Angiotensin receptor agonistic autoantibody is highly prevalent in preeclampsia: correlation with disease severity.

Preeclampsia (PE), a syndrome affecting 5% of pregnancies, characterized by hypertension and proteinuria, is a leading cause of maternal and fetal morbidity and mortality. The condition is often accompanied by the presence of a circulating maternal autoantibody, the angiotensin II type I receptor agonistic autoantibody (AT(1)-AA). However, the prevalence of AT(1)-AA in PE remains unknown, and the correlation of AT(1)-AA titers with the severity of the disease remains undetermined. We used a sensitive and high-throughput luciferase bioassay to detect AT(1)-AA levels in the serum of 30 normal, 37 preeclamptic (10 mild and 27 severe), and 23 gestational hypertensive individuals. Here we report that AT(1)-AA is highly prevalent in PE ( approximately 95%). Next, by comparing the levels of AT(1)-AA among women with mild and severe PE, we found that the titer of AT(1)-AA is proportional to the severity of the disease. Intriguingly, among severe preeclamptic patients, we discovered that the titer of AT(1)-AA is significantly correlated with the clinical features of PE: systolic blood pressure (r=0.56), proteinuria (r=0.70), and soluble fms-like tyrosine kinase-1 level (r=0.71), respectively. Notably, only AT(1)-AA, and not soluble fms-like tyrosine kinase-1, levels are elevated in gestational hypertensive patients. These data serve as compelling clinical evidence that AT(1)-AA is highly prevalent in PE, and its titer is strongly correlated to the severity of the disease.

Maternal and neonatal outcomes by labor onset type and gestational age.

OBJECTIVE: We sought to determine maternal and neonatal outcomes by labor onset type and gestational age. STUDY DESIGN: We used electronic medical records data from 10 US institutions in the Consortium on Safe Labor on 115,528 deliveries from 2002 through 2008. Deliveries were divided by labor onset type (spontaneous, elective induction, indicated induction, unlabored cesarean). Neonatal and maternal outcomes were calculated by labor onset type and gestational age. RESULTS: Neonatal intensive care unit admissions and sepsis improved with each week of gestational age until 39 weeks (P < .001). After adjusting for complications, elective induction of labor was associated with a lower risk of ventilator use (odds ratio [OR], 0.38; 95% confidence interval [CI], 0.28-0.53), sepsis (OR, 0.36; 95% CI, 0.26-0.49), and neonatal intensive care unit admissions (OR, 0.52; 95% CI, 0.48-0.57) compared to spontaneous labor. The relative risk of hysterectomy at term was 3.21 (95% CI, 1.08-9.54) with elective induction, 1.16 (95% CI, 0.24-5.58) with indicated induction, and 6.57 (95% CI, 1.78-24.30) with cesarean without labor compared to spontaneous labor. CONCLUSION: Some neonatal outcomes improved until 39 weeks. Babies born with elective induction are associated with better neonatal outcomes compared to spontaneous labor. Elective induction may be associated with an increased hysterectomy risk.

Introduction of a New Policy of no Nighttime Appendectomies: Impact on Appendiceal Perforation Rates and Postoperative Morbidity

Background Working hour limitations and tight health care budgets have posed significant challenges to emergency surgical services. Since 1 January 2010, surgical interventions at Berne University Hospital between 23:00 and 08:00 h have been restricted to patients with an expected serious adverse outcome if not operated on within 6 h. This study was designed to assess the safety of this new policy that restricts nighttime appendectomies (AEs). Methods The patients that underwent AE from 1 January 2010 to 31 December 2011 (“2010-2011 group”) were compared retrospectively with patients that underwent AE before introduction of the new policy (1 January 2006–31 December 2009; “2006-2009 group”). Results Overall, 390 patients were analyzed. There were 255 patients in the 2006–2009 group and 135 patients in the 2010–2011 group. Patients’ demographics did not differ statistically between the two study groups; however, 45.9 % of the 2006–2009 group and 18.5 % of the 2010–2011 group were operated between 23:00 and 08:00 h (p < 0.001). The rates of appendiceal perforations and surgical site infections did not differ statistically between the 2006–2009 group and the 2010–2011 group (20 vs. 18.5 %, p = 0.725 and 2 vs. 0 %, p = 0.102). Additionally, no difference was found for the hospital length of stay (3.9 ± 7.4 vs. 3.4 ± 6.0 days, p = 0.586). However, the proportion of patients with an in-hospital delay of >12 h was significantly greater in the 2010–2011 group than in the 2006–2009 group [55.6 vs. 43.5 %, p = 0.024, odds ratio (95 % confidence interval 1.62 (1.1–2.47)]. Conclusions Restricting AEs from 23:00 to 08:00 h does not increase the perforation rates and occurrence of clinical outcomes. Therefore, these results suggest that appendicitis may be managed safely in a semielective manner.

Certified nurse midwives effects on catecholamine levels and maternal anxiety during labor

Studies of nurse midwifery care in the last twenty one years have reported excellent birth outcomes (Levy, Wilkenson and Marine, 1971; Platt et al. 1985; Stone et al. 1976). These outcomes are frequently attributed to the special support offered during labor and delivery by nurse midwives. This supportive style is thought to decrease catecholamine levels by reducing maternal anxiety. This prospective observational study evaluated catecholamine levels, anxiety levels, in-hospital costs, obstetrical practices and outcomes between low risk, term, labor and delivery primigravida patients managed by obstetrical residents (n = 55) or by certified nurse-midwives CNM (n = 59). The two groups were similar with regard to obstetrical risk factors present at admission. Each group was selected over the same period of time between March 23, 1994 and November 2, 1994. Specific catecholamines evaluated were epinephrine and norepinephrine. Obstetrical and newborn characteristics were also compared. This study did not prove that there is a decreased level in stress as indicated by lower levels of epinephrine and norepinephrine in nurse-midwife patients compared to obstetrical resident patients after adjusting for the use of epidural anesthesia. There was also no difference found in the perceived anxiety levels between the two groups. This study did confirm that nurse-midwives and obstetrical residents have different practice styles. Nurse-midwife patients had fewer augmented deliveries, fewer operative deliveries, less blood loss, fewer episiotomies and fewer third and fourth degree lacerations. The physician's choice to utilize more interventions such as continuous fetal monitoring and epidural anesthesia did not improve outcomes. The hospital cost of the nurse-midwife patients in this study was 35 percent lower than the physician patients. ^

Content of prenatal care and spontaneous preterm birth: Findings from the 1988 National Maternal and Infant Health Survey

The purposes of this study were to examine (1) the relationship between selected components of the content of prenatal care and spontaneous preterm birth; and (2) the degree of comparability between maternal and caregivers' responses regarding the number of prenatal care visits, selected components of the content of prenatal care, and gestational age, based on analyses of the 1988 National Maternal and Infant Health Survey conducted by the National Centers for Health Statistics. Spontaneous preterm birth was subcategorized into very preterm and moderately preterm births, with term birth as the controls. The study population was limited to non-Hispanic Anglo- and African-American mothers. The racial differences in terms of birth outcomes were also compared.^ This study concluded that: (1) there was not a high degree of comparability (less than 80%) between maternal and prenatal care provider's responses regarding the number of prenatal care visits and the content of prenatal care; (2) there was a low degree of comparability (less than 50%) between maternal and infant's hospital of delivery responses regarding gestational age at birth; (3) there were differences in selected components of the content of prenatal care between the cases and controls, overall and stratified by ethnicity (i.e., hemoglobin/hematocrit test, weight measurement, and breast-feeding counseling), but they were confounded with missing values and associated preterm delivery bias; (4) there were differences in selected components of the content of prenatal care between Anglo- and African-American cases (i.e., vitamin/mineral supplement advice, weight measurement, smoking cessation and drug abuse counseling), but they, too, were difficult to interpret definitively due to item nonresponse and preterm delivery biases; (5) no significant predictive association between selected components of the content of prenatal care and spontaneous preterm birth was found; and (6) inadequate/intermediate prenatal care and birth out of wedlock were found to be associated with moderately preterm birth.^ Future research is needed to examine the validity of maternal and prenatal care providers' responses and identify the sources of disagreement between their responses. In addition, further studies are needed to examine the relationship between the quality of prenatal care and preterm birth. Finally, the completeness and quality of patient and provider data on the utilization and content of prenatal care needs to be strengthened in subsequent studies. ^

The relationship of maternal low birthweight and infant low birthweight among African-American women at term delivery: Findings from the 1988 National Maternal and Infant Health Survey

A cohort study study design was used to study the relationship of maternal low birthweight and infant low birthweight among African American women delivering full term infants. The cohort consisted of 3,157 mother-infant pairs drawn from the 1988 National Maternal and Infant Health Survey conducted by the National Center for Health Statistics. The objectives of the study were (1) to determine if low birthweight, African American mothers delivering term infants experienced higher rates of infant low birthweight and (2) to examine the role of selected contributory variables in the relationship of maternal low birthweight and infant low birthweight. Contributory risk factors examined included maternal marital status, maternal age, maternal education, maternal height, maternal prepregnant weight, birth order, history of a prior low birthweight delivery, timing of prenatal care, number of prenatal visits, gestational length, infant gender, and behavioral factors of smoking, alcohol, and illicit drug use during pregnancy.^ Using logistic regression analysis, risk of infant low birthweight among maternal low birthweight mothers increased after controlling for less than a high school education, less than 20 years of age, prepregnant weight less than 100 lbs, history of a prior low birthweight delivery, birth order, smoking during pregnancy, and use of alcohol and illicit drugs during pregnancy, but was not statistically significant. Loss of statistical significance was attributed to a large reduction in cases available for analysis after including illicit drug use in the model.^ This study demonstrated a consistent pattern of increased rates of infant low birthweight among low birthweight mothers. The force of history remains, hence women with this trait should be carefully monitored and advised during pregnancy to decrease risk of a low birthweight infant, in order to decrease the chain of events leading to future generations of low birthweight mothers. ^

Can infant lung function predict respiratory morbidity during the first year of life in preterm infants?

Compared with term-born infants, preterm infants have increased respiratory morbidity in the first year of life. We investigated whether lung function tests performed near term predict subsequent respiratory morbidity during the first year of life and compared this to standard clinical parameters in preterms.The prospective birth cohort included randomly selected preterm infants with and without bronchopulmonary dysplasia. Lung function (tidal breathing and multiple-breath washout) was measured at 44 weeks post-menstrual age during natural sleep. We assessed respiratory morbidity (wheeze, hospitalisation, inhalation and home oxygen therapy) after 1 year using a standardised questionnaire. We first assessed the association between lung function and subsequent respiratory morbidity. Secondly, we compared the predictive power of standard clinical predictors with and without lung function data.In 166 preterm infants, tidal volume, time to peak tidal expiratory flow/expiratory time ratio and respiratory rate were significantly associated with subsequent wheeze. In comparison with standard clinical predictors, lung function did not improve the prediction of later respiratory morbidity in an individual child.Although associated with later wheeze, noninvasive infant lung function shows large physiological variability and does not add to clinically relevant risk prediction for subsequent respiratory morbidity in an individual preterm.

Genotype and maternal environment affect belowground interactions between Arabidopsis thaliana and its competitors

Ecological interactions between different species are not fixed, but they may depend, at least to some extent, on the particular genotypes involved as well as on the environmental conditions experienced by previous generations. We used a set of natural genotypes of Arabidopsis thaliana, that previously experienced contrasting nutrient and herbivory conditions, to test for the influences of genetic variation and maternal effects on competitive interactions between Arabidopsis and the weedy annuals Anagallis arvensis and Senecio vulgaris. We used activated carbon to discriminate between resource competition and allelopathy components of plant-plant interactions. There was a clear competitive hierarchy: Senecio > Arabidopsis > Anagallis. Although we found no evidence for allelopathic potential of Arabidopsis, our results indicate that both Anagallis and Senecio exerted negative (direct or indirect) allelopathic effects on Arabidopsis. There were significant differences among Arabidopsis genotypes in their competitive effects on both neighbor species, as well as in their response to competition. Maternal environments significantly influenced not only the growth and fitness of Arabidopsis itself, but also its competitive effect on Anagallis. We found, however, no evidence that maternal environments affected the competitive effect on Senecio or overall competitive response of Arabidopsis. Generally, resource competition played a greater role than allelopathy, and genotype effects were more important than maternal effects. Our study demonstrates that ecological interactions, such as plant competition, are complex and multi-layered, and that, in particular, the influence of genetic variation on interactions with other species should not be overlooked.

Parasite- and predator-induced maternal effects in the great tit (Parus major)

Both predators and parasites can elicit behavioral and physiological responses in prey and hosts, respectively. These responses may involve the reallocation of resources and may thus limit each other. We investigated the effects of concurrent pre-laying exposure of great tit females (Parus major) to both a simulated predation risk and a nest-based ectoparasite, the hen flea (Ceratophyllus gallinae), on nestling growth and development. We manipulated perceived predation risk using models and vocalizations of sparrowhawks (Accipiter nisus). At the start of incubation, we swapped whole clutches between treated and untreated nests to separate pre-laying maternal effects from posthatching effects. Since costs and benefits of maternal responses to parasites need to be assessed under parasite pressure, we infested half of the rearing nests with hen fleas. Parasites had negative effects on mass gain and wing growth, both via maternal effects and via direct exposure of nestlings, whereas maternal predation risk had no significant effect. The interaction between predator and parasite treatments was not significant and, thus, suggests the absence of a trade-off between the 2 stressors operating at the level of maternal effects. Alternatively, the complexity of the design, despite a relatively large sample size, may have limited the power for detection of this expected trade-off.

Antipredator defences of young are independently determined by genetic inheritance, maternal effects and own early experience in mouthbrooding cichlids.

1. Predation is a prime force of natural selection. Vulnerability to predation is typically highest early in life, hence effective antipredator defences should work already shortly after birth. Such early defences may be innate, transmitted through non-genetic parental effects or acquired by own early experience. 2. To understand potential joint effects of these sources of antipredator defences on pheno- typic expression, they should be manipulated within the same experiment. We investigated innate, parental and individual experience effects within a single experiment. Females of the African cichlid Simochromis pleurospilus were exposed to the offspring predator Ctenochromis horei or a benign species until spawning. Eggs and larvae were hand-reared, and larvae were then exposed to odour cues signalling the presence or absence of predators in a split-brood design. 3. Shortly after independence of maternal care, S. pleurospilus undergo a habitat shift from a deeper, adult habitat to a shallow juvenile habitat, a phase where young are thought to be par- ticularly exposed to predation risk. Thus, maternal effects induced by offspring predators pres- ent in the adult habitat should take effect mainly shortly after independence, whereas own experience and innate antipredator responses should shape behaviour and life history of S. pleurospilus during the later juvenile period. 4. We found that the manipulated environmental components independently affected different offspring traits. (i) Offspring of predator-exposed mothers grew faster during the first month of life and were thus larger at termination of maternal care, when the young migrate from the adult to the juvenile habitat. (ii) The offspring’s own experience shortly after hatching exerted lasting effects on predator avoidance behaviour. (iii) Finally, our results suggest that S. pleuro- spilus possess a genetically inherited ability to distinguish dangerous from benign species. 5. In S. pleurospilus, maternal effects were limited to a short but critical time window, when young undergo a niche shift. Instead, own environmental sampling of predation risk combined with an innate predisposition to correctly identify predators appears to prepare the young best for the environment, in which they grow up as juveniles.

Screening, Identification and Preliminary Investigation of Target Transporters in Pregnancy Pathologies

Screening, Identification and Preliminary Investigation of Target Transporters in Pregnancy Pathologies. INTRODUCTION: Pre-eclampsia (PE), intrauterine growth restriction (IUGR) and gestational diabetes mellitus (GDM) are major sources of clinical morbidity and mortality in pregnant women worldwide. The mechanisms underlying these gestational diseases are complex and not yet fully understood, but one factor contributing to their development is impaired maternal-fetal nutrient transport. Therefore, we aimed to identify candidate membrane transporters involved in transplacental nutrient transfer associated with PE/IUGR or GDM. METHODS: Using in silico strategies, we analysed various gene expression data sets generated on different platforms focusing on solute carriers, ABC transporters and TRP channels in order to identify transporters that are differently expressed between patients and gestational age-matched controls. These bioinformatic analyses were combined with literature data to define a catalogue of target transporters that could be involved in the development of PE/IUGR or GDM. Transporters of interest were then analysed for gene expression using qRT-PCR in placental tissues of patients and controls. For validating the results on protein and functional level, we started to establish an in vitro assay using freshly isolated primary cytotrophoblast cells polarized on the Transwell® system. RESULTS: Using bioinformatics approaches, we initially identified 37 target membrane proteins which were mainly associated with the transport of amino acids, vitamins, and trace elements. At the current state of analysis, the amino acid transporters SLC7A7, SLC38A2, SLC38A5, and the thiamine transporter SLC19A3 showed significant differences in placental mRNA expression between controls and patients affected by PE and/or IUGR. Subsequent gene expression analysis in our in-house GDM placental tissue bank is still ongoing. CONCLUSIONS: Based on our in silico analyses, literature data and first follow-up in vitro validations, we were able to define potentially interesting candidate transporters implicated in PE/IUGR or GDM. To date, additional newly defined candidate targets are being analysed on mRNA level in PE/IUGR and GDM. Subsequent analyses on protein and functional level will reveal whether these targets could be of diagnostic or therapeutical interest in these pregnancy pathologies.

Placental Uric Acid Transport System: Glucose Transporter 9 (SLC2A9)

Placental Uric Acid Transport System: Glucose Transporter 9 (SLC2A9). INTRODUCTION: Pre-eclampsia, a pregnancy-specific disease, contributes substantially to perinatal morbidity and mortality of both the mother and her child. Pre-eclampsia is often associated with high maternal urate serum levels, which in turn has been shown to play a role in the pathogenesis of this disease. The aim of this study was to investigate the glucose transporter GLUT9-mediated placental uric acid transport system. METHODS: In this study western blot, immunofluorescence techniques as well as a transepithelial transport (Transwell) model were used to assess GLUT9 protein expression and, respectively, uric acid transport activity. Electrophysiological techniques and transmission electron microscopy (TEM) were used to characterize the properties and the structure of GLUT9. RESULTS: Uric acid is transported across a BeWo choriocarcinoma cell monolayer with 530 pmol/min. We could successfully overexpress and for the first time purify the GLUT9b isoform using the Xenopus laevis oocytes expression system. Chloride seems to modulate the urate transport system. TEM revealed that GLUT9b isoform is present as monomer and dimmer in the Xenopus laevis overexpression model. A class average of all the particles allowed us to develop a first model of human GLUT9b structure, which was derived from the published crystal structure of the bacterial homologue of GLUT1-4. CONCLUSIONS: In vitro the “materno-fetal” transport of uric acid is slow indicating that in vivo the fetus might be protected from short-term fluctuations of maternal urate serum levels. The low-resolution structure obtained from TEM validates the proposed homology model regarding the structure of human GLUT9b. In ongoing studies this model is used to perform virtual screening to identify novel modulators of the urate transport system enabling the development of novel therapies in pregnancy complications.