ (6.8 versus 7.3 days, p = 0.384). Risk of intra-amniotic, wound infection, maternal and neonatal sepsis, and composite infectious morbidity did not differ between the GBS-positive and GBS-negative groups. Among patients who underwent cesarean delivery, GBS-negative group had a higher risk of endomyometritis (25%) compared to the GBS-positive group (6%), p = 0.05. CONCLUSION: GBS genital tract colonization on admission does not appear to affect the latency period or increase the risk of intra-amniotic infection in patients with PPROM.

Does preeclampsia predict the risk of late postpartum eclampsia?

Objective To investigate potential predictive symptoms of late postpartum eclampsia (LPE). Study Design Retrospective review of patients delivered at a single academic medical center and diagnosed with eclampsia greater than 48 hours postdelivery. Results Among 19 patients with eclampsia, 5 (26%) patients with confirmed eclampsia seized greater than 48 hours after delivery. None of these patients showed evidence of preeclampsia intrapartum or immediately postpartum and none received intrapartum magnesium sulfate. Prior to seizure activity, 4 of 5 (80%) patients had increased blood pressure and 2 of 5 (40%) had central nervous system symptoms (headache and visual changes). Conclusion Gestational hypertension (GHTN) may be a risk factor for LPE. Consideration of seizure prophylaxis for patients with GHTN may facilitate the prevention of LPE.

Obesity, comorbidities, and the cesarean delivery rate.

OBJECTIVE: To evaluate the effect of comorbidities and induction of labor (IOL) on the cesarean delivery (CD) rate in an obese nulliparous cohort. STUDY DESIGN: This was a retrospective review of medical records of patients who delivered at our institution from January 1, 2010, to January 18, 2011. Nulliparous patients were identified with a body mass index of ≥ 30.0 kg/m2. The rates of IOL and CD for patients with a comorbidity were compared with those patients without a comorbidity. RESULTS: Among 1908 patients, 105 met inclusion criteria. The CD rate was significantly higher in the comorbid group (58.5%) than in the control group (34.6%) [odds ratio (OR) 2.66, 95% confidence interval (CI) 1.21 to 5.87, p = 0.019] [corrected].The IOL rate was significantly higher in the comorbid group (71.7% versus 15.4%; OR 13.93, 95% CI 5.33 to 36.46, p < 0.0001). Preeclampsia (44.7%) was the most common indication for IOL in the comorbid group, whereas postterm pregnancy (50%) was the most common indication in the control group. CONCLUSION: The CD rate in obese women with comorbidities is higher than that of obese women without comorbidity. These results suggest that the higher IOL rate and subsequent failed induction in obese women with comorbidities is a significant factor contributing to this association.

Ertapenem compared to combination drug therapy for the treatment of postpartum endometritis after cesarean delivery.

OBJECTIVE: Ertapenem is a broad spectrum carbapenem approved for the treatment of postpartum endometritis. Data regarding clinical outcomes after treatment with ertapenem for endometritis after cesarean delivery are limited. Our objectives were to compare clinical outcomes and cost of ertapenem versus a multi-drug regimen for treatment of endometritis after cesarean delivery. METHODS: Retrospectively, patients with endometritis after cesarean delivery who were treated with ertapenem (group A) were compared to those treated with a combination regimen (group B). Mann-Whitney U and Fisher's Exact were used for statistical analysis with p value <0.05 considered statistically significant. RESULTS: Sixty-three patients were included: 31 in group A and 32 in group B. Demographics and intrapartum characteristics did not differ. Number of administered doses (A: 3, B: 11.5 p < 0.0001), cost (A: $156.63, B: $54.48 p < 0.0001) and nursing time in minutes (A: 6.6, B: 25.3 p < 0.0001) were different between both groups. Wound complications were higher in group A, occurring in 7 patients compared to 1 patient in group B (p = 0.024). CONCLUSION: Although time and number of administered doses were less in group A, given the high wound complication rate in patients treated with ertapenem, this drug may not be appropriate for all patients with endometritis after CD.

Asymptomatic bacteriuria in pregestational diabetic pregnancies and the role of group B streptococcus.

We sought to determine if gravidas with pregestational diabetes mellitus (DM) are at increased risk for asymptomatic bacteriuria (ASB) compared with nondiabetic gravidas. This is a retrospective case-control study of 150 pregnant patients with pregestational DM and 294 nondiabetic controls. Rates of ASB and any colony count of group B streptococcus (GBS) bacteriuria were reviewed. The incidence of ASB among pregestational diabetics was higher compared with nondiabetic gravidas (18% versus 8.2%, odds ratio [OR] 2.47, 95% confidence interval [CI] 1.37 to 4.45). GBS was the most common organism in diabetic gravidas (26%). There was no difference in incidence of ASB recurrence (OR 1.26, 95% CI 0.37 to 4.36), but antibiotic resistance was higher in the control group (OR 0.28, 95% CI 0.09 to 0.91). Diabetic gravidas with ASB or any level of GBS bacteriuria had higher hemoglobin A (1c) values compared with diabetics without ASB (8.31 +/- 1.89 versus 7.31 +/- 1.84, P = 0.0035). Our results demonstrate that gravidas with DM are at increased risk of ASB including GBS bacteriuria compared with non-diabetic gravidas.

Pregnancy outcomes in young women with perinatally acquired human immunodeficiency virus-1.

OBJECTIVE: The objective of the study was to review pregnancy and neonatal outcomes among perinatally infected pregnant patients at our institution. STUDY DESIGN: A retrospective review of maternal and neonatal records for all 10 perinatally infected adolescents between 1997 and 2007 was performed. Demographics, CD4 and viral load, antiretroviral treatment, medical comorbidities, pregnancy outcomes, and neonatal human immunodeficiency virus (HIV) status were abstracted. RESULTS: The median age at first pregnancy was 18.5 years and 70% were African American. The most common comorbidities were hematologic abnormalities (70%) and cervical dysplasia/sexually transmitted infections (STIs) (80%). Initial median CD4 and viral load were 317 cells/mm(3) and 8780 copies/mL, respectively. The median gestational age at delivery was 38 weeks. The most common obstetrical complications were preeclampsia (23%) and premature rupture of membranes/preterm delivery (31%). The cesarean delivery (CD) rate was 62%, with HIV as the indication in 75%. All infants were born alive; 1 was HIV infected. CONCLUSION: Despite high rates of STIs, CD, preterm delivery, and hypertensive disorders, perinatal outcomes were favorable.

Glutaric aciduria type II and narcolepsy in pregnancy.

BACKGROUND: Glutaric aciduria type II is a rare disorder affecting the metabolism of fatty acid oxidation and several mitochondrial dehydrogenase enzymes. Narcolepsy and cataplexy is a disorder affecting sleep cycles and rapid eye movement activity. There is little information on outcome or management for either disorder in pregnancy. CASE: This is a case of a 16-year-old with glutaric aciduria type II and narcolepsy with cataplexy, treated with L-carnitine, riboflavin, fluoxetine, and modafinil during pregnancy. Intrapartum management included intravenous carnitine administration, and the patient underwent cesarean delivery at term without complication. CONCLUSION: This inborn error of metabolism and sleep disorder can be effectively treated during pregnancy with nutritional supplementation and stimulants. Because of the risk of cataplexy during labor, cesarean delivery is recommended to minimize the patient's risk.

Duration of antimicrobial prophylaxis for group B streptococcus in patients with preterm premature rupture of membranes who are not in labor.

OBJECTIVE: The purpose of this study was to determine the duration of the time that is needed to eradicate group B Streptococcus (GBS) in pregnant women with preterm premature rupture of membranes (PPROM). STUDY DESIGN: A retrospective cohort study was performed of pregnant women with PPROM from January 1, 2000, through December 31, 2005. Vaginal/rectal cultures were performed on admission and repeated daily. Patients received antibiotics until cultures were negative for 3 consecutive days. RESULTS: Two hundred fourteen women were identified with PPROM; 169 of the women met the inclusion criteria. Thirty-three patients were GBS positive on admission and had negative cultures by day 3. Neonatal sepsis occurred in 19 neonates (11.2%); 3 neonates (16%) were from mothers who tested positive for GBS on admission, and 16 neonates (84%) were from mothers who tested negative on admission. There were no cases of neonatal sepsis because of GBS. CONCLUSION: A 3-day regimen of antibiotic prophylaxis appears to be adequate to eradicate GBS from the genital tract of patients with PPROM.