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Sample records for adverse fetal outcomes

  1. Adverse Fetal Outcomes Associated with Immunosuppressive Medications for Chronic Immune Mediated Diseases in Pregnancy

    PubMed Central

    Cooper, William O.; Cheetham, T. Craig; Li, De-Kun; Stein, C. Michael; Callahan, S. Todd; Morgan, Thomas M.; Shintani, Ayumi K.; Chen, Ning; Griffin, Marie R.; Ray, Wayne A.

    2014-01-01

    Objective We assessed the risk of adverse fetal outcomes following exposure to individual immunosuppressive drugs in pregnant women with chronic immune mediated diseases. Methods We used health plan data from Tennessee Medicaid and Kaiser Permanente Northern California and Southern California linked with vital records and medical records. Women with inflammatory arthropathies, systemic lupus erythematosus, and inflammatory bowel disease who filled prescriptions for immunosuppressive treatments during pregnancy were included. Major congenital malformations, fetal deaths, and life-threatening neonatal complications were identified from electronic data and validated with medical record review. Results The cohort included 608 infants, including 437 with exposure during pregnancy (402 first trimester, 35 second and third trimester only) and 171 whose mothers filled prescriptions for immunosuppressives before, but not during, pregnancy. There were 25 pregnancies (4.1% of the cohort) with confirmed major congenital malformations, 10 fetal deaths (1.6%), 23 life-threatening neonatal complications among preterm infants (20.4%), and 10 (2.1%) life-threatening complications among term infants. Compared to the reference group (medication treatment before, but not during, pregnancy), the risk ratios for adverse fetal outcomes associated with immunosuppressive use during pregnancy by exposure category included: methotrexate [risk ratio 1.39 (95% confidence interval 0.43,4.53)], tumor necrosis factor inhibitors [0.98 (0.38,2.55)], hydroxychloroquine [1.33 (0.69,2.55)], and other immunosuppressives [0.98, (0.48,1.98)]. Conclusions We found no evidence of a large increase in risk of adverse fetal outcomes from first trimester exposure to immunosuppressive medications, though confidence intervals for risk ratios were wide. Further studies will be needed as use of these medications increases over time. PMID:24504818

  2. Psychoneuroimmunology in pregnancy: immune pathways linking stress with maternal health, adverse birth outcomes, and fetal development.

    PubMed

    Christian, Lisa M

    2012-01-01

    It is well-established that psychological stress promotes immune dysregulation in nonpregnant humans and animals. Stress promotes inflammation, impairs antibody responses to vaccination, slows wound healing, and suppresses cell-mediated immune function. Importantly, the immune system changes substantially to support healthy pregnancy, with attenuation of inflammatory responses and impairment of cell-mediated immunity. This adaptation is postulated to protect the fetus from rejection by the maternal immune system. Thus, stress-induced immune dysregulation during pregnancy has unique implications for both maternal and fetal health, particularly preterm birth. However, very limited research has examined stress-immune relationships in pregnancy. The application of psychoneuroimmunology research models to the perinatal period holds great promise for elucidating biological pathways by which stress may affect adverse pregnancy outcomes, maternal health, and fetal development.

  3. Psychoneuroimmunology in Pregnancy: Immune Pathways Linking Stress with Maternal Health, Adverse Birth Outcomes, and Fetal Development

    PubMed Central

    Christian, Lisa M.

    2011-01-01

    It is well-established that psychological stress promotes immune dysregulation in nonpregnant humans and animals. Stress promotes inflammation, impairs antibody responses to vaccination, slows wound healing, and suppresses cell-mediated immune function. Importantly, the immune system changes substantially to support healthy pregnancy, with attenuation of inflammatory responses and impairment of cell-mediated immunity. This adaptation is postulated to protect the fetus from rejection by the maternal immune system. Thus, stress-induced immune dysregulation during pregnancy has unique implications for both maternal and fetal health, particularly preterm birth. However, very limited research has examined stress-immune relationships in pregnancy. The application of psychoneuroimmunology research models to the perinatal period holds great promise for elucidating biological pathways by which stress may affect adverse pregnancy outcomes, maternal health, and fetal development. PMID:21787802

  4. Preventive Effects of Folic Acid Supplementation on Adverse Maternal and Fetal Outcomes

    PubMed Central

    Kim, Min Woo; Ahn, Ki Hoon; Ryu, Ki-Jin; Hong, Soon-Cheol; Lee, Ji Sung; Nava-Ocampo, Alejandro A.; Oh, Min-Jeong; Kim, Hai-Joong

    2014-01-01

    Although there is accumulating evidence regarding the additional protective effect of folic acid against adverse pregnancy outcomes other than neural tube defects, these effects have not been elucidated in detail. We evaluated whether folic acid supplementation is associated with favorable maternal and fetal outcomes. This was a secondary analysis of 215 pregnant women who were enrolled in our prior study. With additional data from telephone interviews regarding prenatal folic acid supplementation, existing demographic, maternal and fetal data were statistically analyzed. The concentration of folic acid in maternal blood was significantly higher following folic acid supplementation (24.6 ng/mL vs.11.8 ng/mL). In contrast, homocysteine level in maternal blood decreased with folic acid supplementation (5.5 µmol/mL vs. 6.8 µmol/mL). The rates of both preeclampsia (odds ratio [OR], 0.27; 95% confidence interval [CI], 0.09–0.76) and small for gestational age (SGA; 9.2% vs. 20.0%; OR, 0.42; 95% CI, 0.18–0.99) were lower in the folic acid supplementation group than those in the control group. Other pregnancy outcomes had no association with folic acid supplementation. The findings indicate that folic acid supplementation may help to prevent preeclampsia and SGA. Further studies are warranted to elucidate the favorable effects of folic acid supplementation on pregnancy outcomes. PMID:24842467

  5. Comparison of placental growth factor and fetal flow Doppler ultrasonography to identify fetal adverse outcomes in women with hypertensive disorders of pregnancy: an observational study

    PubMed Central

    2013-01-01

    Background Hypertensive disorders of pregnancy and intrauterine growth restriction (IUGR) are leading causes of maternal and perinatal morbidity and mortality. Failure to detect intrauterine growth restriction in women at high risk has been highlighted as a significant avoidable cause of serious fetal outcome. In this observational study we compare fetal flow using Doppler ultrasonography with a new test for placental growth factor (PlGF) to predict fetal adverse events. Methods Eighty-nine women with hypertensive disorders of pregnancy (24 with chronic hypertension, 17 with gestational hypertension, 12 with HELLP syndrome, 19 with preeclampsia and 17 with superimposed preeclampsia) were enrolled. A single maternal blood sample to measure free PlGF (Alere Triage) taken before 35 weeks of pregnancy was compared to the last Doppler ultrasound measurement of fetal flow before delivery. PlGF was classified as normal (PlGF≥100 pg/ml), low (12fetal flow was defined as either signs of centralisation of the fetal circulation or diastolic block or reverse flow in the umbilical artery or descending aorta; this was a criterion for delivery. Fetal outcomes were intrauterine growth restriction and birth before 37 weeks of pregnancy. Results In total 61/89 women had a preterm birth and 22 infants had IUGR. Of those who delivered preterm, 20/20 women with abnormal fetal flow and 36/41 (87.8%) women with normal fetal flow had low or very low PlGF. Of those infants with IUGR, 22/22 had low or very low maternal PlGF and 10/22 had abnormal fetal flow. Conclusions PlGF may provide useful information before 35th gestational week to identify fetuses requiring urgent delivery, and those at risk of later adverse outcomes not identified by fetal flow Doppler ultrasonography. PMID:23937721

  6. [Electronic fetal monitoring and management of adverse outcomes: how to perform and improve a training program for clinicians?].

    PubMed

    Secourgeon, J-F

    2012-10-01

    Electronic fetal monitoring during labor is the most commonly used method to evaluate the fetal status, but it remains exposed to some criticism. By comparison with intermittent auscultation and in the light of the results of the great studies in the last 30 years, it may be accused its failure to improve the neonatal outcome and its responsibility in the increase on operative deliveries. Actually, the electronic fetal monitoring is a tool whose effectiveness is linked to the accuracy of the analysis developed by the clinician. Studies on assessment of the tracing interpretation indicate that there is always a lack of quality, which may be improved through training programs. It also reveals the benefit of the fetal blood sampling to reduce operative deliveries and the generalization of this method, in addition to electronic fetal monitoring, is recommended by referral agencies. More generally, the continuous monitoring is only a part of the patient safety strategy in the labour ward and we are currently observing, in some European countries and in the United States, the development of training programs concerning the management of the adverse outcomes in obstetrics. The good performances related to the quality of care are demonstrated by the findings of the studies performed in the centers that have implemented an active training policy. In France, the professionals directly involved in the field of the perinatology should benefit from such educational programs that could be organized within the care networks under the authority of referral agencies.

  7. Maternal fructose drives placental uric acid production leading to adverse fetal outcomes

    PubMed Central

    Asghar, Zeenat A.; Thompson, Alysha; Chi, Maggie; Cusumano, Andrew; Scheaffer, Suzanne; Al-Hammadi, Noor; Saben, Jessica L.; Moley, Kelle H.

    2016-01-01

    Maternal metabolic diseases increase offspring risk for low birth weight and cardiometabolic diseases in adulthood. Excess fructose consumption may confer metabolic risks for both women and their offspring. However, the direct consequences of fructose intake per se are unknown. We assessed the impact of a maternal high-fructose diet on the fetal-placental unit in mice in the absence of metabolic syndrome and determined the association between maternal serum fructose and placental uric acid levels in humans. In mice, maternal fructose consumption led to placental inefficiency, fetal growth restriction, elevated fetal serum glucose and triglyceride levels. In the placenta, fructose induced de novo uric acid synthesis by activating the activities of the enzymes AMP deaminase and xanthine oxidase. Moreover, the placentas had increased lipids and altered expression of genes that control oxidative stress. Treatment of mothers with the xanthine oxidase inhibitor allopurinol reduced placental uric acid levels, prevented placental inefficiency, and improved fetal weights and serum triglycerides. Finally, in 18 women delivering at term, maternal serum fructose levels significantly correlated with placental uric acid levels. These findings suggest that in mice, excess maternal fructose consumption impairs placental function via a xanthine oxidase/uric acid-dependent mechanism, and similar effects may occur in humans. PMID:27125896

  8. Indoor exposure and adverse birth outcomes related to fetal growth, miscarriage and prematurity-a systematic review.

    PubMed

    Patelarou, Evridiki; Kelly, Frank J

    2014-06-01

    The purpose of this review was to summarize existing epidemiological evidence of the association between quantitative estimates of indoor air pollution and all-day personal exposure with adverse birth outcomes including fetal growth, prematurity and miscarriage. We carried out a systematic literature search of MEDLINE and EMBASE databases with the aim of summarizing and evaluating the results of peer-reviewed epidemiological studies undertaken in "westernized" countries that have assessed indoor air pollution and all-day personal exposure with specific quantitative methods. This comprehensive literature search identified 16 independent studies which were deemed relevant for further review and two additional studies were added through searching the reference lists of all included studies. Two reviewers independently and critically appraised all eligible articles using the Critical Appraisal Skills Programme (CASP) tool. Of the 18 selected studies, 14 adopted a prospective cohort design, three were case-controls and one was a retrospective cohort study. In terms of pollutants of interest, seven studies assessed exposure to electro-magnetic fields, four studies assessed exposure to polycyclic aromatic hydrocarbons, four studies assessed PM2.5 exposure and three studies assessed benzene, phthalates and noise exposure respectively. Furthermore, 12 studies examined infant growth as the main birth outcome of interest, six examined spontaneous abortion and three studies assessed gestational age at birth and preterm delivery. This survey demonstrates that there is insufficient research on the possible association of indoor exposure and early life effects and that further research is needed. PMID:24896737

  9. Indoor Exposure and Adverse Birth Outcomes Related to Fetal Growth, Miscarriage and Prematurity—A Systematic Review

    PubMed Central

    Patelarou, Evridiki; Kelly, Frank J.

    2014-01-01

    The purpose of this review was to summarize existing epidemiological evidence of the association between quantitative estimates of indoor air pollution and all-day personal exposure with adverse birth outcomes including fetal growth, prematurity and miscarriage. We carried out a systematic literature search of MEDLINE and EMBASE databases with the aim of summarizing and evaluating the results of peer-reviewed epidemiological studies undertaken in “westernized” countries that have assessed indoor air pollution and all-day personal exposure with specific quantitative methods. This comprehensive literature search identified 16 independent studies which were deemed relevant for further review and two additional studies were added through searching the reference lists of all included studies. Two reviewers independently and critically appraised all eligible articles using the Critical Appraisal Skills Programme (CASP) tool. Of the 18 selected studies, 14 adopted a prospective cohort design, three were case-controls and one was a retrospective cohort study. In terms of pollutants of interest, seven studies assessed exposure to electro-magnetic fields, four studies assessed exposure to polycyclic aromatic hydrocarbons, four studies assessed PM2.5 exposure and three studies assessed benzene, phthalates and noise exposure respectively. Furthermore, 12 studies examined infant growth as the main birth outcome of interest, six examined spontaneous abortion and three studies assessed gestational age at birth and preterm delivery. This survey demonstrates that there is insufficient research on the possible association of indoor exposure and early life effects and that further research is needed. PMID:24896737

  10. Early spontaneous multiple fetal pregnancy reduction is associated with adverse perinatal outcomes in in vitro fertilization cycles.

    PubMed

    Petrini, Allison C; Pereira, Nigel; Lekovich, Jovana P; Elias, Rony T; Spandorfer, Steven D

    2016-07-01

    The primary objective of this study is to investigate whether early spontaneous multiple fetal pregnancy reduction, also known as vanishing twin syndrome, is associated with adverse perinatal outcomes in fresh in vitro fertilization cycles. This is a retrospective cohort study of women with live singleton births with and without an early vanishing twin after fresh in vitro fertilization. Characteristics compared included incidence of preterm birth, overall birth weight, overall low birth weight, overall very low birth weight, and term low birth weight. In all, 4049 patients with live singleton births were included-853 and 3196 with and without a vanishing twin, respectively. The vanishing twin group had a lower overall birth weight compared to those without (3279.5 ± 369.9 vs 3368.6 ± 567.5 g; p < 0.01). Early vanishing twin was also associated with an increased odds of overall low birth weight (odds ratio: 1.75; 95% confidence interval: 1.36-2.25; p < 0.01) and increased odds of term low birth weight (odds ratio: 3.44; 95% confidence interval: 2.14-5.53; p < 0.01). Our study suggests that early vanishing twin is associated with lower overall birth weight and higher odds of overall low birth weight and term low birth weight in live singleton births after fresh in vitro fertilization. PMID:27638897

  11. Fetal growth potential and pregnancy outcome.

    PubMed

    Bukowski, Radek

    2004-02-01

    Although the association of fetal growth restriction and adverse pregnancy outcomes is well known, lack of sensitivity limits its clinical value. To a large extent, this limitation is a result of traditionally used method to define growth restriction by comparing fetal or birth weight to population norms. The use of population norms, by virtue of their inability to fully consider individual variation, results in high false positive and negative rates. An alternative, calculating fetal individually optimal growth potential, based on physiological determinants of individual growth, is superior in predicting adverse outcomes of pregnancy. Impairment of fetal growth potential identifes some adverse pregnancy outcomes that are not associated with growth restrction defined by population norms. When compared with traditional population-based norms, fetal growth potential is a better predictor of several important adverse outcomes of pregnancy which include: stillbirth, neonatal mortality and morbidity, and long-term adverse neonatal outcomes like neonatal encephalopathy, cerebral palsy and cognitive abilities. Impairment of individual growth potential is also strongly associated with spontaneous preterm delivery. Although definitive interventional trials have not been conducted as yet to validate the clinical value of fetal growth potential, many observational studies, conducted in various populations, indicate its significant promise in this respect.

  12. Mid-Trimester Maternal Serum hCG and Alpha Fetal Protein Levels: Clinical Significance and Prediction of Adverse Pregnancy Outcome

    PubMed Central

    Androutsopoulos, Georgios; Gkogkos, Panagiotis; Decavalas, Georgios

    2013-01-01

    Context Maternal serum human Chorionic Gonadotropin (hCG) and Alpha Fetal Protein (AFP) were originally introduced to detect trisomy 21 and neural tube defects. However, in the absence of aneuploidy or neural tube defects, mid-trimester maternal serum hCG and/or maternal serum AFP associated with adverse pregnancy outcomes. Pregnancies with unexplained mid-trimester elevation in maternal serum hCG and/or maternal serum AFP, are at increased risk for pregnancy complications resulting from placental insufficiency. Evidence Acquisition Mid-trimester maternal serum hCG>2.5 MoM associated with an increased risk for pregnancy complications including: late fetal loss, gestational hypertension, preeclampsia, intrauterine growth restriction (IUGR), preterm delivery and intrauterine fetal death(IUFD). Mid-trimester maternal serum AFP levels >2.5 MoM are thought to reflect a defect in placentation and associated with an increased risk for pregnancy complications including: late fetal loss, gestational hypertension, preeclampsia, IUGR, preterm delivery and IUFD. Results Combined mid-trimester elevation in maternal serum hCG and AFP levels suggest a more complex type of placental pathology. They have stronger association with pregnancy complications including: late fetal loss, gestational hypertension, preeclampsia, IUGR, preterm delivery and IUFD. Conclusions Mid-trimester maternal serum hCG or AFP levels alone cannot detect all pregnant women with increased risk to develop pregnancy complications. Multiparameter testing of placental function in mid-trimester (maternal serum hCG and AFP screening, uterine artery Doppler and placental morphology) may allow us to identify women with increased risk to develop severe placental insufficiency and pregnancy complications. However, future prospective studies are needed to confirm the prognostic significance of multiparameter testing of placental function in mid-trimester. PMID:23825981

  13. Isolated Short Fetal Femur Length in the Second Trimester and the Association with Adverse Perinatal Outcome: Experiences from a Tertiary Referral Center

    PubMed Central

    Mailath-Pokorny, Mariella; Polterauer, Stephan; Worda, Katharina; Springer, Stephanie; Bettelheim, Dieter

    2015-01-01

    Objective To determine the association between isolated mid-trimester short fetal femur length and adverse perinatal outcome. Methods This is a retrospective cohort study of patients with singleton gestations routinely assessed by second trimester ultrasound examination during 2006-2013. A fetal isolated short femur was defined as a femur length (FL) below the 5th percentile in a fetus with an abdominal circumference greater than the 10th percentile. Cases of aneuploidy, skeletal dysplasia and major anomalies were excluded. Primary outcomes of interest included the risk of small for gestational age neonates, low birth weight and preterm birth (PTB). Secondary outcome parameters were a 5-min Apgar score less than 7 and a neonatal intensive care unit admission. A control group of 200 fetuses with FL ≥ 5th percentile was used to compare primary and secondary outcome parameters within both groups. Chi-square and Student’s t-tests were used where appropriate. Results Out of 608 eligible patients with a short FL, 117 met the inclusion criteria. Isolated short FL was associated with an increased risk for small for gestational age (19.7% versus 8.0%, p = 0.002) neonates, low birth weight (23.9% versus 8.5%, p<0.001), PTB (19.7% versus 6.0%, p<0.001) and neonatal intensive care unit admissions (13.7% versus 3.5%, p = 0.001). The incidence of a 5-min Apgar score less than 7 was similar in both groups. Conclusion Isolated short FL is associated with a subsequent delivery of small for gestational age and Low birth weight neonates as well as an increased risk for PTB. This information should be considered when counseling patients after mid-trimester isolated short FL is diagnosed. PMID:26046665

  14. A/H1N1 pandemic influenza vaccination: A retrospective evaluation of adverse maternal, fetal and neonatal outcomes in a cohort of pregnant women in Italy.

    PubMed

    Fabiani, Massimo; Bella, Antonino; Rota, Maria C; Clagnan, Elena; Gallo, Tolinda; D'Amato, Maurizio; Pezzotti, Patrizio; Ferrara, Lorenza; Demicheli, Vittorio; Martinelli, Domenico; Prato, Rosa; Rizzo, Caterina

    2015-05-01

    Although concerns about safety of influenza vaccination during pregnancy have been raised in the past, vaccination of pregnant women was recommended in many countries during the 2009 A/H1N1 pandemic influenza. A retrospective cohort study was conducted to evaluate the risk of adverse maternal, fetal and neonatal outcomes among pregnant women vaccinated with a MF59-adjuvanted A/H1N1 pandemic influenza vaccine. The study was carried out in four Italian regions (Piemonte, Friuli-Venezia-Giulia, Lazio, and Puglia) among 102,077 pregnant women potentially exposed during the second or third trimester of gestation to the vaccination campaign implemented in 2009/2010. Based on data retrieved from the regional administrative databases, the statistical analysis was performed using the Cox proportional-hazards model, adjusting for the propensity score to account for the potential confounding effect due to the socio-demographic characteristics and the clinical and reproductive history of women. A total of 100,332 pregnant women were eligible for the analysis. Of these, 2003 (2.0%) received the A/H1N1 pandemic influenza vaccination during the second or third trimester of gestation. We did not observe any statistically significant association between the A/H1N1 pandemic influenza vaccination and different maternal outcomes (hospital admissions for influenza, pneumonia, hypertension, eclampsia, diabetes, thyroid disease, and anaemia), fetal outcomes (fetal death after the 22nd gestational week) and neonatal outcomes (pre-term birth, low birth weight, low 5-min Apgar score, and congenital malformations). Pre-existing health-risk conditions (hospital admissions and drug prescriptions for specific diseases before the onset of pregnancy) were observed more frequently among vaccinated women, thus suggesting that concomitant chronic conditions increased vaccination uptake. The results of this study add some evidence on the safety of A/H1N1 pandemic influenza vaccination during

  15. The complement system and adverse pregnancy outcomes.

    PubMed

    Regal, Jean F; Gilbert, Jeffrey S; Burwick, Richard M

    2015-09-01

    Adverse pregnancy outcomes significantly contribute to morbidity and mortality for mother and child, with lifelong health consequences for both. The innate and adaptive immune system must be regulated to insure survival of the fetal allograft, and the complement system is no exception. An intact complement system optimizes placental development and function and is essential to maintain host defense and fetal survival. Complement regulation is apparent at the placental interface from early pregnancy with some degree of complement activation occurring normally throughout gestation. However, a number of pregnancy complications including early pregnancy loss, fetal growth restriction, hypertensive disorders of pregnancy and preterm birth are associated with excessive or misdirected complement activation, and are more frequent in women with inherited or acquired complement system disorders or complement gene mutations. Clinical studies employing complement biomarkers in plasma and urine implicate dysregulated complement activation in components of each of the adverse pregnancy outcomes. In addition, mechanistic studies in rat and mouse models of adverse pregnancy outcomes address the complement pathways or activation products of importance and allow critical analysis of the pathophysiology. Targeted complement therapeutics are already in use to control adverse pregnancy outcomes in select situations. A clearer understanding of the role of the complement system in both normal pregnancy and complicated or failed pregnancy will allow a rational approach to future therapeutic strategies for manipulating complement with the goal of mitigating adverse pregnancy outcomes, preserving host defense, and improving long term outcomes for both mother and child.

  16. The Complement System and Adverse Pregnancy Outcomes

    PubMed Central

    Regal, Jean F.; Gilbert, Jeffrey S.; Burwick, Richard M.

    2015-01-01

    Adverse pregnancy outcomes significantly contribute to morbidity and mortality for mother and child, with lifelong health consequences for both. The innate and adaptive immune system must be regulated to insure survival of the feta allograft, and the complement system is no exception. An intact complement system optimizes placental development and function and is essential to maintain host defense and fetal survival. Complement regulation is apparent at the placental interface from early pregnancy with some degree of complement activation occurring normally throughout gestation. However, a number of pregnancy complications including early pregnancy loss, fetal growth restriction, hypertensive disorders of pregnancy and preterm birth are associated with excessive or misdirected complement activation, and are more frequent in women with inherited or acquired complement system disorders or complement gene mutations. Clinical studies employing complement biomarkers in plasma and urine implicate dysregulated complement activation in components of each of the adverse pregnancy outcomes. In addition, mechanistic studies in rat and mouse models of adverse pregnancy outcomes address the complement pathways or activation products of importance and allow critical analysis of the pathophysiology. Targeted complement therapeutics are already in use to control adverse pregnancy outcomes in select situations. A clearer understanding of the role of the complement system in both normal pregnancy and complicated or failed pregnancy will allow a rational approach to future therapeutic strategies for manipulating complement with the goal of mitigating adverse pregnancy outcomes, preserving host defense, and improving long term outcomes for both mother and child. PMID:25802092

  17. Reverse Engineering Adverse Outcome Pathways

    SciTech Connect

    Perkins, Edward; Chipman, J.K.; Edwards, Stephen; Habib, Tanwir; Falciani, Francesco; Taylor, Ronald C.; Van Aggelen, Graham; Vulpe, Chris; Antczak, Philipp; Loguinov, Alexandre

    2011-01-30

    The toxicological effects of many stressors are mediated through unknown, or poorly characterized, mechanisms of action. We describe the application of reverse engineering complex interaction networks from high dimensional omics data (gene, protein, metabolic, signaling) to characterize adverse outcome pathways (AOPs) for chemicals that disrupt the hypothalamus-pituitary-gonadal endocrine axis in fathead minnows. Gene expression changes in fathead minnow ovaries in response to 7 different chemicals, over different times, doses, and in vivo versus in vitro conditions were captured in a large data set of 868 arrays. We examined potential AOPs of the antiandrogen flutamide using two mutual information theory methods, ARACNE and CLR to infer gene regulatory networks and potential adverse outcome pathways. Representative networks from these studies were used to predict a network path from stressor to adverse outcome as a candidate AOP. The relationship of individual chemicals to an adverse outcome can be determined by following perturbations through the network in response to chemical treatment leading to the nodes associated with the adverse outcome. Identification of candidate pathways allows for formation of testable hypotheses about key biologic processes, biomarkers or alternative endpoints, which could be used to monitor an adverse outcome pathway. Finally, we identify the unique challenges facing the application of this approach in ecotoxicology, and attempt to provide a road map for the utilization of these tools. Key Words: mechanism of action, toxicology, microarray, network inference

  18. A Short-term In vivo Screen using Fetal Testosterone Production, a Key Event in the Phthalate Adverse Outcome Pathway, to Predict Disruption of Sexual Differentiation.

    EPA Science Inventory

    This study was designed to develop and validate a short-term in vivo protocol termed the Fetal Phthalate Screen (FPS) to detect phthalate esters (PEs) and other chemicals that disrupt fetal testosterone synthesis and testis gene expression in rats. We propose that the FPS can be ...

  19. Hyperglycemia and Adverse Pregnancy Outcome (HAPO) Study

    PubMed Central

    2009-01-01

    OBJECTIVE—To examine associations of neonatal adiposity with maternal glucose levels and cord serum C-peptide in a multicenter multinational study, the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) Study, thereby assessing the Pederson hypothesis linking maternal glycemia and fetal hyperinsulinemia to neonatal adiposity. RESEARCH DESIGN AND METHODS—Eligible pregnant women underwent a standard 75-g oral glucose tolerance test between 24 and 32 weeks gestation (as close to 28 weeks as possible). Neonatal anthropometrics and cord serum C-peptide were measured. Associations of maternal glucose and cord serum C-peptide with neonatal adiposity (sum of skin folds >90th percentile or percent body fat >90th percentile) were assessed using multiple logistic regression analyses, with adjustment for potential confounders, including maternal age, parity, BMI, mean arterial pressure, height, gestational age at delivery, and the baby's sex. RESULTS—Among 23,316 HAPO Study participants with glucose levels blinded to caregivers, cord serum C-peptide results were available for 19,885 babies and skin fold measurements for 19,389. For measures of neonatal adiposity, there were strong statistically significant gradients across increasing levels of maternal glucose and cord serum C-peptide, which persisted after adjustment for potential confounders. In fully adjusted continuous variable models, odds ratios ranged from 1.35 to 1.44 for the two measures of adiposity for fasting, 1-h, and 2-h plasma glucose higher by 1 SD. CONCLUSIONS—These findings confirm the link between maternal glucose and neonatal adiposity and suggest that the relationship is mediated by fetal insulin production and that the Pedersen hypothesis describes a basic biological relationship influencing fetal growth. PMID:19011170

  20. Fetal malnutrition and long-term outcomes

    PubMed Central

    Fall, Caroline HD

    2016-01-01

    Epidemiological studies have shown that lower birthweight is associated with a wide range of adverse outcomes in later life, including poorer ‘human capital’ (shorter stature, lower cognitive performance); increased risk factors for later disease, (higher blood pressure and reduced glucose tolerance, and lung, kidney and immune function); clinical disease (diabetes, coronary heart disease, chronic lung and kidney disease); and increased all-cause and cardiovascular mortality. Higher birthweight is associated with an increased risk of cancer, and (if caused by gestational diabetes) obesity and diabetes. The “developmental origins of health and disease” (DOHaD) hypothesis proposes that fetal nutrition has permanent effects on growth, structure and metabolism (‘programming’). This is supported by studies in animals showing that maternal under- and over-nutrition during pregnancy can produce similar abnormalities in the adult offspring. Common chronic diseases could potentially be prevented by achieving optimal fetal nutrition, and this could have additional benefits for survival and human capital. Recent follow-up of children born after randomised nutritional interventions in pregnancy provides weak evidence of beneficial effects on growth, vascular function, lipid concentrations, glucose tolerance and insulin resistance. Animal studies indicate that epigenetic phenomena may be an important mechanism underlying programming, and that nutritional interventions may need to start pre-conceptionally. PMID:23887100

  1. Fetal malnutrition and long-term outcomes.

    PubMed

    Fall, Caroline H D

    2013-01-01

    Epidemiological studies have shown that lower birthweight is associated with a wide range of adverse outcomes in later life, including poorer 'human capital' (shorter stature, lower cognitive performance), increased risk factors for later disease (higher blood pressure and reduced glucose tolerance, and lung, kidney and immune function), clinical disease (diabetes, coronary heart disease, chronic lung and kidney disease), and increased all-cause and cardiovascular mortality. Higher birthweight is associated with an increased risk of cancer and (if caused by gestational diabetes) obesity and diabetes. The 'developmental origins of health and disease' hypothesis proposes that fetal nutrition has permanent effects on growth, structure and metabolism ('programming'). This is supported by studies in animals showing that maternal under- and overnutrition during pregnancy can produce similar abnormalities in the adult offspring. Common chronic diseases could potentially be prevented by achieving optimal fetal nutrition, and this could have additional benefits for survival and human capital. Recent follow-up of children born after randomized nutritional interventions in pregnancy provides weak evidence of beneficial effects on growth, vascular function, lipid concentrations, glucose tolerance and insulin resistance. Animal studies indicate that epigenetic phenomena may be an important mechanism underlying programming, and that nutritional interventions may need to start preconceptionally.

  2. Fetal growth and neurobehavioral outcomes in childhood.

    PubMed

    Chatterji, Pinka; Lahiri, Kajal; Kim, Dohyung

    2014-12-01

    Using a sample of sibling pairs from a nationally representative U.S. survey, we examine the effects of the fetal growth rate on a set of neurobehavioral outcomes in childhood measured by parent-reported diagnosed developmental disabilities and behavior problems. Based on models that include mother fixed effects, we find that the fetal growth rate, a marker for the fetal environment, is negatively associated with lifetime diagnosis of developmental delay. We also find that the fetal growth rate is negatively associated with disruptive behaviors among male children. These results suggest that developmental disabilities and problem behaviors may play a role in explaining the well-documented association between birth weight and human capital outcomes measured in adulthood. PMID:25464342

  3. Fetal Growth and Neurobehavioral Outcomes in Childhood

    PubMed Central

    Chatterji, Pinka; Lahiri, Kajal; Kim, Dohyung

    2014-01-01

    Using a sample of sibling pairs from a nationally representative U.S. survey, we examine the effects of the fetal growth rate on a set of neurobehavioral outcomes in childhood measured by parent-reported diagnosed developmental disabilities and behavior problems. Based on models that include mother fixed effects, we find that the fetal growth rate, a marker for the fetal environment, is negatively associated with lifetime diagnosis of developmental delay. We also find that the fetal growth rate is negatively associated with disruptive behaviors among male children. These results suggest that developmental disabilities and problem behaviors may play a role in explaining the well-documented association between birth weight and human capital outcomes measured in adulthood. PMID:25464342

  4. A Comparison of Midwife-Led and Medical-Led Models of Care and Their Relationship to Adverse Fetal and Neonatal Outcomes: A Retrospective Cohort Study in New Zealand

    PubMed Central

    Wernham, Ellie; Gurney, Jason; Ellison-Loschmann, Lis; Sarfati, Diana

    2016-01-01

    Background Internationally, a typical model of maternity care is a medically led system with varying levels of midwifery input. New Zealand has a midwife-led model of care, and there are movements in other countries to adopt such a system. There is a paucity of systemic evaluation that formally investigates safety-related outcomes in relationship to midwife-led care within an entire maternity service. The main objective of this study was to compare major adverse perinatal outcomes between midwife-led and medical-led maternity care in New Zealand. Methods and Findings This was a population-based retrospective cohort study. Participants were mother/baby pairs for all 244,047 singleton, term deliveries occurring between 1 January 2008 and 31 December 2012 in New Zealand in which no major fetal, neonatal, chromosomal or metabolic abnormality was identified and the mother was first registered with a midwife, obstetrician, or general practitioner as lead maternity carer. Main outcome measures were low Apgar score at five min, intrauterine hypoxia, birth-related asphyxia, neonatal encephalopathy, small for gestational age (as a negative control), and mortality outcomes (perinatal related mortality, stillbirth, and neonatal mortality). Logistic regression models were fitted, with crude and adjusted odds ratios (ORs) generated for each outcome for midwife-led versus medical-led care (based on lead maternity carer at first registration) with 95% confidence intervals. Fully adjusted models included age, ethnicity, deprivation, trimester of registration, parity, smoking, body mass index (BMI), and pre-existing diabetes and/or hypertension in the model. Of the 244,047 pregnancies included in the study, 223,385 (91.5%) were first registered with a midwife lead maternity carer, and 20,662 (8.5%) with a medical lead maternity carer. Adjusted ORs showed that medical-led births were associated with lower odds of an Apgar score of less than seven at 5 min (OR 0.52; 95% confidence

  5. Strategic approaches to adverse outcome pathway development

    EPA Science Inventory

    Adverse outcome pathways (AOPs) are conceptual frameworks for organizing biological and toxicological knowledge in a manner that supports extrapolation of data pertaining to the initiation or early progression of toxicity to an apical adverse outcome that occurs at a level of org...

  6. Collateral Adverse Outcomes After Lumbar Spine Surgery.

    PubMed

    Daniels, Alan H; Gundle, Kenneth; Hart, Robert A

    2016-01-01

    Collateral adverse outcomes are the expected or unavoidable results of a procedure that is performed in a standard manner and typically experienced by the patient. Collateral adverse outcomes do not result from errors, nor are they rare. Collateral adverse outcomes occur as the direct result of a surgical procedure and must be accepted as a trade-off to attain the intended benefits of the surgical procedure. As such, collateral adverse outcomes do not fit into the traditional definition of a complication or adverse event. Examples of collateral adverse outcomes after lumbar spine arthrodesis include lumbar stiffness, postoperative psychological stress, postoperative pain, peri-incisional numbness, paraspinal muscle denervation, and adjacent-level degeneration. Ideally, a comparison of interventions for the treatment of a clinical condition should include information on both the negative consequences (expected and unexpected) and potential benefits of the treatment options. The objective evaluation and reporting of collateral adverse outcomes will provide surgeons with a more complete picture of invasive interventions and, thus, the improved ability to assess alternative treatment options. PMID:27049197

  7. RACIAL RESIDENTIAL SEGREGATION AND ADVERSE BIRTH OUTCOMES

    EPA Science Inventory

    INTRODUCTION. The disparity between black and white women's adverse birth outcomes has been subject to much investigation, yet the factors underlying its persistence remain elusive, which has encouraged research on neighborhood-level influences, including racial residential segr...

  8. Adverse Outcome Pathways: From Definition to Application

    EPA Science Inventory

    A challenge for both human health and ecological toxicologists is the transparent application of mechanistic (e.g., molecular, biochemical, histological) data to risk assessments. The adverse outcome pathway (AOP) is a conceptual framework designed to meet this need. Specifical...

  9. Surgery during pregnancy and fetal outcome

    SciTech Connect

    Brodsky, J.B.; Cohen, E.N.; Brown, B.W.; Wu, M.L.; Whitcher, C.

    1988-01-01

    Information was sought on wives of dentists or female dental assistants who underwent surgery during their pregnancies to determine the effects of anesthesia and surgery on fetal outcome. Occupational exposure to inhalation anesthetics either directly (dental assistants) or indirectly (wives of exposed male dentists) was associated with a significant increase in spontaneous abortion rate over a comparison group during both trimesters. Anesthesia for surgery was also associated with increased fetal loss when administered during the first or second trimesters. The number of congenital abormalities in children born to women who had surgery during pregnancy was not increased. For women surgically exposed to anesthetics and occupationally exposed as well, either directly or indirectly, the risk of spontaneous abortion increased almost threefold above control lvels. The authors conclude that elective surgery should be deferred during early pregnanacy to minimize potential fetal loss.

  10. Putative adverse outcome pathways relevant to neurotoxicity

    PubMed Central

    Bal-Price, Anna; Crofton, Kevin M.; Sachana, Magdalini; Shafer, Timothy J.; Behl, Mamta; Forsby, Anna; Hargreaves, Alan; Landesmann, Brigitte; Lein, Pamela J.; Louisse, Jochem; Monnet-Tschudi, Florianne; Paini, Alicia; Rolaki, Alexandra; Schrattenholz, André; Suñol, Cristina; van Thriel, Christoph; Whelan, Maurice; Fritsche, Ellen

    2016-01-01

    The Adverse Outcome Pathway (AOP) framework provides a template that facilitates understanding of complex biological systems and the pathways of toxicity that result in adverse outcomes (AOs). The AOP starts with an molecular initiating event (MIE) in which a chemical interacts with a biological target(s), followed by a sequential series of KEs, which are cellular, anatomical, and/or functional changes in biological processes, that ultimately result in an AO manifest in individual organisms and populations. It has been developed as a tool for a knowledge-based safety assessment that relies on understanding mechanisms of toxicity, rather than simply observing its adverse outcome. A large number of cellular and molecular processes are known to be crucial to proper development and function of the central (CNS) and peripheral nervous systems (PNS). However, there are relatively few examples of well-documented pathways that include causally linked MIEs and KEs that result in adverse outcomes in the CNS or PNS. As a first step in applying the AOP framework to adverse health outcomes associated with exposure to exogenous neurotoxic substances, the EU Reference Laboratory for Alternatives to Animal Testing (EURL ECVAM) organized a workshop (March 2013, Ispra, Italy) to identify potential AOPs relevant to neurotoxic and developmental neurotoxic outcomes. Although the AOPs outlined during the workshop are not fully described, they could serve as a basis for further, more detailed AOP development and evaluation that could be useful to support human health risk assessment in a variety of ways. PMID:25605028

  11. Drinking water contaminants and adverse pregnancy outcomes: a review.

    PubMed Central

    Bove, Frank; Shim, Youn; Zeitz, Perri

    2002-01-01

    Concern for exposures to drinking water contaminants and their effects on adverse birth outcomes has prompted several studies evaluating chlorination disinfection by-products and chlorinated solvents. Some of these contaminants are found to be teratogenic in animal studies. This review evaluates 14 studies on chlorination disinfection by-products such as trihalomethanes (THMs) and five studies on chlorinated solvents such as trichloroethylene (TCE). The adverse birth outcomes discussed in this review include small for gestational age (SGA), low birth weight, preterm birth, birth defects, spontaneous abortions, and fetal deaths. Because of heterogeneities across the studies in the characterization of birth outcomes, the assessment and categorization of exposures, and the levels and mixtures of contaminants, a qualitative review was conducted. Generally, the chief bias in these studies was exposure misclassification that most likely underestimated the risk, as well as distorted exposure-response relationships. The general lack of confounding bias by risk factors resulted from these factors not being associated with drinking water exposures. The studies of THMs and adverse birth outcomes provide moderate evidence for associations with SGA, neural tube defects (NTDs), and spontaneous abortions. Because fewer studies have been conducted for the chlorinated solvents than for THMs, the evidence for associations is less clear. Nevertheless, the findings of excess NTDs, oral clefts, cardiac defects, and choanal atresia in studies that evaluated TCE-contaminated drinking water deserve follow-up. PMID:11834464

  12. Adverse outcome pathway (AOP) development and evaluation

    EPA Science Inventory

    The Adverse Outcome Pathway provides a construct for assembling mechanistic information at different levels of biological organization in a form designed to support regulatory decision making. In particular, it frames the link between molecular and cellular events that can be mea...

  13. The adverse outcome pathway knowledge base

    EPA Science Inventory

    The rapid advancement of the Adverse Outcome Pathway (AOP) framework has been paralleled by the development of tools to store, analyse, and explore AOPs. The AOP Knowledge Base (AOP-KB) project has brought three independently developed platforms (Effectopedia, AOP-Wiki, and AOP-X...

  14. Are Women With Uterine Fibroids at Increased Risk for Adverse Pregnancy Outcome?

    PubMed

    Ezzedine, Dima; Norwitz, Errol R

    2016-03-01

    Uterine fibroids (leiomyomas) are common in reproductive age women. Most women with fibroids have uneventful pregnancies. The most common complication is painful degeneration. Are fibroids associated with adverse pregnancy outcomes? If so, can we predict which fibroids are most likely to cause complications? And is there anything that can be done to prevent these complications, such as performing a myomectomy before pregnancy? Here we review the published literature looking at the impact of uterine fibroids on adverse pregnancy events, such as miscarriage, preterm labor, placental abruption, fetal growth restriction, and fetal malpresentation. A series of clinical recommendations for the management of pregnancy in women with uterine fibroids are included. PMID:26670833

  15. Are Women With Uterine Fibroids at Increased Risk for Adverse Pregnancy Outcome?

    PubMed

    Ezzedine, Dima; Norwitz, Errol R

    2016-03-01

    Uterine fibroids (leiomyomas) are common in reproductive age women. Most women with fibroids have uneventful pregnancies. The most common complication is painful degeneration. Are fibroids associated with adverse pregnancy outcomes? If so, can we predict which fibroids are most likely to cause complications? And is there anything that can be done to prevent these complications, such as performing a myomectomy before pregnancy? Here we review the published literature looking at the impact of uterine fibroids on adverse pregnancy events, such as miscarriage, preterm labor, placental abruption, fetal growth restriction, and fetal malpresentation. A series of clinical recommendations for the management of pregnancy in women with uterine fibroids are included.

  16. Adverse outcome pathway (AOP) development I: Strategies and principles

    EPA Science Inventory

    An adverse outcome pathway (AOP) is a conceptual framework that organizes existing knowledge concerning biologically plausible, and empirically-supported, links between molecular-level perturbation of a biological system and an adverse outcome at a level of biological organizatio...

  17. Adverse Outcome Pathways – Tailoring Development to Support Use

    EPA Science Inventory

    Adverse Outcome Pathways (AOPs) represent an ideal framework for connecting high-throughput screening (HTS) data and other toxicity testing results to adverse outcomes of regulatory importance. The AOP Knowledgebase (AOP-KB) captures AOP information to facilitate the development,...

  18. Adverse Outcome Pathway (AOP) Network Development for Fatty Liver

    EPA Science Inventory

    Adverse outcome pathways (AOPs) are descriptive biological sequences that start from a molecular initiating event (MIE) and end with an adverse health outcome. AOPs provide biological context for high throughput chemical testing and further prioritize environmental health risk re...

  19. Adverse outcome pathway development II: best practices.

    PubMed

    Villeneuve, Daniel L; Crump, Doug; Garcia-Reyero, Natàlia; Hecker, Markus; Hutchinson, Thomas H; LaLone, Carlie A; Landesmann, Brigitte; Lettieri, Teresa; Munn, Sharon; Nepelska, Malgorzata; Ottinger, Mary Ann; Vergauwen, Lucia; Whelan, Maurice

    2014-12-01

    Organization of existing and emerging toxicological knowledge into adverse outcome pathway (AOP) descriptions can facilitate greater application of mechanistic data, including those derived through high-throughput in vitro, high content omics and imaging, and biomarker approaches, in risk-based decision making. The previously ad hoc process of AOP development is being formalized through development of internationally harmonized guidance and principles. The goal of this article was to outline the information content desired for formal AOP description and some rules of thumb and best practices intended to facilitate reuse and connectivity of elements of an AOP description in a knowledgebase and network context. For example, key events (KEs) are measurements of change in biological state that are indicative of progression of a perturbation toward a specified adverse outcome. Best practices for KE description suggest that each KE should be defined as an independent measurement made at a particular level of biological organization. The concept of "functional equivalence" can help guide both decisions about how many KEs to include in an AOP and the specificity with which they are defined. Likewise, in describing both KEs and evidence that supports a causal linkage or statistical association between them (ie, a key event relationship; KER), best practice is to build from and contribute to existing KE or KER descriptions in the AOP knowledgebase rather than creating redundant descriptions. The best practices proposed address many of the challenges and uncertainties related to AOP development and help promote a consistent and reliable, yet flexible approach. PMID:25466379

  20. Adverse outcome pathway development II: best practices.

    PubMed

    Villeneuve, Daniel L; Crump, Doug; Garcia-Reyero, Natàlia; Hecker, Markus; Hutchinson, Thomas H; LaLone, Carlie A; Landesmann, Brigitte; Lettieri, Teresa; Munn, Sharon; Nepelska, Malgorzata; Ottinger, Mary Ann; Vergauwen, Lucia; Whelan, Maurice

    2014-12-01

    Organization of existing and emerging toxicological knowledge into adverse outcome pathway (AOP) descriptions can facilitate greater application of mechanistic data, including those derived through high-throughput in vitro, high content omics and imaging, and biomarker approaches, in risk-based decision making. The previously ad hoc process of AOP development is being formalized through development of internationally harmonized guidance and principles. The goal of this article was to outline the information content desired for formal AOP description and some rules of thumb and best practices intended to facilitate reuse and connectivity of elements of an AOP description in a knowledgebase and network context. For example, key events (KEs) are measurements of change in biological state that are indicative of progression of a perturbation toward a specified adverse outcome. Best practices for KE description suggest that each KE should be defined as an independent measurement made at a particular level of biological organization. The concept of "functional equivalence" can help guide both decisions about how many KEs to include in an AOP and the specificity with which they are defined. Likewise, in describing both KEs and evidence that supports a causal linkage or statistical association between them (ie, a key event relationship; KER), best practice is to build from and contribute to existing KE or KER descriptions in the AOP knowledgebase rather than creating redundant descriptions. The best practices proposed address many of the challenges and uncertainties related to AOP development and help promote a consistent and reliable, yet flexible approach.

  1. Adverse Outcome Pathway Development II: Best Practices

    PubMed Central

    Villeneuve, Daniel L.; Crump, Doug; Garcia-Reyero, Natàlia; Hecker, Markus; Hutchinson, Thomas H.; LaLone, Carlie A.; Landesmann, Brigitte; Lettieri, Teresa; Munn, Sharon; Nepelska, Malgorzata; Ottinger, Mary Ann; Vergauwen, Lucia; Whelan, Maurice

    2014-01-01

    Organization of existing and emerging toxicological knowledge into adverse outcome pathway (AOP) descriptions can facilitate greater application of mechanistic data, including those derived through high-throughput in vitro, high content omics and imaging, and biomarker approaches, in risk-based decision making. The previously ad hoc process of AOP development is being formalized through development of internationally harmonized guidance and principles. The goal of this article was to outline the information content desired for formal AOP description and some rules of thumb and best practices intended to facilitate reuse and connectivity of elements of an AOP description in a knowledgebase and network context. For example, key events (KEs) are measurements of change in biological state that are indicative of progression of a perturbation toward a specified adverse outcome. Best practices for KE description suggest that each KE should be defined as an independent measurement made at a particular level of biological organization. The concept of “functional equivalence” can help guide both decisions about how many KEs to include in an AOP and the specificity with which they are defined. Likewise, in describing both KEs and evidence that supports a causal linkage or statistical association between them (ie, a key event relationship; KER), best practice is to build from and contribute to existing KE or KER descriptions in the AOP knowledgebase rather than creating redundant descriptions. The best practices proposed address many of the challenges and uncertainties related to AOP development and help promote a consistent and reliable, yet flexible approach. PMID:25466379

  2. Early Childhood Adversity and Pregnancy Outcomes

    PubMed Central

    Smith, Megan V.; Gotman, Nathan; Yonkers, Kimberly A.

    2016-01-01

    Objectives To examine the association between adverse childhood experiences (ACEs) and pregnancy outcomes; to explore mediators of this association including psychiatric illness and health habits. Methods Exposure to ACEs was determined by the Early Trauma Inventory Self Report Short Form; psychiatric diagnoses were generated by the Composite International Diagnostic Interview administered in a cohort of 2303 pregnant women. Linear regression and structural equation modeling bootstrapping approaches tested for multiple mediators. Results Each additional ACE decreased birth weight by 16.33 g and decreased gestational age by 0.063. Smoking was the strongest mediator of the effect on gestational age. Conclusions ACEs have an enduring effect on maternal reproductive health, as manifested by mothers’ delivery of offspring that were of reduced birth weight and shorter gestational age. PMID:26762511

  3. Psoriasis and adverse pregnancy outcomes: a systematic review of observational studies.

    PubMed

    Bobotsis, R; Gulliver, W P; Monaghan, K; Lynde, C; Fleming, P

    2016-09-01

    Psoriasis is a chronic inflammatory disorder with significant physical and psychological sequelae. The majority of individuals experience disease onset in early adult life - for women this often occurs during their reproductive years. While some autoimmune diseases have been shown to affect pregnancy outcomes adversely, such a relationship has not been well studied in psoriasis. We searched PubMed, Embase and the Cochrane database for published articles examining psoriasis and adverse pregnancy outcomes, and included observational studies and clinical trials evaluating direct measures of maternal and fetal morbidity and mortality. Four of the nine included articles reported a statistically significant increase in the risk of at least one outcome, including spontaneous abortion, caesarean delivery, low birth weight, macrosomia, large-for-gestational age, and a composite outcome consisting of both prematurity and low birth weight. However, these associations were not always consistent across studies. Overall, there was no clear evidence of increased adverse outcomes in pregnant women with psoriasis. PMID:26991866

  4. Paternal involvement and fetal morbidity outcomes in HIV/AIDS: a population-based study.

    PubMed

    Alio, Amina P; Mbah, Alfred K; Shah, Krupa; August, Euna M; Dejoy, Sharon; Adegoke, Korede; Marty, Phillip J; Salihu, Hamisu M; Aliyu, Muktar H

    2015-01-01

    Prior research indicates that infants with absent fathers are vulnerable to unfavorable fetal birth outcomes. HIV is a recognized risk factor for adverse birth outcomes. However, the influence of paternal involvement on fetal morbidity outcomes in women with HIV remains poorly understood. Using linked hospital discharge data and vital statistics records for the state of Florida (1998-2007), the authors assessed the association between paternal involvement and fetal growth outcomes (i.e., low birth weight [LBW], very low birth weight [VLBW], preterm birth [PTB], very preterm birth [VPTB], and small for gestational age [SGA]) among HIV-positive mothers (N=4,719). Propensity score matching was used to match cases (absent fathers) to controls (fathers involved). Conditional logistic regression was employed to generate adjusted odds ratios (OR). Mothers of infants with absent fathers were more likely to be Black, younger (<35 years old), and unmarried with at least a high school education (p<.01). They were also more likely to have a history of drug (p<.01) and alcohol (p=.02) abuse. These differences disappeared after propensity score matching. Infants of HIV-positive mothers with absent paternal involvement during pregnancy had elevated risks for adverse fetal outcomes (LBW: OR=1.30, 95% confidence interval [CI]=1.05-1.60; VLBW: OR=1.72, 95% CI=1.05-2.82; PTB: OR=1.38, 95% CI=1.13-1.69; VPTB: OR=1.81, 95% CI=1.13-2.90). Absence of fathers increases the likelihood of adverse fetal morbidity outcomes in women with HIV infection. These findings underscore the importance of paternal involvement during pregnancy, especially as an important component of programs for prevention of mother-to-child transmission of HIV.

  5. Adverse effects of perinatal nicotine exposure on reproductive outcomes.

    PubMed

    Wong, Michael K; Barra, Nicole G; Alfaidy, Nadia; Hardy, Daniel B; Holloway, Alison C

    2015-12-01

    Nicotine exposure during pregnancy through cigarette smoking, nicotine replacement therapies or e-cigarette use continues to be a widespread public health problem, impacting both fetal and postnatal health. Yet, at this time, there remains limited data regarding the safety and efficacy in using these nicotine products during pregnancy. Notably, reports assessing the effect of nicotine exposure on postnatal health outcomes in humans, including reproductive health, are severely lacking. Our current understanding regarding the consequences of nicotine exposure during pregnancy is limited to a few animal studies, which do not comprehensively address the underlying cellular mechanisms involved. This paper aims to critically review the current knowledge from human and animal studies regarding the direct and indirect effects (e.g. obesity) of maternal nicotine exposure, regardless of its source, on reproductive outcomes in pregnancy and postnatal life. Furthermore, this review highlights several key cellular mechanisms involved in these adverse reproductive deficits including oxidative stress, inflammation, and endoplasmic reticulum (ER) stress. By understanding the interplay of the cellular mechanisms involved, further strategies could be developed to prevent the reproductive abnormalities resulting from exposure to nicotine in utero and influence informed clinical guidelines for pregnant women.

  6. Adverse perinatal outcome in the older primipara.

    PubMed

    Dollberg, S; Seidman, D S; Armon, Y; Stevenson, D K; Gale, R

    1996-01-01

    Delayed childbearing has become common and has raised the awareness of the possible risks for the mother and the newborn infant. The increased maternal and neonatal risks have been attributed largely to the lack of proper prenatal care. The aim of this study was to assess whether advanced maternal age is a significant risk factor in mothers who receive good prenatal care. We matched 161 cases 1:1 according to the following criteria: maternal and paternal ethnic origin, chronic diseases, marital status, and smoking during pregnancy. Our results show that the older women had babies with a significantly higher incidence of low birth weight (< 2500 gm, p = 0.001), prematurity (< 37 weeks, p = 0.02), intrauterine growth retardation (p = 0.001), abruptio placentae (p = 0.002), and cesarean section (p < 0.001). The average hospital stay for the babies of the older mothers was longer than that for babies of the younger mothers (8.4 vs 6.1 days, p = 0.003), and the incidence of hospitalization for more than 3 days in the neonatal intensive care unit was increased (10.3% vs 2.2%). Logistic regression did not support maternal age of 35 years and older as being the single significant risk factor for adverse neonatal and maternal outcome. We conclude that maternal age older than 35 years entails a higher risk for the mother and her newborn infant, even when good prenatal care is taken.

  7. Impact of Heart Disease on Maternal and Fetal Outcomes in Pregnant Women.

    PubMed

    Koutrolou-Sotiropoulou, Paraskevi; Parikh, Puja B; Miller, Charles; Lima, Fabio V; Butler, Javed; Stergiopoulos, Kathleen

    2015-08-01

    Pregnant women with underlying heart disease (HD) are at increased risk for adverse maternal and fetal outcomes. In this study, we sought to identify the risk and risk factors for adverse maternal and fetal events in pregnant women with underlying HD. Pregnant women referred for echocardiogram with known or suspected HD were categorized into those with (1) cardiomyopathy, (2) other HD (congenital, coronary, arrhythmia, or valvular), and (3) no HD. Primary outcome was major adverse cardiovascular events (MACE), defined as a composite of death, sustained arrhythmia, myocardial infarction, heart failure, and transient ischemic attack/stroke. Secondary outcome was fetal adverse clinical events (FACE), a composite of infant death, prematurity, underweight status, intracranial hemorrhage, and respiratory distress. Of the 173 pregnancies, 37 (21%) had cardiomyopathy, 65 (38%) had other HD, and 68 (39%) had no HD. MACE was higher in pregnancies with cardiomyopathy (p <0.001) because of higher rates of heart failure and cardiac arrest (up to 6 months postpartum, p <0.001 and 0.023, respectively). FACE rates were higher in cardiomyopathy pregnancies (p <0.001). In multivariate analysis, cardiomyopathy (odds ratio [OR] 11.5, 95% confidence interval [CI] 3.7 to 35.4), hypertension (OR 10.69, 95% CI 3.70 to 30.90), and arrhythmia (OR 7.6, 95% CI 2.1 to 27) were independently associated with higher MACE. Cardiomyopathy (OR 2.7, 95% CI 1.1 to 7.0) and hypertension (OR 3.6, 95% CI 1.4 to 9.0) were also independently predictive of higher FACE. In conclusion, pregnant women with cardiomyopathy had higher rates of adverse MACE and FACE rates. Cardiomyopathy, hypertension, and arrhythmia were independently associated with adverse cardiovascular and fetal clinical events, whereas other HD was not.

  8. Decidual Cox2 inhibition improves fetal and maternal outcomes in a preeclampsia-like mouse model

    PubMed Central

    Sones, Jenny L.; Cha, Jeeyeon; Woods, Ashley K.; Bartos, Amanda; Heyward, Christa Y.; Lob, Heinrich E.; Isroff, Catherine E.; Butler, Scott D.; Shapiro, Stephanie E.; Dey, Sudhansu K.; Davisson, Robin L.

    2016-01-01

    Preeclampsia (PE) is a disorder of pregnancy that manifests as late gestational maternal hypertension and proteinuria and can be life-threatening to both the mother and baby. It is believed that abnormal placentation is responsible for the cascade of events leading to the maternal syndrome. Embryo implantation is critical to establishing a healthy pregnancy. Defective implantation can cause adverse “ripple effects,” leading to abnormal decidualization and placentation, retarded fetal development, and poor pregnancy outcomes, such as PE and fetal growth restriction. The precise mechanism(s) of implantation defects that lead to PE remain elusive. BPH/5 mice, which spontaneously develop the cardinal features of PE, show peri-implantation defects including upregulation of Cox2 and IL-15 at the maternal-fetal interface. This was associated with decreased decidual natural killer (dNK) cells, which have important roles in establishing placental perfusion. Interestingly, a single administration of a Cox2 inhibitor (celecoxib) during decidualization restrained Cox2 and IL-15 expression, restored dNK cell numbers, improved fetal growth, and attenuated late gestational hypertension in BPH/5 female mice. This study provides evidence that decidual overexpression of Cox2 and IL-15 may trigger the adverse pregnancy outcomes reflected in the preeclamptic syndrome, underscoring the idea that Cox2 inhibitor treatment is an effective strategy for the prevention of PE-associated fetal and maternal morbidity and mortality. PMID:27159542

  9. Prevalence of defined ultrasound findings of unknown significance at the second trimester fetal anomaly scan and their association with adverse pregnancy outcomes: the Welsh study of mothers and babies population‐based cohort

    PubMed Central

    Hurt, Lisa; Wright, Melissa; Dunstan, Frank; Thomas, Susan; Brook, Fiona; Morris, Susan; Tucker, David; Wills, Marilyn Ann; Davies, Colin; John, Gareth; Fone, David

    2015-01-01

    Abstract Objective The aim of this article was to estimate the population prevalence of seven defined ultrasound findings of uncertain significance (‘markers’) in the second trimester and the associated risk of adverse pregnancy outcomes. Method A prospective record‐linked cohort study of 30 078 pregnant women who had second trimester anomaly scans between July 2008 and March 2011 in Wales was conducted. Results The prevalence of markers ranged from 43.7 per 1000 singleton pregnancies for cardiac echogenic foci [95% confidence interval (CI): 38.8, 51.1] to 0.6 for mild‐to‐moderate ventriculomegaly (95% CI: 0.3, 1.0). Isolated echogenic bowel was associated with an increased risk of congenital anomalies [risk ratio (RR) 4.54, 95% CI: 2.12, 9.73] and preterm birth (RR 2.30, 95% CI: 1.08, 4.90). Isolated pelvicalyceal dilatation was associated with an increased risk of congenital anomalies (RR 3.82, 95% CI: 2.16, 6.77). Multiple markers were associated with an increased risk of congenital anomalies (RR 5.00, 95% CI: 1.35, 18.40) and preterm birth (RR 3.38, 95% CI 1.20, 9.53). Conclusions These data are useful for counselling families and developing clinical guidance and care pathways following the detection of markers in clinical practice, particularly the need for follow‐up scans to monitor placental function and growth in pregnancies with isolated echogenic bowel, and further investigation for multiple markers. © 2015 The Authors. Prenatal Diagnosis published by John Wiley & Sons Ltd. PMID:26475362

  10. Prenatal exposure to amphetamines. Risks and adverse outcomes in pregnancy.

    PubMed

    Plessinger, M A

    1998-03-01

    Based on findings in humans and the confirmation of prenatal exposures in animals, amphetamines and methamphetamines increase the risk of an adverse outcome when abused during pregnancy. Clefting, cardiac anomalies, and fetal growth reduction deficits that have been seen in infants exposed to amphetamines during pregnancy have all been reproduced in animal studies involving prenatal exposures to amphetamines. The differential effects of amphetamines between genetic strains of mice and between species demonstrate that pharmacokinetics and the genetic disposition of the mother and developing embryo can have an enormous influence on enhancing or reducing these potential risks. The effects of prenatal exposure to amphetamines in producing altered behavior in humans appear less compelling when one considers other confounding variables of human environment, genetics, and polydrug abuse. In view of the animal data concerning altered behavior and learning tasks in comparison with learning deficits observed in humans, the influence of the confounding variables in humans may serve to increase the sensitivity of the developing embryo/fetus to prenatal exposure to amphetamines. These factors and others may predispose the developing conceptus to the damaging effects of amphetamines by actually lowering the threshold of susceptibility at the sites where damage occurs. Knowledge of the effects of prenatal exposure of the fetus and the mother to designer amphetamines is lacking. Based on the few studies in which designer drugs have been examined in animal models, more questions are raised than answered. Possible reasons why no malformations or significant fetal effects were found in the study by St. Omer include the genetic strain of rat used, the conservative exposure profile, or the fact that the placenta metabolized MDMA before reaching the embryo. These questions underscore the need for further investigations concerning the prenatal exposure effects of designer compounds and

  11. Prenatal exposure to amphetamines. Risks and adverse outcomes in pregnancy.

    PubMed

    Plessinger, M A

    1998-03-01

    Based on findings in humans and the confirmation of prenatal exposures in animals, amphetamines and methamphetamines increase the risk of an adverse outcome when abused during pregnancy. Clefting, cardiac anomalies, and fetal growth reduction deficits that have been seen in infants exposed to amphetamines during pregnancy have all been reproduced in animal studies involving prenatal exposures to amphetamines. The differential effects of amphetamines between genetic strains of mice and between species demonstrate that pharmacokinetics and the genetic disposition of the mother and developing embryo can have an enormous influence on enhancing or reducing these potential risks. The effects of prenatal exposure to amphetamines in producing altered behavior in humans appear less compelling when one considers other confounding variables of human environment, genetics, and polydrug abuse. In view of the animal data concerning altered behavior and learning tasks in comparison with learning deficits observed in humans, the influence of the confounding variables in humans may serve to increase the sensitivity of the developing embryo/fetus to prenatal exposure to amphetamines. These factors and others may predispose the developing conceptus to the damaging effects of amphetamines by actually lowering the threshold of susceptibility at the sites where damage occurs. Knowledge of the effects of prenatal exposure of the fetus and the mother to designer amphetamines is lacking. Based on the few studies in which designer drugs have been examined in animal models, more questions are raised than answered. Possible reasons why no malformations or significant fetal effects were found in the study by St. Omer include the genetic strain of rat used, the conservative exposure profile, or the fact that the placenta metabolized MDMA before reaching the embryo. These questions underscore the need for further investigations concerning the prenatal exposure effects of designer compounds and

  12. Adverse Outcome Pathways: From Research to Regulation - Scientific Workshop Report

    EPA Science Inventory

    An adverse outcome pathway (AOP) organizes existing knowledge on chemical mode of action, starting with a molecular initiating event such as receptor binding, continuing through key events, and ending with an adverse outcome such as reproductive impairment. AOPs can help identify...

  13. Fetal Cardiodynamics by Echocardiography in Insulin Dependent Maternal Diabetes and Its Correlation with Pregnancy Outcome

    PubMed Central

    Pilania, Rashmi; Rohit, Manoj K.; Suri, Vanita; Kumar, Praveen

    2016-01-01

    Introduction Maternal diabetes mellitus is associated with an increased risk of fetal and neonatal morbidity and mortality. Usual screening tests have not proved to be good prognostic indicators of fetal distress. Fetal cardiodynamics is potentially a useful screening tool. Aim To determine if cardiodynamics of the fetus differ in pregnancy with diabetes requiring insulin than those without and to determine whether cardiodynamics predict fetal and neonatal outcomes. Materials and Methods This prospective case control study was carried out in 40 pregnant women with diabetes who required insulin for blood sugar control. Twenty uncomplicated pregnant women were taken as controls. Systolic and diastolic cardiac functions along with interventricular septal thickness were assessed at 26-28 weeks and again at 34-36 weeks of gestation in fetuses by echocardiography. Fetal and neonatal adverse outcomes were evaluated in terms of major and minor morbidity. Results Among all parameters, E/A ratio across both mitral and tricuspid valves, myocardial performance index and cardiac output were significantly different in fetuses of diabetic mothers at both gestations. However, pulmonary vein pulsatility index and interventricular septal thickness were similar between the two groups. At 26-28 weeks of gestation myocardial performance index correlated with abnormal biophysical profile whereas cardiac output correlated with minor morbidity. At 34-36 weeks of gestation, cardiac output correlated with abnormal biophysical profile while both MPI and cardiac output correlated with minor morbidity. Conclusion Echocardiographic parameters of fetuses of diabetic women significantly differed from those of uncomplicated non-diabetic women. However, only myocardial performance index and cardiac output correlated with adverse fetal and neonatal outcomes.

  14. Fetal Cardiodynamics by Echocardiography in Insulin Dependent Maternal Diabetes and Its Correlation with Pregnancy Outcome

    PubMed Central

    Pilania, Rashmi; Rohit, Manoj K.; Suri, Vanita; Kumar, Praveen

    2016-01-01

    Introduction Maternal diabetes mellitus is associated with an increased risk of fetal and neonatal morbidity and mortality. Usual screening tests have not proved to be good prognostic indicators of fetal distress. Fetal cardiodynamics is potentially a useful screening tool. Aim To determine if cardiodynamics of the fetus differ in pregnancy with diabetes requiring insulin than those without and to determine whether cardiodynamics predict fetal and neonatal outcomes. Materials and Methods This prospective case control study was carried out in 40 pregnant women with diabetes who required insulin for blood sugar control. Twenty uncomplicated pregnant women were taken as controls. Systolic and diastolic cardiac functions along with interventricular septal thickness were assessed at 26-28 weeks and again at 34-36 weeks of gestation in fetuses by echocardiography. Fetal and neonatal adverse outcomes were evaluated in terms of major and minor morbidity. Results Among all parameters, E/A ratio across both mitral and tricuspid valves, myocardial performance index and cardiac output were significantly different in fetuses of diabetic mothers at both gestations. However, pulmonary vein pulsatility index and interventricular septal thickness were similar between the two groups. At 26-28 weeks of gestation myocardial performance index correlated with abnormal biophysical profile whereas cardiac output correlated with minor morbidity. At 34-36 weeks of gestation, cardiac output correlated with abnormal biophysical profile while both MPI and cardiac output correlated with minor morbidity. Conclusion Echocardiographic parameters of fetuses of diabetic women significantly differed from those of uncomplicated non-diabetic women. However, only myocardial performance index and cardiac output correlated with adverse fetal and neonatal outcomes. PMID:27630907

  15. Adverse Perinatal Outcome in Subsequent Pregnancy after Stillbirth by Placental Vascular Disorders

    PubMed Central

    Monari, Francesca; Pedrielli, Giulia; Vergani, Patrizia; Pozzi, Elisa; Mecacci, Federico; Serena, Caterina; Neri, Isabella; Facchinetti, Fabio

    2016-01-01

    Objective To evaluate outcome in the pregnancy following a stillbirth (SB) by a placental vascular disorders. Study Design A prospective, observational, multicenter study was conducted in woman with a history of stillbirth (> 22 weeks) between 2005 and June 2013, in 3 Italian University Hospitals. Causes of SB were previously identified after extensive investigations. Pregnant women were enrolled within the first trimester. The main outcome was “adverse neonatal outcome”, including perinatal death, fetal growth restriction, early preterm birth <33+6 weeks, hypoxic-ischemic encephalopathy, intracranial hemorrhage or respiratory distress. Results Out of 364 index pregnancies, 320 women (87.9%) had a subsequent pregnancy during the study period. Forty-seven had an early pregnancy loss. Out of 273 babies, 67 (24.5%) had an adverse perinatal outcome, including 1 SB and 1 early neonatal death (3.7/1000). Women who had a SB related to placental vascular disorders (39.6%), were at higher risk of an adverse neonatal outcome compared with women whose SB was unexplained or resulted from other causes (Adj. OR = 2.1, 95%CI: 1.2–3.8). Moreover, also obesity independently predicts an adverse perinatal outcome (Adj OR = 2.1, 95%CI: 1.1–4.3). Conclusion When previous SB is related to placental vascular disorders there is a high risk for adverse neonatal outcomes in the subsequent pregnancy. Maternal obesity is an additional risk factor. PMID:27228078

  16. Fetal outcome in emergency versus elective cesarean sections at Souissi Maternity Hospital, Rabat, Morocco

    PubMed Central

    Benzouina, Soukayna; Boubkraoui, Mohamed El-mahdi; Mrabet, Mustapha; Chahid, Naima; Kharbach, Aicha; El-hassani, Amine; Barkat, Amina

    2016-01-01

    Introduction Perinatal mortality rates have come down in cesarean sections, but fetal morbidity is still high in comparison to vaginal delivery and the complications are more commonly seen in emergency than in elective cesarean sections. The objective of the study was to compare the fetal outcome and the indications in elective versus emergency cesarean section performed in a tertiary maternity hospital. Methods This comparative cross-sectional prospective study of all the cases undergoing elective and emergency cesarean section for any indication at Souissi maternity hospital of Rabat, Morocco, was carried from January 1, to February 28, 2014. Data were analyzed with emphasis on fetal outcome and cesarean sections indications. Mothers who had definite antenatal complications that would adversely affect fetal outcome were excluded from the study. Results There was 588 (17.83%) cesarean sections among 3297 births of which emergency cesarean section accounted for 446 (75.85%) and elective cesarean section for 142 cases (24.15%). Of the various factors analyzed in relation to the two types of cesarean sections, statistically significant associations were found between emergency cesarean section and younger mothers (P < 0.001), maternal illiteracy (P = 0.049), primiparity (P = 0.005), insufficient prenatal care (P < 0.001), referral from other institution for pregnancy complications or delivery (P < 0.001), cesarean section performed under general anesthesia (P < 0.001), lower birth weight (P < 0.016), neonatal morbidity and early mortality (P < 0.001), and admission in neonatal intensive care unit (P = 0.024). The commonest indication of emergency cesarean section was fetal distress (30.49%), while the most frequent indication in elective cesarean section was previous cesarean delivery (47.18%). Conclusion The overall fetal complications rate was higher in emergency cesarean section than in elective cesarean section. Early recognition and referral of mothers who are

  17. Neurocysticercosis in pregnancy: maternal and fetal outcomes.

    PubMed

    D'Cruz, Rebecca F; Ng, Sher M; Dassan, Pooja

    2016-07-01

    Neurocysticercosis (NCC) is a parasitic infection with the larvae of Taenia solium from contaminated pork. It is a leading cause of seizures in the developing world. Symptoms may be secondary to live or degenerating cysts, or previous infection causing calcification or gliosis. Diagnosis is based on clinical presentation, radiological confirmation of intracranial lesions and immunological testing. Management involves symptom control with antiepileptics and antiparasitic agents. Few cases have been described of maternal NCC during pregnancy. We describe a 25-year-old female presenting to a London hospital with secondary generalized seizures. MRI of the brain confirmed a calcified lesion in the right parietal lobe, and she gave a corroborative history of NCC during her childhood in India. She was stabilized initially on antiepileptics, but during her pregnancy presented with breakthrough seizures and radiological evidence of NCC reactivation. She was managed symptomatically with antiepileptics and completed the pregnancy to term with no fetal complications. PMID:27471595

  18. Neurocysticercosis in pregnancy: maternal and fetal outcomes

    PubMed Central

    D'Cruz, Rebecca F.; Ng, Sher M.; Dassan, Pooja

    2016-01-01

    Neurocysticercosis (NCC) is a parasitic infection with the larvae of Taenia solium from contaminated pork. It is a leading cause of seizures in the developing world. Symptoms may be secondary to live or degenerating cysts, or previous infection causing calcification or gliosis. Diagnosis is based on clinical presentation, radiological confirmation of intracranial lesions and immunological testing. Management involves symptom control with antiepileptics and antiparasitic agents. Few cases have been described of maternal NCC during pregnancy. We describe a 25-year-old female presenting to a London hospital with secondary generalized seizures. MRI of the brain confirmed a calcified lesion in the right parietal lobe, and she gave a corroborative history of NCC during her childhood in India. She was stabilized initially on antiepileptics, but during her pregnancy presented with breakthrough seizures and radiological evidence of NCC reactivation. She was managed symptomatically with antiepileptics and completed the pregnancy to term with no fetal complications. PMID:27471595

  19. Experimental primary cytomegalovirus infection in pregnancy: timing and fetal outcome.

    PubMed

    Kumar, M L; Prokay, S L

    1983-01-01

    In contrast to intrauterine rubella infection, the relationship between timing of maternal cytomegalovirus (CMV) infection and fetal outcome has not been clearly defined. In order to investigate this relationship, a guinea pig model was utilized to assess the fetal consequences of maternal CMV infection during the first, second, or third trimester of pregnancy. Congenital infection occurred in 24 of 35 newborn guinea pigs (69%) delivered to mothers infected during the third trimester, with localization of virus to salivary gland in 17 of the 24 infected newborn guinea pigs. In contrast, only one of 28 (5%) progeny sacrificed following first-trimester maternal infection was congenitally infected (p less than 0.01). Second-trimester maternal infection was associated with an intermediate risk of intrauterine infection with transmission of virus to 17 of 54 progeny (33%) (p less than 0.01). Eight of the 10 fetuses delivered after second-trimester infection had virus in multiple organs including the brain. These data suggest that timing of maternal CMV infection is an important variable affecting fetal outcome, with increased risk of intrauterine infection when maternal infection occurs late in pregnancy. However, if fetal infection occurs earlier in pregnancy, it appears to present a greater threat to the fetus, with the potential for dissemination of virus in multiple fetal tissues, including the brain. PMID:6295164

  20. Accelerating Adverse Outcome Pathway Development via Systems Approaches

    EPA Science Inventory

    The Adverse Outcome Pathway has emerged as an internationally harmonized mechanism for organizing biological information in a chemical agnostic manner. This construct is valuable for interpreting the results from high-throughput toxicity (HTT) assessment by providing a mechanisti...

  1. Adverse outcome pathway (AOP) development II: Best practices

    EPA Science Inventory

    Organization of existing and emerging toxicological knowledge into adverse outcome pathway (AOP) descriptions can facilitate greater application of mechanistic data, including high throughput in vitro, high content omics and imaging, and biomarkers, in risk-based decision-making....

  2. Adverse outcome pathway (AOP) development: Guiding principles and best practices

    EPA Science Inventory

    Adverse outcome pathways (AOPs) represent a conceptual framework that can support greater application of mechanistic data in regulatory decision-making. However, in order for the scientific community to collectively address the daunting challenge of describing relevant toxicologi...

  3. Spontaneous remission of membranous glomerulonephritis with successful fetal outcome

    PubMed Central

    Huang, Yan-Mei; Zhou, Hui-Rong; Zhang, Ling; Yang, Ke-Ke; Luo, Jiang-Xi; Zhao, Hai-Lu

    2016-01-01

    Abstract Membranous glomerulonephritis (MGN) represents an immunologically mediated disease characterized by deposition of immune complexes in the glomerular subepithelial space. Persistent proteinuria at diagnosis predicts poor prognosis. Pregnancy with MGN is a risk of fetal loss and may worsen maternal renal function. Here, we report a lady with MGN and proteinuria achieved spontaneous remission and successful fetal outcome naive to any medications. The 26-year old woman had 1-year history of persistent proteinuria (5.5–12.56 g/24 hours) and biopsy-proven MGN. Histopathological characteristics included glomerular basement membrane spikes, subepithelial monoclonal IgG immunofluorescence, and diffuse electron dense deposits. She was sticking to a regular morning exercise routine without any medications. After successful delivery of a full-term baby girl, the mother had improved proteinuria (0.56 g/24 hours) and albuminuria (351.96 g/24 hours contrasting 2281.6 g/24 hours before pregnancy). The baby had normal height and body weight at 4 months old. We identified more pregnancies with MGN in 5 case reports and 5 clinical series review articles (7–33 cases included). Spontaneous remission of maternal MGN with good fetal outcome rarely occurred in mothers on immunosuppressive therapy. Mothers naive to immunosuppressive therapy may achieve spontaneous remission of maternal membranous glomerulonephritis and successful fetal outcome. Theoretically, fetus might donate stem cells to heal mother's kidney. PMID:27368022

  4. Accelerating Adverse Outcome Pathway Development Using Publicly Available Data Sources

    EPA Science Inventory

    The adverse outcome pathway (AOP) concept links molecular perturbations with organism and population-level outcomes to support high-throughput toxicity testing. International efforts are underway to define AOPs and store the information supporting these AOPs in a central knowledg...

  5. Risk of Adverse Pregnancy Outcomes in Women with CKD.

    PubMed

    Piccoli, Giorgina Barbara; Cabiddu, Gianfranca; Attini, Rossella; Vigotti, Federica Neve; Maxia, Stefania; Lepori, Nicola; Tuveri, Milena; Massidda, Marco; Marchi, Cecilia; Mura, Silvia; Coscia, Alessandra; Biolcati, Marilisa; Gaglioti, Pietro; Nichelatti, Michele; Pibiri, Luciana; Chessa, Giuseppe; Pani, Antonello; Todros, Tullia

    2015-08-01

    CKD is increasingly prevalent in pregnancy. In the Torino-Cagliari Observational Study (TOCOS), we assessed whether the risk for adverse pregnancy outcomes is associated with CKD by comparing pregnancy outcomes of 504 pregnancies in women with CKD to outcomes of 836 low-risk pregnancies in women without CKD. The presence of hypertension, proteinuria (>1 g/d), systemic disease, and CKD stage (at referral) were assessed at baseline. The following outcomes were studied: cesarean section, preterm delivery, and early preterm delivery; small for gestational age (SGA); need for neonatal intensive care unit (NICU); new onset of hypertension; new onset/doubling of proteinuria; CKD stage shift; "general" combined outcome (preterm delivery, NICU, SGA); and "severe" combined outcome (early preterm delivery, NICU, SGA). The risk for adverse outcomes increased across stages (for stage 1 versus stages 4-5: "general" combined outcome, 34.1% versus 90.0%; "severe" combined outcome, 21.4% versus 80.0%; P<0.001). In women with stage 1 CKD, preterm delivery was associated with baseline hypertension (odds ratio [OR], 3.42; 95% confidence interval [95% CI], 1.87 to 6.21), systemic disease (OR, 3.13; 95% CI, 1.51 to 6.50), and proteinuria (OR, 3.69; 95% CI, 1.63 to 8.36). However, stage 1 CKD remained associated with adverse pregnancy outcomes (general combined outcome) in women without baseline hypertension, proteinuria, or systemic disease (OR, 1.88; 95% CI, 1.27 to 2.79). The risk of intrauterine death did not differ between patients and controls. Findings from this prospective study suggest a "baseline risk" for adverse pregnancy-related outcomes linked to CKD.

  6. 1991 Gulf War Exposures and Adverse Birth Outcomes

    PubMed Central

    Arnetz, Bengt; Drutchas, Alexis; Sokol, Robert; Kruger, Michael; Jamil, Hikmet

    2014-01-01

    We studied 1991 Gulf War (GW)-related environmental exposures and adverse birth outcomes in Iraqis. A random cross-sectional sample of 307 Iraqi families that immigrated to the United States responded to a structured interview covering socioeconomics, lifestyle, environmental exposures, and birth outcome. Data per each family was collected either from the man or the woman in the respective family. The respondents were divided into those that resided in Iraq during and following the GW (post-GW, n=185) and those that had left before (pre-GW, n=122). The primary outcome was lifetime prevalence of adverse birth outcomes, ie, congenital anomalies, stillbirth, low birth weight, and preterm delivery and its relationship to GW exposures. Mean number of adverse birth outcomes increased from 3.43 (SD=2.11) in the pre-GW to 4.63 (SD=2.63) in the post-GW group (P<.001). Mean chemical (Ch) and nonchemical (NCh) environmental exposure scores increased from pre-GW scores of 0.38 units (SD=1.76) and 0.43 (SD=1.86), respectively, to post-GW scores of 5.65 units (SD=6.23) and 7.26 (SD =5.67), P <.001 between groups for both exposures. There was a significant dose-response relationship between Ch environmental exposure (P=.001), but not NCh exposure, and number of adverse birth outcomes. Exposure to burning oil pits and mustard gas increased the risks for specific adverse birth outcomes by 2 to 4 times. Results indicate that Gulf War Ch, but not NCh exposures are related to adverse birth outcomes. Pregnancies in women with a history of war exposures might benefit from more intensive observation. PMID:23584910

  7. A Quantative Adverse Outcome Pathway Linking Aromatase Inhibition in Fathead Minnows with Population Dynamics

    EPA Science Inventory

    A Quantitative Adverse Outcome Pathway Linking Aromatase Inhibition in Fathead Minnows with Population DynamicsAn adverse outcome pathway (AOP) is a qualitative description linking a molecular initiating event (MIE) with measureable key events leading to an adverse outcome (AO). ...

  8. Screening in high-risk group of gestational diabetes mellitus with its maternal and fetal outcomes

    PubMed Central

    Nilofer, Angadi Rajasab; Raju, V. S.; Dakshayini, B. R.; Zaki, Syed Ahmed

    2012-01-01

    Background: Gestational diabetes mellitus (GDM) is a metabolic disorder defined as glucose intolerance with the onset or first recognition during pregnancy. Women with GDM are at increased risk for adverse obstetric and perinatal outcome. The complications associated with GDM can be prevented by early recognition, intense monitoring and proper treatment. Aims: The present study was done to screen the high-risk pregnancy group for GDM, to find the incidence of abnormal results on screening and to correlate the abnormal results with the maternal and fetal outcomes. The study was done in a tertiary care hospital and teaching institute. It was a prospective cohort study. Materials and Methods: Selective screening for GDM was done in 150 pregnant women with high-risk factors. Screening was done with 50 g glucose challenge test (GCT) after 18 weeks, and if GCT was negative then the test was repeated after 28 weeks of pregnancy. The patients who were having an abnormal GCT were subjected to 100 g oral glucose tolerance test (OGTT). All GDM patients were followed up and treated with diet and/or insulin therapy till delivery to know maternal and fetal outcomes. The period of study was from April 2008 to March 2009. Results: 7.3% of study population was OGCT positive. 6% of the study population was OGTT positive. Age >25 years, obesity, family history of DM, and past history of GDM were the risk factors significantly associated with GDM. One newborn had hypoglycemia and one had hyperbilirubinemia. The fetal and maternal outcome in GDM patients was good in our study due to early diagnosis and intervention. Conclusion: Women with GDM are at an increased risk for adverse obstetric and perinatal outcome. The increased morbidity in GDM is preventable by meticulous antenatal care. PMID:22701851

  9. Characterization of the Risks of Adverse Outcomes Following Rubella Infection in Pregnancy.

    PubMed

    Thompson, Kimberly M; Simons, Emily A; Badizadegan, Kamran; Reef, Susan E; Cooper, Louis Z

    2016-07-01

    Although most infections with the rubella virus result in relatively minor sequelae, rubella infection in early pregnancy may lead to severe adverse outcomes for the fetus. First recognized in 1941, congenital rubella syndrome (CRS) can manifest with a diverse range of symptoms, including congenital cataracts, glaucoma, and cardiac defects, as well as hearing and intellectual disability. The gestational age of the fetus at the time of the maternal rubella infection impacts the probability and severity of outcomes, with infection in early pregnancy increasing the risks of spontaneous termination (miscarriage), fetal death (stillbirth), birth defects, and reduced survival for live-born infants. Rubella vaccination continues to change the epidemiology of rubella and CRS globally, but no models currently exist to evaluate the economic benefits of rubella management. This systematic review provides an overall assessment of the weight of the evidence for the outcomes associated with rubella infections in the first 20 weeks of pregnancy. We identified, evaluated, and graded 31 studies (all from developed countries) that reported on the pregnancy outcomes of at least 30 maternal rubella infections. We used the available evidence to estimate the increased risks of spontaneous termination, fetal death, infant death, and CRS as a function of the timing of rubella infection in pregnancy and decisions about induced termination. These data support the characterization of the disability-adjusted life years for outcomes associated with rubella infection in pregnancy. We find significant impacts associated with maternal rubella infections in early pregnancy, which economic analyses will miss if they only focus on live births of CRS cases. Our estimates of fetal loss from increased induced terminations due to maternal rubella infections provide context that may help to explain the relatively low numbers of observed CRS cases per year despite potentially large burdens of disease. Our

  10. Methamphetamine abuse during pregnancy: outcome and fetal effects.

    PubMed

    Little, B B; Snell, L M; Gilstrap, L C

    1988-10-01

    Methamphetamines are a popular class of recreational drugs sometimes abused by women of childbearing age. The effects of methamphetamine abuse on pregnancy outcome and embryofetal development are not known. In this study, we compared pregnancy and fetal outcome in 52 women who abused methamphetamines with a randomly selected control group of 52 non-drug-abusing women. Body weight, length, and head circumference were significantly decreased in neonates born to mothers who abused methamphetamines during pregnancy. However, the frequency of congenital anomalies was not significantly increased in this group.

  11. Race, racism, and racial disparities in adverse birth outcomes.

    PubMed

    Dominguez, Tyan Parker

    2008-06-01

    While the biologic authenticity of race remains a contentious issue, the social significance of race is indisputable. The chronic stress of racism and the social inequality it engenders may be underlying social determinants of persistent racial disparities in health, including infant mortality, preterm delivery, and low birth weight. This article describes the problem of racial disparities in adverse birth outcomes; outlines the multidimensional nature of racism and the pathways by which it may adversely affect health; and discusses the implications for clinical practice.

  12. Early Gestational Weight Gain Rate and Adverse Pregnancy Outcomes in Korean Women.

    PubMed

    Cho, Eun-Hee; Hur, Junguk; Lee, Kyung-Ju

    2015-01-01

    During pregnancy, many women gain excessive weight, which is related to adverse maternal and neonatal outcomes. In this study, we evaluated whether rate of gestational weight gain (RGWG) in early, mid, and late pregnancy is strongly associated with adverse pregnancy outcomes. A retrospective chart review of 2,789 pregnant Korean women was performed. Weights were recorded at the first clinic visit, during the screening test for fetal anomaly, and during the 50g oral glucose challenge test and delivery, to represent early, mid, and late pregnancy, respectively. A multivariate logistic regression analysis was performed to examine the relationship between RGWG and adverse pregnancy outcomes. At early pregnancy, the RGWG was significantly associated with high risk of developing gestational diabetes mellitus (GDM), pregnancy-induced hypertension (PIH), large for gestational age (LGA) infants, macrosomia, and primary cesarean section (P-CS). The RGWG of mid pregnancy was not significantly associated with any adverse pregnancy outcomes. The RGWG at late pregnancy was significantly associated with a lower risk of developing GDM, preterm birth and P-CS, but with a higher risk of developing LGA infants and macrosomia. When the subjects were divided into three groups (Underweight, Normal, and Obese), based on pre-pregnancy body mass index (BMI), the relationship between early RGWG and adverse pregnancy outcomes was significantly different across the three BMI groups. At early pregnancy, RGWG was not significantly associated to adverse pregnancy outcomes for subjects in the Underweight group. In the Normal group, however, early RGWG was significantly associated with GDM, PIH, LGA infants, macrosomia, P-CS, and small for gestational weight (SGA) infants, whereas early RGWG was significantly associated with only a high risk of PIH in the Obese group. The results of our study suggest that early RGWG is significantly associated with various adverse pregnancy outcomes and that

  13. Frailty as a predictor of short-term adverse outcomes

    PubMed Central

    Coelho, Tiago; Paúl, Constança; Gobbens, Robbert J.J.

    2015-01-01

    The objectives of this study were to compare how different frailty measures (Frailty Phenotype/FP, Groningen Frailty Indicator/GFI and Tilburg Frailty Indicator/TFI) predict short-term adverse outcomes. Secondarily, adopting a multidimensional approach to frailty (integral conceptual model–TFI), this study aims to compare how physical, psychological and social frailty predict the outcomes. A longitudinal study was carried out with 95 community-dwelling elderly. Participants were assessed at baseline for frailty, determinants of frailty, and adverse outcomes (healthcare utilization, quality of life, disability in basic and instrumental activities of daily living/ADL and IADL). Ten months later the outcomes were assessed again. Frailty was associated with specific healthcare utilization indicators: the FP with a greater utilization of informal care; GFI with an increased contact with healthcare professionals; and TFI with a higher amount of contacts with a general practitioner. After controlling for the effect of life-course determinants, comorbidity and adverse outcome at baseline, GFI predicted IADL disability and TFI predicted quality of life. The effect of the FP on the outcomes was not significant, when compared with the other measures. However, when comparing TFI’s domains, the physical domain was the most significant predictor of the outcomes, even explaining part of the variance of ADL disability. Frailty at baseline was associated with adverse outcomes at follow-up. However, the relationship of each frailty measure (FP, GFI and TFI) with the outcomes was different. In spite of the role of psychological frailty, TFI’s physical domain was the determinant factor for predicting disability and most of the quality of life. PMID:26246968

  14. Interventions to prevent adverse fetal programming due to maternal obesity during pregnancy.

    PubMed

    Nathanielsz, Peter W; Ford, Stephen P; Long, Nathan M; Vega, Claudia C; Reyes-Castro, Luis A; Zambrano, Elena

    2013-10-01

    Maternal obesity is a global epidemic affecting both developed and developing countries. Human and animal studies indicate that maternal obesity adversely programs the development of offspring, predisposing them to chronic diseases later in life. Several mechanisms act together to produce these adverse health effects. There is a consequent need for effective interventions that can be used in the management of human pregnancy to prevent these outcomes. The present review analyzes the dietary and exercise intervention studies performed to date in both altricial and precocial animals, rats and sheep, with the aim of preventing adverse offspring outcomes. The results of these interventions present exciting opportunities to prevent, at least in part, adverse metabolic and other outcomes in obese mothers and their offspring.

  15. Fetal umbilical artery Doppler pulsatility index and childhood neurocognitive outcome at 12 years

    PubMed Central

    Mone, Fionnuala; McConnell, Barbara; Thompson, Andrew; Segurado, Ricardo; Hepper, Peter; Stewart, Moira C; Dornan, James C; Ong, Stephen; McAuliffe, Fionnuala M; Shields, Michael D

    2016-01-01

    Objective To determine whether an elevated fetal umbilical artery Doppler (UAD) pulsatility index (PI) at 28 weeks’ gestation, in the absence of fetal growth restriction (FGR) and prematurity, is associated with adverse neurocognitive outcome in children aged 12 years. Methods Prospective cohort study, comparing children with a normal fetal UAD PI (<90th centile) (n=110) and those with an elevated PI (≥90th centile) (n=40). UAD was performed at 28, 32 and 34 weeks gestation. At 12 years of age, all children were assessed under standardised conditions at Queen's University, Belfast, UK to determine cognitive and behavioural outcomes using the British Ability Score-II and Achenbach Child Behavioural Checklist Parent Rated Version under standardised conditions. Regression analysis was performed, controlling for confounders such as gender, socioeconomic status and age at assessment. Results The mean age of follow-up was 12.4 years (±0.5 SD) with 44% of children male (n=63). When UAD was assessed at 28 weeks, the elevated fetal UAD group had lower scores in cognitive assessments of information processing and memory. Parameters included (1) recall of objects immediate verbal (p=0.002), (2) delayed verbal (p=0.008) and (3) recall of objects immediate spatial (p=0.0016). There were no significant differences between the Doppler groups at 32 or 34 weeks' gestation. Conclusions An elevated UAD PI at 28 weeks' gestation in the absence of FGR or prematurity is associated with lower scores of declarative memory in children aged 12 years. A potential explanation for this is an element of placental insufficiency in the presence of the appropriately grown fetus, which affects the development of the fetal hippocampus and information processing and memory long-term. These findings, however, had no impact on overall academic ability, mental processing and reasoning or overall behavioural function. PMID:27311899

  16. Periodontal Disease: A Possible Risk-Factor for Adverse Pregnancy Outcome

    PubMed Central

    Parihar, Anuj Singh; Katoch, Vartika; Rajguru, Sneha A; Rajpoot, Nami; Singh, Pinojj; Wakhle, Sonal

    2015-01-01

    Bacterial invasion in subgingival sites especially of gram-negative organisms are initiators for periodontal diseases. The periodontal pathogens with persistent inflammation lead to destruction of periodontium. In recent years, periodontal diseases have been associated with a number of systemic diseases such as rheumatoid arthritis, cardiovascular-disease, diabetes mellitus, chronic respiratory diseases and adverse pregnancy outcomes including pre-term low-birth weight (PLBW) and pre-eclampsia. The factors like low socio-economic status, mother's age, race, multiple births, tobacco and drug-abuse may be found to increase risk of adverse pregnancy outcome. However, the same are less correlated with PLBW cases. Even the invasion of both aerobic and anerobic may lead to inflammation of gastrointestinal tract and vagina hence contributing to PLBW. The biological mechanism involved between PLBW and Maternal periodontitis is the translocation of chemical mediators of inflammation. Pre-eclampsia is one of the commonest cause of both maternal and fetal morbidity as it is characterized by hypertension and hyperprotenuria. Improving periodontal health before or during pregnancy may prevent or reduce the occurrences of these adverse pregnancy outcomes and, therefore, reduce the maternal and perinatal morbidity and mortality. Hence, this article is an attempt to review the relationship between periodontal condition and altered pregnancy outcome. PMID:26229389

  17. Periodontal Disease: A Possible Risk-Factor for Adverse Pregnancy Outcome.

    PubMed

    Parihar, Anuj Singh; Katoch, Vartika; Rajguru, Sneha A; Rajpoot, Nami; Singh, Pinojj; Wakhle, Sonal

    2015-07-01

    Bacterial invasion in subgingival sites especially of gram-negative organisms are initiators for periodontal diseases. The periodontal pathogens with persistent inflammation lead to destruction of periodontium. In recent years, periodontal diseases have been associated with a number of systemic diseases such as rheumatoid arthritis, cardiovascular-disease, diabetes mellitus, chronic respiratory diseases and adverse pregnancy outcomes including pre-term low-birth weight (PLBW) and pre-eclampsia. The factors like low socio-economic status, mother's age, race, multiple births, tobacco and drug-abuse may be found to increase risk of adverse pregnancy outcome. However, the same are less correlated with PLBW cases. Even the invasion of both aerobic and anerobic may lead to inflammation of gastrointestinal tract and vagina hence contributing to PLBW. The biological mechanism involved between PLBW and Maternal periodontitis is the translocation of chemical mediators of inflammation. Pre-eclampsia is one of the commonest cause of both maternal and fetal morbidity as it is characterized by hypertension and hyperprotenuria. Improving periodontal health before or during pregnancy may prevent or reduce the occurrences of these adverse pregnancy outcomes and, therefore, reduce the maternal and perinatal morbidity and mortality. Hence, this article is an attempt to review the relationship between periodontal condition and altered pregnancy outcome. PMID:26229389

  18. Application of the adverse outcome pathway framework - advances and challenges

    EPA Science Inventory

    The adverse outcome pathway (AOP) framework, while not new in concept, has gained attention in recent years as a set of organizing principles and tools that can help facilitate greater use of mechanistic or pathway-based data in risk assessment and regulatory decision-making. Reg...

  19. Proteomics for Adverse Outcome Pathway Discovery using Human Kidney Cells?

    EPA Science Inventory

    An Adverse Outcome Pathway (AOP) is a conceptual framework that applies molecular-based data for use in risk assessment and regulatory decision support. AOP development is based on effects data of chemicals on biological processes (i.e., molecular initiating events, key intermedi...

  20. Prevention, management and extent of adverse pregnancy outcomes in women with hereditary antithrombin deficiency.

    PubMed

    Rogenhofer, Nina; Bohlmann, Michael K; Beuter-Winkler, Petra; Würfel, Wolfgang; Rank, Andreas; Thaler, Christian J; Toth, Bettina

    2014-03-01

    Antithrombin (AT) deficiency is a rare hereditary thrombophilia with a mean prevalence of 0.02 % in the general population, associated with a more than ten-fold increased risk of venous thromboembolism (VTE). Within this multicenter retrospective clinical analysis, female patients with inherited AT deficiency were evaluated concerning the type of inheritance and extent of AT deficiency, medical treatment during pregnancy and postpartally, VTE risk as well as maternal and neonatal outcome. Statistical analysis was performed with SPPS for Windows (19.0). A total of 18 pregnancies in 7 patients were evaluated, including 11 healthy newborns ≥37th gestational weeks (gw), one small for gestational age premature infant (25th gw), two late-pregnancy losses (21st and 28th gw) and four early miscarriages. Despite low molecular weight heparin (LMWH) administration, three VTE occurred during pregnancy and one postpartally. Several adverse pregnancy outcomes occurred including fetal and neonatal death, as well as severe maternal neurologic disorders occurred. Patients with substitution of AT during pregnancy in addition to LMWH showed the best maternal and neonatal outcome. Close monitoring with appropriate anticoagulant treatment including surveillance of AT levels might help to optimize maternal and fetal outcome in patients with hereditary AT deficiency.

  1. Residential proximity to environmental hazards and adverse health outcomes.

    PubMed

    Brender, Jean D; Maantay, Juliana A; Chakraborty, Jayajit

    2011-12-01

    How living near environmental hazards contributes to poorer health and disproportionate health outcomes is an ongoing concern. We conducted a substantive review and critique of the literature regarding residential proximity to environmental hazards and adverse pregnancy outcomes, childhood cancer, cardiovascular and respiratory illnesses, end-stage renal disease, and diabetes. Several studies have found that living near hazardous wastes sites, industrial sites, cropland with pesticide applications, highly trafficked roads, nuclear power plants, and gas stations or repair shops is related to an increased risk of adverse health outcomes. Government agencies should consider these findings in establishing rules and permitting and enforcement procedures to reduce pollution from environmentally burdensome facilities and land uses. PMID:22028451

  2. Residential Proximity to Environmental Hazards and Adverse Health Outcomes

    PubMed Central

    Maantay, Juliana A.; Chakraborty, Jayajit

    2011-01-01

    How living near environmental hazards contributes to poorer health and disproportionate health outcomes is an ongoing concern. We conducted a substantive review and critique of the literature regarding residential proximity to environmental hazards and adverse pregnancy outcomes, childhood cancer, cardiovascular and respiratory illnesses, end-stage renal disease, and diabetes. Several studies have found that living near hazardous wastes sites, industrial sites, cropland with pesticide applications, highly trafficked roads, nuclear power plants, and gas stations or repair shops is related to an increased risk of adverse health outcomes. Government agencies should consider these findings in establishing rules and permitting and enforcement procedures to reduce pollution from environmentally burdensome facilities and land uses. PMID:22028451

  3. Ethnic/racial disparities in the fetal growth outcomes of Ecuadorian newborns.

    PubMed

    Margaret Weigel, M; Sanchez, Maria Elena Caiza

    2013-02-01

    Size at birth is an important indicator of future infant morbidity and mortality. Ethnic/racial disparities in birth weight and other fetal growth outcomes are well documented for US and Canadian minority groups but not for those in Latin America. The study compared the growth outcomes of 1,227 full-term Ecuadorian newborns delivered by Afro-descendant and indigenous minority women with those of ethnic majority (mestizo) women. Minority newborns had higher risk for congenital microcephaly but no excess risk for low birth weight or stunted linear growth compared to mestizos. However, minority newborns were significantly heavier at birth, weighing an average of 3-5% more than mestizos. Afro-Ecuadorians newborns also were fatter. The risk profile of Ecuadorian ethnic groups for certain fetal growth outcomes differs from some of those reported for North American minorities. Further studies are needed to investigate the origins of these between-group differences and to develop ethnic specific interventions for adverse growth outcomes.

  4. The influence of maternal-fetal attachment and health practices on neonatal outcomes in low-income, urban women.

    PubMed

    Alhusen, Jeanne L; Gross, Deborah; Hayat, Matthew J; Woods, Anne B; Sharps, Phyllis W

    2012-04-01

    Maternal-fetal attachment (MFA) has been associated with health practices during pregnancy, but less is known about this relationship in low-income women, and no identified studies have examined this relationship to neonatal outcomes. This longitudinal descriptive study was conducted to examine the relationships among MFA, health practices during pregnancy, and neonatal outcomes in a sample of low-income, predominantly African-American women and their neonates. MFA was associated with health practices during pregnancy and adverse neonatal outcomes. Health practices during pregnancy mediated the relationships of MFA and adverse neonatal outcomes. The results support the importance of examining MFA in our efforts to better understand the etiology of health disparities in neonatal outcomes. PMID:22262085

  5. The Influence of Maternal-Fetal Attachment and Health Practices on Neonatal Outcomes in Low-Income, Urban Women

    PubMed Central

    Alhusen, Jeanne L.; Gross, Deborah; Hayat, Matthew J.; Woods, Anne B. (Nancy); Sharps, Phyllis W.

    2012-01-01

    Maternal-fetal attachment (MFA) has been associated with health practices during pregnancy, but less is known about this relationship in low-income women, and no identified studies have examined this relationship to neonatal outcomes. This longitudinal descriptive study was conducted to examine the relationships among MFA, health practices during pregnancy, and neonatal outcomes in a sample of low-income, predominantly African-American women and their neonates. MFA was associated with health practices during pregnancy and adverse neonatal outcomes. Health practices during pregnancy mediated the relationships of MFA and adverse neonatal outcomes. The results support the importance of examining MFA in our efforts to better understand the etiology of health disparities in neonatal outcomes. PMID:22262085

  6. Accelerating Adverse Outcome Pathway (AOP) development via computationally predicted AOP networks

    EPA Science Inventory

    The Adverse Outcome Pathway (AOP) framework is increasingly being adopted as a tool for organizing and summarizing the mechanistic information connecting molecular perturbations by environmental stressors with adverse outcomes relevant for ecological and human health outcomes. Ho...

  7. Adverse outcomes following hospitalization in acutely ill older patients

    PubMed Central

    Wong, Roger Y; Miller, William C

    2008-01-01

    Background The longitudinal outcomes of patients admitted to acute care for elders units (ACE) are mixed. We studied the associations between socio-demographic and functional measures with hospital length of stay (LOS), and which variables predicted adverse events (non-independent living, readmission, death) 3 and 6 months later. Methods Prospective cohort study of community-living, medical patients age 75 or over admitted to ACE at a teaching hospital. Results The population included 147 subjects, median LOS of 9 days (interquartile range 5–15 days). All returned home/community after hospitalization. Just prior to discharge, baseline timed up and go test (TUG, P < 0.001), bipedal stance balance (P = 0.001), and clinical frailty scale scores (P = 0.02) predicted LOS, with TUG as the only independent predictor (P < 0.001) in multiple regression analysis. By 3 months, 59.9% of subjects remained free of an adverse event, and by 6 months, 49.0% were event free. The 3 and 6-month mortality was 10.2% and 12.9% respectively. Almost one-third of subjects had developed an adverse event by 6 months, with the highest risk within the first 3 months post discharge. An abnormal TUG score was associated with increased adjusted hazard ratio [HR] 1.28, 95% confidence interval [CI] 1.03 to 1.59, P = 0.03. A higher FMMSE score (adjusted HR 0.89, 95% CI 0.82 to 0.96, P = 0.003) and independent living before hospitalization (adjusted HR 0.42, 95% CI 0.21 to 0.84, P = 0.01) were associated with reduced risk of adverse outcome. Conclusion Some ACE patients demonstrate further functional decline following hospitalization, resulting in loss of independence, repeat hospitalization, or death. Abnormal TUG is associated with prolonged LOS and future adverse outcomes. PMID:18479512

  8. Maternal language and adverse birth outcomes in a statewide analysis.

    PubMed

    Sentell, Tetine; Chang, Ann; Ahn, Hyeong Jun; Miyamura, Jill

    2016-01-01

    Limited English proficiency is associated with disparities across diverse health outcomes. However, evidence regarding adverse birth outcomes across languages is limited, particularly among U.S. Asian and Pacific Islander populations. The study goal was to consider the relationship of maternal language to birth outcomes using statewide hospitalization data. Detailed discharge data from Hawaii childbirth hospitalizations from 2012 (n = 11,419) were compared by maternal language (English language or not) for adverse outcomes using descriptive and multivariable log-binomial regression models, controlling for race/ethnicity, age group, and payer. Ten percent of mothers spoke a language other than English; 93% of these spoke an Asian or Pacific Islander language. In multivariable models, compared to English speakers, non-English speakers had significantly higher risk (adjusted relative risk [ARR]: 2.02; 95% confidence interval [CI]: 1.34-3.04) of obstetric trauma in vaginal deliveries without instrumentation. Some significant variation was seen by language for other birth outcomes, including an increased rate of primary Caesarean sections and vaginal births after Caesarean, among non-English speakers. Non-English speakers had approximately two times higher risk of having an obstetric trauma during a vaginal birth when other factors, including race/ethnicity, were controlled. Non-English speakers also had higher rates of potentially high-risk deliveries.

  9. Adverse outcome pathways and drug-induced liver injury testing

    PubMed Central

    Vinken, Mathieu

    2015-01-01

    Drug-induced liver injury is a prominent reason for premarketing and postmarketing drug withdrawal and can be manifested in a number of ways, such as cholestasis, steatosis and fibrosis. The mechanisms driving these toxicological processes have been well characterized and have been emdedded in adverse outcome pathway frameworks in recent years. This paper reviews these constructs and simultaneously illustrates their use in the preclinical testing of drug-induced liver injury. PMID:26119269

  10. Fetal and neonatal outcomes in women reporting ingestion of licorice (Glycyrrhiza uralensis) during pregnancy.

    PubMed

    Choi, June-Seek; Han, Jung-Yeol; Ahn, Hyun-Kyong; Ryu, Hyun-Mee; Kim, Moon-Young; Chung, Jin-Hoon; Nava-Ocampo, Alejandro A; Koren, Gideon

    2013-01-01

    Maternal intake of licorice from dietary sources has been associated with adverse maternal and fetal outcomes. We prospectively studied the outcome of 185 singleton pregnancies who took over-the-counter or naturopathic formulations containing licorice during their pregnancy, and 370 age-matched singleton pregnant controls that were not exposed to any potential teratogen. The indication in 56.8% of the women taking licorice was for cough and cold control, with the maximum dose of 2104 mg/day and exposure occurring between the 4th day and 25th week of gestation. The rate of stillbirths was marginally higher among women who took licorice than those who did not (OR = 7.9; 95% CI 0.9-71.5; p = 0.048), and significantly higher when compared to the general population in the Republic of Korea (OR = 13.3; 95% CI 4.9-35.8; p < 0.001). Other fetal outcomes assessed in the study were similar between the two study groups, e.g., the OR of major malformations was 3.9 (95% CI 0.4-43.5; p = 0.27). In conclusion, the present study suggests that licorice is not a major teratogen. However, whether licorice may increase the risk of stillbirths requires careful consideration in further studies with a larger sample size.

  11. Maternal hemoglobin level and fetal outcome at low and high altitudes

    PubMed Central

    Steenland, Kyle; Tapia, Vilma

    2009-01-01

    Both, low (<7 g/dl) and high (>14.5 g/dl), maternal hemoglobin (Hb) levels have been related to poor fetal outcome. Most studies have been done at low altitude (LA). Here, we have sought to determine whether this relationship exists at both high and low altitude, and also whether there is an adverse effect of high altitude (HA) on fetal outcome independent of level of maternal hemoglobin. The study is based on a retrospective multicenter analysis of 35,449 pregnancies at LA and six other cities above 3000 meters. In analyses of all women at both LA and HA, those with Hb <9 g/dl had odds ratios (ORs) and 95% confidence intervals (CI) of 4.4 (CI: 2.8–6.7), 2.5 (CI: 1.9–3.2), and 1.4 (CI: 1.1–1.9) for stillbirths, preterm, and small for gestational age (SGA) births, respectively, compared with women with 11–12.9 g/dl of Hb, after adjustment for confounders. These risks by hemoglobin level differed little between women at LA and HA, suggesting that no correction of the definition of anemia is necessary for women at HA. Women living at high altitude with hemoglobin >15.5 g/dl had higher risks for stillbirths (OR: 1.3; CI: 1.05–1.3), preterm (OR: 1.5; CI 1.3–1.8), and SGA births (OR: 2.1, CI 1.8–2.3). There was also a significant adverse effect of living at HA, independent of hemoglobin level for all three outcomes (OR: 3.9, 1.7, and 2.3; CI: 2.8–5.2, 1.5–1.9, and 2.1–2.5) for stillbirths, preterms, and SGA respectively, after adjusting for hemoglobin level. Both, high and low maternal hemoglobin levels were related to poor pregnancy outcome, with similar effect of low hemoglobin in both LA and HA. Our data suggest, that maternal hemoglobin above 11 g/dl but below 13 g/dl is the area of minimal risk of poor adverse outcomes. Living at HA had an adverse effect independent of hemoglobin level. PMID:19741055

  12. Are PRO discharge screens associated with postdischarge adverse outcomes?

    PubMed Central

    Wei, F.; Mark, D.; Hartz, A.; Campbell, C.

    1995-01-01

    OBJECTIVE. We evaluate whether patient outcomes may be affected by possible errors in care at discharge as assessed by Peer Review Organizations (PROs). DATA SOURCES/STUDY SETTING. The three data sources for the study were (1) the generic screen results of a 3 percent random sample of Medicare beneficiaries age 65 years or older who were admitted to California hospitals between 1 July 1987 and 30 June 1988 (n = 20,136 patients); (2) the 1987 and 1988 California Medicare Provided Analysis and Review (MEDPAR) data files; and (3) the American Hospital Association (AHA) 1988 Annual Survey of Hospitals. STUDY DESIGN. Multivariate logistic regression analysis was used to evaluate the association between the results of generic discharge administered by the PROs and two patient outcomes: mortality and readmission within 30 days. The analysis was adjusted for other patient characteristics recorded on the uniform discharge abstract. PRINCIPAL FINDINGS. Four discharge screens indicated an increased risk of an adverse outcome-absence of documentation of discharge planning, elevated temperature, abnormal pulse, and unaddressed abnormal test results at discharge. The other three discharge screens examined-abnormal blood pressure, IV fluids or drugs, and wound drainage before discharge-were unrelated to postdischarge adverse outcomes. CONCLUSIONS. Generic discharge screens based on inadequate discharge planning, abnormal pulse, increased temperature, or unaddressed abnormal tests may be important indicators of substandard care. Other discharge screens apparently do not detect errors in care associated with major consequences for patients. PMID:7649753

  13. Blood rheology at term in normal pregnancy and in patients with adverse outcome events.

    PubMed

    von Tempelhoff, Georg-Friedrich; Velten, Eva; Yilmaz, Asli; Hommel, Gerhard; Heilmann, Lothar; Koscielny, Jürgen

    2009-01-01

    Plasma volume expansion of more than 1.5 l and sustainable activation of the hemostatic system that results in a steady rise of the fibrinogen/fibrin turnover are contemporary physiological events during normal pregnancy. In contrast, adverse outcome of pregnancy i.e. pre-eclampsia commonly coincide with hemo concentration and over activation of blood coagulation both of which alter blood rheology. On the basis of 4,985 consecutively recorded singleton pregnancies values range of blood rheological parameters in women with normal and complicated outcome of pregnancy at the time of their delivery were compared. Plasma viscosity (pv) was determined using KSPV 1 Fresenius and RBC aggregation (stasis: E0 and low shear: E1) using MA1-Aggregometer; Myrenne. Seventy-nine point four percent (n=3,959) had normal pregnancy outcome and 1,026 with adverse outcome of pregnancy had pre-eclampsia (8.4%; n=423), had newborn with a birth-weight < 2,500 g (9.5%; n=473), had early-birth before week 37 (9.3%; n=464), and/or were diagnosed with intra uterine growth retardation (IUGR) (5.0%; n=250). In women with normal pregnancy outcome mean (+/-SD) of pv was 1.31+/-0.09 mPa s, of E0 was 21.6+/-5.3, and of E1 was 38.4+/-7.9 while in women with adverse outcome means for rheological parameters were statistically significantly different i.e. pv: 1.32+/-0.08 mPa s; p=0.006, E0: 22.1+/-5.5; p=0.002 and E1: 39.5+/-8.5; p=0.0006. Subgroup analysis revealed statistical significant lower pv in women who either had pre term delivery or a low birth-weight child (p<0.005) as compared to women who had normal pregnancy outcome while patients with pre-eclampsia had markedly higher low shear and stasis RBC aggregation (p<0.0001). None of the rheological results at term were correlated with either maternal age (r<0.04), BMI (r<0.09), maternal weight gain until delivery (r<0.04), or fetal outcome such as APGAR-score (r<0.09) art. pH in the umbilical cord (-0.05fetal birth-weight (r<0.04). Women

  14. Maternal persistent vegetative state with successful fetal outcome.

    PubMed Central

    Sim, K. B.

    2001-01-01

    A woman suffered from massive blunt injuries in a motor vehicle accident at a presumed 4 weeks' gestation, but she successfully carried the fetus for an additional 29 weeks. Premature labor began at 33 weeks' gestation and a live 1,890 g male was delivered. His development was normal for the 12-months postnatal follow-up period. The patient remained in a persistent vegetative state. Only 12 cases of severely brain-injured pregnant patients who delivered babies have been reported in English literature. Such patients need special maternal and fetal monitoring. As shown in our patient, successful fetal outcome could be obtained in a mother who suffered from hypovolemic shock and diffuse axonal injury, was treated with numerous medications from 4 weeks' gestation, and survived premature labor at 33 weeks' gestation in a persistent vegetative state. This report represents the longest interval from maternal vegetative state to obstetric delivery. From our case, it would seem that no clear limit exists that restricts the physician's ability to support a severely injured pregnant patient. PMID:11641542

  15. Prenatal Depression and Adverse Birth Outcomes: An Updated Systematic Review

    PubMed Central

    Accortt, Eynav Elgavish; Cheadle, Alyssa C. D.; Schetter, Christine Dunkel

    2015-01-01

    Complications related to preterm birth (PTB) and low birth weight (LBW) are leading causes of infant morbidity and mortality. Prenatal depression is a hypothesized psychosocial risk factor for both birth outcomes. The purpose of this systematic review was to examine evidence published between 1977 and 2013 on prenatal depression and risks of these primary adverse birth outcomes. A systematic search of the PUBMED and PsycINFO databases was conducted to identify studies testing the associations between prenatal depressive symptoms, or diagnoses of depression, and risk of PTB or LBW. We systematically selected 50 published reports on PTB and length of gestation, and 33 reports on LBW and BW. Results were reviewed by two independent reviewers and we evaluated the quality of the evidence with an established systematic review method, the Newcastle Ottawa Scale. We then undertook a narrative synthesis of the results following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Less than a quarter of 50 published reports found that prenatal depression was significantly associated with PTB or gestational age. In contrast, slightly more than half of the 33 reports found that prenatal depression was associated with LBW or BW. When weighing methodological features, we determined that the effects of prenatal depression on LBW are more consistent than effects on length of gestation or PTB. Although the evidence may not be strong enough to support routine depression screening for risk of adverse outcomes, screening to enable detection and timely treatment to reduce risk of postpartum depression is warranted. Further rigorous research on prenatal depression and adverse birth outcomes is needed. PMID:25452215

  16. Chemical respiratory allergy: reverse engineering an adverse outcome pathway.

    PubMed

    Kimber, Ian; Dearman, Rebecca J; Basketter, David A; Boverhof, Darrell R

    2014-04-01

    Allergic sensitisation of the respiratory tract by chemicals is associated with rhinitis and asthma and remains an important occupational health issue. Although less than 80 chemicals have been confirmed as respiratory allergens the adverse health effects can be serious, and in rare instances can be fatal, and there are, in addition, related socioeconomic issues. The challenges that chemical respiratory allergy pose for toxicologists are substantial. No validated methods are available for hazard identification and characterisation, and this is due in large part to the fact that there remains considerable uncertainty and debate about the mechanisms through which sensitisation of the respiratory tract is acquired. Despite that uncertainty, there is a need to establish some common understanding of the key events and processes that are involved in respiratory sensitisation to chemicals and that might in turn provide the foundations for novel approaches to safety assessment. In recent years the concept of adverse outcome pathways (AOP) has gained some considerable interest among the toxicology community as a basis for outlining the key steps leading to an adverse health outcome, while also providing a framework for focusing future research, and for developing alternative paradigms for hazard characterisation. Here we explore application of the same general principles to an examination of the induction by chemicals of respiratory sensitisation. In this instance, however, we have chosen to adopt a reverse engineering approach and to model a possible AOP for chemical respiratory allergy working backwards from the elicitation of adverse health effects to the cellular and molecular mechanisms that are implicated in the acquisition of sensitisation.

  17. Infant Aphakia Treatment Study: Effects of persistent fetal vasculature on outcome at 1 year of age

    PubMed Central

    Morrison, David G.; Wilson, M. Edward; Trivedi, Rupal H.; Lambert, Scott R.; Lynn, Michael J.

    2011-01-01

    Background The Infant Aphakia Treatment Study (IATS) is a randomized trial comparing the treatment of unilateral congenital cataract with primary intraocular lens (IOL) implantation versus aphakic contact lens (CL). The purpose of this study was to compare the outcomes for infants with lens opacity associated with persistent fetal vasculature (PFV) to those without. Methods Retrospective subgroup analysis of grating visual acuity at 1 year of age and adverse events up to 1 year after surgery in eyes identified intraoperatively as having evidence of mild PFV from the IATS. Results Of 83 infants, 18 (22%: 11 CL, 7 IOL) had PFV. Median logMAR visual acuity was 0.88 for patients with PFV and 0.80 for patients without PFV (P = 0.46). One or more adverse events up to one year after surgery occurred in 12 infants (67%) with PFV and 30 infants (46%) without PFV (P = 0.18). The incidence of adverse events was significantly higher in patients with PFV compared to patients without PFV in the CL group (55% vs 20%, P = 0.049) but not in the IOL group (86% vs 71%, P = 0.65), possibly because all children receiving IOLs had higher rates of adverse events when compared to aphakic children (73% vs 29%, P < 0.001). Conclusions Aphakic infants with mild PFV treated with CL had a higher incidence of adverse events following lensectomy compared to children with other forms of unilateral congenital cataract; nevertheless, similar visual outcomes at one year after surgery were obtained. PMID:22108353

  18. Adverse neurological outcomes in Nigerian children with sickle cell disease.

    PubMed

    Lagunju, I A; Brown, B J

    2012-12-01

    Sickle cell disease (SCD) is reported to be the most common genetic disorder affecting Nigerians. Children with SCD are at a high risk of neurological morbidity. The main objective of this study was to determine the pattern of adverse neurological outcomes among a cohort of Nigerian children with SCD. All children with SCD seen in the Department of Paediatrics, University College Hospital, Ibadan, Nigeria, over a period of 2 years were carefully evaluated for symptoms and signs of neurological complications, defined as clinical outcomes referable to the central nervous system. Of the 214 children evaluated, 187 were diagnosed with Hb SS disease and 27 with Hb SC disease. Neurological complications were identified in 78 (36.4 %) of the cases. The most common complications were headache (17.8 %), seizure (9.3 %) and stroke (8.4 %). Other less frequent complications included bacterial meningitis (2.8 %), spontaneous visual loss (1.4 %), paraplegia (0.9 %) and transient ischaemic attacks (0.9 %). Neurological complications occurred more frequently in children with sickle cell anaemia than in those with Hb SC disease (P = 0.002, 95 % CI 1.450-82.870). Adverse neurological events are common in Nigerian children with SCD, with a significantly higher risk in Hb SS than Hb SC disease. Stroke represents a major underlying cause of symptomatic epilepsy in SCD. Institution of primary preventive measures for stroke in SCD will significantly reduce the burden of stroke and epilepsy associated with SCD in Nigeria.

  19. Adverse neurological outcomes in Nigerian children with sickle cell disease.

    PubMed

    Lagunju, I A; Brown, B J

    2012-12-01

    Sickle cell disease (SCD) is reported to be the most common genetic disorder affecting Nigerians. Children with SCD are at a high risk of neurological morbidity. The main objective of this study was to determine the pattern of adverse neurological outcomes among a cohort of Nigerian children with SCD. All children with SCD seen in the Department of Paediatrics, University College Hospital, Ibadan, Nigeria, over a period of 2 years were carefully evaluated for symptoms and signs of neurological complications, defined as clinical outcomes referable to the central nervous system. Of the 214 children evaluated, 187 were diagnosed with Hb SS disease and 27 with Hb SC disease. Neurological complications were identified in 78 (36.4 %) of the cases. The most common complications were headache (17.8 %), seizure (9.3 %) and stroke (8.4 %). Other less frequent complications included bacterial meningitis (2.8 %), spontaneous visual loss (1.4 %), paraplegia (0.9 %) and transient ischaemic attacks (0.9 %). Neurological complications occurred more frequently in children with sickle cell anaemia than in those with Hb SC disease (P = 0.002, 95 % CI 1.450-82.870). Adverse neurological events are common in Nigerian children with SCD, with a significantly higher risk in Hb SS than Hb SC disease. Stroke represents a major underlying cause of symptomatic epilepsy in SCD. Institution of primary preventive measures for stroke in SCD will significantly reduce the burden of stroke and epilepsy associated with SCD in Nigeria. PMID:23129067

  20. Constructing, Quantifying, and Validating an Adverse Outcome Pathway for Vascular Developmental Toxicity

    EPA Science Inventory

    Constructing, Quantifying, and Validating an Adverse Outcome Pathway for Vascular Developmental Toxicity The adverse outcome pathway (AOP) for embryonic vascular disruption1 leading to a range of adverse prenatal outcomes was recently entered into the AOP wiki and accepted as par...

  1. Association of Second and Third Trimester Weight Gain in Pregnancy with Maternal and Fetal Outcomes

    PubMed Central

    Drehmer, Michele; Duncan, Bruce Bartholow; Kac, Gilberto; Schmidt, Maria Inês

    2013-01-01

    Objective To investigate the association between weekly weight gain, during the second and third trimesters, classified according to the 2009 Institute of Medicine (IOM/NRC) recommendations, and maternal and fetal outcomes. Methods Gestational weight gain was evaluated in 2,244 pregnant women of the Brazilian Study of Gestational Diabetes (Estudo Brasileiro do Diabetes Gestacional – EBDG). Outcomes were cesarean delivery, preterm birth and small or large for gestational age birth (SGA, LGA). Associations between inadequate weight gain and outcomes were estimated using robust Poisson regression adjusting for pre-pregnancy body mass index, trimester-specific weight gain, age, height, skin color, parity, education, smoking, alcohol consumption, gestational diabetes and hypertensive disorders in pregnancy. Results In fully adjusted models, in the second trimester, insufficient weight gain was associated with SGA (relative risk [RR] 1.72, 95% confidence interval [CI] 1.26–2.33), and excessive weight gain with LGA (RR 1.64, 95% CI 1.16–2.31); in third trimester, excessive weight gain with preterm birth (RR 1.70, 95% CI 1.08–2.70) and cesarean delivery (RR 1.21, 95% CI 1.03–1.44). Women with less than recommended gestational weight gain in the 2nd trimester had a lesser risk of cesarean deliveries (RR 0.82, 95% CI 0.71–0.96) than women with adequate gestational weight gain in this trimester. Conclusion Though insufficient weight gain in the 3rd trimester was not associated with adverse outcomes, other deviations from recommended weight gain during second and third trimester were associated with adverse pregnancy outcomes. These findings support, in part, the 2009 IOM/NRC recommendations for nutritional monitoring during pregnancy. PMID:23382944

  2. Excessive folic acid intake and relation to adverse health outcome.

    PubMed

    Selhub, Jacob; Rosenberg, Irwin H

    2016-07-01

    The recent increase in the intake of folic acid by the general public through fortified foods and supplements, has raised safety concern based on early reports of adverse health outcome in elderly with low B12 status who took high doses of folic acid. These safety concerns are contrary to the 2015 WHO statement that "high folic acid intake has not reliably been shown to be associated with negative healeffects". In the folic acid post-fortification era, we have shown that in elderly participants in NHANES 1999-2002, high plasma folate level is associated with exacerbation of both clinical (anemia and cognitive impairment) and biochemical (high MMA and high Hcy plasma levels) signs of vitamin B12 deficiency. Adverse clinical outcomes in association with high folate intake were also seen among elderly with low plasma B12 levels from the Framingham Original Cohort and in a study from Australia which combined three elderly cohorts. Relation between high folate and adverse biochemical outcomes were also seen in the Sacramento Area Latino Study on Aging (High Hcy, high MMA and lower TC2) and at an outpatient clinic at Yale University where high folate is associated with higher MMA in the elderly but not in the young. Potential detrimental effects of high folic acid intake may not be limited to the elderly nor to those with B12 deficiency. A study from India linked maternal high RBC folate to increased insulin resistance in offspring. Our study suggested that excessive folic acid intake is associated with lower natural killer cells activity in elderly women. In a recent study we found that the risk for unilateral retinoblastoma in offspring is 4 fold higher in women that are homozygotes for the 19 bp deletion in the DHFR gene and took folic acid supplement during pregnancy. In the elderly this polymorphism is associated with lower memory and executive scores, both being significantly worse in those with high plasma folate. These and other data strongly imply that

  3. Excessive folic acid intake and relation to adverse health outcome.

    PubMed

    Selhub, Jacob; Rosenberg, Irwin H

    2016-07-01

    The recent increase in the intake of folic acid by the general public through fortified foods and supplements, has raised safety concern based on early reports of adverse health outcome in elderly with low B12 status who took high doses of folic acid. These safety concerns are contrary to the 2015 WHO statement that "high folic acid intake has not reliably been shown to be associated with negative healeffects". In the folic acid post-fortification era, we have shown that in elderly participants in NHANES 1999-2002, high plasma folate level is associated with exacerbation of both clinical (anemia and cognitive impairment) and biochemical (high MMA and high Hcy plasma levels) signs of vitamin B12 deficiency. Adverse clinical outcomes in association with high folate intake were also seen among elderly with low plasma B12 levels from the Framingham Original Cohort and in a study from Australia which combined three elderly cohorts. Relation between high folate and adverse biochemical outcomes were also seen in the Sacramento Area Latino Study on Aging (High Hcy, high MMA and lower TC2) and at an outpatient clinic at Yale University where high folate is associated with higher MMA in the elderly but not in the young. Potential detrimental effects of high folic acid intake may not be limited to the elderly nor to those with B12 deficiency. A study from India linked maternal high RBC folate to increased insulin resistance in offspring. Our study suggested that excessive folic acid intake is associated with lower natural killer cells activity in elderly women. In a recent study we found that the risk for unilateral retinoblastoma in offspring is 4 fold higher in women that are homozygotes for the 19 bp deletion in the DHFR gene and took folic acid supplement during pregnancy. In the elderly this polymorphism is associated with lower memory and executive scores, both being significantly worse in those with high plasma folate. These and other data strongly imply that

  4. Streptozotocin-Induced Diabetes Models: Pathophysiological Mechanisms and Fetal Outcomes

    PubMed Central

    Damasceno, D. C.; Netto, A. O.; Iessi, I. L.; Gallego, F. Q.; Corvino, S. B.; Dallaqua, B.; Sinzato, Y. K.; Bueno, A.; Calderon, I. M. P.; Rudge, M. V. C.

    2014-01-01

    Glucose homeostasis is controlled by endocrine pancreatic cells, and any pancreatic disturbance can result in diabetes. Because 8% to 12% of diabetic pregnant women present with malformed fetuses, there is great interest in understanding the etiology, pathophysiological mechanisms, and treatment of gestational diabetes. Hyperglycemia enhances the production of reactive oxygen species, leading to oxidative stress, which is involved in diabetic teratogenesis. It has also been suggested that maternal diabetes alters embryonic gene expression, which might cause malformations. Due to ethical issues involving human studies that sometimes have invasive aspects and the multiplicity of uncontrolled variables that can alter the uterine environment during clinical studies, it is necessary to use animal models to better understand diabetic pathophysiology. This review aimed to gather information about pathophysiological mechanisms and fetal outcomes in streptozotocin-induced diabetic rats. To understand the pathophysiological mechanisms and factors involved in diabetes, the use of pancreatic regeneration studies is increasing in an attempt to understand the behavior of pancreatic beta cells. In addition, these studies suggest a new preventive concept as a treatment basis for diabetes, introducing therapeutic efforts to minimize or prevent diabetes-induced oxidative stress, DNA damage, and teratogenesis. PMID:24977161

  5. Perinatal outcome of fetal complete atrioventricular block: a multicenter experience.

    PubMed

    Schmidt, K G; Ulmer, H E; Silverman, N H; Kleinman, C S; Copel, J A

    1991-05-01

    The clinical course and outcome of 55 fetuses with complete atrioventricular (AV) block detected prenatally were studied to identify factors that affect the natural history of this lesion. In 29 fetuses (53%) complete AV block was associated with complex structural heart defects, usually left atrial isomerism (n = 17) or discordant AV connection (n = 7). The other 26 fetuses had normal cardiac anatomy; in 19 cases the mother had connective tissue disease or tested positive for antinuclear antibodies. Six fetuses showed progression from sinus rhythm or second degree block to complete AV block. Of the 55 pregnancies, 5 were terminated and 24 fetuses or neonates died; at the end of the neonatal period 26 fetuses were still alive. Fetal or neonatal death correlated significantly with the presence of structural heart defects (4 of 29 surviving, p less than 0.001), hydrops (0 of 22 surviving, p less than 0.001), an atrial rate less than or equal to 120 beats/min (1 of 12 surviving, p less than 0.005) or a ventricular rate less than or equal to 55 beats/min (3 of 21 surviving, p less than 0.001). Mean atrial and ventricular rates were higher in surviving than in nonsurviving fetuses (142 +/- 8 vs. 127 +/- 21 beats/min, p less than 0.002; 64 +/- 8 vs. 52 +/- 8 beats/min, p less than 0.001, respectively). A slow atrial rate, however, was frequently associated with left atrial isomerism.(ABSTRACT TRUNCATED AT 250 WORDS)

  6. Poverty in childhood and adverse health outcomes in adulthood.

    PubMed

    Raphael, Dennis

    2011-05-01

    The experience of poverty during childhood is a potent predictor of a variety of adverse health outcomes during middle and late adulthood. Children who live in poverty are more likely as adults than their peers to develop and die earlier from a range of diseases. These effects are especially strong for cardiovascular disease and type II diabetes. Most disturbingly, these effects appear in large part to be biologically embedded such that later improved life circumstances have only a modest ameliorative effect. Considering these findings and the relatively high rates of child poverty in nations such as Canada, UK, and USA, those concerned with improving the health of citizens should focus their attention on advocating for public policy that will reduce the incidence of child poverty.

  7. Neighborhood deprivation and adverse birth outcomes among diverse ethnic groups

    PubMed Central

    Janevic, T; Stein, CR; Savitz, DA; Kaufman, JS; Mason, SM; Herring, AH

    2010-01-01

    Purpose Living in a socioeconomically deprived neighborhood has been associated with an increased risk of adverse birth outcomes. However, variation in the effect of neighborhood deprivation among diverse ethnic groups has not been studied. Methods Using linked hospital discharge and birth data for 517,994 singleton live births in New York City from 1998–2002, we examined the association between neighborhood deprivation, preterm birth (PTB), and term low birthweight (TLBW)(≥37 weeks and <2500g). Adjusted odds ratios (aOR) for PTB (<32 and 33–36 weeks) and TLBW were estimated using logistic regression. Results The aOR for PTB <32 weeks for the highest quartile of deprivation compared to the lowest was 1.24 (95% Confidence Interval (CI)=1.13, 1.36), for PTB 33–36 weeks was 1.06 (95%CI=1.01, 1.11), and for TLBW was 1.19 (95%CI=1.11, 1.27). Measures of association varied by ethnicity; AORs of the greatest magnitude for PTB were found among Hispanic Caribbean women (PTB<32weeks: aOR=1.63, 95%CI=1.27, 2.10; PTB 33–36 weeks: aOR=1.32, 95%CI=1.02, 1.70), and for TLBW among African women (aOR=1.47, 95%CI=1.02, 2.13). Conclusions The mechanisms linking neighborhood deprivation to adverse birth outcomes may differ depending on individual ethnicity and/or cultural context and should be investigated in future research. PMID:20470971

  8. Adverse Outcome Pathway (AOP) Development I: Strategies and Principles

    PubMed Central

    Villeneuve, Daniel L.; Crump, Doug; Garcia-Reyero, Natàlia; Hecker, Markus; Hutchinson, Thomas H.; LaLone, Carlie A.; Landesmann, Brigitte; Lettieri, Teresa; Munn, Sharon; Nepelska, Malgorzata; Ottinger, Mary Ann; Vergauwen, Lucia; Whelan, Maurice

    2014-01-01

    An adverse outcome pathway (AOP) is a conceptual framework that organizes existing knowledge concerning biologically plausible, and empirically supported, links between molecular-level perturbation of a biological system and an adverse outcome at a level of biological organization of regulatory relevance. Systematic organization of information into AOP frameworks has potential to improve regulatory decision-making through greater integration and more meaningful use of mechanistic data. However, for the scientific community to collectively develop a useful AOP knowledgebase that encompasses toxicological contexts of concern to human health and ecological risk assessment, it is critical that AOPs be developed in accordance with a consistent set of core principles. Based on the experiences and scientific discourse among a group of AOP practitioners, we propose a set of five fundamental principles that guide AOP development: (1) AOPs are not chemical specific; (2) AOPs are modular and composed of reusable components—notably key events (KEs) and key event relationships (KERs); (3) an individual AOP, composed of a single sequence of KEs and KERs, is a pragmatic unit of AOP development and evaluation; (4) networks composed of multiple AOPs that share common KEs and KERs are likely to be the functional unit of prediction for most real-world scenarios; and (5) AOPs are living documents that will evolve over time as new knowledge is generated. The goal of the present article was to introduce some strategies for AOP development and detail the rationale behind these 5 key principles. Consideration of these principles addresses many of the current uncertainties regarding the AOP framework and its application and is intended to foster greater consistency in AOP development. PMID:25466378

  9. Adverse outcome pathway (AOP) development I: strategies and principles.

    PubMed

    Villeneuve, Daniel L; Crump, Doug; Garcia-Reyero, Natàlia; Hecker, Markus; Hutchinson, Thomas H; LaLone, Carlie A; Landesmann, Brigitte; Lettieri, Teresa; Munn, Sharon; Nepelska, Malgorzata; Ottinger, Mary Ann; Vergauwen, Lucia; Whelan, Maurice

    2014-12-01

    An adverse outcome pathway (AOP) is a conceptual framework that organizes existing knowledge concerning biologically plausible, and empirically supported, links between molecular-level perturbation of a biological system and an adverse outcome at a level of biological organization of regulatory relevance. Systematic organization of information into AOP frameworks has potential to improve regulatory decision-making through greater integration and more meaningful use of mechanistic data. However, for the scientific community to collectively develop a useful AOP knowledgebase that encompasses toxicological contexts of concern to human health and ecological risk assessment, it is critical that AOPs be developed in accordance with a consistent set of core principles. Based on the experiences and scientific discourse among a group of AOP practitioners, we propose a set of five fundamental principles that guide AOP development: (1) AOPs are not chemical specific; (2) AOPs are modular and composed of reusable components-notably key events (KEs) and key event relationships (KERs); (3) an individual AOP, composed of a single sequence of KEs and KERs, is a pragmatic unit of AOP development and evaluation; (4) networks composed of multiple AOPs that share common KEs and KERs are likely to be the functional unit of prediction for most real-world scenarios; and (5) AOPs are living documents that will evolve over time as new knowledge is generated. The goal of the present article was to introduce some strategies for AOP development and detail the rationale behind these 5 key principles. Consideration of these principles addresses many of the current uncertainties regarding the AOP framework and its application and is intended to foster greater consistency in AOP development. PMID:25466378

  10. Association of Chorioamnionitis with Aberrant Neonatal Gut Colonization and Adverse Clinical Outcomes

    PubMed Central

    Ambalavanan, Namasivayam; Schibler, Kurt R.; Morrow, Ardythe L.; Kallapur, Suhas G.

    2016-01-01

    Objective Chorioamnionitis (inflammation of the placenta and fetal membranes) and abnormal gastrointestinal colonization have been associated with an increased risk of sepsis and death in preterm infants, but whether chorioamnionitis causes abnormal pioneering gastrointestinal colonization in infants is not known. We determined the relationship between chorioamnionitis, altered infant fecal microbiome indicating abnormal gastrointestinal colonization, and adverse outcomes. Study Design Preterm infants ≤ 28 weeks at birth were enrolled from 3 level III NICUs in Cincinnati, Ohio and Birmingham, Alabama. Sequencing for 16S microbial gene was performed on stool samples in the first 3 weeks of life. Chorioamnionitis was diagnosed by placental histology. Late onset sepsis and death outcomes were analyzed in relation to fecal microbiota and chorioamnionitis with or without funisitis (inflammation of the umbilical cord). Results Of the 106 enrolled infants, 48 infants had no chorioamnionitis, 32 infants had chorioamnionitis but no funisitis (AC), and 26 infants had chorioamnionitis with funisitis (ACF). The fecal samples from ACF infants collected by day of life 7 had higher relative abundance of family Mycoplasmataceae (phylum Tenericutes), genus Prevotella (phylum Bacteroidetes) and genus Sneathia (phylum Fusobacteria). Further, AC and ACF infants had higher incidence of late-onset sepsis/death as a combined outcome. Presence of specific clades in fecal samples, specifically, order Fusobacteria, genus Sneathia or family Mycoplasmataceae, were significantly associated with higher risk of sepsis or death. Conclusion The results support the hypothesis that specific alterations in the pioneering infant gastrointestinal microbiota induced by chorioamnionitis predispose to neonatal sepsis or death. PMID:27658190

  11. Nutritional indicators of adverse pregnancy outcomes and mother-to-child transmission of HIV among HIV-infected women2

    PubMed Central

    Mehta, Saurabh; Manji, Karim P; Young, Alicia M; Brown, Elizabeth R; Chasela, Charles; Taha, Taha E; Read, Jennifer S; Goldenberg, Robert L; Fawzi, Wafaie W

    2008-01-01

    Background Poor nutrition may be associated with mother-to-child transmission (MTCT) of HIV and other adverse pregnancy outcomes. Objective The objective was to examine the relation of nutritional indicators with adverse pregnancy outcomes among HIV-infected women in Tanzania, Zambia, and Malawi. Design Body mass index (BMI; in kg/m2) and hemoglobin concentrations at enrollment and weight change during pregnancy were prospectively related to fetal loss, neonatal death, low birth weight, preterm birth, and MTCT of HIV. Results In a multivariate analysis, having a BMI < 21.8 was significantly associated with preterm birth [odds ratio (OR): 1.82; 95% CI: 1.34, 2.46] and low birth weight (OR: 2.09; 95% CI: 1.41, 3.08). A U-shaped relation between weight change during pregnancy and preterm birth was observed. Severe anemia was significantly associated with fetal loss or stillbirth (OR: 3.67; 95% CI: 1.16, 11.66), preterm birth (OR: 2.08; 95% CI: 1.39, 3.10), low birth weight (OR: 1.76; 95% CI: 1.07, 2.90), and MTCT of HIV by the time of birth (OR: 2.26; 95% CI: 1.18, 4.34) and by 4−6 wk among those negative at birth (OR: 2.33; 95% CI: 1.15, 4.73). Conclusions Anemia, poor weight gain during pregnancy, and low BMI in HIV-infected pregnant women are associated with increased risks of adverse infant outcomes and MTCT of HIV. Interventions that reduce the risk of wasting or anemia during pregnancy should be evaluated to determine their possible effect on the incidence of adverse pregnancy outcomes and MTCT of HIV. PMID:18541551

  12. Accelerating Adverse Outcome Pathway Development Using Publicly Available Data Sources.

    PubMed

    Oki, Noffisat O; Nelms, Mark D; Bell, Shannon M; Mortensen, Holly M; Edwards, Stephen W

    2016-03-01

    The adverse outcome pathway (AOP) concept links molecular perturbations with organism and population-level outcomes to support high-throughput toxicity (HTT) testing. International efforts are underway to define AOPs and store the information supporting these AOPs in a central knowledge base; however, this process is currently labor-intensive and time-consuming. Publicly available data sources provide a wealth of information that could be used to define computationally predicted AOPs (cpAOPs), which could serve as a basis for creating expert-derived AOPs in a much more efficient way. Computational tools for mining large datasets provide the means for extracting and organizing the information captured in these public data sources. Using cpAOPs as a starting point for expert-derived AOPs should accelerate AOP development. Coupling this with tools to coordinate and facilitate the expert development efforts will increase the number and quality of AOPs produced, which should play a key role in advancing the adoption of HTT testing, thereby reducing the use of animals in toxicity testing and greatly increasing the number of chemicals that can be tested. PMID:26809562

  13. Adverse obstetric and neonatal outcomes in women with mental disorders.

    PubMed

    Hoirisch-Clapauch, Silvia; Brenner, Benjamin; Nardi, Antonio Egidio

    2015-02-01

    The brain and the placenta synthesize identical peptides and proteins, such as brain-derived neurotrophic factor, oxytocin, vascular endothelial growth factor, cortisol, and matrix metalloproteinases. Given the promiscuity between neurochemistry and the mechanism of placentation, it would be expected that mental disorders occurring during pregnancy would increase the risk of adverse obstetric and neonatal outcomes. Indeed, expectant mothers with anxiety disorders, post-traumatic stress disorder, schizophrenia, or depressive disorders are at higher risk of preterm birth, low-birth-weight and small-for-gestational-age infants than controls. These mental illnesses are accompanied by a procoagulant phenotype and low activity of tissue plasminogen activator, which may contribute to placental insufficiency. Another risk factor for pregnancy complications is hyperemesis gravidarum, more common among women with eating disorders or anxiety disorders than in controls. Severe hyperemesis gravidarum is associated with dehydration, electrolyte imbalance and malnutrition, all of which may increase the risk of miscarriages, of low-birth-weight babies and preterm birth. This paper reviews some aspects of mental disorders that may influence pregnancy and neonatal outcomes. PMID:25903540

  14. Systematic review on adverse birth outcomes of climate change

    PubMed Central

    Poursafa, Parinaz; Keikha, Mojtaba; Kelishadi, Roya

    2015-01-01

    Background: Climate change and global warming have significant effects on human health. This systematic review presents the effects of the climate changes on pregnancy outcomes. Materials and Methods: The search process was conducted in electronic databases including ISI Web of Knowledge, PubMed, Scopus, and Google Scholar using key words of “environmental temperature” “pregnancy” “low birth weight (LBW)” “pregnancy outcome,” “climate change,” “preterm birth (PTB),” and a combination of them. We did not consider any time limitation; English-language papers were included. The related papers were selected in three phases. After quality assessment, two reviewers extracted the data while the third reviewer checked their extracted data. Finally, 15 related articles were selected and included in the current study. Results: Approximately all studies have reported a significant relationship between exposure variable and intended outcomes including eclampsia, preeclampsia, cataract, LBW, PTB, hypertension, sex ratio and length of pregnancy. According to conducted studies, decrease in birth weight is more possible in cold months. Increase in temperature was followed by increase in PTB rate. According to most of the studies, eclampsia and preeclampsia were more prevalent in cold and humid seasons. Two spectrums of heat extent, different seasons of the year, sunlight intensity and season of fertilization were associated with higher rates of PTB, hypertension, eclampsia, preeclampsia, and cataract. Conclusion: Climate change has unfavorable effects on eclampsia, preeclampsia, PTB, and cataract. The findings of this review confirm the crucial importance of the adverse health effects of climate change especially in the perinatal period. PMID:26109998

  15. Clinical outcomes and adverse effect monitoring in allergic rhinitis.

    PubMed

    Juniper, Elizabeth F; Ståhl, Elisabeth; Doty, Richard L; Simons, F Estelle R; Allen, David B; Howarth, Peter H

    2005-03-01

    The subjective recording in diary cards of symptoms of itch, sneeze, nose running, and blockage, with the use of a rating scale to indicate the level of severity, is usual for clinical trials in allergic rhinitis. The primary outcome measure is usually a composite score that enables a single total symptoms score endpoint. It is appreciated, however, that rhinitis has a greater effect on the individual than is reflected purely by the recording of anterior nasal symptoms. Nasal obstruction is troublesome and may lead to sleep disturbance in addition to impaired daytime concentration and daytime sleepiness. These impairments affect school and work performance. Individuals with rhinitis find it socially embarrassing to be seen sneezing, sniffing, or blowing their nose. To capture these and other aspects of the disease-specific health-related quality of life, questionnaires such as the Rhinoconjunctivitis Quality of Life Questionnaire have been developed and validated for clinical trial use. The adoption of health-related quality of life questionnaires into clinical trials broadens the information obtained regarding the effect of the therapeutic intervention and helps focus on issues relevant to the individual patient. It must be appreciated that it is not only the disease that may adversely affect health-related quality of life; administered therapy, although intended to be beneficial, may also cause health impairment. Adverse-event monitoring is thus essential in clinical trials. The first-generation H 1 -histamines, because of their effect on central H 1 -receptors, are classically associated with central nervous system (CNS) effects such as sedation. Although this is not always perceived by the patient, it is clearly evident with objective performance testing, and positron emission tomography scanning has directly demonstrated the central H 1 -receptor occupancy. The second-generation H 1 -antihistamines have reduced central H 1 -receptor occupancy and considerably

  16. Adverse health outcomes among cosmetologists and noncosmetologists in the Reproductive Outcomes of Salon Employees (ROSE) study.

    PubMed

    Gallicchio, Lisa; Miller, Susan R; Greene, Teresa; Zacur, Howard; Flaws, Jodi A

    2011-01-01

    The purpose of this study was to examine adverse health outcomes, including those related to cardiovascular and skin health as well as respiratory functions, among cosmetologists aged 21 to 55 yr and to compare data to women of the same age working in other occupations. Self-reported data were analyzed from 450 cosmetologists and 511 women in other occupations who participated in the Reproductive Outcomes of Salon Employees (ROSE) study in Maryland. Odds ratios (OR) and 95% confidence intervals (95% CI) were computed using logistic regression to examine the associations between cosmetologist occupation and each adverse health outcome adjusted for age, education, and smoking status. Cosmetologists were at significantly increased risk of depression compared to noncosmetologists after adjustment for age, education, and smoking status (OR 1.49; 95% CI 1.10, 2.00). There were no statistically significant associations between cosmetology occupation and the other adverse health outcomes, including those related to allergies and skin disorders, in both the unadjusted and adjusted analyses. Cosmetologists may be exposed to chemicals in the salon that lead to depression. Future study needs to be conducted to examine specific chemical exposures in the salon. This will help to provide information required for the development of best occupational safety practices among salon workers. PMID:21120748

  17. Adiponectin supplementation in pregnant mice prevents the adverse effects of maternal obesity on placental function and fetal growth.

    PubMed

    Aye, Irving L M H; Rosario, Fredrick J; Powell, Theresa L; Jansson, Thomas

    2015-10-13

    Mothers with obesity or gestational diabetes mellitus have low circulating levels of adiponectin (ADN) and frequently deliver large babies with increased fat mass, who are susceptible to perinatal complications and to development of metabolic syndrome later in life. It is currently unknown if the inverse correlation between maternal ADN and fetal growth reflects a cause-and-effect relationship. We tested the hypothesis that ADN supplementation in obese pregnant dams improves maternal insulin sensitivity, restores normal placental insulin/mechanistic target of rapamycin complex 1 (mTORC1) signaling and nutrient transport, and prevents fetal overgrowth. Compared with dams on a control diet, female C57BL/6J mice fed an obesogenic diet before mating and throughout gestation had increased fasting serum leptin, insulin, and C-peptide, and reduced high-molecular-weight ADN at embryonic day (E) 18.5. Placental insulin and mTORC1 signaling was activated, peroxisome proliferator-activated receptor-α (PPARα) phosphorylation was reduced, placental transport of glucose and amino acids in vivo was increased, and fetal weights were 29% higher in obese dams. Maternal ADN infusion in obese dams from E14.5 to E18.5 normalized maternal insulin sensitivity, placental insulin/mTORC1 and PPARα signaling, nutrient transport, and fetal growth without affecting maternal fat mass. Using a mouse model with striking similarities to obese pregnant women, we demonstrate that ADN functions as an endocrine link between maternal adipose tissue and fetal growth by regulating placental function. Importantly, maternal ADN supplementation reversed the adverse effects of maternal obesity on placental function and fetal growth. Improving maternal ADN levels may serve as an effective intervention strategy to prevent fetal overgrowth caused by maternal obesity. PMID:26417088

  18. Adiponectin supplementation in pregnant mice prevents the adverse effects of maternal obesity on placental function and fetal growth

    PubMed Central

    Aye, Irving L. M. H.; Rosario, Fredrick J.; Powell, Theresa L.; Jansson, Thomas

    2015-01-01

    Mothers with obesity or gestational diabetes mellitus have low circulating levels of adiponectin (ADN) and frequently deliver large babies with increased fat mass, who are susceptible to perinatal complications and to development of metabolic syndrome later in life. It is currently unknown if the inverse correlation between maternal ADN and fetal growth reflects a cause-and-effect relationship. We tested the hypothesis that ADN supplementation in obese pregnant dams improves maternal insulin sensitivity, restores normal placental insulin/mechanistic target of rapamycin complex 1 (mTORC1) signaling and nutrient transport, and prevents fetal overgrowth. Compared with dams on a control diet, female C57BL/6J mice fed an obesogenic diet before mating and throughout gestation had increased fasting serum leptin, insulin, and C-peptide, and reduced high-molecular-weight ADN at embryonic day (E) 18.5. Placental insulin and mTORC1 signaling was activated, peroxisome proliferator-activated receptor-α (PPARα) phosphorylation was reduced, placental transport of glucose and amino acids in vivo was increased, and fetal weights were 29% higher in obese dams. Maternal ADN infusion in obese dams from E14.5 to E18.5 normalized maternal insulin sensitivity, placental insulin/mTORC1 and PPARα signaling, nutrient transport, and fetal growth without affecting maternal fat mass. Using a mouse model with striking similarities to obese pregnant women, we demonstrate that ADN functions as an endocrine link between maternal adipose tissue and fetal growth by regulating placental function. Importantly, maternal ADN supplementation reversed the adverse effects of maternal obesity on placental function and fetal growth. Improving maternal ADN levels may serve as an effective intervention strategy to prevent fetal overgrowth caused by maternal obesity. PMID:26417088

  19. Adiponectin supplementation in pregnant mice prevents the adverse effects of maternal obesity on placental function and fetal growth.

    PubMed

    Aye, Irving L M H; Rosario, Fredrick J; Powell, Theresa L; Jansson, Thomas

    2015-10-13

    Mothers with obesity or gestational diabetes mellitus have low circulating levels of adiponectin (ADN) and frequently deliver large babies with increased fat mass, who are susceptible to perinatal complications and to development of metabolic syndrome later in life. It is currently unknown if the inverse correlation between maternal ADN and fetal growth reflects a cause-and-effect relationship. We tested the hypothesis that ADN supplementation in obese pregnant dams improves maternal insulin sensitivity, restores normal placental insulin/mechanistic target of rapamycin complex 1 (mTORC1) signaling and nutrient transport, and prevents fetal overgrowth. Compared with dams on a control diet, female C57BL/6J mice fed an obesogenic diet before mating and throughout gestation had increased fasting serum leptin, insulin, and C-peptide, and reduced high-molecular-weight ADN at embryonic day (E) 18.5. Placental insulin and mTORC1 signaling was activated, peroxisome proliferator-activated receptor-α (PPARα) phosphorylation was reduced, placental transport of glucose and amino acids in vivo was increased, and fetal weights were 29% higher in obese dams. Maternal ADN infusion in obese dams from E14.5 to E18.5 normalized maternal insulin sensitivity, placental insulin/mTORC1 and PPARα signaling, nutrient transport, and fetal growth without affecting maternal fat mass. Using a mouse model with striking similarities to obese pregnant women, we demonstrate that ADN functions as an endocrine link between maternal adipose tissue and fetal growth by regulating placental function. Importantly, maternal ADN supplementation reversed the adverse effects of maternal obesity on placental function and fetal growth. Improving maternal ADN levels may serve as an effective intervention strategy to prevent fetal overgrowth caused by maternal obesity.

  20. Antenatal psychosocial risk factors associated with adverse postpartum family outcomes.

    PubMed Central

    Wilson, L M; Reid, A J; Midmer, D K; Biringer, A; Carroll, J C; Stewart, D E

    1996-01-01

    OBJECTIVE: To determine the strength of the association between antenatal psychosocial risk factors and adverse postpartum outcomes in the family, such as assault of women by their partner, child abuse, postpartum depression, marital dysfunction and physical illness. DATA SOURCES: MEDLINE, Cinahl, Famli, Psych Abstracts and the Oxford Database of Perinatal Trials were searched from relevant articles published from Jan. 1, 1980, to Dec. 31, 1993, with the use of MeSH terms "depression, involutional," "child abuse," "child neglect," "domestic violence," "family," "marital adjustment," "family health," "newborn health," "child health," "physical illness," "social support," "psychosocial risk," "prediction," "risk factors," "obstetrics" and "prenatal care." Further articles were identified from bibliographies. STUDY SELECTION: Of the 370 articles identified through the search, 118 were included for review. Studies were included if they examined the association between psychosocial risk factors and the outcomes of interest. Articles were excluded if they were reviews of poor quality or they had one or more of the following features: insufficient description of the sample, a high attrition rate, a lack of standardized outcome measures, outcomes other than the ones of interest or results that had already been reported in a previous study. DATA EXTRACTION: The strength of evidence of each study was evaluated. On the basis of the evidence, each risk factor was assigned a rating of the strength of its association with each of the postpartum outcomes. The ratings were class A (good evidence of association), class B (fair evidence) and class C (no clear evidence). Of the 129 antenatal psychosocial risk factors studied, 15 were found to have a class A association with at least one of the postpartum outcomes. DATA SYNTHESIS: Child abuse and abuse of the mother by her partner were most strongly correlated (class A evidence) with a history of lack of social support, recent life

  1. Adverse outcomes of frailty in the elderly: the Rotterdam Study.

    PubMed

    Lahousse, Lies; Maes, Bastiaan; Ziere, Gijsbertus; Loth, Daan W; Verlinden, Vincentius J A; Zillikens, M Carola; Uitterlinden, André G; Rivadeneira, Fernando; Tiemeier, Henning; Franco, Oscar H; Ikram, M Arfan; Hofman, Albert; Brusselle, Guy G; Stricker, Bruno H

    2014-06-01

    To investigate the prevalence of frailty in a Dutch elderly population and to identify adverse health outcomes associated with the frailty phenotype independent of the comorbidities. Cross-sectional and longitudinal analyses within the Rotterdam Study (the Netherlands), a prospective population-based cohort study in persons aged ≥55 years. Frailty was defined as meeting three or more of five established criteria for frailty, evaluating nutritional status, physical activity, mobility, grip strength and exhaustion. Intermediate frailty was defined as meeting one or two frailty criteria. Comorbidities were objectively measured. Health outcomes were assessed by means of questionnaires, physical examinations and continuous follow-up through general practitioners and municipal health authorities for mortality. Of 2,833 participants (median age 74.0 years, inter quartile range 9) with sufficiently evaluated frailty criteria, 163 (5.8 %) participants were frail and 1,454 (51.3 %) intermediate frail. Frail elderly were more likely to be older and female, to have an impaired quality of life and to have fallen or to have been hospitalized. 108 (72.0 %) frail participants had ≥2 comorbidities, compared to 777 (54.4 %) intermediate frail and 522 (44.8 %) non-frail participants. Adjusted for age, sex and comorbidities, frail elderly had a significantly increased risk of dying within 3 years (HR 3.4; 95 % CI 1.9-6.4), compared to the non-frail elderly. This study in a general Dutch population of community-dwelling elderly able to perform the frailty tests, demonstrates that frailty is common and that frail elderly are at increased risk of death independent of comorbidities. PMID:24935872

  2. Maternal and fetal Acid-base chemistry: a major determinant of perinatal outcome.

    PubMed

    Omo-Aghoja, L

    2014-01-01

    Very small changes in pH may significantly affect the function of various fetal organ systems, such as the central nervous system, and the cardiovascular system with associated fetal distress and poor Apgar score. Review of existing data on maternal-fetal acid-base balance in pregnancy highlight the factors that are associated with derangements of the acid-base status and the impact of the derangements on fetal outcome. Extensive search of electronic databases and manual search of journals for relevant literature on maternal and fetal acid chemistry, clinical studies and case studies were undertaken. There is a substantial reduction in the partial pressure of carbon dioxide (pCO2) in pregnancy. Adequate buffering prevents significant changes in maternal arterial pH. Normal fetal metabolism results in the production of acids which are buffered to maintain extracellular pH within a critical range. Fetal hypoxia can occur when maternal oxygenation is compromised, maternal perfusion of the placenta is reduced, or delivery of oxygenated blood from the placenta to the fetus is impeded. When adequate fetal oxygenation does not occur, metabolisms proceed along with an anaerobic pathway with production of organic acids, such as lactic acid. Accumulation of lactic acid can deplete the buffer system and result in metabolic acidosis with associated low fetal pH, fetal distress and poor Apgar score. There is a significant reduction in pCO2 in pregnancy. This change, however, does not result in a corresponding significant reduction in maternal arterial pH, because of adequate buffering. Very small changes in pH may cause significant derangement in fetal function and outcome.

  3. Developing and applying adverse outcome pathways: What you need to know

    EPA Science Inventory

    Adverse outcome pathways (AOPs) are a conceptual framework for organizing existing information concerning the predictive linkages between the initiation or early progression of a biological perturbation in an organism and the adverse outcome(s) of regulatory relevance (e.g., impa...

  4. Adverse Pregnancy Outcomes and Cardiovascular Risk Factor Management

    PubMed Central

    Mehta, Puja K.; Minissian, Margo; Merz, C. Noel Bairey

    2015-01-01

    Cardiovascular disease (CVD) is the leading health threat to American women. In addition to established risk factors for hypertension, hyperlipidemia, diabetes, smoking, and obesity, adverse pregnancy outcomes (APOs) including pre-eclampsia, eclampsia, and gestational diabetes are now recognized as factors that increase a woman’s risk for future CVD. CVD risk factor burden is disproportionately higher in those of low socioeconomic status and in ethnic/racial minority women. Since younger women often use their obstetrician/gynecologist as their primary health provider, this is an opportune time to diagnose and treat CVD risk factors early. Embedding preventive care providers such as nurse practitioners or physician assistants within OB/GYN practices can be considered, with referral to family medicine or internist for ongoing risk assessment and management. The American Heart Association (AHA)/American Stroke Association (ASA) stroke prevention guidelines tailored to women recommend that women with a history of pre-eclampsia be evaluated for hypertension and other CVD risk factors within 6 months to 1 year post-partum. Given the burden and impact of CVD on women our society, the entire medical community must work to establish feasible practice and referral patterns for assessment and treatment of CVD risk factors. PMID:26159741

  5. Adverse pregnancy outcomes and cardiovascular risk factor management.

    PubMed

    Mehta, Puja K; Minissian, Margo; Bairey Merz, C Noel

    2015-06-01

    Cardiovascular disease (CVD) is the leading health threat to American women. In addition to establish risk factors for hypertension, hyperlipidemia, diabetes, smoking, and obesity, adverse pregnancy outcomes (APOs) including pre-eclampsia, eclampsia, and gestational diabetes are now recognized as factors that increase a woman's risk for future CVD. CVD risk factor burden is disproportionately higher in those of low socioeconomic status and in ethnic/racial minority women. Since younger women often use their obstetrician/gynecologist as their primary health provider, this is an opportune time to diagnose and treat CVD risk factors early. Embedding preventive care providers such as nurse practitioners or physician assistants within OB/GYN practices can be considered, with referral to family medicine or internist for ongoing risk assessment and management. The American Heart Association (AHA)/American Stroke Association (ASA) stroke prevention guidelines tailored to women recommend that women with a history of pre-eclampsia can be evaluated for hypertension and other CVD risk factors within 6 months to 1-year post-partum. Given the burden and impact of CVD on women in our society, the entire medical community must work to establish feasible practice and referral patterns for assessment and treatment of CVD risk factors. PMID:26159741

  6. Adverse pregnancy outcomes and cardiovascular risk factor management.

    PubMed

    Mehta, Puja K; Minissian, Margo; Bairey Merz, C Noel

    2015-06-01

    Cardiovascular disease (CVD) is the leading health threat to American women. In addition to establish risk factors for hypertension, hyperlipidemia, diabetes, smoking, and obesity, adverse pregnancy outcomes (APOs) including pre-eclampsia, eclampsia, and gestational diabetes are now recognized as factors that increase a woman's risk for future CVD. CVD risk factor burden is disproportionately higher in those of low socioeconomic status and in ethnic/racial minority women. Since younger women often use their obstetrician/gynecologist as their primary health provider, this is an opportune time to diagnose and treat CVD risk factors early. Embedding preventive care providers such as nurse practitioners or physician assistants within OB/GYN practices can be considered, with referral to family medicine or internist for ongoing risk assessment and management. The American Heart Association (AHA)/American Stroke Association (ASA) stroke prevention guidelines tailored to women recommend that women with a history of pre-eclampsia can be evaluated for hypertension and other CVD risk factors within 6 months to 1-year post-partum. Given the burden and impact of CVD on women in our society, the entire medical community must work to establish feasible practice and referral patterns for assessment and treatment of CVD risk factors.

  7. Correlation of maternal-fetal attachment and health practices during pregnancy with neonatal outcomes

    PubMed Central

    Maddahi, Maryam Sadat; Dolatian, Mahrokh; khoramabadi, Monirsadat; Talebi, Atefeh

    2016-01-01

    Introduction Low birth weight due to preterm delivery or intrauterine growth restriction (IUGR) is the strongest factor contributing to prenatal, neonatal, and postnatal mortality. Maternal–fetal attachment plays a significant role in maternal and fetal health. Health practices performed by the mother during pregnancy constitute one of the factors that may affect neonatal outcomes. The present study was conducted to identify the relationship between maternal–fetal attachment and health practices during pregnancy with neonatal outcomes. Methods This cross-sectional study was conducted on 315 pregnant women with a gestational age of 33–41 weeks who presented to hospitals in Sirjan (Iran) between December 2014 and February 2015. The data collection tools used included the Health Practices in Pregnancy Questionnaire and the Maternal Fetal Attachment Scale. Data were analyzed using IBM-SPSS version 20, focusing on the Pearson product–moment correlation and the logistic regression model. Statistical significance was set to p<0.05. Results The mean score of maternal–fetal attachment was 60.34, and the mean score of health practices was 123.57. The mean birth weight of the neonates was 3052.38 g. Health practices (p<0.05, r=0.11) and maternal-fetal attachment (p<0.01, r=0.23) were positively and significantly correlated with neonatal outcomes. A significant positive relationship was also observed between maternal–fetal attachment and neonatal outcomes. No significant relationships were observed between health practices during pregnancy and neonatal outcomes. Conclusion Maternal-fetal attachment and health practices during pregnancy are positively and significantly correlated with neonatal outcomes. PMID:27648191

  8. Registration of surgical adverse outcomes: a reliability study in a university hospital

    PubMed Central

    Visser, Annelies; Gouma, Dirk J; Goslings, J Carel

    2012-01-01

    Objective Accurate registration of adverse surgical outcomes is essential to detect areas for improvement of surgical care quality. One reason for inaccurate adverse outcome registration may be the method to collect these outcomes. The authors compared the completeness of the national complication registry database (LHCR) as used in our hospital with relevant information from other available resources. Design Retrospective reliability analysis. Setting University hospital. Participants From the 3252 patients admitted to the surgical wards in 2010, the authors randomly selected a cohort of 180 cases, oversampling those with adverse outcomes. The LHCR contains adverse outcomes as reported during morning hand-offs or in discharge letters. The authors checked if the number and severity of adverse outcomes recorded in the LHCR agreed with those reported in morning hand-offs, discharge letters and medical and nursing files. Results In 135 of 180 patients, all resources could be retrieved completely. Fourteen per cent of the patients with adverse outcomes were not recorded in the LHCR. Missing adverse outcomes were all reversible without the need for (re)operation, for example, postoperative pain, delirium or urinary tract complications. Only 38% of these adverse outcomes were reported in the morning hand-offs and discharge letters but were best reported in the medical and nursing files. Conclusions Registration of surgical adverse outcomes appears largely depending on the reliability of the underlying sources. For a more complete adverse outcome registration, the authors advocate a better hand-off and additional consultation of the patient's dossier. This extra effort allows for improvement actions to eventually avoid ‘mild’ adverse outcomes patients perceive as important and undesirable. PMID:22637372

  9. Risk-Adjusted Models for Adverse Obstetric Outcomes and Variation in Risk Adjusted Outcomes Across Hospitals

    PubMed Central

    Bailit, Jennifer L.; Grobman, William A.; Rice, Madeline Murguia; Spong, Catherine Y.; Wapner, Ronald J.; Varner, Michael W.; Thorp, John M.; Leveno, Kenneth J.; Caritis, Steve N.; Shubert, Phillip J.; Tita, Alan T. N.; Saade, George; Sorokin, Yoram; Rouse, Dwight J.; Blackwell, Sean C.; Tolosa, Jorge E.; Van Dorsten, J. Peter

    2014-01-01

    Objective Regulatory bodies and insurers evaluate hospital quality using obstetrical outcomes, however meaningful comparisons should take pre-existing patient characteristics into account. Furthermore, if risk-adjusted outcomes are consistent within a hospital, fewer measures and resources would be needed to assess obstetrical quality. Our objective was to establish risk-adjusted models for five obstetric outcomes and assess hospital performance across these outcomes. Study Design A cohort study of 115,502 women and their neonates born in 25 hospitals in the United States between March 2008 and February 2011. Hospitals were ranked according to their unadjusted and risk-adjusted frequency of venous thromboembolism, postpartum hemorrhage, peripartum infection, severe perineal laceration, and a composite neonatal adverse outcome. Correlations between hospital risk-adjusted outcome frequencies were assessed. Results Venous thromboembolism occurred too infrequently (0.03%, 95% CI 0.02% – 0.04%) for meaningful assessment. Other outcomes occurred frequently enough for assessment (postpartum hemorrhage 2.29% (95% CI 2.20–2.38), peripartum infection 5.06% (95% CI 4.93–5.19), severe perineal laceration at spontaneous vaginal delivery 2.16% (95% CI 2.06–2.27), neonatal composite 2.73% (95% CI 2.63–2.84)). Although there was high concordance between unadjusted and adjusted hospital rankings, several individual hospitals had an adjusted rank that was substantially different (as much as 12 rank tiers) than their unadjusted rank. None of the correlations between hospital adjusted outcome frequencies was significant. For example, the hospital with the lowest adjusted frequency of peripartum infection had the highest adjusted frequency of severe perineal laceration. Conclusions Evaluations based on a single risk-adjusted outcome cannot be generalized to overall hospital obstetric performance. PMID:23891630

  10. Sexual Dimorphism in Adverse Pregnancy Outcomes - A Retrospective Australian Population Study 1981-2011

    PubMed Central

    Verburg, Petra E.; Tucker, Graeme; Scheil, Wendy; Erwich, Jan Jaap H. M.; Dekker, Gus A.; Roberts, Claire Trelford

    2016-01-01

    Objectives Sexual inequality starts in utero. The contribution of biological sex to the developmental origins of health and disease is increasingly recognized. The aim of this study was to assess and interpret sexual dimorphisms for three major adverse pregnancy outcomes which affect the health of the neonate, child and potentially adult. Methods Retrospective population-based study of 574,358 South Australian singleton live births during 1981–2011. The incidence of three major adverse pregnancy outcomes [preterm birth (PTB), pregnancy induced hypertensive disorders (PIHD) and gestational diabetes mellitus (GDM)] in relation to fetal sex was compared according to traditional and fetus-at-risk (FAR) approaches. Results The traditional approach showed male predominance for PTB [20–24 weeks: Relative Risk (RR) M/F 1.351, 95%-CI 1.274–1.445], spontaneous PTB [25–29 weeks: RR M/F 1.118, 95%-CI 1.044–1.197%], GDM [RR M/F 1.042, 95%-CI 1.011–1.074], overall PIHD [RR M/F 1.053, 95%-CI 1.034–1.072] and PIHD with term birth [RR M/F 1.074, 95%-CI 1.044–1.105]. The FAR approach showed that males were at increased risk for PTB [20–24 weeks: RR M/F 1.273, 95%-CI 1.087–1.490], for spontaneous PTB [25–29 weeks: RR M/F 1.269, 95%-CI 1.143–1.410] and PIHD with term birth [RR M/F 1.074, 95%-CI 1.044–1.105%]. The traditional approach demonstrated female predominance for iatrogenic PTB [25–29 weeks: RR M/F 0.857, 95%-CI 0.780–0.941] and PIHD associated with PTB [25–29 weeks: RR M/F 0.686, 95%-CI 0.581–0.811]. The FAR approach showed that females were at increased risk for PIHD with PTB [25–29 weeks: RR M/F 0.779, 95%-CI 0.648–0.937]. Conclusions This study confirms the presence of sexual dimorphisms and presents a coherent framework based on two analytical approaches to assess and interpret the sexual dimorphisms for major adverse pregnancy outcomes. The mechanisms by which these occur remain elusive, but sex differences in placental gene

  11. Adverse Outcome Pathways for Embryonic Vascular Disruption and Alternative Methods to Identify Chemical Vascular Disruptor

    EPA Science Inventory

    Chemically induced vascular toxicity during embryonic development can result in a wide range of adverse prenatal outcomes. We used information from genetic mouse models linked to phenotypic outcomes and a vascular toxicity knowledge base to construct an embryonic vascular disrupt...

  12. Fetal ovarian cysts: review of imaging spectrum, differential diagnosis, management, and outcome.

    PubMed

    Trinh, Tony W; Kennedy, Anne M

    2015-01-01

    Fetal ovarian cysts are the most common abdominal cysts observed in the female fetus but may be mistaken for genitourinary cysts, gastrointestinal cysts, lymphangiomas, or fetus in fetu. Ultrasonography (US) is the imaging modality of choice for fetal assessment, and magnetic resonance imaging is a useful problem-solving tool when uncertainty remains after careful US evaluation. At US, a fetal ovarian cyst manifests as an anechoic thin-walled cyst superior and parasagittal to the bladder. A daughter cyst may occasionally be observed and is pathognomonic for a cyst of ovarian origin. Fetal ovarian cysts may be simple or complicated and unilateral or bilateral, and they may masquerade as a solid mass when hemorrhage or torsion occurs. Complicated cysts may exhibit multiple septations, fluid-fluid levels, or mobile internal echoes. It is important to differentiate a hemorrhagic ovarian cyst from solid abdominal neoplasms that may be seen in a fetus. Recognition of the pertinent imaging findings will help radiologists distinguish fetal ovarian cysts from other fetal intra-abdominal masses in the differential diagnosis. Malignant ovarian neoplasms are rare in the fetus and neonate and thus are not considered in the differential diagnosis. The current literature on the management and outcome of fetal ovarian cysts is reviewed, with imaging studies presented from the authors' practice. Most fetal ovarian cysts resolve spontaneously; if operative intervention is required, the goal should be ovarian preservation. PMID:25763743

  13. Adverse pregnancy outcomes in relation to water contamination, Santa Clara County, California, 1980-1981

    SciTech Connect

    Deane, M.; Swan, S.H.; Harris, J.A.; Epstein, D.M.; Neutra, R.R.

    1989-05-01

    An epidemiologic study was conducted to investigate a suspected cluster of adverse outcomes of pregnancies conceived in 1980-1981 among women who resided in a census tract in Santa Clara County, California that was thought to be exposed to drinking water from a well contaminated by an organic solvent, trichloroethane. A comparison census tract that received water from a different source was selected on the basis of demographic comparability. The cluster was confirmed; the odds ratio for spontaneous abortion was 2.3 (95% confidence interval (Cl) 1.3-4.2) after adjustment by multiple logistic regression for maternal risk factors, including maternal age, alcohol consumption, smoking, and prior fetal loss. The relative risk for congenital malformations was 3.1 (95% Cl 1.1-10.4). Because of the lack of precise information on the timing and extent of contamination, the pattern of spontaneous abortion rates throughout the study period cannot be used to either support or refute a causal inference.

  14. An “ADME Module” in the Adverse Outcome Pathway Knowledgebase

    EPA Science Inventory

    The Adverse Outcome Pathway (AOP) framework has generated intense interest for its utility to organize knowledge on the toxicity mechanisms, starting from a molecular initiating event (MIE) to an adverse outcome across various levels of biological organization. While the AOP fra...

  15. Evaluation of hypothesized adverse outcome pathway linking thyroid peroxidase inhibition to fish early life stage toxicity

    EPA Science Inventory

    There is an interest in developing alternatives to the fish early-life stage (FELS) test (OECD test guideline 210), for predicting adverse outcomes (e.g., impacts on growth and survival) using less resource-intensive methods. Development and characterization of adverse outcome pa...

  16. The Association between Rural-Urban Continuum, Maternal Education and Adverse Birth Outcomes in Quebec, Canada

    ERIC Educational Resources Information Center

    Auger, Nathalie; Authier, Marie-Andree; Martinez, Jerome; Daniel, Mark

    2009-01-01

    Context: Rural relative to urban area and low socioeconomic status (SES) are associated with adverse birth outcomes. Whether a graded association of increasing magnitude is present across the urban-rural continuum, accounting for SES, is unclear. We examined the association between rural-urban continuum, SES and adverse birth outcomes. Methods:…

  17. Development of Quantitative Adverse Outcome Pathways Using Health-Protective Assumptions to Fill Data Gaps

    EPA Science Inventory

    In an adverse outcome pathway (AOP), the target site dose participates in a molecular initiating event (MIE), which in turn triggers a sequence of key events leading to an adverse outcome (AO). Quantitative AOPs (QAOP) are needed if AOP characterization is to address risk as well...

  18. Development of an adverse outcome pathway for acetylcholinesterase inhibition leading to acute mortality

    EPA Science Inventory

    Adverse outcome pathways (AOPs) are designed to describe linkages of key events (KEs) within a biological pathway that result in an adverse outcome associated with chemical perturbation of a well-defined molecular initiating event (MIE). Risk assessors have traditionally relied ...

  19. Organ-specific systemic lupus erythematosus activity during pregnancy is associated with adverse pregnancy outcomes.

    PubMed

    Tedeschi, Sara K; Guan, Hongshu; Fine, Alexander; Costenbader, Karen H; Bermas, Bonnie

    2016-07-01

    Systemic lupus erythematosus (SLE) is a disease of reproductive-age women, and thus questions regarding how disease influences pregnancy outcomes arise. We investigated whether five specific types of SLE activity during the 6 months before conception or during pregnancy (nephritis, cytopenias, skin disease, arthritis, serositis) were associated with adverse pregnancy outcomes. We performed a retrospective cohort study of pregnancy outcomes among women with SLE at the Brigham and Women's Hospital Lupus Center. Adverse pregnancy outcomes included pre-eclampsia, pre-term delivery, elective termination due to SLE, spontaneous miscarriage at weeks 12-20, and stillbirth. SLE and obstetric history, laboratories, and medications were obtained from electronic medical records. Generalized linear mixed models adjusting for potential confounders were used to identify predictors of any adverse pregnancy outcome. Most pregnancies resulted in a live term delivery (76.5 %). After adjustment for Hispanic ethnicity, prior adverse pregnancy outcome and medication use 6 months before conception, nephritis during pregnancy (odds ratio (OR) 3.6, 95 % confidence interval (CI) 1.0-12.8), cytopenias during pregnancy (OR 3.9, 95 % CI 1.3-11.4), and serositis during pregnancy (OR 5.9, 95 % CI 1.0-34.0) were significantly associated with adverse pregnancy outcome. Specific types of SLE disease activity during pregnancy were related to adverse pregnancy outcome. Nephritis, cytopenias, and serositis carried a higher risk of adverse pregnancy outcome, suggesting that these abnormalities should be carefully monitored during pregnancy. PMID:27166627

  20. Evaluation of Clinical Diagnosis of Fetal Distress and Perinatal Outcome in a Low Resource Nigerian Setting

    PubMed Central

    Ibekwe, Perpetus Chudi; Onu, Fidelis Agwu; Onwe, Ogah Emeka; Ezeonu, Thecla Chinonyelum; Omeje, Innocent

    2016-01-01

    Introduction Fetal distress has been shown to contribute to the increasing caesarean section rate. There has been controversy on the usefulness of clinical diagnosis of fetal distress using only the intermittent counting of the fetal heart rate and/or passage of meconium-stained liquor. Aim To evaluate the clinical diagnosis of fetal distress and the perinatal outcome. Materials and Methods This was a retrospective study in which the case records of the patients, who were diagnosed of fetal distress at Federal Teaching Hospital, Abakaliki, Nigeria, from January 1, 2008 to December 31, 2014, were collated. The statistical analysis was done using the Statistical Package for Social Sciences version 17 software (SPSS Inc., Chicago IL, USA). Results Out of the 15,640 deliveries carried out within the study period, 3,761 (24.05%) deliveries were through caesarean section. A total of 326 (8.9%) of the 3,761 caesarean sections were due to fetal distress within the study period. More so, a total of 227 (70.9%) babies were born with ≥ 7 Apgar score at the 1st minute of delivery. The perinatal mortality rate was 31.25 per 1000 deliveries. Though birth asphyxia was recorded more on babies of mothers that had fresh meconium-stained liquor and whose decision-intervention interval was more than 30 minutes when compared with those without any of the two conditions, there was no statistical significant difference between them. Conclusion The clinical diagnosis of fetal distress is accurate in 29.1% of the cases. However, it has led to an unnecessary caesarean section in the remaining 70.9% of the parturients. In order to reduce this high trend of unnecessary caesarean sections due to clinical diagnosis of fetal distress in this environment, antepartum fetal assessment with non-stress test or biophysical profile and intrapartum use of continuous electronic fetal monitoring should be used to confirm or refute the fetal distress before any surgical intervention. Fetal blood sampling

  1. [Maternal and fetal outcome in Mexican women with rheumatoid arthritis].

    PubMed

    Saavedra, Miguel A; Sánchez, Antonio; Bustamante, Reyna; Miranda-Hernández, Dafhne; Soliz-Antezana, Jimena; Cruz-Domínguez, Pilar; Morales, Sara; Jara, Luis J

    2015-01-01

    Objetivo: reportar la experiencia en el desenlace materno-fetal de mujeres con artritis reumatoide en un centro médico nacional de referencia.Métodos: se realizó un análisis retrospectivo de los expedientes de mujeres embarazadas con artritis reumatoide que fueron atendidas en una clínica de embarazo y enfermedades reumáticas autoinmunes. Se estudió el desenlace materno-fetal considerado como: actividad de la enfermedad, preeclampsia/eclampsia, tasa de nacidos vivos, abortos, óbitos, parto pretérmino, semanas de gestación, peso al nacer, malformaciones congénitas y uso de fármacos antirreumáticos.Resultados: se incluyeron 73 embarazos en 72 pacientes. Se documentó actividad de la enfermedad en el 47.2 % de las pacientes durante el embarazo y/o posparto. El 87.7 % de las pacientes recibió algún fármaco antirreumático. Se desarrolló preeclampsia en el 8.2 % de los casos. La tasa de nacidos vivos fue de 98.6 %, con parto pretérmino en el 15.9 % y bajo peso a término en el 17.6 % de los casos. El 77.1 % de los productos nació vía cesárea. La actividad de la enfermedad no se asoció a un mayor porcentaje de complicaciones materno-fetales.Conclusiones: nuestro estudio mostró que la mayoría de las pacientes no experimenta actividad significativa de la AR durante el embarazo, el desenlace fetal es satisfactorio y la actividad de la enfermedad no influye de manera importante el desenlace obstétrico.

  2. Adverse Birth Outcomes and Maternal Exposure to Trichloroethylene and Tetrachloroethylene through Soil Vapor Intrusion in New York State

    PubMed Central

    Lewis-Michl, Elizabeth L.; Gomez, Marta I.

    2011-01-01

    Background: Industrial spills of volatile organic compounds (VOCs) in Endicott, New York (USA), have led to contamination of groundwater, soil, and soil gas. Previous studies have reported an increase in adverse birth outcomes among women exposed to VOCs in drinking water. Objective: We investigated the prevalence of adverse birth outcomes among mothers exposed to trichloroethylene (TCE) and tetrachloroethylene [or perchloroethylene (PCE)] in indoor air contaminated through soil vapor intrusion. Methods: We examined low birth weight (LBW), preterm birth, fetal growth restriction, and birth defects among births to women in Endicott who were exposed to VOCs, compared with births statewide. We used Poisson regression to analyze births and malformations to estimate the association between maternal exposure to VOCs adjusting for sex, mother’s age, race, education, parity, and prenatal care. Two exposure areas were identified based on environmental sampling data: one area was primarily contaminated with TCE, and the other with PCE. Results: In the TCE-contaminated area, adjusted rate ratios (RRs) were significantly elevated for LBW [RR = 1.36; 95% confidence interval (CI): 1.07, 1.73; n = 76], small for gestational age (RR = 1.23; 95% CI: 1.03, 1.48; n = 117), term LBW (RR = 1.68; 95% CI: 1.20, 2.34; n = 37), cardiac defects (RR = 2.15; 95% CI: 1.27, 3.62; n = 15), and conotruncal defects (RR = 4.91; 95% CI: 1.58, 15.24; n = 3). In the PCE-contaminated area, RRs for cardiac defects (five births) were elevated but not significantly. Residual socioeconomic confounding may have contributed to elevations of LBW outcomes. Conclusions: Maternal residence in both areas was associated with cardiac defects. Residence in the TCE area, but not the PCE area, was associated with LBW and fetal growth restriction. PMID:22142966

  3. Adverse outcome pathways (AOPs): A framework to support predictive toxicology

    EPA Science Inventory

    High throughput and in silico methods are providing the regulatory toxicology community with capacity to rapidly and cost effectively generate data concerning a chemical’s ability to initiate one or more biological perturbations that may culminate in an adverse ecological o...

  4. Interventions designed to prevent adverse programming outcomes resulting from exposure to maternal obesity during development

    PubMed Central

    Nathanielsz, PW; Ford, SP; Long, NM; Vega, CC; Reyes-Castro, LA; Zambrano, E

    2013-01-01

    Maternal obesity is a global epidemic affecting the developed and developing world. Human and animal studies indicate that maternal obesity programs development predisposing offspring to later-life chronic diseases. Several mechanisms act together to produce these adverse health problems. There is a need for effective interventions that prevent these outcomes and guide management in human pregnancy. We report here dietary and exercise intervention studies in both altricial and precocial species, rats and sheep, designed to prevent adverse offspring outcomes. Both interventions present exciting opportunities to at least in part prevent adverse metabolic and other outcomes in mother and offspring. PMID:24147928

  5. Fetal volume measurements with three dimensional ultrasound in the first trimester of pregnancy, related to pregnancy outcome, a prospective cohort study

    PubMed Central

    2012-01-01

    Background First trimester growth restriction is associated with an increased risk of adverse birth outcomes (preterm birth, low birth weight and small for gestational age at birth). The differences between normal and abnormal growth in early pregnancy are small if the fetal size is measured by the crown-rump-length. Three-dimensional ultrasound volume measurements might give more information about fetal development than two-dimensional ultrasound measurements. Detection of the fetus with a small fetal volume might result in earlier detection of high risk pregnancies and a better selection of high risk pregnancies. Methods A prospective cohort study, performed at the Máxima Medical Centre, in Eindhoven-Veldhoven, the Netherlands. During the routine first trimester scan with nuchal translucency measurement 500 fetal volumes will be obtained. The gestational age is based on the first day of the last menstrual period in a regular menstrual cycle and by the crown-rump-length. The acquired datasets are collected and stored on a hard disk for offline processing and volume calculation. The investigator who performs the volume measurements is blinded for the results of the first trimester scan. The manual mode will be used to outline the Region Of Interest, the fetal head and rump, in all cross sections. The fetal volumes are calculated with a rotational step of 9°. First, the relation between fetal volume and gestational age, for a set of participants with normal pregnancies (training set), will be assessed. This model will then be used to determine expected values of fetal volume for a normal pregnancy, which will be referred to as expected normal values. Secondly, for a new set of participants with normal pregnancies and a set of participants with complicated pregnancies (together defined as validation set), the observed fetal volumes (FVobserved) are compared with their expected normal values (FVexpected) and expressed as a percentage of the expected normal value

  6. The effects of prenatal cannabis exposure on fetal development and pregnancy outcomes: a protocol

    PubMed Central

    Gunn, Jayleen K L; Rosales, Cecilia B; Center, Katherine E; Nuñez, Annabelle V; Gibson, Steven J; Ehiri, John E

    2015-01-01

    Introduction The effects of exposure to marijuana in utero on fetal development are not clear. Given that the recent legislation on cannabis in the US is likely to result in increased use, there is a need to assess the effects of prenatal cannabis exposure on fetal development and pregnancy outcomes. The objective of this review is to assess the effects of prenatal exposure to cannabis on pregnancy outcomes (including maternal and child outcomes). Methods and analyses Major databases will be searched from inception to the latest issue, with the aim of identifying studies that reported the effects of prenatal exposure to cannabis on fetal development and pregnancy outcomes. Two investigators will independently review all titles and abstracts to identify potential articles. Discrepancies will be resolved by repeated review, discussion and consensus. Study quality assessment will be undertaken, using standard protocols. To qualify for inclusion, studies must report at least one maternal or neonatal outcome post partum. Cross-sectional, case–control, cohort and randomised controlled trials published in English will be included. In order to rule out the effects of other drugs that may affect fetal development and pregnancy outcomes, studies will only be included if they report outcomes of prenatal exposure to cannabis while excluding other illicit substances. Data from eligible studies will be extracted, and data analysis will include a systematic review and critical appraisal of evidence, and meta-analysis if data permit. Meta-analysis will be conducted if three or more studies report comparable statistics on the same outcome. Ethics and dissemination The review which will result from this protocol has not already been conducted. Preparation of the review will follow the procedures stated in this protocol, and will adhere to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Ethical approval of data will not be required since

  7. Overview of an internationally-harmonized program for adverse outcome pathway development

    EPA Science Inventory

    Adverse outcome pathways (AOPs) are critical frameworks for organizing knowledge concerning the scientifically-credible predictive linkages between toxicological observations made at molecular and cellular levels (e.g., via molecular screening assays, biomarker responses, or chem...

  8. Adverse outcome pathways linked to population models as a methodology for investigating effects of chemical stressors

    EPA Science Inventory

    In addressing the complexity and toxicity of chemical contaminants in Great Lakes ecosystems, we describe an approach to link chemically induced alterations in molecular and biochemical endpoints to adverse outcomes in whole organisms and populations. Analysis of population impac...

  9. Establishing Adverse Outcome Pathways of Thyroid Hormone Disruption in an Amphibian Model

    EPA Science Inventory

    The Adverse Outcome Pathway (AOP) provides a framework for understanding the relevance of toxicology data in ecotoxicological hazard assessments. The AOP concept can be applied to many toxicological pathways including thyroid hormone disruption. Thyroid hormones play a critical r...

  10. Development & Use of Adverse Outcome Pathways for 21st Century Decision Support

    EPA Science Inventory

    The Adverse Outcome Pathway has emerged as an internationally harmonized mechanism for organizing biological information in a chemical agnostic manner. This construct is valuable for interpreting the results from high-throughput toxicity (HTT) assessment by providing a mechanisti...

  11. Experimental Approaches to Systematic Discovery and Development of Reproductive Adverse Outcome Pathways in Fish

    EPA Science Inventory

    Adverse outcome pathways (AOPs) are conceptual frameworks that portray causal and predictive linkages between key events at multiple scales of biological organization that connect molecular initiating events and early cellular perturbations (e.g., initiation of toxicity pathways)...

  12. VIOLENT CRIME EXPOSURE CLASSIFICATION AND ADVERSE BIRTH OUTCOMES: A GEOGRAPHICALLY-DEFINED COHORT STUDY

    EPA Science Inventory

    Background

    Area-level socioeconomic disparities have long been associated with adverse pregnancy outcomes. Crime is an important element of the neighborhood environment inadequately investigated in the public health literature. Using geocoded linked birth, crime and cens...

  13. Adverse Outcome Pathways and Extrapolation Tools to Advance the Three Rs in Ecotoxicology

    EPA Science Inventory

    Adverse outcome pathways (AOPs) are conceptual frameworks for identifying and organizing predictive and causal linkages between cellular-level responses and endpoints conventionally considered in ecological risk assessment (e.g., effects on survival, growth/development, and repro...

  14. Severe and Progressive Fetal Ventriculomegaly Leading to the Diagnosis of Periventricular Nodular Heterotopias with Good Outcome.

    PubMed

    Fluss, Joel; Pellegrinelli, Jean-Marie; Fokstuen, Siv; Moutard, Marie-Laure; Garel, Catherine; Bahi-Buisson, Nadia; Bilieux, Marie-Hélène; Hanquinet, Sylviane

    2016-01-01

    Severe fetal ventriculomegaly is generally associated with poor prognosis in terms of survival and neurodevelopment outcome. As such, many parents opt to terminate the pregnancy independently of a known etiology. We report here the case of a female fetus with severe progressive ventriculomegaly due to the unexpected presence of bilateral nodular periventricular heterotopias visualized on MRI of a fetal brain. Reaching a structural diagnosis was perceived as a relief for the parents and the pregnancy was continued. Neurodevelopment assessment at 3 years of age is normal with no epilepsy. PMID:26569159

  15. In utero fetal urine analysis and renal histology correlate with the outcome in fetal obstructive uropathies.

    PubMed

    Qureshi, F; Jacques, S M; Seifman, B; Quintero, R; Evans, M I; Smith, C; Johnson, M P

    1996-01-01

    We evaluated 8 second-trimester fetuses who had undergone termination because of obstructive uropathies and correlated the renal histopathology with fetal urine biochemical prognostic parameters. Prenatal evaluation included serial vesicocentesis, karyotyping, and sonography. According to the urinary biochemical parameters, 3 fetuses were classified to be in the good prognostic category, 2 in the borderline prognostic category, and 3 in the poor prognostic category. The kidneys were evaluated both grossly and microscopically for hydronephrosis, pelvicaliceal dilatation, cystic changes and fibrosis. Fetuses in the poor prognostic category had severely damaged renal architecture, microcysts, macrocysts, and extensive fibrosis. Fetuses in the good prognostic category had minimal histopathologic changes with preservation of the architecture. Fetuses in the borderline category showed a moderate degree of renal damage but with focally preserved architecture. We conclude (1) that there is a direct correlation between elevation in urinary electrolytes and proteins and extent of underlying renal histopathological damage and (2) that appropriate detailed prenatal evaluation of the renal function can identify fetuses who could potentially benefit from in utero therapy.

  16. Candida Virulence Properties and Adverse Clinical Outcomes in Neonatal Candidiasis

    PubMed Central

    Bliss, Joseph M.; Wong, Angela Y.; Bhak, Grace; Laforce-Nesbitt, Sonia S.; Taylor, Sarah; Tan, Sylvia; Stoll, Barbara J.; Higgins, Rosemary D.; Shankaran, Seetha; Benjamin, Daniel K.

    2012-01-01

    Objective To determine if premature infants with invasive Candida infection caused by strains with increased virulence properties have worse clinical outcomes than those infected with less virulent strains. Study design Clinical isolates were studied from 2 populations; premature infants colonized with Candida (commensal, n=27), and those with invasive candidiasis (n=81). Individual isolates of C. albicans and C. parapsilosis were tested for virulence in each of 3 assays: phenotypic switching, adhesion, and cytotoxicity. Invasive isolates were considered to have enhanced virulence if they measured more than 1 SD above the mean for the commensal isolates in at least 1 assay. Outcomes of patients with invasive isolates with enhanced virulence were compared with those with invasive isolates lacking enhanced virulence characteristics. Results 61% of invasive isolates of C. albicans and 42% of invasive isolates of C. parapsilosis had enhanced virulence. All C. albicans cerebrospinal fluid (CSF) isolates (n=6) and 90% of urine isolates (n=10) had enhanced virulence, compared with 48% of blood isolates (n=40). Infants with more virulent isolates were younger at the time of positive culture and had higher serum creatinine. Conclusions Individual isolates of Candida species vary in their virulence properties. Strains with higher virulence are associated with certain clinical outcomes. PMID:22504098

  17. Impact of fetal and neonatal viral (and parasitic) infections on later development and disease outcome.

    PubMed

    Maldonado, Yvonne A

    2008-01-01

    It is estimated that there are 4 million neonatal deaths and an equal number of stillbirths annually, the majority in the developing world. Neonatal deaths account for one third of deaths in children less than 5 years of age, and at least one third of neonatal deaths are related to infections. Infections also account for 80% of deaths in the postneonatal period through 5 years of age. There are several viral and parasitic infections which produce fetal and neonatal morbidity and mortality. Neonatal infections occur during one or more perinatal periods: in utero (congenital), intrapartum (during labor and delivery), and early or late postpartum. Here the term perinatal refers to all of these stages of fetal or neonatal infections. The mechanisms of perinatal viral and parasitic infections vary depending on the specific pathogen, however, all begin with maternal infection. Following maternal infection, organisms may produce indirect placental infection with or without fetal infection, direct fetal or neonatal infection, or primary maternal infection and subsequent perinatal sequelae without either placental or fetal infection. Some pathogens may produce infections by more than one mechanism. This brief report will provide an overview of the pathogenesis, general outcomes, and known pathogens associated with perinatal viral and parasitic infections. PMID:18196955

  18. Impact of fetal and neonatal viral (and parasitic) infections on later development and disease outcome.

    PubMed

    Maldonado, Yvonne A

    2008-01-01

    It is estimated that there are 4 million neonatal deaths and an equal number of stillbirths annually, the majority in the developing world. Neonatal deaths account for one third of deaths in children less than 5 years of age, and at least one third of neonatal deaths are related to infections. Infections also account for 80% of deaths in the postneonatal period through 5 years of age. There are several viral and parasitic infections which produce fetal and neonatal morbidity and mortality. Neonatal infections occur during one or more perinatal periods: in utero (congenital), intrapartum (during labor and delivery), and early or late postpartum. Here the term perinatal refers to all of these stages of fetal or neonatal infections. The mechanisms of perinatal viral and parasitic infections vary depending on the specific pathogen, however, all begin with maternal infection. Following maternal infection, organisms may produce indirect placental infection with or without fetal infection, direct fetal or neonatal infection, or primary maternal infection and subsequent perinatal sequelae without either placental or fetal infection. Some pathogens may produce infections by more than one mechanism. This brief report will provide an overview of the pathogenesis, general outcomes, and known pathogens associated with perinatal viral and parasitic infections.

  19. Fetal intestinal perforation and meconium peritonitis associated with maternal autoimmune hepatitis.

    PubMed

    Charlagorla, P; Sublett, S; Sy, F; Kessler, E; Gad, A

    2014-01-01

    Autoimmune hepatitis (AIH) in pregnancy can affect both fetal and maternal outcomes. Little is known regarding the fetal outcomes of AIH in pregnancy. The major risks include spontaneous abortions, fetal mortality, perinatal mortality and prematurity. Two common drugs used in the management of AIH, azathioprine and prednisone, may also be associated with adverse fetal outcomes. We present the case of perinatal focal intestinal perforation with a meconium pseudocyst in a preterm infant of a mother with autoimmune hepatitis on azathioprine and methylprednisone.

  20. Attention-deficit/hyperactivity disorder and adverse health outcomes

    PubMed Central

    Nigg, Joel

    2015-01-01

    Attention-deficit/hyperactivity disorder (ADHD) is defined by extreme levels of inattention–disorganization and/or hyperactivity–impulsivity. In DSM-IV, the diagnostic criteria required impairment in social, academic, or occupational functioning. With DSM-5 publication imminent in 2013, further evaluation of impairment in ADHD is timely. This article reviews the current state of knowledge on health-related impairments of ADHD, including smoking, drug abuse, accidental injury, sleep, obesity, hypertension, diabetes, and suicidal behavior. It concludes by suggesting the need for new avenues of research on mechanisms of association and the potential for ADHD to be an early warning sign for secondary prevention of some poor health outcomes. PMID:23298633

  1. Use of Adverse Outcome Pathways for Assessing Effects of the Fungicide Propiconazole on Fish Reproduction

    EPA Science Inventory

    Adverse outcome pathways (AOP) are used to describe the linkage of biological events from a molecular initiating point, to individual-level-endpoints relevant to risk assessment. This study was done to assess toxicity outcomes for the conazole fungicide propiconazole based on a p...

  2. Theoretical Framework to Extend Adverse Outcome Pathways to Include Pharmacokinetic Considerations

    EPA Science Inventory

    Adverse Outcome Pathways (AOPs) have generated intense interest for their utility in linking known population outcomes to a molecular initiating event (MIE) that can be quantified using in vitro methods. While there are tens of thousands of chemicals in commercial use, biology h...

  3. Cortisol Reactivity to Social Stress as a Mediator of Early Adversity on Risk and Adaptive Outcomes

    ERIC Educational Resources Information Center

    Conradt, Elisabeth; Abar, Beau; Lester, Barry M.; LaGasse, Linda L.; Shankaran, Seetha; Bada, Henrietta; Bauer, Charles R.; Whitaker, Toni M.; Hammond, Jane A.

    2014-01-01

    Children chronically exposed to stress early in life are at increased risk for maladaptive outcomes, though the physiological mechanisms driving these effects are unknown. Cortisol reactivity was tested as a mediator of the relation between prenatal substance exposure and/or early adversity on adaptive and maladaptive outcomes. Data were drawn…

  4. Vaginal Fluid Inflammatory Biomarkers and the Risk of Adverse Neonatal Outcomes in Women with PPROM.

    PubMed

    Dorfeuille, Nydia; Morin, Valérie; Tétu, Amélie; Demers, Suzanne; Laforest, Geneviève; Gouin, Katy; Piedboeuf, Bruno; Bujold, Emmanuel

    2016-08-01

    Objective The purpose of this study was to evaluate the predictive value of vaginal fluid biomarkers for chorioamnionitis and adverse perinatal outcomes in women with preterm premature rupture of membranes (PPROM). Methods We recruited women with PPROM, without clinical chorioamnionitis, between 22 and 36 weeks' gestation. Vaginal fluid was collected on admission for the measurement of metalloproteinase-8 (MMP-8), interleukin-6 (IL-6), lactate, and glucose concentration. Placental pathology and neonatal charts were reviewed. Primary outcomes were histological chorioamnionitis and adverse neonatal neurological outcomes (intraventricular hemorrhage grade 2 or 3, periventricular leukomalacia, or hypoxic/ischemic encephalopathy). Linear regression analyses were used to adjust for gestational age at PPROM. Results Twenty-seven women were recruited at a mean gestational age of 31.6 ± 3.1 weeks, including 25 (93%) with successful collection of vaginal fluid sample. Histological chorioamnionitis and adverse neonatal neurological outcomes were observed in nine (33%) and four (15%) cases, respectively. In univariate analysis, MMP-8, IL-6, glucose, and lactate concentrations in vaginal fluid were associated with the risk of chorioamnionitis but not anymore after adjustment for gestational age at PPROM. MMP-8 concentration was the only biomarker associated with adverse neurological outcome, and it remained significant after adjustment for gestational age at PPROM (p = 0.02). Conclusion Vaginal fluid inflammatory biomarkers at admission for PPROM could predict adverse perinatal outcomes. PMID:27120475

  5. HBsAg positivity during pregnancy and adverse maternal outcomes: a retrospective cohort analysis.

    PubMed

    Tan, J; Liu, X; Mao, X; Yu, J; Chen, M; Li, Y; Sun, X

    2016-10-01

    Hepatitis B virus infection characterized by HBsAg positivity during pregnancy is a well-recognized issue in developing countries, but the association between HBsAg positivity and adverse maternal outcomes remains uncertain. To examine the association between HBsAg positivity during pregnancy and adverse maternal outcomes, a retrospective cohort study was conducted in Sichuan province, China. Deliveries were recorded from six hospitals between 1 January 2009 and 31 December 2010. Pre-eclampsia, gestational diabetes mellitus (GDM), postpartum haemorrhage (PPH), intrahepatic cholestasis, Caesarean section and placenta previa were prespecified adverse maternal outcomes. We used two multivariate logistic regression models to assess the association between HBsAg positivity and adverse maternal outcomes. In total, 948 (4.2%) pregnant women were HBsAg positive from 22 374 deliveries. Pregnant women with positive HBsAg had higher risk of GDM (aOR1.41, 95%CI 1.15-1.74), PPH (1.44, 1.13-1.83), intrahepatic cholestasis (1.74, 1.40-2.16) and Caesarean section (1.24, 1.06-1.45). No statistical associations were found between HBsAg positivity and pre-eclampsia (1.36, 0.94-1.97), and placenta previa (1.21, 0.87-1.67). HBsAg positivity during pregnancy was associated with higher risk of multiple adverse maternal outcomes. Although the causality has yet to be established, efforts may be warranted in routine care, particularly in those with high risk for adverse maternal outcomes, given the volume population infected with HBsAg. Future studies are needed to establish causality and examine the impact of HBeAg on the adverse outcomes. PMID:27167604

  6. Maternal smokeless tobacco use and adverse pregnancy outcome.

    PubMed

    Hossain, M M; Rahman, M E; Khan, T H

    2014-01-01

    This study was conducted to determine the association between prolonged smokeless tobacco (ST) use for more than 5 years by mothers and pregnancy outcome. It was a retrospective cohort study done on department of paediatrics and department of gynecology & obstetrics, Dhaka Medical College Hospital, Dhaka from January 2009 to December 2010. A total of 340 mother-neonate pairs were included in the study. A total of 170 mothers using smokeless tobacco for more than 5 years and their recently delivered newborn infants (mother-neonate pair) were enrolled as cases and 170 mother-neonate pairs without history of taking ST as controls. Frequency of spontaneous abortion, stillbirth, preterm delivery and LBW baby in case & control groups was assessed. Smokeless tobacco used by mothers for >5 years had significant association with spontaneous abortion (p<0.01), stillbirth (p<0.01), preterm delivery (p<0.001) & LBW baby (p<0.001) and carries a risk of having spontaneous abortion, stillbirth, preterm delivery & LBW 2.2 times, 2.1 times, 2.9 times & 3.3 times respectively more than non users of smokeless tobacco. It can be concluded that prolonged use of smokeless tobacco for more than 5 years is significantly associated with spontaneous abortion, stillbirth, preterm delivery and LBW baby.

  7. Pre-eclampsia has an adverse impact on maternal and fetal health.

    PubMed

    Lin, Saunders; Leonard, Dean; Co, Mary A M; Mukhopadhyay, Dhriti; Giri, Badri; Perger, Lena; Beeram, Madhava R; Kuehl, Thomas J; Uddin, Mohammad N

    2015-04-01

    Pre-eclampsia (preE) is a multifaceted complication found uniquely in the pregnant patient and one that has puzzled scientists for years. PreE is not a single disorder, but a complex syndrome that is produced by various pathophysiological triggers and mechanisms affecting about 5% of obstetrical patients. PreE is a major cause of premature delivery and maternal and fetal morbidity and mortality. PreE is characterized by de novo development of hypertension and proteinuria after 20 weeks of gestation and affects nearly every organ system, with the most severe consequences being eclampsia, pulmonary edema, intrauterine growth restriction, and thrombocytopenia. PreE alters the intrauterine environment by modulating the pattern of hormonal signals and activating the detrimental cellular signaling that has been transported to the fetus. The fetus has to adapt to this intrauterine environment with detrimental signals. The adaptive changes increase the risk of disease later in life. This review defines the predisposition and causes of preE and the cellular signaling detrimental to maternal health during preE. Moreover, the risk factors for diseases that are transmitted to the offspring have been addressed in this review. The detrimental signaling molecules that have been overexpressed in preE patients raises the possibility that those signals could be therapeutically blocked one day. PMID:25468481

  8. The relationship of maternal and fetal toxicity in developmental toxicology bioassays with notes on the biological significance of the "no observed adverse effect level".

    EPA Science Inventory

    Standard developmental toxicology bioassays are designed to identify agents with the potential to induce adverse effects and include dose levels that induce maternal toxicity. The work reported here was undertaken to evaluate the relationship of maternal and fetal toxicity. It co...

  9. A "cure" for preeclampsia: Improving neonatal outcomes by overcoming excess fetal placental vascular resistance.

    PubMed

    Byrne, T J

    2015-09-01

    From a broad perspective there are only three arterial systems that respond to relative hypoxia with vasoconstriction. They are the placental, the pulmonic and the renal vascular beds. The renal system's adaptation to hypoxia is markedly different from the other two circulatory beds and will not be further considered here. Regional vasoconstriction is adaptive in the placenta and lung because it redirects red blood cells from areas of relative hypoxia to more oxygenated areas thereby maximizing oxygen uptake for a given cardiac output. The fetal placental and pulmonary vascular systems are unique because their smooth muscle cells have a unique and possibly identical potassium channel that responds to hypoxia by closing, thereby depolarizing the cell membrane allowing calcium ion influx and muscle contraction. It may be that a variety of initial causes of temporary or local placental hypoxia initiate a cascade of first fetal placental then maternal vasoconstriction and endothelial activation leading to the clinical syndrome we call preeclampsia. The response cascades seen in preeclampsia, which for purposes of this article I will abbreviate as (PECL), after development of widespread vasoconstriction, will also be seen to be identical or at least parallel in pulmonary hypertension (PAH). This means that some or all of the pharmacotherapies presently used, tested or considered in early PAH may also have a therapeutic effect in PECL by reducing fetal placental arterial resistance thereby increasing fetal placental flow. This would allow increased oxygen and other nutrient uptake and possibly increased fetal cardiac output in the face of reduced fetal cardiac work. This may allow a delay in delivery in which fetuses grow and are better oxygenated in preterm PECL, improving neonatal outcomes. PMID:26105573

  10. Neurobehavioural outcomes of children with fetal alcohol spectrum disorders: A Canadian perspective

    PubMed Central

    Rasmussen, Carmen; Andrew, Gail; Zwaigenbaum, Lonnie; Tough, Suzanne

    2008-01-01

    Fetal alcohol spectrum disorder (FASD) is one of the most common preventable causes of developmental disability and is currently one of the most pressing public health concerns in Canada. FASD refers to the range of physical, mental, behavioural and learning disabilities that an individual may acquire as a result of maternal alcohol consumption. Prenatal exposure to alcohol leads to numerous primary and secondary disabilities in affected children, which can result in poor long-term outcomes. The present paper reviews previous research on the neurobehavioural outcomes of children with FASD, particularly in terms of behavioural, mental health and adaptive outcomes. The role of risk and protective factors on these outcomes and the impact of FASD on the family are also examined. Finally, future directions and implications regarding outcomes research among children with FASD, particularly within a Canadian context, are discussed. PMID:19252695

  11. Prenatal diagnosis of a placental infarction hematoma associated with fetal growth restriction, preeclampsia and fetal death: clinicopathological correlation.

    PubMed

    Aurioles-Garibay, Alma; Hernandez-Andrade, Edgar; Romero, Roberto; Qureshi, Faisal; Ahn, Hyunyoung; Jacques, Suzanne M; Garcia, Maynor; Yeo, Lami; Hassan, Sonia S

    2014-01-01

    The lesion termed 'placental infarction hematoma' is associated with fetal death and adverse perinatal outcome. Such a lesion has been associated with a high risk of fetal death and abruption placentae. The fetal and placental hemodynamic changes associated with placental infarction hematoma have not been reported. This paper describes a case of early and severe growth restriction with preeclampsia, and progressive deterioration of the fetal and placental Doppler parameters in the presence of a placental infarction hematoma.

  12. Diet around conception and during pregnancy--effects on fetal and neonatal outcomes.

    PubMed

    Kind, Karen L; Moore, Vivienne M; Davies, Michael J

    2006-05-01

    Substrate supply to the fetus is a major regulator of prenatal growth. Maternal nutrition influences the availability of nutrients for transfer to the fetus. Animal experiments demonstrate that restriction of maternal protein or energy intake can retard fetal growth. Effects of maternal nutrition vary with the type and timing of the restriction and the species studied. Maternal undernutrition before conception and/or in early pregnancy can alter fetal physiology in late gestation, and influence postnatal function, often without measurable effects on birth size. In contrast, to date, observational and intervention studies in humans provide limited support for a major role of maternal nutrition in determining birth size, except where women are quite malnourished. However, recent studies report associations between newborn size and the balance of macronutrients in women's diets in Western settings. Associations between maternal dietary composition and adult blood pressure of the offspring are also reported in human populations. Most studies in women have focused on dietary content or supplementation during mid-late pregnancy. Further investigation of how maternal dietary composition, before conception and throughout pregnancy, affects fetal physiology and health of the baby will increase the understanding of how maternal diet and nutritional status influence fetal, neonatal and longer-term outcomes.

  13. Associations of prenatal exposure to five chlorophenols with adverse birth outcomes.

    PubMed

    Guo, Jianqiu; Wu, Chunhua; Lv, Shenliang; Lu, Dasheng; Feng, Chao; Qi, Xiaojuan; Liang, Weijiu; Chang, Xiuli; Xu, Hao; Wang, Guoquan; Zhou, Zhijun

    2016-07-01

    Exposures to chlorophenols (CPs) have been linked with adverse health effects on wildlife and humans. This study aimed to evaluate prenatal exposure to five CP compounds using maternal urinary concentrations during pregnancy and the potential associations with birth outcomes of their infants at birth. A total of 1100 mother-newborn pairs were recruited during June 2009 to January 2010 in an agricultural region, China. Urinary concentrations of five CPs from dichlorophenol (DCP) to pentachlorophenol (PCP), namely, 2,5-DCP, 2,4-DCP, 2,4,5-trichlorophenol (2,4,5-TCP), 2,4,6-TCP and PCP, were measured using large-volume-injection gas chromatography-tandem mass spectrometry (LVI-GC-MS-MS), and associations between CP levels and weight, length as well as head circumference at birth were examined. Median urinary creatinine-adjusted concentrations of 2,5-DCP, 2,4-DCP, 2,4,5-TCP, 2,4,6-TCP and PCP were 3.34 μg/g, 1.03 μg/g, < LOD, 1.78 μg/g and 0.39 μg/g creatinine, respectively. We found lower birth weight 30 g [95% confidence interval (CI): -57, -3; p = 0.03] for per SD increase in log10-transformed concentrations of 2,4,6-TCP and lower birth weight 37 g (95% CI: -64, -10; p = 0.04) for PCP, respectively. Similarly, head circumference decrease in associations with creatinine-corrected 2,4,6-TCP and PCP concentrations were also achieved. Considering sex difference, the associations of lower birth weight were only found among male neonates, while head circumference was associated with 2,4-DCP and 2,5-DCP only found among female neonates. This study showed significant negative associations between CPs exposure and reduction in neonatal anthropometric measures. The biological mechanisms concerning CPs exposure on fetal growth deserved further investigations. PMID:27131805

  14. Associations of prenatal exposure to five chlorophenols with adverse birth outcomes.

    PubMed

    Guo, Jianqiu; Wu, Chunhua; Lv, Shenliang; Lu, Dasheng; Feng, Chao; Qi, Xiaojuan; Liang, Weijiu; Chang, Xiuli; Xu, Hao; Wang, Guoquan; Zhou, Zhijun

    2016-07-01

    Exposures to chlorophenols (CPs) have been linked with adverse health effects on wildlife and humans. This study aimed to evaluate prenatal exposure to five CP compounds using maternal urinary concentrations during pregnancy and the potential associations with birth outcomes of their infants at birth. A total of 1100 mother-newborn pairs were recruited during June 2009 to January 2010 in an agricultural region, China. Urinary concentrations of five CPs from dichlorophenol (DCP) to pentachlorophenol (PCP), namely, 2,5-DCP, 2,4-DCP, 2,4,5-trichlorophenol (2,4,5-TCP), 2,4,6-TCP and PCP, were measured using large-volume-injection gas chromatography-tandem mass spectrometry (LVI-GC-MS-MS), and associations between CP levels and weight, length as well as head circumference at birth were examined. Median urinary creatinine-adjusted concentrations of 2,5-DCP, 2,4-DCP, 2,4,5-TCP, 2,4,6-TCP and PCP were 3.34 μg/g, 1.03 μg/g, < LOD, 1.78 μg/g and 0.39 μg/g creatinine, respectively. We found lower birth weight 30 g [95% confidence interval (CI): -57, -3; p = 0.03] for per SD increase in log10-transformed concentrations of 2,4,6-TCP and lower birth weight 37 g (95% CI: -64, -10; p = 0.04) for PCP, respectively. Similarly, head circumference decrease in associations with creatinine-corrected 2,4,6-TCP and PCP concentrations were also achieved. Considering sex difference, the associations of lower birth weight were only found among male neonates, while head circumference was associated with 2,4-DCP and 2,5-DCP only found among female neonates. This study showed significant negative associations between CPs exposure and reduction in neonatal anthropometric measures. The biological mechanisms concerning CPs exposure on fetal growth deserved further investigations.

  15. Emergency Department Discharge Diagnosis and Adverse Health Outcomes in Older Adults

    PubMed Central

    Hastings, S. Nicole; Whitson, Heather E.; Purser, Jama L.; Sloane, Richard J.; Johnson, Kimberly S.

    2010-01-01

    Objectives To determine the relationship between the reason for an emergency department (ED) visit and subsequent risk of adverse health outcomes in older adults discharged from the ED. Design Secondary analysis of data from the Medicare Current Beneficiary Survey. Setting ED. Participants One thousand eight hundred fifty-one community-dwelling Medicare fee-for-service enrollees aged 65 and older discharged from the ED between January 2000 and September 2002. Measurements Independent variables were ED discharge diagnosis groups: injury or musculoskeletal (MSK) (e.g., fracture, open wound), chronic condition (e.g., chronic obstructive pulmonary disorder, heart failure), infection, non-MSK symptom (e.g., chest pain, abdominal pain), and unclassified. Adverse health outcomes were hospitalization or death within 30 days of the index ED visit. Results Injury or MSK was the largest ED diagnosis group (31.4%), followed by non-MSK symptom (22.2%), chronic condition (20.9%), and infection (7.8%); 338 (17.8%) had ED discharge diagnoses that were unclassified. In adjusted analyses, a discharge diagnosis of injury or MSK condition was associated with lower risk of subsequent adverse health outcomes (hazard ratio (HR) = 0.69, 95% confidence interval (CI) = 0.50–0.96) than for all other diagnosis groups. Patients seen in the ED for chronic conditions were at greater risk of adverse outcomes (HR = 1.86, 95% CI = 1.37–2.52) than all others. There were no significant differences in risk between patients with infections, those with non-MSK symptoms, and the unclassified group. Conclusion Adverse health outcomes were common in older patients with an ED discharge diagnosis classified as a chronic condition. ED discharge diagnosis may improve risk assessment and inform the development of targeted interventions to reduce adverse health outcomes in older adults discharged from the ED. PMID:19694872

  16. ENDOCRINOLOGY IN PREGNANCY: Influence of maternal vitamin D status on obstetric outcomes and the fetal skeleton.

    PubMed

    Moon, Rebecca J; Harvey, Nicholas C; Cooper, Cyrus

    2015-08-01

    Vitamin D status has been increasingly associated with wide-ranging clinical outcomes. There is now a wealth of observational studies reporting on its associations with obstetric complications, including pre-eclampsia, gestational diabetes and the mode and timing of delivery. The findings are inconsistent, and currently there is a lack of data from high-quality intervention studies to confirm a causal role for vitamin D in these outcomes. This is similarly true with regards to fetal development, including measures of fetal size and skeletal mineralisation. Overall, there is an indication of possible benefits of vitamin D supplementation during pregnancy for offspring birthweight, calcium concentrations and bone mass as well as for reduced maternal pre-eclampsia. However, for none of these outcomes is the current evidence base conclusive, and the available data justify the instatement of high-quality randomised placebo controlled trials in a range of populations and health care settings to establish the potential efficacy and safety of vitamin D supplementation to improve particular outcomes. PMID:25862787

  17. ENDOCRINOLOGY IN PREGNANCY: Influence of maternal vitamin D status on obstetric outcomes and the fetal skeleton.

    PubMed

    Moon, Rebecca J; Harvey, Nicholas C; Cooper, Cyrus

    2015-08-01

    Vitamin D status has been increasingly associated with wide-ranging clinical outcomes. There is now a wealth of observational studies reporting on its associations with obstetric complications, including pre-eclampsia, gestational diabetes and the mode and timing of delivery. The findings are inconsistent, and currently there is a lack of data from high-quality intervention studies to confirm a causal role for vitamin D in these outcomes. This is similarly true with regards to fetal development, including measures of fetal size and skeletal mineralisation. Overall, there is an indication of possible benefits of vitamin D supplementation during pregnancy for offspring birthweight, calcium concentrations and bone mass as well as for reduced maternal pre-eclampsia. However, for none of these outcomes is the current evidence base conclusive, and the available data justify the instatement of high-quality randomised placebo controlled trials in a range of populations and health care settings to establish the potential efficacy and safety of vitamin D supplementation to improve particular outcomes.

  18. Household Air Pollution from Solid Fuel Use and Risk of Adverse Pregnancy Outcomes: A Systematic Review and Meta-Analysis of the Empirical Evidence

    PubMed Central

    Amegah, Adeladza K.; Quansah, Reginald; Jaakkola, Jouni J. K.

    2014-01-01

    Background About 41% of households globally, mainly in developing countries rely on solid fuels for cooking with consequences for fetal growth and development. Previous reviews were limited in scope, assessing only two outcomes (birth weight, stillbirth). With important evidence accumulating, there is a need to improve the previous estimates and assess additional outcomes. We conducted a systematic review and meta-analysis to evaluate the quality and strength of available evidence on household air pollution (HAP) and the whole range of adverse pregnancy outcomes. Methods PubMed, Ovid Medline, Scopus and CINAHL were searched from their inception to the end of April 2013. All epidemiological study designs were eligible for inclusion in the review. The random-effects model was applied in computing the summary-effect estimates (EE) and their corresponding 95% confidence interval (CI). Results Of 1505 studies screened, 19 studies satisfied the inclusion criteria. Household combustion of solid fuels resulted in an 86.43 g (95% CI: 55.49, 117.37) reduction in birth weight, and a 35% (EE = 1.35, 95% CI: 1.23, 1.48) and 29% (EE = 1.29, 95% CI: 1.18, 1.41) increased risk of LBW and stillbirth respectively. Conclusion Combustion of solid fuels at home increases the risk of a wide range of adverse pregnancy outcomes. Access to clean household energy solutions is the surest way to combat HAP and mitigate their adverse effects. PMID:25463771

  19. Adverse Pregnancy Outcomes after In Vitro Fertilization: Effect of Number of Embryos Transferred and Plurality at Conception

    PubMed Central

    Luke, Barbara; Stern, Judy E.; Kotelchuck, Milton; Declercq, Eugene R.; Hornstein, Mark D.; Gopal, Daksha; Hoang, Lan; Diop, Hafsatou

    2015-01-01

    Objective To evaluate risks for adverse pregnancy outcomes by number of embryos transferred (ET) and fetal heart beats (FHB) in ART conceived singleton live births. Design Longitudinal cohort using cycles reported to the Society for Assisted Reproductive Technology Clinic Outcomes Reporting System between 2004 and 2008 among women who were treated and gave birth in Massachusetts. Setting Clinic-based data. Patients ART data on 6,073 births between 2004 and 2008 were linked to vital records and hospital data. Likelihood of ET ≥3 vs 1–2, FHB >1 vs 1, and risks of preterm birth (PTB, <37 weeks gestation), low birthweight (LBW, <2,500g), and small-for-gestational age birthweight (SGA, <10th%ile) with FHB >1 were modeled with binary logistic regression using a backward-stepping algorithm, and presented as adjusted odds ratios (AORs) and 95% confidence intervals. Interventions None Main Outcome Measures ET≥3, FHB >1, PTB, LBW, and SGA. Results Higher ET was significantly more likely with older maternal age, intracytoplasmic sperm injection, assisted hatching, cleavage-stage embryos, and thawed embryos. The likelihood of FHB>1 with ≥3 ET vs 1–2 ET was 2.04 (1.68–2.48). Risks of PTB and LBW with FHB>1 were 1.63 (1.27–2.09) and 1.81 (1.36– 2.39), respectively; the risk of SGA was not significant. Nulliparity was associated with higher risks of PTB (1.34, 1.12–1.59), LBW (1.48, 1.20–1.83), and SGA (2.17, 1.69–2.78). Conclusions Number of ETs were strongly associated with FHBs, with twice the risk of FHB>1 with ≥3 ET versus 1–2 ET. Increasing FHBs were associated with significantly greater risks for PTB and LBW outcomes. PMID:25956368

  20. Studying Biology to Understand Risk: Dosimetry Models and Quantitative Adverse Outcome Pathways

    EPA Science Inventory

    Confidence in the quantitative prediction of risk is increased when the prediction is based to as great an extent as possible on the relevant biological factors that constitute the pathway from exposure to adverse outcome. With the first examples now over 40 years old, physiologi...

  1. Exposure and Dosimetry Considerations for Adverse Outcome Pathways (AOPs) (NIH-AOP)

    EPA Science Inventory

    Risk is a function of both of hazard and exposure. Toxicokinetic (TK) models can determine whether chemical exposures produce potentially hazardous tissue concentrations. Whether or not the initial molecular event (MIE) in an Adverse Outcome Pathway (AOP) occurs depends on both e...

  2. Physical Performance Characteristics of Assisted Living Residents and Risk for Adverse Health Outcomes

    ERIC Educational Resources Information Center

    Giuliani, Carol A.; Gruber-Baldini, Ann L.; Park, Nan S.; Schrodt, Lori A.; Rokoske, Franzi; Sloane, Philip D.; Zimmerman, Sheryl

    2008-01-01

    Purpose: Researchers know little about the physical performance ability of residential care/assisted living (RC/AL) residents and its relationship to adverse outcomes such as fracture, nursing home placement, functional decline, and death. The purposes of this article are to (a) describe the functional characteristics of RC/AL residents, (b)…

  3. Increased Risk of Adverse Outcomes in Newborns in the Greater San Francisco Bay Area.

    ERIC Educational Resources Information Center

    Braveman, Paula; And Others

    1991-01-01

    To determine whether lack of medical insurance was associated with adverse health outcomes, this study examined hospital data on newborns in California's San Francisco Bay Area. The study also sought to determine which ethnic groups were most at risk. Computerized data on all civilian acute-care hospitalizations in the study area were obtained for…

  4. Defining Adverse Outcome Pathways for Effects of the Fungicide Propiconazole of Fish Reproduction

    EPA Science Inventory

    Adverse outcome pathways (AOPs) are used to describe the linkage of chemical interactions in terms of molecular initiating events to whole organism responses suitable for risk assessment. This study was conducted to develop AOPs for the model fungicide propiconazole relative to r...

  5. Antihistamines and other prognostic factors for adverse outcome in hyperemesis gravidarum

    PubMed Central

    Fejzo, Marlena S.; Magtira, Aromalyn; Schoenberg, Frederic Paik; MacGibbon, Kimber; Mullin, Patrick; Romero, Roberto; Tabsh, Khalil

    2014-01-01

    Objective The purpose of this study is to determine the frequency of adverse perinatal outcome in women with hyperemesis gravidarum and identify prognostic factors. Study design This is a case-control study in which outcomes of first pregnancies were compared between 254 women with hyperemesis gravidarum treated with intravenous fluids and 308 controls. Prognostic factors were identified by comparing the clinical profile of patients with hyperemesis gravidarum with a normal and an adverse pregnancy outcome. Binary responses were analyzed using either a Chi-square or Fisher exact test and continuous responses were analyzed using a t-test. Results Women with hyperemesis gravidarum have over a 4-fold increased risk of poor outcome including preterm birth and lower birth weight (p < 0.0001). Among maternal characteristics, only gestational hypertension had an influence on outcome (p < 0.0001). Treatment as an outpatient and/or by alternative medicine (acupuncture/acupressure/Bowen massage) was associated with a positive outcome (p < 0.0089). Poor outcomes were associated with early start of symptoms (p < 0.019), and treatment with methylprednisolone (p < 0.0217), promethazine (p < 0.0386), and other antihistamines [diphenhy- dramine (Benadryl), dimenhydrinate (Gravol), doxylamine (Unisom), hydroxyzine (Vistaril/Atarax), doxylamine and pyridoxine (Diclectin/Bendectin)] (p < 0.0151) independent of effectiveness. Among these medications, only the other antihistamines were prescribed independent of severity: they were effective in less than 20% of cases and were taken by almost 50% of patients with an adverse outcome. Conclusion Poor outcomes are significantly greater in women with HG and are associated with gestational hypertension, early symptoms, and antihistamine use. Given these results, there is an urgent need to address the safety and effectiveness of medications containing antihistamines in women with severe nausea of pregnancy. PMID:23751910

  6. Prenatal management and perinatal outcome in giant placental chorioangioma complicated with hydrops fetalis, fetal anemia and maternal mirror syndrome

    PubMed Central

    2012-01-01

    Background Giant placental chorioangiomas have been associated with a number of severe fetal complications and high perinatal mortality. Case presentation We report a case of giant chorioangioma with fetal hydrops, additionally complicated by severe anemia, mild cardiomegaly with hyperdinamic heart circulation and maternal mirror syndrome. Intrauterine blood transfusion and amniodrainage was performed at 29 weeks. Worsening of the fetal and maternal condition prompted us to proceed with delivery at 29 + 5 weeks. The newborn died 3 hours later due to pulmonary hypoplasia and hemodynamic failure. Maternal course was favourable, mirror syndrome resolved in the second day and the patient was discharged four days following delivery. Conclusions In the case described here, fetal condition got worse despite of the anemia correction and amniodrainage. Our outcome raises the issue whether additional intrauterine clinical intervention, as intersticial laser, should have been performed to stop further deterioration of the fetal condition when progressive severe hydrops develops. PMID:22840187

  7. Periodontal treatment during pregnancy decreases the rate of adverse pregnancy outcome: a controlled clinical trial

    PubMed Central

    SANT’ANA, Adriana Campos Passanezi; de CAMPOS, Marinele R.; PASSANEZI, Selma Campos; de REZENDE, Maria Lúcia Rubo; GREGHI, Sebastião Luiz Aguiar; PASSANEZI, Euloir

    2011-01-01

    Objectives The aim of this study was to evaluate the effects of non-surgical treatment of periodontal disease during the second trimester of gestation on adverse pregnancy outcomes. Material and Methods Pregnant patients during the 1st and 2nd trimesters at antenatal care in a Public Health Center were divided into 2 groups: NIG – "no intervention" (n=17) or IG- "intervention" (n=16). IG patients were submitted to a non-surgical periodontal treatment performed by a single periodontist consisting of scaling and root planning (SRP), professional prophylaxis (PROPH) and oral hygiene instruction (OHI). NIG received PROPH and OHI during pregnancy and were referred for treatment after delivery. Periodontal evaluation was performed by a single trained examiner, blinded to periodontal treatment, according to probing depth (PD), clinical attachment level (CAL), plaque index (PI) and sulcular bleeding index (SBI) at baseline and 35 gestational weeks-28 days post-partum. Primary adverse pregnancy outcomes were preterm birth (<37 weeks), low birth weight (<2.5 kg), late abortion (14-24 weeks) or abortion (<14 weeks). The results obtained were statistically evaluated according to OR, unpaired t test and paired t test at 5% significance level. Results No significant differences were observed between groups at baseline examination. Periodontal treatment resulted in stabilization of CAL and PI (p>0.05) at IG and worsening of all periodontal parameters at NIG (p<0.0001), except for PI. Significant differences in periodontal conditions of IG and NIG were observed at 2nd examination (p<0.001). The rate of adverse pregnancy outcomes was 47.05% in NIG and 6.25% in IG. Periodontal treatment during pregnancy was associated to a decreased risk of developing adverse pregnancy outcomes [OR=13.50; CI: 1.47-123.45; p=0.02]. Conclusions Periodontal treatment during the second trimester of gestation contributes to decrease adverse pregnancy outcomes. PMID:21552714

  8. Cortisol Reactivity to Social Stress as a Mediator of Early Adversity on Risk and Adaptive Outcomes

    PubMed Central

    Conradt, Elisabeth; Abar, Beau; Lester, Barry M.; LaGasse, Linda L.; Shankaran, Seetha; Bada, Henrietta; Bauer, Charles R.; Whitaker, Toni M.; Hammond, Jane A.

    2014-01-01

    Children chronically exposed to stress early in life are at increased risk for maladaptive outcomes, though the physiological mechanisms driving these effects are unknown. Cortisol reactivity was tested as a mediator of the relation between prenatal substance exposure and/or early adversity on adaptive and maladaptive outcomes. Data were drawn from a prospective longitudinal study of prenatal substance exposure (N = 860). Cortisol reactivity was assessed at age 11. Among African-Americans, prenatal substance exposure exerted an indirect effect through early adversity and cortisol reactivity to predict externalizing behavior, delinquency, and a positive student-teacher relationship at age 11. Decreased cortisol reactivity was related to maladaptive outcomes, and increased cortisol reactivity predicted better executive functioning and a more positive student-teacher relationship. PMID:25376131

  9. Prenatal Diagnosis and Evaluation of Sonographic Predictors for Intervention and Adverse Outcome in Congenital Pulmonary Airway Malformation

    PubMed Central

    Hellmund, Astrid; Berg, Christoph; Geipel, Annegret; Bludau, Meike; Heydweiller, Andreas; Bachour, Haitham; Müller, Andreas; Müller, Annette; Gembruch, Ulrich

    2016-01-01

    Objective To describe antenatal findings and evaluate prenatal risk parameters for adverse outcome or need for intervention in fetuses with congenital pulmonary airway malformation (CPAM). Methods In our retrospective study all fetuses with a prenatal diagnosis of CPAM detected in our tertiary referral center between 2002 and 2013 were analyzed. Sonographic findings were noted and measurements of mass-to-thorax-ratio (MTR), congenital pulmonary airway malformation volume-ratio (CVR) and observed to expected lung-to head-ratio (o/e LHR) were conducted and correlated to fetal or neonatal morbidity and mortality and/or need for prenatal intervention. Results 67 fetuses with CPAM were included in the study. Hydropic fetuses were observed in 16.4% (11/67) of cases, prenatal intervention was undertaken in 9 cases; 7 pregnancies were terminated. The survival rate of non-hydropic fetuses with conservatively managed CPAM was 98.0% (50/51), the survival rate for hydropic fetuses with intention to treat was 42.9% (3/7). 10 (18.2%) children needed respiratory assistance. Fetuses with a CVR of <0.91 were significantly less likely to experience adverse outcome or need for prenatal intervention with sensitivity, specificity and positive/negative predictive value of 0.89, 0.71, 0.62 and 0.93, respectively. A MTR (mass-to-thorax-ratio) of < 0.51 had a positive predictive value of 0.54 and a negative predictive value of 0.96 of adverse events with a sensitivity of 0.95 and a specificity of 0.63. The negative predictive value for o/e LHR of 45% was 0.84 with sensitivity, specificity and positive predictive value of 0.73, 0.68 and 0.52, respectively. Conclusions The majority of cases with CPAM have a favorable outcome. MTR and CVR are able to identify fetuses at risk, the o/e LHR is less sensitive. PMID:26978067

  10. Animal models for clinical and gestational diabetes: maternal and fetal outcomes

    PubMed Central

    Kiss, Ana CI; Lima, Paula HO; Sinzato, Yuri K; Takaku, Mariana; Takeno, Marisa A; Rudge, Marilza VC; Damasceno, Débora C

    2009-01-01

    Background Diabetes in pregnant women is associated with an increased risk of maternal and neonatal morbidity and remains a significant medical challenge. Diabetes during pregnancy may be divided into clinical diabetes and gestational diabetes. Experimental models are developed with the purpose of enhancing understanding of the pathophysiological mechanisms of diseases that affect humans. With regard to diabetes in pregnancy, experimental findings from models will lead to the development of treatment strategies to maintain a normal metabolic intrauterine milieu, improving perinatal development by preventing fetal growth restriction or macrosomia. Based on animal models of diabetes during pregnancy previously reported in the medical literature, the present study aimed to compare the impact of streptozotocin-induced severe (glycemia >300 mg/dl) and mild diabetes (glycemia between 120 and 300 mg/dl) on glycemia and maternal reproductive and fetal outcomes of Wistar rats to evaluate whether the animal model reproduces the maternal and perinatal results of clinical and gestational diabetes in humans. Methods On day 5 of life, 96 female Wistar rats were assigned to three experimental groups: control (n = 16), severe (n = 50) and mild diabetes (n = 30). At day 90 of life, rats were mated. On day 21 of pregnancy, rats were killed and their uterine horns were exposed to count implantation and fetus numbers to determine pre- and post-implantation loss rates. The fetuses were classified according to their birth weight. Results Severe and mild diabetic dams showed different glycemic responses during pregnancy, impairing fetal glycemia and weight, confirming that maternal glycemia is directly associated with fetal development. Newborns from severe diabetic mothers presented growth restriction, but mild diabetic mothers were not associated with an increased rate of macrosomic fetuses. Conclusion Experimental models of severe diabetes during pregnancy reproduced maternal and

  11. Adverse Outcome Pathway for Embryonic Vascular Disruption and Alternative Methods to Identify Chemical Vascular Disruptors During Development

    EPA Science Inventory

    Chemically induced vascular toxicity during embryonic development can result in a wide range of adverse prenatal outcomes. We used information from genetic mouse models linked to phenotypic outcomes and a vascular toxicity knowledge base to construct an embryonic vascular disrupt...

  12. Prognostic indicators of adverse renal outcome and death in acute kidney injury hospital survivors

    PubMed Central

    Hamzić-Mehmedbašić, Aida; Rašić, Senija; Balavac, Merima; Rebić, Damir; Delić-Šarac, Marina; Durak-Nalbantić, Azra

    2016-01-01

    Introduction: Data regarding prognostic factors of post-discharge mortality and adverse renal function outcome in acute kidney injury (AKI) hospital survivors are scarce and controversial. Objectives: We aimed to identify predictors of post-discharge mortality and adverse renal function outcome in AKI hospital survivors. Patients and Methods: The study group consisted of 84 AKI hospital survivors admitted to the tertiary medical center during 2-year period. Baseline clinical parameters, with renal outcome 3 months after discharge and 6-month mortality were evaluated. According survival and renal function outcome, patients were divided into two groups. Results: Patients who did not recover renal function were statistically significantly older (P < 0.007) with higher Charlson comorbidity index (CCI) score (P < 0.000) and more likely to have anuria and oliguria (P = 0.008) compared to those with recovery. Deceased AKI patients were statistically significantly older (P < 0.000), with higher CCI score (P < 0.000), greater prevalence of sepsis (P =0.004), higher levels of C-reactive protein (CRP) (P < 0.017) and ferritin (P < 0.051) and lower concentrations of albumin (P<0.01) compared to survivors. By multivariate analysis, independent predictors of adverse renal outcome were female gender (P =0.033), increasing CCI (P =0.000), presence of pre-existing chronic kidney disease (P =0.000) and diabetes mellitus (P =0.019) as well as acute decompensated heart failure (ADHF) (P =0.032), while protective factor for renal function outcome was higher urine output (P =0.009). Independent predictors of post-discharge mortality were female gender (P =0.04), higher CCI score (P =0.001) and sepsis (P =0.034). Conclusion: Female AKI hospital survivors with increasing burden of comorbidities, diagnosis of sepsis and ADHF seem to be at high-risk for poor post-discharge outcome. PMID:27471736

  13. Maternal Micronutrient Deficiencies and Related Adverse Neonatal Outcomes after Bariatric Surgery: A Systematic Review12

    PubMed Central

    Jans, Goele; Matthys, Christophe; Bogaerts, Annick; Lannoo, Matthias; Verhaeghe, Johan; Van der Schueren, Bart; Devlieger, Roland

    2015-01-01

    Pregnant and postpartum women with a history of bariatric surgery are at risk of micronutrient deficiencies as a result of the combination of physiologic changes related to pregnancy and iatrogenic postoperative alterations in the absorption and metabolism of crucial nutrients. This systematic review investigates micronutrient deficiencies and related adverse clinical outcomes in pregnant and postpartum women after bariatric surgery. A systematic approach involving critical appraisal was conducted independently by 2 researchers to examine deficiencies of phylloquinone, folate, iron, calcium, zinc, magnesium, iodide, copper, and vitamins A, D, and B-12 in pregnant and postpartum women after bariatric surgery, together with subsequent outcomes in the neonates. The search identified 29 relevant cases and 8 cohort studies. The quality of reporting among the case reports was weak according to the criteria based on the CARE (CAse REporting) guidelines as was that for the cohort studies based on the criteria from the Cohort Study Quality Assessment list of the Dutch Cochrane Center. The most common adverse neonatal outcomes related to maternal micronutrient deficiencies include visual complications (vitamin A), intracranial hemorrhage (phylloquinone), neurological and developmental impairment (vitamin B-12), and neural tube defects (folate). On the basis of the systematically collected information, we conclude that the evidence on micronutrient deficiencies in pregnant and postpartum women after bariatric surgery and subsequent adverse neonatal outcomes remains weak and inconclusive. PMID:26178026

  14. Chronic cadmium exposure: relation to male reproductive toxicity and subsequent fetal outcome

    SciTech Connect

    Zenick, H.; Hastings, L.; Goldsmith, M.; Niewenhuis, R.J.

    1982-03-01

    Acute injections of high doses of Cd induced marked testicular necrosis. However, the effects of low-dose, oral Cd exposure on a chronic basis are not well documented. The present investigation was designed to examine the effects of such exposure as reflected in parameters of spermatotoxicity and histology. Moreover, the impact on fetal outcome was measured by evaluating teratological and postnatal neurobehavior endpoints. Male Long-Evans hooded rats (100 d of age) were exposed to 0, 17.2, 34.4, or 68.8 ppm Cd for 70 d. During this period, the animals were maintained on a semipurified diet to control for the contribution of Zn and other trace elements. Near the end of exposure the males were mated to three female rats. One was sacrificed on d 21 of pregnancy for teratological assessment, including fetal weight, and determination of preimplantation and postimplantation loss. The other two dams were allowed to deliver, and their offspring were tested on tasks of exploratory behavior (d 21) and learning (d 90). Subsequently, the male parent was sacrified and a variety of measures recorded including weights of testes and caudae epididymides, sperm count and sperm morphology, and Cd content of liver and kidney. One of the testes was also evaluated histologically. No significant effects were observed on any of the parameters of reproductive toxicity or fetal outcome. These findings suggest that, at the doses employed in this study, Cd did not have signficant deleterious effects on the male reproductive system. Morever, the traditional view of Cd-related testicular insult, based on acute exposure, injection protocols, needs to be reevaluated in terms of environmental relevance.

  15. Chronic cadmium exposure: relation to male reproductive toxicity and subsequent fetal outcome.

    PubMed

    Zenick, H; Hastings, L; Goldsmith, M; Niewenhuis, R J

    1982-03-01

    Acute injections of high doses of Cd induce marked testicular necrosis. However, the effects of low-dose, oral Cd exposure on a chronic basis are not well documented. The present investigation was designed to examine the effects of such exposure as reflected in parameters of spermatotoxicity and histology. Moreover, the impact on fetal outcome was measured by evaluating teratological and postnatal neurobehavior endpoints. Male Long-Evans hooded rats (100 d of age) were exposed to 0, 17.2, 34.4, or 68.8 ppm Cd for 70 d. During this period, the animals were maintained on a semipurified diet to control for the contributions of Zn and other trace elements. Near the end of exposure the males were mated to three female rats. One was sacrificed on d 21 of pregnancy for teratological assessment, including fetal weight, and determination of preimplantation and postimplantation loss. The other two dams were allowed to deliver, and their offspring were tested on tasks of exploratory behavior (d 21) and learning (d 90). Subsequently, the male parent was sacrificed and a variety of measures recorded including weights of testes and caudae epididymides, sperm count and sperm morphology, and Cd content of liver and kidney. One of the testes was also evaluated histologically. No significant effects were observed on any of the parameters of reproductive toxicity or fetal outcome. These findings suggest that, at the doses employed in this study, Cd did not have significant deleterious effects on the male reproductive system. Morever, the traditional view of Cd-related testicular insult, based on acute exposure, injection protocols, needs to be reevaluated in terms of environmental relevance.

  16. Pregnancy outcomes with a primary complaint of perception of reduced fetal movements.

    PubMed

    Nor Azlin, M I; Maisarah, A S; Rahana, A R; Shafiee, M Nasir; Aqmar Suraya, S; Abdul Karim, A K; Jamil, M A

    2015-01-01

    Reduced fetal movement is a worrisome common complaint, not only for mothers but also for the attending medical personnel. The aim of this study was to analyse the pregnancy outcomes of women who presented primarily with reduced fetal movements (RFM). A retrospective study was performed based on patients' perception alone. Obstetric, past medical history, current presentation and outcomes of pregnancy were analysed. A total of 230 case notes were reviewed, with the majority being primigravidae. Less than half (48.7%) of the women had spontaneous labour, 45.7% had induction and 5.6% had elective caesarean section. There were no maternal complications in 97.4% (n = 224) of them. About 0.9% (n = 2) and 1.7% (n = 4) had primary postpartum haemorrhage and extended perineal tear, respectively. Although there was no major neonatal mortality and morbidity, until a randomised trial with a significant sample is conducted in the management of RFM, careful selections for elective delivery or conservative management would prevent untoward complications.

  17. Adverse Pregnancy Outcomes: Opportunity for Analysis of Biospecimens and Co-development of Prognostics | NCI Technology Transfer Center | TTC

    Cancer.gov

    The Eunice Kennedy Shriver National Institute of Child Health and Human Development’s Pregnancy and Perinatology Branch seeks partners interested in collaborative research to: (i) evaluate data and samples taken from women for potential biomarkers indicative for adverse pregnancy outcomes and (ii) co-develop diagnostic kits useful as predictors of adverse pregnancy outcomes.

  18. Baby on board: do responses to stress in the maternal brain mediate adverse pregnancy outcome?

    PubMed

    Douglas, Alison J

    2010-07-01

    Stress and adverse environmental surroundings result in suboptimal conditions in a pregnant mother such that she may experience poor pregnancy outcome including complete pregnancy failure and preterm labor. Furthermore her developing baby is at risk of adverse programming, which confers susceptibility to long term ill health. While some mechanisms at the feto-maternal interface underlying these conditions are understood, the underlying cause for their adverse adaptation is often not clear. Progesterone plays a key role at many levels, including control of neuroendocrine responses to stress, procuring the required immune balance and controlling placental and decidual function, and lack of progesterone can explain many of the unwanted consequences of stress. How stress that is perceived by the mother inhibits progesterone secretion and action is beginning to be investigated. This overview of maternal neuroendocrine responses to stress throughout pregnancy analyses how they interact to compromise progesterone secretion and precipitate undesirable effects in mother and offspring.

  19. Development of computationally predicted Adverse Outcome Pathway (AOP) networks through data mining and integration of publicly available in vivo, in vitro, phenotype, and biological pathway data

    EPA Science Inventory

    The Adverse Outcome Pathway (AOP) framework is increasingly being adopted as a tool for organizing and summarizing the mechanistic information connecting molecular perturbations by environmental stressors with adverse outcomes relevant for ecological and human health outcomes. Ho...

  20. Predictors of Adverse Cosmetic Outcome in the RAPID Trial: An Exploratory Analysis

    SciTech Connect

    Peterson, David; Truong, Pauline T.; Parpia, Sameer; Olivotto, Ivo A.; Berrang, Tanya; Kim, Do-Hoon; Kong, Iwa; Germain, Isabelle; Nichol, Alan; Akra, Mohamed; Roy, Isabelle; Reed, Melanie; Fyles, Anthony; Trotter, Theresa; Perera, Francisco; Balkwill, Susan; Lavertu, Sophie; Elliott, Elizabeth; and others

    2015-04-01

    Purpose: To evaluate factors associated with adverse cosmesis outcome in breast cancer patients randomized to accelerated partial breast irradiation (APBI) using 3-dimensional conformal radiation therapy or whole-breast irradiation in the RAPID (Randomized Trial of Accelerated Partial Breast Irradiation) trial. Methods and Materials: Subjects were trial participants with nurse-assessed global cosmetic scores at baseline and at 3 years. Adverse cosmesis was defined as a score of fair or poor. Cosmetic deterioration was defined as any adverse change in score from baseline to 3 years. The analysis is based on data from the previously reported interim analysis. Logistic regression models were used to assess the association of risk factors for these outcomes among all patients and those treated with APBI only. Results: Clinicopathologic characteristics were similar between subjects randomized to APBI (n=569) or whole-breast irradiation (n=539). For all subjects, factors associated with adverse cosmesis at 3 years were older age, central/inner tumor location, breast infection, smoking, seroma volume, breast volume, and use of APBI; factors associated with cosmetic deterioration were smoking, seroma volume, and use of APBI (P<.05). For APBI subjects, tumor location, smoking, age, and seroma volume were associated with adverse cosmesis (P<.05), and smoking was associated with cosmetic deterioration (P=.02). An independent association between the V95/whole-breast volume ratio and adverse cosmesis (P=.28) or cosmetic deterioration (P=.07) was not detected. On further exploration a V95/whole-breast volume ratio <0.15 was associated with a lower risk of cosmetic deterioration (p=.04), but this accounted for only 11% of patients. Conclusion: In the RAPID trial, a number of patient tumor and treatment-related factors, including the use of APBI, were associated with adverse cosmesis and cosmetic deterioration. For patients treated with APBI alone, the high-dose treatment

  1. Evaluation of Maternal-Fetal Outcomes After Emergency Vaginal Cerclage Performed With Shirodkar-McDonald Combined Modified Technique

    PubMed Central

    Ciancimino, Leonarda; Laganà, Antonio Simone; Imbesi, Giovanna; Chiofalo, Benito; Mancuso, Alfredo; Triolo, Onofrio

    2015-01-01

    Background Several techniques of emergency vaginal cerclage have been proposed in case of unexpected and abrupt cervical incompetence (CI), in order to prolong the pregnancy as much as possible and to reduce the adverse maternal-fetal outcomes. The aim of our study was to evaluate the effectiveness of emergency cervical cerclage, performed with the combined modified Shirodkar-McDonald technique. Methods We selected 12 cases of emergency vaginal cerclage, performed between January 1, 2008 and June 30, 2013. The age of the patients was between 20 and 38 years (mean 29.0 ± standard deviation (SD) 5.69), parity between 0 and 2 (mean 0.7 ± SD 0.65), and gestational age at the time of admission ranged between 17 and 26 weeks (mean 21.0 ± SD 3.44). In all these cases, we used a combined modified Shirodkar-McDonald technique to perform the procedure. Results The neonatal survival rate was 83.3%. The cesarean section rate was 16.7%. The average pregnancy prolongation was 89.9 days, higher than that reported for other studies in the literature. Conclusions We can assume that the emergency vaginal cerclage performed with the combined modified Shirodkar-McDonald technique is the best option of surgical therapy for the treatment of unexpected and abrupt CI. PMID:25780480

  2. Adverse Outcome Pathways as Tools to Assess Drug-Induced Toxicity.

    PubMed

    Vinken, Mathieu

    2016-01-01

    Adverse outcome pathways (AOPs) are novel tools in toxicology and human risk assessment with broad potential. AOPs are designed to provide a clear-cut mechanistic representation of toxicological effects that span over different layers of biological organization. AOPs share a common structure consisting of a molecular initiating event, a series of key events connected by key event relationships, and an adverse outcome. Development and evaluation of AOPs ideally complies with guidelines issued by the Organization for Economic Cooperation and Development. AOP frameworks have yet been proposed for major types of drug-induced injury, especially in the liver, including steatosis, fibrosis, and cholestasis. These newly postulated AOPs can serve a number of purposes pertinent to safety assessment of drugs, in particular the establishment of quantitative structure-activity relationships, the development of novel in vitro toxicity screening tests, and the elaboration of prioritization strategies. PMID:27311472

  3. Adverse birth outcomes in African American women: the social context of persistent reproductive disadvantage.

    PubMed

    Dominguez, Tyan Parker

    2011-01-01

    African Americans have the highest rates of infant mortality and adverse birth outcomes of all major racial/ethnic groups in the United States. The long-standing nature of this disparity suggests the need to shift epidemiologic focus from individual-level risk factors to the larger social forces that shape disease risk in populations. In this article, the African American reproductive disadvantage is discussed within the context of American race relations. The review of the literature focuses on racism as a social determinant of race-based disparities in adverse birth outcomes with specific attention to the viability of genetic explanations, the role of socioeconomic factors, the multidimensional nature of racism, and the stress-induced physiologic pathways by which racism may negatively affect pregnancy. Implications for social work research and practice also are discussed.

  4. Decline in adverse outcomes and death in tuberculosis patients in Malawi: association with HIV interventions.

    PubMed

    Kanyerere, H; Mganga, A; Harries, A D; Tayler-Smith, K; Zachariah, R; Jahn, A; Chimbwandira, F M; Mpunga, J

    2015-06-21

    Between 2000 and 2012, the annual numbers of patients treated for tuberculosis (TB) in Malawi declined by 28%, from 28 234 to 20 463. During this time, the proportion of TB patients tested for the human immunodeficiency virus (HIV) increased from 6% to 87%. Most HIV-infected patients received cotrimoxazole preventive therapy, and the proportion receiving antiretroviral therapy increased to 88%. Between 2000 and 2008 there was a significant decline in all adverse outcomes (from 31% to 14%), and particularly in deaths (from 23% to 10%) and loss to follow-up (from 5.2% to 1.9%, P < 0.001). After 2008, there was no decrease in any adverse outcome. Ways to further reduce TB-associated mortality are discussed.

  5. Maternal serum hormone concentrations for prediction of adverse outcome in threatened miscarriage.

    PubMed

    Johns, J; Muttukrishna, S; Lygnos, M; Groome, N; Jauniaux, E

    2007-10-01

    Many serum markers have been investigated in attempts to predict the outcome of pregnancy in the first trimester, with varying degrees of success. The objective of this study was to investigate whether they can be related to pregnancy outcome in women presenting with first trimester threatened miscarriage. A cohort study of women attending the Early Pregnancy Unit of a London teaching hospital was studied. A total of 122 women presenting with bleeding in the first trimester and an ongoing pregnancy, and 33 women undergoing termination of pregnancy, were recruited. The main outcome measures were gestation at delivery, birth weight and the incidence of adverse pregnancy outcome. Inhibin A, activin A, human chorionic gonadotrophin (HCG), pregnancy-associated plasma protein-A and follistatin concentrations were all significantly lower in women who subsequently miscarried when compared with live births. Serum HCG concentrations were significantly higher in cases of threatened miscarriage compared with controls (P = 0.0009). Logistic regression analysis indicated that inhibin A alone provided the best predictor for first trimester miscarriage. This pilot study suggests that placental hormone concentrations could be useful in predicting adverse pregnancy outcome in women presenting with threatened miscarriage. Inhibin A was best at predicting the likelihood of subsequent miscarriage in this group. PMID:17908404

  6. The predictive effect of insight on adverse clinical outcomes in bipolar I disorder: a two-year prospective study.

    PubMed

    Yen, Cheng-Fang; Chen, Cheng-Sheng; Yen, Ju-Yu; Ko, Chih-Hung

    2008-05-01

    Research has revealed that a lack of insight is associated with poorer clinical outcomes in schizophrenia; however, the predictive value of insight on adverse clinical outcomes among bipolar patients is quite understudied. The aim of this prospective study was to examine the impact of insight on adverse clinical outcomes among the patients with bipolar I disorder over a 2-year period. Sixty-five remitted bipolar I disorder patients received follow-up assessments at 3, 6, 9, 12, 18, and 24 months to detect the adverse clinical outcomes defined by the incidence of bipolar-related psychiatric hospitalization, emergency room visits, violent or suicidal behavior. The Schedule of Assessment of Insight was used to provide a baseline insight score. Cox regression analysis was used to examine the predictive value of insight on the adverse clinical outcomes. Impaired insight into treatment and a greater number of previous hospitalizations significantly increased the risk of adverse clinical outcomes with bipolar disorder in the 2-year period. However, insight into recognition of the illness and re-labeling of psychotic phenomena did not have any significant effect on adverse clinical outcomes. Bipolar patients' insight into treatment is an independent predictor of adverse clinical outcomes. Improving insight into treatment might be a promising target for a better outcome. PMID:17997489

  7. Violent crime exposure classification and adverse birth outcomes: a geographically-defined cohort study

    PubMed Central

    Messer, Lynne C; Kaufman, Jay S; Dole, Nancy; Herring, Amy; Laraia, Barbara A

    2006-01-01

    Background Area-level socioeconomic disparities have long been associated with adverse pregnancy outcomes. Crime is an important element of the neighborhood environment inadequately investigated in the reproductive and public health literature. When crime has been used in research, it has been variably defined, resulting in non-comparable associations across studies. Methods Using geocoded linked birth record, crime and census data in multilevel models, this paper explored the relevance of four spatial violent crime exposures: two proximal violent crime categorizations (count of violent crime within a one-half mile radius of maternal residence and distance from maternal residence to nearest violent crime) and two area-level crime categorizations (count of violent crimes within a block group and block group rate of violent crimes) for adverse birth events among women in living in the city of Raleigh NC crime report area in 1999–2001. Models were adjusted for maternal age and education and area-level deprivation. Results In black and white non-Hispanic race-stratified models, crime characterized as a proximal exposure was not able to distinguish between women experiencing adverse and women experiencing normal birth outcomes. Violent crime characterized as a neighborhood attribute was positively associated with preterm birth and low birth weight among non-Hispanic white and black women. No statistically significant interaction between area-deprivation and violent crime category was observed. Conclusion Crime is variably categorized in the literature, with little rationale provided for crime type or categorization employed. This research represents the first time multiple crime categorizations have been directly compared in association with health outcomes. Finding an effect of area-level violent crime suggests crime may best be characterized as a neighborhood attribute with important implication for adverse birth outcomes. PMID:16707017

  8. Predicting adverse obstetric outcome after early pregnancy events and complications: a review.

    PubMed

    van Oppenraaij, R H F; Jauniaux, E; Christiansen, O B; Horcajadas, J A; Farquharson, R G; Exalto, N

    2009-01-01

    BACKGROUND The aim was to evaluate the impact of early pregnancy events and complications as predictors of adverse obstetric outcome. METHODS We conducted a literature review on the impact of first trimester complications in previous and index pregnancies using Medline and Cochrane databases covering the period 1980-2008. RESULTS Clinically relevant associations of adverse outcome in the subsequent pregnancy with an odds ratio (OR) > 2.0 after complications in a previous pregnancy are the risk of perinatal death after a single previous miscarriage, the risk of very preterm delivery (VPTD) after two or more miscarriages, the risk of placenta praevia, premature preterm rupture of membranes, VPTD and low birthweight (LBW) after recurrent miscarriage and the risk of VPTD after two or more termination of pregnancy. Clinically relevant associations of adverse obstetric outcome in the ongoing pregnancy with an OR > 2.0 after complications in the index pregnancy are the risk of LBW and very low birthweight (VLBW) after a threatened miscarriage, the risk of pregnancy-induced hypertension, pre-eclampsia, placental abruption, preterm delivery (PTD), small for gestational age and low 5-min Apgar score after detection of an intrauterine haematoma, the risk of VPTD and intrauterine growth restriction after a crown-rump length discrepancy, the risk of VPTD, LBW and VLBW after a vanishing twin phenomenon and the risk of PTD, LBW and low 5-min Apgar score in a pregnancy complicated by severe hyperemesis gravidarum. CONCLUSIONS Data from our literature review indicate, by finding significant associations, that specific early pregnancy events and complications are predictors for subsequent adverse obstetric and perinatal outcome. Though, some of these associations are based on limited or small uncontrolled studies. Larger population-based controlled studies are needed to confirm these findings. Nevertheless, identification of these risks will improve obstetric care. PMID:19270317

  9. A Review of Nitrates in Drinking Water: Maternal Exposure and Adverse Reproductive and Developmental Outcomes

    PubMed Central

    Manassaram, Deana M.; Backer, Lorraine C.; Moll, Deborah M.

    2006-01-01

    In this review we present an update on maternal exposure to nitrates in drinking water in relation to possible adverse reproductive and developmental effects, and also discuss nitrates in drinking water in the United States. The current standard for nitrates in drinking water is based on retrospective studies and approximates a level that protects infants from methemoglobinemia, but no safety factor is built into the standard. The current standard applies only to public water systems. Drinking water source was related to nitrate exposure (i.e., private systems water was more likely than community system water to have nitrate levels above the maximum contaminant limit). Animal studies have found adverse reproductive effects resulting from higher doses of nitrate or nitrite. The epidemiologic evidence of a direct exposure–response relationship between drinking water nitrate level and adverse reproductive effect is still not clear. However, some reports have suggested an association between exposure to nitrates in drinking water and spontaneous abortions, intrauterine growth restriction, and various birth defects. Uncertainties in epidemiologic studies include the lack of individual exposure assessment that would rule out confounding of the exposure with some other cause. Nitrates may be just one of the contaminants in drinking water contributing to adverse outcomes. We conclude that the current literature does not provide sufficient evidence of a causal relationship between exposure to nitrates in drinking water and adverse reproductive effects. Future studies incorporating individual exposure assessment about users of private wells—the population most at risk—should be considered. PMID:16507452

  10. Emerging Role of Zika Virus in Adverse Fetal and Neonatal Outcomes.

    PubMed

    Panchaud, Alice; Stojanov, Miloš; Ammerdorffer, Anne; Vouga, Manon; Baud, David

    2016-07-01

    The rapid spread of the Zika virus (ZIKV) in the Americas and its potential association with thousands of suspected cases of microcephaly in Brazil and higher rates of Guillain-Barré syndrome meet the conditions for a Public Health Emergency of International Concern, as stated by the World Health Organization in February 2016. Two months later, the Centers for Disease Control and Prevention (CDC) announced that the current available evidence supports the existence of a causal relationship between prenatal Zika virus infection and microcephaly and other serious brain anomalies. Microcephaly can be caused by several factors, and its clinical course and prognosis are difficult to predict. Other pathogens with proven teratogenicity have been identified long before the current ZIKV epidemic. Despite the growing number of cases with maternal signs of infection and/or presence of ZIKV in tissues of affected newborns or fetuses, it is currently difficult to assess the magnitude of increase of microcephaly prevalence in Brazil, as well as the role of other factors in the development of congenital neurological conditions. Meanwhile, health agencies and medical organizations have issued cautious guidelines advising health care practitioners and expectant couples traveling to, returning from, or living in affected areas. Analogous to dengue virus (DENV) epidemics, ZIKV has the potential to become endemic in all countries infested by Aedes mosquitoes, while new mutations could impact viral replication in humans, leading to increased virulence and consequently heightened chances of viral transmission to additional naive mosquito vectors. Studies are urgently needed to answer the questions surrounding ZIKV and its role in congenital neurological conditions. PMID:27281741

  11. Emerging Role of Zika Virus in Adverse Fetal and Neonatal Outcomes.

    PubMed

    Panchaud, Alice; Stojanov, Miloš; Ammerdorffer, Anne; Vouga, Manon; Baud, David

    2016-07-01

    The rapid spread of the Zika virus (ZIKV) in the Americas and its potential association with thousands of suspected cases of microcephaly in Brazil and higher rates of Guillain-Barré syndrome meet the conditions for a Public Health Emergency of International Concern, as stated by the World Health Organization in February 2016. Two months later, the Centers for Disease Control and Prevention (CDC) announced that the current available evidence supports the existence of a causal relationship between prenatal Zika virus infection and microcephaly and other serious brain anomalies. Microcephaly can be caused by several factors, and its clinical course and prognosis are difficult to predict. Other pathogens with proven teratogenicity have been identified long before the current ZIKV epidemic. Despite the growing number of cases with maternal signs of infection and/or presence of ZIKV in tissues of affected newborns or fetuses, it is currently difficult to assess the magnitude of increase of microcephaly prevalence in Brazil, as well as the role of other factors in the development of congenital neurological conditions. Meanwhile, health agencies and medical organizations have issued cautious guidelines advising health care practitioners and expectant couples traveling to, returning from, or living in affected areas. Analogous to dengue virus (DENV) epidemics, ZIKV has the potential to become endemic in all countries infested by Aedes mosquitoes, while new mutations could impact viral replication in humans, leading to increased virulence and consequently heightened chances of viral transmission to additional naive mosquito vectors. Studies are urgently needed to answer the questions surrounding ZIKV and its role in congenital neurological conditions.

  12. Prenatal Depression Restricts Fetal Growth

    PubMed Central

    Diego, Miguel A.; Field, Tiffany; Hernandez-Reif, Maria; Schanberg, Saul; Kuhn, Cynthia; Gonzalez-Quintero, Victor Hugo

    2009-01-01

    Objective To identify whether prenatal depression is a risk factor for fetal growth restriction. Methods Midgestation (18-20 weeks GA) estimated fetal weight and urine cortisol and birth weight and gestational age at birth data were collected on a sample of 40 depressed and 40 non-depressed women. Estimated fetal weight and birthweight data were then used to compute fetal growth rates. Results Depressed women had a 13% greater incidence of premature delivery (Odds Ratio (OR) = 2.61) and 15% greater incidence of low birthweight (OR = 4.75) than non-depressed women. Depressed women also had elevated prenatal cortisol levels (p = .006) and fetuses who were smaller (p = .001) and who showed slower fetal growth rates (p = .011) and lower birthweights (p = .008). Mediation analyses further revealed that prenatal maternal cortisol levels were a potential mediator for the relationship between maternal symptoms of depression and both gestational age at birth and the rate of fetal growth. After controlling for maternal demographic variables, prenatal maternal cortisol levels were associated with 30% of the variance in gestational age at birth and 14% of the variance in the rate of fetal growth. Conclusion Prenatal depression was associated with adverse perinatal outcomes, including premature delivery and slower fetal growth rates. Prenatal maternal cortisol levels appear to play a role in mediating these outcomes. PMID:18723301

  13. Bendectin and fetal development. A study of Boston City Hospital.

    PubMed

    Morelock, S; Hingson, R; Kayne, H; Dooling, E; Zuckerman, B; Day, N; Alpert, J J; Flowerdew, G

    1982-01-15

    As part of a prospective study investigating maternal characteristics and habits during pregnancy and their impact on fetal development, 1,690 mother/infant pairs were studied. Of the mothers, 375 reported using Bendectin during pregnancy. Multivariate analyses examining birth weight, length, head circumference, gestational age, and congenital malformations as dependent variables demonstrated no associations between Bendectin exposure and adverse fetal outcome.

  14. Maternal Ethnic Ancestry and Adverse Perinatal Outcomes in New York City

    PubMed Central

    Stein, Cheryl R.; Savitz, David A.; Janevic, Teresa; Ananth, Cande V.; Kaufman, Jay S.; Herring, Amy H.; Engel, Stephanie M.

    2009-01-01

    Objective To examine the association between narrowly defined subsets of maternal ethnicity and birth outcomes. Study Design Analysis of 1995-2003 New York City birth certificates linked to hospital discharge data for 949,210 singleton births to examine the multivariable associations between maternal ethnicity and preterm birth, subsets of spontaneous and medically indicated preterm birth, term small for gestational age (SGA), and term birthweight. Results Compared to non-Hispanic whites, Puerto Ricans had an elevated odds ratio (OR 1.9, 95% CI 1.9-2.0) for delivering at 32-36 weeks (adjusted for nativity, maternal age, parity, education, tobacco use, pre-pregnancy weight, birth year). We found an excess of adverse outcomes among most Latino groups. Outcomes also varied within regions, with North African infants nearly 100g (adjusted) heavier than sub-Saharan Africans. Conclusions The considerable heterogeneity in risk of adverse perinatal outcomes is obscured in broad categorizations of maternal race/ethnicity, and may help to formulate etiologic hypotheses. PMID:19729145

  15. Prediction of adverse outcomes of acute coronary syndrome using intelligent fusion of triage information with HUMINT

    NASA Astrophysics Data System (ADS)

    McCullough, Claire L.; Novobilski, Andrew J.; Fesmire, Francis M.

    2006-04-01

    Faculty from the University of Tennessee at Chattanooga and the University of Tennessee College of Medicine, Chattanooga Unit, have used data mining techniques and neural networks to examine a set of fourteen features, data items, and HUMINT assessments for 2,148 emergency room patients with symptoms possibly indicative of Acute Coronary Syndrome. Specifically, the authors have generated Bayesian networks describing linkages and causality in the data, and have compared them with neural networks. The data includes objective information routinely collected during triage and the physician's initial case assessment, a HUMINT appraisal. Both the neural network and the Bayesian network were used to fuse the disparate types of information with the goal of forecasting thirty-day adverse patient outcome. This paper presents details of the methods of data fusion including both the data mining techniques and the neural network. Results are compared using Receiver Operating Characteristic curves describing the outcomes of both methods, both using only objective features and including the subjective physician's assessment. While preliminary, the results of this continuing study are significant both from the perspective of potential use of the intelligent fusion of biomedical informatics to aid the physician in prescribing treatment necessary to prevent serious adverse outcome from ACS and as a model of fusion of objective data with subjective HUMINT assessment. Possible future work includes extension of successfully demonstrated intelligent fusion methods to other medical applications, and use of decision level fusion to combine results from data mining and neural net approaches for even more accurate outcome prediction.

  16. [Fetal myocarditis associated with maternal anti-Ro and anti-La antibodies in the absence of atrioventricular block with good outcome].

    PubMed

    De La Villeon, C-G; Dulac, Y; Ohanessian, G; Ziani, A; Paranon, S; Acar, P

    2010-10-01

    We report a case of fetal myocarditis without conductive abnormality in a pregnant woman with anti-Ro/La antibodies. Fetal echocardiography showed myocarditis with ventricular and valvular hyperechogenicity, which was confirmed by postnatal transthoracic echography. Treatment with dexamethasone (4 mg/day) was started in the 22nd week of gestation. The outcome was good, with the child remaining asymptomatic 2 years later. This observation describes one of the rare forms of fetal myocarditis with favorable outcome.

  17. Fetal endocrinology

    PubMed Central

    Kota, Sunil Kumar; Gayatri, Kotni; Jammula, Sruti; Meher, Lalit Kumar; Kota, Siva Krishna; Krishna, S. V. S.; Modi, Kirtikumar D.

    2013-01-01

    Successful outcome of pregnancy depends upon genetic, cellular, and hormonal interactions, which lead to implantation, placentation, embryonic, and fetal development, parturition and fetal adaptation to extrauterine life. The fetal endocrine system commences development early in gestation and plays a modulating role on the various physiological organ systems and prepares the fetus for life after birth. Our current article provides an overview of the current knowledge of several aspects of this vast field of fetal endocrinology and the role of endocrine system on transition to extrauterine life. We also provide an insight into fetal endocrine adaptations pertinent to various clinically important situations like placental insufficiency and maternal malnutrition. PMID:23961471

  18. Pregnancies exposed to methadone, methadone and other illicit substances, and poly-drugs without methadone: A comparison of fetal neurobehaviors and infant outcomes

    PubMed Central

    Jansson, L.M.; Di Pietro, J.A.; Elko, A.; Williams, E.L.; Milio, L.; Velez, M.

    2011-01-01

    BACKGROUND It is suspected that there is a continuum of impairment among prenatally drug-exposed infants, such that opioid and/or poly-drug exposure confers the highest risk for adverse neonatal outcomes than other classes of substances or single substance exposures. Suitable control groups are difficult to identify. This study compared fetal neurobehavioral development and infant outcomes in offspring of three groups of pregnant women in drug treatment. Exposure groups include: Methadone + other illicit substances (MM+Poly) and two groups currently abstinent for poly drug exposures: Methadone only (MM/A) and Non-methadone (NM/A). METHODS Forty-nine women (19 MM+Poly, 18 MM/A, and 12 NM/A) underwent fetal monitoring at 36 weeks gestation at peak and trough levels of methadone (MM+Poly; MM/A) or at comparable morning and afternoon times (NM/A). Fetal heart rate (FHR), heart rate variability (FHRV) and motor activity (FM) data were collected. Infant measures included birth outcomes and Neonatal Abstinence Syndrome (NAS) assessment. RESULTS As compared to the NM/A group, cardiac measures were decreased in methadone-exposed fetuses at peak levels. FHR was significantly more suppressed in the MM+Poly group. FM was significantly lower in the MM/A versus the NM/A group at both peak and trough, indicative of more persistent exposure effects. The MM+Poly group delivered one week earlier and required NAS pharmacological treatment twice as often as the MM/A group. CONCLUSIONS Results support the notion that poly-drug exposure may potentiate the effects of methadone on the fetus and infant and highlights the need for intensified treatment for methadone-maintained women who abuse other substances. PMID:22041255

  19. Parental drinking and adverse outcomes in children: A scoping review of cohort studies

    PubMed Central

    Felix, Lambert; Keating, Patrick; McCambridge, Jim

    2015-01-01

    Abstract Introduction and Aims There is a growing interest in measuring alcohol's harms to people other than the drinker themselves. ‘Children of alcoholics’ and foetal alcohol spectrum disorder have received widespread attention. Less is known about how children are affected by post‐natal exposure to parental drinking other than alcohol abuse/dependence. In this scoping review, we aim to assemble and map existing evidence from cohort studies on the consequences of parental alcohol use for children, and to identify limitations and gaps in this literature. Design and Methods Systematic review methods were used. Electronic databases were searched (1980 to October 2013) and a total of 3215 abstracts were screened, 326 full text papers examined and 99 eligible for inclusion according to selection criteria including separation of exposure and outcome measurement in time and report of a quantitative effect size. Results The main finding is the large literature available. Adolescent drinking behaviour was the most common outcome measure and outcomes other than substance use were rarely analysed. In almost two of every three published associations, parental drinking was found to be statistically significantly associated with a child harm outcome measure. Several limitations in the literature are noted regarding its potential to address a possible causal role of parental drinking in children's adverse outcomes. Discussion and Conclusions This study identifies targets for further study and provides a platform for more targeted analytic investigations which ascertain risk of bias, and which are capable of considering the appropriateness of causal inferences for the observed associations. [Rossow I, Felix L, Keating P, McCambridge J. Parental drinking and adverse outcomes in children: A scoping review of cohort studies. Drug Alcohol Rev 2016;35:397–405] PMID:26332090

  20. Vitamin D Deficiency Increases the Risk of Adverse Neonatal Outcomes in Gestational Diabetes

    PubMed Central

    Weinert, Letícia Schwerz; Reichelt, Angela Jacob; Schmitt, Leonardo Rauber; Boff, Roberta; Oppermann, Maria Lucia Rocha; Camargo, Joiza Lins; Silveiro, Sandra Pinho

    2016-01-01

    Background Gestational diabetes mellitus (GDM) and vitamin D deficiency have been associated with increased risk of adverse perinatal outcomes but the consequences of both conditions simultaneously present in pregnancy have not yet been evaluated. Our objective was to study the influence of vitamin D deficiency in neonatal outcomes of pregnancies with GDM. Methods 184 pregnant women with GDM referred to specialized prenatal monitoring were included in this cohort and had blood sampled for 25-hydroxyvitamin D measurement. Vitamin D was measured by chemiluminescence and deficiency was defined as < 20 ng/mL. Participants were followed until puerperium and adverse neonatal outcomes were evaluated. Results Newborns of women with vitamin D deficiency had higher incidences of hospitalization in intensive care units (ICU) (32 vs 19%, P = 0.048), of hypoglycemia (any, 17.3 vs 7.1%, P = 0.039requiring ICU, 15.3 vs 3.6%, P = 0.008), and were more frequently small for gestational age (SGA) (17.3 vs 5.9%, P = 0.017). After adjustment, relative risk (RR) for hypoglycemia requiring ICU was 3.63 (95%CI 1.09–12.11) and for SGA was 4.32 (95%CI 1.75–10.66). The incidence of prematurity, jaundice and shoulder dystocia was no statistically different between groups. Conclusions In this cohort of pregnant women with GDM, vitamin D deficiency was associated with a major increase in the incidence of adverse neonatal outcomes such as SGA newborns and neonatal hypoglycemia. PMID:27764194

  1. Associations between Anticholinergic Burden and Adverse Health Outcomes in Parkinson Disease

    PubMed Central

    Crispo, James A. G.; Willis, Allison W.; Thibault, Dylan P.; Fortin, Yannick; Hays, Harlen D.; McNair, Douglas S.; Bjerre, Lise M.; Kohen, Dafna E.; Perez-Lloret, Santiago; Mattison, Donald R.; Krewski, Daniel

    2016-01-01

    Background Elderly adults should avoid medications with anticholinergic effects since they may increase the risk of adverse events, including falls, delirium, and cognitive impairment. However, data on anticholinergic burden are limited in subpopulations, such as individuals with Parkinson disease (PD). The objective of this study was to determine whether anticholinergic burden was associated with adverse outcomes in a PD inpatient population. Methods Using the Cerner Health Facts® database, we retrospectively examined anticholinergic medication use, diagnoses, and hospital revisits within a cohort of 16,302 PD inpatients admitted to a Cerner hospital between 2000 and 2011. Anticholinergic burden was computed using the Anticholinergic Risk Scale (ARS). Primary outcomes were associations between ARS score and diagnosis of fracture and delirium. Secondary outcomes included associations between ARS score and 30-day hospital revisits. Results Many individuals (57.8%) were prescribed non-PD medications with moderate to very strong anticholinergic potential. Individuals with the greatest ARS score (≥4) were more likely to be diagnosed with fractures (adjusted odds ratio (AOR): 1.56, 95% CI: 1.29–1.88) and delirium (AOR: 1.61, 95% CI: 1.08–2.40) relative to those with no anticholinergic burden. Similarly, inpatients with the greatest ARS score were more likely to visit the emergency department (adjusted hazard ratio (AHR): 1.32, 95% CI: 1.10–1.58) and be readmitted (AHR: 1.16, 95% CI: 1.01–1.33) within 30-days of discharge. Conclusions We found a positive association between increased anticholinergic burden and adverse outcomes among individuals with PD. Additional pharmacovigilance studies are needed to better understand risks associated with anticholinergic medication use in PD. PMID:26939130

  2. Intimate partner violence, substance use, and adverse neonatal outcomes among urban women

    PubMed Central

    Alhusen, Jeanne L.; Lucea, Marguerite B.; Bullock, Linda; Sharps, Phyllis

    2013-01-01

    Objective To assess the prevalence of intimate partner violence, substance use, and their co-occurrence during pregnancy and examines their associations with adverse neonatal outcomes. Study design Between February 2009 and February 2010, pregnant women receiving obstetrical care at three urban clinics were screened for intimate partner violence and substance use between 24-28 weeks gestation. A chart review was conducted upon delivery to assess for adverse neonatal outcomes of low birth weight (LBW), preterm birth, and small for gestational age (SGA). Results Maternal and neonatal data were collected on 166 mothers and their neonates. Overall, 19% of the sample reported intimate partner violence during their pregnancies. Of the study's neonates 41% had at least one adverse neonatal outcome. Nearly half of the mothers reported using at least one substance during pregnancy. Women experiencing intimate partner violence had a higher prevalence of marijuana use than their non-abused counterparts (p < 0.01). Experiencing intimate partner violence was associated with a fourfold increase in having a SGA neonate (aOR = 4.00; 95% CI 1.58 – 9.97). Women who reported marijuana use had five times the odds of having a neonate classified as SGA (aOR = 5.16, 95% CI 2.24 – 11.89) or LBW (aOR 5.00; 95% CI 1.98 – 12.65). Conclusions The prevalence of intimate partner violence during pregnancy and substance use is high in urban mothers, the risks of which extend to their neonates. Pediatric providers are urged to routinely screen for both issues and recognize the impact of co-occurrence of these risk factors on poor neonatal and childhood outcomes. PMID:23485028

  3. Acculturation and Adverse Birth Outcomes in a Predominantly Puerto Rican Population.

    PubMed

    Barcelona de Mendoza, Veronica; Harville, Emily; Theall, Katherine; Buekens, Pierre; Chasan-Taber, Lisa

    2016-06-01

    Introduction Latinas in the United States on average have poorer birth outcomes than Whites, yet considerable heterogeneity exists within Latinas. Puerto Ricans have some of the highest rates of adverse outcomes and are understudied. The goal of this study was to determine if acculturation was associated with adverse birth outcomes in a predominantly Puerto Rican population. Methods We conducted a secondary analysis of Proyecto Buena Salud, a prospective cohort study conducted from 2006 to 2011. A convenience sample of pregnant Latina women were recruited from a tertiary care hospital in Massachusetts. Acculturation was measured in early pregnancy; directly via the Psychological Acculturation Scale, and via proxies of language preference and generation in the United States. Birth outcomes (gestational age and birthweight) were abstracted from medical records (n = 1362). Results After adjustment, psychological acculturation, language preference, and generation was not associated with odds of preterm birth. However, every unit increase in psychological acculturation score was associated with an increase in gestational age of 0.22 weeks (SE = 0.1, p = 0.04) among all births. Women who preferred to speak Spanish (β = -0.39, SE = 0.2, p = 0.02) and who were first generation in the US (β = -0.33, SE = 0.1, p = 0.02) had significantly lower gestational ages than women who preferred English or who were later generation, respectively. Similarly, women who were first generation had babies who weighed 76.11 g less (SE = 35.2, p = 0.03) than women who were later generation. Discussion We observed a small, but statistically significant adverse impact of low acculturation on gestational age and birthweight in this predominantly Puerto Rican population. PMID:26694041

  4. Acculturation and Adverse Birth Outcomes in a Predominantly Puerto Rican Population

    PubMed Central

    de Mendoza, Veronica Barcelona; Harville, Emily; Theall, Katherine; Buekens, Pierre; Chasan-Taber, Lisa

    2016-01-01

    Introduction Latinas in the United States on average have poorer birth outcomes than Whites, yet considerable heterogeneity exists within Latinas. Puerto Ricans have some of the highest rates of adverse outcomes and are understudied. The goal of this study was to determine if acculturation was associated with adverse birth outcomes in a predominantly Puerto Rican population. Methods We conducted a secondary analysis of Proyecto Buena Salud, a prospective cohort study conducted from 2006 to 2011. A convenience sample of pregnant Latina women were recruited from a tertiary care hospital in Massachusetts. Acculturation was measured in early pregnancy; directly via the Psychological Acculturation Scale, and via proxies of language preference and generation in the United States. Birth outcomes (gestational age and birthweight) were abstracted from medical records (n = 1362). Results After adjustment, psychological acculturation, language preference, and generation was not associated with odds of preterm birth. However, every unit increase in psychological acculturation score was associated with an increase in gestational age of 0.22 weeks (SE = 0.1, p = 0.04) among all births. Women who preferred to speak Spanish (β = −0.39, SE = 0.2, p = 0.02) and who were first generation in the US (β = −0.33, SE = 0.1, p = 0.02) had significantly lower gestational ages than women who preferred English or who were later generation, respectively. Similarly, women who were first generation had babies who weighed 76.11 g less (SE = 35.2, p = 0.03) than women who were later generation. Discussion We observed a small, but statistically significant adverse impact of low acculturation on gestational age and birthweight in this predominantly Puerto Rican population. PMID:26694041

  5. An Elevated Glycemic Gap is Associated With Adverse Outcomes in Diabetic Patients With Community-Acquired Pneumonia

    PubMed Central

    Chen, Po-Chuan; Liao, Wen-I.; Wang, Ying-Chuan; Chang, Wei-Chou; Hsu, Chin-Wang; Chen, Ying-Hsin; Tsai, Shih-Hung

    2015-01-01

    Abstract Several studies argue against the association between admission hyperglycemia and adverse outcomes in infected diabetic patients. When investigating the association, it is necessary to consider preexisting hyperglycemia. The objective of this study was to assess whether stress-induced hyperglycemia, determined by the glycemic gap between admission glucose levels and A1c-derived average glucose levels adversely affects outcomes in diabetic patients admitted to hospital with community-acquired pneumonia (CAP). We retrospectively analyzed the glycemic gap and adverse outcomes of diabetic patients hospitalized because of CAP from June 1, 2007 to August 31, 2012 in single medical center in Taiwan. A total of 203 patients admitted with principal diagnosis of CAP and available data of glycemic gap. Patients with glycemic gaps ≥40 mg/dL had greater AUROC values for the development of adverse outcomes compared with acute hyperglycemia and long-term glycemic controls. Patients with an elevated glycemic gap had an odds ratio of 3.84 for the incidence of combined adverse outcomes. Incorporation of the glycemic gap into pneumonia severity index, CURB-65 or SMART-COP scores, increased the discriminative performance of predicting the development of adverse outcomes. Glycemic gaps were associated with adverse outcomes of diabetic CAP patients. The discriminative performance of the calculated glycemic gaps was comparable with those of current clinical scoring systems and may further increase the AUROC of each system. PMID:26313809

  6. Recurrent fetal complex ovarian cysts with rupture followed by simple cyst in the neonatal period with no adverse sequelae.

    PubMed

    Dera-Szymanowska, Anna; Malinger, Adam; Madejczyk, Mateusz; Szymanowski, Krzysztof; Bręborowicz, Gregor H; Opala, Tomasz

    2016-01-01

    Fetal ovarian cysts are the most frequent type of abdominal tumors in female fetuses with prenatal detection rate of more than 30%. The etiology of fetal ovarian cysts is unclear, but hormonal stimulation as well as presence of maternal diabetes, hypothyroidism, Rh iso-immune hemolytic disease and toxemia has been generally considered responsible for the disease. Complications of fetal ovarian cysts include compression of other viscera, cyst rupture, hemorrhage and, most frequently, ovarian torsion with consequent loss of the ovary. Management is controversial with several options described in the literature, including watchful expectancy, antenatal aspiration of simple cysts to prevent torsion and ovarian loss and finally, resection of all complex cysts in the neonatal period. To date, no case report has described recurrent complex cysts with rupture in the fetal period and recurrence of simple cyst in neonatal period. By presenting this case, we wanted to show that surgical intervention in case of prenatally diagnosed fetal ovarian cyst should be considered postnatally and only in symptomatic or complicated cases.

  7. Adverse Geriatric Outcomes Secondary to Polypharmacy in a Mouse Model: The Influence of Aging.

    PubMed

    Huizer-Pajkos, Aniko; Kane, Alice E; Howlett, Susan E; Mach, John; Mitchell, Sarah J; de Cabo, Rafael; Le Couteur, David G; Hilmer, Sarah N

    2016-05-01

    We aimed to develop a mouse model of polypharmacy, primarily to establish whether short-term exposure to polypharmacy causes adverse geriatric outcomes. We also investigated whether old age increased susceptibility to any adverse geriatric outcomes of polypharmacy. Young (n= 10) and old (n= 21) male C57BL/6 mice were administered control diet or polypharmacy diet containing therapeutic doses of five commonly used medicines (simvastatin, metoprolol, omeprazole, acetaminophen, and citalopram). Mice were assessed before and after the 2- to 4-week intervention. Over the intervention period, we observed no mortality and no change in food intake, body weight, or serum biochemistry in any age or treatment group. In old mice, polypharmacy caused significant declines in locomotor activity (pre minus postintervention values in control 2 ± 13 counts, polypharmacy 32 ± 7 counts,p< .05) and front paw wire holding impulse (control -2.45 ± 1.02 N s, polypharmacy +1.99 ± 1.19 N s,p< .05), loss of improvement in rotarod latency (control -59 ± 11 s, polypharmacy -1.7 ± 17 s,p< .05), and lowered blood pressure (control -0.2 ± 3 mmHg, polypharmacy 11 ± 4 mmHg,p< .05). In young mice, changes in outcomes over the intervention period did not differ between control and polypharmacy groups. This novel model of polypharmacy is feasible. Even short-term polypharmacy impairs mobility, balance, and strength in old male mice. PMID:25940962

  8. Low Mitochondrial DNA Copy Number is Associated With Adverse Clinical Outcomes in Peritoneal Dialysis Patients

    PubMed Central

    Yoon, Chang-Yun; Park, Jung Tak; Kee, Youn Kyung; Han, Seung Gyu; Han, In Mee; Kwon, Young Eun; Park, Kyoung Sook; Lee, Mi Jung; Han, Seung Hyeok; Kang, Shin-Wook; Yoo, Tae-Hyun

    2016-01-01

    Abstract Mitochondrial dysfunction may play an important role in abnormal glucose metabolism and systemic inflammation. We aimed to investigate the relationship between mitochondrial DNA (mtDNA) copy number and clinical outcomes in peritoneal dialysis (PD) patients. We recruited 120 prevalent PD patients and determined mtDNA copy number by PCR. Primary outcome was all-cause mortality, whereas secondary outcomes included cardiovascular events, technical PD failure, and incident malignancy. Cox proportional hazards analysis determined the independent association of mtDNA copy number with outcomes. The mean patient age was 52.3 years; 42.5% were men. The mean log mtDNA copy number was 3.30 ± 0.50. During a follow-up period of 35.4 ± 19.3 months, all-cause mortality and secondary outcomes were observed in 20.0% and 59.2% of patients, respectively. Secondary outcomes were significantly lower in the highest mtDNA copy number group than in the lower groups. In multiple Cox analysis, the mtDNA copy number was not associated with all-cause mortality (lower two vs highest tertile: hazard ratio [HR] = 1.208, 95% confidence interval [CI] = 0.477–3.061). However, the highest tertile group was significantly associated with lower incidences of secondary outcomes (lower two vs highest tertile: HR [95% CI] = 0.494 [0.277–0.882]) after adjusting for confounding factors. The decreased mtDNA copy number was significantly associated with adverse clinical outcomes in PD patients. PMID:26886611

  9. Aspirin use for primary prophylaxis: Adverse outcomes in non-variceal upper gastrointestinal bleeding

    PubMed Central

    Souk, Karina M; Tamim, Hani M; Abu Daya, Hussein A; Rockey, Don C; Barada, Kassem A

    2016-01-01

    AIM: To compare outcomes of patients with non-variceal upper gastrointestinal bleeding (NVUGIB) taking aspirin for primary prophylaxis to those not taking it. METHODS: Patients not known to have any vascular disease (coronary artery or cerebrovascular disease) who were admitted to the American University of Beirut Medical Center between 1993 and 2010 with NVUGIB were included. The frequencies of in-hospital mortality, re-bleeding, severe bleeding, need for surgery or embolization, and of a composite outcome defined as the occurrence of any of the 4 bleeding related adverse outcomes were compared between patients receiving aspirin and those on no antithrombotics. We also compared frequency of in hospital complications and length of hospital stay between the two groups. RESULTS: Of 357 eligible patients, 94 were on aspirin and 263 patients were on no antithrombotics (control group). Patients in the aspirin group were older, the mean age was 58 years in controls and 67 years in the aspirin group (P < 0.001). Patients in the aspirin group had significantly more co-morbidities, including diabetes mellitus and hypertension [25 (27%) vs 31 (112%) and 44 (47%) vs 74 (28%) respectively, (P = 0.001)], as well as dyslipidemia [21 (22%) vs 16 (6%), P < 0.0001). Smoking was more frequent in the aspirin group [34 (41%) vs 60 (27%), P = 0.02)]. The frequencies of endoscopic therapy and surgery were similar in both groups. Patients who were on aspirin had lower in-hospital mortality rates (2.1% vs 13.7%, P = 0.002), shorter hospital stay (4.9 d vs 7 d, P = 0.01), and fewer composite outcomes (10.6% vs 24%, P = 0.01). The frequencies of in-hospital complications and re-bleeding were similar in the two groups. CONCLUSION: Patients who present with NVUGIB while receiving aspirin for primary prophylaxis had fewer adverse outcomes. Thus aspirin may have a protective effect beyond its cardiovascular benefits. PMID:27462392

  10. Systems Toxicology of Male Reproductive Development: Profiling 774 Chemicals for Molecular Targets and Adverse Outcomes

    PubMed Central

    Leung, Maxwell C.K.; Phuong, Jimmy; Baker, Nancy C.; Sipes, Nisha S.; Klinefelter, Gary R.; Martin, Matthew T.; McLaurin, Keith W.; Setzer, R. Woodrow; Darney, Sally Perreault; Judson, Richard S.; Knudsen, Thomas B.

    2015-01-01

    Background: Trends in male reproductive health have been reported for increased rates of testicular germ cell tumors, low semen quality, cryptorchidism, and hypospadias, which have been associated with prenatal environmental chemical exposure based on human and animal studies. Objective: In the present study we aimed to identify significant correlations between environmental chemicals, molecular targets, and adverse outcomes across a broad chemical landscape with emphasis on developmental toxicity of the male reproductive system. Methods: We used U.S. EPA’s animal study database (ToxRefDB) and a comprehensive literature analysis to identify 774 chemicals that have been evaluated for adverse effects on male reproductive parameters, and then used U.S. EPA’s in vitro high-throughput screening (HTS) database (ToxCastDB) to profile their bioactivity across approximately 800 molecular and cellular features. Results: A phenotypic hierarchy of testicular atrophy, sperm effects, tumors, and malformations, a composite resembling the human testicular dysgenesis syndrome (TDS) hypothesis, was observed in 281 chemicals. A subset of 54 chemicals with male developmental consequences had in vitro bioactivity on molecular targets that could be condensed into 156 gene annotations in a bipartite network. Conclusion: Computational modeling of available in vivo and in vitro data for chemicals that produce adverse effects on male reproductive end points revealed a phenotypic hierarchy across animal studies consistent with the human TDS hypothesis. We confirmed the known role of estrogen and androgen signaling pathways in rodent TDS, and importantly, broadened the list of molecular targets to include retinoic acid signaling, vascular remodeling proteins, G-protein coupled receptors (GPCRs), and cytochrome P450s. Citation: Leung MC, Phuong J, Baker NC, Sipes NS, Klinefelter GR, Martin MT, McLaurin KW, Setzer RW, Darney SP, Judson RS, Knudsen TB. 2016. Systems toxicology of male

  11. Adverse inpatient outcomes during the transition to a new electronic health record system: observational study

    PubMed Central

    Barnett, Michael L; Mehrotra, Ateev

    2016-01-01

    Objective To assess the short term association of inpatient implementation of electronic health records (EHRs) with patient outcomes of mortality, readmissions, and adverse safety events. Design Observational study with difference-in-differences analysis. Setting Medicare, 2011-12. Participants Patients admitted to 17 study hospitals with a verifiable “go live” date for implementation of inpatient EHRs during 2011-12, and 399 control hospitals in the same hospital referral region. Main outcome measures All cause readmission within 30 days of discharge, all cause mortality within 30 days of admission, and adverse safety events as defined by the patient safety for selected indicators (PSI)-90 composite measure among Medicare beneficiaries admitted to one of these hospitals 90 days before and 90 days after implementation of the EHRs (n=28 235 and 26 453 admissions), compared with the control group of all contemporaneous admissions to hospitals in the same hospital referral region (n=284 632 and 276 513 admissions). Analyses were adjusted for beneficiaries’ sociodemographic and clinical characteristics. Results Before and after implementation, characteristics of admissions were similar in both study and control hospitals. Among study hospitals, unadjusted 30 day mortality (6.74% to 7.15%, P=0.06) and adverse safety event rates (10.5 to 11.4 events per 1000 admissions, P=0.34) did not significantly change after implementation of EHRs. There was an unadjusted decrease in 30 day readmission rates, from 19.9% to 19.0% post-implementation (P=0.02). In difference-in-differences analysis, however, there was no significant change in any outcome between pre-implementation and post-implementation periods (all P≥0.13). Conclusions Despite concerns that implementation of EHRs might adversely impact patient care during the acute transition period, we found no overall negative association of such implementation on short term inpatient mortality, adverse safety

  12. Plasma Osteopontin Levels and Adverse Cardiovascular Outcomes in the PEACE Trial

    PubMed Central

    Austin, Erin E.; Gersh, Bernard J.; Solak, Nusret; Rizvi, Syed A.; Bailey, Kent R.; Kullo, Iftikhar J.

    2016-01-01

    Osteopontin (OPN) is a secreted glycophosphoprotein that has a role in inflammation, immune response and calcification. We hypothesized that plasma OPN levels are associated with adverse cardiovascular outcomes in patients with stable coronary artery disease (CAD) and preserved ejection fraction (EF) enrolled in the PEACE trial. We measured plasma OPN levels at baseline in 3567 CAD patients (mean age 64.5 ± 8.1 years, 81% men) by a sandwich chemiluminescent assay (coefficient of variation = 4.1%). OPN levels were natural log (Ln) transformed prior to analyses. We assessed whether Ln OPN levels were associated with the composite primary endpoint of cardiovascular death, non-fatal myocardial infarction and hospitalization for heart failure using multiple event multivariable Cox proportional hazards regression. Adjustment was performed for: (a) age and sex; (b) additional potential confounders; and (c) a parsimonious set of statistically significant 10 variates. During a median follow-up of 4.8 years, 416 adverse cardiovascular outcomes occurred in 366 patients. Ln OPN was significantly associated with the primary endpoint; HR (95% CI) = 1.56 (1.27, 1.92); P <0.001, and remained significant after adjustment for age and sex [1.31 (1.06, 1.61); P = 0.01] and after adjustment for relevant covariates [1.24 (1.01, 1.52); P = 0.04]. In a secondary analysis of the individual event types, Ln OPN was significantly associated with incident hospitalization for heart failure: HR (95% CI) = 2.04 (1.44, 2.89); P <0.001, even after adjustment for age, sex and additional relevant covariates. In conclusion, in patients with stable CAD and preserved EF on optimal medical therapy, plasma OPN levels were independently associated with the composite incident endpoint of adverse cardiovascular outcomes as well as incident hospitalization for heart failure. PMID:27284698

  13. Usefulness of transient and persistent no reflow to predict adverse clinical outcomes following percutaneous coronary intervention.

    PubMed

    Chan, William; Stub, Dion; Clark, David J; Ajani, Andrew E; Andrianopoulos, Nick; Brennan, Angela L; New, Gishel; Black, Alexander; Shaw, James A; Reid, Christopher M; Dart, Anthony M; Duffy, Stephen J

    2012-02-15

    The no reflow phenomenon is reported to occur in >2% of all percutaneous coronary interventions (PCIs) and portends a poor prognosis. We analyzed data from 5,286 consecutive patients who underwent PCI from the Melbourne Interventional Group (MIG) registry from April 2004 through January 2008 who had 30-day follow-up completed. Patients without no reflow (normal reflow, n = 5,031) were compared to 255 (4.8%) with no reflow (n = 217 for transient no reflow, n = 38 for persistent no reflow). Patients with transient or persistent no reflow were more likely to present with ST-elevation myocardial infarction (MI) or cardiogenic shock (p <0.0001 for the 2 comparisons). They were also more likely to have complex lesions (American College of Cardiology/American Heart Association type B2/C), have lesions within a bypass graft, require an intra-aortic balloon pump, receive glycoprotein IIb/IIIa inhibition, and have a longer mean stent length (p <0.0001 for all comparisons). In-hospital outcomes were significantly worse in those patients with transient or persistent no reflow, with increased death, periprocedural MI, renal impairment, and major adverse cardiac events (p <0.0001 for all comparisons). Similarly, transient and persistent no reflow portended worse 30-day clinical outcomes, with a progressive increase in mortality (normal reflow 1.7% vs transient no reflow 5.5% vs persistent no reflow 13.2%, p <0.0001), MI, target vessel revascularization, and major adverse cardiac events (p <0.0001 for all comparisons) compared to patients with normal flow. In conclusion, transient or persistent no reflow complicates approximately 1 in 20 PCIs and results in stepwise increases in in-hospital and 30-day adverse outcomes.

  14. Effect of RAAS blockers on adverse clinical outcomes in high CVD risk subjects with atrial fibrillation

    PubMed Central

    Chaugai, Sandip; Sherpa, Lhamo Yanchang; Sepehry, Amir A.; Arima, Hisatomi; Wang, Dao Wen

    2016-01-01

    Abstract Recent studies have demonstrated that atrial fibrillation significantly increases the risk of adverse clinical outcomes in high cardiovascular disease risk subjects. Application of renin–angiotensin–aldosterone system blockers for prevention of recurrence of atrial fibrillation and adverse clinical outcomes in subjects with atrial fibrillation is a theoretically appealing concept. However, results of clinical trials evaluating the effect of renin–angiotensin–aldosterone blockers on adverse clinical outcomes in high cardiovascular disease risk subjects with atrial fibrillation remain inconclusive. A pooled study of 6 randomized controlled trials assessing the efficacy of renin–angiotensin–aldosterone blockers on subjects with atrial fibrillation was performed. A total of 6 randomized controlled trials enrolled a total of 53,510 patients followed for 1 to 5 years. RAAS blockade therapy was associated with 14% reduction in the incidence of heart failure (OR: 0.86, [95%CI: 0.76– 0.97], P=0.018) and 17% reduction in the incidence of CVE (OR: 0.83, [95%CI: 0.70–0.99], P = 0.038). The corresponding decline in absolute risk against heart failure (ARR: 1.4%, [95%CI: 0.2–2.6%], P = 0.018) and CVE (ARR: 3.5%, [95%CI: 0.0–6.9%], P = 0.045) in the AF group was much higher than the non-AF group for heart failure (ARR: 0.4%, [95%CI: 0.0–0.7%], P = 0.057) and CVE (ARR: 1.6%, [95%CI: –0.1% to 3.3%], P = 0.071). No significant effect was noted on all-cause or cardiovascular mortality, stroke, or myocardial infarction. This study suggests that RAAS blockade offers protection against heart failure and cardiovascular events in high cardiovascular disease risk subjects with atrial fibrillation. PMID:27368043

  15. Merging Adverse Outcome Pathway (AOP) and Mode of Action (MOA) Frameworks: Assembling Knowledge for Use in Risk Assessment

    EPA Science Inventory

    The Adverse Outcome Pathway has emerged as an internationally harmonized mechanism for organizing biological information in a chemical agnostic manner. This construct is valuable for interpreting the results from high-throughput toxicity (HTT) assessment by providing a mechanisti...

  16. Conceptual Model for Assessing Criteria Air Pollutants in a Multipollutant Context: A Modified Adverse Outcome Pathway Approach

    EPA Science Inventory

    Background: Air pollution consists of a complex mixture of particulate and gaseous components. Individual criteria and other hazardous air pollutants have been linked to adverse respiratory and cardiovascular health outcomes. However, assessing risk of air pollutant mixtures is d...

  17. Use of the adverse outcome pathway framework to represent cross-species consequences of specific pathway perturbations

    EPA Science Inventory

    The adverse outcome pathway (AOP) framework has been developed as a means for assembling scientifically defensible descriptions of how particular molecular perturbations, termed molecular initiating events (MIEs), can evoke a set of predictable responses at different levels of bi...

  18. Immunomodulation by dietary long chain omega-3 fatty acids and the potential for adverse health outcomes.

    PubMed

    Fenton, Jenifer I; Hord, Norman G; Ghosh, Sanjoy; Gurzell, Eric A

    2013-01-01

    Recommendations to consume fish for prevention of cardiovascular disease (CVD), along with the U.S. Food and Drug Administration-approved generally recognized as safe (GRAS) status for long chain omega-3 fatty acids, may have had the unanticipated consequence of encouraging long-chain omega-3 (ω-3) fatty acid [(eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)] supplementation and fortification practices. While there is evidence supporting a protective role for EPA/DHA supplementation in reducing sudden cardiac events, the safety and efficacy of supplementation with LCω-3PUFA in the context of other disease outcomes is unclear. Recent studies of bacterial, viral, and fungal infections in animal models of infectious disease demonstrate that LCω-3PUFA intake dampens immunity and alters pathogen clearance and can result in reduced survival. The same physiological properties of EPA/DHA that are responsible for the amelioration of inflammation associated with chronic cardiovascular pathology or autoimmune states, may impair pathogen clearance during acute infections by decreasing host resistance or interfere with tumor surveillance resulting in adverse health outcomes. Recent observations that high serum LCω-3PUFA levels are associated with higher risk of prostate cancer and atrial fibrillation raise concern for adverse outcomes. Given the widespread use of supplements and fortification of common food items with LCω-3PUFA, this review focuses on the immunomodulatory effects of the dietary LCω-3PUFAs, EPA and DHA, the mechanistic basis for potential negative health outcomes, and calls for biomarker development and validation as rational first steps towards setting recommended dietary intake levels.

  19. Immunomodulation by dietary long chain omega-3 fatty acids and the potential for adverse health outcomes.

    PubMed

    Fenton, Jenifer I; Hord, Norman G; Ghosh, Sanjoy; Gurzell, Eric A

    2013-01-01

    Recommendations to consume fish for prevention of cardiovascular disease (CVD), along with the U.S. Food and Drug Administration-approved generally recognized as safe (GRAS) status for long chain omega-3 fatty acids, may have had the unanticipated consequence of encouraging long-chain omega-3 (ω-3) fatty acid [(eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)] supplementation and fortification practices. While there is evidence supporting a protective role for EPA/DHA supplementation in reducing sudden cardiac events, the safety and efficacy of supplementation with LCω-3PUFA in the context of other disease outcomes is unclear. Recent studies of bacterial, viral, and fungal infections in animal models of infectious disease demonstrate that LCω-3PUFA intake dampens immunity and alters pathogen clearance and can result in reduced survival. The same physiological properties of EPA/DHA that are responsible for the amelioration of inflammation associated with chronic cardiovascular pathology or autoimmune states, may impair pathogen clearance during acute infections by decreasing host resistance or interfere with tumor surveillance resulting in adverse health outcomes. Recent observations that high serum LCω-3PUFA levels are associated with higher risk of prostate cancer and atrial fibrillation raise concern for adverse outcomes. Given the widespread use of supplements and fortification of common food items with LCω-3PUFA, this review focuses on the immunomodulatory effects of the dietary LCω-3PUFAs, EPA and DHA, the mechanistic basis for potential negative health outcomes, and calls for biomarker development and validation as rational first steps towards setting recommended dietary intake levels. PMID:24183073

  20. Maternal Snoring May Predict Adverse Pregnancy Outcomes: A Cohort Study in China

    PubMed Central

    Ge, Xing; Tao, Fangbiao

    2016-01-01

    Objective To examine the prevalence of snoring during pregnancy and its effects on key pregnancy outcomes. Methods Pregnant women were consecutively recruited in their first trimester. Habitual snoring was screened by using a questionnaire in the 1st and 3rd trimester, respectively. According to the time of snoring, participants were divided into pregnancy onset snorers, chronic snorers and non-snorers. Logistic regressions were performed to examine the associations between snoring and pregnancy outcomes. Results Of 3 079 pregnant women, 16.6% were habitual snorers, with 11.7% were pregnancy onset snorers and 4.9% were chronic snorers. After adjusting for potential confounders, chronic snorers were independently associated with gestational diabetes mellitus (GDM) (RR 1.66, 95%CI 1.09–2.53). Both pregnancy onset and chronic snorers were independently associated with placental adhesion (RR 1.96, 95%CI 1.17–3.27, and RR 2.33, 95%CI 1.22–4.46, respectively). Pregnancy onset snorers were at higher risk of caesarean delivery (RR 1.37, 95%CI 1.09–1.73) and having macrosomia (RR 1.54, 95%CI 1.05–2.27) and large for gestational age (LGA) (RR 1.71, 95%CI 1.31–2.24) infants. In addition, being overweight or obese before pregnancy plays an important role in mediating snoring and adverse pregnancy outcomes. Conclusions Maternal snoring may increase the risk of adverse pregnancy outcomes, and being overweight or obese before pregnancy with snoring is remarkable for researchers. Further studies are still needed to confirm our results. PMID:26871434

  1. Generation of computationally predicted Adverse Outcome Pathway networks through integration of publicly available in vivo, in vitro, phenotype, and biological pathway data.

    EPA Science Inventory

    The Adverse Outcome Pathway (AOP) framework is becoming a widely used tool for organizing and summarizing the mechanistic information connecting molecular perturbations by environmental stressors with adverse ecological and human health outcomes. However, the conventional process...

  2. Adverse Obstetric and Perinatal Outcomes following Treatment of Adolescent and Young Adult Cancer: A Population-Based Cohort Study

    PubMed Central

    Haggar, Fatima A.; Pereira, Gavin; Preen, David; Holman, C. D'Arcy; Einarsdottir, Kristjana

    2014-01-01

    Objective To investigate obstetric and perinatal outcomes among female survivors of adolescent and young adult (AYA) cancers and their offspring. Methods Using multivariate analysis of statewide linked data, outcomes of all first completed pregnancies (n = 1894) in female survivors of AYA cancer diagnosed in Western Australia during the period 1982–2007 were compared with those among females with no cancer history. Comparison pregnancies were matched by maternal age-group, parity and year of delivery. Results Compared with the non-cancer group, female survivors of AYA cancer had an increased risk of threatened abortion (adjusted relative risk 2.09, 95% confidence interval 1.51–2.74), gestational diabetes (2.65, 2.08–3.57), pre-eclampsia (1.32, 1.04–1.87), post-partum hemorrhage (2.83, 1.92–4.67), cesarean delivery (2.62, 2.22–3.04), and maternal postpartum hospitalization>5 days (3.01, 1.72–5.58), but no excess risk of threatened preterm delivery, antepartum hemorrhage, premature rupture of membranes, failure of labor to progress or retained placenta. Their offspring had an increased risk of premature birth (<37 weeks: 1.68, 1.21–2.08), low birth weight (<2500 g: 1.51, 1.23–2.12), fetal growth restriction (3.27, 2.45–4.56), and neonatal distress indicated by low Apgar score (<7) at 1 minute (2.83, 2.28–3.56), need for resuscitation (1.66, 1.27–2.19) or special care nursery admission (1.44, 1.13–1.78). Congenital abnormalities and perinatal deaths (intrauterine or ≤7 days of birth) were not increased among offspring of survivors. Conclusion Female survivors of AYA cancer have moderate excess risks of adverse obstetric and perinatal outcomes arising from subsequent pregnancies that may require additional surveillance or intervention. PMID:25485774

  3. A clinical risk score of myocardial fibrosis predicts adverse outcomes in aortic stenosis

    PubMed Central

    Chin, Calvin W.L.; Messika-Zeitoun, David; Shah, Anoop S.V.; Lefevre, Guillaume; Bailleul, Sophie; Yeung, Emily N.W.; Koo, Maria; Mirsadraee, Saeed; Mathieu, Tiffany; Semple, Scott I.; Mills, Nicholas L.; Vahanian, Alec; Newby, David E.; Dweck, Marc R.

    2016-01-01

    Aims Midwall myocardial fibrosis on cardiovascular magnetic resonance (CMR) is a marker of early ventricular decompensation and adverse outcomes in aortic stenosis (AS). We aimed to develop and validate a novel clinical score using variables associated with midwall fibrosis. Methods and results One hundred forty-seven patients (peak aortic velocity (Vmax) 3.9 [3.2,4.4] m/s) underwent CMR to determine midwall fibrosis (CMR cohort). Routine clinical variables that demonstrated significant association with midwall fibrosis were included in a multivariate logistic score. We validated the prognostic value of the score in two separate outcome cohorts of asymptomatic patients (internal: n = 127, follow-up 10.3 [5.7,11.2] years; external: n = 289, follow-up 2.6 [1.6,4.5] years). Primary outcome was a composite of AS-related events (cardiovascular death, heart failure, and new angina, dyspnoea, or syncope). The final score consisted of age, sex, Vmax, high-sensitivity troponin I concentration, and electrocardiographic strain pattern [c-statistic 0.85 (95% confidence interval 0.78–0.91), P < 0.001; Hosmer–Lemeshow χ2 = 7.33, P = 0.50]. Patients in the outcome cohorts were classified according to the sensitivity and specificity of this score (both at 98%): low risk (probability score <7%), intermediate risk (7–57%), and high risk (>57%). In the internal outcome cohort, AS-related event rates were >10-fold higher in high-risk patients compared with those at low risk (23.9 vs. 2.1 events/100 patient-years, respectively; log rank P < 0.001). Similar findings were observed in the external outcome cohort (31.6 vs. 4.6 events/100 patient-years, respectively; log rank P < 0.001). Conclusion We propose a clinical score that predicts adverse outcomes in asymptomatic AS patients and potentially identifies high-risk patients who may benefit from early valve replacement. PMID:26491110

  4. Complications and fetal outcome in diabetic pregnancy. Intensified conventional versus insulin pump therapy.

    PubMed

    Burkart, W; Hanker, J P; Schneider, H P

    1988-01-01

    From 1978 to 1986 a total of 189 pregnant diabetic women gave birth at our hospital. In this randomized prospective study the influence of maternal diabetes treatment in normoglycemic patients, continuous subcutaneous insulin infusion (n = 48) versus intensified conventional treatment (n = 41), is evaluated. These two groups of patients are further compared to patients (n = 28) who underwent conventional diabetes treatment during pregnancy. It can be shown from our data that the rate of complications such as preeclampsia, intrauterine growth retardation, premature labor and premature delivery can be reduced by intensified conventional and insulin pump treatment as compared to conventionally treated patients with late onset of pregnancy care. As expected, in the groups of CSII and ICT patients no difference in the rate of pregnancy complications nor in fetal outcome could be demonstrated. Among CSII pregnancies 12/48 were complicated, in the ICT population the respective figure was 13/41 (CT: 20/28). The mean gestational age at the time of delivery ranged between 38 and 40 weeks, depending on the severity of maternal diabetes. CT patients were delivered earlier in all White classes. Fetal morbidity was nearly equal in CSII and ICT children, in CT patients it was greatly enhanced. Also the mortality (perinatal and neonatal) was considerably larger in CT patients (6/28), again, in the CSII and ICT population the mortality was nearly identical (2/48 and 3/41). We conclude, from our prospective information, that insulin pump therapy during pregnancy is indicated if intensified conventional treatment does not lead to normoglycemia.(ABSTRACT TRUNCATED AT 250 WORDS)

  5. The adverse effect of spasticity on 3-month poststroke outcome using a population-based model.

    PubMed

    Belagaje, S R; Lindsell, C; Moomaw, C J; Alwell, K; Flaherty, M L; Woo, D; Dunning, K; Khatri, P; Adeoye, O; Kleindorfer, D; Broderick, J; Kissela, B

    2014-01-01

    Several devices and medications have been used to address poststroke spasticity. Yet, spasticity's impact on outcomes remains controversial. Using data from a cohort of 460 ischemic stroke patients, we previously published a validated multivariable regression model for predicting 3-month modified Rankin Score (mRS) as an indicator of functional outcome. Here, we tested whether including spasticity improved model fit and estimated the effect spasticity had on the outcome. Spasticity was defined by a positive response to the question "Did you have spasticity following your stroke?" on direct interview at 3 months from stroke onset. Patients who had expired by 90 days (n = 30) or did not have spasticity data available (n = 102) were excluded. Spasticity affected the 3-month functional status (β = 0.420, 95 CI = 0.194 to 0.645) after accounting for age, diabetes, leukoaraiosis, and retrospective NIHSS. Using spasticity as a covariable, the model's R (2) changed from 0.599 to 0.622. In our model, the presence of spasticity in the cohort was associated with a worsened 3-month mRS by an average of 0.4 after adjusting for known covariables. This significant adverse effect on functional outcomes adds predictive value beyond previously established factors. PMID:25147752

  6. The Adverse Effect of Spasticity on 3-Month Poststroke Outcome Using a Population-Based Model

    PubMed Central

    Belagaje, S. R.; Lindsell, C.; Moomaw, C. J.; Alwell, K.; Flaherty, M. L.; Woo, D.; Dunning, K.; Khatri, P.; Adeoye, O.; Kleindorfer, D.; Broderick, J.; Kissela, B.

    2014-01-01

    Several devices and medications have been used to address poststroke spasticity. Yet, spasticity's impact on outcomes remains controversial. Using data from a cohort of 460 ischemic stroke patients, we previously published a validated multivariable regression model for predicting 3-month modified Rankin Score (mRS) as an indicator of functional outcome. Here, we tested whether including spasticity improved model fit and estimated the effect spasticity had on the outcome. Spasticity was defined by a positive response to the question “Did you have spasticity following your stroke?” on direct interview at 3 months from stroke onset. Patients who had expired by 90 days (n = 30) or did not have spasticity data available (n = 102) were excluded. Spasticity affected the 3-month functional status (β = 0.420, 95 CI = 0.194 to 0.645) after accounting for age, diabetes, leukoaraiosis, and retrospective NIHSS. Using spasticity as a covariable, the model's R2 changed from 0.599 to 0.622. In our model, the presence of spasticity in the cohort was associated with a worsened 3-month mRS by an average of 0.4 after adjusting for known covariables. This significant adverse effect on functional outcomes adds predictive value beyond previously established factors. PMID:25147752

  7. Laparoscopic donor nephrectomy for the pediatric recipient population: Risk factors for adverse outcomes.

    PubMed

    Walther, Ashley E; Coots, Abigail C; Goebel, Jens W; Alonso, Maria H; Ryckman, Frederick C; Tiao, Greg M; Nathan, Jaimie D

    2015-12-01

    Kidney transplantation is the optimal treatment of ESRD in children. Some studies have reported inferior outcomes in recipients of LDN allografts who are ≤ 5 yr of age. We performed a retrospective review of pediatric recipient outcomes of 110 LDN allografts at our institution and examined predictors of adverse outcomes. Subgroup analysis was performed by dividing recipients into three age categories: 0-5 yr, 6-17 yr, and ≥ 18 yr. There was no significant difference between incidences of DGF or ARE between groups. Kaplan-Meier analysis demonstrated 100% allograft survival in 0- to 5-yr-old recipients, nearly reaching statistical significance (p = 0.07) for outcome superior to that of the two older age groups. Pretransplant HD was associated with increased risk of DGF (p = 0.05). Significant risk factors for ARE were recipient weight >15 kg (p = 0.033) and multiple renal arteries (p = 0.047). Previous ARE was associated with an increased risk of allograft failure (p = 0.02). LDN is not associated with increased risk of DGF, ARE, or allograft failure in the youngest recipients. These findings support an aggressive pursuit of preemptive transplantation even in the youngest pediatric allograft recipients. PMID:26329665

  8. Common Sleep Disorders Increase Risk of Motor Vehicle Crashes and Adverse Health Outcomes in Firefighters

    PubMed Central

    Barger, Laura K.; Rajaratnam, Shantha M.W.; Wang, Wei; O'Brien, Conor S.; Sullivan, Jason P.; Qadri, Salim; Lockley, Steven W.; Czeisler, Charles A.

    2015-01-01

    Study Objectives: Heart attacks and motor vehicle crashes are the leading causes of death in US firefighters. Given that sleep disorders are an independent risk factor for both of these, we examined the prevalence of common sleep disorders in a national sample of firefighters and their association with adverse health and safety outcomes. Methods: Firefighters (n = 6,933) from 66 US fire departments were assessed for common sleep disorders using validated screening tools, as available. Firefighters were also surveyed about health and safety, and documentation was collected for reported motor vehicle crashes. Results: A total of 37.2% of firefighters screened positive for any sleep disorder including obstructive sleep apnea (OSA), 28.4%; insomnia, 6.0%; shift work disorder, 9.1%; and restless legs syndrome, 3.4%. Compared with those who did not screen positive, firefighters who screened positive for a sleep disorder were more likely to report a motor vehicle crash (adjusted odds ratio 2.00, 95% CI 1.29–3.12, p = 0.0021) and were more likely to self-report falling asleep while driving (2.41, 2.06–2.82, p < 0.0001). Firefighters who screened positive for a sleep disorder were more likely to report having cardiovascular disease (2.37, 1.54–3.66, p < 0.0001), diabetes (1.91, 1.31–2.81, p = 0.0009), depression (3.10, 2.49–3.85, p < 0.0001), and anxiety (3.81, 2.87–5.05, p < 0.0001), and to report poorer health status (p < 0.0001) than those who did not screen positive. Adverse health and safety associations persisted when OSA and non-OSA sleep disorders were examined separately. Conclusions: Sleep disorders are prevalent in firefighters and are associated with increased risk of adverse health and safety outcomes. Future research is needed to assess the efficacy of occupational sleep disorders prevention, screening, and treatment programs in fire departments to reduce these safety and health risks. Citation: Barger LK, Rajaratnam SM, Wang W, O'Brien CS

  9. Applying Adverse Outcome Pathways (AOPs) to support Integrated Approaches to Testing and Assessment (IATA).

    PubMed

    Tollefsen, Knut Erik; Scholz, Stefan; Cronin, Mark T; Edwards, Stephen W; de Knecht, Joop; Crofton, Kevin; Garcia-Reyero, Natalia; Hartung, Thomas; Worth, Andrew; Patlewicz, Grace

    2014-12-01

    Chemical regulation is challenged by the large number of chemicals requiring assessment for potential human health and environmental impacts. Current approaches are too resource intensive in terms of time, money and animal use to evaluate all chemicals under development or already on the market. The need for timely and robust decision making demands that regulatory toxicity testing becomes more cost-effective and efficient. One way to realize this goal is by being more strategic in directing testing resources; focusing on chemicals of highest concern, limiting testing to the most probable hazards, or targeting the most vulnerable species. Hypothesis driven Integrated Approaches to Testing and Assessment (IATA) have been proposed as practical solutions to such strategic testing. In parallel, the development of the Adverse Outcome Pathway (AOP) framework, which provides information on the causal links between a molecular initiating event (MIE), intermediate key events (KEs) and an adverse outcome (AO) of regulatory concern, offers the biological context to facilitate development of IATA for regulatory decision making. This manuscript summarizes discussions at the Workshop entitled "Advancing AOPs for Integrated Toxicology and Regulatory Applications" with particular focus on the role AOPs play in informing the development of IATA for different regulatory purposes. PMID:25261300

  10. Adverse Outcome Pathways-Organizing Toxicological Information to Improve Decision Making.

    PubMed

    Edwards, Stephen W; Tan, Yu-Mei; Villeneuve, Daniel L; Meek, M E; McQueen, Charlene A

    2016-01-01

    The number of chemicals for which environmental regulatory decisions are required far exceeds the current capacity for toxicity testing. High-throughput screening commonly used for drug discovery has the potential to increase this capacity. The adverse outcome pathway (AOP) concept has emerged as a framework for connecting high-throughput toxicity testing (HTT) and other results to potential impacts on human and wildlife populations. As a result of international efforts, the AOP development process is now well-defined and efforts are underway to broaden the participation through outreach and training. One key principle is that AOPs represent the chemical-agnostic portions of pathways to increase the generalizability of their application from early key events to overt toxicity. The closely related mode of action framework extends the AOP as needed when evaluating the potential risk of a specific chemical. This in turn enables integrated approaches to testing and assessment (IATA), which incorporate results of assays at various levels of biologic organization such as in silico; HTT; chemical-specific aspects including absorption, distribution, metabolism, and excretion (ADME); and an AOP describing the biologic basis of toxicity. Thus, it is envisaged that provision of limited information regarding both the AOP for critical effects and the ADME for any chemical associated with any adverse outcome would allow for the development of IATA and permit more detailed AOP and ADME research, where higher precision is needed based on the decision context. PMID:26537250

  11. The adverse outcome pathway (AOP) for chemical binding to tubulin in oocytes leading to aneuploid offspring.

    PubMed

    Marchetti, Francesco; Massarotti, Alberto; Yauk, Carole L; Pacchierotti, Francesca; Russo, Antonella

    2016-03-01

    The Organisation for Economic Co-operation and Development (OECD) has launched the Adverse Outcome Pathway (AOP) Programme to advance knowledge of pathways of toxicity and improve the use of mechanistic information in risk assessment. An AOP links a molecular initiating event (MIE) to an adverse outcome (AO) through intermediate key events (KE). Here, we present the scientific evidence in support of an AOP whereby chemicals that bind to tubulin cause microtubule depolymerization resulting in spindle disorganization followed by altered chromosome alignment and segregation and the generation of aneuploidy in female germ cells, ultimately leading to aneuploidy in the offspring. Aneuploidy, an abnormal number of chromosomes that is not an exact multiple of the haploid number, is a well-known cause of human disease and represents a major cause of infertility, pregnancy failure, and serious genetic disorders in the offspring. Among chemicals that induce aneuploidy in female germ cells, a large majority impairs microtubule dynamics and spindle function. Colchicine, a prototypical chemical that binds to tubulin and causes microtubule depolymerization, is used here to illustrate the AOP. This AOP is specific to female germ cells exposed during the periovulation period. Although the majority of the data come from rodent studies, the available evidence suggests that the MIE and KEs are conserved across species and would occur in human oocytes. The development of AOPs related to mutagenicity in germ cells is expected to aid the identification of potential hazards to germ cell genomic integrity and support regulatory efforts to protect population health.

  12. Adverse Outcome Pathways-Organizing Toxicological Information to Improve Decision Making.

    PubMed

    Edwards, Stephen W; Tan, Yu-Mei; Villeneuve, Daniel L; Meek, M E; McQueen, Charlene A

    2016-01-01

    The number of chemicals for which environmental regulatory decisions are required far exceeds the current capacity for toxicity testing. High-throughput screening commonly used for drug discovery has the potential to increase this capacity. The adverse outcome pathway (AOP) concept has emerged as a framework for connecting high-throughput toxicity testing (HTT) and other results to potential impacts on human and wildlife populations. As a result of international efforts, the AOP development process is now well-defined and efforts are underway to broaden the participation through outreach and training. One key principle is that AOPs represent the chemical-agnostic portions of pathways to increase the generalizability of their application from early key events to overt toxicity. The closely related mode of action framework extends the AOP as needed when evaluating the potential risk of a specific chemical. This in turn enables integrated approaches to testing and assessment (IATA), which incorporate results of assays at various levels of biologic organization such as in silico; HTT; chemical-specific aspects including absorption, distribution, metabolism, and excretion (ADME); and an AOP describing the biologic basis of toxicity. Thus, it is envisaged that provision of limited information regarding both the AOP for critical effects and the ADME for any chemical associated with any adverse outcome would allow for the development of IATA and permit more detailed AOP and ADME research, where higher precision is needed based on the decision context.

  13. Defining molecular initiating events in the adverse outcome pathway framework for risk assessment.

    PubMed

    Allen, Timothy E H; Goodman, Jonathan M; Gutsell, Steve; Russell, Paul J

    2014-12-15

    Consumer and environmental safety decisions are based on exposure and hazard data, interpreted using risk assessment approaches. The adverse outcome pathway (AOP) conceptual framework has been presented as a logical sequence of events or processes within biological systems which can be used to understand adverse effects and refine current risk assessment practices in ecotoxicology. This framework can also be applied to human toxicology and is explored on the basis of investigating the molecular initiating events (MIEs) of compounds. The precise definition of the MIE has yet to reach general acceptance. In this work we present a unified MIE definition: an MIE is the initial interaction between a molecule and a biomolecule or biosystem that can be causally linked to an outcome via a pathway. Case studies are presented, and issues with current definitions are addressed. With the development of a unified MIE definition, the field can look toward defining, classifying, and characterizing more MIEs and using knowledge of the chemistry of these processes to aid AOP research and toxicity risk assessment. We also present the role of MIE research in the development of in vitro and in silico toxicology and suggest how, by using a combination of biological and chemical approaches, MIEs can be identified and characterized despite a lack of detailed reports, even for some of the most studied molecules in toxicology.

  14. Adverse Childhood Experiences and Adult Health Outcomes Among Veteran and Non-Veteran Women

    PubMed Central

    Blosnich, John R.; Dichter, Melissa E.

    2015-01-01

    Abstract Background: Women veterans represent a vulnerable population with unique health needs and disparities in access to care. One constellation of exposures related to subsequent poor health includes adverse childhood experiences (ACEs; e.g., physical and sexual child abuse), though research on impacts of ACEs among women veterans is limited. Methods: Data were drawn from the 2010 Behavioral Risk Factor Surveillance System for the 11 states that included the ACE module (n=36,485). Weighted chi-squared tests and multivariable logistic regression were used to assess the prevalence of ACEs among women veterans compared with women non-veterans and differences in the following outcomes, controlling for ACEs: social support, inadequate sleep, life satisfaction, mental distress, smoking, heavy alcohol use, obesity, diabetes, cardiovascular disease symptoms, asthma, and disability. Results: Women veterans (1.6% of the total sample) reported a higher prevalence of 7 out of 11 childhood adversities and higher mean ACE score than women non-veterans. Women veterans were more likely to be current smokers and report a disability, associations which were attenuated when controlling for ACE. Conclusions: Despite women veterans' higher prevalence of ACE, their health outcomes did not differ substantially from non-veterans. Further research is needed to understand the intersections of traumatic experiences and sources of resilience over the lifecourse among women veterans. PMID:26390379

  15. Time-Dependent Effects in Algae for Chemicals with Different Adverse Outcome Pathways: A Novel Approach.

    PubMed

    Vogs, Carolina; Altenburger, Rolf

    2016-07-19

    Chemicals affect unicellular algae as a result of toxicokinetic and toxicodynamic processes. The internal concentration of chemicals in algae cells typically reaches equilibrium within minutes, while damage cumulatively increases over hours. The time gap between the steady state of internal exposure and damage development is thus suspected to span up to hours, mainly due to toxicodynamic processes. The quantification of rate-limited toxicodynamic processes, aggregated as a progressive effect from an initiating molecular event through biological key events toward the adverse outcome on algae growth inhibition, might discriminate between different adverse outcome pathways (AOPs). To support our hypothesis, we selected six chemicals according to different physicochemical properties and three distinctly dissimilar AOPs. The time courses of internal concentrations were linked to the observed affected Scenedesmus vacuolatus growth using toxicokinetic-toxicodynamic modeling. Effects on cell growth were explained by effect progression and not by the time to reach internal equilibrium concentration. Effect progression rates ranged over 6 orders of magnitude for all chemicals but varied by less than 1 order of magnitude within similar AOP (photosystem II inhibitors > reactive chemicals > lipid biosynthesis inhibitors), meaning that inhibitors of photosystem II advance an effect toward algae growth fastest compared to reactive chemicals and inhibitors of lipid biosynthesis. PMID:27149222

  16. Infertility, Pregnancy Loss and Adverse Birth Outcomes in Relation to Maternal Secondhand Tobacco Smoke Exposure

    PubMed Central

    Meeker, John D.; Benedict, Merle D.

    2013-01-01

    A substantial proportion of the etiology involved in female infertility and adverse pregnancy outcomes remains idiopathic. Recent scientific research has suggested a role for environmental factors in these conditions. Secondhand tobacco smoke (STS) contains a number of known or suspected reproductive toxins, and human exposure to STS is prevalent worldwide. Robust evidence exists for the toxic effects of active smoking on fertility and pregnancy, but studies of passive exposure are much more limited in number. While the association between maternal STS exposure and declined birth weight has been fairly well-documented, only recently have epidemiologic studies begun to provide suggestive evidence for delayed conception, altered menstrual cycling, early pregnancy loss (e.g. spontaneous abortion), preterm delivery, and congenital malformations in relation to STS exposure. There is also new evidence that developmental exposures to tobacco smoke may be associated with reproductive effects in adulthood. To date, most studies have estimated maternal STS exposure through self-report even though exposure biomarkers are less prone to error and recall bias. In addition to utilizing biomarkers of STS exposure, future studies should aim to identify vital windows of STS exposure, important environmental co-exposures, individual susceptibility factors, and specific STS constituents associated with female infertility and adverse pregnancy outcomes. The role of paternal exposures/factors should also be investigated. PMID:23888128

  17. Time-Dependent Effects in Algae for Chemicals with Different Adverse Outcome Pathways: A Novel Approach.

    PubMed

    Vogs, Carolina; Altenburger, Rolf

    2016-07-19

    Chemicals affect unicellular algae as a result of toxicokinetic and toxicodynamic processes. The internal concentration of chemicals in algae cells typically reaches equilibrium within minutes, while damage cumulatively increases over hours. The time gap between the steady state of internal exposure and damage development is thus suspected to span up to hours, mainly due to toxicodynamic processes. The quantification of rate-limited toxicodynamic processes, aggregated as a progressive effect from an initiating molecular event through biological key events toward the adverse outcome on algae growth inhibition, might discriminate between different adverse outcome pathways (AOPs). To support our hypothesis, we selected six chemicals according to different physicochemical properties and three distinctly dissimilar AOPs. The time courses of internal concentrations were linked to the observed affected Scenedesmus vacuolatus growth using toxicokinetic-toxicodynamic modeling. Effects on cell growth were explained by effect progression and not by the time to reach internal equilibrium concentration. Effect progression rates ranged over 6 orders of magnitude for all chemicals but varied by less than 1 order of magnitude within similar AOP (photosystem II inhibitors > reactive chemicals > lipid biosynthesis inhibitors), meaning that inhibitors of photosystem II advance an effect toward algae growth fastest compared to reactive chemicals and inhibitors of lipid biosynthesis.

  18. Applying Adverse Outcome Pathways (AOPs) to support Integrated Approaches to Testing and Assessment (IATA).

    PubMed

    Tollefsen, Knut Erik; Scholz, Stefan; Cronin, Mark T; Edwards, Stephen W; de Knecht, Joop; Crofton, Kevin; Garcia-Reyero, Natalia; Hartung, Thomas; Worth, Andrew; Patlewicz, Grace

    2014-12-01

    Chemical regulation is challenged by the large number of chemicals requiring assessment for potential human health and environmental impacts. Current approaches are too resource intensive in terms of time, money and animal use to evaluate all chemicals under development or already on the market. The need for timely and robust decision making demands that regulatory toxicity testing becomes more cost-effective and efficient. One way to realize this goal is by being more strategic in directing testing resources; focusing on chemicals of highest concern, limiting testing to the most probable hazards, or targeting the most vulnerable species. Hypothesis driven Integrated Approaches to Testing and Assessment (IATA) have been proposed as practical solutions to such strategic testing. In parallel, the development of the Adverse Outcome Pathway (AOP) framework, which provides information on the causal links between a molecular initiating event (MIE), intermediate key events (KEs) and an adverse outcome (AO) of regulatory concern, offers the biological context to facilitate development of IATA for regulatory decision making. This manuscript summarizes discussions at the Workshop entitled "Advancing AOPs for Integrated Toxicology and Regulatory Applications" with particular focus on the role AOPs play in informing the development of IATA for different regulatory purposes.

  19. Common variants of the vitamin D binding protein gene and adverse health outcomes

    PubMed Central

    Malik, Suneil; Fu, Lei; Juras, David James; Karmali, Mohamed; Wong, Betty Y. L.; Gozdzik, Agnes

    2013-01-01

    The vitamin D binding protein (DBP) is the major plasma carrier for vitamin D and its metabolites, but it is also an actin scavenger, and is the precursor to the immunomodulatory protein, Gc-MAF. Two missense variants of the DBP gene – rs7041 encoding Asp432Glu and rs4588 encoding Thr436Lys – change the amino acid sequence and alter the protein function. They are common enough to generate population-wide constitutive differences in vitamin D status, based on assay of the serum metabolite, 25-hydroxyvitamin D (25OHD). Whether these variants also influence the role of vitamin D in an immunologic milieu is not known. However, the issue is relevant, given the immunomodulatory effects of DBP and the role of protracted innate immune-related inflammation in response to tissue injury or repeated infection. Indeed, DBP and vitamin D may jointly or independently contribute to a variety of adverse health outcomes unrelated to classical notions of their function in bone and mineral metabolism. This review summarizes the reports to date of associations between DBP variants, and various chronic and infectious diseases. The available information leads us to conclude that DBP variants are a significant and common genetic factor in some common disorders, and therefore, are worthy of closer attention. In view of the heightened interest in vitamin D as a public health target, well-designed studies that look simultaneously at vitamin D and its carrier in relation to genotypes and adverse health outcome should be encouraged. PMID:23427793

  20. Paternal dapoxetine administration induced deterioration in reproductive performance, fetal outcome, sexual behavior and biochemistry of male rats.

    PubMed

    ElMazoudy, R; AbdelHameed, N; ElMasry, A

    2015-01-01

    Dapoxetine, a selective serotonin reuptake inhibitor, is considered an antidepressant drug and has been developed for the treatment of premature ejaculation. Hence the objective was to assess whether dapoxetine administration to male rats adversely affect sexual behavior and pregnancy outcomes after mating with untreated female rats. Proven fertile male rats were gavaged with 0, 2.0, 4.0 and 8.0 mg dapoxetine per kg body weight (bw) per day (DC, DI, DII and DIII groups, respectively) for 70 days prior to mating with untreated female rats. Weight gain, organ weights and feed consumption were decreased significantly in the DII and DIII groups. A significant decline in the number of spermatozoa in the DII and DIII groups is attributed to a significant decrease in testosterone, luteinizing hormone and follicle-stimulating hormone. Levels of prolactin were significantly increased in the DII and DIII groups. Rats treated with a high dose of dapoxetine (8.0 mg kg(-1)) showed a significant inhibition in sperm motility and increment in sperm abnormalities. There was a pronounced decrease in fertility index in females mated with males treated chronically with 4.0 and 8.0 mg per kg bw dapoxetine. In addition, the treatment markedly increased the number of fetal resorptions in female rats impregnated by males in the DII and DIII groups reflecting their infertility. The number of implantation sites and the number of viable fetuses were also notably decreased in female rats impregnated by males given 4.0 or 8.0 mg kg(-1) dapoxetine. These findings suggest that the long-term dapoxetine at high dosages causes failure of the fertilization or successful impregnation of the females mated with dapoxetine-treated male rats, which were clearly able to copulate. A detrimental effect of dapoxetine on fertility parameters was also revealed.

  1. Intimate Partner Violence During Pregnancy and Adverse Neonatal Outcomes in Low-Income Women

    PubMed Central

    Bullock, Linda; Sharps, Phyllis; Schminkey, Donna; Comstock, Emily; Campbell, Jacquelyn

    2014-01-01

    Abstract Background: Intimate partner violence (IPV) affects an estimated 1.5 million U.S. women annually. IPV impacts maternal and neonatal health with higher rates of depression and low birth weight (LBW). Less studied is experiencing IPV and delivering a small for gestational age (SGA) baby. SGA neonates are at increased risk of developmental and behavioral problems. The negative sequelae persist into adulthood with increased rates of diabetes mellitus and coronary heart disease. Methods: In a sample of 239 pregnant women experiencing IPV, in urban and rural settings, we examined cross-sectional associations of severity of IPV and neonatal outcomes (i.e., birth weight and gestational age). Severity of IPV was measured by the Conflict Tactics Scale 2 and neonatal outcomes were collected at the time of delivery. Results: Outcomes were collected on 194 neonates; 14.9% (n=29) were classified as LBW, 19.1% (n=37) classified as SGA, and 9.8% (n=19) as LBW and SGA. Women reporting higher severity of IPV during pregnancy had a greater likelihood of delivering an SGA neonate (odds ratio [OR] 4.81; 95% confidence interval [95% CI] 1.86–12.47), and LBW neonate (OR 4.20; 95% CI 1.46–12.10). Conclusions: In a sample of pregnant women experiencing perinatal IPV, women experiencing greater severities of IPV were more likely to deliver a neonate with an adverse outcome. Early recognition and intervention of IPV is essential to reduce disparities in birth outcomes and long-term health outcomes for these neonates. PMID:25290007

  2. Correlation of Clinical and Dosimetric Factors With Adverse Pulmonary Outcomes in Children After Lung Irradiation

    SciTech Connect

    Venkatramani, Rajkumar; Kamath, Sunil; Wong, Kenneth; Malvar, Jemily; Sposto, Richard; Goodarzian, Fariba; Freyer, David R.; Keens, Thomas G.; and others

    2013-08-01

    Purpose: To identify the incidence and the risk factors for pulmonary toxicity in children treated for cancer with contemporary lung irradiation. Methods and Materials: We analyzed clinical features, radiographic findings, pulmonary function tests, and dosimetric parameters of children receiving irradiation to the lung fields over a 10-year period. Results: We identified 109 patients (75 male patients). The median age at irradiation was 13.8 years (range, 0.04-20.9 years). The median follow-up period was 3.4 years. The median prescribed radiation dose was 21 Gy (range, 0.4-64.8 Gy). Pulmonary toxic chemotherapy included bleomycin in 58.7% of patients and cyclophosphamide in 83.5%. The following pulmonary outcomes were identified and the 5-year cumulative incidence after irradiation was determined: pneumonitis, 6%; chronic cough, 10%; pneumonia, 35%; dyspnea, 11%; supplemental oxygen requirement, 2%; radiographic interstitial lung disease, 40%; and chest wall deformity, 12%. One patient died of progressive respiratory failure. Post-irradiation pulmonary function tests available from 44 patients showed evidence of obstructive lung disease (25%), restrictive disease (11%), hyperinflation (32%), and abnormal diffusion capacity (12%). Thoracic surgery, bleomycin, age, mean lung irradiation dose (MLD), maximum lung dose, prescribed dose, and dosimetric parameters between V{sub 22} (volume of lung exposed to a radiation dose ≥22 Gy) and V{sub 30} (volume of lung exposed to a radiation dose ≥30 Gy) were significant for the development of adverse pulmonary outcomes on univariate analysis. MLD, maximum lung dose, and V{sub dose} (percentage of volume of lung receiving the threshold dose or greater) were highly correlated. On multivariate analysis, MLD was the sole significant predictor of adverse pulmonary outcome (P=.01). Conclusions: Significant pulmonary dysfunction occurs in children receiving lung irradiation by contemporary techniques. MLD rather than prescribed

  3. Integrating Publicly Available Data to Generate Computationally Predicted Adverse Outcome Pathways for Fatty Liver.

    PubMed

    Bell, Shannon M; Angrish, Michelle M; Wood, Charles E; Edwards, Stephen W

    2016-04-01

    Newin vitrotesting strategies make it possible to design testing batteries for large numbers of environmental chemicals. Full utilization of the results requires knowledge of the underlying biological networks and the adverse outcome pathways (AOPs) that describe the route from early molecular perturbations to an adverse outcome. Curation of a formal AOP is a time-intensive process and a rate-limiting step to designing these test batteries. Here, we describe a method for integrating publicly available data in order to generate computationally predicted AOP (cpAOP) scaffolds, which can be leveraged by domain experts to shorten the time for formal AOP development. A network-based workflow was used to facilitate the integration of multiple data types to generate cpAOPs. Edges between graph entities were identified through direct experimental or literature information, or computationally inferred using frequent itemset mining. Data from the TG-GATEs and ToxCast programs were used to channel large-scale toxicogenomics information into a cpAOP network (cpAOPnet) of over 20 000 relationships describing connections between chemical treatments, phenotypes, and perturbed pathways as measured by differential gene expression and high-throughput screening targets. The resulting fatty liver cpAOPnet is available as a resource to the community. Subnetworks of cpAOPs for a reference chemical (carbon tetrachloride, CCl4) and outcome (fatty liver) were compared with published mechanistic descriptions. In both cases, the computational approaches approximated the manually curated AOPs. The cpAOPnet can be used for accelerating expert-curated AOP development and to identify pathway targets that lack genomic markers or high-throughput screening tests. It can also facilitate identification of key events for designing test batteries and for classification and grouping of chemicals for follow up testing.

  4. Illicit Drug Use and Adverse Birth Outcomes: Is It Drugs or Context?

    PubMed Central

    Strobino, Donna M.

    2008-01-01

    Prenatal drug use is commonly associated with adverse birth outcomes, yet no studies have controlled for a comprehensive set of associated social, psychosocial, behavioral, and biomedical risk factors. We examined the degree to which adverse birth outcomes associated with drug use are due to the drugs versus surrounding factors. Data are from a clinical sample of low-income women who delivered at Johns Hopkins Hospital between 1995 and 1996 (n = 808). Use of marijuana, cocaine, and opiates was determined by self-report, medical record, and urine toxicology screens at delivery. Information on various social, psychosocial, behavioral, and biomedical risk factors was gathered from a postpartum interview or the medical record. Multivariable regression models of birth outcomes (continuous birth weight and low birth weight ([LBW] <2,500 g)) were used to assess the effect of drug use independent of associated factors. In unadjusted results, all types of drug use were related to birth weight decrements and increased odds of LBW. However, only the effect of cocaine on continuous birth weight remained significant after adjusting for all associated factors (−142 g, p = 0.05). No drug was significantly related to LBW in fully adjusted models. About 70% of the unadjusted effect of cocaine use on continuous birth weight was explained by surrounding psychosocial and behavioral factors, particularly smoking and stress. Most of the unadjusted effects of opiate use were explained by smoking and lack of early prenatal care. Thus, prevention efforts that aim to improve newborn health must also address the surrounding context in which drug use frequently occurs. PMID:18791865

  5. Fetal outcomes following emergency department point-of-care ultrasound for vaginal bleeding in early pregnancy

    PubMed Central

    Varner, Catherine; Balaban, Dahlia; Borgundvaag, Bjug; McLeod, Shelley; Carver, Sally

    2016-01-01

    Objective To determine 20- and 40-week fetal outcomes following documentation of fetal cardiac activity (FCA) and intrauterine pregnancy (IUP) in women at less than 20 weeks’ gestation presenting to the emergency department (ED) with vaginal bleeding. Design Prospective observational cohort study. Setting Single-centre tertiary care ED. Participants Pregnant women at less than 20 weeks’ gestation presenting to the ED with vaginal bleeding. Intervention All study participants underwent ED point-of-care ultrasound (POCUS) to document IUP and FCA. Main outcome measures Prevalence of spontaneous abortion or pregnancy loss by 40 weeks’ gestational age following ED POCUS documentation of FCA or IUP in women at less than 20 weeks’ gestation. Results A total of 85 of 111 eligible patients were enrolled; FCA and IUP were detected in 43 (50.6%) and 54 (63.5%) participants, respectively. Participants with documented FCA on ED POCUS were less likely to experience pregnancy loss than participants without documented FCA were (5.0% vs 92.7%; Δ = 87.7%; 95% CI 71.0% to 93.7%), and participants with documented IUP were less likely to experience pregnancy loss than participants without documented IUP were (22.0% vs 93.5%; Δ = 71.5%; 95% CI 52.1% to 81.9%). Compared with radiologist-interpreted ultrasound, ED POCUS had sensitivity of 88.9% (95% CI 75.9% to 96.2%) and specificity of 100.0% (95% CI 89.6% to 100.0%) for documenting FCA, and sensitivity of 96.0% (95% CI 86.3% to 99.4%) and specificity of 93.1% (95% CI 77.2% to 99.0%) for documenting IUP. Conclusion In this cohort of women presenting to the ED with bleeding in the first 20 weeks of pregnancy, detection of IUP and especially FCA using POCUS performed by providers certified by the Canadian Emergency Ultrasound Society was associated with ongoing viable pregnancy at 20 and 40 weeks’ gestational age. These data might be useful for ED physicians counseling women with symptomatic early pregnancies about the chance

  6. Elevated Fecal Calprotectin Associates with Adverse Outcomes from Clostridium difficile Infection in Older Adults

    PubMed Central

    Rao, Krishna; Santhosh, Kavitha; Mogle, Jill A.; Higgins, Peter D. R.; Young, Vincent B.

    2016-01-01

    Background Clostridium difficile infection (CDI) causes a mild to moderate colitis in most patients, but some, especially older adults, develop severe, adverse outcomes. Biomarkers predicting outcomes are needed to optimize treatments. This study tested whether fecal calprotectin associated with a composite primary outcome of complicated CDI (intensive care unit admission, colectomy, or death due to CDI within 30 days of diagnosis) and/or 8-week recurrence. Methods Stool was collected in Cary-Blair media at the time of diagnosis from inpatients of age >60 years that tested positive for C. difficile (enzyme immunoassay [EIA] for toxin A/B or polymerase chain reaction for the tcdB gene). Fecal calprotectin was measured and normalized to solid stool weight. Analysis was performed using logistic regression. Variables were selected for the final model using likelihood ratio tests. Results Fifty patients were included with a mean age 72.8 (± 7.5), and 13 (26%) developed the primary outcome. Clinical variables such as age, gender, and comorbid disease did not associate with complicated CDI/recurrence, nor did traditional biomarkers such as serum albumin or white blood cell count. A high normalized fecal calprotectin (>2000 µg/g) associated with the primary outcome in the final model after adjustment for gender and detectable fecal toxin(s) by EIA (OR 24.9, 95% CI 2.4–257.9, P=.007) with a specificity of 91.9%. Conclusion This study provides evidence that fecal calprotectin level associates with complications from CDI in older adults. Further studies are required to validate these findings in larger cohorts and incorporate them into clinical prediction algorithms. PMID:27206404

  7. Linking Prenatal Maternal Adversity to Developmental Outcomes in Infants: The Role of Epigenetic Pathways

    PubMed Central

    Monk, Catherine; Spicer, Julie; Champagne, Frances A.

    2013-01-01

    Prenatal exposure to maternal stress, anxiety, and depression can have lasting effects on infant development with consequences for risk of psychopathology. Though the impact of prenatal maternal distress has been well documented, the potential mechanisms through which maternal psychosocial variables shape development have yet to be fully elucidated. Advances in molecular biology have highlighted the role of epigenetic mechanisms in regulating gene activity, neurobiology, and behavior and the potential role of environmentally-induced epigenetic variation in linking early life exposures to long-term biobehavioral outcomes. In this review, we discuss evidence illustrating the association between maternal prenatal distress and both fetal and infant developmental trajectories and the potential role of epigenetic mechanisms in mediating these effects. Postnatal experiences may have a critical moderating influence on prenatal effects, and here we review findings illustrating prenatal-postnatal interplay and the developmental and epigenetic consequences of postnatal mother-infant interactions. The in utero environment is regulated by placental function and there is emerging evidence that the placenta is highly susceptible to maternal distress and a target of epigenetic dysregulation. Integrating studies of prenatal exposures, placental function, and postnatal maternal care with the exploration of epigenetic mechanisms may provide novel insights into the pathophysiology induced by maternal distress. PMID:23062303

  8. Chlorination disinfection byproducts in water and their association with adverse reproductive outcomes: a review

    PubMed Central

    Nieuwenhuijsen, M.; Toledano, M.; Eaton, N.; Fawell, J.; Elliott, P.

    2000-01-01

    OBJECTIVES AND METHODS—Chlorination has been the major disinfectant process for domestic drinking water for many years. Concern about the potential health effects of the byproducts of chlorination has prompted the investigation of the possible association between exposure to these byproducts and incidence of human cancer, and more recently, with adverse reproductive outcomes. This paper evaluates both the toxicological and epidemiological data involving chlorination disinfection byproducts (DBPs) and adverse reproductive outcomes, and makes recommendations for future research.
RESULTS AND CONCLUSIONS—Relatively few toxicological and epidemiological studies have been carried out examining the effects of DBPs on reproductive health outcomes. The main outcomes of interest so far have been low birth weight, preterm delivery, spontaneous abortions, stillbirth, and birth defects— in particular central nervous system, major cardiac defects, oral cleft, and respiratory, and neural tube defects. Various toxicological and epidemiological studies point towards an association between trihalomethanes (THMs), one of the main DBPs and marker for total DBP load, and (low) birth weight, although the evidence is not conclusive. Administered doses in toxicological studies have been high and even though epidemiological studies have mostly shown excess risks, these were often not significant and the assessment of exposure was often limited. Some studies have shown associations for DBPs and other outcomes such as spontaneous abortions, stillbirth and birth defects, and although the evidence for these associations is weaker it is gaining weight. There is no evidence for an association between THMs and preterm delivery. The main limitation of most studies so far has been the relatively crude methodology, in particular for assessment of exposure.
RECOMMENDATIONS—Large, well designed epidemiological studies focusing on well defined end points taking into account relevant

  9. Different fetal-neonatal outcomes in siblings born to a mother with Graves-Basedow disease after total thyroidectomy: a case series

    PubMed Central

    2010-01-01

    Introduction We describe three different fetal or neonatal outcomes in the offspring of a mother who had persistent circulating thyrotropin receptor antibodies despite having undergone a total thyroidectomy several years before. Case presentation The three different outcomes were an intrauterine death, a mild and transient fetal and neonatal hyperthyroidism and a severe fetal and neonatal hyperthyroidism that required specific therapy. Conclusions The three cases are interesting because of the different outcomes, the absence of a direct correlation between thyrotropin receptor antibody levels and clinical signs, and the persistence of thyrotropin receptor antibodies several years after a total thyroidectomy. PMID:20170485

  10. International migration and adverse birth outcomes: role of ethnicity, region of origin and destination

    PubMed Central

    Glazier, Richard Henry; Blondel, Beatrice; Zeitlin, Jennifer; Gissler, Mika; Macfarlane, Alison; Ng, Edward; Heaman, Maureen; Stray-Pedersen, Babill; Gagnon, Anita J

    2010-01-01

    Background The literature on international migration and birth outcomes shows mixed results. This study examined whether low birth weight (LBW) and preterm birth differed between non-migrants and migrant subgroups, defined by race/ethnicity and world region of origin and destination. Methods A systematic review and meta-regression analyses were conducted using three-level logistic models to account for the heterogeneity between studies and between subgroups within studies. Results Twenty-four studies, involving more than 30 million singleton births, met the inclusion criteria. Compared with US-born black women, black migrant women were at lower odds of delivering LBW and preterm birth babies. Hispanic migrants also exhibited lower odds for these outcomes, but Asian and white migrants did not. Sub-Saharan African and Latin-American and Caribbean women were at higher odds of delivering LBW babies in Europe but not in the USA and south-central Asians were at higher odds in both continents, compared with the native-born populations. Conclusions The association between migration and adverse birth outcomes varies by migrant subgroup and it is sensitive to the definition of the migrant and reference groups. PMID:19692737

  11. Exposure to Mixtures of Metals and Neurodevelopmental Outcomes: A Multidisciplinary Review Using an Adverse Outcome Pathway Framework.

    PubMed

    von Stackelberg, Katherine; Guzy, Elizabeth; Chu, Tian; Claus Henn, Birgit

    2015-06-01

    Current risk assessment guidance calls for an individual chemical-by-chemical approach that fails to capture potential interactive effects of exposure to environmental mixtures and genetic variability. We conducted a review of the literature on relationships between prenatal and early life exposure to mixtures of lead (Pb), arsenic (As), cadmium (Cd), and manganese (Mn) with neurodevelopmental outcomes. We then used an adverse outcome pathway (AOP) framework to integrate lines of evidence from multiple disciplines based on evolving guidance developed by the Organization for Economic Cooperation and Development (OECD). Toxicological evidence suggests a greater than additive effect of combined exposures to As-Pb-Cd and to Mn with any other metal, and several epidemiologic studies also suggest synergistic effects from binary combinations of Pb-As, Pb-Cd, and Pb-Mn. The exposure levels reported in these epidemiologic studies largely fall at the high-end (e.g., 95th percentile) of biomonitoring data from the National Health and Nutrition Examination Survey (NHANES), suggesting a small but significant potential for high-end exposures. This review integrates multiple data sources using an AOP framework and provides an initial application of the OECD guidance in the context of potential neurodevelopmental toxicity of several metals, recognizing the evolving nature of regulatory interpretation and acceptance. PMID:26096925

  12. Hyperglycaemia and risk of adverse perinatal outcomes: systematic review and meta-analysis

    PubMed Central

    Simmonds, Mark; Bryant, Maria; Sheldon, Trevor A; Tuffnell, Derek; Golder, Su; Dunne, Fidelma; Lawlor, Debbie A

    2016-01-01

    Objectives To assess the association between maternal glucose concentrations and adverse perinatal outcomes in women without gestational or existing diabetes and to determine whether clear thresholds for identifying women at risk of perinatal outcomes can be identified. Design Systematic review and meta-analysis of prospective cohort studies and control arms of randomised trials. Data sources Databases including Medline and Embase were searched up to October 2014 and combined with individual participant data from two additional birth cohorts. Eligibility criteria for selecting studies Studies including pregnant women with oral glucose tolerance (OGTT) or challenge (OGCT) test results, with data on at least one adverse perinatal outcome. Appraisal and data extraction Glucose test results were extracted for OGCT (50 g) and OGTT (75 g and 100 g) at fasting and one and two hour post-load timings. Data were extracted on induction of labour; caesarean and instrumental delivery; pregnancy induced hypertension; pre-eclampsia; macrosomia; large for gestational age; preterm birth; birth injury; and neonatal hypoglycaemia. Risk of bias was assessed with a modified version of the critical appraisal skills programme and quality in prognostic studies tools. Results 25 reports from 23 published studies and two individual participant data cohorts were included, with up to 207 172 women (numbers varied by the test and outcome analysed in the meta-analyses). Overall most studies were judged as having a low risk of bias. There were positive linear associations with caesarean section, induction of labour, large for gestational age, macrosomia, and shoulder dystocia for all glucose exposures across the distribution of glucose concentrations. There was no clear evidence of a threshold effect. In general, associations were stronger for fasting concentration than for post-load concentration. For example, the odds ratios for large for gestational age per 1 mmol/L increase of

  13. Maternal, fetal and renal outcomes of pregnancy-associated acute kidney injury requiring dialysis.

    PubMed

    Krishna, A; Singh, R; Prasad, N; Gupta, A; Bhadauria, D; Kaul, A; Sharma, R K; Kapoor, D

    2015-01-01

    Pregnancy-associated acute kidney injury (PAKI) is encountered frequently in developing countries. We evaluated the maternal, fetal and renal outcomes in women with PAKI who needed at least one session of dialysis. Of the total of 98 cases (mean age 28.85 ± 5.13 years; mean parity 2.65 ± 1.28) of PAKI, the most common cause of PAKI was postabortal sepsis. Eighteen patients died; those with oligoanuria, sepsis and central nervous system (CNS) involvement were at greater risk of mortality. The relative risk (RR) of neonatal mortality was lower after with full-term delivery (RR: 0.17, 95% confidence interval (CI): 0.03-0.96, P = 0.02) compared to preterm delivery. Of the 80 surviving patients, 60 (75%) patients achieved complete recovery of renal function at the end of 3 months; and of the remaining 14 had presumed (n = 4) or, biopsy-proven (n = 10) acute patchy cortical necrosis. The RR of non-recovery of renal function was high (RR: 24.7, 95% CI: 3.4- 179.5) in patients who did not recover at 6 weeks. Of the 14 patients with cortical necrosis, 3 (21.42%) became independent of dialysis at 6 months. PAKI patients should be watched for dialysis independency for 6 months. PMID:25838643

  14. Identifying exposure disparities in air pollution epidemiology specific to adverse birth outcomes

    NASA Astrophysics Data System (ADS)

    Geer, Laura A.

    2014-10-01

    More than 147 million people in the US live in areas where pollutant levels are above regulatory limits and pose a risk to health. Most of the vast network of air pollutant monitors in the US are located in places with higher pollution levels and a higher density of pollutant sources (e.g., point sources from industrial pollution). Vulnerable populations are more likely to live closer to pollutant sources, and thus closer to pollutant monitors. These differential exposures have an impact on maternal and child health; maternal air pollutant exposures have been linked to adverse outcomes such as preterm birth and infant low birth weight. Several studies are highlighted that address methodological approaches in the study of air pollution and health disparities.

  15. Malnutrition in Hospitalized Pediatric Patients: Assessment, Prevalence, and Association to Adverse Outcomes.

    PubMed

    Daskalou, Efstratia; Galli-Tsinopoulou, Assimina; Karagiozoglou-Lampoudi, Thomais; Augoustides-Savvopoulou, Persefone

    2016-01-01

    Malnutrition is a frequent finding in pediatric health care settings in the form of undernutrition or excess body weight. Its increasing prevalence and impact on overall health status, which is reflected in the adverse outcomes, renders imperative the application of commonly accepted and evidence-based practices and tools by health care providers. Nutrition risk screening on admission and nutrition status evaluation are key points during clinical management of hospitalized pediatric patients, in order to prevent health deterioration that can lead to serious complications and growth consequences. In addition, anthropometric data based on commonly accepted universal growth standards can give accurate results for nutrition status. Both nutrition risk screening and nutrition status assessment are techniques that should be routinely implemented, based on commonly accepted growth standards and methodology, and linked to clinical outcomes. The aim of the present review was to address the issue of hospital malnutrition in pediatric settings in terms of prevalence, outline nutrition status evaluation and nutrition screening process using different criteria and available tools, and present its relationship with outcome measures. Key teaching points • Malnutrition-underweight or excess body weight-is a frequent imbalance in pediatric settings that affects physical growth and results in undesirable clinical outcomes. • Anthropometry interpretation through growth charts and nutrition screening are cornerstones for the assessment of malnutrition.To date no commonly accepted anthropometric criteria or nutrition screening tools are used in hospitalized pediatric patients. • Commonly accepted nutrition status and screening processes based on the World Health Organization's growth standards can contribute to the overall hospital nutrition care of pediatric patients.

  16. Classification of Individual Well-Being Scores for the Determination of Adverse Health and Productivity Outcomes in Employee Populations

    PubMed Central

    Sears, Lindsay E.; Coberley, Carter R.; Pope, James E.

    2013-01-01

    Abstract Adverse health and productivity outcomes have imposed a considerable economic burden on employers. To facilitate optimal worksite intervention designs tailored to differing employee risk levels, the authors established cutoff points for an Individual Well-Being Score (IWBS) based on a global measure of well-being. Cross-sectional associations between IWBS and adverse health and productivity outcomes, including high health care cost, emergency room visits, short-term disability days, absenteeism, presenteeism, low job performance ratings, and low intentions to stay with the employer, were studied in a sample of 11,702 employees from a large employer. Receiver operating characteristics curves were evaluated to detect a single optimal cutoff value of IWBS for predicting 2 or more adverse outcomes. More granular segmentation was achieved by computing relative risks of each adverse outcome from logistic regressions accounting for sociodemographic characteristics. Results showed strong and significant nonlinear associations between IWBS and health and productivity outcomes. An IWBS of 75 was found to be the optimal single cutoff point to discriminate 2 or more adverse outcomes. Logistic regression models found abrupt reductions of relative risk also clustered at IWBS cutoffs of 53, 66, and 88, in addition to 75, which segmented employees into high, high-medium, medium, low-medium, and low risk groups. To determine validity and generalizability, cutoff values were applied in a smaller employee population (N=1853) and confirmed significant differences between risk groups across health and productivity outcomes. The reported segmentation of IWBS into discrete cohorts based on risk of adverse health and productivity outcomes should facilitate well-being comparisons and worksite interventions. (Population Health Management 2013;16:90–98) PMID:23013034

  17. Classification of individual well-being scores for the determination of adverse health and productivity outcomes in employee populations.

    PubMed

    Shi, Yuyan; Sears, Lindsay E; Coberley, Carter R; Pope, James E

    2013-04-01

    Adverse health and productivity outcomes have imposed a considerable economic burden on employers. To facilitate optimal worksite intervention designs tailored to differing employee risk levels, the authors established cutoff points for an Individual Well-Being Score (IWBS) based on a global measure of well-being. Cross-sectional associations between IWBS and adverse health and productivity outcomes, including high health care cost, emergency room visits, short-term disability days, absenteeism, presenteeism, low job performance ratings, and low intentions to stay with the employer, were studied in a sample of 11,702 employees from a large employer. Receiver operating characteristics curves were evaluated to detect a single optimal cutoff value of IWBS for predicting 2 or more adverse outcomes. More granular segmentation was achieved by computing relative risks of each adverse outcome from logistic regressions accounting for sociodemographic characteristics. Results showed strong and significant nonlinear associations between IWBS and health and productivity outcomes. An IWBS of 75 was found to be the optimal single cutoff point to discriminate 2 or more adverse outcomes. Logistic regression models found abrupt reductions of relative risk also clustered at IWBS cutoffs of 53, 66, and 88, in addition to 75, which segmented employees into high, high-medium, medium, low-medium, and low risk groups. To determine validity and generalizability, cutoff values were applied in a smaller employee population (N=1853) and confirmed significant differences between risk groups across health and productivity outcomes. The reported segmentation of IWBS into discrete cohorts based on risk of adverse health and productivity outcomes should facilitate well-being comparisons and worksite interventions. PMID:23013034

  18. Adverse Outcome Pathways can drive non-animal approaches for safety assessment

    PubMed Central

    Burden, Natalie; Sewell, Fiona; Andersen, Melvin E; Boobis, Alan; Chipman, J Kevin; Cronin, Mark T D; Hutchinson, Thomas H; Kimber, Ian; Whelan, Maurice

    2015-01-01

    Adverse Outcome Pathways (AOPs) provide an opportunity to develop new and more accurate safety assessment processes for drugs and other chemicals, and may ultimately play an important role in regulatory decision making. Not only can the development and application of AOPs pave the way for the development of improved evidence-based approaches for hazard and risk assessment, there is also the promise of a significant impact on animal welfare, with a reduced reliance on animal-based methods. The establishment of a useable and coherent knowledge framework under which AOPs will be developed and applied has been a first critical step towards realizing this opportunity. This article explores how the development of AOPs under this framework, and their application in practice, could benefit the science and practice of safety assessment, while in parallel stimulating a move away from traditional methods towards an increased acceptance of non-animal approaches. We discuss here the key areas where current, and future initiatives should be focused to enable the translation of AOPs into routine chemical safety assessment, and lasting 3Rs benefits. © 2015 The Authors. Journal of Applied Toxicology published by John Wiley & Sons Ltd. This article explores how the development and application of Adverse Outcome Pathways (AOPs) could benefit the science and practice of chemical safety assessment, with a particular focus on how their use in practice could reduce reliance on traditional animal toxicity tests. This includes discussion of the key areas where current and future initiatives should be focused to enable the translation of AOPs into routine chemical safety assessment, and lasting 3Rs benefits. PMID:25943792

  19. Subvalvular apparatus and adverse outcome of balloon valvotomy in rheumatic mitral stenosis☆

    PubMed Central

    Bhalgat, Parag; Karlekar, Shrivallabh; Modani, Santosh; Agrawal, Ashish; Lanjewar, Charan; Nabar, Ashish; Kerkar, Prafulla; Agrawal, Nandu; Vaideeswar, Pradeep

    2015-01-01

    Background Balloon mitral valvotomy (BMV) is a well-established therapeutic modality for rheumatic mitral stenosis (RMS). However, there are chances of procedural failure and the more ominous post-procedural severe mitral regurgitation. There are only a few prospective studies, which have evaluated the pathogenic mechanisms for these major complications of BMV, especially in relation to the subvalvular apparatus (SVA) pathology. Methods All symptomatic patients of RMS suitable for BMV by echocardiographic criteria in a span of 1 year were selected. In addition to the standard echocardiographic assessment of RMS (Wilkins score and score by Padial et al.), a separate grading and scoring system was assigned to evaluate the severity of the SVA pathology. The SVA score was ‘I’, when none of the two SVAs had severe disease, ‘II’ when one of the two SVAs has severe disease, and ‘III’ when both SVAs had severe disease. With these scoring systems, the outcomes of BMV (successful procedure, failure, and post-procedural mitral regurgitation) were analyzed. Emergency valve replacement was performed depending on clinical situation, and in cases of replacement, the pathology of the excised mitral valves were compared with echocardiographic findings. Results Of the 356 BMVs performed in a year, 43 patients had adverse outcomes in the form of failed procedure (14 patients) and mitral regurgitation (29 patients). Forty-one among these had a SVA score of III. The sensitivity and specificity of the MR score was lesser than the SVA score (sensitivity 0.34 vs. 1.00, specificity 0.92 vs. 0.99, respectively). The mitral valvular morphology in 39 patients who underwent post-procedural valve replacements correlated well with echocardiography findings. Conclusion It is important to assess the degree of SVA pathology in the conventional echocardiographic assessment for RMS, as BMV would have adverse events when both SVAs were severely diseased. PMID:26432729

  20. Excess risk of adverse pregnancy outcomes in women with porphyria: a population-based cohort study.

    PubMed

    Tollånes, Mette Christophersen; Aarsand, Aasne Karine; Sandberg, Sverre

    2011-02-01

    The porphyrias comprise a heterogeneous group of rare, primarily hereditary, metabolic diseases caused by a partial deficiency in one of the eight enzymes involved in the heme biosynthesis. Our aim was to assess whether acute or cutaneous porphyria has been associated with excess risks of adverse pregnancy outcomes. A population-based cohort study was designed by record linkage between the Norwegian Porphyria Register, covering 70% of all known porphyria patients in Norway, and the Medical Birth Registry of Norway, based on all births in Norway during 1967-2006. The risks of the adverse pregnancy outcomes preeclampsia, delivery by caesarean section, low birth weight, premature delivery, small for gestational age (SGA), perinatal death, and congenital malformations were compared between porphyric mothers and the rest of the population. The 200 mothers with porphyria had 398 singletons during the study period, whereas the 1,100,391 mothers without porphyria had 2,275,317 singletons. First-time mothers with active acute porphyria had an excess risk of perinatal death [adjusted odds ratio (OR) 4.9, 95% confidence interval (CI) 1.5-16.0], as did mothers with the hereditable form of porphyria cutanea tarda (PCT) (3.0, 1.2-7.7). Sporadic PCT was associated with an excess risk of SGA [adjusted relative risk (RR) 2.0, 1.2-3.4], and for first-time mothers, low birth weight (adjusted OR 3.4, 1.2-10.0) and premature delivery (3.5, 1.2-10.5) in addition. The findings suggest women with porphyria should be monitored closely during pregnancy.

  1. Mechanistic study of chlordecone-induced endocrine disruption: Based on an adverse outcome pathway network.

    PubMed

    Yang, Lihua; Zhou, Bingsheng; Zha, Jinmiao; Wang, Zijian

    2016-10-01

    The adverse outcome pathway (AOP) framework could be helpful for chemical risk assessment and mechanistic research. The aim of the present study was to unravel the mechanism of chlordecone-induced endocrine disruption by illustrating the main molecular initiating event (MIE)/perturbations responsible for the observed effects. In silico simulations were performed to predict the MIE(s), and the results pointed to agonistic interaction with estrogen receptors (ERα, ERβ), androgen receptor (AR), cytochrome P450 (CYP19A) by chlordecone. In vivo endocrine disruptions were evaluated in rare minnow (Gobiocypris rarus) exposed to 0.01, 0.1, 1 and 10 μg L(-1) chlordecone from 2 h post-fertilization until sexually mature. In the females, increases of vitellogenin (vtg) mRNA levels in liver and gonad, plasma estradiol (E2), testosterone (T) and E2/T, and renalsomatic index confirmed the role of agonism of ER and CYP19A as MIEs, but the decreased gonadosomatic index, degenerated ovaries as well as the feed-forward response pointed to other potential but important MIEs and corresponding AOPs. In the males, increased E2/T ratio, increased testis vtg mRNA levels and occurrence of intersex confirmed the roles of agonism of ERα and CYP19A as main MIEs in chlordecone-induced endocrine disruptions. Our results also fetches out the limit of AOPs in predicting the adverse outcomes and explaining the mechanism of chemicals at present, thus reflected a critical need for expanding AOPs and AOP network before using it in chemical risk assessment. PMID:27448318

  2. Patient-reported outcomes and the evolution of adverse event reporting in oncology.

    PubMed

    Trotti, Andy; Colevas, A Dimitrios; Setser, Ann; Basch, Ethan

    2007-11-10

    Adverse event (AE) reporting in oncology has evolved from informal descriptions to a highly systematized process. The Common Terminology Criteria for Adverse Events (CTCAE) is the predominant system for describing the severity of AEs commonly encountered in oncology clinical trials. CTCAE clinical descriptors have been developed empirically during more than 30 years of use. The method of data collection is clinician based. Limitations of the CTC system include potential for incomplete reporting and limited guidance on data analysis and presentation methods. The Medical Dictionary for Regulatory Activities (MedDRA) is a comprehensive medical terminology system used for regulatory reporting and drug labeling. MedDRA does not provide for severity ranking of AEs. CTC-based data presentations are the primary method of AE data reporting used in scientific journals and oncology meetings. Patient-reported outcome instruments (PROs) cover the subjective domain of AEs. Exploratory work suggests PROs can be used with a high degree of patient engagement and compliance. Additional studies are needed to determine how PROs can be used to complement current AE reporting systems. Potential models for integrating PROs into AE reporting are described in this review. AE reporting methods will continue to evolve in response to changing therapies and growing interest in measuring the impact of cancer treatment on health status. Although integration of PROs into AE reporting may ultimately improve the comprehensiveness and quality of collected data, it may also increase the administrative burden and cost of conducting trials. Therefore, care must be used when developing health outcomes and safety data collection plans. PMID:17991931

  3. An integrative data mining approach to identifying adverse outcome pathway signatures.

    PubMed

    Oki, Noffisat O; Edwards, Stephen W

    2016-03-28

    The Adverse Outcome Pathway (AOP) framework is a tool for making biological connections and summarizing key information across different levels of biological organization to connect biological perturbations at the molecular level to adverse outcomes for an individual or population. Computational approaches to explore and determine these connections can accelerate the assembly of AOPs. By leveraging the wealth of publicly available data covering chemical effects on biological systems, computationally-predicted AOPs (cpAOPs) were assembled via data mining of high-throughput screening (HTS) in vitro data, in vivo data and other disease phenotype information. Frequent Itemset Mining (FIM) was used to find associations between the gene targets of ToxCast HTS assays and disease data from Comparative Toxicogenomics Database (CTD) by using the chemicals as the common aggregators between datasets. The method was also used to map gene expression data to disease data from CTD. A cpAOP network was defined by considering genes and diseases as nodes and FIM associations as edges. This network contained 18,283 gene to disease associations for the ToxCast data and 110,253 for CTD gene expression. Two case studies show the value of the cpAOP network by extracting subnetworks focused either on fatty liver disease or the Aryl Hydrocarbon Receptor (AHR). The subnetwork surrounding fatty liver disease included many genes known to play a role in this disease. When querying the cpAOP network with the AHR gene, an interesting subnetwork including glaucoma was identified. While substantial literature exists to support the potential for AHR ligands to elicit glaucoma, it was not explicitly captured in the public annotation information in CTD. The subnetwork from this analysis suggests a cpAOP that includes changes in CYP1B1 expression, which has been previously established in the literature as a primary cause of glaucoma. These case studies highlight the value in integrating multiple data

  4. Associations Between Residential Proximity to Power Plants and Adverse Birth Outcomes

    PubMed Central

    Ha, Sandie; Hu, Hui; Roth, Jeffrey; Kan, Haidong; Xu, Xiaohui

    2015-01-01

    Few studies have assessed the associations between residential proximity to power plants and adverse birth outcomes including preterm delivery (PTD), very preterm delivery (VPTD), and term low birth weight (LBW). We geocoded 423,719 singleton Florida births born from 2004 to 2005 and all active power plants and determined residential proximity to the nearest power plant for each birth. Prenatal exposure to particulate matter less than 2.5 µm in diameter for women living near different types of power plants was also determined by using National Environmental Public Health Tracking Network data. Logistic regression models were used to test the hypothesized associations. Women who lived closer to coal and solid waste power plants were exposed to higher levels of particulate matter less than 2.5 µm in diameter compared with other types. We observed a 1.8% (95% confidence interval (CI): 1.3, 2.3) increased odds for PTD, 2.2% (95% CI: 1.0, 3.4) for VPTD, and 1.1% (95% CI: 0.2, 2.0) for term LBW for each 5 km closer to any power plant. When stratifying by different fuel type, we found that only solid waste had an association with term LBW, whereas oil, gas, and solid waste all had an association with PTD and VPTD. Results were consistent when exposure was categorized by number of power plants. Our study found evidence of increasing odds of adverse birth outcomes among infants born to pregnant women living closer to power plants. More research is warranted to better understand the causal relationship. PMID:26121989

  5. The influence of heart developmental anatomy on cardiotoxicity-based adverse outcome pathways in fish.

    PubMed

    Incardona, John P; Scholz, Nathaniel L

    2016-08-01

    The developing fish heart is vulnerable to a diverse array of toxic chemical contaminants in freshwater, estuarine, and marine habitats. Globally occurring examples of cardiotoxic agents include dioxins, polychlorinated biphenyls (PCBs), and polycyclic aromatic hydrocarbons (PAHs). The disruption of cardiac function during the process of heart morphogenesis can lead to adverse outcome pathways (AOPs) that can negatively affect fish survival at hatching as well as later life stages. Proximal impacts include cardiogenic fluid accumulation (edema) and defects of the body axis and jaw that preclude larval feeding. More subtle changes in heart development can produce permanent structural defects in the heart that reduce cardiac output and swimming performance in older fish. In recent decades, the presence of edema in fish embryos and larvae has been a very common bioindicator of cardiotoxicity. However, the different ways that edema forms in fish from different habitats (i.e., freshwater vs. marine, pelagic vs. demersal) has not been rigorously examined. Oil spills are an important source of PAHs in fish spawning areas worldwide, and research is revealing how patterns of cardiogenic edema are shaped by species-specific differences in developmental anatomy and ionoregulatory physiology. Here we review the visible evidence for circulatory disruption across nine freshwater and marine fish species, exposed to crude oils from different parts of the world. We focus on the close interconnectedness of the cardiovascular and osmoregulatory systems during early development, and corresponding implications for fish in hyperosmotic and hyposmotic habitats. Finally, we suggest there may be poorly understood adverse outcomes pathways related to osmotic gradients and water movement within embryos, the latter causing extreme shifts in tissue osmolality. PMID:27447099

  6. The baboon model (Papio hamadryas) of fetal loss: Maternal weight, age, reproductive history and pregnancy outcome

    PubMed Central

    Schlabritz-Loutsevitch, Natalia; Moore, Charleen M.; Lopez-Alvarenga, Juan Carlos; Dunn, Betty G.; Dudley, Donald; Hubbard, Gene B.

    2010-01-01

    Background Several risk factors are associated with the incidence of human stillbirths. The prevention of stillbirths in women is a pressing clinical problem. Methods We reviewed 402 pathology records of fetal loss occurring in a large baboon (Papio spp.) colony during a 15-year period. Clinical histories of 565 female baboons with one or more fetal losses during a 20-year period were analyzed for weight, age, and reproductive history. Results Fetal loss was most common at term (35.57%) and preterm (28.61%) and less common in the first half of gestation (11.20%) and post-term (5.22%). Greater maternal weight, older age, history of stillbirth and higher parity were independent predictors for stillbirth. An exponential increase in the incidence of fetal loss was observed beginning at age 14 years in baboons. Conclusion Fetal loss and maternal risk factors associated with stillbirths in baboons were similar to those documented in women. PMID:19017195

  7. Sepsis After Cardiac Surgery Early in Infancy and Adverse 4.5-Year Neurocognitive Outcomes

    PubMed Central

    Sidhu, Naveen; Joffe, Ari R; Doughty, Paul; Vatanpour, Shabnam; Dinu, Irina; Alton, Gwen; Acton, Bryan; Robertson, Charlene M T

    2015-01-01

    Background We aimed to determine whether sepsis is associated with neurocognitive outcomes 4.5 years after congenital heart disease surgery in early infancy. Methods and Results A secondary analysis from a prospective inception cohort included all children having congenital heart disease surgery done at ≤6 weeks of age with cardiopulmonary bypass at the Western Canadian referral center from 1996 to 2009. Follow-up at the referral center determined the primary outcomes at 4.5 years with full-scale, performance, and verbal intelligence quotients on the Wechsler Preschool and Primary Scale of Intelligence. Perioperative variables were collected prospectively, and confirmation of blood culture–positive sepsis was done retrospectively. Multiple linear regression models for neurocognitive outcomes and multiple Cox proportional hazards regression for mortality were determined. Sepsis occurred in 97 of 502 patients (19%) overall and in 76 of 396 survivors (19%) with 4.5-year follow-up. By 4.5 years, there were 91 (18%) deaths, and 396 of 411 survivors (96%) had follow-up completed. Extracorporeal membrane oxygenation was associated with worse scores on all neurocognitive outcomes on multivariable regression; the association between extracorporeal membrane oxygenation and full-scale intelligence quotient had a regression coefficient of −13.6 (95% CI −21.3 to −5.9; P =0.001). Sepsis perioperatively was associated with performance and verbal intelligence quotients, with a trend for full-scale intelligence quotient (P =0.058) on multivariable regression. The regression coefficient for sepsis was strongest for performance intelligence quotient (−5.31; 95% CI −9.84 to −0.78; P =0.022). Sepsis was not but extracorporeal membrane oxygenation was associated with mortality by 4.5 years. Conclusions Perioperative sepsis and extracorporeal membrane oxygenation were associated with adverse neurocognitive outcomes on multivariable regression. Quality improvement to

  8. Assessing Adverse Events of Postprostatectomy Radiation Therapy for Prostate Cancer: Evaluation of Outcomes in the Regione Emilia-Romagna, Italy

    SciTech Connect

    Showalter, Timothy N.; Hegarty, Sarah E.; Rabinowitz, Carol; Maio, Vittorio; Hyslop, Terry; Dicker, Adam P.; Louis, Daniel Z.

    2015-03-15

    Purpose: Although the likelihood of radiation-related adverse events influences treatment decisions regarding radiation therapy after prostatectomy for eligible patients, the data available to inform decisions are limited. This study was designed to evaluate the genitourinary, gastrointestinal, and sexual adverse events associated with postprostatectomy radiation therapy and to assess the influence of radiation timing on the risk of adverse events. Methods: The Regione Emilia-Romagna Italian Longitudinal Health Care Utilization Database was queried to identify a cohort of men who received radical prostatectomy for prostate cancer during 2003 to 2009, including patients who received postprostatectomy radiation therapy. Patients with prior radiation therapy were excluded. Outcome measures were genitourinary, gastrointestinal, and sexual adverse events after prostatectomy. Rates of adverse events were compared between the cohorts who did and did not receive postoperative radiation therapy. Multivariable Cox proportional hazards models were developed for each class of adverse events, including models with radiation therapy as a time-varying covariate. Results: A total of 9876 men were included in the analyses: 2176 (22%) who received radiation therapy and 7700 (78%) treated with prostatectomy alone. In multivariable Cox proportional hazards models, the additional exposure to radiation therapy after prostatectomy was associated with increased rates of gastrointestinal (rate ratio [RR] 1.81; 95% confidence interval [CI] 1.44-2.27; P<.001) and urinary nonincontinence events (RR 1.83; 95% CI 1.83-2.80; P<.001) but not urinary incontinence events or erectile dysfunction. The addition of the time from prostatectomy to radiation therapy interaction term was not significant for any of the adverse event outcomes (P>.1 for all outcomes). Conclusion: Radiation therapy after prostatectomy is associated with an increase in gastrointestinal and genitourinary adverse events. However

  9. Adverse psychosocial outcomes associated with drug use among US high school seniors: a comparison of alcohol and marijuana

    PubMed Central

    Palamar, Joseph J.; Fenstermaker, Michael; Kamboukos, Dimitra; Ompad, Danielle C.; Cleland, Charles M.; Weitzman, Michael

    2015-01-01

    Objectives There is debate about whether marijuana (cannabis) use is more dangerous than alcohol use. Although difficult to make objective comparisons, research is needed to compare relative dangers in order to help inform preventive efforts and policy. Methods Data were analyzed from a nationally representative sample of high school seniors in the Monitoring the Future study (2007–2011; Weighted n = 7437; modal age: 18) who reported lifetime use of alcohol or marijuana. Students were asked to indicate whether they experienced various adverse psychosocial outcomes resulting from use of each substance. We examined which outcomes were more prevalent for each substance. Results Compared to alcohol use, marijuana use was more commonly reported to compromise relationships with teachers or supervisors, result in less energy or interest, and result in lower school or job performance. Compared to marijuana use, alcohol was more commonly reported to compromise relationships with friends and significant others; it was also reported to lead to more regret (particularly among females), and driving unsafely. Marijuana users were more likely to report no adverse outcomes. Females and white students were more likely to report various adverse outcomes and higher frequency use of each substance also increased occurrences of reported adverse outcomes. Conclusions Marijuana and alcohol are associated with unique adverse psychosocial outcomes. Outcomes differ by sex and race/ethnicity, and perception or experience of outcomes may also be related to legal status and associated stigma. Public health interventions may be more effective by focusing on harm reduction strategies for these drug-specific outcomes. PMID:25169838

  10. Child marriage and its association with adverse reproductive outcomes for women in Bangladesh.

    PubMed

    Kamal, S M Mostafa; Hassan, Che Hashim

    2015-03-01

    This study examines the prevalence of child marriage and its effect on reproductive outcomes among women in Bangladesh using the most recent 2011 Bangladesh Demographic and Health Survey data. Both bivariate and multivariate statistical techniques used in the study yielded quantitatively important and reliable estimates of child marriage and its impact on adverse reproductive and health outcomes. Overall, 77% of the marriages among women aged 20 to 49 years old took place before the age of 18 years. Women's education is the most single significant determinant of child marriage. Findings revealed that after being adjusted for sociodemographic factors, child marriage significantly (P < .001) increases the likelihood of stillbirth/miscarriage (odds ratio [OR] = 1.80; 95% confidence interval [CI] = 1.45-2.24) and pregnancy termination (OR = 1.24; 95% CI = 1.12-1.38). Programs should aim to retain girls in school for longer periods not only to raise the age at first marriage but also for sound reproductive health and overall social development of Bangladesh.

  11. Effects of a Psychosocial Couple-Based Prevention Program on Adverse Birth Outcomes

    PubMed Central

    Roettger, Michael E.; Jones, Damon E.; Paul, Ian M.; Kan, Marni L.

    2015-01-01

    Although maternal stress and depression have been linked to adverse birth outcomes (ABOs), few studies have investigated preventive interventions targeting maternal mental health as a means of reducing ABOs. This randomized controlled study examines the impact of Family Foundations (FF)—a transition to parenthood program for couples focused on promoting coparenting quality, with previously documented impact on maternal stress and depression—on ABOs. We also examine whether intervention buffers birth outcomes from the negative effect of elevated salivary cortisol levels. We use intent-to-treat analyses to assess the main effects of the FF intervention on ABOs (prematurity, birth weight, pregnancy complications, Cesarean section, and days in hospital for mothers and infants) among 148 expectant mothers. We also test the interaction of cortisol with intervention condition status in predicting ABOs. FF participation was associated with reduced risk of C-section (OR .357, p < 0.05, 95 % CI 0.149, 0.862), but did not have main effects on other ABOs. FF significantly buffered (p < 0.05) the negative impact of maternal cortisol on birth weight, gestational age, and days in hospital for infants; that is, among women with relatively higher levels of prenatal cortisol, the intervention reduced ABOs. These results demonstrate that a psycho-educational program for couples reduces incidence of ABOs among higher risk women. Future work should test whether reduced maternal stress and depression mediate these intervention effects. PMID:24969352

  12. Serum 25-Hydroxyvitamin D Levels are not Associated with Adverse Outcomes in Clostridium Difficile Infection

    PubMed Central

    Micic, Dejan; Rao, Krishna; Trindade, Bruno Caetano; Walk, Seth T.; Chenoweth, Elizabeth; Jain, Ruchika; Trivedi, Itishree; Santhosh, Kavitha; Young, Vincent B.; Aronoff, David M.

    2015-01-01

    Clostridium difficile infection (CDI) is a significant source of healthcare-associated morbidity and mortality. This study investigated whether serum 25-hydroxyvitamin D is associated with adverse outcomes from CDI. Patients with CDI were prospectively enrolled. Charts were reviewed and serum 25-hydroxyvitamin D was measured. The primary outcome was a composite definition of severe disease: fever (temperature >38°C), acute organ dysfunction, or serum white blood cell count >15,000 cells/µL within 24-48 hours of diagnosis; lack of response to therapy by day 5; and intensive care unit admission; colectomy; or death within 30 days. Sixty-seven patients were included in the final analysis. Mean (±SD) serum 25-hydroxyvitamin D was 26.1 (±18.54) ng/mL. Severe disease, which occurred in 26 (39%) participants, was not associated with serum 25-hydroxyvitamin D [odds ratio (OR) 1.00; 95% confidence interval (CI) 0.96-1.04]. In the adjusted model for severe disease only serum albumin (OR 0.12; 95%CI 0.02-0.64) and diagnosis by detection of stool toxin (OR 5.87; 95%CI 1.09-31.7) remained independent predictors. We conclude that serum 25-hydroxyvitamin D is not associated with the development of severe disease in patients with CDI. PMID:26500740

  13. Exposing physicians to reduced residency work hours did not adversely affect patient outcomes after residency.

    PubMed

    Jena, Anupam B; Schoemaker, Lena; Bhattacharya, Jay

    2014-10-01

    In 2003, work hours for physicians-in-training (residents) were capped by regulation at eighty hours per week, leading to the hotly debated but unexplored issue of whether physicians today are less well trained as a result of these work-hour reforms. Using a unique database of nearly all hospitalizations in Florida during 2000-09 that were linked to detailed information on the medical training history of the physician of record for each hospitalization, we studied whether hospital mortality and patients' length-of-stay varied according to the number of years a physician was exposed to the 2003 duty-hour regulations during his or her residency. We examined this database of practicing Florida physicians, using a difference-in-differences analysis that compared trends in outcomes of junior physicians (those with one-year post-residency experience) pre- and post-2003 to a control group of senior physicians (those with ten or more years of post-residency experience) who were not exposed to these reforms during their residency. We found that the duty-hour reforms did not adversely affect hospital mortality and length-of-stay of patients cared for by new attending physicians who were partly or fully exposed to reduced duty hours during their own residency. However, assessment of the impact of the duty-hour reforms on other clinical outcomes is needed.

  14. Effects of a psychosocial couple-based prevention program on adverse birth outcomes.

    PubMed

    Feinberg, Mark E; Roettger, Michael E; Jones, Damon E; Paul, Ian M; Kan, Marni L

    2015-01-01

    Although maternal stress and depression have been linked to adverse birth outcomes (ABOs), few studies have investigated preventive interventions targeting maternal mental health as a means of reducing ABOs. This randomized controlled study examines the impact of Family Foundations (FF)-a transition to parenthood program for couples focused on promoting coparenting quality, with previously documented impact on maternal stress and depression-on ABOs. We also examine whether intervention buffers birth outcomes from the negative effect of elevated salivary cortisol levels. We use intent-to-treat analyses to assess the main effects of the FF intervention on ABOs (prematurity, birth weight, pregnancy complications, Cesarean section, and days in hospital for mothers and infants) among 148 expectant mothers. We also test the interaction of cortisol with intervention condition status in predicting ABOs. FF participation was associated with reduced risk of C-section (OR .357, p < 0.05, 95 % CI 0.149, 0.862), but did not have main effects on other ABOs. FF significantly buffered (p < 0.05) the negative impact of maternal cortisol on birth weight, gestational age, and days in hospital for infants; that is, among women with relatively higher levels of prenatal cortisol, the intervention reduced ABOs. These results demonstrate that a psycho-educational program for couples reduces incidence of ABOs among higher risk women. Future work should test whether reduced maternal stress and depression mediate these intervention effects.

  15. Planned Repeat Cesarean Section at Term and Adverse Childhood Health Outcomes: A Record-Linkage Study

    PubMed Central

    Black, Mairead; Bhattacharya, Siladitya; Philip, Sam; Norman, Jane E.; McLernon, David J.

    2016-01-01

    Background Global cesarean section (CS) rates range from 1% to 52%, with a previous CS being the commonest indication. Labour following a previous CS carries risk of scar rupture, with potential for offspring hypoxic brain injury, leading to high rates of repeat elective CS. However, the effect of delivery by CS on long-term outcomes in children is unclear. Increasing evidence suggests that in avoiding exposure to maternal bowel flora during labour or vaginal birth, offspring delivered by CS may be adversely affected in terms of energy uptake from the gut and immune development, increasing obesity and asthma risks, respectively. This study aimed to address the evidence gap on long-term childhood outcomes following repeat CS by comparing adverse childhood health outcomes after (1) planned repeat CS and (2) unscheduled repeat CS with those that follow vaginal birth after CS (VBAC). Methods and Findings A data-linkage cohort study was performed. All second-born, term, singleton offspring delivered between 1 January 1993 and 31 December 2007 in Scotland, UK, to women with a history of CS (n = 40,145) were followed up until 31 January 2015. Outcomes assessed included obesity at age 5 y, hospitalisation with asthma, learning disability, cerebral palsy, and death. Cox regression and binary logistic regression were used as appropriate to compare outcomes following planned repeat CS (n = 17,919) and unscheduled repeat CS (n = 8,847) with those following VBAC (n = 13,379). Risk of hospitalisation with asthma was greater following both unscheduled repeat CS (3.7% versus 3.3%, adjusted hazard ratio [HR] 1.18, 95% CI 1.05–1.33) and planned repeat CS (3.6% versus 3.3%, adjusted HR 1.24, 95% CI 1.09–1.42) compared with VBAC. Learning disability and death were more common following unscheduled repeat CS compared with VBAC (3.7% versus 2.3%, adjusted odds ratio 1.64, 95% CI 1.17–2.29, and 0.5% versus 0.4%, adjusted HR 1.50, 95% CI 1.00–2.25, respectively). Risk of obesity

  16. Characteristics of Adolescents with Type 1 Diabetes Who Exhibit Adverse Outcomes

    PubMed Central

    Johns, Carla; Faulkner, Melissa Spezia; Quinn, Lauretta

    2008-01-01

    Purpose The primary purpose of this study was to determine differences in key characteristics between adolescents with type 1 diabetes who experienced the adverse outcomes of poor glycemic control, hypoglycemic events, and hospitalizations due to their disease versus those who do not experience such events. A secondary purpose was to examine differences in outcomes for adolescents using insulin pumps versus daily insulin injections (≥ 2). Methods Data from 108 adolescents were divided according to glycemic control (HbA1c <8% vs. ≥8%), hypoglycemic reactions and hospitalizations in the past year (0 vs. ≥ 1 episode of each), and pump versus injection delivery of insulin. The following variables were compared within each grouping: body mass index (BMI) insulin dose, caloric intake, parental educational level, marital status, annual family income, race, and gender. HbA1c was examined in relation to the number of hypoglycemic reactions and hospitalizations in the past year, as well as for any differences between those receiving insulin via pump therapy versus daily injections (≥ 2). Results Subjects receiving insulin via pump had better glucose control and were on lower insulin doses than those receiving insulin injections. Subjects with adequate versus inadequate glucose control used a lower insulin dose, checked their blood sugar more frequently, and had fathers with a higher education level. Finally, those with inadequate control were more likely to come from a single parent home, a lower income family, and from an ethnic minority. Conclusions Pump therapy for adolescents should be encouraged when appropriate. Also, certain groups of adolescents need increased supervision to manage their disease appropriately. Further research needs to explore what interventions will bring more favorable outcomes for such groups. PMID:18832292

  17. Hypertension: An Unstudied Potential Risk Factor for Adverse Outcomes during Continuous Flow Ventricular Assist Device Support

    PubMed Central

    Wasson, Lauren T.; Yuzefpolskaya, Melana; Wakabayashi, Michiyori; Takayama, Hiroo; Naka, Yoshifumi; Uriel, Nir; Jorde, Ulrich P.; Demmer, Ryan T.; Colombo, Paolo C.

    2014-01-01

    In end-stage heart failure, left ventricular assist devices (LVADs) represent an exciting new frontier in which post-device-implantation survival approaches that of heart transplant. However, expansion of this technology is still limited by complications that impact morbidity and mortality. Thus, it is essential to identify and optimize modifiable predictors of poor outcomes. One such predictor may be hypertension (HTN). Not only may chronic HTN as a traditional cardiovascular risk factor be present during long-term LVAD support, but HTN may also contribute to device malfunction or device-associated complications. Although current guidelines identify blood pressure (BP) control as important to outpatient continuous flow (CF) LVAD management, there is no evidence base to support these guidelines. Indeed, our comprehensive literature search did not identify any studies that evaluated post-device-implantation HTN as a potential predictor of adverse CF-LVAD outcomes. Hypertension among CF-LVAD patients is likely a relatively unstudied factor because of difficulties using standard non-invasive techniques to measure BP in the setting of reduced pulsatile flow. Fortunately, recent research has elucidated the meaning of Doppler BP measurements and validated a slow-deflation cuff system for BP measurements in the setting of CF-LVAD support. Therefore, CF-LVAD researchers and clinicians may i) consider potential mechanisms relating HTN to poor outcomes, ii) realize that HTN management is a stated goal despite scarce evidence, and iii) utilize the new reliable and valid methods for outpatient BP measurement that make research and management possible. It is critical and now feasible that research on HTN in the CF-LVAD patient population move forward. PMID:25283767

  18. Hypertension: an unstudied potential risk factor for adverse outcomes during continuous flow ventricular assist device support.

    PubMed

    Wasson, Lauren T; Yuzefpolskaya, Melana; Wakabayashi, Michiyori; Takayama, Hiroo; Naka, Yoshifumi; Uriel, Nir; Jorde, Ulrich P; Demmer, Ryan T; Colombo, Paolo C

    2015-05-01

    In end-stage heart failure, left ventricular assist devices (LVADs) represent an exciting new frontier in which post-device implantation survival approaches that of heart transplant. However, expansion of this technology is still limited by complications that impact morbidity and mortality. Thus, it is essential to identify and optimize modifiable predictors of poor outcomes. One such predictor may be hypertension (HTN). Not only may chronic HTN as a traditional cardiovascular risk factor be present during long-term LVAD support, but HTN may also contribute to device malfunction or device-associated complications. Although current guidelines identify blood pressure (BP) control as important to outpatient continuous flow (CF) LVAD management, there is no evidence base to support these guidelines. Indeed, our comprehensive literature search did not identify any studies that evaluated post-device implantation HTN as a potential predictor of adverse CF-LVAD outcomes. HTN among CF-LVAD patients is likely a relatively unstudied factor because of difficulties using standard noninvasive techniques to measure BP in the setting of reduced pulsatile flow. Fortunately, recent research has elucidated the meaning of Doppler BP measurements and validated a slow-cuff deflation system for BP measurements in the setting of CF-LVAD support. Therefore, CF-LVAD researchers and clinicians may (1) consider potential mechanisms relating HTN to poor outcomes, (2) realize that HTN management is a stated goal despite scarce evidence, and (3) utilize the new reliable and valid methods for outpatient BP measurement that make research and management possible. It is critical and now feasible that research on HTN in the CF-LVAD patient population move forward.

  19. Highly Active Antiretroviral Therapy and Adverse Birth Outcomes Among HIV-Infected Women in Botswana

    PubMed Central

    Chen, Jennifer Y.; Ribaudo, Heather J.; Souda, Sajini; Parekh, Natasha; Ogwu, Anthony; Lockman, Shahin; Powis, Kathleen; Dryden-Peterson, Scott; Creek, Tracy; Jimbo, William; Madidimalo, Tebogo; Makhema, Joseph; Essex, Max; Shapiro, Roger L

    2012-01-01

    Background. It is unknown whether adverse birth outcomes are associated with maternal highly active antiretroviral therapy (HAART) in pregnancy, particularly in resource-limited settings. Methods. We abstracted obstetrical records at 6 sites in Botswana for 24 months. Outcomes included stillbirths (SBs), preterm delivery (PTD), small for gestational age (SGA), and neonatal death (NND). Among human immunodeficiency virus (HIV)–infected women, comparisons were limited to HAART exposure status at conception, and those with similar opportunities for outcomes. Comparisons were adjusted for CD4+ lymphocyte cell count. Results. Of 33 148 women, 32 113 (97%) were tested for HIV, of whom 9504 (30%) were HIV infected. Maternal HIV was significantly associated with SB, PTD, SGA, and NND. Compared with all other HIV-infected women, those continuing HAART from before pregnancy had higher odds of PTD (adjusted odds ratio [AOR], 1.2; 95% confidence interval [CI], 1.1, 1.4), SGA (AOR, 1.8; 95% CI, 1.6, 2.1) and SB (AOR, 1.5; 95% CI, 1.2, 1.8). Among women initiating antiretroviral therapy in pregnancy, HAART use (vs zidovudine) was associated with higher odds of PTD (AOR, 1.4; 95% CI, 1.2, 1.8), SGA (AOR, 1.5; 95% CI, 1.2, 1.9), and SB (AOR, 2.5; 95% CI, 1.6, 3.9). Low CD4+ was independently associated with SB and SGA, and maternal hypertension during pregnancy with PTD, SGA, and SB. Conclusions. HAART receipt during pregnancy was associated with increased PTD, SGA, and SB. PMID:23066160

  20. Population-based study of smoking behaviour throughout pregnancy and adverse perinatal outcomes.

    PubMed

    Murphy, Deirdre J; Dunney, Clare; Mullally, Aoife; Adnan, Nita; Deane, Richard

    2013-08-27

    There has been limited research addressing whether behavioural change in relation to smoking is maintained throughout pregnancy and the effect on perinatal outcomes. A cohort study addressed lifestyle behaviours of 907 women who booked for antenatal care and delivered in a large urban teaching hospital in 2010-2011. Adverse perinatal outcomes were compared for "non-smokers", "ex-smokers" and "current smokers". Of the 907 women, 270 (30%) reported smoking in the six months prior to pregnancy, and of those 160 (59%) had stopped smoking and 110 (41%) continued to smoke at the time of the first antenatal visit. There was virtually no change in smoking behaviour between the first antenatal visit and the third trimester of pregnancy. Factors associated with continuing to smoke included unplanned pregnancy (OR 1.9; 95% CI 1.3, 2.9), alcohol use (OR 3.4; 95% CI 2.1, 6.0) and previous illicit drug use (OR 3.6; 95% CI 2.1, 6.0). Ex-smokers had similar perinatal outcomes to non-smokers. Current smoking was associated with an average reduction in birth weight of 191 g (95% CI -294, -88) and an increased incidence of intrauterine growth restriction (24% versus 13%, adjusted OR 1.39 (95% CI 1.06, 1.84). Public Health campaigns emphasise the health benefits of quitting smoking in pregnancy. The greatest success appears to be pre-pregnancy and during the first trimester where women are largely self-motivated to quit.

  1. Hypertension: an unstudied potential risk factor for adverse outcomes during continuous flow ventricular assist device support.

    PubMed

    Wasson, Lauren T; Yuzefpolskaya, Melana; Wakabayashi, Michiyori; Takayama, Hiroo; Naka, Yoshifumi; Uriel, Nir; Jorde, Ulrich P; Demmer, Ryan T; Colombo, Paolo C

    2015-05-01

    In end-stage heart failure, left ventricular assist devices (LVADs) represent an exciting new frontier in which post-device implantation survival approaches that of heart transplant. However, expansion of this technology is still limited by complications that impact morbidity and mortality. Thus, it is essential to identify and optimize modifiable predictors of poor outcomes. One such predictor may be hypertension (HTN). Not only may chronic HTN as a traditional cardiovascular risk factor be present during long-term LVAD support, but HTN may also contribute to device malfunction or device-associated complications. Although current guidelines identify blood pressure (BP) control as important to outpatient continuous flow (CF) LVAD management, there is no evidence base to support these guidelines. Indeed, our comprehensive literature search did not identify any studies that evaluated post-device implantation HTN as a potential predictor of adverse CF-LVAD outcomes. HTN among CF-LVAD patients is likely a relatively unstudied factor because of difficulties using standard noninvasive techniques to measure BP in the setting of reduced pulsatile flow. Fortunately, recent research has elucidated the meaning of Doppler BP measurements and validated a slow-cuff deflation system for BP measurements in the setting of CF-LVAD support. Therefore, CF-LVAD researchers and clinicians may (1) consider potential mechanisms relating HTN to poor outcomes, (2) realize that HTN management is a stated goal despite scarce evidence, and (3) utilize the new reliable and valid methods for outpatient BP measurement that make research and management possible. It is critical and now feasible that research on HTN in the CF-LVAD patient population move forward. PMID:25283767

  2. The Impact of Inherited Thrombophilia Types and Low Molecular Weight Heparin Treatment on Pregnancy Complications in Women with Previous Adverse Outcome

    PubMed Central

    Aracic, Nada; Roje, Damir; Jakus, Ivana Alujevic; Bakotin, Marinela

    2016-01-01

    Purpose To assess the distribution of births and spontaneous abortions, first-trimester abortion (FTA) and mid-trimester abortion (MTA), in untreated (n=128) and low molecular weight heparin (LMWH) treated pregnancies (n=50) of the same women with inherited thrombophilias and adverse pregnancy outcome (APO) in previous pregnancies. We particularly investigated the impact of LMWH on reducing the pregnancy complications in two thrombophilia types, "Conventional" and "Novel". Materials and Methods 50 women with inherited thrombophilia (26 Conventional and 24 Novel) and APO in previous pregnancies were included in the study. Conventional group included factor V Leiden (FVL), prothrombin G20210A (PT) mutations and antithrombin (AT), protein S (PS), and protein C (PC) deficiency, while the Novel group included methylentetrahydrofolate-reductase (MTHFR), plasminogen activator inhibitor-1 (PAI-1), and angiotensin converting enzyme (ACE) polymorphism. APO was defined as one of the following: preterm birth (PTB), fetal growth restriction (FGR), preeclampsia (PE), intrauterine fetal death (IUFD), placental abruption (PA) and deep venous thrombosis (DVT). Results There was no difference in distribution of births and spontaneous abortions between Conventional and Novel thrombophilia in untreated pregnancies (χ2=2.7; p=0.100) and LMWH treated pregnancies (χ2=0.442; p=0.506). In untreaed pregnancies thrombophilia type did not have any impact on the frequency of FTA and MTA (χ2=0.14; p=0.711). In birth-ended pregnancies LMWH treatement reduced the incidence of IUFD (p=0.011) in Conventional and FGR, IUFD, and PTB in Novel thrombophilia group. Conclusion The equal impact of two thrombophilia types on the pregnancy outcomes and a more favorable effect of LMWH therapy on pregnancy complications in Novel thrombophilia group point the need for Novel thrombophilias screening and the future studies on this issue should be recommended. PMID:27401656

  3. A Meta Analysis on Risks of Adverse Pregnancy Outcomes in Toxoplasma gondii Infection

    PubMed Central

    Zhang, Hao; Peng, Hong-Juan; Lindsay, David S.

    2014-01-01

    Objective Quantified risks of congenital Toxoplasma gondii infection and abnormal pregnancy outcomes following primary maternal infection were evaluated with meta- analysis based on published studies. Methods The related literatures were searched in multiple literature databases regardless of languages. Odds ratio (OR) and 95% confidence interval (CI) were used to evaluate the risks of vertical transmission of Toxoplasma gondii and abnormal pregnancy outcomes following primary maternal infection with meta-analysis. Results 53 of the 2632 searched literatures were included in our analysis. The incidence of abnormal pregnancy outcomes in T. gondii infected pregnant women (infected group) was significantly higher than that in the uninfected pregnant women (control group) (OR = 5.10; 95% CI, 3.85–6.75). Toxoplasma gondii infection rate in the abnormal-pregnancy-outcome group was significantly higher than in the normal-pregnancy group (OR = 3.71; 95% CI, 3.31–4.15). The pooled rate of vertical transmission was 20% (95% CI, 15%–26%) in maternal infection of T. gondii. The incidences of vertical transmission in women who were infected in the first, second or third trimester of pregnancy were 5% (95%CI, 2%–16%), 13% (95%CI, 7%–23%), and 32% (95%CI, 24%–41%), respectively. The rates of vertical transmission in women who were treated with spiramycin-only, PSF (pyrimethamine + sulfadiazine + folinic acid) or PS (pyrimethamine + sulfadiazine) combined with spiramycin, or other untypical treatments were 13% (95%CI, 7%–22%), 13%(95%CI, 7%–25%), and 24%(95%CI, 18%–32%), respectively. Conclusions Toxoplasma gondii infection can result in adverse pregnancy outcomes in pregnant women. The pooled rate of vertical transmission was 20% in maternal infection and the incidences of vertical transmission increased in the first, second or third trimester of pregnancy. The pooled rates of transmission in groups treated with spiramycin-only, PSF or PS combined with

  4. Contraceptive Methods and Informed Consent among Women Receiving Medications with Potential for Adverse Fetal Effects: A Washington, Wyoming, Alaska, Montana, Idaho (WWAMI) Region Study

    PubMed Central

    Force, Rex W.; Keppel, Gina A.; Guirguis-Blake, Janelle; Gould, Debra A.; Vincent, Chris; Chunchu, Kavitha; Monger, Robert M.; Holmes, John T.; Cauffield, Jacintha; Baldwin, Laura-Mae

    2013-01-01

    Background Increasing diabetes, hypertension, and hypercholesterolemia rates expose some young women to medications with potential adverse fetal effects, such as angiotensin-converting enzyme inhibitors (ACE-Is), angiotensin receptor blockers (ARBs), and statins. This study examined whether quality improvement (QI) interventions promote informed consent and contraception to minimize risks with use of ACE-I/ARB/statins. Methods This longitudinal cohort study at 7 clinics abstracted medical records of 328 women aged 18 to 44 with ≥1 prescription for ACE-I/ARB/statins and ≥1 visit for hypertension, diabetes, or hypercholesterolemia during the previous year. We measured informed consent documentation and contraceptive methods before and after QI interventions in which providers contacted their patients to discuss medication risks and benefits. Results Of 179 women who were not surgically sterilized, only 11.7% had documented informed consent related to the risks of ACE-I/ARB/statin use. One hundred fifty-eight women were eligible for the QI intervention (not surgically sterilized, no documented informed consent); only 76 (48.1%) received the intervention. Before the intervention, 23.7% of these 76 were “at risk” of an adverse fetal effect. After the intervention, only 7.9% (P ≤ .001) were “at risk” because some women started contraception, discontinued ACE-I/ARB/statins, or changed drug class. Conclusions Women prescribed ACE-I/ARB/statins were not consistently using contraception or were not consistently informed of the risks. Provider-implemented QI interventions improved care but were difficult to accomplish, suggesting that new interventions are needed. PMID:22956701

  5. Fetal Aortic Valvuloplasty for Evolving Hypoplastic Left Heart Syndrome: Postnatal Outcomes of the First 100 Patients

    PubMed Central

    Freud, Lindsay R.; McElhinney, Doff B.; Marshall, Audrey C.; Marx, Gerald R.; Friedman, Kevin G.; del Nido, Pedro J.; Emani, Sitaram M.; Lafranchi, Terra; Silva, Virginia; Wilkins-Haug, Louise E.; Benson, Carol B.; Lock, James E.; Tworetzky, Wayne

    2015-01-01

    Background Fetal aortic valvuloplasty (FAV) can be performed for severe mid-gestation aortic stenosis (AS) in an attempt to prevent progression to hypoplastic left heart syndrome (HLHS). A subset of patients has achieved a biventricular (BV) circulation after FAV. The postnatal outcomes and survival of the BV patients, compared to those managed as HLHS, have not been reported. Methods and Results We included 100 patients who underwent FAV for severe mid-gestation AS with evolving HLHS from March 2000 to January 2013. Patients were categorized based on postnatal management as BV or HLHS. Clinical records were reviewed. Eighty-eight fetuses were live-born, and 38 had a BV circulation (31 from birth, 7 converted after initial univentricular palliation). Left-sided structures, namely aortic and mitral valve sizes and LV volume, were significantly larger in the BV group at the time of birth (p-values <0.01). After a median follow-up of 5.4 years, freedom from cardiac death among all BV patients was 96±4% at 5 years and 84±12% at 10 years, which was better than HLHS patients (log-rank p=0.04). There was no cardiac mortality in patients with a BV circulation from birth. All but 1 of the BV patients required postnatal intervention; 42% underwent aortic and/or mitral valve replacement. On most recent echocardiogram, the median LV end-diastolic volume z-score was +1.7 (range: -1.3, +8.2), and 80% had normal ejection fraction. Conclusions Short- and intermediate-term survival among patients who underwent FAV and achieved a BV circulation postnatally is encouraging. However, morbidity still exists, and on-going assessment is warranted. PMID:25052401

  6. Geospatial association between adverse birth outcomes and arsenic in groundwater in New Hampshire, USA

    USGS Publications Warehouse

    Xun Shi,; Ayotte, Joseph; Akikazu Onda,; Stephanie Miller,; Judy Rees,; Diane Gilbert-Diamond,; Onega, Tracy L; Gui, Jiang; Karagas, Margaret R.; Moeschler, John B

    2015-01-01

    There is increasing evidence of the role of arsenic in the etiology of adverse human reproductive outcomes. Because drinking water can be a major source of arsenic to pregnant women, the effect of arsenic exposure through drinking water on human birth may be revealed by a geospatial association between arsenic concentration in groundwater and birth problems, particularly in a region where private wells substantially account for water supply, like New Hampshire, USA. We calculated town-level rates of preterm birth and term low birth weight (term LBW) for New Hampshire, by using data for 1997–2009 stratified by maternal age. We smoothed the rates by using a locally weighted averaging method to increase the statistical stability. The town-level groundwater arsenic probability values are from three GIS data layers generated by the US Geological Survey: probability of local groundwater arsenic concentration >1 µg/L, probability >5 µg/L, and probability >10 µg/L. We calculated Pearson’s correlation coefficients (r) between the reproductive outcomes (preterm birth and term LBW) and the arsenic probability values, at both state and county levels. For preterm birth, younger mothers (maternal age <20) have a statewider = 0.70 between the rates smoothed with a threshold = 2,000 births and the town mean arsenic level based on the data of probability >10 µg/L; for older mothers, r = 0.19 when the smoothing threshold = 3,500; a majority of county level r values are positive based on the arsenic data of probability >10 µg/L. For term LBW, younger mothers (maternal age <25) have a statewide r = 0.44 between the rates smoothed with a threshold = 3,500 and town minimum arsenic concentration based on the data of probability >1 µg/L; for older mothers, r = 0.14 when the rates are smoothed with a threshold = 1,000 births and also adjusted by town median household income in 1999, and the arsenic values are the town minimum based on probability

  7. Geospatial association between adverse birth outcomes and arsenic in groundwater in New Hampshire, USA.

    PubMed

    Shi, Xun; Ayotte, Joseph D; Onda, Akikazu; Miller, Stephanie; Rees, Judy; Gilbert-Diamond, Diane; Onega, Tracy; Gui, Jiang; Karagas, Margaret; Moeschler, John

    2015-04-01

    There is increasing evidence of the role of arsenic in the etiology of adverse human reproductive outcomes. Because drinking water can be a major source of arsenic to pregnant women, the effect of arsenic exposure through drinking water on human birth may be revealed by a geospatial association between arsenic concentration in groundwater and birth problems, particularly in a region where private wells substantially account for water supply, like New Hampshire, USA. We calculated town-level rates of preterm birth and term low birth weight (term LBW) for New Hampshire, by using data for 1997-2009 stratified by maternal age. We smoothed the rates by using a locally weighted averaging method to increase the statistical stability. The town-level groundwater arsenic probability values are from three GIS data layers generated by the US Geological Survey: probability of local groundwater arsenic concentration >1 µg/L, probability >5 µg/L, and probability >10 µg/L. We calculated Pearson's correlation coefficients (r) between the reproductive outcomes (preterm birth and term LBW) and the arsenic probability values, at both state and county levels. For preterm birth, younger mothers (maternal age <20) have a statewide r = 0.70 between the rates smoothed with a threshold = 2,000 births and the town mean arsenic level based on the data of probability >10 µg/L; for older mothers, r = 0.19 when the smoothing threshold = 3,500; a majority of county level r values are positive based on the arsenic data of probability >10 µg/L. For term LBW, younger mothers (maternal age <25) have a statewide r = 0.44 between the rates smoothed with a threshold = 3,500 and town minimum arsenic concentration based on the data of probability >1 µg/L; for older mothers, r = 0.14 when the rates are smoothed with a threshold = 1,000 births and also adjusted by town median household income in 1999, and the arsenic values are the town minimum based on probability >10 µg/L. At the county level for

  8. Retinal artery and vein thrombotic occlusion during pregnancy: markers for familial thrombophilia and adverse pregnancy outcomes

    PubMed Central

    Kurtz, Will S; Glueck, Charles J; Hutchins, Robert K; Sisk, Robert A; Wang, Ping

    2016-01-01

    Background Ocular vascular occlusion (OVO), first diagnosed during or immediately after giving birth, often reflects superposition of the physiologic thrombophilia of pregnancy on previously undiagnosed underlying familial or acquired thrombophilia associated with spontaneous abortion, eclampsia, or maternal thrombosis. Specific aim We describe OVO, first diagnosed during pregnancy or immediately postpartum, in three young females (ages 32, 35, 40) associated with previously undiagnosed familial thrombophilia. Results Branch retinal artery occlusion (BRAO) occurred at 9 and 13 weeks gestation in two females, aged 32 and 35. Central retinal vein occlusion occurred immediately postpartum in a 40-year-old. One of the two females with BRAO subsequently developed eclampsia, and one had a history of unexplained first trimester spontaneous abortion. All three females were found to have previously unexplained familial thrombophilia. The two females with BRAO had low first trimester free protein S 42 (41%), lower normal limit (50%), and one of these two had high factor VIII (165%, upper normal limit 150%). The woman with central retinal vein occlusion had high factor XI (169%, upper normal limit 150%). Enoxaparin (40–60 mg/day) was started and continued throughout pregnancy in both females with BRAO to prevent maternal–placental thrombosis, and of these two females, one had an uncomplicated pregnancy course and term delivery, and the second was at gestational week 22 without complications at the time of this manuscript. There were no further OVO events in the two females treated with enoxaparin or in the untreated patient with postpartum eclampsia. Conclusion OVO during pregnancy may be a marker for familial or acquired thrombophilia, which confers increased thrombotic risk to the mother and pregnancy, associated with spontaneous abortion or eclampsia. OVO during pregnancy, particularly when coupled with antecedent adverse pregnancy outcomes, should prompt urgent

  9. North-South Gradients in Adverse Birth Outcomes for First Nations and Others in Manitoba, Canada.

    PubMed

    Martens, Patricia J; Heaman, Maureen; Hart, Lyna; Wilkins, Russell; Smylie, Janet; Wassimi, Spogmai; Simonet, Fabienne; Wu, Yuquan; Fraser, William D; Luo, Zhong-Cheng

    2010-01-01

    OBJECTIVE: to determine the relationship of north-south place of residence to adverse birth outcomes among First Nations and non-First Nations in Manitoba, Canada, a setting with universal health insurance. STUDY DESIGN: Live birth records (n=151,472) for the province of Manitoba, Canada 1991-2000 were analyzed, including 25,743 First Nations and 125,729 non-First Nations infants. North-south and rural-urban residence was determined for each birth through geocoding. RESULTS: Comparing First Nations to non-First Nations, crude rates in North (and South) were: 7.0% versus 8.4% (9.3% versus 7.5%) for preterm birth; 6.1% versus 8.4% (8.7% versus 10.0%) for small-for-gestational-age birth, 4.2% versus 6.5% (6.2% versus 5.7%) for low birth weight, and 20.6% versus 13.7% (17.0% versus 11.0%) for large-for-gestational-age birth; and mortality per 1000 - neonatal 3.2 versus 6.2 (3.8 versus 3.3), post-neonatal 6.4 versus 6.4 (5.8 versus 1.5), and infant 9.5 versus 12.6 (9.6 versus 4.8). Adjusting for observed maternal and infant characteristics and rural versus urban residence, the North was high risk for large-for-gestational-age birth for both First Nations and non-First Nations. First Nations' risk of preterm, small-for-gestational-age and low birth weight was lowest in the North, but for non-First Nations, the North was lower only for small-for-gestational-age. First Nations mortality indicators were similar North to South, but for non-First Nations, the North was high risk. CONCLUSION: North-South place of residence does matter for adverse birth outcomes, but the effects may differ by ethnicity and could require different intervention strategies.

  10. Mercury in fish and adverse reproductive outcomes: results from South Carolina

    PubMed Central

    2014-01-01

    Background Mercury is a metal with widespread distribution in aquatic ecosystems and significant neurodevelopmental toxicity in humans. Fish biomonitoring for total mercury has been conducted in South Carolina (SC) since 1976, and consumption advisories have been posted for many SC waterways. However, there is limited information on the potential reproductive impacts of mercury due to recreational or subsistence fish consumption. Methods To address this issue, geocoded residential locations for live births from the Vital Statistics Registry (1995–2005, N = 362,625) were linked with spatially interpolated total mercury concentrations in fish to estimate potential mercury exposure from consumption of locally caught fish. Generalized estimating equations were used to test the hypothesis that risk of low birth weight (LBW, <2,500 grams) or preterm birth (PTB, <37 weeks clinical gestation) was greater among women living in areas with elevated total mercury in fish, after adjustment for confounding. Separate analyses estimated term LBW and PTB risks using residential proximity to rivers with fish consumption advisories to characterize exposure. Results Term LBW was more likely among women residing in areas in the upper quartile of predicted total mercury in fish (odds ratio [OR] = 1.04; 95% confidence interval [CI]: 1.00-1.09) or within 8 kilometers of a river with a ‘do not eat’ fish advisory (1.05; 1.00-1.11) compared to the lowest quartile, or rivers without fish consumption restrictions, respectively. When stratified by race, risks for term LBW or PTB were 10-18% more likely among African-American (AA) mothers living in areas with the highest total fish mercury concentrations. Conclusions To our knowledge, this is the first study to examine the relationship between fish total mercury concentrations and adverse reproductive outcomes in a large population-based sample that included AA women. The ecologic nature of exposure assessment in this study

  11. Prenatal Exposure to Tetrachloroethylene-Contaminated Drinking Water and the Risk of Adverse Birth Outcomes

    PubMed Central

    Aschengrau, Ann; Weinberg, Janice; Rogers, Sarah; Gallagher, Lisa; Winter, Michael; Vieira, Veronica; Webster, Thomas; Ozonoff, David

    2008-01-01

    Background Prior studies of prenatal exposure to tetrachloroethylene (PCE) have shown mixed results regarding its effect on birth weight and gestational age. Objectives In this retrospective cohort study we examined whether PCE contamination of public drinking-water supplies in Massachusetts influenced the birth weight and gestational duration of children whose mothers were exposed before the child’s delivery. Methods The study included 1,353 children whose mothers were exposed to PCE-contaminated drinking water and a comparable group of 772 children of unexposed mothers. Birth records were used to identify subjects and provide information on the outcomes. Mothers completed a questionnaire to gather information on residential histories and confounding variables. PCE exposure was estimated using EPANET water distribution system modeling software that incorporated a fate and transport model. Results We found no meaningful associations between PCE exposure and birth weight or gestational duration. Compared with children whose mothers were unexposed during the year of the last menstrual period (LMP), adjusted mean differences in birth weight were 20.9, 6.2, 30.1, and 15.2 g for children whose mothers’ average monthly exposure during the LMP year ranged from the lowest to highest quartile. Similarly, compared with unexposed children, adjusted mean differences in gestational age were −0.2, 0.1, −0.1, and −0.2 weeks for children whose mothers’ average monthly exposure ranged from the lowest to highest quartile. Similar results were observed for two other measures of prenatal exposure. Conclusions These results suggest that prenatal PCE exposure does not have an adverse effect on these birth outcomes at the exposure levels experienced by this population. PMID:18560539

  12. Postoperative adverse outcomes among physicians receiving major surgeries: A nationwide retrospective cohort study.

    PubMed

    Yeh, Chun-Chieh; Liao, Chien-Chang; Shih, Chun-Chuan; Jeng, Long-Bin; Chen, Ta-Liang

    2016-09-01

    Outcomes after surgeries involving physicians as patients have not been researched. This study compares postoperative adverse events between physicians as surgical patients and nonhealth professional controls.Using reimbursement claims data from Taiwan's National Health Insurance Program, we conducted a matched retrospective cohort study of 7973 physicians as surgical patients and 7973 propensity score-matched nonphysician controls receiving in-hospital major surgeries between 2004 and 2010. We compared postoperative major complications, length of hospital stay, intensive care unit (ICU), medical expenditure, and 30-day mortality.Compared with nonphysician controls, physicians as surgical patients had lower adjusted odds ratios (ORs) with 95% confidence intervals (CIs) of postoperative deep wound infection (OR 0.63, 95% CI 0.40-0.99; P < 0.05), prolonged length of stay (OR 0.68, 95% CI 0.62-0.75; P < 0.0001), ICU admission (OR 0.74, 95% CI 0.66-0.83; P < 0.0001), and increased medical expenditure (OR 0.80, 95% CI 0.73-0.88; P < 0.0001). Physicians as surgical patients were not associated with 30-day in-hospital mortality after surgery. Physicians working at medical centers (P < 0.05 for all), dentists (P < 0.05 for all), and those with fewer coexisting medical conditions (P < 0.05 for all) had lower risks for postoperative prolonged length of stay, ICU admission, and increased medical expenditure.Although our study's findings suggest that physicians as surgical patients have better outcomes after surgery, future clinical prospective studies are needed for validation. PMID:27684836

  13. Inadequate gestational weight gain and adverse pregnancy outcomes among normal weight women in China

    PubMed Central

    Wen, Tingyuan; Lv, Yanwei

    2015-01-01

    Objective: The objective of the paper is to find the association between inadequate gestational weight gain and pregnancy outcomes in normal weight women in China. Method: A retrospective study was conducted among 13,776 normal weight pregnant women who received antenatal care and delivered singleton infants at the participating hospital during August, 2009 to July, 2013. Adverse pregnancy outcomes like low birth weight (LBW), preterm birth, birth asphyxia, neonatal intensive care unit (NICU) admission and length of hospital stay were compared and analyzed between two groups with inadequate and adequate gestational weight gain. Results: According to the IOM recommendations, inadequate gestational weight gain was found to be 14.7% in this study. Women with inadequate gestational weight gain (GWG) were found to be at a higher risk for LBW (aOR = 2.13, 95% CI: 1.75, 2.86) and preterm birth (aOR = 1.44, 95% CI: 1.21, 1.67) than those in the adequate gestational weight gain group, after adjusting for monthly family income, maternal education, occupation, and whether they received any advice regarding benefits of gestational weight gain and residential area. However, inadequate GWG was not associated with longer hospital stay (aOR = 1.13, 95% CI: 0.91-1.43) in adjusted model. In addition, the rate of birth asphyxia and NICU admission were similar in both groups (P > 0.05). Conclusions: Normal weight pregnant women with GWG below the recommended AIOM 2009 guidelines were found to be at an increased risk of low birth weight and preterm birth. PMID:25932249

  14. A Workflow to Investigate Exposure and Pharmacokinetic Influences on High-Throughput in Vitro Chemical Screening Based on Adverse Outcome Pathways

    EPA Science Inventory

    Background: Adverse outcome pathways (AOPs) link adverse effects in individuals or populations to a molecular initiating event (MIE) that can be quantified using in vitro methods. Practical application of AOPs in chemical-specific risk assessment requires incorporation of knowled...

  15. High birth weight in a suburban hospital in Cameroon: an analysis of the clinical cut-off, prevalence, predictors and adverse outcomes

    PubMed Central

    Choukem, Simeon-Pierre; Njim, Tsi; Atashili, Julius; Hamilton-Shield, Julian P; Mbu, Robinson

    2016-01-01

    Background and aims High birth weight (HBW) increases the risk of maternal and fetal morbidity and mortality. Its prevalence and adverse outcomes may be reduced if risk factors are identified and managed during pregnancy. The cut-off value for HBW remains debatable. The objectives of this study were to identify the optimal cut-off value and determine the prevalence, predictors and adverse outcomes of HBW in a suburban area of Cameroon. Design A 6-year retrospective register analysis and a 3-month prospective phase. Setting A secondary care level (regional) hospital in the city of Buea (southwest region of Cameroon). Participants Women who delivered in this hospital over a 6-year period (retrospective phase) and consenting pregnant mothers and their infants (singletons, born at >28 weeks gestation) (prospective phase). Outcome measures 90th centile of birth weights; prevalence of HBW defined as birth weight above the 90th centile; sociodemographic, maternal and obstetrical factors associated with HBW; maternal and neonatal adverse outcomes of HBW. Results Of the 4941 newborns reviewed in registers, the 90th centile of birth weights was 3850 g. Using this new cut-off, we obtained a prevalence of 14.0% for HBW in the 200 newborns included in the prospective phase. This was significantly higher than the prevalence (9.5%) yielded when the traditional cut-off of 4000 g was used (p=0.003). None of the factors assessed was independently associated with HBW. Newborns with HBW were more likely to have shoulder dystocia (p<0.01), and their mothers more likely to suffer from prolonged labour (p=0.01) and postpartum haemorrhage (p<0.01). Conclusions The results of this study suggest that the cut-off for HBW in this population should be 3850 g. Thus, 3 of every 10 babies born with HBW in this hospital are likely not receiving optimal postnatal care because 4000 g is currently used to qualify for additional support. PMID:27357199

  16. Periodontal disease and some adverse perinatal outcomes in a cohort of low risk pregnant women

    PubMed Central

    2010-01-01

    Objective To evaluate the association of periodontal disease (PD) in pregnancy with some adverse perinatal outcomes. Method This cohort study included 327 pregnant women divided in groups with or without PD. Indexes of plaque and gingival bleeding on probing, probing pocket depth, clinical attachment level and gingival recession were evaluated at one periodontal examination below 32 weeks of gestation. The rates of preterm birth (PTB), low birth weight (LBW), small for gestational age (SGA) neonates and prelabor rupture of membranes (PROM) were evaluated using Risk Ratios (95%CI) and Population Attributable Risk Fractions. Results PD was associated with a higher risk of PTB (RRadj. 3.47 95%CI 1.62-7.43), LBW (RRadj. 2.93 95%CI 1.36-6.34) and PROM (RRadj. 2.48 95%CI 1.35-4.56), but not with SGA neonates (RR 2.38 95%CI 0.93 - 6.10). Conclusions PD was a risk factor for PT, LBW and PROM among Brazilian low risk pregnant women. PMID:21047427

  17. Adverse Outcome Pathways can drive non-animal approaches for safety assessment.

    PubMed

    Burden, Natalie; Sewell, Fiona; Andersen, Melvin E; Boobis, Alan; Chipman, J Kevin; Cronin, Mark T D; Hutchinson, Thomas H; Kimber, Ian; Whelan, Maurice

    2015-09-01

    Adverse Outcome Pathways (AOPs) provide an opportunity to develop new and more accurate safety assessment processes for drugs and other chemicals, and may ultimately play an important role in regulatory decision making. Not only can the development and application of AOPs pave the way for the development of improved evidence-based approaches for hazard and risk assessment, there is also the promise of a significant impact on animal welfare, with a reduced reliance on animal-based methods. The establishment of a useable and coherent knowledge framework under which AOPs will be developed and applied has been a first critical step towards realizing this opportunity. This article explores how the development of AOPs under this framework, and their application in practice, could benefit the science and practice of safety assessment, while in parallel stimulating a move away from traditional methods towards an increased acceptance of non-animal approaches. We discuss here the key areas where current, and future initiatives should be focused to enable the translation of AOPs into routine chemical safety assessment, and lasting 3Rs benefits.

  18. ED 07-4 IS EXERCISE-INDUCED HYPERTENSION ASSOCIATED WITH ADVERSE CARDIOVASCULAR OUTCOMES?

    PubMed

    Sharman, James

    2016-09-01

    Millions of clinical exercise stress tests are conducted annually worldwide. The fundamental rationale underlying the conduct of these tests is that cardiovascular irregularities may be revealed during an exercise bout that would otherwise remain unnoticed if testing was only conducted under resting conditions. In order to reveal electrocardiographic abnormalities indicative of cardiac disease, maximal intensity exercise may need to be undertaken, whereas the presence of hypertension can be revealed by the blood pressure response at low to moderate intensity exercise. Therefore, exercise blood pressure measured carefully under standardised conditions should be a useful tool to identify individuals at increased cardiovascular risk. Independent investigators have consistently shown that exercise blood pressure at low to moderate intensities predicts adverse cardiovascular outcomes independent from resting blood pressure and conventional cardiovascular risk factors. This talk will present evidence in support of exercise-induced hypertension as a clinical observation requiring additional follow up care. Future needs in terms of better understanding the mechanisms of exercise hypertension and determination of exercise hypertension thresholds will also be detailed. PMID:27642909

  19. Acute Colonic Pseudo-obstruction: Defining the Epidemiology, Treatment, and Adverse Outcomes of Ogilvie's Syndrome.

    PubMed

    Ross, Samuel W; Oommen, Bindhu; Wormer, Blair A; Walters, Amanda L; Augenstein, Vedra A; Heniford, B Todd; Sing, Ronald F; Christmas, A Britton

    2016-02-01

    Acute colonic pseudo-obstruction (ACPO) is a rare but often fatal disease. Herein, we present the largest study to date on ACPO. The National Inpatient Sample was queried for ACPO diagnoses from 1998 to 2011. Patients were analyzed by treatment into four groups: medical management (MM), colonoscopy alone [(endoscopy-only group) ENDO], surgery alone (SURG), or surgery and colonoscopy (SAC). Logistic regression was used to identify predictors of adverse outcomes by treatment group. There were 106,784 cases of ACPO: 96,657 (90.5%) MM, 2,915 (2.7%) ENDO, 6,731 (6.3%) SURG, and 481 (0.5%) SAC. The medical complication (45.7%), procedural complication (15.9%), and mortality rates (7.7%) were high. Increasing procedure invasiveness was independently associated with higher odds of medical complications, procedural complications, and death (P < 0.0125). The odds of death were significantly higher in the ENDO [odds ratio (OR) = 1.2], SURG (OR 1.4), and SAC (OR = 1.8) groups (P < 0.0125). Those who fail MM and require procedures have increasing morbidity and mortality with increasing invasiveness, likely reflecting the severity of their conditions.

  20. Internal exposure dynamics drive the Adverse Outcome Pathways of synthetic glucocorticoids in fish

    PubMed Central

    Margiotta-Casaluci, Luigi; Owen, Stewart F.; Huerta, Belinda; Rodríguez-Mozaz, Sara; Kugathas, Subramanian; Barceló, Damià; Rand-Weaver, Mariann; Sumpter, John P.

    2016-01-01

    The Adverse Outcome Pathway (AOP) framework represents a valuable conceptual tool to systematically integrate existing toxicological knowledge from a mechanistic perspective to facilitate predictions of chemical-induced effects across species. However, its application for decision-making requires the transition from qualitative to quantitative AOP (qAOP). Here we used a fish model and the synthetic glucocorticoid beclomethasone dipropionate (BDP) to investigate the role of chemical-specific properties, pharmacokinetics, and internal exposure dynamics in the development of qAOPs. We generated a qAOP network based on drug plasma concentrations and focused on immunodepression, skin androgenisation, disruption of gluconeogenesis and reproductive performance. We showed that internal exposure dynamics and chemical-specific properties influence the development of qAOPs and their predictive power. Comparing the effects of two different glucocorticoids, we highlight how relatively similar in vitro hazard-based indicators can lead to different in vivo risk. This discrepancy can be predicted by their different uptake potential, pharmacokinetic (PK) and pharmacodynamic (PD) profiles. We recommend that the development phase of qAOPs should include the application of species-species uptake and physiologically-based PK/PD models. This integration will significantly enhance the predictive power, enabling a more accurate assessment of the risk and the reliable transferability of qAOPs across chemicals. PMID:26917256

  1. Mechanisms of lung fibrosis induced by carbon nanotubes: towards an Adverse Outcome Pathway (AOP).

    PubMed

    Vietti, Giulia; Lison, Dominique; van den Brule, Sybille

    2016-02-29

    Several experimental studies have shown that carbon nanotubes (CNT) can induce respiratory effects, including lung fibrosis. The cellular and molecular events through which these effects develop are, however, not clearly elucidated. The purpose of the present review was to analyze the key events involved in the lung fibrotic reaction induced by CNT and to assess their relationships. We thus address current knowledge and gaps with a view to draft an Adverse Outcome Pathway (AOP) concerning the fibrotic potential of CNT.As for many inhaled particles, CNT can indirectly activate fibroblasts through the release of pro-inflammatory (IL-1β) and pro-fibrotic (PDGF and TGF-β) mediators by inflammatory cells (macrophages and epithelial cells) via the induction of oxidative stress, inflammasome or NF-kB. We also highlight here direct effects of CNT on fibroblasts, which appear as a new mode of toxicity relatively specific for CNT. Direct effects of CNT on fibroblasts include the induction of fibroblast proliferation, differentiation and collagen production via ERK 1/2 or Smad signaling. We also point out the physico-chemical properties of CNT important for their toxicity and the relationship between in vitro and in vivo effects. This knowledge provides evidence to draft an AOP for the fibrogenic activity of CNT, which allows developing simple in vitro models contributing to predict the CNT effects in lung fibrosis, and risk assessment tools for regulatory decision.

  2. Systemic effects of periodontitis: lessons learned from research on atherosclerotic vascular disease and adverse pregnancy outcomes.

    PubMed

    Papapanou, Panos N

    2015-12-01

    Studies conducted over the past 25 years have focussed on the role of periodontitis, an inflammatory condition of microbial aetiology that destroys the tooth-supporting tissues, as a systemic inflammatory stressor that can act as an independent risk factor of atherosclerotic vascular disease (AVSD) and adverse pregnancy outcomes (APOs). It has been suggested that periodontitis-associated bacteraemias and systemic dissemination of inflammatory mediators produced in the periodontal tissues may result in systemic inflammation and endothelial dysfunction, and that bacteria of oral origin may translocate into the feto-placental unit. Epidemiological studies largely support an association between periodontitis and ASVD/APOs, independently of known confounders; indeed, periodontitis has been shown to confer statistically significantly elevated risk for clinical events associated with ASVD and APOs in multivariable adjustments. On the other hand, intervention studies demonstrate that although periodontal therapy reduces systemic inflammation and improves endothelial function, it has no positive effect on the incidence of APOs. Studies of the effects of periodontal interventions on ASVD-related clinical events are lacking. This review summarises key findings from mechanistic, association and intervention studies and attempts to reconcile the seemingly contradictory evidence that originates from different lines of investigation.

  3. Internal exposure dynamics drive the Adverse Outcome Pathways of synthetic glucocorticoids in fish

    NASA Astrophysics Data System (ADS)

    Margiotta-Casaluci, Luigi; Owen, Stewart F.; Huerta, Belinda; Rodríguez-Mozaz, Sara; Kugathas, Subramanian; Barceló, Damià; Rand-Weaver, Mariann; Sumpter, John P.

    2016-02-01

    The Adverse Outcome Pathway (AOP) framework represents a valuable conceptual tool to systematically integrate existing toxicological knowledge from a mechanistic perspective to facilitate predictions of chemical-induced effects across species. However, its application for decision-making requires the transition from qualitative to quantitative AOP (qAOP). Here we used a fish model and the synthetic glucocorticoid beclomethasone dipropionate (BDP) to investigate the role of chemical-specific properties, pharmacokinetics, and internal exposure dynamics in the development of qAOPs. We generated a qAOP network based on drug plasma concentrations and focused on immunodepression, skin androgenisation, disruption of gluconeogenesis and reproductive performance. We showed that internal exposure dynamics and chemical-specific properties influence the development of qAOPs and their predictive power. Comparing the effects of two different glucocorticoids, we highlight how relatively similar in vitro hazard-based indicators can lead to different in vivo risk. This discrepancy can be predicted by their different uptake potential, pharmacokinetic (PK) and pharmacodynamic (PD) profiles. We recommend that the development phase of qAOPs should include the application of species-species uptake and physiologically-based PK/PD models. This integration will significantly enhance the predictive power, enabling a more accurate assessment of the risk and the reliable transferability of qAOPs across chemicals.

  4. Adverse outcome pathway and risks of anticoagulant rodenticides to predatory wildlife

    USGS Publications Warehouse

    Rattner, Barnett A.; Lazarus, Rebecca; Elliott, John E.; Shore, Richard F.; van den Brink, Nico

    2014-01-01

    Despite a long history of successful use, routine application of some anticoagulant rodenticides (ARs) may be at a crossroad due to new regulatory guidelines intended to mitigate risk. An adverse outcome pathway for ARs was developed to identify information gaps and end points to assess the effectiveness of regulations. This framework describes chemical properties of ARs, established macromolecular interactions by inhibition of vitamin K epoxide reductase, cellular responses including altered clotting factor processing and coagulopathy, organ level effects such as hemorrhage, organism responses with linkages to reduced fitness and mortality, and potential consequences to predator populations. Risk assessments have led to restrictions affecting use of some second-generation ARs (SGARs) in North America. While the European regulatory community highlighted significant or unacceptable risk of ARs to nontarget wildlife, use of SGARs in most EU member states remains authorized due to public health concerns and the absence of safe alternatives. For purposes of conservation and restoration of island habitats, SGARs remain a mainstay for eradication of invasive species. There are significant data gaps related to exposure pathways, comparative species sensitivity, consequences of sublethal effects, potential hazards of greater AR residues in genetically resistant prey, effects of low-level exposure to multiple rodenticides, and quantitative data on the magnitude of nontarget wildlife mortality.

  5. Taxonomic applicability of inflammatory cytokines in adverse outcome pathway (AOP) development.

    PubMed

    Angrish, Michelle M; Pleil, Joachim D; Stiegel, Matthew A; Madden, Michael C; Moser, Virginia C; Herr, David W

    2016-01-01

    Cytokines, low-molecular-weight messenger proteins that act as intercellular immunomodulatory signals, have become a mainstream preclinical marker for assessing the systemic inflammatory response to external stressors. The challenge is to quantitate from healthy subjects cytokine levels that are below or at baseline and relate those dynamic and complex cytokine signatures of exposures with the inflammatory and repair pathways. Thus, highly sensitive, specific, and precise analytical and statistical methods are critically important. Investigators at the U.S. Environmental Protection Agency (EPA) have implemented advanced technologies and developed statistics for evaluating panels of inflammatory cytokines in human blood, exhaled breath condensate, urine samples, and murine biological media. Advanced multiplex, bead-based, and automated analytical platforms provided sufficient sensitivity, precision, and accuracy over the traditional enzyme-linked immunosorbent assay (ELISA). Thus, baseline cytokine levels can be quantified from healthy human subjects and animals and compared to an in vivo exposure response from an environmental chemical. Specifically, patterns of cytokine responses in humans exposed to environmental levels of ozone and diesel exhaust, and in rodents exposed to selected pesticides (such as fipronil and carbaryl), were used as case studies to generally assess the taxonomic applicability of cytokine responses. The findings in this study may aid in the application of measureable cytokine markers in future adverse outcome pathway (AOP)-based toxicity testing. Data from human and animal studies were coalesced and the possibility of using cytokines as key events (KE) to bridge species responses to external stressors in an AOP-based framework was explored.

  6. Adverse Outcome Pathways and Ecological Risk Assessment: Bridging to Population-Level Effects

    SciTech Connect

    Kramer, Vincent J.; Etterson, Matthew A.; Hecker, Markus; Murphy, Cheryl A.; Roesijadi, Guritno; Spade, Daniel J.; Spromberg, Julann A.; Wang, Magnus; Ankley, Gerald T.

    2010-11-24

    The viability of populations of plants and animals is a key focus for environmental regulation. Population-level responses integrate the cumulative effects of chemical stressors on individuals as those individuals interact with and are affected by their con-specifics, competitors, predators, prey, habitat and other biotic and abiotic factors. Models of population-level effects of contaminants can integrate information from lower levels of biological organization and feed that information into higher-level community and ecosystem models. As individual-level endpoints are utilized to predict population responses, this requires that biological responses at lower levels of organization be translated into a form that is useable by the population modeler. In this paper we describe how mechanistic data, as captured in adverse outcome pathways, can be translated into modeling focused on population-level risk assessments. First, we present a succinct overview of different approaches to population modeling, and discuss the types of data needed for these models. Then we discuss how toxicity data are used currently for population modeling, and provide recommendations as to how testing might be modified to better generate information to support modeling. From this we describe how different key processes measured at the level of the individual serve as the bridge between mechanistic toxicology data and predictions of population status, and provide case examples of how this linkage has been/can be achieved.

  7. Do sugar-sweetened beverages cause adverse health outcomes in children? A systematic review protocol

    PubMed Central

    2014-01-01

    Background Cardiovascular disease and type 2 diabetes are examples of chronic diseases that impose significant morbidity and mortality in the general population worldwide. Most chronic diseases are associated with underlying preventable risk factors, such as elevated blood pressure, high blood glucose or glucose intolerance, high lipid levels, physical inactivity, excessive sedentary behaviours, and overweight/obesity. The occurrence of intermediate outcomes during childhood increases the risk of disease in adulthood. Sugar-sweetened beverages are known to be significant sources of additional caloric intake, and given recent attention to their contribution in the development of chronic diseases, a systematic review is warranted. We will assess whether the consumption of sugar-sweetened beverages in children is associated with adverse health outcomes and what the potential moderating factors are. Methods/Design Of interest are studies addressing sugar-sweetened beverage consumption, taking a broad perspective. Both direct consumption studies as well as those evaluating interventions that influence consumption (e.g. school policy, educational) will be relevant. Non-specific or multi-faceted behavioural, educational, or policy interventions may also be included subject to the level of evidence that exists for the other interventions/exposures. Comparisons of interest and endpoints of interest are pre-specified. We will include randomized controlled trials, controlled clinical trials, interrupted time series studies, controlled before-after studies, prospective and retrospective comparative cohort studies, case–control studies, and nested case–control designs. The MEDLINE®, Embase, The Cochrane Library, CINAHL, ERIC, and PsycINFO® databases and grey literature sources will be searched. The processes for selecting studies, abstracting data, and resolving conflicts are described. We will assess risk of bias using design-specific tools. To determine sets of

  8. Adverse Outcome Pathway (AOP) for a Mutagenic Mode of Action for Cancer: AFB1 and Hepatocellular Carcinoma (HCC)

    EPA Science Inventory

    AOPs provide a framework to describe a sequence of measureable key events (KEs), beginning with a molecular initiating event (MIE), followed by a series of identified KEs linked to one another by KE Relationships (KERs), all anchored by a specific adverse outcome (AO). Each KE/KE...

  9. The Impact of Postnatal Depression and Associated Adversity on Early Mother-Infant Interactions and Later Infant Outcome.

    ERIC Educational Resources Information Center

    Murray, Lynne; And Others

    1996-01-01

    Examined the impact of maternal depression and adversity on mother-infant face-to-face interactions at 2 months, and on subsequent infant cognitive development and attachment. Disturbances in early mother-infant interactions were found to be predictive of poorer infant cognitive outcomes at 18 months. (MDM)

  10. Increasing scientific confidence in adverse outcome pathways: Application of tailored Bradford-Hill considerations for evaluating weight of evidence

    EPA Science Inventory

    Systematic consideration of scientific support is a critical element in developing and, ultimately, using adverse outcome pathways (AOPs) for various regulatory applications. Though weight of evidence (WoE) analysis has been proposed as a basis for assessment of the maturity and...

  11. Physiologically-based Pharmacokinetic(PBPK) Models Application to Screen Environmental Hazards Related to Adverse Outcome Pathways(AOPs)

    EPA Science Inventory

    PBPK models are useful in estimating exposure levels based on in vitro to in vivo extrapolation (IVIVE) calculations. Linkage of large sets of chemically screened vitro signature effects to in vivo adverse outcomes using IVIVE is central to the concepts of toxicology in the 21st ...

  12. Discovering and annotating fish early life-stage (FELS) adverse outcome pathways: Putting the research strategy into practice

    EPA Science Inventory

    In May 2012, a HESI-sponsored expert workshop yielded a proposed research strategy for systematically discovering, characterizing, and annotating fish early life-stage (FELS) adverse outcome pathways (AOPs) as well as prioritizing AOP development in light of current restrictions ...

  13. Using adverse outcome pathway analysis to guide development of high-throughput screening assays for thyroid-disruptors

    EPA Science Inventory

    Using Adverse Outcome Pathway Analysis to Guide Development of High-Throughput Screening Assays for Thyroid-Disruptors Katie B. Paul1,2, Joan M. Hedge2, Daniel M. Rotroff4, Kevin M. Crofton4, Michael W. Hornung3, Steven O. Simmons2 1Oak Ridge Institute for Science Education Post...

  14. Weight of evidence evaluation of adverse outcome pathways converging at impaired vitellogenin synthesis leading to reproductive impairment

    EPA Science Inventory

    Adverse outcome pathways (AOPs) provide a framework that supports greater use of mechanistic data measured at lower levels of biological organization as a basis for regulatory decision-making. However, it is recognized that different types of regulatory applications and decisions...

  15. Building an Adverse Outcome Pathway Framework through HTS Data and Literature Mining Integration (FutureToxII)

    EPA Science Inventory

    Interpreting EPA’s ToxCast in vitro assay data in the context of Adverse Outcome Pathway (AOP) development is a significant challenge. While chemical activation in these assays may shed light on the molecular initiating event, the downstream effect of these activities at higher ...

  16. Maternal adverse effects of different antenatal magnesium sulphate regimens for improving maternal and infant outcomes: a systematic review

    PubMed Central

    2013-01-01

    Background Antenatal magnesium sulphate, widely used in obstetrics to improve maternal and infant outcomes, may be associated with adverse effects for the mother sufficient for treatment cessation. This systematic review aimed to quantify maternal adverse effects attributed to treatment, assess how adverse effects vary according to different regimens, and explore women’s experiences with this treatment. Methods Bibliographic databases were searched from their inceptions to July 2012 for studies of any design that reported on maternal adverse effects associated with antenatal magnesium sulphate given to improve maternal or infant outcomes. Primary outcomes were life-threatening adverse effects of treatment (death, cardiac arrest, respiratory arrest). For randomised controlled trials, data were meta-analysed, and risk ratios (RR) pooled using fixed-effects or random-effects models. For non-randomised studies, data were tabulated by design, and presented as RR, odds ratios or percentages, and summarised narratively. Results A total of 143 publications were included (21 randomised trials, 15 non-randomised comparative studies, 32 case series and 75 reports of individual cases), of mixed methodological quality. Compared with placebo or no treatment, magnesium sulphate was not associated with an increased risk of maternal death, cardiac arrest or respiratory arrest. Magnesium sulphate significantly increased the risk of 'any adverse effects’ overall (RR 4.62, 95% CI 2.42-8.83; 4 trials, 13,322 women), and treatment cessation due to adverse effects (RR 2.77; 95% CI 2.32-3.30; 5 trials, 13,666 women). Few subgroup differences were observed (between indications for use and treatment regimens). In one trial, a lower dose regimen (2 g/3 hours) compared with a higher dose regimen (5 g/4 hours) significantly reduced treatment cessation (RR 0.05; 95% CI 0.01-0.39, 126 women). Adverse effect estimates from studies of other designs largely supported data from randomised

  17. Fetal Alcohol Spectrum Disorders.

    PubMed

    Williams, Janet F; Smith, Vincent C

    2015-11-01

    Prenatal exposure to alcohol can damage the developing fetus and is the leading preventable cause of birth defects and intellectual and neurodevelopmental disabilities. In 1973, fetal alcohol syndrome was first described as a specific cluster of birth defects resulting from alcohol exposure in utero. Subsequently, research unequivocally revealed that prenatal alcohol exposure causes a broad range of adverse developmental effects. Fetal alcohol spectrum disorder (FASD) is the general term that encompasses the range of adverse effects associated with prenatal alcohol exposure. The diagnostic criteria for fetal alcohol syndrome are specific, and comprehensive efforts are ongoing to establish definitive criteria for diagnosing the other FASDs. A large and growing body of research has led to evidence-based FASD education of professionals and the public, broader prevention initiatives, and recommended treatment approaches based on the following premises:▪ Alcohol-related birth defects and developmental disabilities are completely preventable when pregnant women abstain from alcohol use.▪ Neurocognitive and behavioral problems resulting from prenatal alcohol exposure are lifelong.▪ Early recognition, diagnosis, and therapy for any condition along the FASD continuum can result in improved outcomes.▪ During pregnancy:◦no amount of alcohol intake should be considered safe;◦there is no safe trimester to drink alcohol;◦all forms of alcohol, such as beer, wine, and liquor, pose similar risk; and◦binge drinking poses dose-related risk to the developing fetus.

  18. Fetal Alcohol Spectrum Disorders.

    PubMed

    Williams, Janet F; Smith, Vincent C

    2015-11-01

    Prenatal exposure to alcohol can damage the developing fetus and is the leading preventable cause of birth defects and intellectual and neurodevelopmental disabilities. In 1973, fetal alcohol syndrome was first described as a specific cluster of birth defects resulting from alcohol exposure in utero. Subsequently, research unequivocally revealed that prenatal alcohol exposure causes a broad range of adverse developmental effects. Fetal alcohol spectrum disorder (FASD) is the general term that encompasses the range of adverse effects associated with prenatal alcohol exposure. The diagnostic criteria for fetal alcohol syndrome are specific, and comprehensive efforts are ongoing to establish definitive criteria for diagnosing the other FASDs. A large and growing body of research has led to evidence-based FASD education of professionals and the public, broader prevention initiatives, and recommended treatment approaches based on the following premises:▪ Alcohol-related birth defects and developmental disabilities are completely preventable when pregnant women abstain from alcohol use.▪ Neurocognitive and behavioral problems resulting from prenatal alcohol exposure are lifelong.▪ Early recognition, diagnosis, and therapy for any condition along the FASD continuum can result in improved outcomes.▪ During pregnancy:◦no amount of alcohol intake should be considered safe;◦there is no safe trimester to drink alcohol;◦all forms of alcohol, such as beer, wine, and liquor, pose similar risk; and◦binge drinking poses dose-related risk to the developing fetus. PMID:26482673

  19. Impact of Different Childhood Adversities on 1-Year Outcomes of Psychotic Disorder in the Genetics and Psychosis Study

    PubMed Central

    Trotta, Antonella; Murray, Robin M.; David, Anthony S.; Kolliakou, Anna; O’Connor, Jennifer; Di Forti, Marta; Dazzan, Paola; Mondelli, Valeria; Morgan, Craig; Fisher, Helen L.

    2016-01-01

    While the role of childhood adversity in increasing the risk of psychosis has been extensively investigated, it is not clear what the impact of early adverse experiences is on the outcomes of psychotic disorders. Therefore, we investigated associations between childhood adversity and 1-year outcomes in 285 first-presentation psychosis patients. Exposure to childhood adversity prior to 17 years of age was assessed using the Childhood Experience of Care and Abuse Questionnaire. Data on illness course, symptom remission, length of psychiatric hospitalization, compliance with medication, employment, and relationship status were extracted from clinical records for the year following first contact with mental health services for psychosis. Seventy-one percent of patients reported exposure to at least 1 type of childhood adversity (physical abuse, sexual abuse, parental separation, parental death, disrupted family arrangements, or being taken into care). No robust associations were found between childhood adversity and illness course or remission. However, childhood physical abuse was associated with almost 3-fold increased odds of not being in a relationship at 1-year follow-up compared to patients who did not report such adverse experiences. There was also evidence of a significant association between parental separation in childhood and longer admissions to psychiatric wards during 1-year follow-up and 2-fold increased odds of noncompliance with medication compared to those not separated from their parents. Therefore, our findings suggest that there may be some specificity in the impact of childhood adversity on service use and social functioning among psychosis patients over the first year following presentation to mental health services. PMID:26373540

  20. The effect of warfarin dosage on maternal and fetal outcomes in pregnant women with prosthetic heart valves

    PubMed Central

    Soma-Pillay, P; Nene, Z; Mathivha, T M; Macdonald, A P

    2011-01-01

    There are several challenges in the management of pregnant women with mechanical heart valves. Pregnancy increases the risk of thromboembolism and there is currently no consensus on the safest anticoagulation method during pregnancy. The objective of the study was to determine the correlation between the warfarin dose and pregnancy outcome in pregnant women with prosthetic heart valves. Warfarin in pregnancy was associated with a low risk of valve thrombosis or maternal death. The risk for fetal abnormalities was not related to the maternal warfarin dosage. However, the risk for stillbirth was significantly increased with increasing doses of warfarin. PMID:27579092

  1. Immigrants’ duration of residence and adverse birth outcomes: a population-based study

    PubMed Central

    Urquia, ML; Frank, JW; Moineddin, R; Glazier, RH

    2010-01-01

    Please cite this paper as: Urquia M, Frank J, Moineddin R, Glazier R. Immigrants’ duration of residence and adverse birth outcomes: a population-based study. BJOG 2010;117:591–601. Objective This study aimed to examine preterm and small-for-gestational-age (SGA) births among immigrants, by duration of residence, and to compare them with the Canadian-born population. Design Population-based cross-sectional study with retrospective assessment of immigration. Setting Metropolitan areas of Ontario, Canada. Population A total of 83 233 singleton newborns born to immigrant mothers and 314 237 newborns born to non-immigrant mothers. Methods We linked a database of immigrants acquiring permanent residence in Ontario, Canada, in the period 1985–2000 with mother–infant hospital records (2002–2007). Duration of residence was measured as completed years from arrival to Canada to delivery/birth. Logistic regression models were used to estimate the effects of duration of residence with adjusted odds ratios and 95% confidence intervals. In analyses restricted to immigrants only, hierarchical models were used to account for the clustering of births into maternal countries of birth. Main outcome measures Preterm birth (PTB) and SGA birth. Results Recent immigrants (<5 years) had a lower risk of PTB (4.7%) than non-immigrants (6.2%), but those with ≥15 years of stay were at higher risk (7.4%). Among immigrants, a 5-year increase in Canadian residence was associated with an increase in PTB (AOR 1.14, 95% CI 1.10–1.19), but not in SGA birth (AOR 0.99, 95% CI 0.96–1.02). Conclusions Time since migration was associated with increases in the risk of PTB, but was not associated with an increase in SGA births. Ignoring duration of residence may mask important disparities in preterm delivery between immigrants and non-immigrants, and between immigrant subgroups categorised by their duration of residence. PMID:20374596

  2. Do sugar-sweetened beverages cause adverse health outcomes in adults? A systematic review protocol

    PubMed Central

    2014-01-01

    Background Chronic diseases, such as cardiovascular disease and type 2 diabetes, impose significant burden to public health. Most chronic diseases are associated with underlying preventable risk factors, such as elevated blood pressure, blood glucose, and lipids, physical inactivity, excessive sedentary behaviours, overweight and obesity, and tobacco usage. Sugar-sweetened beverages are known to be significant sources of additional caloric intake, and given recent attention to their contribution in the development of chronic diseases, a systematic review is warranted. We will assess whether the consumption of sugar-sweetened beverages in adults is associated with adverse health outcomes and what the potential moderating factors are. Methods/Design Of interest are studies addressing sugar-sweetened beverage consumption, taking a broad perspective. Both direct consumption studies as well as those evaluating interventions that influence consumption (e.g. school policy, educational) will be relevant. Non-specific or multi-faceted behavioural, educational, or policy interventions may also be included subject to the level of evidence that exists for the other interventions/exposures. Comparisons of interest and endpoints of interest are pre-specified. We will include randomized controlled trials, controlled clinical trials, interrupted time series studies, controlled before-after studies, prospective and retrospective comparative cohort studies, case-control studies, and nested case-control designs. The MEDLINE®, Embase, The Cochrane Library, CINAHL, ERIC, and PsycINFO® databases and grey literature sources will be searched. The processes for selecting studies, abstracting data, and resolving conflicts are described. We will assess risk of bias using design-specific tools. To determine sets of confounding variables that should be adjusted for, we have developed causal directed acyclic graphs and will use those to inform our risk of bias assessments. Meta-analysis will

  3. Clinical outcomes of adverse cardiovascular events in patients with acute dapsone poisoning

    PubMed Central

    Kang, Kyung Sik; Kim, Hyung Il; Kim, Oh Hyun; Cha, Kyoung Chul; Kim, Hyun; Lee, Kang Hyun; Hwang, Sung Oh; Cha, Yong Sung

    2016-01-01

    Objective Adverse cardiovascular events (ACVEs) account for a large proportion of the morbidities and mortalities associated with drug overdose emergencies. However, there are no published reports regarding outcomes of ACVEs associated with acute dapsone poisoning. Here, the authors retrospectively analyzed ACVEs reported within 48 hours of treatment in patients with acute dapsone poisoning and assessed the significance of ACVEs as early predictors of mortality. Methods Sixty-one consecutive cases of acute dapsone poisoning that were diagnosed and treated at a regional emergency center between 2006 and 2014 were included in the study. An ACVE was defined as myocardial injury, shock, ventricular dysrhythmia, cardiac arrest, or any combination of these occurring within the first 48 hours of treatment for acute dapsone poisoning. Results Nineteen patients (31.1%) had evidence of myocardial injury (elevation of serum troponin-I level or electrocardiography signs of ischemia) after dapsone overdose, and there were a total of 19 ACVEs (31.1%), including one case of shock (1.6%). Fourteen patients (23.0%) died from pneumonia or multiple organ failure, and the incidence of ACVEs was significantly higher among non-survivors than among survivors (64.3% vs. 21.3%, P=0.006). ACVE was a significant predictor of mortality (odds ratio, 5.690; 95% confidence interval, 1.428 to 22.675; P=0.014). Conclusion The incidence of ACVE was significantly higher among patients who died after acute dapsone poisoning. ACVE is a significant predictor of mortality after dapsone overdose, and evidence of ACVE should be carefully sought in these patients. PMID:27752614

  4. Porphyromonas gingivalis within Placental Villous Mesenchyme and Umbilical Cord Stroma Is Associated with Adverse Pregnancy Outcome

    PubMed Central

    Vanterpool, Sizzle F.; Been, Jasper V.; Houben, Michiel L.; Nikkels, Peter G. J.; De Krijger, Ronald R.; Zimmermann, Luc J. I.; Kramer, Boris W.; Progulske-Fox, Ann; Reyes, Leticia

    2016-01-01

    Intrauterine presence of Porphyromonas gingivalis (Pg), a common oral pathobiont, is implicated in preterm birth. Our aim was to determine if the location of Pg within placental and/or umbilical cord sections was associated with a specific delivery diagnosis at preterm delivery (histologic chorioamnionitis, chorioamnionitis with funisitis, preeclampsia, and preeclampsia with HELLP-syndrome, small for gestational age). The prevalence and location of Pg within archived placental and umbilical cord specimens from preterm (25 to 32 weeks gestation) and term control cohorts were evaluated by immunofluorescent histology. Detection of Pg was performed blinded to pregnancy characteristics. Multivariate analyses were performed to evaluate independent effects of gestational age, being small for gestational age, specific preterm delivery diagnosis, antenatal steroids, and delivery mode, on the odds of having Pg in the preterm tissue. Within the preterm cohort, 49 of 97 (51%) placentas and 40 of 97 (41%) umbilical cord specimens were positive for Pg. Pg within the placenta was significantly associated with shorter gestation lengths (OR 0.63 (95%CI: 0.48–0.85; p = 0.002) per week) and delivery via caesarean section (OR 4.02 (95%CI: 1.15–14.04; p = 0.03), but not with histological chorioamnionitis or preeclampsia. However, the presence of Pg in the umbilical cord was significantly associated with preeclampsia: OR 6.73 (95%CI: 1.31–36.67; p = 0.02). In the term cohort, 2 of 35 (6%) placentas and no umbilical cord term specimens were positive for Pg. The location of Pg within the placenta was different between preterm and term groups in that Pg within the villous mesenchyme was only detected in the preterm cohort, whereas Pg associated with syncytiotrophoblasts was found in both preterm and term placentas. Taken together, our results suggest that the presence of Pg within the villous stroma or umbilical cord may be an important determinant in Pg-associated adverse pregnancy

  5. Risk Factors for Adverse Outcomes in Patients Hospitalized With Lower Gastrointestinal Bleeding

    PubMed Central

    Sengupta, Neil; Tapper, Elliot B.; Patwardhan, Vilas R.; Ketwaroo, Gyanprakash A.; Thaker, Adarsh M.; Leffler, Daniel A.; Feuerstein, Joseph D.

    2016-01-01

    Objective To determine which risk factors and subtypes of lower gastrointestinal bleeding (LGIB) are associated with adverse outcomes after hospital discharge (30-day readmissions, recurrent LGIB, and death). Patients and Methods We conducted a prospective observational study of consecutive patients admitted with LGIB to Beth Israel Deaconess Medical Center from April 1, 2013, through March 30, 2014. Patients were contacted 30 days after discharge to determine hospital readmissions, recurrent LGIB, and death. Multivariable Cox proportional hazards regression models were used to describe associations of variables with 30-day readmissions or recurrent LGIB. Logistic regression was used to determine association with mortality. Results There were 277 patients hospitalized with LGIB. Of the 271 patients surviving to discharge, 21% (n=57) were readmitted within 30 days, 21 of whom were admitted for recurrent LGIB. The following factors were associated with 30-day readmissions: developing in-hospital LGIB (hazard ratio [HR], 2.26; 95% CI, 1.08–4.28), anticoagulation (HR, 1.82; 95% CI, 1.05–3.10), and active malignancy (HR, 2.33; 95% CI, 1.11–4.42). Patients discharged while taking anticoagulants had higher rates of recurrent bleeding (HR, 2.93; 95% CI, 1.15–6.95). Patients with higher Charlson Comorbidity Index scores (odds ratio [OR], 1.57; 95% CI, 1.25–2.08), active malignancy (OR, 6.57; 95% CI, 1.28–28.7), and in-hospital LGIB (OR, 11.5; 95% CI, 2.56–52.0) had increased 30-day mortality risk. Conclusion In-hospital LGIB, anticoagulation, and active malignancy are risk factors for 30-day readmissions in patients hospitalized with LGIB. In-hospital LGIB, Charlson Comorbidity Index scores, and active malignancy are risk factors for 30-day mortality. PMID:26141075

  6. Postoperative Adverse Outcomes in Intellectually Disabled Surgical Patients: A Nationwide Population-Based Study

    PubMed Central

    Lin, Jui-An; Liao, Chien-Chang; Chang, Chuen-Chau; Chang, Hang; Chen, Ta-Liang

    2011-01-01

    Background Intellectually disabled patients have various comorbidities, but their risks of adverse surgical outcomes have not been examined. This study assesses pre-existing comorbidities, adjusted risks of postoperative major morbidities and mortality in intellectually disabled surgical patients. Methods A nationwide population-based study was conducted in patients who underwent inpatient major surgery in Taiwan between 2004 and 2007. Four controls for each patient were randomly selected from the National Health Insurance Research Database. Preoperative major comorbidities, postoperative major complications and 30-day in-hospital mortality were compared between patients with and without intellectual disability. Use of medical services also was analyzed. Adjusted odds ratios using multivariate logistic regression analyses with 95% confidence intervals were applied to verify intellectual disability's impact. Results Controls were compared with 3983 surgical patients with intellectual disability. Risks for postoperative major complications were increased in patients with intellectual disability, including acute renal failure (odds ratio 3.81, 95% confidence interval 2.28 to 6.37), pneumonia (odds ratio 2.01, 1.61 to 2.49), postoperative bleeding (odds ratio 1.35, 1.09 to 1.68) and septicemia (odds ratio 2.43, 1.85 to 3.21) without significant differences in overall mortality. Disability severity was positively correlated with postoperative septicemia risk. Medical service use was also significantly higher in surgical patients with intellectual disability. Conclusion Intellectual disability significantly increases the risk of overall major complications after major surgery. Our findings show a need for integrated and revised protocols for postoperative management to improve care for intellectually disabled surgical patients. PMID:22046425

  7. Cannabis and Neuropsychiatry, 2: The Longitudinal Risk of Psychosis as an Adverse Outcome.

    PubMed

    Andrade, Chittaranjan

    2016-06-01

    Psychosis is one of the most serious among the adverse effects associated with cannabis use. The association between cannabis use and psychosis has been variously explored in a series of recent meta-analyses. The results of these meta-analyses show that persons who develop psychosis experience onset of psychosis about 2-3 years earlier if they are cannabis users; this effect is not observed with alcohol or other substance use. Higher levels of cannabis use are associated with greater risk of psychosis. Current cannabis abuse or dependence (but not past use or lower levels of current use) increases the risk of transition into psychosis in persons at ultrahigh risk of psychosis. About a third of patients with first-episode psychosis are cannabis users, and, at follow-up, about half of these users are found to continue their cannabis use. Continued cannabis use (in those who are treated after developing psychosis) is associated with higher risk of relapse into psychosis, and discontinuation of cannabis use reduces the risk of relapse to that in cannabis nonusers. Finally, persons with psychosis who continue to use cannabis have more severe positive symptoms and poorer levels of functioning. Because experimental studies in humans show that cannabinoids and cannabis can induce psychotic symptoms, it is reasonable to assume that the epidemiologic data indicate a causal effect of cannabis in anticipating, triggering, or exacerbating psychosis in vulnerable individuals and in worsening the course and outcome of the illness in those who continue to use the substance. Given the public health implications of these findings, the trend to legalize medical marijuana must be viewed with concern, and efforts are necessary to educate patients and the public about the serious mental and physical health risks associated with cannabis use and abuse.

  8. Taxonomic applicability of inflammatory cytokines in adverse outcome pathway (AOP) development.

    PubMed

    Angrish, Michelle M; Pleil, Joachim D; Stiegel, Matthew A; Madden, Michael C; Moser, Virginia C; Herr, David W

    2016-01-01

    Cytokines, low-molecular-weight messenger proteins that act as intercellular immunomodulatory signals, have become a mainstream preclinical marker for assessing the systemic inflammatory response to external stressors. The challenge is to quantitate from healthy subjects cytokine levels that are below or at baseline and relate those dynamic and complex cytokine signatures of exposures with the inflammatory and repair pathways. Thus, highly sensitive, specific, and precise analytical and statistical methods are critically important. Investigators at the U.S. Environmental Protection Agency (EPA) have implemented advanced technologies and developed statistics for evaluating panels of inflammatory cytokines in human blood, exhaled breath condensate, urine samples, and murine biological media. Advanced multiplex, bead-based, and automated analytical platforms provided sufficient sensitivity, precision, and accuracy over the traditional enzyme-linked immunosorbent assay (ELISA). Thus, baseline cytokine levels can be quantified from healthy human subjects and animals and compared to an in vivo exposure response from an environmental chemical. Specifically, patterns of cytokine responses in humans exposed to environmental levels of ozone and diesel exhaust, and in rodents exposed to selected pesticides (such as fipronil and carbaryl), were used as case studies to generally assess the taxonomic applicability of cytokine responses. The findings in this study may aid in the application of measureable cytokine markers in future adverse outcome pathway (AOP)-based toxicity testing. Data from human and animal studies were coalesced and the possibility of using cytokines as key events (KE) to bridge species responses to external stressors in an AOP-based framework was explored. PMID:26914248

  9. Maternal Factors and Adverse Perinatal Outcomes in Women with Preeclampsia in Maceió, Alagoas

    PubMed Central

    de Oliveira, Alane Cabral Menezes; Santos, Arianne Albuquerque; Bezerra, Alexandra Rodrigues; de Barros, Amanda Maria Rocha; Tavares, Myrian Cicyanne Machado

    2016-01-01

    Background Preeclampsia has been associated with several risk factors and events. However, it still deserves further investigation, considering the multitude of related factors that affect different populations. Objective To evaluate the maternal factors and adverse perinatal outcomes in a cohort of pregnant women with preeclampsia receiving care in the public health network of the city of Maceió. Methods Prospective cohort study carried out in 2014 in the public health network of the city with a sample of pregnant women calculated based on a prevalence of preeclampsia of 17%, confidence level of 90%, power of 80%, and ratio of 1:1. We applied a questionnaire to collect socioeconomic, personal, and anthropometric data, and retrieved perinatal variables from medical records and certificates of live birth. The analysis was performed with Poisson regression and chi-square test considering p values < 0.05 as significant. Results We evaluated 90 pregnant women with preeclampsia (PWP) and 90 pregnant women without preeclampsia (PWoP). A previous history of preeclampsia (prevalence ratio [PR] = 1.57, 95% confidence interval [95% CI] 1.47 - 1.67, p = 0.000) and black skin color (PR = 1.15, 95% CI 1.00 - 1.33, p = 0.040) were associated with the occurrence of preeclampsia. Among the newborns of PWP and PWoP, respectively, 12.5% and 13.1% (p = 0.907) were small for gestational age and 25.0% and 23.2% (p = 0.994) were large for gestational age. There was a predominance of cesarean delivery. Conclusion Personal history of preeclampsia and black skin color were associated with the occurrence of preeclampsia. There was a high frequency of birth weight deviations and cesarean deliveries. PMID:26761076

  10. Limitations of toxicity characterization in life cycle assessment: Can adverse outcome pathways provide a new foundation?

    PubMed

    Gust, Kurt A; Collier, Zachary A; Mayo, Michael L; Stanley, Jacob K; Gong, Ping; Chappell, Mark A

    2016-07-01

    Life cycle assessment (LCA) has considerable merit for holistic evaluation of product planning, development, production, and disposal, with the inherent benefit of providing a forecast of potential health and environmental impacts. However, a technical review of current life cycle impact assessment (LCIA) methods revealed limitations within the biological effects assessment protocols, including: simplistic assessment approaches and models; an inability to integrate emerging types of toxicity data; a reliance on linear impact assessment models; a lack of methods to mitigate uncertainty; and no explicit consideration of effects in species of concern. The purpose of the current study is to demonstrate that a new concept in toxicological and regulatory assessment, the adverse outcome pathway (AOP), has many useful attributes of potential use to ameliorate many of these problems, to expand data utility and model robustness, and to enable more accurate and defensible biological effects assessments within LCIA. Background, context, and examples have been provided to demonstrate these potential benefits. We additionally propose that these benefits can be most effectively realized through development of quantitative AOPs (qAOPs) crafted to meet the needs of the LCIA framework. As a means to stimulate qAOP research and development in support of LCIA, we propose 3 conceptual classes of qAOP, each with unique inherent attributes for supporting LCIA: 1) mechanistic, including computational toxicology models; 2) probabilistic, including Bayesian networks and supervised machine learning models; and 3) weight of evidence, including models built using decision-analytic methods. Overall, we have highlighted a number of potential applications of qAOPs that can refine and add value to LCIA. As the AOP concept and support framework matures, we see the potential for qAOPs to serve a foundational role for next-generation effects characterization within LCIA. Integr Environ Assess Manag

  11. Birth malformations and other adverse perinatal outcomes in four U.S. Wheat-producing states.

    PubMed

    Schreinemachers, Dina M

    2003-07-01

    Chlorophenoxy herbicides are widely used in the United States and Western Europe for broadleaf weed control in grain farming and park maintenance. Most of the spring and durum wheat produced in the United States is grown in Minnesota, Montana, North Dakota, and South Dakota, with more than 85% of the acreage treated with chlorophenoxy herbicides such as 2,4-dichlorophenoxyacetic acid (2,4-D) and 4-chloro-2-methylphenoxyacetic acid (MCPA). Rates of adverse birth outcomes in rural, agricultural counties of these states during 1995-1997 were studied by comparing counties with a high proportion of wheat acreage and those with a lower proportion. Information routinely collected and made available by federal agencies was used for this ecologic study. Significant increases in birth malformations were observed for the circulatory/respiratory category for combined sexes [odds ratio (OR) = 1.65; 95% confidence interval (CI), 1.07-2.55]. A stronger effect was observed for the subcategory, which excluded heart malformations (OR = 2.03; 95% CI, 1.14-3.59). In addition, infants conceived during April-June--the time of herbicide application--had an increased chance of being diagnosed with circulatory/respiratory (excluding heart) malformations compared with births conceived during other months of the year (OR = 1.75; 95% CI, 1.09-2.80). Musculoskeletal/integumental anomalies increased for combined sexes in the high-wheat counties (OR = 1.50; 95% CI, 1.06-2.12). Infant death from congenital anomalies significantly increased in high-wheat counties for males (OR = 2.66; 95% CI, 1.52-4.65) but not for females (OR = 0.48; 95% CI, 0.20-1.15). These results are especially of concern because of widespread use of chlorophenoxy herbicides. PMID:12842783

  12. Cannabis and Neuropsychiatry, 2: The Longitudinal Risk of Psychosis as an Adverse Outcome.

    PubMed

    Andrade, Chittaranjan

    2016-06-01

    Psychosis is one of the most serious among the adverse effects associated with cannabis use. The association between cannabis use and psychosis has been variously explored in a series of recent meta-analyses. The results of these meta-analyses show that persons who develop psychosis experience onset of psychosis about 2-3 years earlier if they are cannabis users; this effect is not observed with alcohol or other substance use. Higher levels of cannabis use are associated with greater risk of psychosis. Current cannabis abuse or dependence (but not past use or lower levels of current use) increases the risk of transition into psychosis in persons at ultrahigh risk of psychosis. About a third of patients with first-episode psychosis are cannabis users, and, at follow-up, about half of these users are found to continue their cannabis use. Continued cannabis use (in those who are treated after developing psychosis) is associated with higher risk of relapse into psychosis, and discontinuation of cannabis use reduces the risk of relapse to that in cannabis nonusers. Finally, persons with psychosis who continue to use cannabis have more severe positive symptoms and poorer levels of functioning. Because experimental studies in humans show that cannabinoids and cannabis can induce psychotic symptoms, it is reasonable to assume that the epidemiologic data indicate a causal effect of cannabis in anticipating, triggering, or exacerbating psychosis in vulnerable individuals and in worsening the course and outcome of the illness in those who continue to use the substance. Given the public health implications of these findings, the trend to legalize medical marijuana must be viewed with concern, and efforts are necessary to educate patients and the public about the serious mental and physical health risks associated with cannabis use and abuse. PMID:27337422

  13. Vital Sign Prediction of Adverse Maternal Outcomes in Women with Hypovolemic Shock: The Role of Shock Index

    PubMed Central

    El Ayadi, Alison M.; Nathan, Hannah L.; Seed, Paul T.; Butrick, Elizabeth A.; Hezelgrave, Natasha L.; Shennan, Andrew H.; Miller, Suellen

    2016-01-01

    Objective To determine the optimal vital sign predictor of adverse maternal outcomes in women with hypovolemic shock secondary to obstetric hemorrhage and to develop thresholds for referral/intensive monitoring and need for urgent intervention to inform a vital sign alert device for low-resource settings. Study Design We conducted secondary analyses of a dataset of pregnant/postpartum women with hypovolemic shock in low-resource settings (n = 958). Using receiver-operating curve analysis, we evaluated the predictive ability of pulse, systolic blood pressure, diastolic blood pressure, shock index, mean arterial pressure, and pulse pressure for three adverse maternal outcomes: (1) death, (2) severe maternal outcome (death or severe end organ dysfunction morbidity); and (3) a combined severe maternal and critical interventions outcome comprising death, severe end organ dysfunction morbidity, intensive care admission, blood transfusion ≥ 5 units, or emergency hysterectomy. Two threshold parameters with optimal rule-in and rule-out characteristics were selected based on sensitivities, specificities, and positive and negative predictive values. Results Shock index was consistently among the top two predictors across adverse maternal outcomes. Its discriminatory ability was significantly better than pulse and pulse pressure for maternal death (p<0.05 and p<0.01, respectively), diastolic blood pressure and pulse pressure for severe maternal outcome (p<0.01), and systolic and diastolic blood pressure, mean arterial pressure and pulse pressure for severe maternal outcome and critical interventions (p<0.01). A shock index threshold of ≥ 0.9 maintained high sensitivity (100.0) with clinical practicality, ≥ 1.4 balanced specificity (range 70.0–74.8) with negative predictive value (range 93.2–99.2), and ≥ 1.7 further improved specificity (range 80.7–90.8) without compromising negative predictive value (range 88.8–98.5). Conclusions For women with hypovolemic

  14. Vitamin D deficiency during pregnancy may impair maternal and fetal outcomes.

    PubMed

    Lapillonne, Alexandre

    2010-01-01

    Over the past decade, new evidence has shown that vitamin D deficiency may contribute to the risk of developing a wide range of common chronic diseases that are different from the classic action on calcium and bone homeostasis. Acting through the vitamin D receptor, vitamin D can produce a wide array of favorable biological effects via genomic, non-genomic or intracrine mechanisms and, therefore, contributes to the improvement of human health in humans. We hypothesize that some of these effects may be even more critical during pregnancy. The focus of this paper is to review the data on the classic and non-classic actions of vitamin D with regards to pregnancy. It appears that vitamin D insufficiency during pregnancy is potentially associated with increased risk of preeclampsia, insulin resistance and gestational diabetes mellitus. Furthermore, experimental data also anticipate that vitamin D sufficiency is critical for fetal development, and especially for fetal brain development and immunological functions. Vitamin D deficiency during pregnancy may, therefore, not only impair maternal skeletal preservation and fetal skeletal formation but also be vital to the fetal "imprinting" that may affect chronic disease susceptibility soon after birth as well as later in life. PMID:19692182

  15. Fetal Heart Rate and Variability: Stability and Prediction to Developmental Outcomes in Early Childhood

    ERIC Educational Resources Information Center

    DiPietro, Janet A.; Bornstein, Marc H.; Hahn, Chun-Shin; Costigan, Kathleen; Achy-Brou, Aristide

    2007-01-01

    Stability in cardiac indicators before birth and their utility in predicting variation in postnatal development were examined. Fetal heart rate and variability were measured longitudinally from 20 through 38 weeks gestation (n = 137) and again at age 2 (n = 79). Significant within-individual stability during the prenatal period and into childhood…

  16. Adverse School Context Moderates the Outcomes of Selective Interventions for Aggressive Children

    ERIC Educational Resources Information Center

    Hughes, Jan N.; Cavell, Timothy A.; Meehan, Barbara T.; Zhang, Duan; Collie, Claire

    2005-01-01

    Drawing on social ecological theory and empirical studies on the role of school context in aggression, the authors argue that school adversity is an important consideration in choosing selective interventions for aggressive children. The moderating role of school adversity on intervention effectiveness is illustrated with data from a randomized…

  17. Attention-deficit/hyperactivity disorder and adverse health outcomes in adults.

    PubMed

    Spencer, Thomas J; Faraone, Stephen V; Tarko, Laura; McDermott, Katie; Biederman, Joseph

    2014-10-01

    Whereas the adverse impact of attention-deficit/hyperactivity disorder (ADHD) on emotional and psychosocial well-being has been well investigated, its impact on physical health has not. The main aim of this study was to assess the impact of ADHD on lifestyle behaviors and measures of adverse health risk indicators. Subjects were 100 untreated adults with ADHD and 100 adults without ADHD of similar age and sex. Unhealthy lifestyle indicators included assessments of bad health habits, frequency of visits to healthcare providers, and follow through with recommended prophylactic tests. Assessments of adverse health risk indicators included measurements of cardiovascular and metabolic parameters, weight, body mass index, and waist circumference. No differences were identified in health habits between subjects with and without ADHD, but robust differences were found in a wide range of adverse health risk indicators. ADHD is associated with an adverse impact in health risk indicators well known to be associated with high morbidity and mortality. PMID:25211634

  18. Long-term neurodevelopmental and cardiovascular outcome after intrauterine transfusions for fetal anaemia: a review.

    PubMed

    Lindenburg, Irene T M; van Klink, Jeanine M; Smits-Wintjens, Vivianne E H J; van Kamp, Inge L; Oepkes, Dick; Lopriore, Enrico

    2013-09-01

    Perinatal survival rates after intrauterine transfusions (IUT) for red cell alloimmunisation now exceed 90%, which demonstrates the safety and efficacy of one of the most successful procedures in fetal therapy. However, improved perinatal survival could lead to an increased number of children with long-term disabilities. The importance of long-term follow-up studies in fetal therapy lies in both the necessity of evaluation of antenatal management as well as in evidence-based preconceptional and prenatal counselling. This review describes the possible long-term cardiovascular and neurodevelopmental sequelae after IUT treatment for different indications including red cell alloimmunisation, parvovirus B19 infection, fetomaternal haemorrhage and twin anaemia-polycythaemia sequence.

  19. Systems Toxicology of Male Reproductive Development: Profiling 774 Chemicals for Molecular Targets and Adverse Outcomes

    EPA Science Inventory

    Adverse trends in male reproductive health have been reported for increased rates of testicular germ cell tumor, low semen quality, cryptorchidism, and hypospadias. An association with prenatal environmental exposure has been inferred from human and animal studies underlying male...

  20. TOXICOLOGY OF MALE REPRODUCTIVE DEVELOPMENT: PROFILING 774 CHEMICALS FOR MOLECULAR TARGETS AND ADVERSE OUTCOMES (SOT)

    EPA Science Inventory

    Adverse trends in male reproductive health have been reported for increased rates of testicular germ cell tumor, low semen quality, cryptorchidism, and hypospadias. An association with prenatal environmental exposure has been inferred from human and animal studies underlying male...

  1. Can aircraft noise less than or equal 115 to dBA adversely affect reproductive outcome in USAF women?

    NASA Astrophysics Data System (ADS)

    Brubaker, P. A.

    1985-06-01

    It has been suggested, mainly through animal studies, that exposure to high noise levels may be associated with lower birth weight, reduced gestational length and other adverse reproductive outcomes. Few studies have been done on humans to show this association. The Air Force employs pregnant women in areas where there is a high potential for exposure to high noise levels. This study proposes a method to determine if there is an association between high frequency noise levels or = 115 dBA and adverse reproductive outcomes through a review of records and self-administered questionnaires in a case-comparison design. Prevelance rates will be calculated and a multiple logistic regression analysis computed for the independent variables that can affect reproduction.

  2. Placental origins of adverse pregnancy outcomes: potential molecular targets: an Executive Workshop Summary of the Eunice Kennedy Shriver National Institute of Child Health and Human Development.

    PubMed

    Ilekis, John V; Tsilou, Ekaterini; Fisher, Susan; Abrahams, Vikki M; Soares, Michael J; Cross, James C; Zamudio, Stacy; Illsley, Nicholas P; Myatt, Leslie; Colvis, Christine; Costantine, Maged M; Haas, David M; Sadovsky, Yoel; Weiner, Carl; Rytting, Erik; Bidwell, Gene

    2016-07-01

    Although much progress is being made in understanding the molecular pathways in the placenta that are involved in the pathophysiology of pregnancy-related disorders, a significant gap exists in the utilization of this information for the development of new drug therapies to improve pregnancy outcome. On March 5-6, 2015, the Eunice Kennedy Shriver National Institute of Child Health and Human Development of the National Institutes of Health sponsored a 2-day workshop titled Placental Origins of Adverse Pregnancy Outcomes: Potential Molecular Targets to begin to address this gap. Particular emphasis was given to the identification of important molecular pathways that could serve as drug targets and the advantages and disadvantages of targeting these particular pathways. This article is a summary of the proceedings of that workshop. A broad number of topics were covered that ranged from basic placental biology to clinical trials. This included research in the basic biology of placentation, such as trophoblast migration and spiral artery remodeling, and trophoblast sensing and response to infectious and noninfectious agents. Research findings in these areas will be critical for the formulation of the development of future treatments and the development of therapies for the prevention of a number of pregnancy disorders of placental origin that include preeclampsia, fetal growth restriction, and uterine inflammation. Research was also presented that summarized ongoing clinical efforts in the United States and in Europe that has tested novel interventions for preeclampsia and fetal growth restriction, including agents such as oral arginine supplementation, sildenafil, pravastatin, gene therapy with virally delivered vascular endothelial growth factor, and oxygen supplementation therapy. Strategies were also proposed to improve fetal growth by the enhancement of nutrient transport to the fetus by modulation of their placental transporters and the targeting of placental

  3. Placental origins of adverse pregnancy outcomes: potential molecular targets: an Executive Workshop Summary of the Eunice Kennedy Shriver National Institute of Child Health and Human Development.

    PubMed

    Ilekis, John V; Tsilou, Ekaterini; Fisher, Susan; Abrahams, Vikki M; Soares, Michael J; Cross, James C; Zamudio, Stacy; Illsley, Nicholas P; Myatt, Leslie; Colvis, Christine; Costantine, Maged M; Haas, David M; Sadovsky, Yoel; Weiner, Carl; Rytting, Erik; Bidwell, Gene

    2016-07-01

    Although much progress is being made in understanding the molecular pathways in the placenta that are involved in the pathophysiology of pregnancy-related disorders, a significant gap exists in the utilization of this information for the development of new drug therapies to improve pregnancy outcome. On March 5-6, 2015, the Eunice Kennedy Shriver National Institute of Child Health and Human Development of the National Institutes of Health sponsored a 2-day workshop titled Placental Origins of Adverse Pregnancy Outcomes: Potential Molecular Targets to begin to address this gap. Particular emphasis was given to the identification of important molecular pathways that could serve as drug targets and the advantages and disadvantages of targeting these particular pathways. This article is a summary of the proceedings of that workshop. A broad number of topics were covered that ranged from basic placental biology to clinical trials. This included research in the basic biology of placentation, such as trophoblast migration and spiral artery remodeling, and trophoblast sensing and response to infectious and noninfectious agents. Research findings in these areas will be critical for the formulation of the development of future treatments and the development of therapies for the prevention of a number of pregnancy disorders of placental origin that include preeclampsia, fetal growth restriction, and uterine inflammation. Research was also presented that summarized ongoing clinical efforts in the United States and in Europe that has tested novel interventions for preeclampsia and fetal growth restriction, including agents such as oral arginine supplementation, sildenafil, pravastatin, gene therapy with virally delivered vascular endothelial growth factor, and oxygen supplementation therapy. Strategies were also proposed to improve fetal growth by the enhancement of nutrient transport to the fetus by modulation of their placental transporters and the targeting of placental

  4. Conceptual model for assessing criteria air pollutants in a multipollutant context: A modified adverse outcome pathway approach.

    PubMed

    Buckley, Barbara; Farraj, Aimen

    2015-09-01

    Air pollution consists of a complex mixture of particulate and gaseous components. Individual criteria and other hazardous air pollutants have been linked to adverse respiratory and cardiovascular health outcomes. However, assessing risk of air pollutant mixtures is difficult since components are present in different combinations and concentrations in ambient air. Recent mechanistic studies have limited utility because of the inability to link measured changes to adverse outcomes that are relevant to risk assessment. New approaches are needed to address this challenge. The purpose of this manuscript is to describe a conceptual model, based on the adverse outcome pathway approach, which connects initiating events at the cellular and molecular level to population-wide impacts. This may facilitate hazard assessment of air pollution mixtures. In the case reports presented here, airway hyperresponsiveness and endothelial dysfunction are measurable endpoints that serve to integrate the effects of individual criteria air pollutants found in inhaled mixtures. This approach incorporates information from experimental and observational studies into a sequential series of higher order effects. The proposed model has the potential to facilitate multipollutant risk assessment by providing a framework that can be used to converge the effects of air pollutants in light of common underlying mechanisms. This approach may provide a ready-to-use tool to facilitate evaluation of health effects resulting from exposure to air pollution mixtures.

  5. Salmonella enterica serovar Enteritidis enterocolitis during late stages of gestation induces an adverse pregnancy outcome in the murine model.

    PubMed

    Noto Llana, Mariángeles; Sarnacki, Sebastián Hernán; Aya Castañeda, María del Rosario; Pustovrh, María Carolina; Gartner, Alejandra Sonia; Buzzola, Fernanda Roxana; Cerquetti, María Cristina; Giacomodonato, Mónica Nancy

    2014-01-01

    Foodborne diseases caused by Salmonella enterica serovar Enteritidis (S. Enteritidis) are a significant health problem. Pregnancy, state of immunological tolerance, is a predisposing condition for the development of infections with intracellular pathogens. Salmonella species can cause pregnancy complications such as chorioamnionitis, transplacental fetal infection, pre term labor, abortions, neonatal and maternal septicemia. However, the specific mechanisms by which Salmonella infections trigger these alterations are not clear. In the present work, using a self-limiting enterocolitis murine model, we show that the ingestion of a low dose of S. Enteritidis at late stages of pregnancy (day 15 of gestation) is sufficient to induce massive maternal infection. We found that Salmonella infection leads to 40% of pre term delivery, 33% of abortion and fetal growth restriction. Placental dysfunction during S. Enteritidis enterocolitis was confirmed through cellular infiltration and hypoxia markers (MPO activity and COX-1 and COX-2 expression, respectively). Apoptosis in placental tissue due to Salmonella infection was also evident at day 18 of gestation when investigated by morphometric procedure, DNA fragmentation and Fas/FasL expression. Also, the expression of IFN-γ, TNF-α, IL-17 and IL-10 was up regulated in response to Salmonella not only in placenta, but also in amniotic fluid and maternal serum. Altogether, our results demonstrate that S. Enteritidis enterocolitis during late stages of gestation causes detrimental effect on pregnancy outcome.

  6. Systematic review of methods used in meta-analyses where a primary outcome is an adverse or unintended event

    PubMed Central

    2012-01-01

    Background Adverse consequences of medical interventions are a source of concern, but clinical trials may lack power to detect elevated rates of such events, while observational studies have inherent limitations. Meta-analysis allows the combination of individual studies, which can increase power and provide stronger evidence relating to adverse events. However, meta-analysis of adverse events has associated methodological challenges. The aim of this study was to systematically identify and review the methodology used in meta-analyses where a primary outcome is an adverse or unintended event, following a therapeutic intervention. Methods Using a collection of reviews identified previously, 166 references including a meta-analysis were selected for review. At least one of the primary outcomes in each review was an adverse or unintended event. The nature of the intervention, source of funding, number of individual meta-analyses performed, number of primary studies included in the review, and use of meta-analytic methods were all recorded. Specific areas of interest relating to the methods used included the choice of outcome metric, methods of dealing with sparse events, heterogeneity, publication bias and use of individual patient data. Results The 166 included reviews were published between 1994 and 2006. Interventions included drugs and surgery among other interventions. Many of the references being reviewed included multiple meta-analyses with 44.6% (74/166) including more than ten. Randomised trials only were included in 42.2% of meta-analyses (70/166), observational studies only in 33.7% (56/166) and a mix of observational studies and trials in 15.7% (26/166). Sparse data, in the form of zero events in one or both arms where the outcome was a count of events, was found in 64 reviews of two-arm studies, of which 41 (64.1%) had zero events in both arms. Conclusions Meta-analyses of adverse events data are common and useful in terms of increasing the power to

  7. Burden of severe maternal morbidity and association with adverse birth outcomes in sub–Saharan Africa and south Asia: protocol for a prospective cohort study

    PubMed Central

    2016-01-01

    Objectives The AMANHI morbidity study aims to quantify and describe severe maternal morbidities and assess their associations with adverse maternal, fetal and newborn outcomes in predominantly rural areas of nine sites in eight South Asian and sub–Saharan African countries. Methods AMANHI takes advantage of on–going population–based cohort studies covering approximately 2 million women of reproductive age with 1– to 3–monthly pregnancy surveillance to enrol pregnant women. Morbidity information is collected at five follow–up home visits – three during the antenatal period at 24–28 weeks, 32–36 weeks and 37+ weeks of pregnancy and two during the postpartum period at 1–6 days and after 42–60 days after birth. Structured–questionnaires are used to collect self–reported maternal morbidities including hemorrhage, hypertensive disorders, infections, difficulty in labor and obstetric fistula, as well as care–seeking for these morbidities and outcomes for mothers and babies. Additionally, structured questionnaires are used to interview birth attendants who attended women’s deliveries. All protocols were harmonised across the sites including training, implementation and operationalising definitions for maternal morbidities. Importance of the AMANHI morbidity study Availability of reliable data to synthesize evidence for policy direction, interventions and programmes, remains a crucial step for prioritization and ensuring equitable delivery of maternal health interventions especially in high burden areas. AMANHI is one of the first large harmonized population–based cohort studies being conducted in several rural centres in South Asia and sub–Saharan Africa, and is expected to make substantial contributions to global knowledge on maternal morbidity burden and its implications. PMID:27648256

  8. Burden of severe maternal morbidity and association with adverse birth outcomes in sub–Saharan Africa and south Asia: protocol for a prospective cohort study

    PubMed Central

    2016-01-01

    Objectives The AMANHI morbidity study aims to quantify and describe severe maternal morbidities and assess their associations with adverse maternal, fetal and newborn outcomes in predominantly rural areas of nine sites in eight South Asian and sub–Saharan African countries. Methods AMANHI takes advantage of on–going population–based cohort studies covering approximately 2 million women of reproductive age with 1– to 3–monthly pregnancy surveillance to enrol pregnant women. Morbidity information is collected at five follow–up home visits – three during the antenatal period at 24–28 weeks, 32–36 weeks and 37+ weeks of pregnancy and two during the postpartum period at 1–6 days and after 42–60 days after birth. Structured–questionnaires are used to collect self–reported maternal morbidities including hemorrhage, hypertensive disorders, infections, difficulty in labor and obstetric fistula, as well as care–seeking for these morbidities and outcomes for mothers and babies. Additionally, structured questionnaires are used to interview birth attendants who attended women’s deliveries. All protocols were harmonised across the sites including training, implementation and operationalising definitions for maternal morbidities. Importance of the AMANHI morbidity study Availability of reliable data to synthesize evidence for policy direction, interventions and programmes, remains a crucial step for prioritization and ensuring equitable delivery of maternal health interventions especially in high burden areas. AMANHI is one of the first large harmonized population–based cohort studies being conducted in several rural centres in South Asia and sub–Saharan Africa, and is expected to make substantial contributions to global knowledge on maternal morbidity burden and its implications.

  9. Outcome of isolated fetal choroid plexus cyst detected in prenatal sonography among infertile patients referred to Royan Institute: A 3-year study

    PubMed Central

    Irani, Shohreh; Ahmadi, Firoozeh; Javam, Maryam; Vosough Taghi dizaj, Ahmad; Niknejad, Fatemeh

    2015-01-01

    Background: Several studies have assessed the correlation of fetal choroid plexus cyst (CPC) and the risk of congenital anomalies, but few ones have discussed isolated CPC (with no other abnormal sonographic finding). Objective: The aim of this study was to determine the outcome of isolated fetal choroid plexus cyst and to specify its clinical significance. Materials and Methods: This cross sectional study was carried out at Royan Institute in Tehran, Iran, between April 2009 and December 2012. All prenatal sonographies in this period of time were assessed using a computerized database and fetuses who had isolated CPC were recruited in the study. Sonography reports, mother serum screening test results, fetal echocardiography and amniocentesis were evaluated until birth. A follow-up phone call was made to all individuals to learn about the neonatal outcomes. Results: Overall, 6240 prenatal sonographies were performed in this setting during this period. Isolated CPC was detected in 64 fetuses. The results of double test (N=30), triple test (N=5) and fetal echocardiography (N =24) were normal. Quadruple test result showed 3 abnormal out of 29 cases that all had normal karyotypes. Four samples were dropped out due to premature rupture of membranes (N=3) and intrauterine fetal death (N=1). It was found that the outcomes of all remaining fetuses (N=60) were normal and no anomaly ones were seen until birth. Conclusion: Isolated CPC is a benign regressive condition with no clinical significance. PMID:26568762

  10. Household and community-level Adverse Childhood Experiences and adult health outcomes in a diverse urban population.

    PubMed

    Wade, Roy; Cronholm, Peter F; Fein, Joel A; Forke, Christine M; Davis, Martha B; Harkins-Schwarz, Mary; Pachter, Lee M; Bair-Merritt, Megan H

    2016-02-01

    Adverse Childhood Experiences (ACEs), which include family dysfunction and community-level stressors, negatively impact the health and well being of children throughout the life course. While several studies have examined the impact of these childhood exposures amongst racially and socially diverse populations, the contribution of ACEs in the persistence of socioeconomic disparities in health is poorly understood. To determine the association between ACEs and health outcomes amongst a sample of adults living in Philadelphia and examine the moderating effect of Socioeconomic Status (SES) on this association, we conducted a cross-sectional survey of 1,784 Philadelphia adults, ages 18 and older, using random digit dialing methodology to assess Conventional ACEs (experiences related to family dysfunction), Expanded ACEs (community-level stressors), and health outcomes. Using weighted, multivariable logistic regression analyses along with SES stratified models, we examined the relationship between ACEs and health outcomes as well as the modifying effect of current SES. High Conventional ACE scores were significantly associated with health risk behaviors, physical and mental illness, while elevated Expanded ACE scores were associated only with substance abuse history and sexually transmitted infections. ACEs did have some differential impacts on health outcomes based on SES. Given the robust impact of Conventional ACEs on health, our results support prior research highlighting the primacy of family relationships on a child's life course trajectory and the importance of interventions designed to support families. Our findings related to the modifying effect of SES may provide additional insight into the complex relationship between poverty and childhood adversity.

  11. Association between Intimate Partner Violence during Pregnancy and Adverse Pregnancy Outcomes in Vietnam: A Prospective Cohort Study

    PubMed Central

    Van, Toan Ngo; Gammeltoft, Tine; W. Meyrowitsch, Dan; Nguyen Thi Thuy, Hanh; Rasch, Vibeke

    2016-01-01

    Background Violence against pregnant women is an increasing public health concern particularly in low- and middle-income countries. The purpose of this study was to measure the association between intimate partner violence (IPV) during pregnancy and the risk of adverse birth outcomes. Methods Prospective cohort study of 1276 pregnant women in Dong Anh district, Vietnam. Women with gestational age less than 24 weeks were enrolled and interviewed. Repeated interviews were performed at 30–34 weeks gestation to assess experience of IPV during pregnancy and again 48 hours post-delivery to assess the birth outcome including birth weight and gestational age at delivery. Results There was a statistically significant association between exposure to physical violence during pregnancy and preterm birth (PTB) or low birth weight (LBW). After adjustment for age, education, occupation, body mass index (BMI), haemoglobin level, previous adverse pregnancy outcomes, the pregnant women who were exposed to physical violence during pregnancy were five times more likely to have PTB (AOR = 5.5; 95%CI: 2.1–14.1) and were nearly six times more likely to give birth to a child of LBW (AOR = 5.7; 95%CI: 2.2–14.9) as compared to those who were not exposed to physical violence. Conclusion Exposure to IPV during pregnancy increases the risk of PTB and LBW. Case-finding for violence in relation to antenatal care may help protect pregnant women and improve pregnancy outcomes. PMID:27631968

  12. Statin therapy and long-term adverse limb outcomes in patients with peripheral artery disease: insights from the REACH registry

    PubMed Central

    Kumbhani, Dharam J.; Steg, Ph. Gabriel; Cannon, Christopher P.; Eagle, Kim A.; Smith, Sidney C.; Goto, Shinya; Ohman, E. Magnus; Elbez, Yedid; Sritara, Piyamitr; Baumgartner, Iris; Banerjee, Subhash; Creager, Mark A.; Bhatt, Deepak L.

    2014-01-01

    Aims Due to a high burden of systemic cardiovascular events, current guidelines recommend the use of statins in all patients with peripheral artery disease (PAD). We sought to study the impact of statin use on limb prognosis in patients with symptomatic PAD enrolled in the international REACH registry. Methods Statin use was assessed at study enrolment, as well as a time-varying covariate. Rates of the primary adverse limb outcome (worsening claudication/new episode of critical limb ischaemia, new percutaneous/surgical revascularization, or amputation) at 4 years and the composite of cardiovascular death/myocardial infarction/stroke were compared among statin users vs. non-users. Results A total of 5861 patients with symptomatic PAD were included. Statin use at baseline was 62.2%. Patients who were on statins had a significantly lower risk of the primary adverse limb outcome at 4 years when compared with those who were not taking statins [22.0 vs. 26.2%; hazard ratio (HR), 0.82; 95% confidence interval (CI), 0.72–0.92; P = 0.0013]. Results were similar when statin use was considered as a time-dependent variable (P = 0.018) and on propensity analysis (P < 0.0001). The composite of cardiovascular death/myocardial infarction/stroke was similarly reduced (HR, 0.83; 95% CI, 0.73–0.96; P = 0.01). Conclusion Among patients with PAD in the REACH registry, statin use was associated with an ∼18% lower rate of adverse limb outcomes, including worsening symptoms, peripheral revascularization, and ischaemic amputations. These findings suggest that statin therapy not only reduces the risk of adverse cardiovascular events, but also favourably affects limb prognosis in patients with PAD. PMID:24585266

  13. Effects of Environmental Exposures on Fetal and Childhood Growth Trajectories.

    PubMed

    Zheng, Tongzhang; Zhang, Jie; Sommer, Kathryn; Bassig, Bryan A; Zhang, Xichi; Braun, Jospeh; Xu, Shuangqing; Boyle, Peter; Zhang, Bin; Shi, Kunchong; Buka, Stephen; Liu, Siming; Li, Yuanyuan; Qian, Zengmin; Dai, Min; Romano, Megan; Zou, Aifen; Kelsey, Karl

    2016-01-01

    Delayed fetal growth and adverse birth outcomes are some of the greatest public health threats to this generation of children worldwide because these conditions are major determinants of mortality, morbidity, and disability in infancy and childhood and are also associated with diseases in adult life. A number of studies have investigated the impacts of a range of environmental conditions during pregnancy (including air pollution, endocrine disruptors, persistent organic pollutants, heavy metals) on fetal and child development. The results, while provocative, have been largely inconsistent. This review summarizes up to date epidemiologic studies linking major environmental pollutants to fetal and child development and suggested future directions for further investigation. PMID:27325067

  14. A Swedish Population-based Study of Adverse Birth Outcomes among Pregnant Women Treated with Buprenorphine or Methadone: Preliminary Findings

    PubMed Central

    Wurst, Keele E.; Zedler, Barbara K.; Joyce, Andrew R.; Sasinowski, Maciek; Murrelle, E. Lenn

    2016-01-01

    BACKGROUND Untreated opioid dependence in pregnant women is associated with adverse birth outcomes. Buprenorphine and methadone are options for opioid agonist medication-assisted treatment during pregnancy. OBJECTIVE The aim of this study was to describe adverse birth outcomes observed with buprenorphine or methadone treatment compared to the general population in Sweden. METHODS Pregnant women and their corresponding births during 2005–2011 were identified in the Swedish Medical Birth Register. Data on stillbirth, neonatal/infant death, mode of delivery, gestational age at birth, Apgar score, growth outcomes, neonatal abstinence syndrome, and congenital malformations were examined. Frequencies were compared using two-sided Fisher’s exact tests. Unadjusted estimates of birth outcomes for women treated with buprenorphine or methadone were compared to the registered general population. RESULTS A total of 746,257 pregnancies among 538,178 unique women resulted in 746,485 live births. Among the 194 women treated with buprenorphine (N = 176) or methadone (N = 52), no stillbirths or neonatal/infant deaths occurred. Neonatal abstinence syndrome developed in 23.3% and 38.5% of infants born to mothers treated with buprenorphine and methadone, respectively. The frequency of the selected adverse birth outcomes assessed in women treated with buprenorphine as compared to the general population was not significantly different. However, a significantly higher frequency of preterm birth and congenital malformations was observed in women treated with methadone as compared to the general population. Compared with the general population, methadone-treated women were significantly older than buprenorphine-treated women, and both treatment groups began prenatal care later, were more likely to smoke cigarettes, and did not cohabitate with the baby’s father. CONCLUSIONS An increased frequency of the selected adverse birth outcomes was not observed with buprenorphine treatment

  15. A Swedish Population-based Study of Adverse Birth Outcomes among Pregnant Women Treated with Buprenorphine or Methadone: Preliminary Findings

    PubMed Central

    Wurst, Keele E.; Zedler, Barbara K.; Joyce, Andrew R.; Sasinowski, Maciek; Murrelle, E. Lenn

    2016-01-01

    BACKGROUND Untreated opioid dependence in pregnant women is associated with adverse birth outcomes. Buprenorphine and methadone are options for opioid agonist medication-assisted treatment during pregnancy. OBJECTIVE The aim of this study was to describe adverse birth outcomes observed with buprenorphine or methadone treatment compared to the general population in Sweden. METHODS Pregnant women and their corresponding births during 2005–2011 were identified in the Swedish Medical Birth Register. Data on stillbirth, neonatal/infant death, mode of delivery, gestational age at birth, Apgar score, growth outcomes, neonatal abstinence syndrome, and congenital malformations were examined. Frequencies were compared using two-sided Fisher’s exact tests. Unadjusted estimates of birth outcomes for women treated with buprenorphine or methadone were compared to the registered general population. RESULTS A total of 746,257 pregnancies among 538,178 unique women resulted in 746,485 live births. Among the 194 women treated with buprenorphine (N = 176) or methadone (N = 52), no stillbirths or neonatal/infant deaths occurred. Neonatal abstinence syndrome developed in 23.3% and 38.5% of infants born to mothers treated with buprenorphine and methadone, respectively. The frequency of the selected adverse birth outcomes assessed in women treated with buprenorphine as compared to the general population was not significantly different. However, a significantly higher frequency of preterm birth and congenital malformations was observed in women treated with methadone as compared to the general population. Compared with the general population, methadone-treated women were significantly older than buprenorphine-treated women, and both treatment groups began prenatal care later, were more likely to smoke cigarettes, and did not cohabitate with the baby’s father. CONCLUSIONS An increased frequency of the selected adverse birth outcomes was not observed with buprenorphine treatment

  16. Childhood Adverse Events and Health Outcomes among Methamphetamine-Dependent Men and Women

    ERIC Educational Resources Information Center

    Messina, Nena P.; Marinelli-Casey, Patricia; Hillhouse, Maureen; Ang, Alfonso; Hunter, Jeremy; Rawson, Richard

    2008-01-01

    To describe the prevalence of childhood adverse events (CAEs) among methamphetamine-dependent men and women, and assess the relationship of cumulative CAEs to health problems. Data for 236 men and 351 women were analyzed assessing CAEs. Dependent variables included 14 self-reported health problems or psychiatric symptom domains. Mental health was…

  17. Potential roles of omics data in the use of adverse outcome pathways for environmental risk assessment

    EPA Science Inventory

    The current approach to assessing adverse effects of chemicals in the environment is largely based on a battery of in-vivo study methods and a limited number of accepted in-silico approaches. For most substances the pool of data from which to predict ecosystem effects is limited ...

  18. Childhood adversity and behavioral health outcomes for youth: An investigation using state administrative data.

    PubMed

    Lucenko, Barbara A; Sharkova, Irina V; Huber, Alice; Jemelka, Ron; Mancuso, David

    2015-09-01

    This study aimed to measure the relative contribution of adverse experiences to adolescent behavioral health problems using administrative data. Specifically, we sought to understand the predictive value of adverse experiences on the presence of mental health and substance abuse problems for youth receiving publicly funded social and health services. Medicaid claims and other service records were analyzed for 125,123 youth age 12-17 and their biological parents. Measures from administrative records reflected presence of parental domestic violence, mental illness, substance abuse, criminal justice involvement, child abuse and/or neglect, homelessness, and death of a biological parent. Mental health and substance abuse status of adolescents were analyzed as functions of adverse experiences and other youth characteristics using logistic regression. In multivariate analyses, all predictors except parental domestic violence were statistically significant for substance abuse; parental death, parental mental illness, child abuse or neglect and homelessness were statistically significant for mental illness. Odds ratios for child abuse/neglect were particularly high in both models. The ability to identify risks during childhood using administrative data suggests the potential to target prevention and early intervention efforts for children with specific family risk factors who are at increased risk for developing behavioral health problems during adolescence. This study illustrates the utility of administrative data in understanding adverse experiences on children and the advantages and disadvantages of this approach.

  19. Adverse outcome pathways (AOPs): A framework to support predictive toxicology (presentation)

    EPA Science Inventory

    High throughput and in silico methods are providing the regulatory toxicology community with capacity to rapidly and cost effectively generate data concerning a chemical’s ability to initiate one or more biological perturbations that may culminate in an adverse ecological o...

  20. Associations between maternal serum free beta human chorionic gonadotropin (β-hCG) levels and adverse pregnancy outcomes.

    PubMed

    Sirikunalai, P; Wanapirak, C; Sirichotiyakul, S; Tongprasert, F; Srisupundit, K; Luewan, S; Traisrisilp, K; Tongsong, T

    2016-01-01

    The objective was to determine the strength of relationship between maternal free beta human chorionic gonadotropin (β-hCG) concentrations and rates of adverse pregnancy outcomes. Consecutive records of the database of our Down screening project were assessed for free β-hCG levels and pregnancy outcomes. Pregnancies with foetal chromosomal or structural anomalies and those with underlying disease were excluded. Free β-hCG levels of < 0.5, > 0.5 and < 2.0, and ≥ 2.0 MoM were categorised as low, normal and high, respectively. Of 17,082 screened women, 13,620 were available for analysis. In the first trimester (n = 8150), low β-hCG levels significantly increased risk for intrauterine growth restriction (IUGR), preterm birth, low birth weight (LBW) and low Apgar score with relative risk of 1.66, 1.43, 1.83 and 2.89; whereas high β-hCG group had a significant decreased risk of preterm birth and GDM with relative risk of 0.73 and 0.62. In the second trimester (n = 5470), both low and high β-hCG groups had significant increased risks of the most common adverse outcomes, i.e. spontaneous abortion, IUGR and preterm birth. In conclusion, abnormally low (< 0.5MoM) or high (> 2.0 MoM) free β-hCG levels are generally associated with an increased risk of adverse pregnancy outcomes. Nevertheless, high free β-hCG levels in the first trimester may possibly decrease risk of preterm delivery and GDM. PMID:26368010

  1. Increasing Number and Proportion of Adverse Obstetrical Outcomes among Women Living with HIV in the Ottawa Area: A 20-Year Clinical Case Series.

    PubMed

    Buchan, Sarah; Muldoon, Katherine A; Spaans, Johanna N; Balfour, Louise; Samson, Lindy; Walker, Mark; Cameron, D William

    2016-01-01

    Background. The prevalence and associated risks with adverse obstetrical outcomes among women living with HIV are not well measured. The objective of this study was to longitudinally investigate the prevalence and correlates of adverse obstetrical outcomes among women with HIV. Methods. This 20-year (1990-2010) clinical case series assessed the prevalence of adverse obstetrical outcomes among pregnant women with HIV receiving care at The Ottawa Hospital (TOH). General estimating equation modeling was used to identify factors independently associated with adverse obstetrical outcomes, while controlling for year of childbirth clustering. Results. At TOH, there were 127 deliveries among 94 women (1990-2010): 22 preterm births, 9 births with low birth weight, 12 births small for gestational age, and 4 stillbirths. Per year, the odds of adverse obstetrical outcomes increased by 15% (OR: 1.15, 95% CI: 1.03-1.30). Psychiatric illness (AOR: 2.64, 95% CI: 1.12-6.24), teen pregnancy (AOR: 3.35, 95% CI: 1.04-1.46), and recent immigrant status (AOR: 7.24, 95% CI: 1.30-40.28) were the strongest correlates of adverse obstetrical outcomes. Conclusions. The increasing number and proportion of adverse obstetrical outcomes among pregnant women with HIV over the past 20 years highlight the need for social supports and maternal and child health interventions, especially among adolescents, new immigrants, and those with a history of mental illness. PMID:27528877

  2. Increasing Number and Proportion of Adverse Obstetrical Outcomes among Women Living with HIV in the Ottawa Area: A 20-Year Clinical Case Series

    PubMed Central

    Buchan, Sarah; Spaans, Johanna N.; Balfour, Louise

    2016-01-01

    Background. The prevalence and associated risks with adverse obstetrical outcomes among women living with HIV are not well measured. The objective of this study was to longitudinally investigate the prevalence and correlates of adverse obstetrical outcomes among women with HIV. Methods. This 20-year (1990–2010) clinical case series assessed the prevalence of adverse obstetrical outcomes among pregnant women with HIV receiving care at The Ottawa Hospital (TOH). General estimating equation modeling was used to identify factors independently associated with adverse obstetrical outcomes, while controlling for year of childbirth clustering. Results. At TOH, there were 127 deliveries among 94 women (1990–2010): 22 preterm births, 9 births with low birth weight, 12 births small for gestational age, and 4 stillbirths. Per year, the odds of adverse obstetrical outcomes increased by 15% (OR: 1.15, 95% CI: 1.03–1.30). Psychiatric illness (AOR: 2.64, 95% CI: 1.12–6.24), teen pregnancy (AOR: 3.35, 95% CI: 1.04–1.46), and recent immigrant status (AOR: 7.24, 95% CI: 1.30–40.28) were the strongest correlates of adverse obstetrical outcomes. Conclusions. The increasing number and proportion of adverse obstetrical outcomes among pregnant women with HIV over the past 20 years highlight the need for social supports and maternal and child health interventions, especially among adolescents, new immigrants, and those with a history of mental illness. PMID:27528877

  3. High level amplification of N-MYC is not associated with adverse histology or outcome in primary retinoblastoma tumours

    PubMed Central

    Lillington, D M; Goff, L K; Kingston, J E; Onadim, Z; Price, E; Domizio, P; Young, B D

    2002-01-01

    Twenty-five primary retinoblastoma tumours were analysed by real-time quantitative polymerase chain reaction to determine the genomic copy number of the N-MYC gene (2p24) relative to the copy number for REL, B2M, ALB, AF10 and MLL. Twenty-one of these tumours were shown by Comparative Genomic Hybridization to contain variable copy number increases of chromosomal material mapping to 2p. High level amplification (>30-fold) of N-MYC was found in three tumours, none of which showed adverse histological features and all patients are surviving at between 54 and 108 months post enucleation. Furthermore, the three tumours associated with metastasis and adverse patient outcome showed normal N-MYC copy number. Although high level amplification of N-MYC is an unfavourable prognostic indicator in neuroblastoma, these data show no evidence of a correlation between amplification of N-MYC and adverse outcome in retinoblastoma. British Journal of Cancer (2002) 87, 779–782. doi:10.1038/sj.bjc.6600532 www.bjcancer.com © 2002 Cancer Research UK PMID:12232763

  4. A randomized clinical trial on the effects of remote intercessory prayer in the adverse outcomes of pregnancies.

    PubMed

    da Rosa, Maria Inês; Silva, Fabio Rosa; Silva, Bruno Rosa; Costa, Luciana Carvalho; Bergamo, Angela Mendes; Silva, Napoleão Chiaramonte; Medeiros, Lidia Rosi de Freitas; Battisti, Iara Denise Endruweit; Azevedo, Rafael

    2013-08-01

    The scope of this article was to investigate whether intercessory prayer (IP) influences the adverse outcomes of pregnancies. A double-blind, randomized clinical trial was conducted with 564 pregnant women attending a prenatal public health care service. The women were randomly assigned to an IP group or to a control group (n = 289 per group). They were simultaneously and randomly assigned to practice prayer off-site or not. The following parameters were evaluated: Apgar scores, type of delivery and birth weight. The mean age of the women was 25.1 years of age (± 7.4), and the average gestational age was 23.4 weeks (± 8.1). The average number of years of schooling for the women was 8.1 years (± 3.1). The women in the IP and control groups presented a similar number of adverse medical events with non-significant p. No significant differences were detected in the frequency of adverse outcomes in pregnant women who practiced IP and those in the control group.

  5. Application of in silico and in vitro methods in the development of adverse outcome pathway constructs in wildlife

    PubMed Central

    Madden, Judith C.; Rogiers, Vera; Vinken, Mathieu

    2014-01-01

    There is a long history of using both in silico and in vitro methods to predict adverse effects in humans and environmental species where toxicity data are lacking. Currently, there is a great deal of interest in applying these methods to the development of so-called ‘adverse outcome pathway’ (AOP) constructs. The AOP approach provides a framework for organizing information at the chemical and biological level, allowing evidence from both in silico and in vitro studies to be rationally combined to fill gaps in knowledge concerning toxicological events. Fundamental to this new paradigm is a greater understanding of the mechanisms of toxicity and, in particular, where these mechanisms may be conserved across taxa, such as between model animals and related wild species. This presents an opportunity to make predictions across diverse species, where empirical data are unlikely to become available as is the case for most species of wildlife. PMID:25405971

  6. Application of in silico and in vitro methods in the development of adverse outcome pathway constructs in wildlife.

    PubMed

    Madden, Judith C; Rogiers, Vera; Vinken, Mathieu

    2014-11-19

    There is a long history of using both in silico and in vitro methods to predict adverse effects in humans and environmental species where toxicity data are lacking. Currently, there is a great deal of interest in applying these methods to the development of so-called 'adverse outcome pathway' (AOP) constructs. The AOP approach provides a framework for organizing information at the chemical and biological level, allowing evidence from both in silico and in vitro studies to be rationally combined to fill gaps in knowledge concerning toxicological events. Fundamental to this new paradigm is a greater understanding of the mechanisms of toxicity and, in particular, where these mechanisms may be conserved across taxa, such as between model animals and related wild species. This presents an opportunity to make predictions across diverse species, where empirical data are unlikely to become available as is the case for most species of wildlife.

  7. Protein Carbamylation in Chronic Systolic Heart Failure: Relation to Renal Impairment and Adverse Long-Term Outcomes

    PubMed Central

    Wilson Tang, W. H.; Shrestha, Kevin; Wang, Zeneng; Borowski, Allen G.; Troughton, Richard W.; Klein, Allan L.; Hazen, Stanley L.

    2013-01-01

    Background Protein carbamylation, a post-translational modification promoted during uremia and catalyzed by myeloperoxidase (MPO) at sites of inflammation, is linked to altered protein structure, vascular dysfunction, and poor prognosis. We examine the relationship between plasma protein-bound homocitrulline (PBHCit) levels, a marker of protein lysine residue carbamylation, with cardio-renal function and long-term outcomes in chronic systolic heart failure. Methods and Results In 115 patients with chronic systolic HF (LVEF≤35%), we measured plasma PBHCit by quantitative mass spectrometry and performed comprehensive echocardiography with assessment of cardiac structure and performance. Adverse long-term events (death, cardiac transplant) were tracked for 5 years. In our study cohort, the median PBHCit level was 87 [IQR: 59, 128] μmol/mol Lysine. Higher plasma PBHcit levels were associated with poorer renal function (eGFR Spearman’s r= −0.37, p<0.001); cystatin C (r=0.31, p=0.001), and elevated plasma NT-proBNP levels (r= 0.26, 0.006), but not with markers of systemic inflammation or oxidant stress (hsCRP and MPO, p>0.10 for each). Furthermore, elevated plasma PBHCit levels were not related to indices of cardiac structure or function (p>0.10 for all examined) except modestly with increased right atrial volume index (RAVi; r=0.31, p=0.002). PBHCit levels predicted adverse long-term events (Hazard ratio [HR]: 1.8, 95% CI 1.3– 2.6, p<0.001), including following adjustment for age, eGFR, MPO and NT-proBNP (HR: 1.9, 95% CI: 1.2–3.1, p=0.006). Conclusions In chronic systolic HF, protein carbamylation is associated with poorer renal but not cardiac function, and portends poorer long-term adverse clinical outcomes even when adjusted for cardio-renal indices of adverse prognosis. PMID:23582087

  8. Young adolescent girls are at high risk for adverse pregnancy outcomes in sub-Saharan Africa: an observational multicountry study

    PubMed Central

    Mombo-Ngoma, Ghyslain; Mackanga, Jean Rodolphe; González, Raquel; Ouedraogo, Smaila; Kakolwa, Mwaka A; Manego, Rella Zoleko; Basra, Arti; Rupérez, María; Cot, Michel; Kabanywany, Abdunoor M; Matsiegui, Pierre-Blaise; Agnandji, Seldiji T; Vala, Anifa; Massougbodji, Achille; Abdulla, Salim; Adegnika, Ayôla A; Sevene, Esperança; Macete, Eusebio; Yazdanbakhsh, Maria; Kremsner, Peter G; Aponte, John J; Menéndez, Clara; Ramharter, Michael

    2016-01-01

    Objectives One of Africa's most important challenges is to improve maternal and neonatal health. The identification of groups at highest risk for adverse pregnancy outcomes is important for developing and implementing targeted prevention programmes. This study assessed whether young adolescent girls constitute a group at increased risk for adverse birth outcomes among pregnant women in sub-Saharan Africa. Setting Data were collected prospectively as part of a large randomised controlled clinical trial evaluating intermittent preventive treatment of malaria in pregnancy (NCT00811421—Clinical Trials.gov), conducted between September 2009 and December 2013 in Benin, Gabon, Mozambique and Tanzania. Participants Of 4749 participants, pregnancy outcomes were collected for 4388 deliveries with 4183 live births including 83 multiple gestations. Of 4100 mothers with a singleton live birth delivery, 24% (975/4100) were adolescents (≤19 years of age) and 6% (248/4100) were aged ≤16 years. Primary and secondary outcome measures Primary outcomes of this predefined analysis were preterm delivery and low birth weight. Results The overall prevalence of low birthweight infants and preterm delivery was 10% (371/3851) and 4% (159/3862), respectively. Mothers aged ≤16 years showed higher risk for the delivery of a low birthweight infant (OR: 1.96; 95% CI 1.35 to 2.83). Similarly, preterm delivery was associated with young maternal age (≤16 years; OR: 2.62; 95% CI 1.59 to 4.30). In a subanalysis restricted to primiparous women: preterm delivery, OR 4.28; 95% CI 2.05 to 8.93; low birth weight, OR: 1.29; 95% CI 0.82 to 2.01. Conclusions Young maternal age increases the risk for adverse pregnancy outcomes and it is a stronger predictor for low birth weight and preterm delivery than other established risk factors in sub-Saharan Africa. This finding highlights the need to improve adolescent reproductive health in sub-Saharan Africa. Trial registration number NCT00811421

  9. Adverse maternal and perinatal outcomes in adolescent pregnancies: The Global Network’s Maternal Newborn Health Registry study

    PubMed Central

    2015-01-01

    Background Adolescent girls between 15 and 19 years give birth to around 16 million babies each year, around 11% of births worldwide. We sought to determine whether adolescent mothers are at higher risk of maternal and perinatal adverse outcomes compared with mothers aged 20–24 years in a prospective, population-based observational study of newborn outcomes in low resource settings. Methods We undertook a prospective, population-based multi-country research study of all pregnant women in defined geographic areas across 7 sites in six low-middle income countries (Kenya, Zambia, India, Pakistan, Guatemala and Argentina). The study population for this analysis was restricted to women aged 24 years or less, who gave birth to infants of at least 20 weeks’ gestation and 500g or more. We compared adverse pregnancy maternal and perinatal outcomes among pregnant adolescents 15-19 years, <15 years, and adults 20-24 years. Results A total of 269,273 women were enrolled from January 2010 to December 2013. Of all pregnancies 11.9% (32,097/269,273) were in adolescents 15-19 years, while 0.14% (370/269,273) occurred among girls <15 years. Pregnancy among adolescents 15-19 years ranged from 2% in Pakistan to 26% in Argentina, and adolescent pregnancies <15 year were only observed in sub-Saharan Africa and Latin America. Compared to adults, adolescents did not show increased risk of maternal adverse outcomes. Risks of preterm birth and LBW were significantly higher among both early and older adolescents, with the highest risks observed in the <15 years group. Neonatal and perinatal mortality followed a similar trend in sub-Saharan Africa and Latin America, with the highest risk in early adolescents, although the differences in this age group were not significant. However, in South Asia the risks of neonatal and perinatal death were not different among adolescents 15-19 years compared to adults. Conclusions This study suggests that pregnancy among adolescents is not associated

  10. Association of Arsenic with Adverse Pregnancy Outcomes/Infant Mortality: A Systematic Review and Meta-Analysis

    PubMed Central

    Armah, Frederick Ato; Essumang, David Kofi; Luginaah, Isaac; Clarke, Edith; Marfoh, Kissinger; Cobbina, Samuel Jerry; Nketiah-Amponsah, Edward; Namujju, Proscovia Bazanya; Obiri, Samuel; Dzodzomenyo, Mawuli

    2015-01-01

    Background Exposure to arsenic is one of the major global health problems, affecting > 300 million people worldwide, but arsenic’s effects on human reproduction are uncertain. Objectives We conducted a systematic review and meta-analysis to examine the association between arsenic and adverse pregnancy outcomes/infant mortality. Methods We searched PubMed and Ovid MEDLINE (from 1946 through July 2013) and EMBASE (from 1988 through July 2013) databases and the reference lists of reviews and relevant articles. Studies satisfying our a priori eligibility criteria were evaluated independently by two authors. Results Our systematic search yielded 888 articles; of these, 23 were included in the systematic review. Sixteen provided sufficient data for our quantitative analysis. Arsenic in groundwater (≥ 50 μg/L) was associated with increased risk of spontaneous abortion (6 studies: OR = 1.98; 95% CI: 1.27, 3.10), stillbirth (9 studies: OR = 1.77; 95% CI: 1.32, 2.36), moderate risk of neonatal mortality (5 studies: OR = 1.51; 95% CI: 1.28, 1.78), and infant mortality (7 studies: OR = 1.35; 95% CI: 1.12, 1.62). Exposure to environmental arsenic was associated with a significant reduction in birth weight (4 studies: β = –53.2 g; 95% CI: –94.9, –11.4). There was paucity of evidence for low-to-moderate arsenic dose. Conclusions Arsenic is associated with adverse pregnancy outcomes and infant mortality. The interpretation of the causal association is hampered by methodological challenges and limited number of studies on dose response. Exposure to arsenic continues to be a major global health issue, and we therefore advocate for high-quality prospective studies that include individual-level data to quantify the impact of arsenic on adverse pregnancy outcomes/infant mortality. Citation Quansah R, Armah FA, Essumang DK, Luginaah I, Clarke E, Marfoh K, Cobbina SJ, Nketiah-Amponsah E, Namujju PB, Obiri S, Dzodzomenyo M. 2015. Association of arsenic with adverse pregnancy

  11. Risk of Performance Decrements and Adverse Health Outcomes Resulting from Sleep Loss, Circadian Desynchronization, and Work Overload

    NASA Technical Reports Server (NTRS)

    Evans-Flynn, Erin; Gregory, Kevin; Arsintescu, Lucia; Whitmire, Alexandra; Leveton, Lauren B.; Vessey, William

    2015-01-01

    Sleep loss, circadian desynchronization, and work overload occur to some extent for ground and flight crews, prior to and during spaceflight missions. Ground evidence indicates that such risk factors may lead to performance decrements and adverse health outcomes, which could potentially compromise mission objectives. Efforts are needed to identify the environmental and mission conditions that interfere with sleep and circadian alignment, as well as individual differences in vulnerability and resiliency to sleep loss and circadian desynchronization. Specifically, this report highlights a collection of new evidence to better characterize the risk and reveals new gaps in this risk.

  12. The effect of maternal near miss on adverse infant nutritional outcomes

    PubMed Central

    Zanardi, Dulce M; Moura, Erly C; Santos, Leonor P; Leal, Maria C; Cecatti, Jose G

    2016-01-01

    OBJECTIVES: To evaluate the association between self-reported maternal near miss and adverse nutritional status in children under one year of age. METHODS: This study is a secondary analysis of a study in which women who took their children under one year of age to the national vaccine campaign were interviewed. The self-reported condition of maternal near miss used the criteria of Intensive Care Unit admission; eclampsia; blood transfusion and hysterectomy; and their potential associations with any type of nutritional disorder in children, including deficits in weight-for-age, deficits in height-for-age, obesity and breastfeeding. The rates of near miss for the country, regions and states were initially estimated. The relative risks of infant adverse nutritional status according to near miss and maternal/childbirth characteristics were estimated with their 95% CIs using bivariate and multiple analyses. RESULTS: The overall prevalence of near miss was 2.9% and was slightly higher for the Legal Amazon than for other regions. No significant associations were found with nutritional disorders in children. Only a 12% decrease in overall maternal breastfeeding was associated with near miss. Living in the countryside and child over 6 months of age increased the risk of altered nutritional status by approximately 15%, while female child gender decreased this risk by 30%. Maternal near miss was not associated with an increased risk of any alteration in infant nutritional status. CONCLUSIONS: There was no association between maternal near miss and altered nutritional status in children up to one year of age. The risk of infant adverse nutritional status was greater in women living in the countryside, for children over 6 months of age and for male gender. PMID:27759848

  13. [What is known about the outcome as adults for children with fetal alcohol syndrome (FAS)/fetal alcohol spectrum disorders (FASD)?].

    PubMed

    Walloch, J E; Burger, P H; Kornhuber, J

    2012-06-01

    In the field of adult psychiatry in German-speaking countries, little attention is as yet paid to the psychic defects that a fetus can sustain as a result of prenatal exposure to alcohol. Although children of alcohol-dependent mothers do present to psychiatric institutions as adults with manifold symptoms, e. g., attention deficit disorders, affective disorders or intellectual disability, fetal alcohol spectrum disorders are rarely diagnosed as an underlying cause. Appropriate therapy guidelines do not exist. Current review papers within the German-speaking countries usually stem from paediatric and adolescent psychiatry or medicine. Based on a selected review of the literature, the following paper addresses and discusses the disease entity of fetal alcohol spectrum disorders and fetal alcohol syndrome and their significance for adult psychiatry and also identifies open questions and research requirements, e. g., the development of diagnostic instruments or the establishment of diagnostic categories.

  14. [What is known about the outcome as adults for children with fetal alcohol syndrome (FAS)/fetal alcohol spectrum disorders (FASD)?].

    PubMed

    Walloch, J E; Burger, P H; Kornhuber, J

    2012-06-01

    In the field of adult psychiatry in German-speaking countries, little attention is as yet paid to the psychic defects that a fetus can sustain as a result of prenatal exposure to alcohol. Although children of alcohol-dependent mothers do present to psychiatric institutions as adults with manifold symptoms, e. g., attention deficit disorders, affective disorders or intellectual disability, fetal alcohol spectrum disorders are rarely diagnosed as an underlying cause. Appropriate therapy guidelines do not exist. Current review papers within the German-speaking countries usually stem from paediatric and adolescent psychiatry or medicine. Based on a selected review of the literature, the following paper addresses and discusses the disease entity of fetal alcohol spectrum disorders and fetal alcohol syndrome and their significance for adult psychiatry and also identifies open questions and research requirements, e. g., the development of diagnostic instruments or the establishment of diagnostic categories. PMID:22173965

  15. Women with Intellectual Disability at Risk of Adverse Pregnancy and Birth Outcomes

    ERIC Educational Resources Information Center

    Mcconnell, D.; Mayes, R.; Llewellyn, G.

    2008-01-01

    Background: An increasing number of women with intellectual disability (ID) have children. Cross-sectional, clinical population data suggest that these women face an increased risk of delivering preterm and/or low birthweight babies. The aim of this study was to explore the prevalence of poor pregnancy and birth outcomes in women with ID and/or…

  16. Human adverse reproductive outcomes and electromagnetic field exposures: review of epidemiologic studies.

    PubMed Central

    Shaw, G M; Croen, L A

    1993-01-01

    Concerns have been raised regarding a relation between residential and occupational electromagnetic (EM) field exposures and adverse reproductive effects. This paper reviews the epidemiologic evidence for this possible relation, including some pertinent methodologic issues, notes relevant findings from the experimental literature, and discusses areas for future research. Evidence is lacking for a strong association between a woman's use of a video display terminal (VDT) during pregnancy and spontaneous abortion. The evidence for a strong association between a women's use of a VDT and other adverse reproductive endpoints is also lacking, with some suggestive findings for congenital malformations and too few data to reach a conclusion about other endpoints. With respect to low-level EM field exposures other than VDTs, the paucity of data prevents one from determining whether there are reproductive health risks associated with such exposures. Therefore, this is an area that needs further investigation. Given that altered growth may be an underlying biologic effect of EM field exposures, endpoints that might be pursued in future studies include congenital malformations not associated with chromosomal anomalies, intrauterine growth retardation, and chromosomally normal spontaneous abortions. PMID:8206019

  17. Household and community-level Adverse Childhood Experiences and adult health outcomes in a diverse urban population.

    PubMed

    Wade, Roy; Cronholm, Peter F; Fein, Joel A; Forke, Christine M; Davis, Martha B; Harkins-Schwarz, Mary; Pachter, Lee M; Bair-Merritt, Megan H

    2016-02-01

    Adverse Childhood Experiences (ACEs), which include family dysfunction and community-level stressors, negatively impact the health and well being of children throughout the life course. While several studies have examined the impact of these childhood exposures amongst racially and socially diverse populations, the contribution of ACEs in the persistence of socioeconomic disparities in health is poorly understood. To determine the association between ACEs and health outcomes amongst a sample of adults living in Philadelphia and examine the moderating effect of Socioeconomic Status (SES) on this association, we conducted a cross-sectional survey of 1,784 Philadelphia adults, ages 18 and older, using random digit dialing methodology to assess Conventional ACEs (experiences related to family dysfunction), Expanded ACEs (community-level stressors), and health outcomes. Using weighted, multivariable logistic regression analyses along with SES stratified models, we examined the relationship between ACEs and health outcomes as well as the modifying effect of current SES. High Conventional ACE scores were significantly associated with health risk behaviors, physical and mental illness, while elevated Expanded ACE scores were associated only with substance abuse history and sexually transmitted infections. ACEs did have some differential impacts on health outcomes based on SES. Given the robust impact of Conventional ACEs on health, our results support prior research highlighting the primacy of family relationships on a child's life course trajectory and the importance of interventions designed to support families. Our findings related to the modifying effect of SES may provide additional insight into the complex relationship between poverty and childhood adversity. PMID:26726759

  18. Comparison of maternal and fetal outcomes of IVF and spontaneously conceived twin pregnancies: three year experience of a tertiary hospital

    PubMed Central

    Göçmen, Ahmet; Güven, Şirin; Bağci, Simge; Çekmez, Yasemin; Şanlıkan, Fatih

    2015-01-01

    Objectives: The aim of this study was to compare maternal and fetal outcomes of spontaneously conceived and in-vitro fertilization (IVF) twin pregnancies that were admitted to our obstetric clinic and delivered between January 1, 2011 to November 1, 2014. Material method: A total of 84 twin pregnancies were enrolled for the study and divided into two groups: group 1 as IVF (n = 19) and group 2 as spontaneously conceived (n = 65) twin pregnancies. Data of neonatal various morbidities needs neonatal intensive care unit (NICU) such as necrotizing enterocolitis (NEC), bronchopulmonary dysplasia (BPD), sepsis, retinopathy of prematurity (ROP), and intraventricular hemorrhage (IVH) and maternal morbidities such as preeclampsia, eclampsia, postpartum bleeding, gestational diabetes mellitus(GDM) were collected by hospital records. Results: There were no statistical difference between two groups regarding hypertension related to pregnancy, intrauterine growth retardation, Apgar scores, NICU needs, birth weight and height (P > 0.05). The rate of premature rupture of membranes, maternal age, antenatal anemia and premature birth were detected higher in IVF group when compared with the other group (P < 0.05). Conclusion: Although twin pregnancies, regardless of conception method are high risk pregnancies in terms of obstetric and perinatal outcomes, premature rupture of membranes, maternal age, antenatal anemia and premature birth risks are higher in IVF twin pregnancies. PMID:26131238

  19. Effect of essential oil from Citrus aurantium in maternal reproductive outcome and fetal anomaly frequency in rats.

    PubMed

    Volpato, Gustavo T; Francia-Farje, Luis A D; Damasceno, Débora C; Oliveira, Renata V; Hiruma-Lima, Clélia A; Kempinas, Wilma G

    2015-03-01

    Citrus aurantium L., commonly known as bitter orange, is widely used in folk medicine, but there is little data in the literature about the effects on pregnancy. The aim of the present study was to evaluate the influence of essential oil obtained from fruits of Citrus aurantium on the maternal reproductive outcome and fetal anomaly incidence in rats. Pregnant Wistar rats were randomized into four groups (n minimum = 12 animals/group): G1 = control, G2 to G4 = treated with essential oil from C. aurantium at dose 125, 250 and 500 mg/kg, respectively. Rats were orally treated, by gavage, with plant essential oil or vehicle during pre-implantation and organogenic period (gestational day 0-14). On gestational day 20 the rats were anaesthetized and the gravid uterus was weighed with its contents and the fetuses were analyzed. Results showed that the treated group with 500 mg/kg presented decreased placental weights and placental index, although the treatment with bitter orange essential oil did not show any alteration in maternal reproductive performance, toxicological effect, changes in ossification sites, and malformation index. In conclusion, the treatment of Citrus aurantium essential oil was not teratogenic and did not alter the maternal reproductive outcome. PMID:25806990

  20. Frequency of changing enteral alimentation bags and tubing, and adverse clinical outcomes in patients in a long term care facility.

    PubMed

    Graham, S; McIntyre, M; Chicoine, J; Gerard, B; Laughren, R; Cowley, G; Morrison, J; Aoki, F Y; Nicolle, L E

    1993-01-01

    Enteral alimentation, given via nasogastric or gastrostomy tubes, is a well established practice to provide nutrition for patients with significant neurological injury. The frequency with which enteral feeding bags and tubes require change and potential adverse effects associated with bacterial contamination of tube feeds remain controversial. The authors studied different times between enteral feeding bag and tube changes, and the effect on adverse clinical outcomes in residents of a long term care facility. In the first study, residents were randomized to 24 h (n = 2), 48 h (n = 3) or 72 h (n = 6) tube feeding and bag changes with clinical status monitored in a standardized fashion for six months. In the second study, patients were randomized to 24 h (n = 6) or 72 h (n = 6) changes. Patient-days of follow-up were 382, 574 and 1000 for the three arms of the first study period and 556 and 496 for the two arms of the second study. No differences in potential clinical adverse events--including fever, gastrointestinal symptoms or pneumonia--were observed with different durations of tubing change. This study suggests it is appropriate to change alimentation tube and feeding bags every 72 h (rather than every 24 h). The less frequent changes will decrease supply costs and free nursing time for other activities.

  1. Associations of meteorology with adverse pregnancy outcomes: a systematic review of preeclampsia, preterm birth and birth weight.

    PubMed

    Beltran, Alyssa J; Wu, Jun; Laurent, Olivier

    2013-12-20

    The relationships between meteorology and pregnancy outcomes are not well known. This article reviews available evidence on the relationships between seasonality or meteorology and three major pregnancy outcomes: the hypertensive disorders of pregnancy (including preeclampsia, eclampsia and gestational hypertension), gestational length and birth weight. In total 35, 28 and 27 studies were identified for each of these outcomes. The risks of preeclampsia appear higher for women with conception during the warmest months, and delivery in the coldest months of the year. Delivery in the coldest months is also associated with a higher eclampsia risk. Patterns of decreased gestational lengths have been observed for births in winter, as well as summer months. Most analytical studies also report decreases in gestational lengths associated with heat. Birth weights are lower for deliveries occurring in winter and in summer months. Only a limited number of studies have investigated the effects of barometric pressure on gestational length or the effects of temperature and sunshine exposure on birth weight, but these questions appear worth investigating further. Available results should encourage further etiological research aiming at enhancing our understanding of the relationships between meteorology and adverse pregnancy outcomes, ideally via harmonized multicentric studies.

  2. Associations of Meteorology with Adverse Pregnancy Outcomes: A Systematic Review of Preeclampsia, Preterm Birth and Birth Weight

    PubMed Central

    Beltran, Alyssa J.; Wu, Jun; Laurent, Olivier

    2013-01-01

    The relationships between meteorology and pregnancy outcomes are not well known. This article reviews available evidence on the relationships between seasonality or meteorology and three major pregnancy outcomes: the hypertensive disorders of pregnancy (including preeclampsia, eclampsia and gestational hypertension), gestational length and birth weight. In total 35, 28 and 27 studies were identified for each of these outcomes. The risks of preeclampsia appear higher for women with conception during the warmest months, and delivery in the coldest months of the year. Delivery in the coldest months is also associated with a higher eclampsia risk. Patterns of decreased gestational lengths have been observed for births in winter, as well as summer months. Most analytical studies also report decreases in gestational lengths associated with heat. Birth weights are lower for deliveries occurring in winter and in summer months. Only a limited number of studies have investigated the effects of barometric pressure on gestational length or the effects of temperature and sunshine exposure on birth weight, but these questions appear worth investigating further. Available results should encourage further etiological research aiming at enhancing our understanding of the relationships between meteorology and adverse pregnancy outcomes, ideally via harmonized multicentric studies. PMID:24362545

  3. Adverse Outcome Pathways for Regulatory Applications: Examination of Four Case Studies With Different Degrees of Completeness and Scientific Confidence.

    PubMed

    Perkins, Edward J; Antczak, Philipp; Burgoon, Lyle; Falciani, Francesco; Garcia-Reyero, Natàlia; Gutsell, Steve; Hodges, Geoff; Kienzler, Aude; Knapen, Dries; McBride, Mary; Willett, Catherine

    2015-11-01

    Adverse outcome pathways (AOPs) offer a pathway-based toxicological framework to support hazard assessment and regulatory decision-making. However, little has been discussed about the scientific confidence needed, or how complete a pathway should be, before use in a specific regulatory application. Here we review four case studies to explore the degree of scientific confidence and extent of completeness (in terms of causal events) that is required for an AOP to be useful for a specific purpose in a regulatory application: (i) Membrane disruption (Narcosis) leading to respiratory failure (low confidence), (ii) Hepatocellular proliferation leading to cancer (partial pathway, moderate confidence), (iii) Covalent binding to proteins leading to skin sensitization (high confidence), and (iv) Aromatase inhibition leading to reproductive dysfunction in fish (high confidence). Partially complete AOPs with unknown molecular initiating events, such as 'Hepatocellular proliferation leading to cancer', were found to be valuable. We demonstrate that scientific confidence in these pathways can be increased though the use of unconventional information (eg, computational identification of potential initiators). AOPs at all levels of confidence can contribute to specific uses. A significant statistical or quantitative relationship between events and/or the adverse outcome relationships is a common characteristic of AOPs, both incomplete and complete, that have specific regulatory uses. For AOPs to be useful in a regulatory context they must be at least as useful as the tools that regulators currently possess, or the techniques currently employed by regulators. PMID:26500288

  4. Rising disparities in severe adverse birth outcomes among Haitians in Québec, Canada, 1981-2006.

    PubMed

    Auger, Nathalie; Chery, Martine; Daniel, Mark

    2012-04-01

    Perinatal health data for Haitians are scant. We evaluated adverse birth outcomes for Haitians in Québec, Canada. We analyzed 2,124,909 live births from 1981 to 2006. Haitian ethnicity was assessed using maternal birth country (Haiti, other Caribbean country, other foreign country, Canada) and home language (Creole, French/English but Creole mother tongue, French/English, other). Associations between ethnicity and preterm birth (PTB), low birth weight (LBW), and small-for-gestational-age (SGA) birth were calculated. Adverse birth outcomes were more common among mothers with Haitian ethnicity. Relative to Canadian-born mothers, odds for Haitian-born mothers were 4 times greater for extreme PTB (≤27 weeks), twice greater for very PTB (28-31 weeks), and 25% higher for moderate PTB (32-36 weeks). Patterns were similar for SGA birth and severe cases of LBW. Despite overall decreases LBW and SGA birth, relative and absolute inequalities increased over time. Perinatal health inequalities are increasing for Haitian-born mothers.

  5. Serum metabolomics identifies citrulline as a predictor of adverse outcomes in an equine model of gut-derived sepsis.

    PubMed

    Steelman, Samantha M; Johnson, Philip; Jackson, Amy; Schulze, James; Chowdhary, Bhanu P

    2014-05-15

    Acute laminitis is an inflammatory disease of the equine foot that often occurs secondarily to sepsis or systemic inflammation associated with gastrointestinal disease. It has been suggested that laminitis is similar to multiple organ dysfunction syndrome in humans, although in horses the weight-bearing laminar epithelium of the foot appears to be the tissue most sensitive to insult and the first "organ" to fail. Metabolomics performed on serum samples collected before (Con) and after (Lmn) experimental induction of gastrointestinal-associated sepsis in six horses detected 1,177 metabolites of both mammalian and bacterial origin in equine serum. Network and correlation analyses suggested a dysregulation of fatty acid metabolism in the Lmn group, as well as an accumulation of organic acids such as lactate. Furthermore, concentrations of the amino acid citrulline were decreased in Lmn samples from all study animals, suggesting that citrulline might be useful as a biomarker to identify critically ill animals that are at risk of developing laminitis. We therefore established normal ranges of plasma citrulline concentrations in a separate group of horses (n = 36) and tested the ability of citrulline to predict adverse outcomes (laminitis or death) in critically ill horses (n = 23). Plasma citrulline was significantly lower in critically ill horses that went on to experience adverse outcomes (n = 6). Further study is required to accurately determine a diagnostic cutoff, but the present data are suggestive of the predictive value of citrulline as a biomarker for laminar failure in equine sepsis. PMID:24619519

  6. Adverse Outcome Pathways for Regulatory Applications: Examination of Four Case Studies With Different Degrees of Completeness and Scientific Confidence.

    PubMed

    Perkins, Edward J; Antczak, Philipp; Burgoon, Lyle; Falciani, Francesco; Garcia-Reyero, Natàlia; Gutsell, Steve; Hodges, Geoff; Kienzler, Aude; Knapen, Dries; McBride, Mary; Willett, Catherine

    2015-11-01

    Adverse outcome pathways (AOPs) offer a pathway-based toxicological framework to support hazard assessment and regulatory decision-making. However, little has been discussed about the scientific confidence needed, or how complete a pathway should be, before use in a specific regulatory application. Here we review four case studies to explore the degree of scientific confidence and extent of completeness (in terms of causal events) that is required for an AOP to be useful for a specific purpose in a regulatory application: (i) Membrane disruption (Narcosis) leading to respiratory failure (low confidence), (ii) Hepatocellular proliferation leading to cancer (partial pathway, moderate confidence), (iii) Covalent binding to proteins leading to skin sensitization (high confidence), and (iv) Aromatase inhibition leading to reproductive dysfunction in fish (high confidence). Partially complete AOPs with unknown molecular initiating events, such as 'Hepatocellular proliferation leading to cancer', were found to be valuable. We demonstrate that scientific confidence in these pathways can be increased though the use of unconventional information (eg, computational identification of potential initiators). AOPs at all levels of confidence can contribute to specific uses. A significant statistical or quantitative relationship between events and/or the adverse outcome relationships is a common characteristic of AOPs, both incomplete and complete, that have specific regulatory uses. For AOPs to be useful in a regulatory context they must be at least as useful as the tools that regulators currently possess, or the techniques currently employed by regulators.

  7. Current Perspectives on Arthroplasty in Systemic Lupus Erythematosus: Rates, Outcomes, and Adverse Events.

    PubMed

    Kasturi, Shanthini; Goodman, Susan

    2016-09-01

    Systemic lupus erythematosus (SLE) is a chronic debilitating condition with significant impact on the musculoskeletal system. Arthroplasty may be indicated for damage related to active lupus or its treatment. As therapies for SLE have advanced, morbidity and mortality have declined, while the rate of joint replacement has increased. The age of SLE patients undergoing arthroplasty is increasing, and the indication for surgery is evolving-while avascular necrosis was previously the predominant indication for arthroplasty, osteoarthritis now accounts for a larger proportion of surgeries. Pain and functional outcomes of arthroplasty in SLE patients are comparable to those of the general population with osteoarthritis, but lupus remains an independent risk factor for post-hip arthroplasty complications and mortality. Further research is needed to characterize the impact of lupus disease activity and severity on arthroplasty outcomes. PMID:27443850

  8. Club foot, an adverse outcome of early amniocentesis: disruption or deformation?

    PubMed Central

    Farrell, S; Summers, A; Dallaire, L; Singer, J; Johnson, J.; Wilson, R

    1999-01-01

    An association between the occurrence of club foot and early amniocentesis has been reported. The largest of these randomised studies was the Canadian Early and Mid-Trimester Amniocentesis Trial. Data describing the neonatal outcome, focusing on this association, are presented. Possible mechanisms for the association and the implications for the development of club foot are discussed.


Keywords: amniocentesis; early amniocentesis; club foot PMID:10544229

  9. Adverse Symptom Event Reporting by Patients vs Clinicians: Relationships With Clinical Outcomes

    PubMed Central

    Jia, Xiaoyu; Heller, Glenn; Barz, Allison; Sit, Laura; Fruscione, Michael; Appawu, Mark; Iasonos, Alexia; Atkinson, Thomas; Goldfarb, Shari; Culkin, Ann; Kris, Mark G.; Schrag, Deborah

    2009-01-01

    Background In cancer treatment trials, the standard source of adverse symptom data is clinician reporting by use of items from the National Cancer Institute’s Common Terminology Criteria for Adverse Events (CTCAE). Patient self-reporting has been proposed as an additional data source, but the implications of such a shift are not understood. Methods Patients with lung cancer receiving chemotherapy and their clinicians independently reported six CTCAE symptoms and Karnofsky Performance Status longitudinally at sequential office visits. To compare how patient's vs clinician's reports relate to sentinel clinical events, a time-dependent Cox regression model was used to measure associations between reaching particular CTCAE grade severity thresholds with the risk of death and emergency room visits. To measure concordance of CTCAE reports with indices of daily health status, Kendall tau rank correlation coefficients were calculated for each symptom with EuroQoL EQ-5D questionnaire and global question scores. Statistical tests were two-sided. Results A total of 163 patients were enrolled for an average of 12 months (range = 1–28 months), with a mean of 11 visits and 67 (41%) deaths. CTCAE reports were submitted by clinicians at 95% of visits and by patients at 80% of visits. Patients generally reported symptoms earlier and more frequently than clinicians. Statistically significant associations with death and emergency room admissions were seen for clinician reports of fatigue (P < .001), nausea (P = .01), constipation (P = .038), and Karnofsky Performance Status (P < .001) but not for patient reports of these items. Higher concordance with EuroQoL EQ-5D questionnaire and global question scores was observed for patient-reported symptoms than for clinician-reported symptoms. Conclusions Longitudinally collected clinician CTCAE assessments better predict unfavorable clinical events, whereas patient reports better reflect daily health status. These perspectives are

  10. Circulating Influenza Virus and Adverse Pregnancy Outcomes: A Time-Series Study.

    PubMed

    Fell, Deshayne B; Buckeridge, David L; Platt, Robert W; Kaufman, Jay S; Basso, Olga; Wilson, Kumanan

    2016-08-01

    Individual-level epidemiologic studies of pregnancy outcomes after maternal influenza are limited in number and quality and have produced inconsistent results. We used a time-series design to investigate whether fluctuation in influenza virus circulation was associated with short-term variation in population-level rates of preterm birth, stillbirth, and perinatal death in Ontario between 2003 and 2012. Using Poisson regression, we assessed the association between weekly levels of circulating influenza virus and counts of outcomes offset by the number of at-risk gestations during 3 gestational exposure windows. The rate of preterm birth was not associated with circulating influenza level in the week preceding birth (adjusted rate ratio = 1.01, 95% confidence interval: 1.00, 1.02) or in any other exposure window. These findings were robust to alternate specifications of the model and adjustment for potential confounding. Stillbirth and perinatal death rates were similarly not associated with gestational exposure to influenza circulation during late pregnancy. We could not assess mortality outcomes relative to early gestational exposure because of missing dates of conception for many stillbirths. In this time-series study, population-level influenza circulation was not associated with short-term variation in rates of preterm birth, stillbirth, or perinatal death. PMID:27449415

  11. Elevated depressive affect is associated with adverse cardiovascular outcomes among African Americans with chronic kidney disease

    PubMed Central

    Fischer, Michael J.; Kimmel, Paul L.; Greene, Tom; Gassman, Jennifer J.; Wang, Xuelei; Brooks, Deborah H.; Charleston, Jeanne; Dowie, Donna; Thornley-Brown, Denyse; Cooper, Lisa A.; Bruce, Marino A.; Kusek, John W.; Norris, Keith C.; Lash, James P.

    2011-01-01

    This study was designed to examine the impact of elevated depressive affect on health outcomes among participants with hypertensive chronic kidney disease in the African-American Study of Kidney Disease and Hypertension (AASK) Cohort Study. Elevated depressive affect was defined by Beck Depression Inventory II (BDI-II) thresholds of 11 or more, above 14, and by 5-Unit increments in the score. Cox regression analyses were used to relate cardiovascular death/hospitalization, doubling of serum creatinine/end-stage renal disease, overall hospitalization, and all-cause death to depressive affect evaluated at baseline, the most recent annual visit (time-varying), or average from baseline to the most recent visit (cumulative). Among 628 participants at baseline, 42% had BDI-II scores of 11 or more and 26% had a score above 14. During a 5-year follow-up, the cumulative incidence of cardiovascular death/hospitalization was significantly greater for participants with baseline BDI-II scores of 11 or more compared with those with scores <11. The baseline, time-varying, and cumulative elevated depressive affect were each associated with a significant higher risk of cardiovascular death/hospitalization, especially with a time-varying BDI-II score over 14 (adjusted HR 1.63) but not with the other outcomes. Thus, elevated depressive affect is associated with unfavorable cardiovascular outcomes in African Americans with hypertensive chronic kidney disease. PMID:21633409

  12. Adverse Outcomes of IVF/ICSI Pregnancies Vary Depending on Aetiology of Infertility

    PubMed Central

    Kuivasaari-Pirinen, Paula; Raatikainen, Kaisa; Hippeläinen, Maritta; Heinonen, Seppo

    2012-01-01

    In vitro fertilization (IVF) is a risk factor for pregnancy, but there have been few studies on the effect of infertility's aetiology. Thus, we have assessed the role of aetiology on IVF pregnancy outcomes in a retrospective cohort study comparing the outcomes of IVF singleton pregnancies with those of spontaneous pregnancies in the general Finnish population. The study group consisted of 255 women with births resulting from singleton IVF pregnancies. Six subgroups were formed according to the following causes of infertility: anovulation (27%), endometriosis (19%), male factor (17%), tubal factor (15%), polycystic ovary syndrome (11%), and unexplained infertility (12%). The reference group consisted of 26,870 naturally conceived women. Adjusted odds ratios (AORs), for confounding factors such as age and parity, were estimated using logistic regression analysis. Women with endometriosis and anovulation had increased risks of preterm birth (AOR 3.25, 95% CI 1.5–7.1 and AOR 2.1, and 95% CI 1.0–4.2, resp.), while women in couples with male factor infertility had a twofold risk of admission to neonatal intensive care (AOR 2.5, 95% CI 1.2–5.3). The findings show that the aetiology of infertility influenced the obstetrics outcome, and that pooling results may obscure some increased risks among subgroups. PMID:22570795

  13. Fetal ventriculomegaly: Pregnancy outcomes and follow-ups in ten years.

    PubMed

    Chu, Nan; Zhang, Yueping; Yan, Yingliu; Ren, Yunyun; Wang, Ling; Zhang, Bin

    2016-05-23

    The aim of this study is to evaluate the pregnancy outcomes and prognoses for fetuses with ventriculomegaly. Two hundred and forty-one cases of fetuses with ventriculomegaly were included in this study. The subjects were divided into three groups according to their lateral ventricular width: "Mild Ventriculomegaly" (10 ‒ < 12 mm), "Moderate Ventriculomegaly" (12 ‒ < 15 mm) and "Severe Ventriculomegaly" (≥ 15 mm). Pediatric examination records and telephone interviews were conducted to track the outcomes of children until the age of 9 years. Eight-two cases were Isolated Ventriculomegaly (34.0%), while Non-Isolated Ventriculomegaly was found in 159 cases (66.0%). The pregnancy was terminated in 91 cases, and a higher abortion ratio was found in the NIVM (Non-Isolated Ventriculomegaly) group compared with the IVM (Isolated Ventriculomegaly) group. The fetuses were delivered in 150 cases, and four infants suffered deaths with NIVM. Of the surviving fetuses, 7 with IVM and 9 with NIVM showed significant abnormalities. The Mild and Moderate VM groups had more favorable prognoses compared with the Severe VM group. Regarding the outcomes and progression of lateral ventricular width, 1 out of 42 cases in the regressed group and 19 out of 108 cases in the stable group showed significant abnormalities. This study suggests that the degree and the progression of ventricular dilatation are main factors that affect pregnancy outcomes and prognoses.

  14. Spiral artery remodeling and trophoblast invasion in preeclampsia and fetal growth restriction: relationship to clinical outcome.

    PubMed

    Lyall, Fiona; Robson, Stephen C; Bulmer, Judith N

    2013-12-01

    Failure to transform uteroplacental spiral arteries is thought to underpin disorders of pregnancy, including preeclampsia and fetal growth restriction (FGR). In this study, spiral artery remodeling and extravillous-cytotrophoblast were examined in placental bed biopsies from normal pregnancy (n = 25), preeclampsia (n = 22), and severe FGR (n = 10) and then compared with clinical parameters. Biopsies were immunostained to determine vessel wall integrity, extravillous-cytotrophoblast location/density, periarterial fibrinoid, and endothelium. Muscle disruption was reduced in myometrial spiral arteries in preeclampsia (P = 0.0001) and FGR (P = 0.0001) compared with controls. Myometrial vessels from cases with birth weight <5th percentile (P<0.001), abnormal uterine Doppler (P<0.01), abnormal umbilical artery Doppler (P<0.001), and preterm delivery (P<0.001) had less muscle destruction compared with >5th percentile. Fewer extravillous-cytotrophoblast surrounded both decidual and myometrial vessels in the normal group and preeclampsia group compared with the FGR group (P = 0.001). For myometrial vessels, the normal group contained more intramural extravillous-cytotrophoblast than in preeclampsia (P = 0.015). Decidual vessels in the FGR group had less fibrinoid deposition compared with controls (P = 0.013). For myometrial vessels, less fibrinoid was deposited in both the preeclampsia group (P = 0.0001) and the FGR group (P = 0.01) when compared with controls, and less fibrinoid was deposited in the preeclampsia group when compared with FGR group (P<0.001). Myometrial vessels obtained from birth weights <5th percentile had less periarterial fibrinoid than those with >5th percentile (P<0.02). A major defect in myometrial spiral artery remodeling occurs in preeclampsia and FGR that is linked to clinical parameters. Interstitial extravillous-cytotrophoblast is not reduced in preeclampsia but is increased in FGR. PMID:24060885

  15. Prolonged time to pregnancy is associated with a greater risk of adverse outcomes.

    PubMed

    Raatikainen, Kaisa; Harju, Maija; Hippeläinen, Maritta; Heinonen, Seppo

    2010-08-01

    Births with known time to pregnancy (TTP) during the period 1989-2007 (n=17,114) were analyzed to investigate associations between TTP and pregnancy outcome among couples that conceived spontaneously. The adjusted odds ratio (95% confidence interval) for poor neonatal health, including low Apgar score, low umbilical vein pH, and need for neonatal intensive care, was 1.51 (1.09-2.09) in women who had a TTP of 25-36 months and 1.60 (1.18-2.19) in women who had a TTP of >or=37 months compared with women with a TTP of 0-6 months.

  16. Association between Environmental Dioxin-Related Toxicants Exposure and Adverse Pregnancy Outcome: Systematic Review and Meta-Analysis.

    PubMed

    Pan, Xinjuan; Liu, Xiaozhuan; Li, Xing; Niu, Nannan; Yin, Xinjuan; Li, Ning; Yu, Zengli

    2015-01-01

    Dioxin-related compounds are associated with teratogenic and mutagenic risks in laboratory animals, and result in adverse pregnancy outcomes. However, there were inconsistent results in epidemiology studies. In view of this difference, we conducted a systematic review and meta-analysis to examine this association and to assess the heterogeneity among studies. Comprehensive literature searches were performed to search for relevant articles published in English up to 15 May 2012. In total, we identified 15 studies which included 9 cohort and 6 case control studies. The Cochrane Q test and index of heterogeneity (I(2)) were used to evaluate heterogeneity. In either cohort studies (I(2)=0.89, p<0.0001) or case control studies (I(2)=0.69, p=0.02), significant heterogeneity of risk estimates were observed. Subgroup analyses found no significant increased risk of adverse pregnancy outcome with air dioxin-related compounds exposure (RR=0.99, 95% CI:0.85-1.16), no significant increased risk of spontaneous abortion (SAB) with exposure to food dioxin-related compounds (RR=1.05, 95% CI:0.80-1.37), higher significant risks of low birth weight (LBW) with exposure to food dioxin-related compounds (RR=1.55, 95% CI:1.24-1.94), and higher significant risks of birth defects with maternal solid contaminants dioxin exposure (OR=1.24, 95% CI:1.19-1.29). In conclusion, more evidences are needed to confirm the association between environmental dioxin-related compounds exposure and pregnancy outcome. PMID:25780516

  17. Clinical Characteristics and Predictors of Adverse Outcome in Adult and Pediatric Patients With Healthcare-Associated Ventriculitis and Meningitis

    PubMed Central

    Srihawan, Chanunya; Castelblanco, Rodrigo Lopez; Salazar, Lucrecia; Wootton, Susan H.; Aguilera, Elizabeth; Ostrosky-Zeichner, Luis; Sandberg, David I.; Choi, HuiMahn A.; Lee, Kiwon; Kitigawa, Ryan; Tandon, Nitin; Hasbun, Rodrigo

    2016-01-01

    Background. Healthcare-associated meningitis or ventriculitis is a serious and life-threatening complication of invasive neurosurgical procedures or penetrating head trauma. Methods. We performed a retrospective study of adults and children with the diagnosis of healthcare-associated meningitis or ventriculitis, as defined by the 2015 Centers of Disease Control and Prevention case definition, at 2 large tertiary care hospitals in Houston, Texas from July 2003 to November 2014. Patients were identified by infection control practitioners and by screening cerebrospinal fluid samples sent to the central laboratory. We collected data on demographics, clinical presentations, laboratory results, imaging studies, treatments, and outcomes. Results. A total of 215 patients were included (166 adults and 49 children). A positive cerebrospinal fluid culture was seen in 106 (49%) patients, with the majority of the etiologies being Staphylococcus and Gram-negative rods. An adverse clinical outcome was seen in 167 patients (77.7%) and was defined as death in 20 patients (9.3%), persistent vegetative state in 31 patients (14.4%), severe disability in 77 patients (35.8%), or moderate disability in 39 patients (18.1%). On logistic regression analysis, age >45 years (adjusted odds ratio [OR], 6.47; 95% confidence interval [CI], 2.31–18.11; P ≤ .001), abnormal neurological exam (adjusted OR, 3.04; 95% CI, 1.27–7.29; P = .013), and mechanical ventilation (adjusted OR, 5.34; 95% CI, 1.51–18.92; P = .01) were associated with an adverse outcome. Conclusions. Healthcare-associated meningitis or ventriculitis is associated with significant morbidity and mortality. PMID:27419154

  18. Adverse Outcomes After Palliative Radiation Therapy for Uncomplicated Spine Metastases: Role of Spinal Instability and Single-Fraction Radiation Therapy

    SciTech Connect

    Lam, Tai-Chung; Krishnan, Monica; Groff, Michael; Cheney, Matthew; Balboni, Tracy

    2015-10-01

    Purpose: Level I evidence demonstrates equivalent pain response after single-fraction (SF) or multifraction (MF) radiation therapy (RT) for bone metastases. The purpose of this study is to provide additional data to inform the incidence and predictors of adverse outcomes after RT for spine metastases. Methods and Materials: At a single institution, 299 uncomplicated spine metastases (without cord compression, prior RT, or surgery) treated with RT from 2008 to 2013 were retrospectively reviewed. The spinal instability neoplastic score (SINS) was used to assess spinal instability. The primary outcome was time to first spinal adverse event (SAE) at the site, including symptomatic vertebral fracture, hospitalization for site-related pain, salvage surgery, interventional procedure, new neurologic symptoms, or cord compression. Fine and Gray's multivariable model assessed associations of the primary outcome with SINS, SF RT, and other significant baseline factors. Propensity score matched analysis further assessed the relationship of SF RT to first SAEs. Results: The cumulative incidence of first SAE after SF RT (n=66) was 6.8% at 30 days, 16.9% at 90 days, and 23.6% at 180 days. For MF RT (n=233), the incidence was 3.5%, 6.4%, and 9.2%, respectively. In multivariable analysis, SF RT (hazard ratio [HR] = 2.8, 95% confidence interval [CI] 1.5-5.2, P=.001) and SINS ≥11 (HR=2.5 , 95% CI 1.3-4.9, P=.007) were predictors of the incidence of first SAE. In propensity score matched analysis, first SAEs had developed in 22% of patients with SF RT versus 6% of those with MF RT cases (HR=3.9, 95% CI 1.6-9.6, P=.003) at 90 days after RT. Conclusion: In uncomplicated spinal metastases treated with RT alone, spinal instability with SINS ≥11 and SF RT were associated with a higher rate of SAEs.

  19. Clinical Characteristics and Predictors of Adverse Outcome in Adult and Pediatric Patients With Healthcare-Associated Ventriculitis and Meningitis.

    PubMed

    Srihawan, Chanunya; Castelblanco, Rodrigo Lopez; Salazar, Lucrecia; Wootton, Susan H; Aguilera, Elizabeth; Ostrosky-Zeichner, Luis; Sandberg, David I; Choi, HuiMahn A; Lee, Kiwon; Kitigawa, Ryan; Tandon, Nitin; Hasbun, Rodrigo

    2016-04-01

    Background.  Healthcare-associated meningitis or ventriculitis is a serious and life-threatening complication of invasive neurosurgical procedures or penetrating head trauma. Methods.  We performed a retrospective study of adults and children with the diagnosis of healthcare-associated meningitis or ventriculitis, as defined by the 2015 Centers of Disease Control and Prevention case definition, at 2 large tertiary care hospitals in Houston, Texas from July 2003 to November 2014. Patients were identified by infection control practitioners and by screening cerebrospinal fluid samples sent to the central laboratory. We collected data on demographics, clinical presentations, laboratory results, imaging studies, treatments, and outcomes. Results.  A total of 215 patients were included (166 adults and 49 children). A positive cerebrospinal fluid culture was seen in 106 (49%) patients, with the majority of the etiologies being Staphylococcus and Gram-negative rods. An adverse clinical outcome was seen in 167 patients (77.7%) and was defined as death in 20 patients (9.3%), persistent vegetative state in 31 patients (14.4%), severe disability in 77 patients (35.8%), or moderate disability in 39 patients (18.1%). On logistic regression analysis, age >45 years (adjusted odds ratio [OR], 6.47; 95% confidence interval [CI], 2.31-18.11; P ≤ .001), abnormal neurological exam (adjusted OR, 3.04; 95% CI, 1.27-7.29; P = .013), and mechanical ventilation (adjusted OR, 5.34; 95% CI, 1.51-18.92; P = .01) were associated with an adverse outcome. Conclusions.  Healthcare-associated meningitis or ventriculitis is associated with significant morbidity and mortality. PMID:27419154

  20. Association between Environmental Dioxin-Related Toxicants Exposure and Adverse Pregnancy Outcome: Systematic Review and Meta-Analysis

    PubMed Central

    Pan, Xinjuan; Liu, Xiaozhuan; Li, Xing; Niu, Nannan; Yin, Xinjuan; Li, Ning; Yu, Zengli

    2015-01-01

    Dioxin-related compounds are associated with teratogenic and mutagenic risks in laboratory animals, and result in adverse pregnancy outcomes. However, there were inconsistent results in epidemiology studies. In view of this difference, we conducted a systematic review and meta-analysis to examine this association and to assess the heterogeneity among studies. Comprehensive literature searches were performed to search for relevant articles published in English up to 15 May 2012. In total, we identified 15 studies which included 9 cohort and 6 case control studies. The Cochrane Q test and index of heterogeneity (I2) were used to evaluate heterogeneity. In either cohort studies (I2=0.89, p<0.0001) or case control studies (I2=0.69, p=0.02), significant heterogeneity of risk estimates were observed. Subgroup analyses found no significant increased risk of adverse pregnancy outcome with air dioxin-related compounds exposure (RR=0.99, 95% CI:0.85–1.16), no significant increased risk of spontaneous abortion (SAB) with exposure to food dioxin-related compounds (RR=1.05, 95% CI:0.80–1.37), higher significant risks of low birth weight (LBW) with exposure to food dioxin-related compounds (RR=1.55, 95% CI:1.24–1.94), and higher significant risks of birth defects with maternal solid contaminants dioxin exposure (OR=1.24, 95% CI:1.19–1.29). In conclusion, more evidences are needed to confirm the association between environmental dioxin-related compounds exposure and pregnancy outcome. PMID:25780516

  1. Long-term adverse outcomes in survivors of childhood bone sarcoma: the British Childhood Cancer Survivor Study

    PubMed Central

    Fidler, M M; Frobisher, C; Guha, J; Wong, K; Kelly, J; Winter, D L; Sugden, E; Duncan, R; Whelan, J; Reulen, R C; Hawkins, M M

    2015-01-01

    Background: With improved survival, more bone sarcoma survivors are approaching middle age making it crucial to investigate the late effects of their cancer and its treatment. We investigated the long-term risks of adverse outcomes among 5-year bone sarcoma survivors within the British Childhood Cancer Survivor Study. Methods: Cause-specific mortality and risk of subsequent primary neoplasms (SPNs) were investigated for 664 bone sarcoma survivors. Use of health services, health and marital status, alcohol and smoking habits, and educational qualifications were investigated for survivors who completed a questionnaire. Results: Survivors were seven times more likely to experience all-cause mortality than expected, and there were substantial differences in risk depending on tumour type. Beyond 25 years follow-up the risk of dying from all-causes was comparable to the general population. This is in contrast to dying before 25 years where the risk was 12.7-fold that expected. Survivors were also four times more likely to develop a SPN than expected, where the excess was restricted to 5–24 years post diagnosis. Increased health-care usage and poor health status were also found. Nonetheless, for some psychosocial outcomes survivors were better off than expected. Conclusions: Up to 25 years after 5-year survival, bone sarcoma survivors are at substantial risk of death and SPNs, but this is greatly reduced thereafter. As 95% of all excess deaths before 25 years follow-up were due to recurrences and SPNs, increased monitoring of survivors could prevent mortality. Furthermore, bone and breast SPNs should be a particular concern. Since there are variations in the magnitude of excess risk depending on the specific adverse outcome under investigation and whether the survivors were initially diagnosed with osteosarcoma or Ewing sarcoma, risks need to be assessed in relation to these factors. These findings should provide useful evidence for risk stratification and updating

  2. Sleep apnoea adversely affects the outcome in patients who undergo posterior lumbar fusion

    PubMed Central

    Stundner, O.; Chiu, Y-L.; Sun, X.; Ramachandran, S-K.; Gerner, P.; Vougioukas, V.; Mazumdar, M.; Memtsoudis, S. G.

    2014-01-01

    Despite the increasing prevalence of sleep apnoea, little information is available regarding its impact on the peri-operative outcome of patients undergoing posterior lumbar fusion. Using a national database, patients who underwent lumbar fusion between 2006 and 2010 were identified, sub-grouped by diagnosis of sleep apnoea and compared. The impact of sleep apnoea on various outcome measures was assessed by regression analysis. The records of 84 655 patients undergoing posterior lumbar fusion were identified and 7.28% also had a diagnostic code for sleep apnoea. Compared with patients without sleep apnoea, these patients were older, more frequently female, had a higher comorbidity burden and higher rates of peri-operative complications, post-operative mechanical ventilation, blood transfusion, and intensive care. Patients with sleep apnoea also had longer and more costly periods of hospitalisation. In the regression analysis, sleep apnoea emerged as an independent risk factor for the development of peri-operative complications (Odds Ratio (OR) 1.50, Confidence Interval (CI) 1.38;1.62), blood transfusions (OR 1.12, CI 1.03;1.23), mechanical ventilation (OR 6.97, CI 5.90;8.23), critical care services (OR 1.86, CI 1.71;2.03), prolonged hospitalisation and increased cost (OR 1.28, CI 1.19;1.37; OR 1.10, CI 1.03;1.18). Patients with sleep apnoea who undergo posterior lumbar fusion pose significant challenges to clinicians. PMID:24493191

  3. Adverse Clinical Outcome Associated With Mutations That Typify African American Colorectal Cancers.

    PubMed

    Wang, Zhenghe; Li, Li; Guda, Kishore; Chen, Zhengyi; Barnholtz-Sloan, Jill; Park, Young Soo; Markowitz, Sanford D; Willis, Joseph

    2016-12-01

    African Americans have the highest incidence and mortality from colorectal cancer (CRC) of any US racial group. We recently described a panel of 15 genes that are statistically significantly more likely to be mutated in CRCs from African Americans than in Caucasians (AA-CRC genes). The current study investigated the outcomes associated with these mutations in African American CRCs (AA-CRCs). In a cohort of 66 patients with stage I-III CRCs, eight of 27 CRCs with AA-CRC gene mutations (Mut+) developed metastatic disease vs only four of 39 mutation-negative (Mut-) cases (P = .03, Cox regression model with two-sided Wald test). Moreover, among stage III cases (n = 33), Mut+ cancers were nearly three times more likely to relapse as Mut- cases (7 of 15 Mut+ vs 3 of 18 Mut-; P = .03, Cox regression model with two-sided Wald test). AA-CRC mutations may thus define a high-risk subset of CRCs that contributes to the overall disparity in CRC outcomes observed in African Americans.

  4. Adverse Clinical Outcome Associated With Mutations That Typify African American Colorectal Cancers.

    PubMed

    Wang, Zhenghe; Li, Li; Guda, Kishore; Chen, Zhengyi; Barnholtz-Sloan, Jill; Park, Young Soo; Markowitz, Sanford D; Willis, Joseph

    2016-12-01

    African Americans have the highest incidence and mortality from colorectal cancer (CRC) of any US racial group. We recently described a panel of 15 genes that are statistically significantly more likely to be mutated in CRCs from African Americans than in Caucasians (AA-CRC genes). The current study investigated the outcomes associated with these mutations in African American CRCs (AA-CRCs). In a cohort of 66 patients with stage I-III CRCs, eight of 27 CRCs with AA-CRC gene mutations (Mut+) developed metastatic disease vs only four of 39 mutation-negative (Mut-) cases (P = .03, Cox regression model with two-sided Wald test). Moreover, among stage III cases (n = 33), Mut+ cancers were nearly three times more likely to relapse as Mut- cases (7 of 15 Mut+ vs 3 of 18 Mut-; P = .03, Cox regression model with two-sided Wald test). AA-CRC mutations may thus define a high-risk subset of CRCs that contributes to the overall disparity in CRC outcomes observed in African Americans. PMID:27582379

  5. An Elevated Glycemic Gap is Associated with Adverse Outcomes in Diabetic Patients with Acute Myocardial Infarction

    PubMed Central

    Liao, Wen-I; Lin, Chin-Sheng; Lee, Chien-Hsing; Wu, Ya-Chieh; Chang, Wei-Chou; Hsu, Chin-Wang; Wang, Jen-Chun; Tsai, Shih-Hung

    2016-01-01

    Acute hyperglycemia is a frequent finding in patients presenting to the emergency department (ED) with acute myocardial infarction (AMI). The prognostic role of hyperglycemia in diabetic patients with AMI remains controversial. We retrospectively reviewed patients’ medical records to obtain demographic data, clinical presentation, major adverse cardiac events (MACEs), several clinical scores and laboratory data, including the plasma glucose level at initial presentation and HbA1c levels. The glycemic gap, which represents changes in serum glucose levels during the index event, was calculated from the glucose level upon ED admission minus the HbA1c-derived average glucose (ADAG). We enrolled 331 patients after the review of medical records. An elevated glycemic gap between admission serum glucose levels and ADAG were associated with an increased risk of mortality in patients. The glycemic gap showed superior discriminative power regarding the development of MACEs when compared with the admission glucose level. The calculation of the glycemic gap may increase the discriminative powers of established clinical scoring systems in diabetic patients presenting to the ED with AMI. In conclusion, the glycemic gap could be used as an adjunct parameter to assess the severity and prognosis of diabetic patients presenting with AMI. However, the usefulness of the glycemic gap should be further explored in prospective longitudinal studies. PMID:27291987

  6. Patient-Reported Outcomes in Cancer Clinical Trials: Measuring Symptomatic Adverse Events With the National Cancer Institute's Patient-Reported Outcomes Version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE).

    PubMed

    Kluetz, Paul G; Chingos, Diana T; Basch, Ethan M; Mitchell, Sandra A

    2016-01-01

    Systematic capture of the patient perspective can inform the development of new cancer therapies. Patient-reported outcomes (PROs) are commonly included in cancer clinical trials; however, there is heterogeneity in the constructs, measures, and analytic approaches that have been used making these endpoints challenging to interpret. There is renewed effort to identify rigorous methods to obtain high-quality and informative PRO data from cancer clinical trials. In this setting, PROs are used to address specific research objectives, and an important objective that spans the product development life cycle is the assessment of safety and tolerability. The U.S. Food and Drug Administration's (FDA) Office of Hematology and Oncology Products (OHOP) has identified symptomatic adverse events (AEs) as a central PRO concept, and a systematic assessment of patient-reported symptomatic AEs can provide data to complement clinician reporting. The National Cancer Institute's Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) is being evaluated by multiple stakeholders, including the FDA, and is considered a promising tool to provide a standard yet flexible method to assess symptomatic AEs from the patient perspective. In this article, we briefly review the FDA OHOP's perspective on PROs in cancer trials submitted to the FDA and focus on the assessment of symptomatic AEs using PRO-CTCAE. We conclude by discussing further work that must be done to broaden the use of PRO-CTCAE as a method to provide patient-centered data that can complement existing safety and tolerability assessments across cancer clinical trials. PMID:27249687

  7. Dynamical System Modeling of Immune Reconstitution after Allogeneic Stem Cell Transplantation Identifies Patients at Risk for Adverse Outcomes

    PubMed Central

    Toor, Amir A.; Sabo, Roy T.; Roberts, Catherine H.; Moore, Bonny L.; Salman, Salman R.; Scalora, Allison F.; Aziz, May T.; Shubar Ali, Ali S.; Hall, Charles E.; Meier, Jeremy; Thorn, Radhika M.; Wang, Elaine; Song, Shiyu; Miller, Kristin; Rizzo, Kathryn; Clark, William B.; McCarty, John M.; Chung, Harold M.; Manjili, Masoud H.; Neale, Michael C.

    2016-01-01

    Systems that evolve over time and follow mathematical laws as they evolve are called dynamical systems. Lymphocyte recovery and clinical outcomes in 41 allograft recipients conditioned using antithymocyte globulin (ATG) and 4.5-Gy total body irradiation were studied to determine if immune reconstitution could be described as a dynamical system. Survival, relapse, and graft-versus-host disease (GVHD) were not significantly different in 2 cohorts of patients receiving different doses of ATG. However, donor-derived CD3+ cell reconstitution was superior in the lower ATG dose cohort, and there were fewer instances of donor lymphocyte infusion (DLI). Lymphoid recovery was plotted in each individual over time and demonstrated 1 of 3 sigmoid growth patterns: Pattern A (n = 15) had rapid growth with high lymphocyte counts, pattern B (n = 14) had slower growth with intermediate recovery, and pattern C (n = 10) had poor lymphocyte reconstitution. There was a significant association between lymphocyte recovery patterns and both the rate of change of donor-derived CD3+ at day 30 after stem cell transplantation (SCT) and clinical outcomes. GVHD was observed more frequently with pattern A, relapse and DLI more so with pattern C, with a consequent survival advantage in patients with patterns A and B. We conclude that evaluating immune reconstitution after SCT as a dynamical system may differentiate patients at risk of adverse outcomes and allow early intervention to modulate that risk. PMID:25849208

  8. A workflow to investigate exposure and pharmacokinetic influences on high-throughput in vitro chemical screening based on adverse outcome pathways, OpenTox USA 2015 Poster

    EPA Science Inventory

    Adverse outcome pathways (AOP) link known population outcomes to a molecular initiating event (MIE) that can be quantified using high-throughput in vitro methods. Practical application of AOPs in chemical-specific risk assessment requires consideration of exposure and absorption,...

  9. Adverse health outcomes, perpetrator characteristics, and sexual violence victimization among U.S. adult males.

    PubMed

    Choudhary, Ekta; Coben, Jeffrey; Bossarte, Robert M

    2010-08-01

    In the United States, an estimated three million men are victims of sexual violence each year, yet the majority of existing studies have evaluated the consequences and characteristics of victimization among women alone. The result has been a gap in the existing literature examining the physical and psychological consequences of sexual assault among men. The main objective of this study was to identify health outcomes, risk behaviors, and perpetrator/victim relationship characteristics among men who have experienced an attempted or completed sexual assault using data from the sexual violence module of the Behavioral Risk Factor Surveillance System survey. A total of 59,511 male respondents participated in the sexual violence module, and the majority of participants were White (73.7%), between the ages of 35 to 44 years (19.8%), married (69.0%), graduated from college (34.6%), and had an annual household income of more than US$50,000 (49.9%). Stratified multivariate logistic regression models were conducted to test the associations between victimization and health outcomes and risk behaviors controlling for age, marital status, race/ethnicity, income, education, and other potential confounders. Results of these analyses suggest important associations between health and sexual violence victimization. Specifically, men who reported unwanted attempted intercourse and attempted and completed intercourse were more likely to report poor mental health, poor life satisfaction, activity limitations, and lower emotional and social support. The current study extends knowledge of consequences of male sexual violence by considering characteristics of sexual assault and by identifying associations between victimization and a broad range of health indicators.

  10. Testing the association between psychosocial job strain and adverse birth outcomes - design and methods

    PubMed Central

    2011-01-01

    Background A number of studies have examined the effects of prenatal exposure to stress on birth outcomes but few have specifically focused on psychosocial job strain. In the present protocol, we aim to examine if work characterised by high demands and low control, during pregnancy, is associated with the risk of giving birth to a child born preterm or small for gestational age. Methods and design We will use the Danish National Birth Cohort where 100.000 children are included at baseline. In the present study 49,340 pregnancies will be included. Multinomial logistic regression will be applied to estimate odds ratios for the outcomes: preterm; full term but small for gestational age; full term but large for gestational age, as a function of job-strain (high strain, active and passive versus low strain). In the analysis we control for maternal age, Body Mass Index, parity, exercise, smoking, alcohol use, coffee consumption, type of work (manual versus non-manual), maternal serious disease and parents' heights as well as gestational age at interview. Discussion The prospective nature of the design and the high number of participants strengthen the study. The large statistical power allows for interpretable results regardless of whether or not the hypotheses are confirmed. This is, however, not a controlled study since all kinds of 'natural' interventions takes place throughout pregnancy (e.g. work absence, medical treatment and job-redesign). The analysis will be performed from a public health perspective. From this perspective, we are not primarily interested in the effect of job strain per se but if there is residual effect of job strain after naturally occurring preventive measures have been taken. PMID:21510894

  11. Adverse health outcomes, perpetrator characteristics, and sexual violence victimization among U.S. adult males.

    PubMed

    Choudhary, Ekta; Coben, Jeffrey; Bossarte, Robert M

    2010-08-01

    In the United States, an estimated three million men are victims of sexual violence each year, yet the majority of existing studies have evaluated the consequences and characteristics of victimization among women alone. The result has been a gap in the existing literature examining the physical and psychological consequences of sexual assault among men. The main objective of this study was to identify health outcomes, risk behaviors, and perpetrator/victim relationship characteristics among men who have experienced an attempted or completed sexual assault using data from the sexual violence module of the Behavioral Risk Factor Surveillance System survey. A total of 59,511 male respondents participated in the sexual violence module, and the majority of participants were White (73.7%), between the ages of 35 to 44 years (19.8%), married (69.0%), graduated from college (34.6%), and had an annual household income of more than US$50,000 (49.9%). Stratified multivariate logistic regression models were conducted to test the associations between victimization and health outcomes and risk behaviors controlling for age, marital status, race/ethnicity, income, education, and other potential confounders. Results of these analyses suggest important associations between health and sexual violence victimization. Specifically, men who reported unwanted attempted intercourse and attempted and completed intercourse were more likely to report poor mental health, poor life satisfaction, activity limitations, and lower emotional and social support. The current study extends knowledge of consequences of male sexual violence by considering characteristics of sexual assault and by identifying associations between victimization and a broad range of health indicators. PMID:19940163

  12. Plasma neutrophil gelatinase-associated lipocalin as a potential predictor of adverse renal outcomes in immunoglobulin A nephropathy

    PubMed Central

    Park, Ga-Young; Yu, Chung-Hoon; Kim, Jun-Seop; Kang, Yun-Jeong; Kwon, Owen; Choi, Ji-Young; Cho, Jang-Hee; Kim, Chan-Duck; Kim, Yong-Lim

    2015-01-01

    Background/Aims Neutrophil gelatinase-associated lipocalin (NGAL) is a well-known biomarker of acute kidney injury. We evaluated the value of plasma NGAL (pNGAL) as an independent predictor of prognosis in immunoglobulin A nephropathy (IgAN). Methods In total, 91 patients with biopsy-proven IgAN at a single center were evaluated. pNGAL was measured using a commercial enzyme-linked immunosorbent assay kit (R&D Systems). Adverse renal outcome was defined as chronic kidney disease (CKD) stage 3 or above at the last follow-up. Pearson correlation coefficient and Cox regression were used for analyses. Results The mean age of all patients (male:female, 48:43) was 35 years (range, 18 to 77). pNGAL ranged between 21.68 and 446.40 ng/mL (median, 123.97) and showed a correlation with age (r = 0.332, p = 0.001), creatinine (r = 0.336, p = 0.001), estimated glomerular filtration rate (r = -0.397, p < 0.001), uric acid (r = 0.289, p = 0.006), and the protein-to-creatinine ratio (r = 0.288, p = 0.006). During a mean follow-up period of 37.6 months, 11 patients (12.1%) had CKD stage 3 or above. In a multivariate Cox regression model, hypertension (hazard ratio [HR], 8.779; 95% confidence interval [CI], 1.526 to 50.496; p = 0.015), proteinuria > 1 g/day (HR, 5.184; 95% CI, 1.124 to 23.921; p = 0.035), and pNGAL (HR, 1.012; 95% CI, 1.003 to 1.022; p = 0.013) were independent predictors associated with adverse renal outcome. Conclusions pNGAL showed strong correlations with other clinical prognostic factors and was also an independent predictor of adverse renal outcome. We suggest pNGAL as a potential predictor for prognosis in IgAN, while further studies are needed to confirm the clinical value. PMID:25995665

  13. The adverse effects of smoking on postoperative outcomes in cancer patients

    PubMed Central

    Gajdos, Csaba; Hawn, Mary T; Campagna, Elizabeth J; Henderson, William G.; Singh, Jasvinder A.; Houston, Thomas

    2014-01-01

    Background The possible negative effects of smoking on postoperative outcomes have not been well-studied in cancer patients. Methods We used the VA Surgical Quality Improvement Program (VASQIP) database for the years 2002–2008, which assesses pre-operative risk factors and post-operative outcomes for patients undergoing major surgery within the VA healthcare system. Results Compared to never smokers, prior smokers and current smokers with GI malignancies were significantly more likely to have surgical site infection (SSI)( Odds ratio, OR:1.25, 95%CI:1.09–1.44)(OR:1.20, 95%CI:1.05–1.38), combined pulmonary complications (CPO: pneumonia, failure to wean from ventilator, reintubation) (OR:1.60, 95%CI:1.38–1.87)(OR:1.96, 95%CI:1.68–2.29) and return to the operating room (OR:1.20, 95%CI:1.03–1.39)(OR:1.31 95%CI:1.13–1.53), respectively. Both prior and current smokers had a significantly higher mortality at 30 days (OR:1.50, 95%CI:1.19–1.89)(OR: 1.41, 95%CI:1.08–1.82) and one year (OR:1.22, 95%CI:1.08–1.38)(OR:1.62, 95%C I:1.43–1.85). Thoracic surgery patients who were current smokers were more likely to develop CPO (OR:1.62, 95%CI:1.25–2.11), and mortality within one year (OR:1.50, 95%CI:1.17–1.92) compared to non-smokers, but SSI rates were not affected by smoking status. Current smokers had a significant increase in postsurgical length of stay (overall 4.3% [p<0.001], GI 4.7% [p=0.003], thoracic 9.0% [p<0.001]) compared to prior smokers. Conclusions Prior and current smoking status is a significant risk factor for major postoperative complications and mortality following GI cancer and thoracic operations in veterans. Smoking cessation should be encouraged prior to all major cancer surgery in the VA population to decrease postoperative complications and length of stay. PMID:22065194

  14. Effect of radial-to-femoral access crossover on adverse outcomes in primary percutaneous coronary intervention.

    PubMed

    Azzalini, Lorenzo; Khan, Razi; Al-Hawwas, Malek; Hatem, Raja; Fortier, Annik; L'Allier, Philippe L; Ly, Hung Q

    2014-10-15

    We aimed to describe the impact of the vascular access used when patients are treated with primary percutaneous coronary intervention (PPCI) and to assess whether this translates into differences in angiographic outcomes. Patients with ST-elevation myocardial infarction who underwent PPCI were divided into 3 groups: successful radial access (RA), successful femoral access (FA), and Crossover (failed RA with need for bailout FA) groups. Vascular access-related time (VART) was defined as the delay in PPCI that can be attributed to vascular access-related issues. Study end point was the final corrected Thrombolysis In Myocardial Infarction frame count. Multivariable analysis was used to identify predictors of RA failure (RAF: FA + Crossover). We included 241 patients (RA, n = 172; FA, n = 49; Crossover, n = 20). Mean VART was longer in Crossover (10.3 [8.8 to 12.4] minutes), relative to RA (4.1 [3.2 to 5.5] minutes) and FA (4.6 [3.4 to 8.4] minutes, p <0.001). A similar situation was found for time-to-first device (Crossover 22.5 [20.3 to 32.0], RA 15.0 [12.0 to 19.8]; FA 17.9 [13.5 to 22.3] minutes, p <0.001) and total procedure time (Crossover 60.3 [51.6 to 71.5], RA 46.8 [38.1 to 59.7], FA 52.3 [41.9 to 74.7] minutes, p <0.001). No differences in corrected Thrombolysis In Myocardial Infarction frame count were observed (Crossover 26 [18 to 32] frames, RA 24 [18 to 32] frames, FA 25 [16 to 34] frames, p = 0.625). Killip class IV (odds ratio [OR] 3.628, 95% confidence interval [CI] 1.098 to 11.981, p = 0.035), cardiopulmonary resuscitation before arrival (OR 3.572, 95% CI 1.028 to 12.407, p = 0.045), and glomerular filtration rate (OR 0.861, 95% CI 0.758 to 0.978, p = 0.021) were independent predictors of RA failure. In conclusion, in the setting of PPCI, radial-to-FA crossover can lead to VART delays that do not affect angiographic outcomes, in comparison with successful RA.

  15. Impact of adverse pancreatic injury at surgical procurement upon islet isolation outcome.

    PubMed

    Andres, Axel; Kin, Tatsuya; O'Gorman, Doug; Bigam, David; Kneteman, Norman; Senior, Peter; Shapiro, Am James

    2014-11-01

    The consequence of a pancreas injury during the procurement for islet isolation purpose is unknown. The goal of this work was to assess the injuries of the pancreata procured for islet isolation, and to determine their effect on the islet yield. Between January 2007 and October 2013, we prospectively documented every injury of the pancreata processed in our centre for islet isolation. Injuries involving the main duct were classified as major, the others as minor. Donors' characteristics and islet yields were compared between the groups of injuries. A pancreas injury was identified in 42 of 452 pancreata received for islet isolation (9.3%). In 15 cases, the injury was major (3.3% of all pancreata). Although a minor injury did not affect the islet yield, a major injury was significantly associated with unfavourable outcomes (postpurification mean islet equivalent of 364 ± 181, 405 ± 190 and 230 ± 115 × 10(3) for absence of injury, minor injury and major injury, respectively). A major injury was significantly more prevalent in lean and short donors. We recommend assessing the quality of the pancreas in the islet isolation centre before starting the isolation procedure. Each centre should determine its own policy based on its financial resources and on the wait list.

  16. Regulation of Calcitriol Biosynthesis and Activity: Focus on Gestational Vitamin D Deficiency and Adverse Pregnancy Outcomes

    PubMed Central

    Olmos-Ortiz, Andrea; Avila, Euclides; Durand-Carbajal, Marta; Díaz, Lorenza

    2015-01-01

    Vitamin D has garnered a great deal of attention in recent years due to a global prevalence of vitamin D deficiency associated with an increased risk of a variety of human diseases. Specifically, hypovitaminosis D in pregnant women is highly common and has important implications for the mother and lifelong health of the child, since it has been linked to maternal and child infections, small-for-gestational age, preterm delivery, preeclampsia, gestational diabetes, as well as imprinting on the infant for life chronic diseases. Therefore, factors that regulate vitamin D metabolism are of main importance, especially during pregnancy. The hormonal form and most active metabolite of vitamin D is calcitriol. This hormone mediates its biological effects through a specific nuclear receptor, which is found in many tissues including the placenta. Calcitriol synthesis and degradation depend on the expression and activity of CYP27B1 and CYP24A1 cytochromes, respectively, for which regulation is tissue specific. Among the factors that modify these cytochromes expression and/or activity are calcitriol itself, parathyroid hormone, fibroblast growth factor 23, cytokines, calcium and phosphate. This review provides a current overview on the regulation of vitamin D metabolism, focusing on vitamin D deficiency during gestation and its impact on pregnancy outcomes. PMID:25584965

  17. Sexual Hookups and Adverse Health Outcomes: A Longitudinal Study of First-Year College Women

    PubMed Central

    Fielder, Robyn L.; Walsh, Jennifer L.; Carey, Kate B.; Carey, Michael P.

    2013-01-01

    “Hookups” are sexual encounters between partners who are not in a romantic relationship and do not expect commitment. We examined the associations between sexual hookup behavior and depression, sexual victimization (SV), and sexually transmitted infections (STIs) among first-year college women. In this longitudinal study, 483 women completed 13 monthly surveys assessing oral and vaginal sex with hookup and romantic partners, depression, SV, and self-reported STIs. Participants also provided biological specimens that were tested for STIs. During the study, 50% of participants reported hookup sex, and 62% reported romantic sex. Covariates included previous levels of the outcome, alcohol use, impulsivity, sensation-seeking, and romantic sex. Autoregressive cross-lagged models showed that controlling for covariates, hookup behavior during college was correlated with depression, Bs = .21, ps < .05, and SV, Bs = .19, ps < .05. Additionally, pre-college hookup behavior predicted SV early in college, B = .62, p < .05. Hookup sex, OR 1.32, p < .05, and romantic sex, OR 1.19, p < .05, were associated with STIs. Overall, sexual hookup behavior among college women was positively correlated with experiencing depression, SV, and STIs, but the nature of these associations remains unclear, and hooking up did not predict future depression. PMID:24350600

  18. Is ABO blood group truly a risk factor for thrombosis and adverse outcomes?

    PubMed Central

    Zhou, Shan; Welsby, Ian

    2014-01-01

    ABO blood type is one of the most readily available laboratory tests, and serves as a vital determinant in blood transfusion and organ transplantation. The ABO antigens are expressed not only on red blood cell membranes, determining the compatibility of transfusion, but also on the surface of other human cells, including epithelium, platelet and vascular endothelium, therefore extending the research into other involvements of cardiovascular disease and postoperative outcomes. ABO blood group has been recognized as a risk factor of venous thrombosis embolism since the 1960’s, effects now understood to be related to ABO dependent variations are procoagulant factor VIII (FVIII) and von Willebrand factor (vWF) levels. Levels of vWF, mostly genetically determined, are strongly associated with venous thromboembolism (VTE). It mediates platelet adhesion aggregation and stabilizes FVIII in plasma. Moreover, many studies have tried to identify the relationship between ABO blood types and ischemic heart disease. Unlike the clear and convincing associations between VTE and ABO blood type, the link between ABO blood type and ischemic heart disease is less consistent and may be confusing. Other than genetic factors, ischemic heart disease is strongly related to diet, race, lipid metabolism and economic status. In this review, we’ll summarize the data relating race and genetics, including ABO blood type, to VTE, ischemic heart disease and postoperative bleeding after cardiac surgery. PMID:25276299

  19. Postoperative Adverse Outcomes in Patients With Asthma: A Nationwide Population-based Cohort Study.

    PubMed

    Lin, Chao-Shun; Chang, Chuen-Chau; Yeh, Chun-Chieh; Chung, Chi-Li; Chen, Ta-Liang; Liao, Chien-Chang

    2016-01-01

    Outcome after surgery in patients with asthma remains unknown. The purpose of this study is to investigate postoperative major complications and mortality in surgical patients with asthma.Using reimbursement claims from the Taiwan National Health Insurance Research Database, the authors identified 24,109 surgical patients with preoperative asthma and 24,109 nonasthma patients undergoing major surgeries using matching procedure with propensity score by sociodemographics, coexisting medical conditions, and surgical characteristics. Adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for 30-day postoperative complications and mortality associated with asthma were analyzed in the multivariate logistic regressions.Asthma increased postoperative pneumonia (OR 1.48; 95% CI 1.34-1.64), septicemia (OR 1.11; 95% CI 1.02-1.21), and urinary tract infection (OR 1.17; 95% CI 1.09-1.26). Preoperative emergency care for asthma was significantly associated with postoperative 30-day in-hospital mortality, with an OR of 1.84 (95% CI 1.11-3.04). Preoperative emergency service, hospitalizations, admission to intensive care unit, and systemic use of corticosteroids for asthma were also associated with higher postoperative complication rates for asthmatic patients.Postoperative complications and mortality were significantly increased in asthmatic patients. We suggest urgent efforts to revise protocols for asthma patients' perioperative care.

  20. Preeclampsia-Eclampsia Adverse Outcomes Reduction: The Preeclampsia-Eclampsia Checklist.

    PubMed

    Nwanodi, Oroma B

    2016-01-01

    Globally, preeclampsia-eclampsia (PE-E) is a major cause of puerperal intensive care unit admission, accounting for up to 10% of maternal deaths. PE-E primary prevention is possible. Antepartum low-dose aspirin prophylaxis, costing USD $10-24 can cut the incidence of PE-E in half. Antepartum low molecular weight heparin combined with low-dose aspirin prophylaxis can cut the incidence of early onset PE-E and fetuses that are small for their gestational age in half. Despite predictive antepartum models for PE-E prophylaxis, said prophylaxis is not routinely provided. Therefore, magnesium sulfate secondary prevention of eclampsia remains the globally recommended intervention. Implementation of a PE-E checklist is a continuous quality improvement (CQI) tool facilitating appropriate antepartum PE-E prophylaxis and maternal care from the first trimester through the postpartum fourth trimester inter-partum interval. A novel clinical PE-E checklist and implementation strategy are presented below. CQI PE-E checklist implementation and appropriate PE-E prophylaxis provides clinicians and healthcare systems an opportunity to achieve Millennium Development Goals 4 and 5, reducing child mortality and improving maternal health. While CQI checklist implementation may be a tedious ongoing process requiring healthcare team resiliency, improved healthcare outcomes are well worth the effort. PMID:27417614

  1. ASSOCIATION BETWEEN CHILDHOOD SEXUAL ABUSE (CSA) AND ADVERSE PSYCHOLOGICAL OUTCOMES AMONG YOUTH IN TAIPEI

    PubMed Central

    Li, Nan; Ahmed, Saifuddin; Zabin, Laurie S.

    2014-01-01

    Purpose The objective of this study is to examine the relationship between a history of CSA and negative psychological consequences in adulthood controlling for family environments and Confucian values. Methods The data used in this study was collected from Taipei. 4084 participants aged 15-24 composed the final analysis sample. Three sets of logistic regression models were fitted to verify the association between CSA and negative psychological outcomes. Socio-demographic variables, household instability and parenting variables, as well as Confucian value variables were controlled in models step by step. The overall prevalence of CSA in our analysis sample was 5.2 %. Results The overall prevalence of depression, anxiety and suicidal ideation among Taipei respondents were 11.8 %, 16.4 % and 16.7 %, respectively, but young people who experienced CSA had significantly higher rates of all three than young adults who had not experienced CSA. After controlled for other covariates, the odds ratios of depression, anxiety and suicidal ideation associated with a history of CSA were 1.78 (95% CI: 1.25-2.54), 1.77 (95% CI: 1.28-2.44) and 2.56 (95% CI: 1.56-4.29), respectively. Conclusion Our findings suggested that CSA is an independent predictor of negative psychological consequences in adulthood. In our analysis, we controlled for household, parenting and Confucian culture factors which provides a better understanding of how they work together to affect adult psychological status. PMID:22340856

  2. Preeclampsia-Eclampsia Adverse Outcomes Reduction: The Preeclampsia-Eclampsia Checklist

    PubMed Central

    Nwanodi, Oroma B.

    2016-01-01

    Globally, preeclampsia-eclampsia (PE-E) is a major cause of puerperal intensive care unit admission, accounting for up to 10% of maternal deaths. PE-E primary prevention is possible. Antepartum low-dose aspirin prophylaxis, costing USD $10–24 can cut the incidence of PE-E in half. Antepartum low molecular weight heparin combined with low-dose aspirin prophylaxis can cut the incidence of early onset PE-E and fetuses that are small for their gestational age in half. Despite predictive antepartum models for PE-E prophylaxis, said prophylaxis is not routinely provided. Therefore, magnesium sulfate secondary prevention of eclampsia remains the globally recommended intervention. Implementation of a PE-E checklist is a continuous quality improvement (CQI) tool facilitating appropriate antepartum PE-E prophylaxis and maternal care from the first trimester through the postpartum fourth trimester inter-partum interval. A novel clinical PE-E checklist and implementation strategy are presented below. CQI PE-E checklist implementation and appropriate PE-E prophylaxis provides clinicians and healthcare systems an opportunity to achieve Millennium Development Goals 4 and 5, reducing child mortality and improving maternal health. While CQI checklist implementation may be a tedious ongoing process requiring healthcare team resiliency, improved healthcare outcomes are well worth the effort. PMID:27417614

  3. To err is human: supporting the patient care provider in the aftermath of an unanticipated adverse clinical outcome.

    PubMed

    Devencenzi, Tony; O'Keefe, Jerry

    2006-01-01

    This article will detail how the Kaiser Permanente Healthcare Organization responded to the 2000 Institute of Medicine's report which cited statistics regarding patient safety and the cost and consequences of medical errors. It will then reveal the important role Kaiser Permanente's Employee and Physician Assistance Program serves in support of Kaiser's patient care providers who are working to reduce the medical errors that lead to adverse outcomes. While striving to increase patient safety, Kaiser Permanente's Responsible Reporting and Accountability Policy will be reviewed, with a primary focus on the components of the policy which describes how the Employee and Physician Assistance Program utilizes a model of support intended to maintain and restore the functioning and well-being of Kaiser Permanente's patient care providers.

  4. Acquired Activated Protein C Resistance, Thrombophilia and Adverse Pregnancy Outcomes: A Study Performed in an Irish Cohort of Pregnant Women

    PubMed Central

    Sedano-Balbás, Sara; Lyons, Mark; Cleary, Brendan; Murray, Margaret; Gaffney, Geraldine; Maher, Majella

    2011-01-01

    The combination of thrombophilia and pregnancy increases the risk of thrombosis and the potential for adverse outcomes during pregnancy. The most significant common inherited risk factor for thrombophilia is activated protein C resistance (APCR), a poor anticoagulant response of APC in haemostasis, which is mainly caused by an inherited single-nucleotide polymorphism (SNP), factor V G1691A (FV Leiden) (FVL), referred as inherited APCR. Changes in the levels of coagulation factors: FV, FVIII, and FIX, and anticoagulant factors: protein S (PS) and protein C (PC) can alter APC function causing acquired APCR. Prothrombin G20210A and methylenetetrahydrofolate reductase (MTHFR) C677T are prothrombotic SNPs which in association with APCR can also increase the risk of thrombosis amongst Caucasians. In this study, a correlation between an acquired APCR phenotype and increased levels of factors V, VIII, and IX was demonstrated. Thrombophilic mutations amongst our acquired APCR pregnant women cohort are relatively common but do not appear to exert a severe undue adverse effect on pregnancy. PMID:21869933

  5. A State of Double Jeopardy: Impact of Prenatal Alcohol Exposure and Adverse Environments on the Social Communicative Abilities of School-Age Children with Fetal Alcohol Spectrum Disorder

    ERIC Educational Resources Information Center

    Coggins, Truman E.; Timler, Geralyn R.; Olswang, Lesley B.

    2007-01-01

    Purpose: This article is a retrospective examination of environmental risk, language performance, and narrative discourse data from a clinical database of school-age children with fetal alcohol spectrum disorder (FASD). Method: A case-defined diagnostic approach for measuring and reporting the full spectrum of disabilities in children with…

  6. Women participating in a web-based preconception study have a high prevalence of risk factors for adverse pregnancy outcomes

    PubMed Central

    2014-01-01

    Background Adverse pregnancy outcomes (APOs) can be increased by preconception risk factors and lifestyles. We measured the prevalence of preconception risk factors for APOs in a population of Italian women of childbearing age enrolled in a web-based