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Objective: Marinobufagenin (MBG), a cardiotonic steroid, is distinctly elevated in preeclampsia (preE) and may directly contribute to pathogenesis, possibly through deleterious signaling in cytotrophoblast (CTB) cells. In this study, we evaluate the effects of anti-MBG human monoclonal antibodies on cellular signaling in CTB cells and in a rat model of preE. Methods: CTB cell proliferation in response to MBG with and without anti-MBG was measured using a Cell Titer assay. Pro-angiogenic factors (VEGF and PlGF) and anti-angiogenic factors (sFlt-1 and sEng) in response to MBG with and without antibody were measured. Finally, we evaluated the lead anti-MBG antibody in comparison with the parent murine antibody in a previously described rat model of preE which recapitulates the hypertension, proteinuria, and fetal growth effects of human preE. Results: CTB cells exposed to ≥ 1 nM MBG showed decreased ( p < 0.05) proliferation, decreased secretion of VEGF and PIGF, and increased secretion of sFlt-1 and sEng. Pretreatment with anti-MBG significantly ( p < 0.05) attenuated the MBG-induced modulation of cell proliferation and expression of VEGF, PIGF, sFlt-1, and sEng. In the rat model, anti-MBG treatment normalized blood pressure, reduced proteinuria, and eliminated fetal effects. Conclusions: MBG has the potential to be a causative agent for preE as it causes dysfunction in CTB cells due to the anti-angiogenic milieu. Our study suggests that anti-MBG antibodies can bind to MBG, neutralizing it, and preventing downstream signaling in vitro. In a saline-induced rat model of preE, treatment with anti-MBG antibody was effective at normalizing blood pressure, kidney function, and fetal birth weights. These data suggest that a human monoclonal antibody with high specificity and affinity for MBG has potential as a therapeutic for preE.

Hydrogen peroxide (H2O2) plays an important role physiologically as the second messenger and pathologically as an inducer of oxidative stress in injury, ischemia and other conditions. However, it is unclear how H2O2 influences various cellular functions in health and disease differentially, particularly in the blood-brain barrier (BBB). We hypothesized that the change in cellular concentrations of H2O2 is a major contributor in regulation of angiogenesis, barrier integrity/permeability and cell death/apoptosis in BBB endothelial cells. Rat brain microvascular endothelial cells were exposed to various concentrations of H2O2 (1 nM to 25 mM). BBB tight junction protein (zonula ocludens-1; ZO-1) localization and expression, cytoskeletal organization, monolayer permeability, angiogenesis, cell viability and apoptosis were evaluated. H2O2 at low concentrations (0.001 μM to 1 μM) increased endothelial cell tube formation indicating enhanced angiogenesis. H2O2 at 100 μM and above induced monolayer hyperpermeability significantly (p 2O2 at 10 mM and above decreased cell viability and induced apoptosis (p 2O2, but had no effect on protein expression. Cytoskeletal disorganizations were observed starting at 1 μm. In conclusion H2O2 influences angiogenesis, permeability, and cell death/apoptosis in a tri-phasic and concentration-dependent manner in microvascular endothelial cells of the blood-brain barrier.

Background In the United States (U.S.), annual influenza vaccination has been recommended for all persons aged ≥6 months with the Healthy People 2020 coverage target of 70%. However, vaccination coverage has remained around 42–49% during the past eight influenza seasons. We sought to quantify influenza vaccination coverage and factors associated with vaccination in persons seeking outpatient medical care for an acute respiratory illness (ARI). Methods We enrolled outpatients aged ≥6 months with ARI from >50 U.S. clinics from 2011 to 2012 through 2018–2019 influenza seasons and tested for influenza with molecular assays. Vaccination status was based on documented receipt of the current season’s influenza vaccine. We estimated vaccination coverage among influenza-negative study participants by study site, age, and season, and compared to state-level influenza coverage estimates in the general population based on annual immunization surveys. We used multivariable logistic regression to examine factors independently associated with receipt of influenza vaccines. Results We enrolled 45,424 study participants with ARI who tested negative for influenza during the study period. Annual vaccination coverage among influenza-negative ARI patients and the general population in the participating states averaged 55% (range: 47–62%), and 52% (range: 46–54%), respectively. Among enrollees, coverage was highest among adults aged ≥65 years (82%; range, 80–85%) and lowest among adolescents aged 13–17 years (38%; range, 35–41%). Factors significantly associated with non-vaccination included non-White race, no college degree, exposure to cigarette smoke, absence of high-risk conditions, and not receiving prior season influenza vaccine. Conclusions Influenza vaccination coverage over eight seasons among outpatients with non-influenza respiratory illness was slightly higher than coverage in the general population but 15% lower than national targets. Increased efforts to promote vaccination especially in groups with lower coverage are warranted to attain optimal health benefits of influenza vaccine.

Blood-brain barrier (BBB) breakdown and the associated microvascular hyperpermeability followed by brain edema are hallmark features of several brain pathologies, including traumatic brain injuries (TBI). Recent studies indicate that pro-inflammatory cytokine interleukin-1β (IL-1β) that is up-regulated following traumatic injuries also promotes BBB dysfunction and hyperpermeability, but the underlying mechanisms are not clearly known. The objective of this study was to determine the role of calpains in mediating BBB dysfunction and hyperpermeability and to test the effect of calpain inhibition on the BBB following traumatic insults to the brain. In these studies, rat brain microvascular endothelial cell monolayers exposed to calpain inhibitors (calpain inhibitor III and calpastatin) or transfected with calpain-1 siRNA demonstrated attenuation of IL-1β-induced monolayer hyperpermeability. Calpain inhibition led to protection against IL-1β-induced loss of zonula occludens-1 (ZO-1) at the tight junctions and alterations in F-actin cytoskeletal assembly. IL-1β treatment had no effect on ZO-1 gene (tjp1) or protein expression. Calpain inhibition via calpain inhibitor III and calpastatin decreased IL-1β-induced calpain activity significantly (p < 0.05). IL-1β had no detectable effect on intracellular calcium mobilization or endothelial cell viability. Furthermore, calpain inhibition preserved BBB integrity/permeability in a mouse controlled cortical impact model of TBI when studied using Evans blue assay and intravital microscopy. These studies demonstrate that calpain-1 acts as a mediator of IL-1β-induced loss of BBB integrity and permeability by altering tight junction integrity, promoting the displacement of ZO-1, and disorganization of cytoskeletal assembly. IL-1β-mediated alterations in permeability are neither due to the changes in ZO-1 expression nor cell viability. Calpain inhibition has beneficial effects against TBI-induced BBB hyperpermeability.

Diabetes in pregnancy is associated with microvascular complications and a higher incidence of preeclampsia. The regulatory signaling pathways involving nitric oxide, cGMP, and cGMP-dependent protein kinase (PKG) have been shown to be down-regulated under diabetic conditions and contribute to the pathogenesis of vascular complications in diabetes. The present study was undertaken to investigate how high glucose concentrations regulate PKG expression in cytotrophoblast cells (CTBs). Human CTBs (Sw. 71) were treated with 45, 135, 225, 495, or 945 mg/dL glucose for 48 h. Some cells were pretreated with a p38 inhibitor (10 μM SB203580) or 10 μM rosiglitazone. After treatment, the cell lysates were subjected to measure the expression of protein kinase G1α (PKG1α), protein kinase G1β (PKG1β), soluble guanylate cyclase 1α (sGC1α), and soluble guanylate cyclase 1 β (sGC1β) by Western blot. Statistical comparisons were performed using analysis of variance with Duncan's post hoc test. The expressions of PKG1α, PKG1β, sGC1α, and sGC1β were significantly down-regulated (p0.05) in CTBs treated with135 mg/dL glucose compared to basal (45 mg/dL). The hyperglycemia-induced down-regulation of cGMP and cGMP-dependent PKG were attenuated by the SB203580 or rosiglitazone pretreatment. Exposure of CTBs to excess glucose down-regulates cGMP and cGMP-dependent PKG, contributing to the development of vascular complications in diabetic mothers during pregnancy. The attenuation of hyperglycemia-induced down-regulation of PKG proteins by SB203580 or rosiglitazone pretreatment further suggests the involvement of stress signaling mechanisms in this process.

OBJECTIVE Preeclampsia (preE), a syndrome of hypertension, proteinuria, and edema, has many elusive triggers. The renin-angiotensin system has been implicated in preE pathogenesis. In this study, we test the hypothesis that (pro)renin levels are increased in preE patients and that levels of (pro)renin and (pro)renin receptor ((P)RR) are elevated in a rat model of preE. METHODS We recruited 30 preE and 43 normal pregnant consenting patients. We used normally pregnant rats (NP, n = 10) and pregnant rats receiving weekly injections of desoxycorticosterone acetate and whose drinking water was replaced with 0.9% saline (preE, n = 10). Plasma and placental levels of (pro)renin were assayed by ELISA. Placental and kidney (P)RR was measured both by immunoblotting and immunohistochemistry. RESULTS The mean plasma (pro)renin of 27.1±5.2 in preE patients differs from that in patients without preE: 14.8±5.2 ng Ang I/ml/hour (P < 0.0001). In rats, both plasma (NP: 22.7±4.3 and preE: 49.2±10.0 ng Ang I/ml/hour) and placental (NP: 152±24 and preE: 302±39 ng/g tissue) levels of (pro)renin were higher (P < 0.001) in preE compared to NP rats. (P)RR expression was greater (P < 0.05) in placental tissue of preE rats, while kidney (P)RR expression was similar. CONCLUSION Elevated levels of circulating (pro)renin have been observed in preE patients and in a rat model of preE. We also found the increased expression of placental (P)RR in preE rats.

This double-blinded, randomized, crossover study evaluated the safety and effectiveness of 20 mL/kg aliquots of packed red blood cell (PRBC) transfusions versus 15 mL/kg aliquot transfusions in very low birth weight (VLBW) infants with anemia. The study enrolled 22 hemodynamically stable VLBW infants requiring PRBC transfusions, with a mean gestational age of 25.7 ± 2.2 weeks and birth weight of 804 ± 261 g. Each infant was randomized to receive one of two treatment sequences: 15 mL/kg followed by 20 mL/kg or 20 mL/kg followed by 15 mL/kg. The infants were monitored during and after transfusions, and the efficacy and safety of the treatments were evaluated. Infants had higher posttransfusion hemoglobin (13.2 g/dL vs 11.8 g/dL, P < 0.01) and hematocrit levels (38.6 g/dL vs 34.4 g/dL, P < 0.01) following 20 mL/kg PRBC transfusions when compared to 15 mL/kg transfusions. There were no differences in the incidence of tachypnea, hepatomegaly, edema, hypoxia, necrotizing enterocolitis, or vital sign instability between groups. In conclusion, high-volume PRBC transfusions (20 mL/kg) were associated with higher posttransfusion hemoglobin and hematocrit levels but no adverse effects. Higher-volume transfusions may reduce the need for multiple transfusions and therefore the number of donors the infant is exposed to.

The interaction between pre-eclampsia and diabetes mellitus (DM) is far from being completely understood. In this study, we compared normal pregnancies with those complicated with pre-eclampsia, gestational DM, and/or pre-existing diabetes to assess the effects of hyperglycemia on placental development. AnInstitutional Review Board (IRB) approved retrospective cross-sectional study with 621 subjects was performed. Statistical analysis was performed using Duncan's post hoc test and analysis of variance. Regardless of diabetes status, patients with pre-eclampsia delivered prematurely. Patients in the group with pre-eclampsia and pregestational diabetes delivered much earlier, at 35.0±0.4 weeks, when compared with the patients that had pre-eclampsia with gestational diabetes and pre-eclampsia with no diabetes (*P

Background In the US, approximately 12.7% of all live births are preterm, 8.2% of live births were low birth weight (LBW), and 1.5% are very low birth weight (VLBW). Although technological advances have improved mortality rates among preterm and LBW infants, improving overall rates of prematurity and LBW remains a national priority. Monitoring short- and long-term outcomes is critical for advancing medical treatment and minimizing morbidities associated with prematurity or LBW; however, studying these infants can be challenging. Several large, multi-center neonatal databases have been developed to improve research and quality improvement of treatments for and outcomes of premature and LBW infants. The purpose of this systematic review was to describe three multi-center neonatal databases. Methods We conducted a literature search using PubMed and Google Scholar over the period 1990 to August 2014. Studies were included in our review if one of the databases was used as a primary source of data or comparison. Included studies were categorized by year of publication; study design employed, and research focus. Results A total of 343 studies published between 1991 and 2014 were included. Studies of premature and LBW infants using these databases have increased over time, and provide evidence for both neonatology and community-based pediatric practice. Conclusions Research into treatment and outcomes of premature and LBW infants is expanding, partially due to the availability of large, multicenter databases. The consistency of clinical conditions and neonatal outcomes studied since 1990 demonstrates that there are dedicated research agendas and resources that allow for long-term, and potentially replicable, studies within this population. Electronic supplementary material The online version of this article (doi:10.1186/s13104-016-2336-4) contains supplementary material, which is available to authorized users.

Preeclampsia (preE) is a hypertensive disorder seen in 3-10% of human pregnancies and is diagnosed by de novo onset of hypertension and proteinuria. Several research groups provided evidence for reduced aldosterone (Aldo) and progesterone (Prog) availability in preE. The aim of this study was to determine the levels of Aldo and Prog in preE.Normal pregnant (NP; n = 39) and preE (n = 30) patients were recruited to have their blood drawn between 21 and 40 weeks of pregnancy. Two groups of rats were used in this study: NP rats (n = 10) and preE rats (n = 10), which were given weekly injections of desoxycorticosterone acetate and 0.9% saline to drink. Aldo and Prog levels were assayed in plasma and urine samples by ELISA kits.In preE patients, the mean Aldo and Prog levels were suppressed (p 0.05) compared to NP patients. NP patients exhibited a trend of increased levels of Aldo with an increase in gestational age; however, preE patients had the opposite trend. Both normal and preE patients exhibited a trend of increased levels of Prog with an increase in gestational age. The plasma and urinary Aldo and Prog levels were lower (p 0.05) in preE rats compared to NP rats.We have demonstrated using a rat model and patients that both Aldo and Prog are suppressed in preE and thus may be used as biomarkers for preE.

A synthetic tripodal-based thiourea receptor (PNTTU) was used to explore the receptor/ligand binding affinity using CTB cells. The human extravillous CTB cells (Sw.71) used in this study were derived from first trimester chorionic villus tissue. The cell proliferation, migration and angiogenic factors were evaluated in PNTTU-treated CTB cells. The PNTTU inhibited the CTBs proliferation and migration. The soluble fms-like tyrosine kinase-1 (sFlt-1) secretion was increased while vascular endothelial growth factor (VEGF) was decreased in the culture media of CTB cells treated with ≥1 nM PNTTU. The angiotensin II receptor type 2 (AT2) expression was significantly upregulated in ≥1 nM PNTTU-treated CTB cells in compared to basal, however, the angiotensin II receptor, type 1 (AT1) and vascular endothelial growth factor receptor 1 (VEGFR-1) expression was downregulated. The anti-proliferative and anti-angiogenic effect of this compound on CTB cells are similar to the effect of CTSs. The receptor/ligand affinity of PNTTU on CTBs provides us the clue to design a potent inhibitor to prevent the CTS-induced impairment of CTB cells.

Objective Microvascular hyperpermeability that occurs due to breakdown of the BBB is a major contributor of brain vasogenic edema, following IR injury. In microvascular endothelial cells, increased ROS formation leads to caspase-3 activation following IR injury. The specific mechanisms, by which ROS mediates microvascular hyperpermeability following IR, are not clearly known. We utilized an OGD-R in vitro model of IR injury to study this. Methods RBMEC were subjected to OGD-R in presence of a caspase-3 inhibitor Z-DEVD, caspase-3 siRNA or an ROS inhibitor L-AA. Cytochrome c levels were measured by ELISA and caspase-3 activity was measured fluorometrically. TJ integrity and cytoskeletal assembly were studied using ZO-1 immunofluorescence and rhodamine phalloidin staining for f-actin, respectively. Results OGD-R significantly increased monolayer permeability, ROS formation, cytochrome c levels, and caspase-3 activity (p

To understand factors contributing to the neonatal mortality rate (NMR), we studied trends in the NMR during 2000 to 2009 with respect to demographic factors and health care resources. Birth- and death-linked mortality data for 14,168 neonatal deaths that occurred between 2000 and 2009 were obtained from the Texas Department of Health and Human Services. Demographic factors and health care resource data were analyzed using analysis of variance, chi-square tests, and linear regression analysis. The average NMR increased from 3.37 in 2000 to 3.77 in 2009. The NMR in blacks ranged from 6.57 to 8.97 during the study period. Among the babies who died, the mean birthweight decreased from 1505 to 1275 g (P < 0.001) and the mean gestational age decreased from 28.4 to 27.8 weeks (P < 0.001). Cesarean section deliveries increased from 32.7% to 44.9% (P < 0.001). The percentage of mothers receiving prenatal care increased from 81.4% to 86.6% (P < 0.001). Mothers with a college education increased from 8.8% to 20.5% (P < 0.001). The median household income increased from $41,047 to $49,189 (P < 0.001). The number of neonatal intensive care unit beds increased from 33.4 to 56 per 10,000 births, and the number of neonatologists increased from 0.27 to 0.40 per 10,000 women of 15 to 44 years of age. In conclusion, the NMR didn't improve despite improvements in demographic factors and health care resources. Racial disparities persist, with a high NMR in the black population. We speculate a possible genetic predisposition related to ethnicity, and a potentially higher rate of extreme prematurity might have contributed to a high NMR in the study population.

Bilateral congenital pseudoarthrosis of the clavicles is extremely rare. We report a case of this entity presenting in the neonatal period. We highlight the importance of the differential diagnosis when clavicular fracture shows no evidence of healing or occurs bilaterally.

Background: Preeclampsia (PreE) is de novo development of hypertension and proteinuria after 20 weeks of gestation with multiple pathophysiologic triggers affecting 3-8% of pregnancies. PreE has a significant link to alterations of feto-placental stress that pass to the offspring causing detrimental effects. We assessed and compared the pregnancy outcomes between patients with and without PreE. Methods: We recruited 35 normal pregnant (NP) and 25 PreE consenting patients in an IRB approved prospective study at Scott & White Memorial Hospital, Temple, Texas. We evaluated maternal age, body mass index (BMI), blood pressures, proteinuria, and gestational age at delivery. We divided the PreE subjects into early (before 34 weeks) and late PreE (after 34 weeks) groups and compared their outcomes. Placental thickness and volumes were measured. We also evaluated neonates for intrauterine growth restriction (IUGR), gestational age at birth, anthropometric measurements including Ponderal Index (PI), length of hospitalization and other neonatal complications. Comparisons were performed using Student’s t test. Results: Maternal: The systolic blood pressure (SBP) and diastolic blood pressure (DBP) were higher in PreE (SBP 166 ± 11; DBP 93 ± 10) compared to normal pregnancies (SBP 122 ± 10; DBP 74 ± 9; p Placenta: The placental thickness in early PreE subjects was 25mm compared to 32mm in late PreE (p 3 compared to 393cm 3 (p Neonatal: The average GA at delivery was lower in PreE (34.8 wks. ± 4) compared to NP (39.2 weeks ± 0.3; p

Background: Preeclampsia (PreE), a de novo development of Hypertension in consort with proteinuria after 20 weeks of gestation is the leading cause of morbidity and mortality in mother and the offspring. It affects approximately 3-8% of overall pregnancies. Although, specific etiologies remain unknown, it has been supported by various studies that PreE is not just a single disorder, but a syndrome of pertinent multiple pathophysiological factors. Methods: An IRB approved retrospective chart review over a year (January 2014 to December 2014) was conducted of all pregnancies occurred at Baylor Scott and White Health System, Temple, Texas (N = 3704). We divided all pregnancies into two separate groups: PreE (N = 299) vs. Non PreE (N = 3405). We compared the neonatal outcomes between two groups including their offspring’s gestational age, birth weight, admission rate to Neonatal Intensive Care Unit (NICU), occurrence of bronchopulmonary dysplasia (BPD), necrotizing enterocolitis (NEC), hypoglycemia, thrombocytopenia, intraventricular hemorrhage (IVH) and length of hospital stay (LOS). Results: We found amongst these two groups, infants born to PreE mothers have significantly lower birthweight (Mean = 2807 grams, SD = 841 grams) compared to Non PreE mothers (Mean = 3383 grams, SD = 619 grams) (P Conclusion: We can conclude from this retrospective analysis that infants born to PreE mothers have lower birth weight indicating the intrauterine growth restriction and the lower gestational age indicating preterm birth. Moreover, the data indicate the higher rate of BPD, hypoglycemia, thrombocytopenia and requirement of increased length of hospital stay in infants born to PreE mothers compared to Non PreE mothers.

Similar pro-inflammatory responses are present in pre-eclampsia (PE) and necrotizing enterocolitis (NEC). We hypothesized that maternal PE is an independent risk factor for the development of NEC.A retrospective database of all live births (2008-2011) at a tertiary center was constructed. Infant and maternal characteristics were gathered. Babies born to mothers with or without PE were compared. Data were analyzed using Mann-Whitney U, Pearson's χ(2), binary logistic regression and relative risks.Incidence of NEC was 1.5% in non-PE and 4.6% in the PE group (p 0.001), but once controlled for gestational age and birth weight, the difference lost statistical significance. PE babies were more frequently preterm (41.4% versus 14.5%, p 0.001) and had intrauterine growth restriction (IUGR) (10.2% versus 6.3%, p 0.001). Within preterm babies, 9.0% of non-PE and 10.8% of PE babies developed NEC (p = 0.25). Effect of PE was significant in sub-group of IUGR babies, with NEC in 1.5% of non-PE and 13.6% in PE babies (p 0.001).Maternal PE is an independent risk factor for the development of NEC in some sub-groups of babies, most notably with IUGR. Fetal hypoxia caused by abnormal placentation in PE leads to restricted growth, and may be the underlying mechanism that predisposes the newborn to NEC.

Background Normal pregnancy relies on a careful balance between immune tolerance and suppression. It is known that strict regulation of maternal immune function, in addition to components of inflammation, is paramount to successful pregnancy, and any imbalance between proinflammatory and anti-inflammatory cytokines and chemokines can lead to aberrant inflammation, often seen in complicated pregnancies. Inflammation in complicated pregnancies is directly associated with increased mortality and morbidity of the mother and offspring. Aberrant inflammatory reactions in complicated pregnancies often lead to adverse outcomes, such as spontaneous abortion, preterm labor, intrauterine growth restriction, and fetal demise. The role of inflammation in different stages of normal pregnancy is reviewed, compared, and contrasted with aberrant inflammation in complicated pregnancies. The complications addressed are preterm labor, pregnancy loss, infection, preeclampsia, maternal obesity, gestational diabetes mellitus, autoimmune diseases, and inflammatory bowel disease. Aim This article examines the role of various inflammatory factors contributing to aberrant inflammation in complicated pregnancies. By understanding the aberrant inflammatory process in complicated pregnancies, novel diagnostic tools and therapeutic interventions for modulating it appropriately can be identified.

Introduction Preeclampsia (preE) is pregnancy-induced hypertension affecting a significant proportion of pregnant women worldwide and can cause detrimental effects in the mother and newborn. Some of the effects in the newborn include neonatal thrombocytopenia. Pertaining specifically to neonatal thrombocytopenia, several questions remain unanswered. Discussion According to the current literature, neonatal thrombocytopenia due to maternal preE is highly prevalent in the general population and the incidence is reported to be around 30% worldwide. This review gives an insight into the syndrome and summarizes the possible pathological mechanisms, the diagnostic approach, complications, and therapeutic interventions of neonatal thrombocytopenia. It also identifies the involvement of other cell lines, apart from platelets in the newborns. Furthermore, we suggest a future prospective study to investigate the pathogenesis of preE and plan a study involving animal models to come up with a possible therapeutic intervention to prevent preE and its various consequences in neonates.

Congenital midline nasal anomalies are rare, with a prevalence of 1 in 20,000 to 40,000 births and with 5% to 7% of them being nasal glioma. Differential diagnoses of nasal anomalies include nasal dermoid cysts, gliomas, encephaloceles, nasal polyps, and some other rare anomalies. Due to current medical technological advancements, most of these anomalies are easily correctable, though delaying management may lead to fatal effects. This report describes two cases—one of nasal glioma and one of nevus lipomatosus cutaneous superficialis—that presented as respiratory distress in a newborn. Approximately 10 to 20 cases of these two conditions have been described; notably, this is the second documented case of nevus lipomatosus cutaneous superficialis with nasal presentation.

Objective: Preeclampsia (PreE) and diabetes mellitus (DM) in pregnancy share many risk factors and consequences. Thus, the interactions between these two disease-processes need to be further examined. We compared normal pregnancies to those complicated with preE, gestational diabetes (GDM), and/or pre-existing DM to assess the effect of DM on placental development and outcomes when this condition is complicated by preE. Methods: Chart reviews were performed in an IRB approved retrospective case-control design with pregnancies resulting in live born singletons. Total 178 subjects with preE with and without DM or GDM and live born singletons were selected from deliveries in 2008 through 2011 at Scott & White Memorial Hospital, Temple, Texas. These were compared to 443 without preE and with and without DM or GDM. Statistical analysis was performed using ANOVA and Duncan’s post-hoc test. Results: Patients who developed preE had higher systolic and diastolic pressures compared to groups without preE (p < 0.05). Patients with DM or GDM were older (p < 0.05). There was no difference among groups for gravidity (p = 0.21) with the average gravidity of 2.7 (1.8 SD) for 621 subjects having a range of 1 to 14 pregnancies. Patients with preE delivered earlier in pregnancy than those without preE regardless of diabetes status. However, those with preE and DM delivered earlier at 35.0 ± 0.4 weeks than the other two preE groups (p < 0.05), suggesting a more severe condition. Patients with DM who developed preE delivered smaller (p < 0.05) babies (correcting for gestational age at delivery) than those with DM without preE (1.00 ± 0.03 versus 1.16 ± 0.04, respectively). Development of GDM did not result in smaller babies for those pregnancies with preE (1.07 versus 1.09). Conclusions: The development of preE in those with pre-existing DM led to growth restriction and more severe disease as evidenced by lower birth weights corrected for gestational age and earlier gestational ages at delivery. These differences were not seen in GDM pregnancies. This observation supports the concept that elevated glucose levels during first trimester placental development may alter the placenta and lead to restriction later in pregnancy when a second stimulus triggers preE.

Objective: Approximately 20% of the diabetic pregnant women develop preeclampsia (preE). In a recent study, we have shown that hyperglycemia impairs CTB function via stress signaling. In the present study, we assess the CTBs apoptotic signaling. Study Design: Human extravillous CTBs were treated with 0, 100, 200, 300 or 400 mg/dL glucose for 48h. Some cells were pretreated with a p38 inhibitor or a peroxisome proliferator-activated receptor gamma (PPARγ) ligand. Other cells were treated with D-Mannitol. Cell migration was performed by Matrigel migration kit. Cell lysates were utilized to measure PPARγ, p38 MAPK phosphorylation, and apoptotic signaling proteins; Bcl-2-associated X protein (Bax), anti-apoptotic Bcl-2 and caspase-9 and cyclooxygenase-2 (Cox-2) by western blot. Results: CTBs migration was inhibited by 蠅 150 mg/dL of glucose compared to basal (100 mg/dL) (p 150 mg/dL glucose. The expression of Bax/Bcl...

Objective: Preeclampsia (preE), a syndrome of hypertension and proteinuria in pregnancy, is thought to be initiated with alterations of placental function. Hypoxia and oxidative stress can lead to placental apoptotic signaling, which pass the placental barrier and leave persistent defect in the circulation of the offspring that may predispose to a pathological response later in life. We assessed apoptotic signaling in placentas and umbilical cords from patients with or without preE. We also evaluated the pregnancy outcomes. Methods: In this study, we recruited 20 normal pregnant (NP) and 20 preE consenting patients in an IRB approved prospective study from Scott & White hospital, Temple, Texas. Inclusion criteria for determination of preE patients include blood pressure >140/90 and presence of proteinuria >300 mg of protein/24h urine. Samples of placenta and umbilical cord were collected from those subjects after deliveries. Apoptotic and stress signaling proteins; pro-apoptotic Bcl-2-associated X protein (Bax), anti-apoptotic Bcl-2 protein, caspase 9 and pro-inflammatory protein cyclooxygenase-2 (Cox-2) expression were assayed both by western blot and immunohistochemistry. The p38 mitogen-activated protein kinase (p38 MAPK) phosphorylation was evaluated by western blot. Comparisons were performed using ANOVA with Duncan’s post-hoc test. Results: The ratio of Bax/Bcl-2 expression (Placenta: 1.2 fold, Cord: 1.5 fold), Cox-2 (Placenta: 0.8 fold, Cord: 2.5 fold), Caspase 9 (Placenta: 1.5 fold, Cord: 1.8 fold), and p38 MAPK phosphorylation (Placenta: 1.5 fold, Cord: 1.7 fold) were up-regulated (p Conclusions: Apoptotic signaling is augmented in preE which alters the intrauterine environment by modulating the pattern of hormonal signals and activating the detrimental cellular signaling that has been transported to the fetus.

Pre-eclampsia (preE) is a multifaceted complication found uniquely in the pregnant patient and one that has puzzled scientists for years. PreE is not a single disorder, but a complex syndrome that is produced by various pathophysiological triggers and mechanisms affecting about 5% of obstetrical patients. PreE is a major cause of premature delivery and maternal and fetal morbidity and mortality. PreE is characterized by de novo development of hypertension and proteinuria after 20 weeks of gestation and affects nearly every organ system, with the most severe consequences being eclampsia, pulmonary edema, intrauterine growth restriction, and thrombocytopenia. PreE alters the intrauterine environment by modulating the pattern of hormonal signals and activating the detrimental cellular signaling that has been transported to the fetus. The fetus has to adapt to this intrauterine environment with detrimental signals. The adaptive changes increase the risk of disease later in life. This review defines the predisposition and causes of preE and the cellular signaling detrimental to maternal health during preE. Moreover, the risk factors for diseases that are transmitted to the offspring have been addressed in this review. The detrimental signaling molecules that have been overexpressed in preE patients raises the possibility that those signals could be therapeutically blocked one day.

Objective: Preeclampsia (preE) is a hypertensive disorder unique to pregnancy with abnormal placentation. We have demonstrated that cardiotonic steroids (CTSs) impair cytotrophoblast (CTB) function...

Purpose The aim of this study was to determine the relationship of birth weight and gestational age with regulatory T cells (T regs ) in cord blood of human newborns. Methods Cord blood mononuclear cells (CBMCs) of 210 newborns were analyzed using flow cytometry to identify T regs (CD3 + , CD4 + , CD25 high , FoxP3 high ) and measure FoxP3 mean fluorescence intensity (MFI). Suppressive index (SI) was calculated as FoxP3 MFI per T reg . Results Mode of delivery had no significant effect on T regs at birth. Term babies with growth restriction had fewer T regs than their appropriate weight counterparts but equivalent SI. Preterm babies had higher percentages of T regs , but lower SI than term controls. SI steadily increased through gestation. Conclusions Intrauterine growth restriction is correlated with fewer circulating T regs and prematurity with decreased functionality of T regs compared to term appropriate weight infants. This may have implications in diseases such as necrotizing enterocolitis that disproportionately affect premature and lower birth weight infants.

One of the most common causes of small bowel obstruction in newborns is ileal atresia, and one of the most common causes of colonic obstruction in neonates is aganglionic megacolon (Hirschsprung disease). However, atresias of the small intestinal tract associated with Hirschsprung disease are extremely rare. We describe an infant born with both ileal atresia and Hirschsprung disease. This is the 19th known report of the case of an infant who had ileal atresia associated with Hirschsprung disease.

OBJECTIVE: To evaluate the usefulness of lumbar puncture (LP) in the initial evaluation of symptom-free infants for congenital syphilis. STUDY DESIGN: We retrospectively studied infants who had successful LPs and were born to untreated or inadequately treated seropositive women between 1990 and 1993 in two hospitals in Washington, D.C. We identified 329 such symptom-free infants (syphilis group). The cerebrospinal fluid (CSF) VDRL was reactive in two (0.6%) infants. The CSF leukocyte and protein concentrations of these infants were compared with those in 84 symptom-free control infants who were born to seronegative women and who had LPs performed in 1993 to rule out sepsis because of associated risk factors. Control infants had negative results for bacterial cultures (CSF and blood) and bacterial antigen tests (CSF and urine). RESULTS: Thirty control subjects and 67 infants in the syphilis group had traumatic taps (CSF erythrocytes >500 × 10 6 /L), and hence were excluded from the analysis of cell count and proteins. Birth weights and gestational ages were similar in both groups. The CSF leukocyte and protein values were similar in the syphilis group and in control infants: mean CSF leukocytes 7.7 × 10 6 /L (mean 7.7/mm 3 , range 0 to 57/mm 3 , SD 8.8) versus 6.9 × 10 6 /L (mean 6.9/mm> 3 , range 0 to 31/mm 3 , SD 7), p = 0.5, and mean protein concentration 981 mg/L (range 270 to 2280 mg/L, SD 376) versus 936 mg/L (range 360 to 1750 mg/L, SD 368), p = 0.96, respectively. The combination of CSF leukocyte values >5 × 10 6 /L (>5/mm 3 ) or protein values >400 mg/L (>40 mg/dl) was found in 97.8% of the infants in the syphilis group, compared with 95.3% of the control group. CONCLUSION: Because of the low yield of reactive CSF VDRL and the similar CSF leukocyte and protein values in the syphilis group and the control infants, the role of routine LP in the initial evaluation of symptom-free infants for congenital syphilis should be reconsidered. (J P EDIATR 1996;128:125-9)

Recently, a number of infants have been born at home, in an ambulance, car, etc., before arrival at the District of Columbia General Hospital. Many of these infants had poor outcome. To evaluate the prevalence and outcome of these infants, we reviewed medical records of all infants born before arrival at the hospital (out-born infants) and compared them with in-hospital deliveries from July 1988 to June 1992. Data were analyzed using Fisher's Exact Test and chi-square test. There were 151 (1.8%) out-born infants and 8,169 (98.2%) in-born infants during this 4-year period. Infants in both groups were predominantly black (85%). The following were significant differences (P

Microvascular hyperpermeability that occurs at the level of the blood-brain barrier (BBB) often leads to vasogenic brain edema and elevated intracranial pressure following traumatic brain injury (TBI). At a cellular level, tight junction proteins (TJPs) between neighboring endothelial cells maintain the integrity of the BBB via TJ associated proteins particularly, zonula occludens-1 (ZO-1) that binds to the transmembrane TJPs and actin cytoskeleton intracellularly. The pro-inflammatory cytokine, interleukin-1β (IL-1β) as well as the proteolytic enzymes, matrix metalloproteinase-9 (MMP-9) are key mediators of trauma-associated brain edema. Recent studies indicate that melatonin a pineal hormone directly binds to MMP-9 and also might act as its endogenous inhibitor. We hypothesized that melatonin treatment will provide protection against TBI-induced BBB hyperpermeability via MMP-9 inhibition. Rat brain microvascular endothelial cells grown as monolayers were used as an in vitro model of the BBB and a mouse model of TBI using a controlled cortical impactor was used for all in vivo studies. IL-1β (10 ng/mL; 2 hours)-induced endothelial monolayer hyperpermeability was significantly attenuated by melatonin (10 μg/mL; 1 hour), GM6001 (broad spectrum MMP inhibitor; 10 μM; 1 hour), MMP-9 inhibitor-1 (MMP-9 specific inhibitor; 5 nM; 1 hour) or MMP-9 siRNA transfection (48 hours) in vitro. Melatonin and MMP-9 inhibitor-1 pretreatment attenuated IL-1β-induced MMP-9 activity, loss of ZO-1 junctional integrity and f-actin stress fiber formation. IL-1β treatment neither affected ZO-1 protein or mRNA expression or cell viability. Acute melatonin treatment attenuated BBB hyperpermeability in a mouse controlled cortical impact model of TBI in vivo. In conclusion, one of the protective effects of melatonin against BBB hyperpermeability occurs due to enhanced BBB integrity via MMP-9 inhibition. In addition, acute melatonin treatment provides protection against BBB hyperpermeability in a mouse model of TBI indicating its potential as a therapeutic agent for brain edema when established in humans.

Objective. To evaluate reliability of umbilical cord blood (UCB) for complete blood count (CBC) and blood cultures compared with the infant’s blood from peripheral site for group B streptococcal (GBS) sepsis screening. Methods. A total of 200 neonates, at risk for GBS infection, were studied prospectively. After birth, UCB sample was obtained for CBC and blood cultures from umbilical vein. Peripheral arterial/venous blood was obtained from the neonate. Results. In 200 neonates, CBC counts were similar for clinical significance except for leukopenia (6% in UCB vs 1.2% in peripheral blood, P = .02). One UCB sample grew GBS and another grew microaerophilic streptococcus, a contaminant. A neonatal sample grew Escherichia coli, a pathogen and another neonatal sample grew Staphylococcus auricularis, a contaminant. Conclusion. CBC results were similar from UCB and the infant for the purpose of GBS screening. Contamination of UCB sample for culture is uncommon. Hence, UCB may be used for GBS sepsis screen.

Objectives Preeclampsia (preE), a syndrome of hypertension and proteinuria in pregnancy, is thought to be initiated with alterations of placental function. Hypoxia and oxidative stress can lead to placental apoptotic signaling, which pass the placental barrier and leave persistent defect in the circulation of the offspring that may predispose to a pathological response later in life. We assessed apoptotic signaling in placentas and umbilical cords from patients with or without preE. We also evaluated the pregnancy outcomes. Methods In this study, we recruited 20 normal pregnant (NP) and 20 preE consenting patients in an IRB approved prospective study. Inclusion criteria of preE patients include blood pressure >140/90 and proteinuria >300 mg of protein/24 h urine. Samples of placenta and umbilical cord were collected after deliveries. Pro-apoptotic Bcl-2-associated X protein (Bax), anti-apoptotic Bcl-2 protein, caspase 9 and pro-inflammatory protein cyclooxygenase-2 (Cox-2) expression were assayed both by western blot and immunohistochemistry. The p38 MAPK phosphorylation was evaluated by western blot. Comparisons were performed using ANOVA with Duncan’s post-hoc test. Results The ratio of Bax/Bcl-2 expression (Placenta: 1.2 fold, Cord: 1.5 fold), Cox-2 (Placenta: 0.8 fold, Cord: 2.5 fold), Caspase 9 (Placenta: 1.5 fold, Cord: 1.8 fold), and p38 phosphorylation (Placenta: 1.5 fold, Cord: 1.7 fold) were up-regulated (p Conclusions Apoptotic signaling is augmented in preE which alters the intrauterine environment by modulating the pattern of hormonal signals and activating the detrimental cellular signaling that has been transported to the fetus. Disclosures M.M. Co: None. D. Leonard: None. L. Perger: None. V.P. Govande: None. M.R. Beeram: None. R.O. Jones: None. S.R. Allen: None. T.J. Kuehl: None. M.N. Uddin: None.

Objectives Preeclampsia (preE), a syndrome of hypertension and proteinuria. Most recently it was demonstrated that high circulating levels of soluble (pro) renin receptor s(P)RR at delivery were associated with preE. In this study the placental expression of (P)RR were evaluated in preE patients and in a rat model of preE as well as in nonhuman primates. We also evaluated the circulatory levels of s(P)RR. Methods (1) Placental samples were collected from 20 NP and 20 preE consenting patients in an IRB approved prospective study. (2) An established rat model of preE and NP rats ( n = 10 each) were used. (3) The placental samples from squirrel monkey (NP; n = 10) and owl monkey (both early and term, NP, n = 1) were collected. The (P)RR expression were measured both by western blotting (WB) and Immunohistochemistry (IHC) using anti-ATP6IP2. The levels of serum s(P)RR were measured by ELISA. Results The placental expression of (P)RR were higher ( p Conclusions These data suggest that increased expression of (P)RR in the placenta are related to the occurrence of preE in both patients and rat models. These data also reconfirmed that the high level of circulatory s(P)RR is associated with preE. The higher expression of (P)RR in early owl monkey in compare to term placenta suggests that the (P)RR is important for normal placental development. The expression of (P)RR in nonhuman primates reveals the approach of future studies on owl monkey and squirrel monkey preE models. Disclosures J. Stucker: None. D. Leonard: None. J. Thomason: None. L. Perger: None. S.R. Allen: None. M.R. Beeram: None. T.J. Kuehl: None. M.N. Uddin: None.

Objectives Preeclampsia (preE) is a pregnancy disorder characterized by the de novo development of hypertension and proteinuria with multiple pathophysiologic triggers and mechanisms. Approximately 20% of the diabetic pregnant women develop preE. The mechanisms contributing to this effect is not well characterized. In a recent study, we show that hyperglycemia impairs cytotrophoblast (CTB) function via stress signaling. In the present study, we assess the apoptotic signaling mechanisms of excess glucose-induced CTBs dysfunction. Methods Human CTBs (Sw. 71) were treated with 0, 100, 200, 300 or 400 mg/dL glucose for 48 h. Some cells were pretreated with a p38 inhibitor (SB203580) or a peroxisome proliferator-activated receptor gamma (PPARγ) ligand (rosiglitazone). Some cells were treated with D-Mannitol to evaluate the osmotic effect. Thereafter, cell lysates were utilized to measure PPARγ expression and p38 MAPK phosphorylation and apoptotic and stress signaling proteins; Bcl-2-associated X protein (Bax), anti-apoptotic Bcl-2 and caspase-3 and 9 and pro-inflammatory cyclooxygenase-2 (Cox-2) expression were assayed by western blot. Statistical comparisons were performed using analysis of variance with Duncan’s post hoc test. Results Both the p38 MAPK phosphorylation and PPARγ expression were upregulated (p 100 mg/dL glucose compared to basal (100 mg/dL). The expression of Bax/Bcl-2, Cox-2, caspase-3 and 9 were up-regulated (p Conclusions Hyperglycemia induced the apoptotic signaling in CTBs by upregulating the Bax/Bcl2, and caspase-3 and 9 Cox-2 expression. The attenuation of hyperglycemia-induced upregulation of apoptotic and stress signaling proteins by SB203580 or rosiglitazone pretreatment suggests the involvement of apoptotic signaling mechanisms in CTBs dysfunction. Disclosures C. Cawyer: None. D. Leonard: None. N. Drever: None. R.R. Jones: None. S.R. Allen: None. M.R. Beeram: None. T.J. Kuehl: None. M.N. Uddin: None.

Sir .—Abandonment of children is a major social and financial problem facing city hospitals. 1 It has become more prevalent since the epidemic use of illicit drugs such as crack cocaine. 1,2 Newborn nurseries at the District of Columbia General Hospital (DCGH), Washington, are overcrowded with abandoned infants, making it difficult to provide adequate health care in an acute-care setting. We designed a retrospective study to identify risk factors for abandonment and to assess the financial and social impact of this phenomenon on health care. Patient Report. —From January 1990 through June 1991, 3252infants (1674 boys and 1578 girls) were born at DCGH during the 18-month study period. Of these infants, 2759 were of normal birth weight (>2500 g) and 493 were of low birth weight (≤2500 g). Infants included 2737 (84.2%) African Americans, 473 (14.5%) Hispanics, 22 (0.7%) whites, and 20 (0.6%) who were of other ethnic origins. Of

We would like to thank Dr Neuspiel for sharing his views on this complex issue. It may be his experience that the child welfare system in his jurisdiction is excessively punitive. However, in the District of Columbia that is not the case, sometimes to the surprise of health care professionals. Visits by a public health nurse are done to evaluate the suitability of the caregiver's home and to determine the presence of physical necessities to address the needs of any infant. Social services are alerted if these basic items are not available, and assistance is provided to obtain these items. Children are not removed simply because the mother has a history of substance abuse or even if the infant's urine is positive for illicit substances. Every effort is made to keep babies with their mothers. However, when a mother walks out of the hospital, leaves no correct address

Objective Preeclampsia (preE) has a significant link to alterations of placental function leading to stress and apoptotic signaling, which pass the placental barrier and leave persistent defect in the circulation of the offspring. We assessed apoptotic signaling in placentas and umbilical cords from patients with and without preE. Methods We collected placental and cord tissues from 27 normal pregnant (NP) women and 20 preE consenting patients after delivery in an IRB approved prospective study. p38 mitogen-activated protein kinase (p38 MAPK) phosphorylation, pro-apoptotic Bcl-2-associated X (Bax), anti-apoptotic Bcl-2, caspase-9, and pro-inflammatory cyclooxygenase-2 (Cox-2) were evaluated by western blot and immunohistochemistry. Comparisons were performed using Student's t-test. Results p38 phosphorylation (Placenta: 1.5 fold, Cord: 1.7 fold), ratio of Bax/Bcl-2 (Placenta: 1.7 fold, Cord: 2.2 fold), caspase-9 (Placenta: 1.5 fold, Cord: 1.8 fold) and Cox-2 (Placenta: 2.5 fold, Cord: 2.3 fold) were up-regulated (p