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The amniotic membrane (AM) and amniotic fluid (AF) have a long history of use in surgical and prenatal diagnostic applications, respectively. In addition, the discovery of cell populations in AM and AF which are widely accessible, nontumorigenic and capable of differentiating into a variety of cell types has stimulated a flurry of research aimed at characterizing the cells and evaluating their potential utility in regenerative medicine. While a major focus of research has been the use of amniotic membrane and fluid in tissue engineering and cell replacement, AM- and AF-derived cells may also have capabilities in protecting and stimulating the repair of injured tissues via paracrine actions, and acting as vectors for biodelivery of exogenous factors to treat injury and diseases. Much progress has been made since the discovery of AM and AF cells with stem cell characteristics nearly a decade ago, but there remain a number of problematic issues stemming from the inherent heterogeneity of these cells as well as inconsistencies in isolation and culturing methods which must be addressed to advance the field towards the development of cell-based therapies. Here, we provide an overview of the recent progress and future perspectives in the use of AM- and AF-derived cells for therapeutic applications. [ABSTRACT FROM AUTHOR]

Recently, human amniotic fluid (AF) cells have attracted a great deal of attention as an alternative cell source for transplantation and tissue engineering. AF contains a variety of cell types derived from fetal tissues, of which a small percentage is believed to represent stem cell sub-population(s). In contrast to human embryonic stem (ES) cells, AF cells are not subject to extensive legal or ethical considerations; nor are they limited by lineage commitment characteristic of adult stem cells. However, to become therapeutically valuable, better protocols for the isolation of AF stem cell sub-populations need to be developed. This study was designed to examine the molecular components involved in self-renewal, neural commitment and differentiation of AF cells obtained at different gestational ages. Our results showed that, although morphologically heterogeneous, AF cells derived from early gestational periods ubiquitously expressed KERATIN 8 (K8), suggesting that the majority of these cells may have an epithelial origin. In addition, AF cells expressed various components of NOTCH signaling (ligands, receptors and target genes), a pathway involved in stem cell maintenance, determination and differentiation. A sub-population of K8 positive cells (<10%) co-expressed NESTIN, a marker detected in the neuroepithelium, neural stem cells and neural progenitors. Throughout the gestational periods, a much smaller AF cell sub-population (<1%) expressed pluripotency markers, OCT4a, NANOG and SOX2, from which SOX2 positive AF cells could be isolated through single cell cloning. The SOX2 expressing AF clones showed the capacity to give rise to a neuron-like phenotype in culture, expressing neuronal markers such as MAP2, NFL and NSE. Taken together, our findings demonstrated the presence of fetal cells with stem cell characteristics in the amniotic fluid, highlighting the need for further research on their biology and clinical applications. [ABSTRACT FROM AUTHOR]

Smoking during pregnancy has been shown to result in an increased risk of low birth weight. However, the mechanisms underlying this association are poorly understood. The insulin-like growth factor (IGF) system plays a critical role in the regulation of feto-placental growth and development, and abnormal processing of proIGF-II may alter its biological function. Our goal was to investigate the effects of exposure to nicotine on maternal, fetal, and neonatal IGF-II processing. Nulliparous female Wistar rats were randomly assigned to receive saline (vehicle) or nicotine bitartrate (1 mg⋅kg-1⋅d-1). After mating, dams were euthanized at embryonic days 15, 18, and 21, and fetal body weight was recorded. Serum (fetal and maternal) was collected for determination of the IGF-II profile by Western blot analysis. Nicotine exposure prevented the decrease in maternal IGF-II processing seen in controls with advancing gestation. However, there was no influence of nicotine on fetal levels of IGF-II. Postnatally (postnatal day [PND] 21), pups exposed to nicotine in utero had decreased levels of big IGF-II. Our results show, for the first time, that nicotine exposure prevents the decrease of IGF-II processing in the maternal compartment. This may represent a compensatory mechanism allowing the mother to counteract the negative influence of nicotine on fetal growth and development. Our postnatal findings of suppressed IGF-II may help explain some of the long-term health complications seen in individuals exposed to smoking in utero. [ABSTRACT FROM AUTHOR]

Abstract: Multiple sclerosis (MS) is an autoimmune disease associated with environmental factors, possibly including several viruses such as the coronaviruses. Indeed, murine coronavirus (MHV) infection provides a well-known experimental model for MS studies. Intracerebral infection of C57BL/6 mice with MHV-A59 revealed that viral replication was efficient and that clearance of infectious virus occurred as soon as 7 days post-infection. Using cDNA arrays, analysis of gene expression profile in the brain revealed a modulation of 80 different genes following infection, with at least 27 of these genes having previously been directly related to innate or acquired immune responses. Concordingly, an important activation of auto-reactive T cells specific to myelin basic protein was demonstrated. Altogether, these results indicate that an MHV infection of the central nervous system (CNS) leads to an important host genomic response implicating immunity-related genes and to the activation of myelin-reactive autoimmune T cells. [Copyright &y& Elsevier]

The authors reflect on a study by K. A. Salvesen and colleagues on the significance of maternal exercise in fetal health. They suggest that the study has limited application to the inactive maternal population although it is timely with respect to te fetal response to external levels of maternal exertion in competitive Olympic athletes. They also explore the study finding that fetal heart rate (HR) was within the normal range as long as maternal exertion was below 90% maternal HRmax.

The process of uterine spiral artery remodeling in the first trimester of human pregnancy is an essential part of establishing adequate blood perfusion of the placenta that will allow optimal nutrient/waste exchange to meet fetal demands during later development. Key regulators of spiral artery remodeling are the uterine natural killer cells and the invasive extravillous trophoblasts. The functions of these cells as well as regulation of their activation states and temporal regulation of their localization within the uterine tissue are beginning to be known. In this review, we discuss the roles of these two cell lineages in arterial remodeling events, their interaction/influence on one another and the outcomes of altered temporal, and spatial regulation of these cells in pregnancy complications. [ABSTRACT FROM AUTHOR]

Women who develop preeclampsia (PE) are at high risk for cardiovascular disease (CVD). Early identification of women with PE who may benefit the most from early cardiovascular risk screening and interventions remains challenging. Our objective was to assess whether cytokine and immune cell profiles after PE are helpful in distinguishing women at low and high CVD risk at 6-months postpartum. Individuals who developed PE were followed for immune cell phenotyping and plasma cytokine quantification at delivery, at 3-months, and at 6-months postpartum. Lifetime CVD risk was assessed at 6-months postpartum, and the immune cell and cytokine profiles were compared between risk groups at each time point. Among 31 participants, 18 (58.1%) exhibited high CVD-risk profiles at 6-months postpartum. The proportion of circulating NK-cells was significantly lower in high-risk participants at delivery (p = 0.04). At 3-months postpartum, high-risk participants exhibited a lower proportion of FoxP3+ regulatory T-cells (p = 0.01), a greater proportion of CD8+ T cells (p = 0.02) and a lower CD4+:CD8+ ratio (p = 0.02). There were no differences in immune cell populations at 6-months postpartum. There were no differences in plasma cytokines levels between risk groups at any time point. Subtle differences in immune cell profiles may help distinguish individuals at low and high CVD risk in the early postpartum period and warrants further investigation. [ABSTRACT FROM AUTHOR]

The quality of the intrauterine environment influences maternal-fetal health and also offspring predisposition to obesity and cardiometabolic disease later in life. Several determinants, including but not limited to pregravid obesity and excessive gestational weight gain, alter the developmental milieu, fetal growth, and child obesity risk. However, the role of sleep and its relationship to healthy pregnancy is not fully established.Given the host of psychosocial and physiological complications associatedwith childhood obesity, targeting the gestational period is purported to be an opportune time for preventive intervention.Many longitudinal studies suggest that short sleep duration is a risk factor for the development of impaired glycemia and obesity. However, there is a dearth of information concerning the role of sleep hygiene and its role in a healthy pregnancy. Reports note disrupted and poorer quality of sleep during gestation and highlight an association between reduced sleep and risk of gestational diabetes mellitus. Given the lack of well-designed human trials assessing the value of sleep and healthy pregnancy outcomes, this review summarizes current evidence which suggests that incorporating sleep recommendations and utilizing time management strategies that encourage a healthful night's sleep may improve the health of the mom and the baby. [ABSTRACT FROM AUTHOR]

Background: Excessive gestational weight gain (GWG) increases risk of large for gestational age neonates and subsequent tracking of excess weight throughout the life course for both mother and child. Although the physiological mechanisms underlying these associations are incomplete, the insulin-like growth factor (IGF) axis has garnered attention for its role in fetal growth and development. Our purpose was to characterize the IGF axis protein expression patterns in mother-infant dyads in respect of excessive GWG. Methods: We obtained fasting serum samples and corresponding cord blood from eight controls (ADHERE group: ie, those who gained in accordance with 2009 Institute of Medicine GWG recommendations) and 13 exceeders (EXCEED group: ie, those who exceeded Institute of Medicine GWG recommendations). At study completion, we examined protein expression of IGF-I, IGF-II, IGF binding protein (IGFBP)-1, IGFBP-3, IGFBP-4, and hormone concentrations in both maternal and cord blood. Results: Between-group comparisons were made and revealed elevated maternal leptin (P ⩽0.05) concentrations in gravidas who exceeded recommendations. There was a significantly higher number of obese women in the EXCEED group (P<0.05). After adjustment, maternal leptin levels were positively correlated with maternal homeostasis model of assessment for insulin resistance score and excessive GWG (P ⩽0.01). However, serum IGFBP-3 expression in the EXCEED mothers was greater than that in the ADHERE group (P ⩽0.05). Conclusion: These findings provide preliminary evidence suggesting that small deviations in IGFBP-regulated IGF bioavailability arising from excessive GWG/positive energy balance may affect adipocyte differentiation through subclinical insulin resistance. [ABSTRACT FROM AUTHOR]

Background. Serum lipids including total cholesterol (TC), triglycerides (TG), and low density lipoprotein cholesterol (LDL-C) are increased in pregnancy. Serum proprotein convertase subtilisin kexin 9 (PCSK9) is a significant player in lipoprotein metabolism. Circulating PCSK9 downregulates the LDL receptor on the surface of the liver, inhibiting clearance of LDL-C. Therefore, our study assessed serum PCSK9 concentrations at parturition (Maternal) compared to a nonpregnant (Control) cohort, as well as between mother and newborn (Maternal and Newborn). Methods. Blood was collected from women at parturition and from umbilical cords. Serumlipids and PCSK9 were measured and data were analysed for significance by Mann-Whitney U test at P < 0.05 and presented as median levels. Spearman's correlations were made at a 95% confidence interval. Results. Serum PCSK9 was significantly higher in Maternal versus Control cohorts (493.1 versus 289.7 ng/mL; P < 0.001, resp.), while the Newborn cohort was significantly lower than Maternal (278.2 versus 493.1 ng/mL; P < 0.0001, resp.). PCSK9 was significantly correlated with TC and HDL-C in Maternal and with TC, LDL-C, and HDL-C in Newborn cohorts. Conclusions. Our study provides the first quantitative report on PCSK9 in pregnancy (at parturition) and in umbilical cord blood. Further research will determine how these changes may affect lipoprotein levels during this physiological state. [ABSTRACT FROM AUTHOR]

Background. Serum lipids including total cholesterol (TC), triglycerides (TG), and low density lipoprotein cholesterol (LDL-C) are increased in pregnancy. Serum proprotein convertase subtilisin kexin 9 (PCSK9) is a significant player in lipoprotein metabolism. Circulating PCSK9 downregulates the LDL receptor on the surface of the liver, inhibiting clearance of LDL-C. Therefore, our study assessed serum PCSK9 concentrations at parturition (Maternal) compared to a nonpregnant (Control) cohort, as well as between mother and newborn (Maternal and Newborn). Methods. Blood was collected from women at parturition and from umbilical cords. Serumlipids and PCSK9 were measured and data were analysed for significance by Mann-Whitney U test at P < 0.05 and presented as median levels. Spearman's correlations were made at a 95% confidence interval. Results. Serum PCSK9 was significantly higher in Maternal versus Control cohorts (493.1 versus 289.7 ng/mL; P < 0.001, resp.), while the Newborn cohort was significantly lower than Maternal (278.2 versus 493.1 ng/mL; P < 0.0001, resp.). PCSK9 was significantly correlated with TC and HDL-C in Maternal and with TC, LDL-C, and HDL-C in Newborn cohorts. Conclusions. Our study provides the first quantitative report on PCSK9 in pregnancy (at parturition) and in umbilical cord blood. Further research will determine how these changes may affect lipoprotein levels during this physiological state. [ABSTRACT FROM AUTHOR]

Recent evidence indicates that CXCR2 signaling is crucial for cancer progression, and its antagonist SB225002 induces apoptosis in Wilms' tumor cells. Here, we investigated the effect of SB225002 on cell cycle progression and apoptosis induction in vitro, using CDDP-sensitive and -resistant OVCA cell lines with different p53 status (wild type, mutant or null). Adenovirus infection of wild-type p53 or transfection of p53 siRNA was used to over-express or knock-down p53. Cell cycle and apoptosis were determined by flow cytometry or Hoechst staining and observation of nuclear morphology. Our data demonstrated that SB225002 induced apoptosis in both wild-type and p53-deficient ovarian cancer (OVCA) cells through alternative mechanisms. SB225002 promoted mitotic catastrophe, as evidenced by the accumulation of mitotic cells with spindle abnormalities, chromosome mis-segregation, multi-polar cell division, multiple nuclei, aneuploidy/polyploidy and subsequent extensive apoptosis. SB225002-induced mitotic catastrophe appeared to be mediated by down-regulation of checkpoint kinase Chk1 and Cdk1-cyclin B activation. In cells expressing wild-type p53 (OV2008 and C13*), SB225002 increased total and phospho-Ser p53 levels, and p53 knock-down decreased SB225002-induced apoptosis, without affecting premature mitosis. These results suggest that SB225002 induces p53-dependent apoptosis, and provokes mitotic catastrophe in p53-independent manner in p53 wild-type cells. Reconstitution with wild-type P53 in P53-null SKOV3 cell attenuated SB225002-induced mitotic catastrophe, suggesting p53 prevented mitotic catastrophe induced by SB225002 in p53-deficient OVCA cells. Finally, the effect of SB225002 could not be prevented by pretreatment with CXCR2 ligand or its neutralizing antibody. The present studies demonstrate for the first time that SB225002 has dual actions in OVCA cells, inducing classic apoptosis through p53 activation and provoking mitotic catastrophe in both p53 wild-type and deficient cells by Chk1 inhibition and Cdk activation. These findings raise the possibility of SB225002 as a new candidate molecule for OVCA therapy independent of the p53 status. [ABSTRACT FROM AUTHOR]

STUDY QUESTION Does maternal obesity affect insulin-like growth factor (IGF) axis protein expression patterns in maternal and cord blood? SUMMARY ANSWER Maternal obesity attenuates cord blood expression of IGF-binding protein (IGFBP)-4. WHAT IS KNOWN AND WHAT THIS PAPER ADDS The IGF axis plays a critical role in fetal growth and development. Maternal obesity compromises IGF axis protein expression in fetal circulation, which is consistent with the findings of epidemiological studies suggesting that maternal obesity has an independent effect on fetal growth signals during in utero development. STUDY DESIGN This cross-sectional case–control study involved 12 lean [body mass index (BMI) 18.5–24.9 kg/m2] and 12 obese (BMI ≥ 30 kg/m2) women and their neonates at term. At the completion of the study, IGF axis protein expression and hormone concentrations in both maternal and cord blood were examined. PARTICIPANTS AND SETTING We obtained fasting serum samples from cases and controls matched for age, gestation, mode of delivery, parity and glucose tolerance prior to and immediately following elective caesarean section. The corresponding umbilical cord blood was also collected at birth. MAIN RESULTS AND THE ROLE OF CHANCE Between-group comparisons revealed elevated maternal insulin (P = 0.03) and leptin (P < 0.01) concentrations in obese gravidas. After adjustment, the maternal homeostasis model of assessment—insulin resistance (HOMA-IR) score was positively correlated with both maternal BMI and leptin levels (P < 0.01). Umbilical cord blood levels of IGFBP-3 showed an inverse trend to maternal HOMA-IR (P = 0.03) but were directly related to the fetal–placental weight ratio (P < 0.01). In cord serum from obese mothers, IGFBP-4 expression was attenuated compared with the controls (P < 0.05). LIMITATIONS The limitations of our study include the cross-sectional design and relatively small sample size. WIDER IMPLICATIONS Our results provide preliminary evidence for the applicability of our findings to other ethnic groups when pregnancy is complicated by obesity. STUDY FUNDING/COMPETING INTERESTS This work was supported by the University of Ottawa, Faculty of Health Sciences/Children's Hospital of Eastern Ontario Research Partnership Grant awarded to K.B.A. and Z.M.F. The authors have no conflicts of interest to declare. [ABSTRACT FROM AUTHOR]

Substance use disorders (SUDs) in pregnancy are becoming increasingly prevalent. Our study aimed to measure the effect of a teaching module on alcohol, tobacco, and drug use on the attitude of second year medical students toward pregnant women with SUDs. A questionnaire was administered to 84 medical students before a 5-week systems block on human reproduction, which included specific learning events related to SUDs. The questionnaire was readministered at the completion of the block. Pre- and postintervention scores were compared. Students showed significant improvement (p < .05, reliability coefficient 0.90) in their level of comfort in dealing with womenwith SUD in pregnancy. Other positive trends relating to attitudes toward drug- and alcohol-dependent women during pregnancy were also identified. SUD teaching interventions among medical students can improve their comfort level and attitude toward pregnant women with SUDs. This supports the current initiative of Project CREATE (Curriculum Renewal and Evaluation of Addiction Training and Education) to implement a comprehensive undergraduate SUD teaching program in Canadian medical schools. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Numerous studies have assesed the significance of meconium-stained amniotic fluid (MSAF) at term. However, to date, there has been very little documentation on the incidence and significance of meconium in the preterm population. Our objective was to define the incidence of MSAF in patients delivering prematurely (<37 weeks) and examine its association with underlying fetal acidosis, Apgars and admission to the neonatal intensive care unit (NICU). METHOD: All patients delivering at a single tertiary care center between June 1994 and September 1997 were reviewed for the presence of meconium and gestational age < 37 weeks at delivery. Maternal demographics and birth outcomes including cord gases, Apgar scores and admission to the NICU were collected. Exclusion criteria included multiple gestations, breech presentations, fetal anomalies and patients not in labor. RESULTS: Out of a total of 9570 patients there were 506 (5.3%) preterm births meeting the inclusion criteria, of whom 24 (4.8%) had MSAF noted either during labor or at delivery. Comparing the preterm group with and without meconium, there were no differences in maternal age, gravidity, rate of Cesarean section, or gestational age at delivery. Cord pH (7.27 meconium vs. 7.29 no meconium) and base excess (-5.1 meconium vs. -4.0 no meconium) were similar in both groups. There were no clinically significant differences in mean Apgar scores at 1 and 5 minutes. However, an increased number of NICU admissions were noted in the group with meconium (75% vs. 53%, p = 0.04). CONCLUSION: The incidence of meconium staining of the amniotic fluid in labor in the preterm population is less than 5% and by itself is not a significant marker of fetal acidosis. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To determine whether fetal erythropoietin (Epo) concentrations are increased in pregnancies extending beyond 41 weeks' gestation and whether this is influenced by the presence of meconium-stained amniotic fluid. METHODS: Epo concentrations were measured in 116 fetal umbilical cord blood samples from otherwise uncomplicated pregnancies between 37 to 43 weeks' gestation during the period of October 1996 to October 1997. An enzyme-linked immunosorbent assay kit was used to measure Epo. Maternal demographics and birth outcomes including Apgar score, cord blood pH, and base deficit were obtained. Fetuses born between 41 and 43 weeks' gestation (post-term) were compared with matched controls born between 37 and 40 weeks' gestation (term). In addition, both post-term and term fetuses with meconium-stained amniotic fluid were compared with matched controls without meconium. RESULTS: Post-term fetuses without meconium had significantly higher Epo levels compared with term fetuses (mean ± SEM: 50.6 ± 6.5 versus 29.5 ± 3.3 mIU/ml, p = 0.002). When matched for gestational age, fetuses with meconium-stained amniotic fluid had significantly greater Epo concentrations compared with controls without meconium (post-term, 80.7 versus 50.6 mIU/ml; term, 61.4 versus 29.5 mIU/ml; p < 0.05). However, no significant difference in Epo levels was found between post-term fetuses with meconium and term fetuses with meconium (80.7 ± 15.7 mIU/ml versus 61.4 ± 12.8 mIU/ml, respectively). Mean cord blood pH and base deficit values for all groups were within normal clinical range. CONCLUSION: Cord blood Epo concentrations were significantly increased in pregnancies extending beyond 41 weeks. Irrespective of gestational age, meconium-stained amniotic fluid was associated with a significant rise in Epo. High Epo levels in these pregnancies imply subacute or chronic fetal hypoxia. Close clinical monitoring of post-term fetuses and those with... [ABSTRACT FROM AUTHOR]

Background Previous studies have shown that older people can experience a considerable change in their physical performance (PP) over time. Objectives To identify PP trajectories and their association with mortality among nursing home residents who were followed up for 3 years. Design Three-year longitudinal observational study. Setting Subjects of the SENIOR cohort. Subjects Six hundred and four nursing home residents with a mean age of 82.9 ± 9.1 years. Methods Baseline characteristics and the date of death were collected from the medical records. PP was assessed annually by the short physical performance battery (SPPB) test. Multiple imputations were performed to manage the missing data. PP trajectory groups were estimated using latent growth curve analysis. Cox proportional hazard regression models were applied to examine the risk of mortality according to the PP trajectory groups. Results Three PP trajectory groups were identified: slow decline (N  = 96), moderate decline (N  = 234) and fast decline (N  = 274). After adjustments for potential confounding variables and the baseline SPPB scores, the residents in the fast decline and moderate decline trajectory groups had an increased risk of mortality compared to those in the slow decline trajectory group, with hazard ratio values of 1.78 (95% confidence interval [CI] = 1.34–2.26) and 1.37 (95% CI = 1.10–1.66), respectively. Conclusions PP trajectories provide value-added information to baseline geriatric assessments and could be used for predicting 3-year mortality among nursing home residents. It may be important to regularly monitor the SPPB score and signal an alert when a fast decline in PP is detected in older people. [ABSTRACT FROM AUTHOR]

Background: This study aimed to evaluate the predictive value of the domains of intrinsic capacity (ie, cognition, locomotion, sensory, vitality, and psychosocial) proposed by the World Health Organization (WHO) on the 3-year adverse health outcomes of nursing home residents.Methods: A 3-year incidence of mortality, falls, repeated falls, and autonomy decline (ie, a one-unit increase in the Katz score) was assessed in a cohort of Belgian nursing home residents. Cognition was assessed using the Mini-Mental State Examination (MMSE). For locomotion, balance, gait speed and chair stand performance were evaluated by the Short Physical Performance Battery test. The sensory domain was measured using the Strawbridge questionnaire for audition and vision. For vitality, abdominal circumference, body mass index, nutritional status (by Mini Nutritional Assessment [MNA]) and handgrip strength were assessed. Psychosocial status was evaluated by the EQ-5D and the Center for Epidemiological Studies Depression scale. Missing data were handled by multiple imputations. Cox proportional hazard models, logistic regressions, and analysis of variance were used for the analyses.Results: In the multivariable model, a one-unit increase in balance performance and in the nutrition score decreased the probability of death by 12% (Hazard ratio [HR] = 0.88; 95% confidence interval [CI] 0.78-0.99) and 4% (HR = 0.96; 95% CI 0.93-0.99), respectively. The risk of falling decreased when there was a one-unit increase in balance performance (HR = 0.87, 95% CI 0.79-0.96) and in the nutrition score (HR = 0.96, 95% CI 0.93-0.98). No association was found for intrinsic capacity and repeated falls. Low scores in nutrition (odds ratio = 0.86, 95% CI 0.77-0.96) were associated with a higher probability of autonomy decline.Conclusion: Some domains of intrinsic capacity predicted health outcomes among nursing home residents. Nutrition and balance should be regularly checked among this population. [ABSTRACT FROM AUTHOR]

Objective: To compare women's views about blood pressure (BP) control in CHIPS (Control of Hypertension In Pregnancy Study) (NCT01192412).Design: Quantitative and qualitative analysis of questionnaire responses.Setting: International randomised trial (94 sites, 15 countries).Population/sample: 911 (92.9%) women randomised to 'tight' (target diastolic blood pressure, 85mmHg) or 'less tight' (target diastolic blood pressure, 100mmHg) who completed questionnaires.Methods: A questionnaire was administered at ∼6-12 weeks postpartum regarding post-discharge morbidity and views about trial participation. Questionnaires were administered by the site co-ordinator, and contact was made by phone, home or clinic visit; rarely, data was collected from medical records. Quantitative analyses were Chi-square or Fisher's exact test for categorical variables, mixed effects multinomial logistic regression to adjust for confounders, and p<0.001 for statistical significance. NVivo software was used for thematic analysis of women's views.Main Outcome Measures: Satisfaction, measured as willingness to have the same treatment in another pregnancy or recommend that treatment to a friend.Results: Among the 533 women in 'tight' (N=265) vs. 'less tight' (N=268) control who provided comments for qualitative analysis, women in 'tight' (vs. 'less tight') control made fewer positive comments about the amount of medication taken (5 vs. 28 women, respectively) and intensity of BP monitoring (7 vs. 17, respectively). However, this did not translate into less willingness to either have the same treatment in another pregnancy (434, 95.8% vs. 423, 92.4%, respectively; p=0.14) or recommend that treatment to a friend (435, 96.0% and 428, 93.4%, respectively; p=0.17). Importantly, although satisfaction remained high among women with an adverse outcome, those in 'tight' control who suffered an adverse outcome (vs. those who did not) were not consistently less satisfied, whereas this was not the case among women in 'less tight' control among whom satisfaction was consistently lower for the CHIPS primary outcome (p<0.001), severe hypertension (p≤0.01), and pre-eclampsia (p<0.001).Conclusions: Women in 'tight' (vs. 'less tight') control were equally satisfied with their care, and more so in the face of adverse perinatal or maternal outcomes. [ABSTRACT FROM AUTHOR]

Introduction: For women with chronic or gestational hypertension in CHIPS (Control of Hypertension In Pregnancy Study, NCT01192412), we aimed to examine whether clinical predictors collected at randomization could predict adverse outcomes.Material and Methods: This was a planned, secondary analysis of data from the 987 women in the CHIPS Trial. Logistic regression was used to examine the impact of 19 candidate predictors on the probability of adverse perinatal (pregnancy loss or high level neonatal care for >48 h, or birthweight <10th percentile) or maternal outcomes (severe hypertension, preeclampsia, or delivery at <34 or <37 weeks). A model containing all candidate predictors was used to start the stepwise regression process based on goodness of fit as measured by the Akaike information criterion. For face validity, these variables were forced into the model: treatment group ("less tight" or "tight" control), antihypertensive type at randomization, and blood pressure within 1 week before randomization. Continuous variables were represented continuously or dichotomized based on the smaller p-value in univariate analyses. An area-under-the-receiver-operating-curve (AUC ROC) of ≥0.70 was taken to reflect a potentially useful model.Results: Point estimates for AUC ROC were <0.70 for all but severe hypertension (0.70, 95% CI 0.67-0.74) and delivery at <34 weeks (0.71, 95% CI 0.66-0.75). Therefore, no model warranted further assessment of performance.Conclusions: CHIPS data suggest that when women with chronic hypertension develop an elevated blood pressure in pregnancy, or formerly normotensive women develop new gestational hypertension, maternal and current pregnancy clinical characteristics cannot predict adverse outcomes in the index pregnancy. [ABSTRACT FROM AUTHOR]

Objective: To determine whether the difference in outcomes between 'less tight' (target diastolic blood pressure [dBP] of 100 mmHg) versus 'tight' control (target dBP of 85 mmHg) in the CHIPS Trial (ISRCTN 71416914, http://pre-empt.cfri.ca/;CHIPS) depended on the choice of labetalol or methyldopa, the two most commonly used antihypertensive agents in CHIPS.Design: Secondary analysis of CHIPS Trial data.Setting: International multicentre randomised controlled trial (94 sites, 15 countries).Population or Sample: A total of 987 women with non-severe non-proteinuric pregnancy hypertension.Methods: Logistic regression was used for comparisons of 'less tight' versus 'tight' control among women treated with labetalol (but not methydopa) versus methyldopa (but not labetalol). Analyses were adjusted for the influence of baseline factors, including use of any antihypertensive therapy at randomisation.Main Outcome Measures: Main CHIPS Trial outcomes: primary (perinatal loss or high-level neonatal care for > 48 hours), secondary (serious maternal complications), birthweight < 10th centile, severe maternal hypertension, pre-eclampsia, and delivery at < 34 or < 37 weeks.Results: Of 987 women in CHIPS, antihypertensive therapy was taken by 566 women at randomisation (labetalol 111 ['less tight'] versus 127 ['tight'] or methyldopa 126 ['less tight'] versus 117 ['tight']) and 815 women after randomisation (labetalol 186 ['less tight'] versus 247 ['tight'] and methyldopa by 98 ['less tight'] versus 126 ['tight']). Following adjustment, odds ratios for outcomes in 'less tight' versus 'tight' control were similar between antihypertensive groups according to 'at randomisation' and 'after randomisation' therapy.Conclusion: Outcomes for 'less tight' versus 'tight' control were not dependent on use of methyldopa or labetalol.Tweetable Abstract: In the CHIPS Trial, maternal and infant outcomes were not dependent on use of labetalol or methyldopa. [ABSTRACT FROM AUTHOR]

Objective: To compare pregnancy outcomes, accounting for allocated group, between methyldopa-treated and labetalol-treated women in the CHIPS Trial (ISRCTN 71416914) of 'less tight' versus 'tight' control of pregnancy hypertension.Design: Secondary analysis of CHIPS Trial cohort.Setting: International randomised controlled trial (94 sites, 15 countries).Population or Sample: Of 987 CHIPS recruits, 481/566 (85.0%) women treated with antihypertensive therapy at randomisation. Of 981 (99.4%) women followed to delivery, 656/745 (88.1%) treated postrandomisation.Methods: Logistic regression to compare outcomes among women who took methyldopa or labetalol, adjusted for the influence of baseline factors.Main Outcome Measures: CHIPS primary (perinatal loss or high level neonatal care for >48 hours) and secondary (serious maternal complications) outcomes, birthweight <10th centile, severe maternal hypertension, pre-eclampsia and delivery at <34 or <37 weeks.Results: Methyldopa and labetalol were used commonly at randomisation (243/987, 24.6% and 238/987, 24.6%, respectively) and post-randomisation (224/981, 22.8% and 433/981, 44.1%, respectively). Following adjusted analyses, methyldopa (versus labetalol) at randomisation was associated with fewer babies with birthweight <10th centile [adjusted odds ratio (aOR) 0.48; 95% CI 0.20-0.87]. Methyldopa (versus labetalol) postrandomisation was associated with fewer CHIPS primary outcomes (aOR 0.64; 95% CI 0.40-1.00), birthweight <10th centile (aOR 0.54; 95% CI 0.32-0.92), severe hypertension (aOR 0.51; 95% CI 0.31-0.83), pre-eclampsia (aOR 0.55; 95% CI 0.36-0.85), and delivery at <34 weeks (aOR 0.53; 95% CI 0.29-0.96) or <37 weeks (aOR 0.55; 95% CI 0.35-0.85).Conclusion: These nonrandomised comparisons are subject to residual confounding, but women treated with methyldopa (versus labetalol), particularly those with pre-existing hypertension, may have had better outcomes.Tweetable Abstract: There was no evidence that women treated with methyldopa versus labetalol had worse outcomes. [ABSTRACT FROM AUTHOR]

Objective:Placenta-mediated diseases (PMDs) including preeclampsia and fetal growth restriction are often characterized by shallow trophoblast invasion and incomplete spiral artery remodeling leading to impaired placental perfusion. In this context, umbilical artery (UA) Doppler can be used to detect high resistance to flow characteristic of very late-stage placental disease. We propose that evaluation of intraplacental villous artery (IPVA) resistance can provide earlier detection of increased resistance in placental flow.Study Design:Seventy-five patients were recruited from the Ottawa Hospital. All had scans at 18 to 20, 28 and 34 weeks of gestation. IPVAs arising perpendicular to the chorionic plate in three regions (placental tips 4 cm away from cord insertion and within 1 cm from cord insertion) were sampled at each gestational age for resistance index (RI) and pulsatility index (PI). UA Doppler was also obtained from a free loop of cord. Pregnancy outcomes were collected from a chart review. Data were analyzed using SAS version 9.4 and standard statistic tests (mean±s.d., Student's t-test, mixed-effects modeling).Result:A total of 53 patients completed the study. Of these, 38 had normal pregnancy outcomes (controls) and 15 (cases) developed PMD (preeclampsia, n=8 and low birth weight/intrauterine growth restriction, n=7). Mean birth weight in the study group was 2482.1±518.85 g. At 18 to 20, 28 and 34 weeks gestation, the mean IPVA resistance indices in the control group were 0.86±0.16, 0.81±0.12 and 0.71±0.12 for PI and 0.57±0.07, 0.55±0.06 and 0.49±0.06 for RI, respectively. However, in the cases developing PMDs, the PIs were 1.09±0.17, 0.95±0.21 and 0.78±0.07 and RIs 0.66±0.07, 0.60±0.07 and 0.54±0.04, respectively (P<0.05). UA PI and RI Doppler did not differ between the groups as early as 18 to 20 weeks gestation.Conclusion:Doppler measures of IPVA appear superior to UA in detecting early changes related to PMD. IPVA PI and RI Doppler may be useful in the early identification of patients at risk of PMD. [ABSTRACT FROM AUTHOR]

The success of pregnancy is dependent on the precise regulation of the immune response within the utero-placental environment. Rats are beginning to be widely used as a model for human immune-related pregnancy complications. However, our knowledge of immune cells and cytokine localization in the rat utero-placental tissue is limited. The current study aimed to localize the immune cell populations, including uterine natural killer (uNK) cells, neutrophils, and macrophages within the rat utero-placental unit at two crucial gestational ages, gestational days 15.5 and 18.5. In addition, we characterized the distribution of the cytokines TNFα, IFNγ, and IL-10 in the utero-placental regions at both the above-mentioned gestational ages. Our study has demonstrated co-localization TNFα and IFNγ with uNK cells in perivascular regions of the rat mesometrial triangle at both gestational ages. Neutrophils and IL-10-positive cells were localized at the maternal–fetal interface and in the spiral artery lumen of the rat mesometrial triangle at both gestational ages. TNFα and IL-10 demonstrated a temporal change in the localization from GD15.5 to GD18.5, which coincides with the leading edge of trophoblast invasion into the mesometrial triangle. The current study furthers our knowledge of the localization of uterine immune cells and relevant cytokines, and provides a base from which to research the function of these immune cells and cytokines during rat pregnancy as a model to study human immune-related pregnancy complications. [ABSTRACT FROM AUTHOR]

BACKGROUND Emerging evidence from clinical and epidemiological studies suggests that dietary polyphenols play an important role in the prevention of chronic diseases, including cancer, cardiovascular disease, diabetes and neurodegenerative disorders. Although these beneficial health claims are supported by experimental data for many subpopulation groups, some studies purport that excessive polyphenol consumption may have negative health effects in other subpopulations. The ever-growing interest and public awareness surrounding the potential benefits of natural health products and polyphenols, in addition to their widespread availability and accessibility through nutritional supplements and fortified foods, has led to increased consumption throughout gestation. Therefore, understanding the implications of polyphenol intake on obstetrical health outcomes is of utmost importance with respect to safe consumption during pregnancy. METHODS Using relevant keywords, a literature search was performed to gather information regarding polyphenol pharmacology and the molecular mechanisms by which polyphenols exert their biological effects. The primary focus of this paper is to understand the relevance of these findings in the context of reproductive physiology and medicine. RESULTS Evidence from both in vitro experiments and in vivo studies using animals and humans demonstrates that polyphenols regulate key targets related to oxidative stress, inflammation and advanced glycation end products. Although the majority of these studies have been conducted in the context of chronic diseases, such as cancer and diabetes, several of the key targets influenced by polyphenols are also related to a variety of obstetrical complications, including pre-eclampsia, intrauterine growth restriction and preterm birth. Polyphenols have also been shown to influence fertility and sexual development, fetal health and the bioavailability of nutrients. CONCLUSIONS Further research leading to a thorough understanding of the physiological roles and potential clinical value that polyphenol consumption may play in pregnancy is urgently needed to help inform patient safety. [ABSTRACT FROM PUBLISHER]

The article focuses on the influence of hypertension management on pregnancy complications, which was investigated by the authors' open, international, multicenter trial involving pregnant women with nonproteinuric preexisting gestational hypertension. Topics discussed centered on comparing less-tight and tight control of gestational hypertension including patient adherence and cointerventions. Also mentioned is impact of blood pressure level on birth weight.

Recent studies have consistently found pregnancy-associated plasma protein A2 (PAPP-A2) to be upregulated in preeclamptic placentae at term. We tested whether first-trimester circulating PAPP-A2 levels differed between complicated and uncomplicated pregnancies. We measured maternal PAPP-A2 levels at 10 to 14 weeks of gestational age in 17 pregnancies resulting in small-for-gestational-age (SGA) infants, 6 which developed preeclampsia (PE), 1 which developed PE and resulted in an SGA infant, and 37 gestational age-matched controls. The concentration of the PAPP-A2 isoform corresponding to the full-length protein was significantly higher in pregnancies that developed PE (35 ng/mL) compared with those that did not (23 ng/mL; P < .044). In contrast, we found no difference in PAPP-A2 levels between pregnancies that did or did not result in an SGA infant. The upregulation of PAPP-A2 that has previously been observed in PE at term appears to begin early in pregnancy, well before the symptoms develop. [ABSTRACT FROM AUTHOR]

Maternal obesity is associated with an increased risk of a number of pregnancy complications, including fetal demise, which may be linked to impaired placental development as a result of altered trophoblast invasion and vessel remodeling. Therefore, we examined these parameters in pregnant rats fed a control (normal weight) or high fat (HF) diet (obese) at 2 critical times of rat placental development. Early trophoblast invasion was increased by approximately 2-fold in HF-fed dams with a concomitant increase in the expression of matrix metalloproteinase 9 protein, a mediator of tissue remodeling and invasion. Furthermore, we observed significantly higher levels of smooth muscle actin surrounding the placental spiral arteries of HF-fed dams, suggesting impaired spiral artery remodeling. Taken together, the results of this study suggest that altered placental development is an important contributor to the poor pregnancy outcomes and increased fetal demise in our model of lifelong maternal obesity. [ABSTRACT FROM AUTHOR]

Brain injury continues to be one of the leading causes of disability worldwide. Despite decades of research, there is currently no pharmacologically effective treatment for preventing neuronal loss and repairing the brain. As a result, novel therapeutic approaches, such as cell-based therapies, are being actively pursued to repair tissue damage and restore neurological function after injury. In this study, we examined the neuroprotective potential of amniotic fluid (AF) single cell clones, engineered to secrete glial cell derived neurotrophic factor (AF-GDNF), both in vitro and in a surgically induced model of brain injury. Our results show that pre-treatment with GDNF significantly increases cell survival in cultures of AF cells or cortical neurons exposed to hydrogen peroxide. Since improving the efficacy of cell transplantation depends on enhanced graft cell survival, we investigated whether AF-GDNF cells seeded on polyglycolic acid (PGA) scaffolds could enhance graft survival following implantation into the lesion cavity. Encouragingly, the AF-GDNF cells survived longer than control AF cells in serum-free conditions and continued to secrete GDNF both in vitro and following implantation into the injured motor cortex. AF-GDNF implantation in the acute period following injury was sufficient to activate the MAPK/ERK signaling pathway in host neural cells in the peri-lesion area, potentially boosting endogenous neuroprotective pathways. These results were complemented with promising trends in beam walk tasks in AF-GDNF/PGA animals during the 7 day timeframe. Further investigation is required to determine whether significant behavioural improvement can be achieved at a longer timeframe. [ABSTRACT FROM AUTHOR]

Maternal floor infarction is a relatively rare condition characterized clinically by severe early onset fetal growth restriction with features of uteroplacental insufficiency. It has a very high recurrence rate and carries a significant risk or fetal demise. Pathological characteristics include massive and diffuse fibrin deposition along the decidua basalis and the perivillous space of the basal plate. We present a case of recurrent maternal floor infarction and propose diagnostic clues as well as potential therapeutic options. [ABSTRACT FROM AUTHOR]

Intro: Binge eating disorder (BED) affects 3.5% of the population and is characterized by binge eating for at least 2 days a week for 6 months. Treatment options include cognitive behavioral therapy, interpersonal psychotherapy, and pharmacotherapy which are associated with varied success. Little is known about the biology of BED. Since there is evidence that the insulin like growth factor system is implicated in regulation of body weight, insulin sensitivity and feeding behavior, we speculated it may be involved in BED. Methods: A cross-sectional comparison was made between three groups of women: overweight with BED, overweight without BED and normal weight without BED. Women were assigned to Group Psychodynamic Interpersonal Psychotherapy. Blood was collected before therapy, at completion and at 6months follow up for evaluation of IGF-II using Western blot. Results: 97 overweight women with BED contributed to the cross-sectional comparison. The two control groups comprised 53 overweight women without BED, and 50 age matched normal weight women without BED. Obese women had significantly lower Big IGF-II than normal weight women, p = .028; Overweight women with BED had higher Mature IGF-II than normal weight women, p<.05. Big IGF-II showed a significant decreasing slope from pre- to post- to six months post-group psychological treatment, unrelated to changes in BMI (p = .008). Conclusion: Levels of IGF-II isoforms differed significantly between overweight and normal weight women. Overweight women with BED display abnormal levels of circulating IGF-II isoforms. BED is characterized by elevated mature IGF-II, an isoform shown to carry significant bioactivity. This finding is not related to BMI or to changes in body weight. The results also provide preliminary evidence that BIG IGF-II is sensitive to change due to group psychological treatment. We suggest that abnormalities in IGF-II processing may be involved in the neurobiology of BED. [ABSTRACT FROM AUTHOR]

There is a need for improved therapy for acquired brain injury, which has proven resistant to treatment by numerous drugs in clinical trials and continues to represent one of the leading causes of disability worldwide. Research into cell-based therapies for the treatment of brain injury is growing rapidly, but the ideal cell source has yet to be determined. Subpopulations of cells found in amniotic fluid, which is readily obtained during routine amniocentesis, can be easily expanded in culture, have multipotent differentiation capacity, are non-tumourigenic, and avoid the ethical complications associated with embryonic stem cells, making them a promising cell source for therapeutic purposes. Beneficial effects of amniotic fluid cell transplantation have been reported in various models of nervous system injury. However, evidence that amniotic fluid cells can differentiate into mature, functional neurons in vivo and incorporate into the existing circuitry to replace lost or damaged neurons is lacking. The mechanisms by which amniotic fluid cells improve outcomes after experimental nervous system injury remain unclear. However, studies reporting the expression and release of neurotrophic, angiogenic, and immunomodulatory factors by amniotic fluid cells suggest they may provide neuroprotection and (or) stimulate endogenous repair and remodelling processes in the injured nervous system. In this paper, we address recent research related to the neuronal differentiation of amniotic fluid-derived cells, the therapeutic efficacy of these cells in animal models of nervous system injury, and the possible mechanisms mediating the positive outcomes achieved by amniotic fluid cell transplantation. [ABSTRACT FROM AUTHOR]

An abstract of the article "Sonography cervical surveillance with ultrasound-indicated cervical cerclage as compared to prophylatic cerclage in pregnants with clinical risk factors for preterm birth," by F. M. Moretti, T. Al Jishi, and A. Gruslin is presented.

Maternal obesity results in a number of obstetrical and fetal complications with both immediate and long-term consequences. The increased prevalence of obesity has resulted in increasing numbers of women of reproductive age in this high-risk group. Since many of these obese women have been subjected to hypercaloric diets from early childhood we have developed a rodent model of life-long maternal obesity to more clearly understand the mechanisms that contribute to adverse pregnancy outcomes in obese women. Female Sprague Dawley rats were fed a control diet (CON - 16% of calories from fat) or high fat diet (HF - 45% of calories from fat) from 3 to 19 weeks of age. Prior to pregnancy HF-fed dams exhibited significant increases in body fat, serum leptin and triglycerides. A subset of dams was sacrificed at gestational day 15 to evaluate fetal and placental development. The remaining animals were allowed to deliver normally. HF-fed dams exhibited a more than 3-fold increase in fetal death and decreased neonatal survival. These outcomes were associated with altered vascular development in the placenta, as well as increased hypoxia in the labyrinth. We propose that the altered placental vasculature may result in reduced oxygenation of the fetal tissues contributing to premature demise and poor neonatal survival. [ABSTRACT FROM AUTHOR]

The usage of stem cells is a promising strategy for the repair of damaged tissue in the injured brain. Recently, amniotic fluid (AF) cells have received a lot of attention as an alternative source of stem cells for cell-based therapies. However, the success of this approach relies significantly on proper interactions between graft and host tissue. In particular, the reestablishment of functional brain networks requires formation of gap junctions, as a key step to provide sufficient intercellular communication. In this study, we show that AF cells express high levels of CX43 (GJA1) and are able to establish functional gap junctions with cortical cultures. Furthermore, we report an induction of Cx43 expression in astrocytes following injury to the mousemotor cortex and demonstrate for the first time CX43 expression at the interface between implanted AF cells and host brain cells. These findings suggest that CX43-mediated intercellular communication between AF cells and cortical astrocytes may contribute to the reconstruction of damaged tissue by mediating modulatory, homeostatic, and protective factors in the injured brain and hence warrants further investigation. [ABSTRACT FROM AUTHOR]

Please cite this paper as: von Dadelszen P, Dwinnell S, Magee LA, Carleton BC, Gruslin A, Lee B, Lim KI, Liston RM, Miller SP, Rurak D, Sherlock RL, Skoll MA, Wareing MM, Baker PN, for the Research into Advanced Fetal Diagnosis and Therapy (RAFT) Group. Sildenafil citrate therapy for severe early-onset intrauterine growth restriction. BJOG 2011;118:624-628. Currently, there is no effective therapy for severe early-onset intrauterine growth restriction (IUGR). Sildenafil citrate vasodilates the myometrial arteries isolated from women with IUGR-complicated pregnancies. Women were offered Sildenafil (25 mg three times daily until delivery) if their pregnancy was complicated by early-onset IUGR [abdominal circumference (AC) < 5th percentile] and either the gestational age was <25 weeks or an estimate of the fetal weight was <600 g (excluding known fetal anomaly/syndrome and/or planned termination). Sildenafil treatment was associated with increased fetal AC growth [odds ratio, 12.9; 95% confidence interval (CI), 1.3, 126; compared with institutional Sildenafil-naive early-onset IUGR controls]. Randomised controlled trial data are required to determine whether Sildenafil improves perinatal outcomes for early-onset IUGR-complicated pregnancies. [ABSTRACT FROM AUTHOR]

The article presents a study which developed and validated the fullPIERS model to determine the risk of fatal or life-threatening complications in women with pre-eclampsia within 48 hours of hospital admission for the disorder. It identified the predictors of adverse maternal outcome which include gestational age, chest pain or dyspnoea, oxygen saturation and platelet count. It concluded that the fullPIERS model succeeded in predicting adverse maternal outcomes within 48 hours of study eligibility.

The NOTCH signaling pathway plays important roles in stem cell maintenance, cell-fate determination and differentiation during development. Following ligand binding, the cleaved NOTCH intracellular domain (NICD) interacts directly with the recombinant signal binding protein for immunoglobulin kappa J region (RBPJ) transcription factor and the resulting complex targets gene expression in the nucleus. To date, four human RBPJ isoforms have been described in Entrez Gene, varying in the first 5′coding exons. Using an improved protocol, we were able to further identify all four known and five novel RBPJ transcript variants in human amniotic fluid (AF) cells, a cell type known for its stem cell characteristics. In addition, we used human embryonal carcinoma (EC) NTera2/D1 (NT2) cells and NT2-derived neuron and astrocytes to compare the expression pattern of RBPJ transcripts. Further examination of RBPJ transcripts showed that the novel splice variants contain open reading frames in-frame with the known isoforms, suggesting that they can putatively generate similar function proteins. All known and novel RBPJ transcripts contain the putative nuclear localization signal (NLS), an important component of RBPJ-mediated gene regulation. [ABSTRACT FROM AUTHOR]

Abstract: Objective: This document summarizes the limited experience of SARS in pregnancy and suggests guidelines for management. Outcomes: Cases reported from Asia suggest that maternal and fetal outcomes are worsened by SARS during pregnancy. Evidence: Medline was searched for relevant articles published in English from 2000 to 2007. Case reports were reviewed and expert opinion sought. Values: Recommendations were made according to the guidelines developed by the Canadian Task Force on Preventive Health Care. [Copyright &y& Elsevier]

Objective: To determine the association between adverse maternal/perinatal outcomes and Canadian and U.S. preeclampsia severity criteria. Methods: Using PIERS data (Preeclampsia Integrated Estimate of RiSk), an international continuous quality improvement project for women hospitalized with preeclampsia, we examined the association between preeclampsia severity criteria and adverse maternal and perinatal outcomes (univariable analysis, Fisher's exact test). Not evaluated were variables performed in <80% of pregnancies (e.g., 24-hour proteinuria). Results: Few of the evaluated variables were associated with adverse maternal (chest pain/dyspnea, thrombocytopenia, 'elevated liver enzymes', HELLP syndrome, and creatinine >110 μM) or perinatal outcomes (dBP >110 mm Hg and suspected abruption) (at p < 0.01). Conclusions: In the PIERS cohort, most factors used in the Canadian or American classifications of severe preeclampsia do not predict adverse maternal and/or perinatal outcomes. Future classification systems should take this into account. [ABSTRACT FROM AUTHOR]

Background: Satisfaction with maternity care is strongly related to the patient-caregiver relationship and involvement in the decision-making process. We sought to compare women's views about their care in a randomized trial of 'less tight' vs. 'tight' control of non-proteinuric pre-existing or gestational hypertension in pregnancy. Methods: In the CHIPS Pilot Trial, women completed a postpartum questionnaire to assess their likes and dislikes about their blood pressure (BP) management and trial participation. Comparisons were descriptive. Results: Baseline information was similar for the 'less tight' and 'tight' control groups. Of 132 women, 126 (95.5%) from 17 centers completed a postpartum questionnaire, usually within days of delivery. At least 90% of women in both groups were satisfied with their care, and would be willing to participate again or recommend participation to a friend. Women in both the 'less tight' and 'tight' groups were satisfied with BP management (98.4% vs. 95.1%), and the frequency of tests of maternal and fetal well being. Half of women in both groups perceived that their BP was too high and that caregivers thought that their BP was too high. More women in the 'less tight' (vs. the 'tight') control group took less medication than expected (71.7% vs. 38.2%). More women in the 'tight' (vs. the 'less tight') group took more medication than they expected (60.0% vs. 22.2%). At least 60% of all women used home BP monitoring. Conclusion: In the CHIPS Pilot Trial, while women stated that they were satisfied with their BP management and care, a surprising 50% in both groups thought that their BP was too high. The majority of women used home BP monitoring, the role of which must be further defined in hypertensive pregnancies. [ABSTRACT FROM AUTHOR]

Fetal growth restriction (intrauterine growth restriction, IUGR) is a leading cause of perinatal mortality. However, the causes of aberrant development of the placenta and, thus, of the fetus, are not currently known. Insulin-like growth factor II (IGF-ll) has been shown to be an important regulator of fetoplacental growth. This growth factor must undergo posttranslational processing, and, thus, we hypothesized that aberrant processing of pro-IGF-ll to IGF-ll may be a cause of IUGR. Here, we have found that the proprotein convertase PC4 is expressed in the human placenta and that it cleaves pro-lGF-ll to generate the intermediate processed form, IGF-ll (1-102) and, subsequently, mature IGF-ll (1-67), which are accounted for by the removal of terminal basic residues by carboxypeptidases. This processing confers the ability of IGF-lI to activate invasive trophoblast cells through AKT phosphorylation, whereas inhibition of PC4 by a PC4-specific inhibitor blocks pro- IGF-ll processing and reduces trophoblast cell migration, which can be partly restored by addition of mature IGF-Il. Consistent with the hypothesis that IGF-ll processing is implicated in IUGR, sera of patients carrying IUGR fetuses displayed elevated levels of pro- IGF-ll. Thus, abnormal processing of IGF-ll by PC4 may represent a previously uncharacterized mechanism involved in the pathophysiology of fetoplacental growth restriction, and elevated pro-IGF-ll may be a useful clinical marker for risk of IUGR. [ABSTRACT FROM AUTHOR]

Abstract: The abundance of leukocytes at the maternal–fetal interface could influence the fate and invasion of extravillous trophoblasts. However, the mechanism(s) involved in determining the number of leukocytes present at the maternal–fetal interface as well as the nature of the interactions between invading fetal trophoblasts, maternal leukocytes and decidual cells are not well understood. In the present studies, we examined Fas ligand (FasL)/Fas expression at the maternal–fetal interface in human placental tissues of early pregnancy by immunohistochemistry. The types of cells and their localization were also characterized by specific cell markers (cytokeratin, vimentin and CD45 for trophoblast, decidual cells and leukocytes, respectively). The cells undergoing apoptosis and specific apoptotic trophoblasts were detected by TUNEL assay and M30 cytoDEATH immunostaining, respectively. Using single or double immunostaining, we found that FasL expression in decidual cells was negatively correlated with the number of Fas-expressing leukocytes in the same region. Furthermore, the density of leukocytes had an inverse relationship with the number of interstitial trophoblasts present in the same area. We observed also that extravillous trophoblasts are viable despite expressing Fas and being in close proximity to decidual cell-derived FasL. These data support our hypothesis that maternal decidual cell-derived FasL may be involved in preventing the recruitment of Fas-bearing leukocytes at the maternal–fetal interface through apoptosis induction by Fas/FasL interaction, thereby promoting trophoblast invasion. [Copyright &y& Elsevier]

BACKGROUND: How Canadian practitioners are diagnosing and managing the hypertensive disorders of pregnancy (HDP), particularly in relation to the 1997 recommendations published by the Canadian Hypertension Society (CHS), is not known. METHODS: A survey, with French and English versions (and covering diagnosis, evaluation, and management of pregnancy hypertension), was mailed to all members of the Society of Obstetricians and Gynaecologists of Canada (SOGC) (N = 1757, including obstetricians, family doctors practicing obstetrics, and midwives). Additionally, internists [i.e., all nephrologists (N = 191) and a random sample of 25% of general internists (N = 450)] registered with the Royal College of Physicians and Surgeons of Canada were sampled. The survey was distributed in two mailings and one reminder card. Data were entered into Microsoft Access, and Graph Pad Prism used to summarize responses [N (%)]. Differences in practice between specialties were examined, with a Bonferonni correction used to calculate a significant p value based on the number of comparisons and alpha of 0.05. RESULTS: Respondents numbered 1187 (49.5%), with 466 not informative for the purpose of the study (due to retirement, or practices that do not include pregnant women with hypertension). The final analysis included 721 completed surveys. Most (609, 84.5% of) respondents take blood pressure (BP) with women in the sitting position, and use a mercury sphygmomanometer (79%) and the 5th Korotkoff (61%) sound to designate diastolic BP (dBP). To monitor pregnancies complicated by preeclampsia, most clinicians use the proposed laboratory tests of maternal well-being (usually at least once/week), fetal well-being [nonstress test (NST, at least once/week), and ultrasonographic studies (once weekly to every two weeks)]. There is general agreement that women with preeclampsia should be delivered for uncontrolled hypertension, end-organ dysfunction, or fetal compromise (nonreassuring NST, severe oligohydramnios, biophysical profile < 4, estimated fetal weight < 5th centile, and reversed end-diastolic flow by umbilical artery Doppler velocimetry). Less consensus was seen for delivery for preeclampsia at > 34 weeks, mild asymptomatic HELLP syndrome, hyperreflexia, and absent end-diastolic flow by umbilical artery Doppler velocimetry. Interpretation: This survey has clarified the current state of practice with respect to the diagnosis and evaluation of women with all types of HDP. In particular, we have identified areas of potential variability in BP measurement, and provided data on the feasibility of enrolling women with sub types of preeclampsia into intervention studies aimed at prolonging pregnancy. [ABSTRACT FROM AUTHOR]

BACKGROUND: How Canadian practitioners are managing the hypertensive disorders of pregnancy (HDP) is not known, particularly in relation to the 1997 guidelines published by the Canadian Hypertension Society (CHS). METHODS: A survey, with French and English versions (and covering diagnosis, evaluation, and management of pregnancy hypertension), was mailed to all members of the Society of Obstetricians and Gynaecologists of Canada (SOGC) (N = 1757, including obstetricians, family doctors practicing obstetrics, and midwives). Additionally, internists [i.e., all nephrologists (N = 191) and a random sample of 25% of general internists (N = 450)] registered with the Royal College of Physicians and Surgeons of Canada were sampled. The survey was distributed in two mailings and one reminder card. Data were entered into Microsoft Access, and Graph Pad Prism used to summarize responses [N (%)]. Differences in practice between specialties were examined, with a Bonferroni correction used to calculate a significant p value based on the number of comparisons and alpha of 0.05. RESULTS: Respondents numbered 1187 (49.5%), with 466 not informative for the purpose of the study (due to retirement, or practices that do not include pregnant women with hypertension). The final analysis included 721 completed surveys. For all types of HDP, most internists, family doctors, and midwives initiate nonpharmacological therapy (most common advice to quit work) at dBP 80–89 mmHg (i.e., primary prevention). Only for preeclampsia do obstetricians most frequently use this threshold; otherwise, dBP 90–99 mmHg is usually chosen. For nonsevere hypertension, antihypertensive drug therapy (most commonly methyldopa or labetalol) is started by most practitioners at dBP 90–99 mmHg, although obstetricians are more likely to choose a higher threshold (p < 0.0001). There is little agreement about dBP treatment goal; most internists and family doctors normalize dBP, whereas obstetricians appear to be divided on dBP goals of 80–89 (46–51%) vs. 90–99 mmHg (41–44%) for all HDP (p = 0.66). Severe hypertension is commonly treated with parenteral hydralazine, labetalol, or magnesium sulphate. Short-acting or sustained release nifedipine is used rarely/never by most practitioners. Approximately one-third of obstetricians and family doctors use diazepam to treat eclampsia. The vast majority use MgSO4 prophylactically in women with preeclampsia. Interpretation: This survey has clarified current stated management of women with HDP, and identified the need for both research into the dBP treatment goal that optimizes pregnancy outcomes among women with HDP, and translation of definitive studies into clinical practice. [ABSTRACT FROM AUTHOR]

• Subjects with low peak expiratory flow have low physical and muscular capacity. • Peak expiratory flow is not an independent predictor of adverse health outcomes. • Peak expiratory flow has limited added value compared to the SPPB test. To correlate peak expiratory flow (PEF) with the incidence of frailty, deaths and falls among nursing home residents. This is a 1-year longitudinal analysis performed on the clinical data of the SENIOR cohort. PEF, measured by peak flow meter, was considered as "low" when the observed value was ≤80% of the theoretical value. Physical capacity was evaluated using Short Physical Performance Battery, balance and gait using Tinetti test and muscle strength using a dynamometer. The incidence of frailty was defined as the transition from a "robust" or "prefrail" status to a "frail" status following Fried's criteria. Deaths and falls were also collected. Among 646 subjects included at baseline (83.2 ± 9 years and 72.1% women), 297 (45.7%) displayed a low PEF. In this subgroup, physical capacity (p-values from 0.01 to <0.001), muscle strength (p < 0.001), balance and gait score (p < 0.001) were significantly lower compared to subjects displaying normal PEF. Subjects who became frail after one year displayed a lower % of the theoretical PEF value compared to those that did not (88.52 ± 45.06 vs 102.78 ± 50.29, respectively, p = 0.03). After adjustment for potential confounding variables (calf circumference, Tinetti test, SPPB test and handgrip strength), PEF was no longer associated with the occurrence of frailty. There was no association between PEF and mortality and falls. In a nursing home setting, PEF is not an independent factor associated with the incidence of frailty, deaths and falls. [ABSTRACT FROM AUTHOR]