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Sample records for adverse fetal outcome

  1. Acidosis: A potential explanation for adverse fetal outcome in intrahepatic cholestasis of pregnancy. A case report

    PubMed Central

    Visser, W; Smit, LS; Cornette, J

    2014-01-01

    Background Intrahepatic cholestasis of pregnancy is a cholestatic disorder with an increased risk for adverse perinatal outcome. The mechanism underlying intrauterine demise is poorly understood. Case A nulliparous woman with gestational age of 36 plus 6 weeks presented with suspected intrahepatic cholestasis. Continuous CTG monitoring evolved from a normal pattern towards a non-reassuring pattern. A male neonate was delivered by caesarean section. Apgar scores 0, 1 and 4 at 1, 5 and 10 min. Fetal cord gas analysis showed pH 6.98, base deficit –15 mmol/L. Blood results showed maternal serum bile acid concentration of 220 µmol/L. Conclusion Our case suggests gradual evolution towards hypoxia and acidosis. It is unknown whether certain components in the bile acid concentrations might contribute to a fetal metabolic component of the acidosis.

  2. [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. PMID:22819781

  3. Ondansetron in pregnancy and risk of adverse fetal outcomes in the United States.

    PubMed

    Fejzo, Marlena S; MacGibbon, Kimber W; Mullin, Patrick M

    2016-07-01

    This is an analysis of fetal outcome in pregnancies exposed to ondansetron to treat Hyperemesis Gravidarum (HG). In this retrospective cohort study, U.S. data on outcome were collected on 1070 pregnancies exposed to ondansetron and compared to outcomes in two control groups: 771 pregnancies in women with a history of HG with no ondansetron exposure and 1555 pregnancies with neither a history of HG nor ondansetron exposure. Ventricular septal defects were reported in 2/952 of infants in the HG/Ondansetron-exposure group and 4/1286 in the No HG/No Ondansetron-exposure group. Cleft palate was reported in 1/952 live births in the HG/Ondansetron and 2/1286 in the No HG/No Ondansetron-exposure groups. Women with a history of HG who took ondansetron reported less miscarriages and terminations, and higher live birth rates. The overall results do not support evidence of teratogenicity of ondansetron. PMID:27151373

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

    PubMed

    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

  5. 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

  6. 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

  7. 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

  8. 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.

    PubMed

    Furr, Johnathan R; Lambright, Christy S; Wilson, Vickie S; Foster, Paul M; Gray, Leon E

    2014-08-01

    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 used to screen chemicals that produce adverse developmental outcomes via disruption of the androgen synthesis pathway more rapidly and efficiently, and with fewer animals than a postnatal one-generation study. Pregnant rats were dosed from gestational day (GD) 14 to 18 at one dose level with one of 27 chemicals including PEs, PE alternatives, pesticides known to inhibit steroidogenesis, an estrogen and a potent PPARα agonist and ex vivo testis testosterone production (T Prod) was measured on GD 18. We also included some chemicals with "unknown" activity including DMEP, DHeP, DHEH, DPHCH, DAP, TOTM, tetrabromo-diethyl hexyl phthalate (BrDEHP), and a relatively potent environmental estrogen BPAF. Dose-response studies also were conducted with this protocol with 11 of the above chemicals to determine their relative potencies. CD-1 mice also were exposed to varying dose levels of DPeP from GD 13 to 17 to determine if DPeP reduced T Prod in this species since there is a discrepancy among the results of in utero studies of PEs in mice. Compared to the known male reproductive effects of the PEs in rats the FPS correctly identified all known "positives" and "negatives" tested. Seven of eight "unknowns" tested were "negatives", they did not reduce T Prod, whereas DAP produced an "equivocal" response. Finally, a dose-response study with DPeP in CD-1 mice revealed that fetal T Prod can be inhibited by exposure to a PE in utero in this species, but at a higher dose level than required in rats.Key words. Phthalate Syndrome, Fetal endocrine biomarkers, Phthalate adverse outcome pathway, testosterone production, fetal rat testis. PMID:24798384

  9. Adverse Fetal and Neonatal Outcomes Associated with a Life-Long High Fat Diet: Role of Altered Development of the Placental Vasculature

    PubMed Central

    Petrik, Jim J.; Storozhuk, Yaryna; Paez-Parent, Sabrina; Dai, Qin; Samjoo, Imtiaz A.; Mansell, Margaret; Gruslin, Andree; Holloway, Alison C.; Raha, Sandeep

    2012-01-01

    Maternal obesity results in a number of obstetrical and fetal complications with both immediate and long-term consequences. The increased prevalence of obesity has resulted in increasing numbers of women of reproductive age in this high-risk group. Since many of these obese women have been subjected to hypercaloric diets from early childhood we have developed a rodent model of life-long maternal obesity to more clearly understand the mechanisms that contribute to adverse pregnancy outcomes in obese women. Female Sprague Dawley rats were fed a control diet (CON - 16% of calories from fat) or high fat diet (HF - 45% of calories from fat) from 3 to 19 weeks of age. Prior to pregnancy HF-fed dams exhibited significant increases in body fat, serum leptin and triglycerides. A subset of dams was sacrificed at gestational day 15 to evaluate fetal and placental development. The remaining animals were allowed to deliver normally. HF-fed dams exhibited a more than 3-fold increase in fetal death and decreased neonatal survival. These outcomes were associated with altered vascular development in the placenta, as well as increased hypoxia in the labyrinth. We propose that the altered placental vasculature may result in reduced oxygenation of the fetal tissues contributing to premature demise and poor neonatal survival. PMID:22442686

  10. Cerebroplacental ratio in prediction of adverse perinatal outcome and fetal heart rate disturbances in uncomplicated pregnancy at 40 weeks and beyond

    PubMed Central

    Korbelak, Tomasz; Świder-Musielak, Joanna; Breborowicz, Grzegorz

    2015-01-01

    Introduction The aim of the study was to determine the usefulness of Doppler velocimetry, based on cerebroplacental ratio (C/U) evaluation, in predicting intrapartum fetal heart rate abnormalities and adverse neonatal outcome in uncomplicated pregnancies at 40 weeks and beyond. Material and methods One hundred and forty-eight women in uncomplicated pregnancies, between 40 and 42 completed weeks, were divided into control and study groups: with the absence (n = 79) and with the presence of a fetal brain-sparing effect (n = 69), respectively. Pulsatility and resistance indices in the middle cerebral, the umbilical artery and the C/U ratio were evaluated daily by Doppler ultrasonography. C/U < 1.1 was reported as suggestive of a brain-sparing effect. Abnormal flow indices were analyzed and compared to adverse pregnancy and neonatal outcome determinants. Results In the abnormal C/U group the abnormal CTG records were significantly more frequently observed (62.3%) than in normal C/U group (19.0%) (p = 0.0001). The comparison of selected Doppler indices revealed that C/U showed the highest sensitivity in prediction of both the intrapartum abnormal FHR (74.1%) and the adverse neonatal outcome (87.8%). Conclusions The C/U index shows the highest sensitivity in prediction of FHR abnormalities and adverse neonatal outcome in uncomplicated pregnancies at 40 weeks and beyond. The C/U index is useful in clinical practice in antenatal monitoring of these women in order to select those at high risk of intra- and postpartum complications. PMID:25861301

  11. 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

  12. 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

    PubMed Central

    Wilson, Vickie S.; Foster, Paul M.; Gray, Leon E.

    2014-01-01

    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 used to screen chemicals that produce adverse developmental outcomes via disruption of the androgen synthesis pathway more rapidly and efficiently, and with fewer animals than a postnatal one-generation study. Pregnant rats were dosed from gestational day (GD) 14 to 18 at one dose level with one of 27 chemicals including PEs, PE alternatives, pesticides known to inhibit steroidogenesis, an estrogen and a potent PPARα agonist and ex vivo testis testosterone production (T Prod) was measured on GD 18. We also included some chemicals with “unknown” activity including DMEP, DHeP, DHEH, DPHCH, DAP, TOTM, tetrabromo-diethyl hexyl phthalate (BrDEHP), and a relatively potent environmental estrogen BPAF. Dose-response studies also were conducted with this protocol with 11 of the above chemicals to determine their relative potencies. CD-1 mice also were exposed to varying dose levels of DPeP from GD 13 to 17 to determine if DPeP reduced T Prod in this species since there is a discrepancy among the results of in utero studies of PEs in mice. Compared to the known male reproductive effects of the PEs in rats the FPS correctly identified all known “positives” and “negatives” tested. Seven of eight “unknowns” tested were “negatives”, they did not reduce T Prod, whereas DAP produced an “equivocal” response. Finally, a dose-response study with DPeP in CD-1 mice revealed that fetal T Prod can be inhibited by exposure to a PE in utero in this species, but at a higher dose level than required in rats.Key words. Phthalate Syndrome, Fetal endocrine biomarkers, Phthalate adverse outcome pathway, testosterone production, fetal rat testis. PMID:24798384

  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. 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. PMID:25802092

  15. 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

  16. 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 ...

  17. Adverse Pregnancy Outcomes after Abnormal First Trimester Screening for Aneuploidy

    PubMed Central

    Goetzl, Laura

    2010-01-01

    Women with abnormal first trimester screening but with a normal karyotype are at risk for adverse pregnancy outcomes. A nuchal translucency >3.5mm is associated with an increased risk of subsequent pregnancy loss, fetal infection, fetal heart abnormalities and other structural abnormalities. Abnormal first trimester analytes are also associated with adverse pregnancy outcomes but the predictive value is less impressive. As a single marker, PAPP-A <1st%ile has a good predictive value for subsequent fetal growth restriction. Women with PAPP-A<5th%ile should undergo subsequent risk assessment with routine MSAFP screening with the possible addition of uterine artery PI assessment in the midtrimester. PMID:20638576

  18. 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. PMID:23887100

  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. Placental Features of Late-Onset Adverse Pregnancy Outcome

    PubMed Central

    Higgins, Lucy E.; Wareing, Mark; Greenwood, Susan L.; Jones, Rebecca L.; Sibley, Colin P.; Johnstone, Edward D.; Heazell, Alexander E. P.

    2015-01-01

    Objective Currently, no investigations reliably identify placental dysfunction in late pregnancy. To facilitate the development of such investigations we aimed to identify placental features that differ between normal and adverse outcome in late pregnancy in a group of pregnancies with reduced fetal movement. Methods Following third trimester presentation with reduced fetal movement (N = 100), placental structure ex vivo was measured. Placental function was then assessed in terms of (i) chorionic plate artery agonist responses and length-tension characteristics using wire myography and (ii) production and release of placentally derived hormones (by quantitative polymerase chain reaction and enzyme linked immunosorbant assay of villous tissue and explant conditioned culture medium). Results Placentas from pregnancies ending in adverse outcome (N = 23) were ~25% smaller in weight, volume, length, width and disc area (all p<0.0001) compared with those from normal outcome pregnancies. Villous and trophoblast areas were unchanged, but villous vascularity was reduced (median (interquartile range): adverse outcome 10 (10–12) vessels/mm2 vs. normal outcome 13 (12–15), p = 0.002). Adverse outcome pregnancy placental arteries were relatively insensitive to nitric oxide donated by sodium nitroprusside compared to normal outcome pregnancy placental arteries (50% Effective Concentration 30 (19–50) nM vs. 12 (6–24), p = 0.02). Adverse outcome pregnancy placental tissue contained less human chorionic gonadotrophin (20 (11–50) vs. 55 (24–102) mIU/mg, p = 0.007) and human placental lactogen (11 (6–14) vs. 27 (9–50) mg/mg, p = 0.006) and released more soluble fms-like tyrosine kinase-1 (21 (13–29) vs. 5 (2–15) ng/mg, p = 0.01) compared with normal outcome pregnancy placental tissue. Conclusion These data provide a description of the placental phenotype of adverse outcome in late pregnancy. Antenatal tests that accurately reflect elements of this phenotype may

  1. 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...

  2. 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

  3. 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...

  4. 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...

  5. 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.

  6. Mycoplasma, Ureaplasma, and Adverse Pregnancy Outcomes: A Fresh Look

    PubMed Central

    Larsen, Bryan; Hwang, Joseph

    2010-01-01

    Recent work on the Molicutes that associate with genital tract tissues focuses on four species that may be of interest in potential maternal, fetal, and neonatal infection and in contributing to adverse pregnancy outcomes. Mycoplasma hominis and Ureaplasma urealyticum have historically been the subject of attention, but Mycoplasma genitalis which causes male urethritis in addition to colonizing the female genital tract and the division of Ureaplasma into two species, urealyticum and parvum, has also added new taxonomic clarity. The role of these genital tract inhabitants in infection during pregnancy and their ability to invade and infect placental and fetal tissue is discussed. In particular, the role of some of these organisms in prematurity may be mechanistically related to their ability to induce inflammatory cytokines, thereby triggering pathways leading to preterm labor. A review of this intensifying exploration of the mycoplasmas in relation to pregnancy yields several questions which will be important to examine in future research. PMID:20706675

  7. 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

  8. 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...

  9. 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...

  10. Maternal Serum Screening Markers and Adverse Outcome: A New Perspective

    PubMed Central

    Krantz, David; Hallahan, Terrence; Janik, David; Carmichael, Jonathan

    2014-01-01

    There have been a number of studies evaluating the association of aneuploidy serum markers with adverse pregnancy outcome. More recently, the development of potential treatments for these adverse outcomes as well as the introduction of cell-free fetal DNA (cffDNA) screening for aneuploidy necessitates a re-evaluation of the benefit of serum markers in the identification of adverse outcomes. Analysis of the literature indicates that the serum markers tend to perform better in identifying pregnancies at risk for the more severe but less frequent form of individual pregnancy complications rather than the more frequent but milder forms of the condition. As a result, studies which evaluate the association of biomarkers with a broad definition of a given condition may underestimate the ability of such markers to identify pregnancies that are destined to develop the more severe form of the condition. Consideration of general population screening using cffDNA solely must be weighed against the fact that traditional screening using serum markers enables detection of severe pregnancy complications, not detectable with cffDNA, of which many may be amenable to treatment options. PMID:26237472

  11. Maternal Serum Screening Markers and Adverse Outcome: A New Perspective.

    PubMed

    Krantz, David; Hallahan, Terrence; Janik, David; Carmichael, Jonathan

    2014-01-01

    There have been a number of studies evaluating the association of aneuploidy serum markers with adverse pregnancy outcome. More recently, the development of potential treatments for these adverse outcomes as well as the introduction of cell-free fetal DNA (cffDNA) screening for aneuploidy necessitates a re-evaluation of the benefit of serum markers in the identification of adverse outcomes. Analysis of the literature indicates that the serum markers tend to perform better in identifying pregnancies at risk for the more severe but less frequent form of individual pregnancy complications rather than the more frequent but milder forms of the condition. As a result, studies which evaluate the association of biomarkers with a broad definition of a given condition may underestimate the ability of such markers to identify pregnancies that are destined to develop the more severe form of the condition. Consideration of general population screening using cffDNA solely must be weighed against the fact that traditional screening using serum markers enables detection of severe pregnancy complications, not detectable with cffDNA, of which many may be amenable to treatment options. PMID:26237472

  12. Fetal and neonatal outcome in celiac disease.

    PubMed

    Suciu, Nicolae; Pop, Liviu; Panaitescu, Eugenia; Suciu, Ioan Dumitru; Popp, Alina; Anca, Ioana

    2014-05-01

    Celiac disease (CD) is characterized by an abnormal immune response in susceptible individuals to dietary gluten derived from wheat, rye and barley. The disease affects not only the small bowel mucosa, but also many other extraintestinal organs resulting bone, liver, neurologic, skin and reproductive system disorders. The details of the pathogenic mechanism are not perfectly clear yet, but it is now proved that both humoral and cellular immune responses are triggered and autoimmune mechanisms are implicated. Studies have shown association of different pregnancy outcomes with maternal celiac disease. In this review, the most frequent fetal and neonatal outcome related to CD are presented, with a special focus on intrautherine growth restriction (IUGR) and prematurity. The need of active case finding of CD is discussed. PMID:23998909

  13. MARKERS OF INDIVIDUAL SUSCEPTIBILITY AND OUTCOME RELATED TO FETAL AND INFANT GROWTH AND DEVELOPMENT

    EPA Science Inventory

    To evaluate whether exposures to environmental toxins and psychological stress were related to impaired fetal growth or other adverse pregnancy outcomes, we established a prospective epidemiologic study of 187 women who were pregnant and at or near the World Trade Center (...

  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. Adverse Pregnancy Outcomes Following Motor Vehicle Crashes

    PubMed Central

    Vladutiu, Catherine J.; Marshall, Stephen W.; Poole, Charles; Casteel, Carri; Menard, M. Kathryn; Weiss, Harold B.

    2013-01-01

    Background Motor vehicle crashes are a leading cause of serious trauma during pregnancy, but little is known about their relationships with pregnancy outcomes. Purpose To estimate the association between motor vehicle crashes and adverse pregnancy outcomes. Methods A retrospective cohort study of 878,546 pregnant women, aged 16–46 years, who delivered a singleton infant in North Carolina (NC) from 2001 to 2008. Pregnant drivers in crashes were identified by probabilistic linkage of vital records and crash reports. Poisson regression modeled the association among crashes, vehicle safety features, and adverse pregnancy outcomes. Analyses were conducted in 2012. Results In 2001–2008, 2.9% of pregnant NC women were drivers in one or more crashes. After a single crash, compared to not being in a crash, pregnant drivers had slightly elevated rates of preterm birth (adjusted rate ratio, aRR=1.23, 95% CI=1.19, 1.28); placental abruption (aRR=1.34, 95% CI=1.15, 1.56); and premature rupture of the membranes (PROM; aRR=1.32, 95% CI=1.21, 1.43). Following a second or subsequent crash, pregnant drivers had more highly elevated rates of preterm birth (aRR=1.54, 95% CI=1.24, 1.90); stillbirth (aRR=4.82, 95% CI=2.85, 8.14); placental abruption (aRR=2.97, 95% CI=1.60, 5.53); and PROM (aRR=1.95, 95% CI=1.27, 2.99). Stillbirth rates were elevated following crashes involving unbelted pregnant drivers (aRR=2.77, 95% CI=1.22, 6.28) compared to belted pregnant drivers. Conclusions Crashes while driving during pregnancy were associated with elevated rates of adverse pregnancy outcomes, and multiple crashes were associated with even higher rates of adverse pregnancy outcomes. Crashes were especially harmful if drivers were unbelted. PMID:24139777

  16. Adverse blood transfusion outcomes: establishing causation.

    PubMed

    Isbister, James P; Shander, Aryeh; Spahn, Donat R; Erhard, Jochen; Farmer, Shannon L; Hofmann, Axel

    2011-04-01

    The transfusion of allogeneic red blood cells (RBCs) and other blood components is ingrained in modern medical practice. The rationale for administering transfusions is based on key assumptions that efficacy is established and risks are acceptable and minimized. Despite the cliché that, "the blood supply is safer than ever," data about risks and lack of efficacy of RBC transfusions in several clinical settings have steadily accumulated. Frequentist statisticians and clinicians demand evidence from randomized clinical trials (RCTs); however, causation for the recognized serious hazards of allogeneic transfusion has never been established in this manner. On the other hand, the preponderance of evidence implicating RBC transfusions in adverse clinical outcomes related to immunomodulation and the storage lesion comes from observational studies, and a broad and critical analysis to evaluate causation is overdue. It is suggested in several circumstances that this cannot wait for the design, execution, and conduct of rigorous RCTs. We begin by examining the nature and definition of causation with relevant examples from transfusion medicine. Deductive deterministic methods may be applied to most of the well-accepted and understood serious hazards of transfusion, with modified Koch's postulates being fulfilled in most circumstances. On the other hand, when several possible interacting risk factors exist and RBC transfusions are associated with adverse clinical outcomes, establishing causation requires inferential probabilistic methodology. In the latter circumstances, the case for RBC transfusions being causal for adverse clinical outcomes can be strengthened by applying modified Bradford Hill criteria to the plethora of existing observational studies. This being the case, a greater precautionary approach to RBC transfusion is necessary and equipoise that justifying RCTs may become problematic. PMID:21345639

  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 (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...

  20. 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

  1. Fetal outcome in murine Lyme disease.

    PubMed

    Silver, R M; Yang, L; Daynes, R A; Branch, D W; Salafia, C M; Weis, J J

    1995-01-01

    Lyme disease is an inflammatory syndrome caused by infection with Borrelia burgdorferi. Although this syndrome has important implications for human pregnancy, little is known about gestational infection with B. burgdorferi. Fetal death occurred in 33 of 280 gestational sacs (12%) in 39 C3H/HeN female mice infected by intradermal injection of B. burgdorferi 4 days after mating (acute infection), compared with 0 of 191 sacs in 25 control mice (P = 0.0001). Forty-six percent of acutely infected mice suffered at least one fetal death, compared with none of the control animals (P = 0.0002). There were no fetal deaths in 18 C3H/HeN mice infected 3 weeks prior to mating (chronic infection). A sensitive PCR technique detected B. burgdorferi DNA in the uteri of acutely infected mice but did not detect DNA in the uteri of controls or chronically infected mice. Spirochete DNA was only rarely detected in fetal tissues, and its presence was not required for fetal death. The inclusion of an internal competitive PCR target indicated that the lack of B. burgdorferi sequences in fetal DNA was not due to the presence of a PCR inhibitor. Histologic analysis of gestational tissues from infected animals demonstrated nonspecific pathology consistent with fetal death. These findings indicate an association between murine fetal death and acute infection with B. burgdorferi early in gestation but not with chronic infection. Our data suggest that fetal death is due to a maternal response to infection rather than fetal infection. These findings could provide an explanation for observations in humans in which sporadic cases of fetal death in women infected with B. burgdorferi during pregnancy have been reported, while previous infection has not been associated with fetal death. PMID:7806385

  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. Early Childhood Adversity and Pregnancy Outcomes.

    PubMed

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

    2016-04-01

    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

  4. Azathioprine during pregnancy in systemic lupus erythematosus patients is not associated with poor fetal outcome.

    PubMed

    Saavedra, Miguel Ángel; Sánchez, Antonio; Morales, Sara; Ángeles, Ulises; Jara, Luis Javier

    2015-07-01

    The objective of this study was to evaluate the risk of adverse fetal outcome in systemic lupus erythematosus (SLE) women exposed to azathioprine during pregnancy. We reviewed the medical records of SLE pregnant women followed from January 2005 to April 2013. The patients were evaluated at least once in each trimester and postpartum. Relevant fetal outcomes were extracted, such as rate of liveborns, fetal loss (spontaneous abortion and stillbirth), term delivery, preterm birth, neonatal death, low birth weight, low birth weight at term, and congenital malformations. A detailed history of drug use during pregnancy was obtained. We studied 178 pregnancies (in 172 women), 87 of them were exposed to azathioprine (AZA-group) and the remaining 91 were not exposed (NO AZA-group). Exposure to other drugs was similar in both groups. The rate of live births, spontaneous abortions mean birth weight, weeks of gestation, rate of birth weight <2500 g, and low birth weight at term did not differ between groups. No infant had major congenital abnormalities. Multivariate analysis showed that preeclampsia, premature rupture of membranes (PROM), lupus flare, and anti-DNA positive were associated with an increased risk of poor fetal outcome. Our study suggests that the use of azathioprine is safe and lacks of teratogenity in patients with SLE and pregnancy. Exposure to azathioprine during pregnancy is not associated with poor fetal outcome. PMID:26050103

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

    PubMed Central

    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

  6. Sequential analysis of uncommon adverse outcomes.

    PubMed

    Morton, A; Mengersen, K; Waterhouse, M; Steiner, S; Looke, D

    2010-10-01

    Sequential analysis of uncommon adverse outcomes (AEs) such as surgical site infections (SSIs) is desirable. Short postoperative lengths of stay (LOS) result in many SSIs occurring after discharge and they are often superficial. Deep and organ space (complex) SSIs occur less frequently but are detected more reliably and are suitable for monitoring wound care. Those occurring post-discharge usually require readmissison and can be counted accurately. Sequential analysis of meticillin-resistant Staphylococcus aureus bacteraemia is also needed. The key to prevention is to implement systems based on evidence, e.g. using 'bundles' and checklists. Regular mortality and morbidity audit meetings are required and these may need to be followed by independent audits. Sequential statistical analysis is desirable for data presentation, to detect changes, and to discourage tampering with processes when occasional AEs occur in a reliable system. Tabulations and cumulative observed minus expected (O-E) charts and funnel plots are valuable, supplemented in the presence of apparent 'runs' of AEs by cumulative sum analysis. Used prospectively, they may enable staff to visualise and detect patterns or shifts in rates and counts that might not otherwise be apparent. PMID:20656377

  7. 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

  8. 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

  9. 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.

  10. Development of a Screening Tool for Predicting Adverse Outcomes of Gestational Diabetes Mellitus

    PubMed Central

    Park, Jee Soo; Kim, Deok Won; Kwon, Ja-Young; Park, Yong Won; Kim, Young Han; Cho, Hee Young

    2016-01-01

    Abstract Gestational diabetes mellitus (GDM) is a common disease in pregnancy causing maternal and fetal complications. To prevent these adverse outcomes, optimal screening and diagnostic criteria must be adequate, timely, and efficient. This study suggests a novel approach that is practical, efficient, and patient- and clinician-friendly in predicting adverse outcomes of GDM. The authors conducted a retrospective cohort study via medical record review of patients admitted between March 2001 and April 2013 at the Severance Hospital, Seoul, South Korea. Patients diagnosed by a conventional 2-step method were evaluated according to the presence of adverse outcomes (neonatal hypoglycemia, hyperbilirubinemia, and hyperinsulinemia; admission to the neonatal intensive care unit; large for gestational age; gestational insulin therapy; and gestational hypertension). Of 802 women who had an abnormal 50-g, 1-hour glucose challenge test, 306 were diagnosed with GDM and 496 did not have GDM (false-positive group). In the GDM group, 218 women (71.2%) had adverse outcomes. In contrast, 240 women (48.4%) in the false-positive group had adverse outcomes. Women with adverse outcomes had a significantly higher body mass index (BMI) at entry (P = 0.03) and fasting blood glucose (FBG) (P = 0.03). Our logistic regression model derived from 2 variables, BMI at entry and FBG, predicted GDM adverse outcome with an area under the curve of 0.642, accuracy of 61.3%, sensitivity of 57.2%, and specificity of 66.9% compared with the conventional 2-step method with an area under the curve of 0.610, accuracy of 59.1%, sensitivity of 47.6%, and specificity of 74.4%. Our model performed better in predicting GDM adverse outcomes than the conventional 2-step method using only BMI at entry and FBG. Moreover, our model represents a practical, inexpensive, efficient, reproducible, easy, and patient- and clinician-friendly approach. PMID:26735528

  11. 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...

  12. Intimate Partner Violence, PTSD, and Adverse Health Outcomes

    ERIC Educational Resources Information Center

    Dutton, Mary Ann; Green, Bonnie L.; Kaltman, Stacey I.; Roesch, Darren M.; Zeffiro, Thomas A.; Krause, Elizabeth D.

    2006-01-01

    The high prevalence of adverse health outcomes related to intimate partner violence (IPV) is well documented. Yet we know little about the pathways that lead to adverse health outcomes. Research concerning the psychological, biological, neurological, behavioral, and physiological alterations following exposure to IPV--many of which are associated…

  13. 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

  14. 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

  15. Sleep Disordered Breathing and Adverse Pregnancy Outcomes.

    PubMed

    Cain, Mary Ashley; Louis, Judette M

    2016-06-01

    Sleep disordered breathing (SDB) occurs in 0.6% to 15% of reproductive-aged women. Because of an overlap in symptoms of SDB and normal pregnancy findings, the diagnosis of SDB in pregnancy is challenging. The repetitive arousals, sleep fragmentation, and hypoxias experienced by patients with SDB lead to an increase in oxidative stress and inflammation. In the nonpregnant population SDB is associated with an increased risk of diabetes mellitus, heart disease, and stroke. Increasing evidence identifies an association between SDB in pregnancy and gestational diabetes, preeclampsia, and fetal growth abnormalities. PMID:27235923

  16. 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

  17. 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

  18. 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

  19. Adverse neonatal outcomes in women with pre-eclampsia in Mulago Hospital, Kampala, Uganda: a cross-sectional study

    PubMed Central

    Kiondo, Paul; Tumwesigye, Nazarius Mbona; Wandabwa, Julius; Wamuyu-Maina, Gakenia; Bimenya, Gabriel S; Okong, Pius

    2014-01-01

    Introduction Pre-eclampsia, which is more prevalent in resource-limited settings, contributes significantly to maternal, fetal and neonatal morbidity and mortality. However, the factors associated with these adverse outcomes are poorly understood in low resource settings. In this paper we examine the risk factors for adverse neonatal outcomes among women with pre-eclampsia at Mulago Hospital in Kampala, Uganda. Methods Pre-eclampsia, which is more prevalent in resource-limited settings, contributes significantly to maternal, fetal and neonatal morbidity and mortality. However, the factors associated with these adverse outcomes are poorly understood in low resource settings. In this paper we examine the risk factors for adverse neonatal outcomes among women with pre-eclampsia at Mulago Hospital in Kampala, Uganda. Resuls Predictors of adverse neonatal outcomes were: preterm delivery (OR 5.97, 95% CI: 2.97-12.7) and severe pre-eclampsia (OR 5.17, 95% CI: 2.36-11.3). Conclusion Predictors of adverse neonatal outcomes among women with pre-eclampsia were preterm delivery and severe pre-eclampsia. Health workers need to identify women at risk, offer them counseling and, refer them if necessary to a hospital where they can be managed successfully. This may in turn reduce the neonatal morbidity and mortality associated with pre-eclampsia. PMID:24643210

  20. 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...

  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. 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...

  3. Kinetics of Betamethasone and Fetal Cardiovascular Adverse Effects in Pregnant Sheep After Different Doses

    PubMed Central

    Schwab, Matthias; Coksaygan, Turhan; Samtani, Mahesh N.; Jusko, William J.; Nathanielsz, Peter W.

    2014-01-01

    OBJECTIVE To study the pharmacokinetics of different betamethasone doses and preparations used to enhance fetal lung maturation in the maternal and fetal circulation of sheep and the adverse effects on fetal blood pressure. METHODS Doses of 170 (n = 6) and 110 µg/kg (n = 6) betamethasone phosphate equivalent to 12 or 8mg, respectively, administered to a 70kg pregnant woman or 170 µg/kg (n = 6) of a depot formulation (50% betamethasone phosphate and 50% betamethasone acetate) were injected intramuscularly to chronically instrumented pregnant sheep. RESULTS Both betamethasone preparations produced highest maternal concentrations after 15 min followed by an exponential decline with a t1/2 of about 3 hours. The drug fell below the limit of detection at 8 to 12 hours. Betamethasone was first detectable in the fetal circulation at 1 hour, peaked at 3 hours, and decreased below the limit of detection at 8 hours independently of the dose or preparation. Maternal and fetal betamethasone concentrations achieved with the phosphate and acetate formulation were one half of those obtained with betamethasone phosphate, suggesting that very little betamethasone is released from the acetate within the first 8 hours when the effect on lung maturation is needed. Betamethasone led to a maximal increase of mean fetal blood pressure from 42 ± 1 to 51 ± 1 mm Hg (P<.05) and did not differ between the doses and preparations, although plasma concentrations showed a clear dose–concentration relationship. CONCLUSION The doses of betamethasone used in obstetrics are supramaximal in terms of cardiovascular effects in sheep. Risk-benefit studies are needed to find the effective steroid dose with the least adverse effects. PMID:16946223

  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. The epidemiology of disasters and adverse reproductive outcomes: lessons learned.

    PubMed

    Cordero, J F

    1993-07-01

    A disaster has been defined as a disruption of human ecology that exceeds the capacity of the community to function normally. Little is known about the adverse effects of natural disasters on reproductive outcomes. Important lessons can be derived from several disasters caused by human factors, such as the Minamata Bay disaster. Adverse reproductive outcomes include infertility, early pregnancy loss, stillbirths, congenital malformations, and serious developmental disabilities such as cerebral palsy and mental retardation. Recent disasters like the Chernobyl and Bhopal explosions have provided important lessons on the need for accurate and sound information about the risk of prenatal exposures for adverse reproductive outcomes. To study questions of adverse reproductive outcomes and disasters requires a well-planned approach. It should include early development of surveillance for adverse reproductive outcomes, analytic studies on the risk of disasters from direct and indirect effects, sensitive methods to measure early pregnancy loss, and long-term follow-up programs to assess outcomes such as developmental disabilities. PMID:8243383

  6. The epidemiology of disasters and adverse reproductive outcomes: lessons learned.

    PubMed Central

    Cordero, J F

    1993-01-01

    A disaster has been defined as a disruption of human ecology that exceeds the capacity of the community to function normally. Little is known about the adverse effects of natural disasters on reproductive outcomes. Important lessons can be derived from several disasters caused by human factors, such as the Minamata Bay disaster. Adverse reproductive outcomes include infertility, early pregnancy loss, stillbirths, congenital malformations, and serious developmental disabilities such as cerebral palsy and mental retardation. Recent disasters like the Chernobyl and Bhopal explosions have provided important lessons on the need for accurate and sound information about the risk of prenatal exposures for adverse reproductive outcomes. To study questions of adverse reproductive outcomes and disasters requires a well-planned approach. It should include early development of surveillance for adverse reproductive outcomes, analytic studies on the risk of disasters from direct and indirect effects, sensitive methods to measure early pregnancy loss, and long-term follow-up programs to assess outcomes such as developmental disabilities. PMID:8243383

  7. 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

  8. 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

  9. 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). ...

  10. 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

  11. Modeling risk for severe adverse outcomes using angiogenic factor measurements in women with suspected preterm preeclampsia

    PubMed Central

    Palomaki, Glenn E; Haddow, James E; Haddow, Hamish R M; Salahuddin, Saira; Geahchan, Carl; Cerdeira, Ana Sofia; Verlohren, Stefan; Perschel, Frank H; Horowitz, Gary; Thadhani, Ravi; Karumanchi, S Ananth; Rana, Sarosh

    2015-01-01

    Introduction Preeclampsia (PE) is a pregnancy-specific syndrome associated with adverse maternal and fetal outcomes. Patient-specific risks based on angiogenic factors might better categorize those who might have a severe adverse outcome. Methods Women evaluated for suspected PE at a tertiary hospital (2009–2012) had pregnancy outcomes categorized as ‘referent’ or ‘severe’, based solely on maternal/fetal findings. Outcomes that may have been influenced by a PE diagnosis were considered ‘unclassified’. Soluble fms-like tyrosine kinase (sFlt1) and placental growth factor (PlGF) were subjected to bivariate discriminant modeling, allowing patient-specific risks to be assigned for severe outcomes. Results Three hundred twenty-eight singleton pregnancies presented at ≤34.0 weeks' gestation. sFlt1 and PlGF levels were adjusted for gestational age. Risks above 5 : 1 (10-fold over background) occurred in 77% of severe (95% CI 66 to 87%) and 0.7% of referent (95% CI <0.1 to 3.8%) outcomes. Positive likelihood ratios for the modeling and validation datasets were 19 (95% CI 6.2–58) and 15 (95% CI 5.8–40) fold, respectively. Conclusions This validated model assigns patient-specific risks of any severe outcome among women attending PE triage. In practice, women with high risks would receive close surveillance with the added potential for reducing unnecessary preterm deliveries among remaining women. © 2015 The Authors. Prenatal Diagnosis published by John Wiley & Sons Ltd. PMID:25641027

  12. 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

  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. Women, poverty and adverse maternal outcomes in Nairobi, Kenya

    PubMed Central

    2010-01-01

    Background The link between poverty and adverse maternal outcomes has been studied largely by means of quantitative data. We explore poor urban Kenyan women's views and lived experiences of the relationship between economic disadvantage and unpleasant maternal outcomes. Method Secondary analysis of focus group discussions and in-depth individual interviews data with women in two slums in Nairobi, Kenya. Results Urban poor women in Nairobi associate poverty with adverse maternal outcomes. However, their accounts and lived experiences of the impact of poverty on maternal outcomes underscore dynamics other than those typically stressed in the extant literature. To them, poverty primarily generates adverse maternal outcomes by exposing women to exceedingly hard and heavy workloads during pregnancy and the period surrounding it; to intimate partner violence; as well as to inhospitable and unpleasant treatment by service providers. Conclusions Poverty has wider and more intricate implications for maternal outcomes than are acknowledged in extant research. To deliver their expected impact, current efforts to promote better maternal outcomes must be guided by a more thorough perspective of the link between women's livelihoods and their health and wellbeing. PMID:21122118

  15. 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

  16. 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

  17. Placental DNA Methylation Related to Both Infant Toenail Mercury and Adverse Neurobehavioral Outcomes

    PubMed Central

    Maccani, Jennifer Z.J.; Koestler, Devin C.; Lester, Barry; Houseman, E. Andrés; Armstrong, David A.; Kelsey, Karl T.

    2015-01-01

    Background Prenatal mercury (Hg) exposure is associated with adverse child neurobehavioral outcomes. Because Hg can interfere with placental functioning and cross the placenta to target the fetal brain, prenatal Hg exposure can inhibit fetal growth and development directly and indirectly. Objectives We examined potential associations between prenatal Hg exposure assessed through infant toenail Hg, placental DNA methylation changes, and newborn neurobehavioral outcomes. Methods The methylation status of > 485,000 CpG loci was interrogated in 192 placental samples using Illumina’s Infinium HumanMethylation450 BeadArray. Hg concentrations were analyzed in toenail clippings from a subset of 41 infants; neurobehavior was assessed using the NICU Network Neurobehavioral Scales (NNNS) in an independent subset of 151 infants. Results We identified 339 loci with an average methylation difference > 0.125 between any two toenail Hg tertiles. Variation among these loci was subsequently found to be associated with a high-risk neurodevelopmental profile (omnibus p-value = 0.007) characterized by the NNNS. Ten loci had p < 0.01 for the association between methylation and the high-risk NNNS profile. Six of 10 loci reside in the EMID2 gene and were hypomethylated in the 16 high-risk profile infants’ placentas. Methylation at these loci was moderately correlated (correlation coefficients range, –0.33 to –0.45) with EMID2 expression. Conclusions EMID2 hypomethylation may represent a novel mechanism linking in utero Hg exposure and adverse infant neurobehavioral outcomes. Citation Maccani JZ, Koestler DC, Lester B, Houseman EA, Armstrong DA, Kelsey KT, Marsit CJ. 2015. Placental DNA methylation related to both infant toenail mercury and adverse neurobehavioral outcomes. Environ Health Perspect 123:723–729; http://dx.doi.org/10.1289/ehp.1408561 PMID:25748564

  18. 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...

  19. Thyroid-Disrupting Chemicals: Interpreting Upstream Biomarkers of Adverse Outcomes

    PubMed Central

    Miller, Mark D.; Crofton, Kevin M.; Rice, Deborah C.; Zoeller, R. Thomas

    2009-01-01

    Background There is increasing evidence in humans and in experimental animals for a relationship between exposure to specific environmental chemicals and perturbations in levels of critically important thyroid hormones (THs). Identification and proper interpretation of these relationships are required for accurate assessment of risk to public health. Objectives We review the role of TH in nervous system development and specific outcomes in adults, the impact of xenobiotics on thyroid signaling, the relationship between adverse outcomes of thyroid disruption and upstream causal biomarkers, and the societal implications of perturbations in thyroid signaling by xenobiotic chemicals. Data sources We drew on an extensive body of epidemiologic, toxicologic, and mechanistic studies. Data synthesis THs are critical for normal nervous system development, and decreased maternal TH levels are associated with adverse neuropsychological development in children. In adult humans, increased thyroid-stimulating hormone is associated with increased blood pressure and poorer blood lipid profiles, both risk factors for cardiovascular disease and death. These effects of thyroid suppression are observed even within the “normal” range for the population. Environmental chemicals may affect thyroid homeostasis by a number of mechanisms, and multiple chemicals have been identified that interfere with thyroid function by each of the identified mechanisms. Conclusions Individuals are potentially vulnerable to adverse effects as a consequence of exposure to thyroid-disrupting chemicals. Any degree of thyroid disruption that affects TH levels on a population basis should be considered a biomarker of adverse outcomes, which may have important societal outcomes. PMID:19654909

  20. 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...

  1. 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

  2. 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

  3. 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

  4. [Development and application of adverse outcome pathway in toxicology research].

    PubMed

    Wang, Yanhua; Duan, Huawei

    2015-12-01

    Adverse outcome pathway (AOP) was a conceptual construct that integrated existing knowledge concerning the pathway of causal linkages between a molecular initiating event (MIE) and a final adverse effect at individual or population levels. The AOP methodology could be used as a basis for effects extrapolation and was an approach towards providing a framework for collecting and evaluating relevant chemical, biological and toxicological information. The framework would play an important role in risk assessment. We reviewed the concept of AOP, the development and assessment of the framework and the established models in toxicology researches. And the prospects and challenges of its application in toxicology were also introduced. PMID:26887310

  5. Development of a Screening Tool for Predicting Adverse Outcomes of Gestational Diabetes Mellitus: A Retrospective Cohort Study.

    PubMed

    Park, Jee Soo; Kim, Deok Won; Kwon, Ja-Young; Park, Yong Won; Kim, Young Han; Cho, Hee Young

    2016-01-01

    Gestational diabetes mellitus (GDM) is a common disease in pregnancy causing maternal and fetal complications. To prevent these adverse outcomes, optimal screening and diagnostic criteria must be adequate, timely, and efficient. This study suggests a novel approach that is practical, efficient, and patient- and clinician-friendly in predicting adverse outcomes of GDM. The authors conducted a retrospective cohort study via medical record review of patients admitted between March 2001 and April 2013 at the Severance Hospital, Seoul, South Korea. Patients diagnosed by a conventional 2-step method were evaluated according to the presence of adverse outcomes (neonatal hypoglycemia, hyperbilirubinemia, and hyperinsulinemia; admission to the neonatal intensive care unit; large for gestational age; gestational insulin therapy; and gestational hypertension). Of 802 women who had an abnormal 50-g, 1-hour glucose challenge test, 306 were diagnosed with GDM and 496 did not have GDM (false-positive group). In the GDM group, 218 women (71.2%) had adverse outcomes. In contrast, 240 women (48.4%) in the false-positive group had adverse outcomes. Women with adverse outcomes had a significantly higher body mass index (BMI) at entry (P = 0.03) and fasting blood glucose (FBG) (P = 0.03). Our logistic regression model derived from 2 variables, BMI at entry and FBG, predicted GDM adverse outcome with an area under the curve of 0.642, accuracy of 61.3%, sensitivity of 57.2%, and specificity of 66.9% compared with the conventional 2-step method with an area under the curve of 0.610, accuracy of 59.1%, sensitivity of 47.6%, and specificity of 74.4%. Our model performed better in predicting GDM adverse outcomes than the conventional 2-step method using only BMI at entry and FBG. Moreover, our model represents a practical, inexpensive, efficient, reproducible, easy, and patient- and clinician-friendly approach. PMID:26735528

  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. The degree of fetal metformin exposure does not influence fetal outcome in gestational diabetes mellitus.

    PubMed

    Tertti, Kristiina; Laine, Kari; Ekblad, Ulla; Rinne, Valtteri; Rönnemaa, Tapani

    2014-10-01

    The purpose of the study was to examine in vivo placental transfer of metformin, its association with neonatal outcome in metformin-treated gestational diabetes (GDM) patients, and influence of metformin exposure on maternal glycemic control and weight gain. Two hundred and seventeen GDM patients were randomized to metformin or insulin in Turku University Hospital, Finland. Metformin concentrations were determined by mass spectrometry in maternal serum at 36 gestational weeks (gw) and at birth, and in umbilical cord blood. Main outcome measures were birth weight, gw at birth, umbilical artery pH and neonatal hypoglycemia, maternal weight gain, HbA1c and fructosamine concentration. Median umbilical cord/maternal serum metformin concentration ratio was 0.73. There were no differences in birth weight measured in grams or SD units (p = 0.49), or gw at birth (p always ≥0.49) between insulin- and metformin-treated patients stratified by trough metformin concentration tertiles measured at 36 gw. Rate of neonatal hypoglycemia (p = 0.92) and umbilical artery pH value (p = 0.78) was similar in insulin- and metformin-treated patients stratified by cord metformin concentration tertiles. Maternal glycemic control was similar in metformin concentration tertiles at 36 gw. Maternal weight gain was 223 g greater per week (p = 0.038) in the lowest metformin tertile compared to other tertiles combined. Maternal and fetal exposure to metformin is similar. Maternal or fetal metformin concentrations do not predict maternal glycemic control or neonatal outcome, but low maternal exposure may lead to greater maternal weight gain. PMID:24633859

  8. The adverse outcome pathway concept: a pragmatic tool in toxicology.

    PubMed

    Vinken, Mathieu

    2013-10-01

    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 critical toxicological effects that span over different layers of biological organization. AOPs share a common structure consisting of a molecular initiating event, a series of intermediate steps and key events, and an adverse outcome. Development of AOPs ideally complies with OECD guidelines. This also holds true for AOP evaluation, which includes consideration of the Bradford Hill criteria for weight-of-evidence assessment and meeting a set of key questions defined by the OECD. Elaborate AOP frameworks have yet been proposed for chemical-induced skin sensitization, cholestasis, liver fibrosis and liver steatosis. These newly postulated AOPs can serve a number of ubiquitous purposes, including the establishment of (quantitative) structure-activity relationships, the development of novel in vitro toxicity screening tests and the elaboration of prioritization strategies. PMID:23978457

  9. Factors associated with adverse clinical outcomes among obstetric trainees

    PubMed Central

    Aiken PhD, Catherine E.; Aiken, Abigail; Park, Hannah; Brockelsby, Jeremy C.; Prentice, Andrew

    2016-01-01

    Objective To determine whether UK obstetric trainees transitioning from directly to indirectly-supervised practice have a higher likelihood of adverse patient outcomes from operative deliveries compared to other indirectly supervised trainees and to examine whether performing more procedures under direct supervision is associated with fewer adverse outcomes in initial indirect practice. Methods We examined all deliveries (13,861) conducted by obstetricians at a single centre over 5 years (2008-2013). Mixed-effects logistic regression models were used to compare estimated blood loss, maternal trauma, umbilical arterial pH, delayed neonatal respiration, failed instrumental delivery, and critical incidents for trainees in their first indirectly-supervised year with trainees in all other years of indirect practice. Outcomes for trainees in their first indirectly-supervised 3 months were compared to their outcomes for the remainder of the year. Linear regression was used to examine the relationship between number of procedures performed under direct supervision and initial outcomes under indirect supervision. Results Trainees in their first indirectly-supervised year had a higher likelihood of >2 litres estimated blood loss at any delivery (OR 1.32;CI(1.01-1.64) p<0.05) and of failed instrumental delivery (OR 2.33;CI(1.37-3.29) p<0.05) compared with other indirectly-supervised trainees. Other measured outcomes showed no significant differences. Within the first three months of indirect supervision, the likelihood of operative vaginal deliveries with >1litre estimated blood loss (OR 2.54;CI(1.88-3.20) p<0.05) was higher compared to the remainder of the first year. Performing more deliveries under direct supervision prior to beginning indirectly-supervised training was associated with decreased risk of >1litre estimated blood loss (p<0.05). Conclusions Obstetric trainees in their first year of indirectly-supervised practice have a higher likelihood of immediate adverse

  10. Adverse Outcome Pathways and Drug-Induced Liver Injury Testing.

    PubMed

    Vinken, Mathieu

    2015-07-20

    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 review evaluates these constructs and simultaneously illustrates their use in the preclinical testing of drug-induced liver injury. PMID:26119269

  11. 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

  12. Adverse outcome pathways: From research to regulation scientific workshop report.

    PubMed

    Kleinstreuer, Nicole C; Sullivan, Kristie; Allen, David; Edwards, Stephen; Mendrick, Donna L; Embry, Michelle; Matheson, Joanna; Rowlands, J Craig; Munn, Sharon; Maull, Elizabeth; Casey, Warren

    2016-04-01

    An adverse outcome pathway (AOP) helps to organize 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 knowledge gaps where more research is needed to understand the underlying mechanisms, aid in chemical hazard characterization, and guide the development of new testing approaches that use fewer or no animals. A September 2014 workshop in Bethesda, Maryland considered how the AOP concept could improve regulatory assessments of chemical toxicity. Scientists from 21 countries, representing industry, academia, regulatory agencies, and special interest groups, attended the workshop, titled Adverse Outcome Pathways: From Research to Regulation. Workshop plenary presentations were followed by breakout sessions that considered regulatory acceptance of AOPs and AOP-based tools, criteria for building confidence in an AOP for regulatory use, and requirements to build quantitative AOPs and AOP networks. Discussions during the closing session emphasized a need to increase transparent and inclusive collaboration, especially with disciplines outside of toxicology. Additionally, to increase impact, working groups should be established to systematically prioritize and develop AOPs. Multiple collaborative projects and follow-up activities resulted from the workshop. PMID:26774756

  13. Renal function trajectory over time and adverse clinical outcomes.

    PubMed

    Sohel, Badrul Munir; Rumana, Nahid; Ohsawa, Masaki; Turin, Tanvir Chowdhury; Kelly, Martina Ann; Al Mamun, Mohammad

    2016-06-01

    The growing burden of chronic kidney disease (CKD), with its associated morbidity and mortality, is recognized as a major public health problem globally and causing substantial load on health care systems. The current framework for the definition and staging of CKD, based on eGFR levels or presence of kidney damage, is useful for clinical classification of patients, but identifies a huge number of people as having CKD which is too many to target for intervention. The ability to identify a subset of patients, at high risk for adverse outcomes, would be useful to inform clinical management. The current staging system applies static definitions of kidney function that fail to capture the dynamic nature of the kidney disease over time. Now-a-days, it is possible to capture multiple measurements of different laboratory test results for an individual including eGFR values. A new possibility for identifying individuals at higher risk of adverse outcomes is being explored through assessment and consideration of the rate of change in kidney function over time, and this approach will be feasible in the current context of digitalization of health record keeping system. On the basis of the existing evidence, this paper summarizes important findings that support the concept of dynamic changes in kidney function over time, and discusses how the magnitude of these changes affect the future adverse outcomes of kidney disease, particularly the End Stage Renal Disease (ESRD), CVD and mortality. PMID:26728745

  14. Maternal and fetal outcomes in term premature rupture of membrane

    PubMed Central

    Endale, Tigist; Fentahun, Netsanet; Gemada, Desta; Hussen, Mamusha Aman

    2016-01-01

    BACKGROUND: Premature rupture of membrane (PROM) is linked to significant maternal prenatal mortalities and morbidity. In Ethiopia, where maternal mortality is still high, the maternal and fetal outcomes in PROM is very important to decrease maternal and child mortality and for better management and prevention of complications. Thus, this study aimed to detect the maternal and fetal outcomes and associated factors in term PROM at Mizan-Aman General Hospital, south-west Ethiopia. METHODS: A retrospective cross sectional study was conducted using data available at Mizan-Aman General Hospital during a period of 3 years (January 2011 to December 2013). We examined records of 4 525 women who gave birth in the hospital; out of these women, 185 were diagnosed with term PROM and all of them were included in the study. The data of these women were collected using a checklist based on registration books. The data were analyzed using SPSS version 20.0 statistical package. The association between independent and dependent variables was assessed by bivariate and multiple logistic regression analyses. 95%CI and P value less than 0.05 were considered statistically significant. RESULTS: Of the 4 525 women who gave birth in the hospital, 202 were complicated by term PROM. About 22.2% of the women showed unfavorable maternal outcomes. The most common cause of maternal morbidity and mortality was puerperal sepsis. About 33.5% of neonates experienced unfavorable outcomes. The duration of PROM >12 hours (AOR=5.6, 95%CI 1.3–24.1) latency >24 hours (AOR=2.8, 95%CI 1.7–11.8), residing in rural areas (AOR=4.2, 95%CI 3.96–29.4) and birth weight less than 2 500 g were associated with unfavorable outcomes. CONCLUSION: Women residing in rural areas, long latency, and neonates with birth weight less 2 500 g may have unfavorable outcomes. Therefore, optimum obstetric and medical care is essential for the reduction of the devastating complications related to disorders. PMID:27313811

  15. 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

  16. 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

  17. Magnitude of income-related disparities in adverse perinatal outcomes

    PubMed Central

    2014-01-01

    Background To assess and compare multiple measurements of socioeconomic position (SEP) in order to determine the relationship with adverse perinatal outcomes across various contexts. Methods A birth registry, the Nova Scotia Atlee Perinatal Database, was confidentially linked to income tax and related information for the year in which delivery occurred. Multiple logistic regression was used to examine odds ratios between multiple indicators of SEP and multiple adverse perinatal outcomes in 117734 singleton births between 1988 and 2003. Models for after tax family income were also adjusted for neighborhood deprivation to gauge the relative magnitude of effects related to SEP at both levels. Effects of SEP were stratified by single- versus multiple-parent family composition, and by urban versus rural location of residence. Results The risk of small for gestational age and spontaneous preterm birth was higher across all the indicators of lower SEP, while risk for large for gestational age was lower across indicators of lower SEP. Higher risk of postneonatal death was demonstrated for several measures of lower SEP. Higher material deprivation in the neighborhood of residence was associated with increased risk for perinatal death, small for gestational age birth, and iatrogenic and spontaneous preterm birth. Family composition and urbanicity were shown to modify the association between income and some perinatal outcomes. Conclusions This study highlights the importance of understanding the definitions of SEP and the mechanisms that lead to the association between income and poor perinatal outcomes, and broadening the types of SEP measures used in some cases. PMID:24589212

  18. 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

  19. 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

  20. Neonatal and fetal exposure to trans-fatty acid retards early growth and adiposity while adversely affecting glucose in mice

    PubMed Central

    Kavanagh, Kylie; Sajadian, Soraya; Jenkins, Kurt A.; Wilson, Martha D.; Carr, J. Jeffery; Wagner, Janice D.; Rudel, Lawrence L.

    2010-01-01

    Industrially produced trans fatty acids (TFAs) consumed in western diets are incorporated into maternal and fetal tissues, and are passed linearly to offspring via breast milk. We hypothesized that TFA exposure in utero and during lactation in infants would promote obesity and poor glycemic control as compared to unmodified fatty acids. We further hypothesized that in utero exposure alone may program for these outcomes in adulthood. To test this hypothesis we fed female C57/BL6 mice identical western diets that differed only in cis- or trans-isomers of C18:1 and then aimed to determine whether maternal transfer of TFAs through pregnancy and lactation alters growth, body composition and glucose metabolism. Mice were unexposed, exposed during pregnancy, during lactation, or throughout pregnancy and lactation to TFA. Body weight and composition (by computed tomography), and glucose metabolism we assessed at weaning and adulthood. TFA exposure through breast milk caused significant early growth retardation (p<0.001) and higher fasting glucose (p=0.01) but insulin sensitivity was not different. Elevated plasma insulin-like growth factor-1 in mice consuming TFA-enriched milk (p=0.02) may contribute to later catch-up growth, leanness and preserved peripheral insulin sensitivity observed in these mice. Mice exposed to TFA in utero underwent rapid early neonatal growth with TFA-free breast milk and had significantly impaired insulin sensitivity (p<0.05) and greater abdominal fat (p=0.01). We conclude that very early catch-up growth resulted in impaired peripheral insulin sensitivity in this model of diet-related fetal and neonatal programming. TFA surprisingly retarded growth and adiposity while still adversely affecting glucose metabolism. PMID:20650350

  1. The role of Mycoplasma and Ureaplasma in adverse pregnancy outcomes.

    PubMed

    Murtha, Amy P; Edwards, James M

    2014-12-01

    Genital mycoplasmas are frequently found in the vaginal flora across socioeconomic and ethnic groups and have been demonstrated to be involved in adverse perinatal outcomes. Both Mycoplasma and Ureaplasma spp cause inflammation potentially leading to spontaneous preterm birth and PPROM as well as postdelivery infectious complications and neonatal infections. Herein we have provided an overview of the existing literature and supportive evidence for genital mycoplasma's role in perinatal complications. Future research will need to focus on clearly delineating the species, allowing for discrimination of their effects. PMID:25454994

  2. 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

  3. Altered fetal skeletal muscle nutrient metabolism following an adverse in utero environment and the modulation of later life insulin sensitivity.

    PubMed

    Dunlop, Kristyn; Cedrone, Megan; Staples, James F; Regnault, Timothy R H

    2015-01-01

    The importance of the in utero environment as a contributor to later life metabolic disease has been demonstrated in both human and animal studies. In this review, we consider how disruption of normal fetal growth may impact skeletal muscle metabolic development, ultimately leading to insulin resistance and decreased insulin sensitivity, a key precursor to later life metabolic disease. In cases of intrauterine growth restriction (IUGR) associated with hypoxia, where the fetus fails to reach its full growth potential, low birth weight (LBW) is often the outcome, and early in postnatal life, LBW individuals display modifications in the insulin-signaling pathway, a critical precursor to insulin resistance. In this review, we will present literature detailing the classical development of insulin resistance in IUGR, but also discuss how this impaired development, when challenged with a postnatal Western diet, may potentially contribute to the development of later life insulin resistance. Considering the important role of the skeletal muscle in insulin resistance pathogenesis, understanding the in utero programmed origins of skeletal muscle deficiencies in insulin sensitivity and how they may interact with an adverse postnatal environment, is an important step in highlighting potential therapeutic options for LBW offspring born of pregnancies characterized by placental insufficiency. PMID:25685986

  4. Altered Fetal Skeletal Muscle Nutrient Metabolism Following an Adverse In Utero Environment and the Modulation of Later Life Insulin Sensitivity

    PubMed Central

    Dunlop, Kristyn; Cedrone, Megan; Staples, James F.; Regnault, Timothy R.H.

    2015-01-01

    The importance of the in utero environment as a contributor to later life metabolic disease has been demonstrated in both human and animal studies. In this review, we consider how disruption of normal fetal growth may impact skeletal muscle metabolic development, ultimately leading to insulin resistance and decreased insulin sensitivity, a key precursor to later life metabolic disease. In cases of intrauterine growth restriction (IUGR) associated with hypoxia, where the fetus fails to reach its full growth potential, low birth weight (LBW) is often the outcome, and early in postnatal life, LBW individuals display modifications in the insulin-signaling pathway, a critical precursor to insulin resistance. In this review, we will present literature detailing the classical development of insulin resistance in IUGR, but also discuss how this impaired development, when challenged with a postnatal Western diet, may potentially contribute to the development of later life insulin resistance. Considering the important role of the skeletal muscle in insulin resistance pathogenesis, understanding the in utero programmed origins of skeletal muscle deficiencies in insulin sensitivity and how they may interact with an adverse postnatal environment, is an important step in highlighting potential therapeutic options for LBW offspring born of pregnancies characterized by placental insufficiency. PMID:25685986

  5. Periodontal Disease and Adverse Birth Outcomes: A Study from Pakistan

    PubMed Central

    Mobeen, N; Jehan, I; Banjay, N; Moore, J; McClure, EM; Pasha, O; Wright, LL; Goldenberg, RL

    2013-01-01

    OBJECTIVES Periodontal disease may increase the risk of adverse birth outcomes; however, results have been mixed. Few studies have examined periodontal disease in developing countries. We describe the relationship between periodontal disease and birth outcomes in a community setting in Pakistan. METHODS Enrollment occurred at 20–26 wks. A study dentist performed the periodontal examination to assess probing depth (PD), clinical attachment level (CAL), gingivitis index (GI) and plaque index (PI). Outcomes included stillbirth, neonatal mortality, <32 wk preterm birth (PTB), 32–36 wk PTB, and low birthweight (LBW), and are presented for increasing periodontal disease severity by quartiles (Q1-4). RESULTS Dental examinations and outcome data were completed for 1152 women. 81% were multiparous with a mean age of 27 yrs. 33% had no education. Dental caries were present in 47%, missing teeth in 27%, and 92% had no dental care in the last year. Periodontal disease was common: 87% had ≥ 4 teeth with a PD of >3mm, 54% had ≥4 teeth with a PI = 3, and 58% had ≥ 4 teeth with a GI = 3. In general, as the measure of periodontal disease increased, stillbirth, PTB <32 wks and neonatal mortality also increased. Late PTB and LBW were not related to measures of periodontal disease. Adjustment for demographic characteristics did not significantly change the relationships. CONCLUSION Pregnant Pakistani women have high levels of moderate to severe dental disease. Both stillbirth and neonatal mortality increased with the severity of periodontal disease. PMID:18455527

  6. Paternal employment in solvent related occupations and adverse pregnancy outcomes.

    PubMed

    Daniell, W E; Vaughan, T L

    1988-03-01

    Washington State birth certificates were examined for associations between adverse pregnancy outcomes and paternal employment in solvent exposed occupations. Four cohorts defined by live, singleton births to fathers usually employed as auto body shop workers, painters (construction and maintenance), printers, or fibreglass workers were compared retrospectively with both a systematically selected control cohort and a low solvent exposed, occupationally defined control cohort (paternal electricians). The effects of maternal race and medical illness were controlled by sample restriction; maternal age and gravidity by stratified analysis. There was evidence of increased risk of low birth weight for infants born to fathers employed as body shop workers (relative risk = 1.6; 95% confidence interval = 1.1-2.4) or painters (RR = 1.4; CI = 0.9-2.1) when compared with the systematically selected controls but not with the electrician controls. The excess risk appeared stronger when only term infants were analysed suggesting a mechanism of growth retardation rather than prematurity. There was no evidence of increased risk among the other exposed cohorts or for other adverse pregnancy outcomes. Several design features limit the interpretation of the findings and confirmation by other studies is needed. PMID:3348995

  7. Spousal Military Deployment During Pregnancy and Adverse Birth Outcomes.

    PubMed

    Spieker, Amy; Schiff, Melissa A; Davis, Beth E

    2016-03-01

    Pregnant women with a military-deployed spouse have increased risk of depression and self-reported stress. In nonmilitary populations, depression and stress during pregnancy are associated with adverse birth outcomes. This study assesses the association between a spouse's military deployment and adverse birth outcomes. We conducted a retrospective cohort study at a large military medicine center in the Northwest and evaluated records of singleton deliveries to dependent Army spouses from September 2001 to September 2011. We used logistic regression to estimate relative risks and 95% confidence intervals (CI) of the associations between deployment and low birth weight (<2,500 g), preterm delivery (<37 weeks), small for gestational age (SGA, <10 percentile for gestational age), and cesarean delivery. We identified 10,536 births; 1,364 (12.9%) spouses were deployed at delivery. No associations were observed in the overall population. Among women with two or more children, we observed an 81% increased risk of SGA (95% CI 1.18-2.79). Women 30 to 34 years old had an 82% (95% CI 1.06-3.14) increased risk of low birth weight and an 84% increased risk of SGA (95% CI 1.13-2.98). Deployment's effects vary by maternal age and the number of children in the household. These findings may inform programs and practitioners to best serve women with military-deployed spouses. PMID:26926749

  8. Evaluating competing adverse and beneficial outcomes using a mixture model

    PubMed Central

    Lau, Bryan; Cole, Stephen R.; Moore, Richard D.; Gange, Stephen J.

    2008-01-01

    SUMMARY A competing risk framework occurs when individuals have the potential to experience only one of several mutually exclusive outcomes. Standard survival methods often overestimate the cumulative incidence of events when competing events are censored. Mixture distributions have been previously applied to the competing risk framework to obtain inferences regarding the subdistribution of an event of interest. Often the competing event is treated as a nuisance, but it may be of interest to compare adverse events against the beneficial outcome when dealing with an intervention. In this paper, methods for using a mixture model to estimate an adverse-benefit ratio curve (ratio of the cumulative incidence curves for the two competing events) and the ratio of the subhazards for the two competing events are presented. Both parametric and semi-parametric approaches are described with some remarks for extending the model to include uncertainty in the event type that occurred, left-truncation in order to allow for time-dependent analyses, and uncertainty in the timing of the event resulting in interval censoring. The methods are illustrated with data from a HIV clinical cohort examining whether individuals initiating effective antiretroviral therapy have a greater risk of antiretroviral discontinuation or switching compared to HIV RNA suppression. PMID:18416435

  9. 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...

  10. The effects of air pollution on adverse birth outcomes

    PubMed Central

    Ha, Sandie; Hu, Hui; Roussos-Ross, Dikea; Haidong, Kan; Roth, Jeffrey; Xu, Xiaohui

    2014-01-01

    Background Air pollution has been shown to have adverse effects on many health outcomes including cardiorespiratory diseases and cancer. However, evidence on the effects of prenatal exposure is still limited. The purpose of this retrospective cohort study is to evaluate the effects of prenatal exposure to air pollutants including particulate matter with aerodynamic diameter less than 2.5 micrometer (PM2.5) and ozone (O3) on the risk of adverse birth outcomes (ABOs) including term low birth weight (LBW), preterm delivery (PTD) and very PTD (VPTD). Methods Singleton births from 2004–2005 in Florida were included in the study (N=423,719). Trimester-specific exposures to O3 and PM2.5 at maternal residence at delivery were estimated using the National Environmental Public Health Tracking Network data, which were interpolated using Hierarchical Bayesian models. Results After adjustment for potential confounders such as demographics, medical and lifestyle factors PM2.5 exposures in all trimesters were found to be significantly and positively associated with the risk of all ABOs. Second-trimester exposure had the strongest effects. For an interquartile range (IQR) increase in PM2.5 during the second trimester, the risk of term LBW, PTD and VPTD increased by 3% [95% confidence interval (CI): 1–6%)], 12% (11–14%) and 22% (18–25%), respectively. O3 was also found to be positively associated with PTD and VPTD with the strongest effects over the whole pregnancy period [3% (1–5%) for PTD and 13% (7–19%) for VPTD for each IQR increase]. However, O3 was observed to have protective effects on term LBW. Results were consistent for multi-pollutant models. Conclusion PM2.5 has consistent adverse effects on ABOs whereas O3 has inconsistent effects. These findings warrant further investigation. PMID:25173052

  11. Association of assisted reproductive technology with adverse pregnancy outcomes

    PubMed Central

    Jie, Zhang; Yiling, Ding; Ling, Yu

    2015-01-01

    Background: More and more infertile patients have accepted the assisted reproductive technique (ART) therapy. Concerns have been raised over an increased risk of adverse maternal outcomes in ART populations as compared with natural conception (NC). Objective: The aim was to improve the ART in clinicial work and to reduce the incidence of pregnancy complications in ART group according to analyzing the reasons of high incidence of pregnancy complications in ART group, comparing the incidence of pregnancy complications in different controlled ovarian hyperstimulation (COH) programs and evaluating the effects of ART which attribute to adverse pregnancy outcomes. Materials and Methods: In this prospective population-based cohort study,3216 pregnant women with gestational age ≤12 weeks, regular antenatal examination,and ultrasound identification of intrauterine pregnancy were enrolled from January 2010 to June 2013. According to having ART history, the participantswere divided into two groups: ART group (contains fresh embryo transfer group or frozen-thawed embryo transfer group) and NC group. We compared the incidence of pregnancy complications between different groups and evaluated the factors which could affect the occurrence of these complications. Results: When compared to NC group, significantly increased rates of gestational diabetes mellitus (GDM) (p<0.01), preeclampsia (PE) (p<0.01) and intrahepatic cholestasis of pregnancy (ICP) (p˂0.01) were observed in ART group. There was no significant difference in the incidence of birth defect between the two groups (p=0.07). Multiple pregnancies and Gonadotropin (Gn) were risk factors in GDM, PE, and ICP. The exogenous progesterone treatment had no effect on GDM, PE or ICP. Conclusion: ART increases the risk of adverse maternal complications such as GDM, PE and ICP. The dosages of Gn should be reduced to an extent and the number of embryo implantation should be controlled. Exogenous progesterone treatment is safe

  12. Perfluorinated Compounds in Umbilical Cord Blood and Adverse Birth Outcomes

    PubMed Central

    Chen, Mei-Huei; Ha, Eun-Hee; Wen, Ting-Wen; Su, Yi-Ning; Lien, Guang-Wen; Chen, Chia-Yang; Chen, Pau-Chung; Hsieh, Wu-Shiun

    2012-01-01

    Background Previous animal studies have shown that perfluorinated compounds (PFCs) have adverse impacts on birth outcomes, but the results have been inconclusive in humans. We investigated associations between prenatal exposure to perfluorooctanoic acid (PFOA), perfluorooctyl sulfonate (PFOS), perfluorononanoic acid (PFNA), and perfluoroundecanoic acid (PFUA) and birth outcomes. Methods In total, 429 mother-infant pairs were recruited from the Taiwan Birth Panel Study (TBPS). Demographic data were obtained by interviewing mothers using a structured questionnaire and birth outcomes were extracted from medical records. Cord blood was collected for PFOA, PFOS, PFNA, and PFUA analysis by ultra-high-performance liquid chromatography/tandem mass spectrometry. Results The geometric mean (standard deviation) levels of PFOA, PFOS, PFNA, and PFUA in cord blood plasma were 1.84 (2.23), 5.94 (1.95), 2.36(4.74), and 10.26 (3.07) ng/mL, respectively. Only PFOS levels were found to be inversely associated with gestational age, birth weight, and head circumference [per ln unit: adjusted β (95% confidence interval, CI) = −0.37 (−0.60, −0.13) wks, −110.2 (−176.0, −44.5) gm and −0.25 (−0.46, −0.05) cm]. Additionally, the odds ratio of preterm birth, low birth weight, and small for gestational age increased with PFOS exposure [per ln unit: adjusted odds ratio (OR) (95%CI) = 2.45 (1.47, 4.08), 2.61(0.85, 8.03) and 2.27 (1.25, 4.15)]. When PFOS levels were divided into quartiles, a dose-response relation was observed. However, PFOA, PFNA, and PFUA were not observed to have any convincing impact on birth outcomes. Conclusions An adverse dose-dependent association was observed between prenatal PFOS exposure and birth outcomes. However, no associations were found for the other examined PFCs. PMID:22879996

  13. Adverse obstetric outcome for the vanishing twin syndrome.

    PubMed

    Almog, Benny; Levin, Ishai; Wagman, Israel; Kapustiansky, Rita; Lessing, Joseph B; Amit, Ami; Azem, Foad

    2010-02-01

    The aim was to compare obstetric outcomes of IVF singleton pregnancies diagnosed with vanishing twin (VT) syndrome with those pregnancies originating as singleton pregnancies and with twin pregnancies. In this case control study, 57 patients diagnosed with VT syndrome were matched and compared with 171 singleton controls and 171 twin controls. Mean gestational age was 35.1+/-3.7 versus 38.2+/-2.6 weeks (P=0.001) for patients and singleton controls respectively. Birth weights were 2834.4+/-821.2 versus 3036+/-489.3g (P=0.02), proportion of low birth weight (< 2500 g) was 33.3 versus 11.7% (P=0.0001) and very low birth weight (< 1500 g) 3.5 versus 0.6% for patients and singleton controls respectively. The proportion of deliveries before 28 weeks of gestation was 7.0 versus 1.2% (P=0.01) for patients and singleton controls respectively. When comparing the study group to twin control pregnancies, a similar gestational age at delivery (35 weeks) and rate of preterm birth (23%) were found. In conclusion, pregnancies diagnosed with the VT syndrome after IVF carry a higher rate of adverse obstetric outcomes in terms of preterm deliveries and lower birth weight, compared with IVF pregnancies that were originally singleton. Additionally, significant similarities were observed in the obstetrics outcome of vanishing twin pregnancies and twin pregnancies. PMID:20113963

  14. 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

  15. Chronic kidney disease in pregnancy: Maternal and fetal outcomes and progression of kidney disease

    PubMed Central

    Wolski, Penny; Callaway, Leonie K; Barrett, Helen L; Fagermo, Narelle; Lust, Karin; Shakhovskoy, Rebekah E

    2015-01-01

    Background There is a paucity of Australian data regarding renal disease in pregnancy. We undertook a retrospective cohort study at a tertiary institution to examine the impact of renal disease on pregnancy outcomes and the effect of pregnancy on disease progression. Methods A total of 55 pregnancies of patients with renal disease admitted from 2003 to 2010 to the Royal Brisbane and Women’s Hospital were analysed. Pre-conception variables, fetal/delivery and maternal outcomes were analysed in this group and in a control group of women with normal kidney function pre-pregnancy. Results Of the 55 pregnancies, 71% experienced pre-term delivery, 38% had intra-uterine growth restriction and 62% required caesarean section. Of all, 60% of neonates required neonatal intensive care unit (NICU) admission and six perinatal deaths occurred. Of all, 67% of women suffered preeclampsia, 47% anaemia and 3 patients required dialysis in pregnancy. Postpartum deterioration of renal function occurred in patients with pre-conception chronic kidney disease stage 3–5. Conclusions Chronic kidney disease of all stages is a risk factor for adverse pregnancy outcomes. In a tertiary institution however, there is a high rate of successful pregnancy (84%).

  16. 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

  17. 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

  18. 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

  19. 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

  20. 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

  1. 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

  2. Evidence for adverse reproductive outcomes among women microelectronic assembly workers.

    PubMed Central

    Huel, G; Mergler, D; Bowler, R

    1990-01-01

    Microelectronics assembly entails complex processes where several potentially fetotoxic chemical compounds are used extensively. This study was undertaken to assess the potential adverse reproductive outcomes among former women workers in a microelectronics assembly plant in New Mexico with respect to a comparable population from the same geographical region and to examine the relation between these outcomes and employment history in this plant. After matching a pool of 143 former microelectronic female workers and 105 referents, 90 former microelectronic female worker-referent pairs were constituted (representing 302 and 324 pregnancies in former workers and referents respectively). The odds ratio (for pair matching design) of spontaneous abortion among women workers, before beginning to assemble microelectronic components, was 0.9 (chi 2 = 0.04; NS). After the beginning of employment this odds ratio became 5.6 (chi 2 = 9.8; p less than 1%). This estimated odds ratio decreased to 4.0, taking into account the increased risk for spontaneous abortion in previous pregnancies before employment (chi 2 = 5.4; p less than 5%). It was not possible to determine if this effect was reversible owing to the small number of pairs available after employment. The findings of this study corroborate the results of former studies that suggest a potential association between electronic manufacturing activity and risk of spontaneous abortion. Although the organic solvents were suspected of being the potential risk factor, this study was inconclusive from this point of view. Nevertheless, these investigations may provide some insight into reproductive outcomes among female workers exposed to solvents. PMID:2378817

  3. 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

  4. 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

  5. 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...

  6. 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

  7. 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

  8. 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

  9. Human Cytomegalovirus-Induces Cytokine Changes in the Placenta with Implications for Adverse Pregnancy Outcomes

    PubMed Central

    Hamilton, Stuart T.; Scott, Gillian; Naing, Zin; Iwasenko, Jenna; Hall, Beverley; Graf, Nicole; Arbuckle, Susan; Craig, Maria E.; Rawlinson, William D.

    2012-01-01

    Human cytomegalovirus (CMV) infection of the developing fetus can result in adverse pregnancy outcomes including death in utero. Fetal injury results from direct viral cytopathic damage to the CMV-infected fetus, although evidence suggests CMV placental infection may indirectly cause injury to the fetus, possibly via immune dysregulation with placental dysfunction. This study investigated the effects of CMV infection on expression of the chemokine MCP-1 (CCL2) and cytokine TNF-α in placentae from naturally infected stillborn babies, and compared these changes with those found in placental villous explant histocultures acutely infected with CMV ex vivo. Tissue cytokine protein levels were assessed using quantitative immunohistochemistry. CMV-infected placentae from stillborn babies had significantly elevated MCP-1 and TNF-α levels compared with uninfected placentae (p = 0.001 and p = 0.007), which was not observed in placentae infected with other microorganisms (p = 0.62 and p = 0.71) (n = 7 per group). Modelling acute clinical infection using ex vivo placental explant histocultures showed infection with CMV laboratory strain AD169 (0.2 pfu/ml) caused significantly elevated expression of MCP-1 and TNF-α compared with uninfected explants (p = 0.0003 and p<0.0001) (n = 25 per group). Explant infection with wild-type Merlin at a tenfold lower multiplicity of infection (0.02 pfu/ml), caused a significant positive correlation between increased explant infection and upregulation of MCP-1 and TNF-α expression (p = 0.0001 and p = 0.017). Cytokine dysregulation has been associated with adverse outcomes of pregnancy, and can negatively affect placental development and function. These novel findings demonstrate CMV infection modulates the placental immune environment in vivo and in a multicellular ex vivo model, suggesting CMV-induced cytokine modulation as a potential initiator and/or exacerbator of placental and fetal injury. PMID

  10. Perinatal programming of childhood asthma: early fetal size, growth trajectory during infancy, and childhood asthma outcomes.

    PubMed

    Turner, Steve

    2012-01-01

    The "fetal origins hypothesis" or concept of "developmental programming" suggests that faltering fetal growth and subsequent catch-up growth are implicated in the aetiology of cardiovascular disease. Associations between reduced birth weight, rapid postnatal weight gain, and asthma suggest that there are fetal origins to respiratory disease. The present paper first summarises the literature relating birth weight and post natal growth trajectories to asthma outcomes. Second, issues regarding the interpretation of antenatal fetal ultrasound measurements are discussed. Finally, recent reports linking antenatal measurement and growth trajectory to early childhood asthma outcomes are discussed. Understanding the nature and timing of factors which influence antenatal growth may give important insight into the antecedents of early-onset asthma with implications for interventions. PMID:22400043

  11. Peri-Implantation Hormonal Milieu: Elucidating Mechanisms of Adverse Neurodevelopmental Outcomes.

    PubMed

    Mainigi, Monica; Rosenzweig, Jason M; Lei, Jun; Mensah, Virginia; Thomaier, Lauren; Talbot, C Conover; Olalere, Devvora; Ord, Teri; Rozzah, Rayyan; Johnston, Michael V; Burd, Irina

    2016-06-01

    While live births resulting from assisted reproductive technology (ART) exceed 1% of total births annually, the effect of ART on fetal development is not well understood. Data have demonstrated that IVF leads to alterations in DNA methylation and gene expression in the placenta that may have long-term effects on health and disease. Studies have linked adverse neurodevelopmental outcomes to ART, although human studies are inconclusive. In order to isolate the peri-implantation environment and its effects on brain development, we utilized a mouse model with and without superovulation and examined the effect of adult behavior as well as adult cortical neuronal density. Adult offspring of superovulated dams showed increased anxiety-like behavior compared to offspring of naturally mated dams (P < .05). There was no difference in memory and learning tests between the 2 groups. The adult brains from offspring of superovulated recipients had fewer neurons per field compared to naturally mated control offspring (P < .05). In order to examine potential pathways leading to these changes, we measured messenger RNA and microRNA (miRNA) expression in fetal brains at E18.5. Microarray analysis found that miRNAs miR-122, miR-144, and miR-211, involved in regulation of neuronal migration and differentiation, were downregulated in brains of offspring exposed to a superovulated environment(P < .05). There was also altered expression of genes involved in neuronal development. These results suggest that the peri-implantation environment can affect neurodevelopment and can lead to behavioral changes in adulthood. Human studies with long-term follow-up of children from ART are necessary to further investigate the influence of ART on the offspring. PMID:26614264

  12. 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

  13. 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...

  14. 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

  15. 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.

  16. Increased systolic load causes adverse remodeling of fetal aortic and mitral valves.

    PubMed

    Tibayan, Frederick A; Louey, Samantha; Jonker, Sonnet; Espinoza, Herbert; Chattergoon, Natasha; You, Fanglei; Thornburg, Kent L; Giraud, George

    2015-12-15

    While abnormal hemodynamic forces alter fetal myocardial growth, little is known about whether such insults affect fetal cardiac valve development. We hypothesized that chronically elevated systolic load would detrimentally alter fetal valve growth. Chronically instrumented fetal sheep received either a continuous infusion of adult sheep plasma to increase fetal blood pressure, or a lactated Ringer's infusion as a volume control beginning on day 126 ± 4 of gestation. After 8 days, mean arterial pressure was higher in the plasma infusion group (63.0 mmHg vs. 41.8 mmHg, P < 0.05). Mitral annular septal-lateral diameter (11.9 mm vs. 9.1 mm, P < 0.05), anterior leaflet length (7.7 mm vs. 6.4 mm, P < 0.05), and posterior leaflet length (P2; 4.0 mm vs. 3.0 mm, P < 0.05) were greater in the elevated load group. mRNA levels of Notch-1, TGF-β2, Wnt-2b, BMP-1, and versican were suppressed in aortic and mitral valve leaflets; elastin and α1 type I collagen mRNA levels were suppressed in the aortic valves only. We conclude that sustained elevated arterial pressure load on the fetal heart valve leads to anatomic remodeling and, surprisingly, suppression of signaling and extracellular matrix genes that are important to valve development. These novel findings have important implications on the developmental origins of valve disease and may have long-term consequences on valve function and durability. PMID:26354842

  17. Experimental analysis of the relationship between simulated low-velocity rear-end collisions and fetal outcomes of pregnant rats.

    PubMed

    Hitosugi, Masahito; Motozawa, Yasuki; Kawato, Hitoshi; Nagai, Toshiaki; Tokudome, Shogo

    2009-07-01

    Our study aimed to define the risk for a human fetus of rear-end vehicle collisions. We therefore performed drop tests using pregnant SLC Wistar rats. Pressure applied to the rat uterus and rectum at various stages of acceleration was measured. After being dropped, rats were observed throughout pregnancy. At birth, the numbers, weight and the occurrence of physical anomalies among pups were followed-up for 28 days. Uterine pressure increased exponentially from 2.1 +/- 0.3 kPa at 19-fold gravity (G) to 13.9 +/- 0.8 kPa at 92-fold G. These values are much lower than the mechanical failure level of human fetal membrane tissue or of those at risk of adverse fetal outcomes. Neither the average number of offspring per pregnant rat nor the average body weight of newborn pups differed significantly between control pregnant rats and those which had been exposed to acceleration of 46-fold or 92-fold G. Other variables such as maternal mental distress, motion effects of amniotic fluid or seatbelt-induced uterine injuries might contribute to fetal loss. PMID:19787994

  18. 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...

  19. 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:…

  20. 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 ...

  1. 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...

  2. 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...

  3. Combined Effect of Fetal Sex and Advanced Maternal Age on Pregnancy Outcomes

    PubMed Central

    Weissmann-Brenner, Alina; Simchen, Michal J.; Zilberberg, Eran; Kalter, Anat; Dulitzky, Mordechai

    2015-01-01

    Background Fetal sex and maternal age are each known to affect outcomes of pregnancies. The objective of the present study was to investigate the influence of the combination of maternal age and fetal sex on pregnancy outcomes in term and post-term singleton pregnancies. Material/Methods This was a retrospective study on term singleton pregnancies delivered between 2004 and 2008 at the Chaim Sheba Medical Center. Data collected included maternal age, fetal sex, and maternal and neonatal complications. The combined effect of fetal sex and maternal age on complications of pregnancy was assessed by multivariable logistic regression models. Results The study population comprised 37,327 pregnancies. The risk of operative deliveries increased with maternal age ≥40 and in pregnancies with male fetuses. The risk of maternal diabetes and of longer hospitalization increased as maternal age increased, and in women <40 carrying male fetuses. The risk of hypertensive disorders increased in pregnancies with males as maternal age advanced. The risk of shoulder dystocia and neonatal respiratory complications increased in male neonates born to women<40. The risk of neonatal hypoglycemia increased in males for all maternal ages. Conclusions Risk assessment for fetal sex and advanced maternal age were given for different pregnancy complications. Knowledge of fetal sex adds value to the risk assessment of pregnancies as maternal age increases. PMID:25892459

  4. 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

  5. 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

  6. Postnatal Outcome of Fetal Left Ventricular Hypertrabeculation/Noncompaction.

    PubMed

    Stöllberger, Claudia; Wegner, Christian; Benatar, Abraham; Chin, Thomas K; Dangel, Joanna; Majoor-Krakauer, Danielle; Mondal, Tapas K; Sivanandam, Shanthi; Silverman, Norman H; van Waning, Jaap; Finsterer, Josef

    2016-06-01

    Left ventricular hypertrabeculation/noncompaction (LVHT) is a cardiac abnormality of unknown etiology. Prenatal diagnosis of LVHT can be established by fetal echocardiography. A review of 106 published cases showed that 46 cases with prenatally diagnosed LVHT were alive 0.5-120 months after birth. Since the course of cases with prenatally LVHT after publication is unknown, we aimed to collect follow-up-information. Information regarding vital status, cardiac and extracardiac morbidity was gathered by contacting the authors of the 46 cases. Fourteen of the 28 authors answered and gave information about 18 cases (six females, seven males, five gender-unknown, age 18 months to 10 years, mean follow-up 60 months). No differences were found between the 18 cases with follow-up and the 28 cases without follow-up regarding age, gender, cardiac or extracardiac comorbidities, and interventions. Three of the 18 cases had died subsequently from heart failure, osteosarcoma, and enterocolitis, respectively. Mutations or chromosomal abnormalities were found in six of the seven examined patients, extracardiac abnormalities in nine patients. Three patients received a pacemaker because of complete AV block, and two patients underwent heart transplantation. Cardiac surgical or interventional procedures were carried out in four patients. None suffered from malignant arrhythmias or had a cardioverter-defibrillator implanted. Based on the limited information, there are indications that cases with fetal diagnosis of LVHT have a continuing morbidity and mortality, even if they receive appropriate care. Since fetal LVHT is frequently associated with genetic abnormalities, further research about survival and underlying genetic causes is needed. PMID:27033242

  7. Oligohydramnios in Women with Preterm Prelabor Rupture of Membranes and Adverse Pregnancy and Neonatal Outcomes

    PubMed Central

    Kacerovsky, Marian; Musilova, Ivana; Andrys, Ctirad; Drahosova, Marcela; Hornychova, Helena; Rezac, Adam; Kostal, Milan; Jacobsson, Bo

    2014-01-01

    Objective To determine the association between the presence of oligohydramnios, determined as an amniotic fluid index ≤ 5 cm and the intra-amniotic inflammatory response, fetal inflammatory response and neonatal outcomes in actively managed preterm prelabor rupture of membranes (PPROM). Methods Women with singleton pregnancies complicated by PPROM at a gestational age of between 24+0 and 36+6 weeks were included in the study. Ultrasound assessments of the amniotic fluid index and evaluation of the amniotic fluid interleukin (IL)-6 levels were performed at admission. The umbilical cord blood IL-6 levels were evaluated after delivery. Results In total, 74 women were included. The women with oligohydramnios did not have different amniotic fluid IL-6 levels [with oligohydramnios: median 342 pg/mL, interquartile range (IQR) 110-1809 vs. without oligohydramnios: median 256 pg/mL, IQR 122–748; p = 0.71] or umbilical cord blood IL-6 levels (with oligohydramnios: median 8.2 pg/mL, IQR 3.8–146.9 vs. without oligohydramnios: median 5.9 pg/mL, IQR 2.1–27.9; p = 0.14) than those without oligohydramnios. No association between oligohydramnios and neonatal morbidity was found. A correlation between the amniotic fluid index and the interval from rupture of membranes to amniocentesis was observed (rho = −0.34; p = 0.003). Conclusion The presence of oligohydramnios is not associated with an adverse outcome in actively managed PPROM in singleton pregnancies in the absence of other complications. PMID:25171293

  8. 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

  9. Long-term developmental outcome of children with a fetal diagnosis of isolated inferior vermian hypoplasia

    PubMed Central

    Tarui, Tomo; Limperopoulos, Catherine; Sullivan, Nancy R; Robertson, Richard L; du Plessis, Adre J

    2015-01-01

    Objectives Isolated inferior vermian hypoplasia (iiVH) is one of the most common fetal cerebellar anomalies presenting for fetal neurological counselling with controversial postnatal neurodevelopmental outcome. In the present study, we characterised the long-term neurodevelopmental outcome of prenatally diagnosed iiVH at school age. Design and patients We prospectively followed 20 children with fetal MRI diagnosis of iiVH including their postnatal MRI result and developmental outcome at school age (mean 6.1 years±1.9 years SD) using a comprehensive age-appropriate developmental testing battery, which encompassed cognitive, language, social and behavioural domains. Parental stress level and socioeconomic status were also evaluated. Results All children with postnatally confirmed iiVH had a normal neurodevelopmental outcome. A subgroup of children (2/20) who demonstrated cognitive delays and behavioural impairments had more extensive cerebellar malformation. Despite a normal developmental outcome, the parents of children with postnatally confirmed iiVH had higher parental stress compared with those parents whose children had normal postnatal MRI. Conclusions Children with postnatally confirmed iiVH show age appropriate functioning at school age. Postnatal MRI is important to confirm the diagnosis of iiVH and to exclude associated anomalies that impact neurodevelopmental outcome. A diagnosis of iiVH is associated with persistent elevated parental stress despite normal developmental outcomes in these children suggesting the need for ongoing parental support. PMID:23964086

  10. Perinatal Mortality and Adverse Pregnancy Outcomes in a Low-Income Rural Population of Women who Smoke

    PubMed Central

    McElroy, Jane A.; Bloom, Tina; Moore, Kelly; Geden, Beth; Everett, Kevin; Bullock, Linda F.

    2012-01-01

    SUMMARY We describe adverse pregnancy outcomes, including congenital anomalies, fetal, neonatal, and infant mortality among a Missouri population of low- income, rural mothers who participated in two randomized smoking cessation trials. In the Baby Beep (BB) trial, 695 rural women were recruited from 21 WIC clinics with 650 women’s pregnancy outcomes known (93.5% retention rate). Following the BB trial, 298 women, who had a live infant after November 2004 were re-recruited into and completed the Baby Beep for Kids (BBK) trial. Simple statistics describing the population, perinatal and postneonatal mortality rates were calculated. Of the adverse pregnancy outcomes (n=79), 29% were spontaneous abortions of <20 weeks gestation, 23% were premature births and 49% were identified birth defects. The perinatal mortality rate was 15.9 per 1,000 births (BB study) compared to 8.6 per 1,000 births (state of MO) and 8.5 per 1,000 births (U.S.) The postneonatal infant mortality rate was 13.4 per 1,000 live births (BBK) compared to 2.1 per 1,000 live births (U.S.). The health disparity in this population of impoverished rural pregnant women who smoke, particular with regard to perinatal and infant deaths, warrants attention. PMID:22371350

  11. 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...

  12. Determinants and outcome of fetal macrosomia in a Nigerian tertiary hospital

    PubMed Central

    Olokor, Oghenefegor Edwin; Onakewhor, Joseph Ubini; Aderoba, Adeniyi Kolade

    2015-01-01

    Background: To determine the incidence and risk factors of fetal macrosomia and maternal and perinatal outcome. Patients and Methods: This was a 1-year prospective case–control study of singleton pregnancies in a Nigerian tertiary hospital. Only women who gave consent were recruited for the study. The maternal and perinatal outcomes in women who delivered macrosomic infants (birth weight ≥ 4000 g) were compared with the next consecutive delivery of normal birth weight (2500–3999 g) infants. Results: The total deliveries for the study period were 2437, of which 135 were macrosomic babies. The incidence of fetal macrosomia was 5.5%. The mean birth weights of macrosomic and nonmacrosomic babies were 4.26 ± 0.29 kg and 3.20 ± 0.38 kg, respectively, P = 0.000. Mothers with macrosomic babies were more likely to be older (P = 0.047), of higher parity (0.001), taller (P = 0.007), and weighed more at delivery (P = 0.000). Previous history of fetal macrosomia (P = 0.000) and maternal diabetes (P = 0.007) were factors strongly associated with the delivery of macrosomic infants. Pregnancies associated with fetal macrosomia had increased duration of labor (P = 0.007), interventional deliveries (P = 0.000), shoulder dystocia, and genital laceration (P = 0.000). There was no significant difference in the incidence of primary postpartum hemorrhage (P = 0.790), birth asphyxia, and perinatal mortality (P = 0.197). Conclusion: Fetal macrosomia is associated with maternal and fetal morbidities. The presence of the observed risk factors should elicit the suspicion of a macrosomic fetus and the need for appropriate management to reduce maternal and fetal morbidities. PMID:26903699

  13. 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

  14. Relationship of serum uric acid, serum creatinine and serum cystatin C with maternal and fetal outcomes in rural Indian pregnant women

    PubMed Central

    Yalamati, Padma; Bhongir, Aparna Varma; Betha, Kalpana; Verma, Ritika; Dandge, Shailendra

    2015-01-01

    Background Hypertensive disorders are the most common in pregnancy. Several studies showed a positive correlation between elevated maternal serum uric acid (UA), serum creatinine and adverse maternal and fetal outcomes, but only a few studies are available on serum cystatin C and maternal and fetal outcomes. The present study was undertaken to study the association of serum UA, creatinine and cystatin C with maternal and fetal outcomes. Methods Out of 116 pregnant women 69 women had no hypertension and 47 had hypertension with or without proteinuria. Serum UA, creatinine and cystatin C was measured by modified Uricase method, modified kinetic Jaffe’s reaction and particle-enhanced immunonephelometric assay respectively. Multivariate logistic regression was performed to determine the independent effects of serum UA, creatinine and cystatin C on maternal and fetal outcomes using stata 13.1. Results The adjusted odds ratio (OR) was 3.73 (95% CI: 1.18-11.75; P=0.024) for UA; 15.79 (95% CI: 3.04-81.94; P=0.001) for creatinine and 2.03 (95% CI: 0.70-5.87; P=0.192) for cystatin C in hypertensive disorders of pregnancy. All the three renal parameters were not significantly associated with birth weight, gestational age of delivery and mode of delivery after adjusting for the confounding factors. Conclusions Serum creatinine and uric acid are independent risk factors for hypertensive disorders of pregnancy. High serum uric acid is associated with low birth weight and delivery by caesarian section whereas high serum creatinine with preterm delivery only before adjustment for confounding factors and not after adjustment. Serum cystatin C was not significantly associated with the maternal and fetal outcomes. PMID:26583159

  15. 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

  16. Spontaneous remission of membranous glomerulonephritis with successful fetal outcome: A case report and literature review.

    PubMed

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

    2016-06-01

    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

  17. Fetal chlorpyrifos exposure: adverse effects on brain cell development and cholinergic biomarkers emerge postnatally and continue into adolescence and adulthood.

    PubMed Central

    Qiao, Dan; Seidler, Frederic J; Tate, Charlotte A; Cousins, Mandy M; Slotkin, Theodore A

    2003-01-01

    Fetal and childhood exposures to widely used organophosphate pesticides, especially chlorpyrifos (CPF), have raised concerns about developmental neurotoxicity. Previously, biomarkers for brain cell number, cell packing density, and cell size indicated that neonatal rats were more sensitive to CPF than were fetal rats, yet animals exposed prenatally still developed behavioral deficits in adolescence and adulthood. In the present study, we administered CPF to pregnant rats on gestational days 17-20, using regimens devoid of overt fetal toxicity. We then examined subsequent development of acetylcholine systems in forebrain regions involved in cognitive function and compared the effects with those on general biomarkers of cell development. Choline acetyltransferase, a constitutive marker for cholinergic nerve terminals, showed only minor CPF-induced changes during the period of rapid synaptogenesis. In contrast, hemicholinium-3 binding to the presynaptic choline transporter, which is responsive to nerve impulse activity, displayed marked suppression in the animals exposed to CPF; despite a return to nearly normal values by weaning, deficits were again apparent in adolescence and adulthood. There was no compensatory up-regulation of cholinergic receptors, as m2-muscarinic cholinergic receptor binding was unchanged. CPF also elicited delayed-onset alterations in biomarkers for general aspects of cell integrity, with reductions in cell packing density, increases in relative cell size, and contraction of neuritic extensions; however, neither the magnitude nor timing of these changes was predictive of the cholinergic defects. The present findings indicate a wide window of vulnerability of cholinergic systems to CPF, extending from prenatal through postnatal periods, occurring independently of adverse effects on general cellular neurotoxicity. PMID:12676612

  18. 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...

  19. 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...

  20. 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...

  1. 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...

  2. 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...

  3. 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...

  4. 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)...

  5. Screening for fetal growth restriction with universal third trimester ultrasonography in nulliparous women in the Pregnancy Outcome Prediction (POP) study: a prospective cohort study

    PubMed Central

    Sovio, Ulla; White, Ian R; Dacey, Alison; Pasupathy, Dharmintra; Smith, Gordon C S

    2015-01-01

    Summary Background Fetal growth restriction is a major determinant of adverse perinatal outcome. Screening procedures for fetal growth restriction need to identify small babies and then differentiate between those that are healthy and those that are pathologically small. We sought to determine the diagnostic effectiveness of universal ultrasonic fetal biometry in the third trimester as a screening test for small-for-gestational-age (SGA) infants, and whether the risk of morbidity associated with being small differed in the presence or absence of ultrasonic markers of fetal growth restriction. Methods The Pregnancy Outcome Prediction (POP) study was a prospective cohort study of nulliparous women with a viable singleton pregnancy at the time of the dating ultrasound scan. Women participating had clinically indicated ultrasonography in the third trimester as per routine clinical care and these results were reported as usual (selective ultrasonography). Additionally, all participants had research ultrasonography, including fetal biometry at 28 and 36 weeks' gestational age. These results were not made available to participants or treating clinicians (universal ultrasonography). We regarded SGA as a birthweight of less than the 10th percentile for gestational age and screen positive for SGA an ultrasonographic estimated fetal weight of less than the 10th percentile for gestational age. Markers of fetal growth restriction included biometric ratios, utero-placental Doppler, and fetal growth velocity. We assessed outcomes for consenting participants who attended research scans and had a livebirth at the Rosie Hospital (Cambridge, UK) after the 28 weeks' research scan. Findings Between Jan 14, 2008, and July 31, 2012, 4512 women provided written informed consent of whom 3977 (88%) were eligible for analysis. Sensitivity for detection of SGA infants was 20% (95% CI 15–24; 69 of 352 fetuses) for selective ultrasonography and 57% (51–62; 199 of 352 fetuses) for universal

  6. Alanine aminotransferase as a predictor of adverse perinatal outcomes in women with intrahepatic cholestasis of pregnancy

    PubMed Central

    Ekiz, Ali; Kaya, Basak; Avci, Muhittin Eftal; Polat, Ibrahim; Dikmen, Selin; Yildirim, Gokhan

    2016-01-01

    Objective: To evaluate the associations between adverse perinatal outcomes and serum transaminase levels at the time of diagnosis in patients with intrahepatic cholestasis of pregnancy. Methods: We performed a retrospective analysis of patients hospitalized for evaluation of intrahepatic cholestasis of pregnancy from January 2013 to June 2014 in a tertiary center. Seventy-one patients were divided into two groups according to the presence (Group I) or absence of adverse perinatal outcomes (Group II). Results: The mean aminotransferase levels and conjugated bilirubin levels at the time of diagnosis were significantly higher in Group I than in Group II. Receiver operating characteristic curve analysis revealed that the alanine aminotransferase level could predict adverse perinatal outcomes with 76.47% sensitivity and 78.38% specificity, and the cut-off value was 95 IU/L. Among patients with intrahepatic cholestasis of pregnancy, those with adverse perinatal outcomes were significantly older, had an earlier diagnosis, and had higher alanine aminotransferase levels. Using the 95-IU/L cut-off value, patients with intrahepatic cholestasis of pregnancy had a 3.54-fold increased risk for adverse perinatal outcomes. Conclusions: Patients with intrahepatic cholestasis of pregnancy and high alanineaminotransferase levels should be followed up for possible adverse perinatal outcomes.

  7. 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

  8. 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...

  9. 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...

  10. 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…

  11. 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...

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

    PubMed Central

    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 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 communication 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. PMID:24852332

  13. 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

  14. Adverse pregnancy outcome in a petrochemical polluted area in Taiwan.

    PubMed

    Lin, M C; Yu, H S; Tsai, S S; Cheng, B H; Hsu, T Y; Wu, T N; Yang, C Y

    2001-08-24

    The petrochemical industry is the main source of industrial air pollution in Taiwan. Reported here are the results from an ongoing study of outdoor air pollution and the health of individuals living in a community in close proximity to petrochemical industrial complexes. The prevalences of term low birth weight (LBW) in the petrochemical municipality and control municipality were 3.22%, and 1.84%, respectively. After controlling for several possible confounders (including maternal age, season, marital status, maternal education, and infant sex), the adjusted odds ratio was 1.767 (1.002-3.116) for term LBW in the petrochemical municipality. Data provide further support for the hypothesis that air pollution can affect the outcome of pregnancy. PMID:11549116

  15. 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

  16. Substantiation and adverse appeal outcomes: content analysis and testing of Drake's harm/evidence model.

    PubMed

    Fakunmoju, Sunday Bolanle

    2009-02-01

    Little is known about the influence of evidentiary and case characteristics on adverse appeal outcomes for substantiated cases of maltreatment. This article, therefore, reports on a sample of adverse appeal outcomes during a 2-year period. Using Drake's Harm/Evidence model to examine the adverse outcomes, the study describes differences between substantiated cases that were "modified" versus "overturned" during appeal, as well as differences in their evidentiary characteristics across different types of maltreatment. Content analysis and logistic regression analysis of administrative data were used to predict overturned versus modified outcome. Overall, child neglect, substantiated cases that did not meet basic evidentiary standards, and cases that were deemed as not credible were more likely to be overturned in comparison to being modified. A substantiation assessment framework (SAF) is developed and implications of Drake's Harm/Evidence model for investigating maltreatment as well as for understanding judicial decision making in appealed cases of maltreatment is highlighted. PMID:18612040

  17. Maternal and Fetal Outcomes in Pregnant Women with a Prosthetic Mechanical Heart Valve

    PubMed Central

    Ayad, Sherif W.; Hassanein, Mahmoud M.; Mohamed, Elsayed A.; Gohar, Ahmed M.

    2016-01-01

    BACKGROUND Pregnancy is associated with several cardiocirculatory changes that can significantly impact underlying cardiac disease. These changes include an increase in cardiac output, sodium, and water retention leading to blood volume expansion, and reductions in systemic vascular resistance and systemic blood pressure. In addition, pregnancy results in a hypercoagulable state that increases the risk of thromboembolic complications. OBJECTIVES The aim of this study is to assess the maternal and fetal outcomes of pregnant women with mechanical prosthetic heart valves (PHVs). METHODS This is a prospective observational study that included 100 pregnant patients with cardiac mechanical valve prostheses on anticoagulant therapy. The main maternal outcomes included thromboembolic or hemorrhagic complications, prosthetic valve thrombosis, and acute decompensated heart failure. Fetal outcomes included miscarriage, fetal death, live birth, small-for-gestational age, and warfarin embryopathy. The relationship between the following were observed: – Maternal and fetal complications and the site of the replaced valve (mitral, aortic, or double)– Maternal and fetal complications and warfarin dosage (≤5 mg, >5 mg)– Maternal and fetal complications and the type of anticoagulation administered during the first trimester RESULTS This study included 60 patients (60%) with mitral valve replacement (MVR), 22 patients (22%) with aortic valve replacement (AVR), and 18 patients (18%) with double valve replacement (DVR). A total of 65 patients (65%) received >5 mg of oral anticoagulant (warfarin), 33 patients (33%) received ≤5 mg of warfarin, and 2 patients (2%) received low-molecular-weight heparin (LMWH; enoxaparin sodium) throughout the pregnancy. A total of 17 patients (17%) received oral anticoagulant (warfarin) during the first trimester: 9 patients received a daily warfarin dose of >5 mg while the remaining 8 patients received a daily dose of ≤5 mg. Twenty

  18. Late childbearing and changing risks of adverse birth outcomes in Korea.

    PubMed

    Cho, Youngtae; Hummer, Robert A; Choi, Yoon-Jung; Jung, Sung Won

    2011-05-01

    This study aimed to examine whether the relative importance of maternal age as a correlate of adverse birth outcomes has changed and to investigate if social inequalities in birth outcomes have widened during the past decade when the marriage and fertility related social environment has undergone tremendous change in Korea. Probabilities of adverse birth outcomes (prematurity and intrauterine growth retardation [IUGR]) were estimated with multinomial logistic regression models, utilizing the Korean birth registration data of 1995 and 2005. The main effects of maternal age and parental socioeconomic characteristics were compared between two study years, net of infant sex, birth order, and plurality. The association between maternal age and adverse birth outcomes, relative to the maternal and parental social characteristics, has clearly diminished between 1995 and 2005. During this period, differences in prematurity and IUGR by maternal age have also diminished, while those by parental social characteristics, particularly maternal education, have substantially widened. The intensified overall socioeconomic polarization since the economic crisis of the late 1990s is most likely responsible for the increased social inequality in adverse birth outcomes in Korea. A massive structural change in macro-economic conditions and culture during the study period may have modified the relationship between maternal age and birth outcomes. PMID:20432060

  19. 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

  20. 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

  1. 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

  2. First- and second-trimester maternal serum markers for aneuploidy and adverse obstetric outcomes.

    PubMed

    Dugoff, Lorraine

    2010-05-01

    Maternal serum levels of the first- and second-trimester markers for aneuploidy have been shown to be associated with adverse obstetric outcomes in the absence of aneuploidy or neural-tube defects. The likelihood of an adverse obstetric outcome increases as the values of the marker become more extreme, and as the number of abnormal markers increases. Although many of the associations between maternal serum markers for aneuploidy and adverse obstetric outcomes are statistically significant, the sensitivity and positive predictive values for the individual outcomes are too low for them to be clinically useful as screening tests. Currently in the United States there is not a uniformly accepted practice for the care of women with abnormal maternal serum markers regarding risk of future obstetric complications. There are no randomized trials assessing any type of intervention or treatment for patients with abnormal serum markers. Various strategies to manage patients with unexplained abnormal serum markers have been proposed. This article reviews the relationships between these markers and adverse obstetric outcomes. In addition, potential management strategies and future areas of research are discussed. PMID:20410782

  3. 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

  4. Prenatal Ultrasound Screening for Fetal Anomalies and Outcomes in High-Risk Pregnancies due to Maternal HIV Infection: A Retrospective Study

    PubMed Central

    Reitter, A.; Stücker, A. U.; Buxmann, H.; Herrmann, E.; Haberl, A. E.; Schlößer, R.; Louwen, F.

    2013-01-01

    Objective. To assess the prevalence of prenatal screening and of adverse outcome in high-risk pregnancies due to maternal HIV infection. Study Design. The prevalence of prenatal screening in 330 pregnancies of HIV-positive women attending the department for prenatal screening and/or during labour between January 1, 2002 and December 31, 2012, was recorded. Screening results were compared with the postnatal outcome and maternal morbidity, and mother-to-child transmission (MTCT) was evaluated. Results. One hundred of 330 women (30.5%) had an early anomaly scan, 252 (74.5%) had a detailed scan at 20–22 weeks, 18 (5.5%) had a detailed scan prior to birth, and three (0.9%) had an amniocentesis. In seven cases (2.12%), a fetal anomaly was detected prenatally and confirmed postnatally, while in eight (2.42%) an anomaly was only detected postnatally, even though a prenatal scan was performed. There were no anomalies in the unscreened group. MTCT occurred in three cases (0.9%) and seven fetal and neonatal deaths (2.1%) were reported. Conclusion. The overall prevalence of prenatal ultrasound screening in our cohort is 74.5%, but often the opportunity for prenatal ultrasonography in the first trimester is missed. In general, the aim should be to offer prenatal ultrasonography in the first trimester in all pregnancies. This allows early reassurance or if fetal disease is suspected, further steps can be taken. PMID:24194633

  5. 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

  6. 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...

  7. 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)…

  8. 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...

  9. 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...

  10. USE OF CASE REPORTS IN ASSESSING ADVERSE OUTCOMES OF HUMAN PRENATAL DRUG EXPOSURES: AN APPROACH

    EPA Science Inventory

    The use of case reports for assessing the developmental consequences of prenatal drug exposure is limited by the inability to determine the incidence of adverse outcomes and by the high likelihood for bias. Yet, because it is impossible to conduct clinical trials for the assessme...

  11. A study of mild fetal pyelectasia - outcome and proposed strategy of management.

    PubMed

    Kent, A; Cox, D; Downey, P; James, S L

    2000-03-01

    Mild fetal pyelectasia, defined as a renal pelvic anteroposterior (AP) diameter of 4-10 mm, has become a frequent finding on fetal ultrasonography. The natural history of such dilatation is unclear, resulting in confusion as to appropriate postnatal investigation and management. The aim of this study was to examine the urinary tract outcome of a series of infants with mild fetal pyelectasia demonstrated on routine morphology ultrasonogram between 16 and 21 weeks' gestation. Of the 37 cases identified, 13 (35%) went on to require medical or surgical intervention for significant urinary tract anomalies. These anomalies included pelvi-ureteric junction obstruction, dysplastic kidney, vesicoureteric reflux and posterior urethral valves. On initial scan all cases had an AP diameter of 4-8 mm and did not predict those infants who would go on to require intervention. An AP diameter of greater than 7 mm on repeat scans performed after 27 weeks' gestation had a positive predictive value of 0.92 and a negative predictive value of 0.76 for significant urinary tract anomaly requiring intervention. The specificity was 0. 94 and sensitivity 0.70. A protocol of one repeat antenatal ultrasound at 28-34 weeks' gestation would be able to identify those infants who would require postnatal investigation, using a measurement of >/=7 mm. The fetus with a normal repeat ultrasound would not require postnatal follow-up. PMID:10719322

  12. 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

  13. 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

  14. Population Attributable Risk Fractions of Maternal Overweight and Obesity for Adverse Perinatal Outcomes.

    PubMed

    MacInnis, Natasha; Woolcott, Christy G; McDonald, Sarah; Kuhle, Stefan

    2016-01-01

    The objective of the current study was to determine the proportion of adverse perinatal outcomes that could be potentially prevented if maternal obesity were to be reduced or eliminated (population attributable risk fractions, PARF); and the number needed to treat (NNT) of overweight or obese women to prevent one case of adverse perinatal outcome. Data from the Atlee Perinatal Database on 66,689 singleton infants born in Nova Scotia, Canada, between 2004 and 2014, and their mothers were used. Multivariable-adjusted PARFs and NNTs of maternal pre-pregnancy weight status were determined for various perinatal outcomes under three scenarios: If all overweight and obese women were to i) become normal weight before pregnancy; ii) shift down one weight class; or iii) lose 10% of their body weight, significant relative reductions would be seen for gestational diabetes mellitus (GDM, 57/33/15%), hypertensive disorders of pregnancy (HDP, 26/16/6%), caesarean section (CS, 18/10/3%), and large for gestational age births (LGA, 24/14/3%). The NNT were lowest for the outcomes GDM, induction of labour, CS, and LGA, where they ranged from 13 to 73. The study suggests that a substantial proportion of adverse perinatal outcomes may be preventable through reductions in maternal pre-pregnancy weight. PMID:26961675

  15. 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

  16. Understanding the Association of Biomedical, Psychosocial and Behavioral Risks with Adverse Pregnancy Outcomes

    PubMed Central

    Kiely, Michele; El-Mohandes, Ayman A.E.; Gantz, Marie G.; Chowdhury, Dhuly; Thornberry, Jutta S.; El-Khorazaty, M. Nabil

    2011-01-01

    Objectives This study investigates the relationship between diabetes, hypertension, preeclampsia, and Body Mass Index (BMI) -- the most common and interrelated medical conditions occurring during pregnancy; sociodemographic and behavioral risk factors; and adverse pregnancy outcomes in high-risk urban African American women in Washington, DC. Methods Data are from a randomized controlled trial conducted in 6 prenatal clinics. Women in their 1st or 2nd trimester were screened for behavioral risks (smoking, environmental tobacco smoke exposure, depression, and intimate partner violence) and demographic eligibility. 1,044 were eligible, interviewed and followed through their pregnancies. Classification and Regression Trees (CART) methodology was used to: 1) explore the relationship between medical and behavioral risks (reported at enrollment), sociodemographic factors and pregnancy outcomes, 2) identify the relative importance of various predictors of adverse pregnancy outcomes, and 3) characterize women at the highest risk of poor pregnancy outcomes. Results Overall, the strongest predictors of poor outcomes were prepregnancy BMI, preconceptional diabetes, employment status, intimate partner violence, and depression. In CART analysis, preeclampsia was the first splitter for low birthweight; preconceptional diabetes was the first splitter for preterm birth (PTB) and neonatal intensive care admission; BMI was the first splitter for very PTB, large for gestational age, Cesarean section and perinatal death; and employment was the first splitter for miscarriage. Conclusions Preconceptional factors play a very important role in pregnancy outcomes. For many of these women, the risks that they bring into the pregnancy were more likely to impact their pregnancy outcome than events during pregnancy. PMID:21785892

  17. 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...

  18. Adverse pregnancy outcomes with assisted reproductive technology in non-obese women with polycystic ovary syndrome: a case-control study

    PubMed Central

    Han, Ae Ra; Cha, Sun Wha; Park, Chan Woo; Kim, Jin Yeong; Yang, Kwang Moon; Song, In Ok; Koong, Mi Kyoung; Kang, Inn Soo

    2011-01-01

    Objective To investigate adverse pregnancy outcomes in non-obese women with polycystic ovary syndrome (PCOS) compared with obese-PCOS and control groups. Methods Women with PCOS who underwent assisted reproductive technology (ART) from August, 2003 to December, 2007, were considered. A total of 336 women with PCOS were included in the study group and 1,003 infertile women who had tubal factor as an indication for ART were collected as controls. They were divided into four groups: a non-obese PCOS group, obese-PCOS group, non-obese tubal factor group, and obese tubal factor group, with obesity defined by a body mass index over 25 kg/m2, and reviewed focusing on the basal characteristics, ART outcomes, and adverse pregnancy outcomes. Results There was no difference among the groups' the clinical pregnancy rate or live birth rate. Regarding adverse pregnancy outcomes, the miscarriage rate, multiple pregnancy rate, and prevalence of preterm delivery and pregnancy induced hypertension were not different among the four groups. The incidence of small for gestational age infant was higher in the PCOS groups than the tubal factor groups (p<0.02). On the other hand, the morbidity of gestational diabetes mellitus (GDM) was not high in the non-obese PCOS group but was in the obese groups. And in the obese PCOS group, the newborns were heavier than in the other groups (p<0.02). Conclusion Non-obese PCOS presents many differences compared with obese PCOS, not only in the IVF-parameters but also in the morbidity of adverse pregnancy outcomes, especially in GDM and fetal macrosomia. PMID:22384427

  19. 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.

  20. Maternal nutrition--effect on fetal growth and outcome of pregnancy.

    PubMed

    Ramachandran, Prema

    2002-05-01

    During the first half of the 20th century, chronic energy undernutrition due to low dietary intake, repeated infections, and rapid succession of pregnancy were the factors most responsible for maternal undernutrition and consequent adverse outcomes of pregnancy. Efforts to improve dietary intake, treatment of infections, and provision of contraceptive care were the major focuses of intervention from 1950 to 1990. These interventions resulted in reduction in severe grades of undernutrition. However, there was no reduction in mild and moderate degrees of undernutrition and anemia during pregnancy and there was no significant improvement in the course and outcome of pregnancy, or in birth weight. During the 1990s, among the middle- and upper-income groups, there has been a progressive rise in obesity and consequent adverse effects. The advent of HIV infection in India in the 1980s will inevitably lead to increases in severe undernutrition associated with HIV infection in pregnancy and an adverse impact of maternal HIV infection on the fetus. Practicing physicians and nutritionists in the new millennium will therefore have to assess each person individually and provide appropriate advice regarding diet, exercise, fertility, and infection prevention and control in order to achieve optimum health and nutrition status during pregnancy and to prevent adverse pregnancy outcomes. PMID:12035855

  1. Clinical picture and outcome of Serious Adverse Events in the treatment of Onchocerciasis

    PubMed Central

    Awadzi, Kwablah

    2003-01-01

    Ivermectin (Mectizan®) is the only drug currently recommended for the treatment and control of onchocerciasis. Serious adverse events rarely occur during treatment, except in subjects heavily infected with Loa Loa. This review of drug-related serious adverse events in the treatment of onchocerciasis therefore revisited the pre-Mectizan® reference drugs, DEC and suramin, and other candidate drugs studied extensively for the treatment of human onchocerciasis. The benzimidazole carbamate derivatives and the antibiotic doxycycline were excluded, since no serious adverse events have been reported regarding their use. Using recommended definitions, serious adverse events reported or observed after the use of each drug were summarised, the level of attribution determined, and the results tabulated. Prominence was given to treatment-related deaths. The clinical picture of severe symptomatic postural hypotension is described and used to illustrate the difference between the severity and the seriousness of an adverse event. The epidemiology, management and outcome of serious adverse events are presented. The role of future research is discussed. PMID:14975063

  2. 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

  3. Risk for Gestational Diabetes Mellitus and Adverse Birth Outcomes in Chinese Women with Polycystic Ovary Syndrome

    PubMed Central

    Xiao, Qing; Cui, Yong-Yi; Lu, Jine; Zhang, Guo-Zheng

    2016-01-01

    Objective. To examine the association of polycystic ovary syndrome (PCOS) in early pregnancy with gestational diabetes mellitus (GDM) and adverse birth outcomes. Methods. In this retrospective cohort study including 2389 pregnant women, the medical records of 352 women diagnosed with PCOS were evaluated. Outcomes included GDM, preterm birth, low birth weight, macrosomia, and being small and large for gestational age. Multivariable logistic regression models were used to examine the association of the risk for GDM and adverse birth outcomes with PCOS after adjusting for confounders. Results. Women previously diagnosed with PCOS had a higher risk of GDM (adjusted odds ratio [OR] 1.55, 95% confidence interval [CI]: 1.14–2.09). A strong association was seen between PCOS and preterm birth (adjusted OR 1.69, 95% CI: 1.08–2.67). On stratified analysis, the adjusted OR for GDM among women with PCOS undergoing assisted reproductive technology was 1.44 (95% CI: 1.03–1.92) and among women with PCOS who conceived spontaneously was 1.60 (1.18–2.15). No increased risk for other adverse birth outcomes was observed. Conclusions. Women with PCOS were more likely to experience GDM and preterm birth. PMID:27066074

  4. 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

  5. Fetal tachycardias: management and outcome of 127 consecutive cases

    PubMed Central

    Simpson, J; Sharland, G

    1998-01-01

    Objective—To review the management and outcome of fetal tachycardia, and to determine the problems encountered with various treatment protocols.
Study design—Retrospective analysis.
Subjects—127 consecutive fetuses with a tachycardia presenting between 1980 and 1996 to a single tertiary centre for fetal cardiology. The median gestational age at presentation was 32 weeks (range 18 to 42).
Results—105 fetuses had a supraventricular tachycardia and 22 had atrial flutter. Overall, 52 fetuses were hydropic and 75 non-hydropic. Prenatal control of the tachycardia was achieved in 83% of treated non-hydropic fetuses compared with 66% of the treated hydropic fetuses. Digoxin monotherapy converted most (62%) of the treated non-hydropic fetuses, and 96% survived through the neonatal period. First line drug treatment for hydropic fetuses was more diverse, including digoxin (n = 5), digoxin plus verapamil (n = 14), and flecainide (n = 27). The response rates to these drugs were 20%, 57%, and 59%, respectively, confirming that digoxin monotherapy is a poor choice for the hydropic fetus. Response to flecainide was faster than to the other drugs. Direct fetal treatment was used in four fetuses, of whom two survived. Overall, 73% (n = 38) of the hydropic fetuses survived. Postnatally, 4% of the non-hydropic group had ECG evidence of pre-excitation, compared with 16% of the hydropic group; 57% of non-hydropic fetuses were treated with long term antiarrhythmics compared with 79% of hydropic fetuses.
Conclusions—Non-hydropic fetuses with tachycardias have a very good prognosis with transplacental treatment. Most arrhythmias associated with fetal hydrops can be controlled with transplacental treatment, but the mortality in this group is 27%. At present, there is no ideal treatment protocol for these fetuses and a large prospective multicentre trial is required to optimise treatment of both hydropic and non-hydropic fetuses.

 Keywords: fetal

  6. 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

  7. 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...

  8. 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.

  9. 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. PMID:20546772

  10. 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

  11. 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

  12. Adverse reproductive outcomes in families of atomic veterans: The feasibility of epidemiologic studies

    SciTech Connect

    1995-12-31

    This is an outstanding report from a distinguished academy committee, which in 71 pages of text provides the scientific basis for the carefully crafted 8-page executive summary. The principles and issues of the required epidemiological study are presented calmly and concisely, as are the ensuing short chapters on radiation biology, genetics and risk estimation, and all other adverse reproductive outcomes. The committee was mandated by Congress to determine the feasibility, cost and duration of a study on adverse reproductive outcomes in families of atomic veteran. The committee found that a scientifically adequate and epidemiologically valid study could not be mounted and the cost would be tens of millions of dollars lasting a decade. The Committee presents a number of well-discussed approaches in support of their position.

  13. 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

  14. [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. PMID:20541376

  15. 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

  16. 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

  17. Fetal Diagnostics and Fetal Intervention.

    PubMed

    McLaughlin, Ericka S; Schlosser, Brian A; Border, William L

    2016-03-01

    Advances in ultrasound technology and specialized training have allowed clinicians to diagnose congenital heart disease in utero and counsel families on perinatal outcomes and management strategies, including fetal cardiac interventions and fetal surgery. This article gives a detailed approach to fetal cardiac assessment and provides the reader with accompanying figures and video clips to illustrate unique views and sweeps invaluable to diagnosing congenital heart disease. We demonstrate that using a sequential segmental approach to evaluate cardiac anatomy enables one to decipher the most complex forms of congenital heart disease. Also provided is a review of fetal cardiac intervention and surgery from the fetal cardiologist's perspective. PMID:26876119

  18. Vitamin D Deficiency Strongly Predicts Adverse Medical Outcome Across Different Medical Inpatient Populations

    PubMed Central

    Graedel, Lena; Merker, Meret; Felder, Susan; Kutz, Alexander; Haubitz, Sebastian; Faessler, Lukas; Kaeslin, Martha; Huber, Andreas; Mueller, Beat; Schuetz, Philipp

    2016-01-01

    Abstract Vitamin D deficiency has been associated with several adverse outcomes mainly in the outpatient setting. The objective of this study was to examine the prevalence of vitamin D deficiency and its association with risk of adverse clinical outcomes in a large prospective cohort of medical inpatients. We collected clinical data and measured 25(OH)D levels in adult medical patients upon hospital admission and followed them for 30 days. Regression analyses adjusted for age, gender, comorbidities, and main medical diagnosis were performed to study the effect of vitamin D deficiency on several hospital outcomes. Of 4257 included patients, 1510 (35.47%) had 25(OH)D levels of 25 to 50 nmol/L (vitamin D insufficiency) and 797 (18.72%) had levels of <25nmol/L (severe deficiency). Vitamin D insufficiency and severe deficiency were associated (OR/HR, 95%CI) with an increased risk of 30-day mortality (OR 1.70, 1.22–2.36 and 2.70, 1.22–2.36) and increased length of stay (HR 0.88, 0.81–0.97 and 0.72, 0.65–0.81). Severe deficiency was associated with risk of falls (OR 1.77, 1.18–2.63), impaired Barthel index (OR 1.80, 1.42–2.28), and impairment in quality of life. Most associations remained robust after multivariate adjustment and in subgroups stratified by gender, age, comorbidities, and main diagnoses (P for interaction >0.05). In this comprehensive and large medical inpatient cohort, vitamin D deficiency was highly prevalent and strongly associated with adverse clinical outcome. Interventional research is urgently needed to prove the effect of vitamin D supplementation on these outcomes. PMID:27175650

  19. 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.

  20. 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

  1. The Violence Proneness Scale of the DUSI-R predicts adverse outcomes associated with substance abuse.

    PubMed

    Kirisci, Levent; Tarter, Ralph; Reynolds, Maureen

    2009-01-01

    Accuracy of the Violence Proneness Scale (VPS) of the Drug Use Screening Inventory (DUSI-R) was evaluated in 328 boys for predicting use of illegal drugs, DUI, selling drugs, sexually transmitted disease, car accident while under acute effects of drugs/alcohol, trading drugs for sex, injuries from a fight, and traumatic head injury. Boys were prospectively tracked from age 16 to 19 at which time these outcomes were documented in the interim period. The results demonstrated that the VPS score is a significant predictor of all outcomes. Prediction accuracy ranged between 62%-83%. These findings suggest that the VPS may be useful for identifying youths who are at high risk for using illicit drugs and commonly associated adverse outcomes. PMID:19283571

  2. 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. PMID:25567557

  3. 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

  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. 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

  6. 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

  7. 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

  8. Pivmecillinam and adverse birth and neonatal outcomes: a population-based cohort study.

    PubMed

    Vinther Skriver, Mette; Nørgaard, Mette; Pedersen, Lars; Carl Schønheyder, Henrik; Sørensen, Henrik Toft

    2004-01-01

    A previous study unexpectedly showed an increased, statistically imprecise, risk of low Apgar score in children of women redeeming prescriptions for pivmecillinam in late pregnancy. To improve statistical precision we extended the previous dataset with data for 5 more y, and in addition added more neonatal outcomes. We thus examined the risk of adverse birth and neonatal outcomes among pregnant users of pivmecillinam based on population-based registries in North Jutland County, Denmark. We included 63,659 women with a live birth, or stillbirth after the 28th week of gestation. 2031 had redeemed prescriptions for pivmecillinam any time during pregnancy, 559 in the first trimester and 371 within 28 d before delivery. Adjusted odds ratios were: birth defects 0.83 (95% confidence interval (95% CI) 0.53-1.32) for exposure during first trimester, preterm delivery 0.96 (95% CI 0.79-1.18) and low birth weight 0.79 (95% CI 0.52-1.20) for exposure any time during pregnancy, and stillbirth 1.19 (95% CI 0.30-4.80), low Apgar score 1.17 (95% CI 0.37-3.66), hypoglycaemia 1.03 (95% CI 0.53-2.00), and respiratory distress syndrome 0.79 (95% CI 0.38-1.68) for exposure within 28 d before delivery. Use of pivmecillinam during pregnancy did not appear to increase the risk of adverse birth and neonatal outcomes; however, statistical precision is still low. PMID:15513399

  9. 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

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

    PubMed

    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

    2016-02-01

    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

  11. 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

  12. 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

  13. Adolescent Alcohol Abuse and Adverse Adult Outcomes: Evaluating Confounds with Drinking-Discordant Twins

    PubMed Central

    Rose, Richard J.; Winter, Torsten; Viken, Richard J.; Kaprio, Jaakko

    2014-01-01

    Background Adolescent alcohol abuse is associated with adverse outcomes in early adulthood, but differences in familial status and structure and household and community environments correlate with both adolescent drinking and adverse adult outcomes and may explain their association. We studied drinking-discordant twin pairs to evaluate such confounds to ask: Will between-family associations replicate in within-family comparisons? Methods With longitudinal data from > 3,000 Finnish twins, we associated drinking problems at age 18½ with 13 outcomes assessed at age 25; included were sustained substance abuse, poor health, physical symptoms, early coital debut, multiple sexual partners, life dissatisfaction, truncated education, and financial problems. We assessed associations among twins as individuals with linear regression adjusted for correlated observations; within-family analyses of discordant twin pairs followed, comparing paired means for adult outcomes among co-twins discordant for adolescent problem drinking. Defining discordance by extreme scores on self-reported problem drinking at age 18½ permitted parallel analyses of twins as individuals and discordant twin pairs. Alternate definitions of pair-wise discordance and difference score correlations across the entire twin sample yielded supplementary analyses. Results All individual associations were highly significant for all definitions of discordance we employed. Depending on definitions of discordance, 11 to 13 comparisons of all drinking-discordant twin pairs and 3 to 6 comparisons of discordant monozygotic twin pairs replicated between-family associations. For most outcomes, effect size attenuated from individual level analysis to that within discordant MZ twin pairs providing evidence of partial confounding in associations reported in earlier research. The exception was the General Health Questionnaire; at age 25, GHQ-12 had equivalent associations with age 18½ RAPI across all comparisons

  14. 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

  15. 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

  16. 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

  17. Defining and Modeling Known Adverse Outcome Pathways: Domoic Acid and Neuronal Signaling as a Case Study

    SciTech Connect

    Watanabe, Karen H.; Andersen, Melvin E.; Basu, Nil; Carvan, Michael J.; Crofton, Kevin M.; King, Kerensa A.; Sunol, Cristina; Tiffany-Castiglioni, Evelyn; Schultz, Irvin R.

    2011-01-01

    An adverse outcome pathway (AOP) is a sequence of key events from a molecular-level initiating event and an ensuing cascade of steps to an adverse outcome with population level significance. To implement a predictive strategy for ecotoxicology, the multiscale nature of an AOP requires computational models to link salient processes (e.g., in chemical uptake, toxicokinetics, toxicodynamics, and population dynamics). A case study with domoic acid was used to demonstrate strategies and enable generic recommendations for developing computational models in an effort to move toward a toxicity testing paradigm focused on toxicity pathway perturbations applicable to ecological risk assessment. Domoic acid, an algal toxin with adverse effects on both wildlife and humans, is a potent agonist for kainate receptors (ionotropic glutamate receptors whose activation leads to the influx of Na+ and Ca2+). Increased Ca2+ concentrations result in neuronal excitotoxicity and cell death primarily in the hippocampus, which produces seizures, impairs learning and memory, and alters behavior in some species. Altered neuronal Ca2+ is a key process in domoic acid toxicity which can be evaluated in vitro. Further, results of these assays would be amenable to mechanistic modeling for identifying domoic acid concentrations and Ca2+ perturbations that are normal, adaptive, or clearly toxic. In vitro assays with outputs amenable to measurement in exposed populations can link in vitro to in vivo conditions, and toxicokinetic information will aid in linking in vitro results to the individual organism. Development of an AOP required an iterative process with three important outcomes: (1) a critically reviewed, stressor-specific AOP; (2) identification of key processes suitable for evaluation with in vitro assays; and (3) strategies for model development.

  18. Hyperactive children as young adults: driving abilities, safe driving behavior, and adverse driving outcomes.

    PubMed

    Fischer, Mariellen; Barkley, Russell A; Smallish, Lori; Fletcher, Kenneth

    2007-01-01

    ADHD has been linked to poorer driving abilities and greater adverse outcomes (crashes, citations) in clinic-referred cases of teens and adults with ADHD. No study, however, has focused systematically on ADHD children followed into adulthood. The present paper does so while measuring driving-related cognitive abilities, driving behavior, and history of adverse driving outcomes. A multi-method, multi-source battery of driving measures was collected at the young adult follow-up on hyperactive (H; N=147; mean age=21.1) and community control children (CC; N=71; mean age=20.5) followed for more than 13 years. More of the H than CC groups had been ticketed for reckless driving, driving without a license, hit-and-run crashes, and had their licenses suspended or revoked. Official driving records found more of the H group having received traffic citations and a greater frequency of license suspensions. The cost of damage in their initial crashes was also significantly greater in the H than CC group. Both self-report and other ratings of actual driving behavior revealed less safe driving practices being used by the H group. Observations by driving instructors during a behind-the-wheel road test indicated significantly more impulsive errors. Performance on a simulator further revealed slower and more variable reaction times, greater errors of impulsiveness (false alarms, poor rule following), more steering variability, and more scrapes and crashes of the simulated vehicle against road boundaries in the H than in the CC group. These findings suggest that children growing up with ADHD may either have fewer driving risks or possibly under-report those risks relative to clinic-referred adults with this disorder. Deficits in simulator performance and safe driving behavior, however, are consistent with clinic-referred adults with ADHD suggesting ongoing risks for such adverse driving outcomes in children growing up with ADHD. PMID:16919226

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

    PubMed Central

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

    2013-01-01

    Purpose Little is known 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 paper are to: 1) describe the functional characteristics of RC/AL residents; 2) examine the relationships between resident- and facility-characteristics and physical performance; and 3) determine the predictive value of physical performance for adverse outcomes. Design and Methods Data were derived from 1791 residents in 189 RC/AL facilities, participating in the Collaborative Studies of Long-Term Care. At baseline, residents were tested on four performance measures (grip strength, chair rise, balance, and walking speed), and other resident- and facility-level information was collected. Adverse outcomes were measured over one year. Results Average grip strength was 14 ± 7 kg; 61% of residents walked < 0.6 m/second (average 0.41 m/second); 26% could perform five chair rises; and only 19% could perform a tandem stand for a least one second. Multivariable analyses showed that more cognitive and functional impairment, depressive symptoms and comorbid conditions, and for-profit ownership, were associated with poorer physical performance. Controlling for individual characteristics, better performance on the four physical performance measures was associated with a reduced risk of nursing home placement, fracture, and decline in function over one year. Implication Simple performance measures identify modifiable functional deficits, and suggest targeted interventions to prolong independent mobility and aging in place in RC/AL facilities. PMID:18483432

  20. 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

  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. 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. PMID:26399566

  3. 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...

  4. 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...

  5. 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...

  6. Should we continue using amphotericin B deoxycholate for the treatment of fungal infections? Adverse events and clinical outcomes.

    PubMed

    Garbino, Jorge; Markham, Lydia; Matulionyte, Raimonda; Rives, Vincent; Lew, Daniel

    2006-01-01

    Amphotericin B deoxycholate (AmBd) has been a standard therapy for IFI but is associated with high adverse event and mortality rates. A retrospective review was undertaken to describe adverse events and clinical outcomes in adult patients with IFI treated with only AmBd as initial therapy. PMID:16449001

  7. 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

  8. 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

  9. Bisphenol A--Why an adverse outcome pathway framework needs to be applied.

    PubMed

    FitzGerald, R E; Wilks, M F

    2014-10-15

    Bisphenol A (BPA) is one of the most widely used and extensively studied chemicals. Numerous studies have reported in vitro effects or animal adverse findings at BPA doses lower than the no observed adverse effect levels (NOAELs) established in regulatory toxicity studies and used for human health risk assessment. Intensive discussions on the adequacy and relevance of test systems have not satisfactorily resolved whether positive or negative animal and/or in vitro findings are more relevant for human health risk assessment purposes. BPA imperfectly mimics endogenous estrogens at membrane-bound estrogen receptors in the fM-nM concentration range, and may have downstream pleiotropic effects such as human seminoma proliferation and mammary gland hyperplasia after in utero exposure which are not detectable in regulatory toxicology studies. We argue that a structured approach like the OECD Adverse Outcome Pathway (AOP) framework is needed to help researchers in designing relevant studies, and risk assessors in evaluating them. The huge amount of experimental data generated for BPA has highlighted data gaps in basic biology and the shortcomings of current approaches to hazard characterization and risk assessment. Establishing AOPs for BPA, and other endocrine active chemicals, will require major scientific as well as training investments by all responsible stakeholders. PMID:24831966

  10. 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

  11. 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

  12. 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

  13. Management and outcome of Bacille Calmette-Guérin vaccine adverse reactions

    PubMed Central

    Venkataraman, Aishwarya; Yusuff, Michael; Liebeschuetz, Susan; Riddell, Anna; Prendergast, Andrew J.

    2015-01-01

    Background Bacille Calmette-Guérin (BCG) vaccine is one of the most widely used vaccines globally. Management of local BCG complications (injection site reactions and suppurative or non-suppurative lymphadenitis) varies between clinicians, and the optimal approach remains uncertain. Aim To determine the clinical features, management and outcome of BCG complications at two large acute hospitals in London, United Kingdom. Methods All children presenting with complications of BCG vaccination between January 2008 and December 2013 were included in this observational study. Medical and electronic laboratory records were reviewed to determine clinical features, treatment and outcome. Results Sixty children presented with adverse reactions. Two-thirds (65%) presented with BCG lymphadenitis, one-third (30%) presented with injection site complications and two children (3%) presented with both injection site reaction and lymphadenitis; only one child (2%) had disseminated BCG disease. The majority (88%) of children with injection site reactions were managed conservatively; overall, 95% showed complete resolution within 6 months. Among children with lymphadenitis, 46% were managed conservatively, whilst 54% had anti-tuberculous therapy and/or a procedure (aspiration mostly, or surgery); complete resolution was seen in 59% of cases. Conclusions Injection site reactions and non-suppurative lymphadenitis were generally managed conservatively, with good outcomes. There was more variation in management and outcome of suppurative lymphadenitis and the optimal approach remains uncertain. PMID:26275478

  14. 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

  15. 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

  16. 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

  17. 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. PMID:26581746

  18. 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

  19. 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

  20. 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

  1. 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

  2. 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

  3. 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

  4. The Effects of Interpregnancy Intervals and Previous Pregnancy Outcome on Fetal Loss in Rwanda (1996–2010)

    PubMed Central

    Habimana-Kabano, Ignace; Broekhuis, Annelet; Hooimeijer, Pieter

    2015-01-01

    In 2005, a WHO consultation meeting on pregnancy intervals recommended a minimum interval of 6 months after a pregnancy disruption and an interval of two years after a live birth before attempting another pregnancy. Since then, studies have found contradictory evidence on the effect of shorter intervals after a pregnancy disruption. A binary regression analysis on 21532 last pregnancy outcomes from the 2000, 2005, and 2010 Rwanda Demographic and Health Surveys was done to assess the combined effects of the preceding pregnancy outcome and the interpregnancy intervals (IPIs) on fetal mortality in Rwanda. Risks of pregnancy loss are higher for primigravida and for mothers who lost the previous pregnancy and conceived again within 24 months. After a live birth, interpregnancy intervals less than two years do not increase the risk of a pregnancy loss. This study also confirms higher risks of fetal death when IPIs are beyond 5 years. An IPI of longer than 12 months after a fetal death is recommended in Rwanda. Particular attention needs to be directed to postpregnancy abortion care and family planning programs geared to spacing pregnancies should also include spacing after a fetal death. PMID:26613103

  5. Cytomegalovirus Seroprevalence in Pregnant Women and Association with Adverse Pregnancy/Neonatal Outcomes in Jiangsu Province, China

    PubMed Central

    Chen, Jie; Xu, Biyun; Zhou, Yi-Hua; Hu, Yali

    2014-01-01

    Background In this study, we aimed to determine the provincial population-based seroprevalence in pregnant women and to further explore the association of maternal CMV infection status and adverse pregnancy/neonatal/growth outcomes in Jiangsu, China. Methods In this case-control study, the sera from 527 pregnant women with adverse pregnancy/neonatal outcomes and 496 mothers of healthy infants in Jiangsu Province, collected at gestation age of 15–20 weeks, were tested for anti-CMV IgG, IgM and IgG avidity. Adverse pregnancy/neonatal outcomes were identified based on pregnancy/neonatal outcomes. Results The overall seroprevalence of anti-CMV IgG was 98.7%, with 99.4% and 98.0% in the case and control groups, respectively (P = 0.039). The prevalence of anti-CMV IgG+/IgM+, was higher in the case group than that in the control group (3.8% vs. 1.6%, P = 0.033). Anti-CMV IgG avidity assay showed that none in the control group were primarily infected, but five (0.9%) in the case group underwent primary infection (P = 0.084); all five infants of these women presented severe adverse neonatal/growth outcomes. Exact logistic regression analysis showed that anti-CMV IgG+/IgM+ was associated with adverse pregnancy/neonatal/growth outcomes (aOR = 2.44, 95% CI 1.01–6.48, P = 0.047). Maternal low education level and prior abnormal pregnancies also were risk factors for adverse pregnancy/neonatal outcomes. Conclusions In populations with very high prevalence of latent CMV infection, active maternal CMV infection during pregnancy might be a risk factor for adverse pregnancy/neonatal outcomes. PMID:25211647

  6. 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. PMID:26895641

  7. 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

  8. 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

  9. Indications for Cardiopulmonary Bypass During Pregnancy and Impact on Fetal Outcomes.

    PubMed

    Yuan, S-M

    2014-01-01

    Background: Cardiac operations in pregnant patients are a challenge for physicians in multidisciplinary teams due to the complexity of the condition which affects both mother and baby. Management strategies vary on a case-by-case basis. Feto-neonatal and maternal outcomes after cardiopulmonary bypass (CPB) in pregnancy, especially long-term follow-up results, have not been sufficiently described. Methods: This review was based on a complete literature retrieval of articles published between 1991 and April 30, 2013. Results: Indications for CPB during pregnancy were cardiac surgery in 150 (96.8 %) patients, most of which consisted of valve replacements for mitral and/or aortic valve disorders, resuscitation due to amniotic fluid embolism, autotransfusion, and circulatory support during cesarean section to improve patient survival in 5 (3.2 %) patients. During CPB, fetuses showed either a brief heart rate drop with natural recovery after surgery or, in most cases, fetal heart rate remained normal throughout the whole course of CPB. Overall feto-neonatal mortality was 18.6 %. In comparison with pregnant patients whose baby survived, feto-neonatal death occurred after a significantly shorter gestational period at the time of onset of cardiac symptoms, cardiac surgery/resuscitation under CPB in the whole patient setting, or cardiac surgery/resuscitation with CPB prior to delivery. Conclusions: The most common surgical indications for CPB during pregnancy were cardiac surgery, followed by resuscitation for cardiopulmonary collapse. CPB was used most frequently in maternal cardiac surgery/resuscitation in the second trimester. Improved CPB conditions including high flow, high pressure and normothermia or mild hypothermia during pregnancy have benefited maternal and feto-neonatal outcomes. A shorter gestational period and the use of CPB during pregnancy were closely associated with feto-neonatal mortality. It is therefore important to attempt delivery ahead of

  10. Sex Differences in Device Therapy for Heart Failure: Utilization, Outcomes, and Adverse Events

    PubMed Central

    Herz, Naomi D.; Engeda, Joseph; Zusterzeel, Robbert; Sanders, William E.; O'Callaghan, Kathryn M.; Strauss, David G.; Jacobs, Samantha B.; Selzman, Kimberly A.; Piña, Ileana L.

    2015-01-01

    Abstract Background: Multiple studies of heart failure patients demonstrated significant improvement in exercise capacity, quality of life, cardiac left ventricular function, and survival from cardiac resynchronization therapy (CRT), but the underenrollment of women in these studies is notable. Etiological and pathophysiological differences may result in different outcomes in response to this treatment by sex. The observed disproportionate representation of women suggests that many women with heart failure either do not meet current clinical criteria to receive CRT in trials or are not properly recruited and maintained in these studies. Methods: We performed a systematic literature review through May 2014 of clinical trials and registries of CRT use that stratified outcomes by sex or reported percent women included. One-hundred eighty-three studies contained sex-specific information. Results: Ninety percent of the studies evaluated included ≤35% women. Fifty-six articles included effectiveness data that reported response with regard to specific outcome parameters. When compared with men, women exhibited more dramatic improvement in specific parameters. In the studies reporting hazard ratios for hospitalization or death, women generally had greater benefit from CRT. Conclusions: Our review confirms women are markedly underrepresented in CRT trials, and when a CRT device is implanted, women have a therapeutic response that is equivalent to or better than in men, while there is no difference in adverse events reported by sex. PMID:25793483

  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. 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

  13. 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.

  14. Association of Increased Epicardial Adipose Tissue Thickness With Adverse Cardiovascular Outcomes in Patients With Atrial Fibrillation

    PubMed Central

    Chu, Chun-Yuan; Lee, Wen-Hsien; Hsu, Po-Chao; Lee, Meng-Kuang; Lee, Hung-Hao; Chiu, Cheng-An; Lin, Tsung-Hsien; Lee, Chee-Siong; Yen, Hsueh-Wei; Voon, Wen-Chol; Lai, Wen-Ter; Sheu, Sheng-Hsiung; Su, Ho-Ming

    2016-01-01

    Abstract The thickness of epicardial adipose tissue (EAT) was reported to be highly associated with the incidence and severity of atrial fibrillation (AF). This study was conducted to analyze the ability of EAT thickness in predicting adverse cardiovascular (CV) events in AF. In 190 persistent AF patients, we performed a comprehensive transthoracic echocardiographic examination with assessment of EAT thickness. The definition of CV events included CV mortality, hospitalization for heart failure, myocardial infarction, and stroke. There were 69 CV events including 19 CV deaths, 32 hospitalizations for heart failure, 3 myocardial infarctions, and 15 strokes during a mean follow-up of 29 (25th–75th percentile: 17–36) months. The multivariable analysis demonstrates that chronic heart failure, increased left ventricular (LV) mass index and the ratio of transmitral E-wave velocity to early diastolic mitral annulus velocity, decreased body mass index, and increased EAT thickness (per 1-mm increase, odds ratio 1.224, 95% confidence interval [CI] 1.096–1.368, P < 0.001) were associated with adverse CV events. Additionally, the addition of EAT thickness to a model containing CHA2DS2-VASc score, left atrial volume index, and LV systolic and diastolic function significantly improved the values in predicting CV events (global χ2 increase 14.65, P < 0.001 and integrated discrimination improvement 0.10, 95% CI 0.04–0.16, P < 0.001). In AF, EAT thickness was useful in predicting adverse CV events. Additionally, EAT thickness could provide incremental value for CV outcome prediction over traditional clinical and echocardiographic parameters in AF. PMID:26986099

  15. Association of Increased Epicardial Adipose Tissue Thickness With Adverse Cardiovascular Outcomes in Patients With Atrial Fibrillation.

    PubMed

    Chu, Chun-Yuan; Lee, Wen-Hsien; Hsu, Po-Chao; Lee, Meng-Kuang; Lee, Hung-Hao; Chiu, Cheng-An; Lin, Tsung-Hsien; Lee, Chee-Siong; Yen, Hsueh-Wei; Voon, Wen-Chol; Lai, Wen-Ter; Sheu, Sheng-Hsiung; Su, Ho-Ming

    2016-03-01

    The thickness of epicardial adipose tissue (EAT) was reported to be highly associated with the incidence and severity of atrial fibrillation (AF). This study was conducted to analyze the ability of EAT thickness in predicting adverse cardiovascular (CV) events in AF.In 190 persistent AF patients, we performed a comprehensive transthoracic echocardiographic examination with assessment of EAT thickness. The definition of CV events included CV mortality, hospitalization for heart failure, myocardial infarction, and stroke.There were 69 CV events including 19 CV deaths, 32 hospitalizations for heart failure, 3 myocardial infarctions, and 15 strokes during a mean follow-up of 29 (25th-75th percentile: 17-36) months. The multivariable analysis demonstrates that chronic heart failure, increased left ventricular (LV) mass index and the ratio of transmitral E-wave velocity to early diastolic mitral annulus velocity, decreased body mass index, and increased EAT thickness (per 1-mm increase, odds ratio 1.224, 95% confidence interval [CI] 1.096-1.368, P < 0.001) were associated with adverse CV events. Additionally, the addition of EAT thickness to a model containing CHA2DS2-VASc score, left atrial volume index, and LV systolic and diastolic function significantly improved the values in predicting CV events (global χ increase 14.65, P < 0.001 and integrated discrimination improvement 0.10, 95% CI 0.04-0.16, P < 0.001).In AF, EAT thickness was useful in predicting adverse CV events. Additionally, EAT thickness could provide incremental value for CV outcome prediction over traditional clinical and echocardiographic parameters in AF. PMID:26986099

  16. Adverse Outcomes After Hospitalization and Delirium in Persons With Alzheimer Disease

    PubMed Central

    Fong, Tamara G.; Jones, Richard N.; Marcantonio, Edward R.; Tommet, Douglas; Gross, Alden L.; Habtemariam, Daniel; Schmitt, Eva; Yap, Liang; Inouye, Sharon K.

    2012-01-01

    Background Hospitalization, frequently complicated by delirium, can be a life-changing event for patients with Alzheimer disease (AD). Objective To determine risks for institutionalization, cognitive decline, or death associated with hospitalization and delirium in patients with AD. Design Prospective cohort enrolled between 1991 and 2006 into the Massachusetts Alzheimer’s Disease Research Center (MADRC) patient registry. Setting Community-based. Participants 771 persons aged 65 years or older with a clinical diagnosis of AD. Measurements Hospitalization, delirium, death, and institutionalization were identified through administrative databases. Cognitive decline was defined as a decrease of 4 or more points on the Blessed Information-Memory-Concentration test score. Multivariate analysis was used to calculate adjusted relative risks (RRs). Results Of 771 participants with AD, 367 (48%) were hospitalized and 194 (25%) developed delirium. Hospitalized patients who did not have delirium had an increased risk for death (adjusted RR, 4.7 [95% CI, 1.9 to 11.6]) and institutionalization (adjusted RR, 6.9 [CI, 4.0 to 11.7]). With delirium, risk for death (adjusted RR, 5.4 [CI, 2.3 to 12.5]) and institutionalization (adjusted RR, 9.3 [CI, 5.5 to 15.7]) increased further. With hospitalization and delirium, the adjusted RR for cognitive decline for patients with AD was 1.6 (CI, 1.2 to 2.3). Among hospitalized patients with AD, 21% of the incidences of cognitive decline, 15% of institutionalization, and 6% of deaths were associated with delirium. Limitations Cognitive outcome was missing in 291 patients. Sensitivity analysis was performed to test the effect of missing data, and a composite outcome was used to decrease the effect of missing data. Conclusion Approximately 1 in 8 hospitalized patients with AD who develop delirium will have at least 1 adverse outcome, including death, institutionalization, or cognitive decline, associated with delirium. Delirium prevention may

  17. Chlorinated drinking water, cancers and adverse health outcomes in Gangtok, Sikkim, India.

    PubMed

    Sharma, Rabi N; Goel, Sudha

    2007-10-01

    Long-term impacts of drinking chlorinated water on the incidence of cancers and other adverse health outcomes were assessed in a population-based cross-sectional study. The study was conducted by comparing a group exposed to chlorinated drinking water for more than thirty years with control groups with less or no exposure to chlorine. A house-to-house survey was completed to gather information on residential history, age, education, income, source and extent of treatment of water and health characteristics. All residents below thirty years of age were excluded from the database used for analyses to ensure that the groups were comparable. Fourteen cancer cases were found in the long-term exposed groups of 1085 persons and 9 cancer cases in the two control populations of 725 persons. The odds ratio for cancers (OR) was 1.05 (95% CI = 0.43-2.65) and is not statistically significant. Reciprocal or inverse odds [corrected] ratios for gastrointestinal disorders, kidney problems and skin infections were statistically significant ranging from 2.06 (95% CI = 1.01-4.17) to 2.2 (95% CI = 1.45-3.33). These OR values indicate that there is no significant association between the incidence of cancer and exposure to chlorinated water while chlorinating drinking water significantly reduced the incidence of non-carcinogenic adverse health effects like gastrointestinal diseases, skin infections, and kidney diseases. PMID:18476370

  18. Is growth-discordance in twins a substantial risk factor in adverse neonatal outcomes?

    PubMed

    Frezza, Simonetta; Gallini, Francesca; Puopolo, Maria; De Carolis, Maria P; D'Andrea, Vito; Guidone, Paola I; Luciano, Rita; Zuppa, Antonio A; Romagnoli, Costantino

    2011-10-01

    To evaluate whether growth discordance is an independent risk factor in the neonatal outcome of the smaller twin, all medical records of twin pregnancies delivered between 26 and 41 weeks during a 5-year period (January 2004-December 2008) were reviewed. Among the 49 selected twins, weight discordance was 15-20% in 7 infants, 21-30% in 16 infants, 31-40% in 16 infants and > 40% in 10 infants. No significant differences between the four groups were found with regards to obstetric complications and neonatal disease. Occurrence of birthweight below the 10th percentile and rate of admission to the neonatal intensive care unit significantly increased as intra-pair birthweight difference increased (p = .03). The > 40% discordant group had a significantly lower gestational age (p = .03), lower birthweight (p = .007) and a significantly higher mortality rate (4/10 versus 3/39 p = .04) in comparison with the other discordant groups. Multiple logistic regression analysis showed that birthweight was the single independent and consistent factor associated with elevated risks of mortality. For every 250 g increase in birthweight, the risk for mortality decreased by about 84% [RR 0.16(CI 0.00-0.70)]. Gestational age was the most reliable predictor for major neonatal complications. For every 1-week increase in gestational age a significant decreased risk for all outcomes was found. Discordance alone should not be considered as a predictor for adverse neonatal outcome. Neonatal outcome in discordant twins appears to be related to gestational age and birthweight rather than to the degree of discordance. PMID:21962140

  19. Periodontal Treatment for Preventing Adverse Pregnancy Outcomes: A Meta- and Trial Sequential Analysis

    PubMed Central

    Schwendicke, Falk; Karimbux, Nadeem; Allareddy, Veerasathpurush; Gluud, Christian

    2015-01-01

    Objectives Periodontal treatment might reduce adverse pregnancy outcomes. The efficacy of periodontal treatment to prevent preterm birth, low birth weight, and perinatal mortality was evaluated using meta-analysis and trial sequential analysis. Methods An existing systematic review was updated and meta-analyses performed. Risk of bias, heterogeneity, and publication bias were evaluated, and meta-regression performed. Subgroup analysis was used to compare different studies with low and high risk of bias and different populations, i.e., risk groups. Trial sequential analysis was used to assess risk of random errors. Results Thirteen randomized clinical trials evaluating 6283 pregnant women were meta-analyzed. Four and nine trials had low and high risk of bias, respectively. Overall, periodontal treatment had no significant effect on preterm birth (odds ratio [95% confidence interval] 0.79 [0.57-1.10]) or low birth weight (0.69 [0.43-1.13]). Trial sequential analysis demonstrated that futility was not reached for any of the outcomes. For populations with moderate occurrence (<20%) of preterm birth or low birth weight, periodontal treatment was not efficacious for any of the outcomes, and trial sequential analyses indicated that further trials might be futile. For populations with high occurrence (≥20%) of preterm birth and low birth weight, periodontal treatment seemed to reduce the risk of preterm birth (0.42 [0.24-0.73]) and low birth weight (0.32 [0.15-0.67]), but trial sequential analyses showed that firm evidence was not reached. Periodontal treatment did not significantly affect perinatal mortality, and firm evidence was not reached. Risk of bias, but not publication bias or patients’ age modified the effect estimates. Conclusions Providing periodontal treatment to pregnant women could potentially reduce the risks of perinatal outcomes, especially in mothers with high risks. Conclusive evidence could not be reached due to risks of bias, risks of random

  20. 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. PMID:26709552

  1. Waterlow score as a surrogate marker for predicting adverse outcome in acute pancreatitis.

    PubMed

    Gillick, K; Elbeltagi, H; Bhattacharya, S

    2016-01-01

    Introduction Introduced originally to stratify risk for developing decubitus ulcers, the Waterlow scoring system is recorded routinely for surgical admissions. It is a composite score, reflecting patients' general condition and co-morbidities. The aim of this study was to investigate whether the Waterlow score can be used as an independent surrogate marker to predict severity and adverse outcome in acute pancreatitis. Methods In this retrospective analysis, a consecutive cohort was studied of 250 patients presenting with acute pancreatitis, all of whom had their Waterlow score calculated on admission. Primary outcome measures were length of hospital stay and mortality. Secondary outcome measures included rate of intensive care unit (ICU) admission and development of complications such as peripancreatic free fluid, pancreatic necrosis and pseudocyst formation. Correlation of the Waterlow score with some known markers of disease severity and outcomes was also analysed. Results The Waterlow score correlated strongly with the most commonly used marker of disease severity, the Glasgow score (analysis of variance, p=0.0012). Inpatient mortality, rate of ICU admission and length of hospital stay increased with a higher Waterlow score (Mann-Whitney U test, p=0.0007, p=0.049 and p=0.0002 respectively). There was, however, no significant association between the Waterlow score and the incidence of three known complications of pancreatitis: presence of peripancreatic fluid, pancreatic pseudocyst formation and pancreatic necrosis. Receiver operating characteristic curve analysis demonstrated good predictive power of the Waterlow score for mortality (area under the curve [AUC]: 0.73), ICU admission (AUC: 0.65) and length of stay >7 days (AUC: 0.64). This is comparable with the predictive power of the Glasgow score and C-reactive protein. Conclusions The Waterlow score for patients admitted with acute pancreatitis could provide a useful tool in prospective assessment of disease

  2. Adverse events and outcomes of procedural sedation and analgesia in major trauma patients

    PubMed Central

    Green, Robert S.; Butler, Michael B.; Campbell, Samuel G.; Erdogan, Mete

    2015-01-01

    Context: Trauma patients requiring procedural sedation and analgesia (PSA) may have increased risk of adverse events (AEs) and poor outcomes. Aims: To determine the incidence of AEs in adult major trauma patients who received PSA and to evaluate their postprocedural outcomes. Settings and Design: Retrospective analysis of adult patients (age >16) who received PSA between 2006 and 2014 at a Canadian academic tertiary care center. Materials and Methods: We compared the incidence of PSA-related AEs in trauma patients with nontrauma patients. Postprocedural outcomes including Intensive Care Unit admission, length of hospital stay, and mortality were compared between trauma patients who did or did not receive PSA. Statistical Analysis Used: Descriptive statistics and multivariable logistic regression. Results: Overall, 4324 patients received PSA during their procedure, of which 101 were trauma patients (107 procedures). The majority (77%) of these 101 trauma patients were male, relatively healthy (78% with American Society of Anesthesiologists Physical Status [ASA-PS] 1), and most (85%) of the 107 procedures were orthopedic manipulations. PSA-related AEs were experienced by 45.5% of the trauma group and 45.9% of the nontrauma group. In the trauma group, the most common AEs were tachypnea (23%) and hypotension (20%). After controlling for age, gender, and ASA-PS, trauma patients were more likely than nontrauma patients to develop hypotension (odds ratio 1.79; 95% confidence interval 1.11-2.89). Conclusion: Although trauma patients were more likely than nontrauma patients to develop hypotension during PSA, their outcomes were not worse compared to trauma patients who did not have PSA. PMID:26604527

  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. 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

  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. 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

  7. 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

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

    PubMed

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

    2015-08-01

    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

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

    PubMed Central

    Aarsand, Aasne Karine; Sandberg, Sverre

    2010-01-01

    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. PMID:20978938

  10. 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

  11. 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

  12. Cardiovascular recovery from psychological and physiological challenge and risk for adverse cardiovascular outcomes and all-cause mortality

    PubMed Central

    Panaite, Vanessa; Salomon, Kristen; Jin, Alvin; Rottenberg, Jonathan

    2015-01-01

    Objective Exaggerated cardiovascular (CV) reactivity to laboratory challenge has been shown to predict future CV morbidity and mortality. CV recovery, has been less studied, and has yielded inconsistent findings, possibly due to presence of moderators. Reviews on the relationship between CV recovery and CV outcomes have been limited to cross-sectional studies and have not considered methodological factors. We performed a comprehensive meta-analytic review of the prospective literature investigating CV recovery to physical and psychological challenge and adverse cardiovascular outcomes. Methods We searched PsycINFO and PubMed for prospective studies investigating the relationship between CV recovery and adverse CV outcomes. Studies were coded for variables of interest and for effect sizes (ES). We conducted a random effects weighted meta-analysis. Moderators were examined with ANOVA-analog and meta-regression analyses. Results Thirty seven studies met inclusion criteria (N=125386). Impaired recovery from challenge predicted adverse cardiovascular outcomes (summary effect, r = .17, p < .001). Physical challenge was associated with larger predictive effects than psychological challenge. Moderator analyses revealed that recovery measured at 1 minute post-exercise, passive recovery, use of mortality as an outcome measure, and older sample age were associated with larger effects. Conclusions Poor recovery from laboratory challenges predicts adverse CV outcomes, with recovery from exercise serving as a particularly strong predictor of CV outcomes. The overall ES for recovery and CV outcomes is similar to that observed for CV reactivity and suggests that the study of recovery may have incremental value for understanding adverse CV outcomes. PMID:25829236

  13. 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

  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. PMID:24969352

  15. Adverse birth outcomes in the vicinity of industrial installations in Spain 2004-2008.

    PubMed

    Castelló, Adela; Río, Isabel; García-Pérez, Javier; Fernández-Navarro, Pablo; Waller, Lance A; Clennon, Julie A; Bolúmar, Francisco; López-Abente, Gonzalo

    2013-07-01

    Industrial activity is one of the main sources of ambient pollution in developed countries. However, research analyzing its effect on birth outcomes is inconclusive. We analyzed the association between proximity of mother's municipality of residence to industries from 24 different activity groups and risk of very (VPTB) and moderate (MPTB) preterm birth, very (VLBW) and moderate (MLBW) low birth weight, and small for gestational age (SGA) in Spain, 2004-2008. An ecological study was defined, and a "near vs. far" analysis (3.5 km threshold) was carried out using Hierarchical Bayesian models implemented via Integrated Nested Laplace Approximation. VPTB risk was higher for mothers living near pharmaceutical companies. Proximity to galvanization and hazardous waste management industries increased the risk of MPTB. Risk of VLBW was higher for mothers residing near pharmaceutical and non-hazardous or animal waste management industries. For MLBW many associations were found, being notable the proximity to mining, biocides and animal waste management plants. The strongest association for SGA was found with proximity to management animal waste plants. These results highlight the importance of further research on the relationship between proximity to industrial sites and the occurrence of adverse birth outcomes especially for the case of pharmaceutical and animal waste management activities. PMID:23322413

  16. 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

  17. 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. PMID:25288430

  18. 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

  19. 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. PMID:24097938

  20. 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

  1. Vitamin D in pregnancy and lactation: maternal, fetal, and neonatal outcomes from human and animal studies.

    PubMed

    Kovacs, Christophers S

    2008-08-01

    During pregnancy and lactation, mothers require significant amounts of calcium to pass on to the developing fetus and suckling neonate, respectively. Given the dependence of adult calcium concentrations and bone metabolism on vitamin D, one might anticipate that vitamin D sufficiency would be even more critical during pregnancy and lactation. However, maternal adaptations during pregnancy and lactation and fetal adaptations provide the necessary calcium relatively independently of vitamin D status. It is the vitamin D-deficient or insufficient neonate who is at risk of problems, including hypocalcemia and rickets. Due to poor penetrance of vitamin D and 25-hydroxyvitamin D [25(OH)D] into milk, exclusively breastfed infants are at higher risk of vitamin D deficiency than are formula-fed infants. Dosing recommendations for women during pregnancy and lactation might be best directed toward ensuring that the neonate is vitamin D-sufficient and that this sufficiency is maintained during infancy and beyond. A dose of vitamin D that provides 25(OH)D sufficiency in the mother during pregnancy should provide normal cord blood concentrations of 25(OH)D. Research has shown that during lactation, supplements administered directly to the infant can easily achieve vitamin D sufficiency; the mother needs much higher doses (100 mug or 4000 IU per day) to achieve adult-normal 25(OH)D concentrations in her exclusively breastfed infant. In addition, the relation (if any) of vitamin D insufficiency in the fetus or neonate to long-term nonskeletal outcomes such as type 1 diabetes and other chronic diseases needs to be investigated. PMID:18689394

  2. 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

  3. 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

  4. 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

  5. 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

  6. 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

  7. 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

  8. 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

  9. A comparison between amniotic fluid index and the single deepest vertical pocket technique in predicting adverse outcome in prolonged pregnancy

    PubMed Central

    Rosati, Paolo; Guariglia, Lorenzo; Cavaliere, Anna Franca; Ciliberti, Paola; Buongiorno, Silvia; Ciardulli, Andrea; Cianci, Stefano; Vitale, Salvatore Giovanni; Cignini, Pietro; Mappa, Ilenia

    2015-01-01

    Objective to compare perinatal outcome in induced postterm pregnancies with normal amniotic volume and in patients with prolonged pregnancy undergone induction for oligohydramnios, evaluated by two different ultrasonographic methods. Methods amniotic fluid volume was measured, using Single Deepest Vertical Pocket (SDVP) and Amniotic Fluid Index (AFI), in 961 singleton uncomplicated prolonged pregnancies. In 109 of these patients, hospitalization was planned for induction of labor, during or after 42 weeks of gestation, for oligohydramnios, postterm pregnancy and other indications in 47, 51 and 11 cases, respectively. Perinatal outcome included: rate of caesarean section, fetal distress, non reassuring fetal heart tracing, presence of meconium, umbilical artery pH < 7.1, Apgar score at 5 minutes < 7, admission to neonatal intensive care unit (NICU). Results oligohydramnios was diagnosed in 4.89% of cases, when at least one of the two methods was used. A reduced AFI and SDVP value identified 4.47% and 3.75% of cases, respectively, even if without statistical difference. No statistical differences were reported in perinatal outcomes in postterm versus prolonged pregnancies with oligohydramnios, also in relation to the two different ultrasonographic methods. Conclusions oligohydramnios is more frequently diagnosed using AFI than SDVP, consequently determining a higher rate of induction of labor. Moreover, perinatal outcome in prolonged induced pregnancies is not affected by oligohydramnios. PMID:26918093

  10. 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

  11. Independent Determinants of Maternal and Fetal Outcomes in a Sample of Pregnant Outpatients With Normal Blood Pressure, Chronic Hypertension, Gestational Hypertension, and Preeclampsia.

    PubMed

    Cicero, Arrigo F G; Degli Esposti, Daniela; Immordino, Vincenzo; Morbini, Martino; Baronio, Cristina; Rosticci, Martina; Borghi, Claudio

    2015-10-01

    The aim of this retrospective study was to evaluate the main independent prognostic factors of negative maternal and fetal outcomes in a relatively large sample of pregnant outpatients (N=906) who were normotensive or affected by chronic hypertension, gestational hypertension, or preeclampsia. Among the studied parameters, the ones significantly associated with negative maternal outcomes were a diagnosis of preeclampsia (vs other forms of hypertension or normotension) and higher serum uric acid level, while antihypertensive treatment, number of previous deliveries, and blood pressure (BP) control at deliveries seemed to be protective. Regarding negative fetal outcomes, the parameters significantly associated with a negative maternal outcome were a diagnosis of preeclampsia (vs other forms of hypertension or normotension) and mother pre-pregnancy body mass index, while antihypertensive treatment and BP control at delivery seemed to be protective. Specific patient characteristics should help to predict the risk of negative maternal and fetal outcomes. PMID:26173048

  12. 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

  13. 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

  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. 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

  17. 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

  18. Prevalence of Adverse Pregnancy Outcomes, by Maternal Diabetes Status at First and Second Deliveries, Massachusetts, 1998–2007

    PubMed Central

    Kotelchuck, Milton; Wilson, Hoyt G.; Diop, Hafsatou; Shapiro-Mendoza, Carrie K.; England, Lucinda J.

    2015-01-01

    Introduction Understanding patterns of diabetes prevalence and diabetes-related complications across pregnancies could inform chronic disease prevention efforts. We examined adverse birth outcomes by diabetes status among women with sequential, live singleton deliveries. Methods We used data from the 1998–2007 Massachusetts Pregnancy to Early Life Longitudinal Data System, a population-based cohort of deliveries. We restricted the sample to sets of parity 1 and 2 deliveries. We created 8 diabetes categories using gestational diabetes mellitus (GDM) and chronic diabetes mellitus (CDM) status for the 2 deliveries. Adverse outcomes included large for gestational age (LGA), macrosomia, preterm birth, and cesarean delivery. We computed prevalence estimates for each outcome by diabetes status. Results We identified 133,633 women with both parity 1 and 2 deliveries. Compared with women who had no diabetes in either pregnancy, women with GDM or CDM during any pregnancy had increased risk for adverse birth outcomes; the prevalence of adverse outcomes was higher in parity 1 deliveries among women with no diabetes in parity 1 and GDM in parity 2 (for LGA [8.5% vs 15.1%], macrosomia [9.7% vs. 14.9%], cesarean delivery [24.7% vs 31.3%], and preterm birth [7.7% vs 12.9%]); and higher in parity 2 deliveries among those with GDM in parity 1 and no diabetes in parity 2 (for LGA [12.3% vs 18.2%], macrosomia [12.3% vs 17.2%], and cesarean delivery [27.0% vs 37.9%]). Conclusions Women with GDM during one of 2 sequential pregnancies had elevated risk for adverse outcomes in the unaffected pregnancy, whether the diabetes-affected pregnancy preceded or followed it. PMID:26652218

  19. Fetal and infant origins of asthma.

    PubMed

    Duijts, Liesbeth

    2012-01-01

    Previous studies have suggested that asthma, like other common diseases, has at least part of its origin early in life. Low birth weight has been shown to be associated with increased risks of asthma, chronic obstructive airway disease, and impaired lung function in adults, and increased risks of respiratory symptoms in early childhood. The developmental plasticity hypothesis suggests that the associations between low birth weight and diseases in later life are explained by adaptation mechanisms in fetal life and infancy in response to various adverse exposures. Various pathways leading from adverse fetal and infant exposures to growth adaptations and respiratory health outcomes have been studied, including fetal and early infant growth patterns, maternal smoking and diet, children's diet, respiratory tract infections and acetaminophen use, and genetic susceptibility. Still, the specific adverse exposures in fetal and early postnatal life leading to respiratory disease in adult life are not yet fully understood. Current studies suggest that both environmental and genetic factors in various periods of life, and their epigenetic mechanisms may underlie the complex associations of low birth weight with respiratory disease in later life. New well-designed epidemiological studies are needed to identify the specific underlying mechanisms. This review is focused on specific adverse fetal and infant growth patterns and exposures, genetic susceptibility, possible respiratory adaptations and perspectives for new studies. PMID:22350146

  20. 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.

  1. Adverse Outcomes Among Homeless Adolescents and Young Adults Who Report a History of Traumatic Brain Injury

    PubMed Central

    Harpin, Scott B.; Grubenhoff, Joseph A.; Rivara, Frederick P.

    2014-01-01

    Objectives. We examined the prevalence of self-reported traumatic brain injury (TBI) among homeless young people and explored whether sociodemographic characteristics, mental health diagnoses, substance use, exposure to violence, or difficulties with activities of daily living (ADLs) were associated with TBI. Methods. We analyzed data from the Wilder Homelessness Study, in which participants were recruited in 2006 and 2009 from streets, shelters, and locations in Minnesota that provide services to homeless individuals. Participants completed 30-minute interviews to collect information about history of TBI, homelessness, health status, exposure to violence (e.g., childhood abuse, assault), and other aspects of functioning. Results. Of the 2732 participating adolescents and young adults, 43% reported a history of TBI. Participants with TBI became homeless at a younger age and were more likely to report mental health diagnoses, substance use, suicidality, victimization, and difficulties with ADLs. The majority of participants (51%) reported sustaining their first injury prior to becoming homeless or at the same age of their first homeless episode (10%). Conclusions. TBI occurs frequently among homeless young people and is a marker of adverse outcomes such as mental health difficulties, suicidal behavior, substance use, and victimization. PMID:25122029

  2. 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.

  3. 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

  4. 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

  5. Internal exposure dynamics drive the Adverse Outcome Pathways of synthetic glucocorticoids in fish.

    PubMed

    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

  6. 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.

  7. 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. PMID:25943792

  8. Quantitative Adverse Outcome Pathway Analysis of Hatching in Zebrafish with CuO Nanoparticles.

    PubMed

    Muller, Erik B; Lin, Sijie; Nisbet, Roger M

    2015-10-01

    This study develops and evaluates a mechanistic model of the hatching of zebrafish eggs that were exposed to CuO engineered nanoparticles (ENP) in a high-throughput screening system and places this model in an adverse outcome pathway (AOP) that also includes CuO ENP dissolution and Cu bioaccumulation. Cu(2+) inhibits the proteolytic activity of Zebrafish Hatching Enzyme 1 and thereby delay or impair hatching success. This study demonstrates that noncompetitive inhibition kinetics describe the impact of dissolved Cu on hatching; it is estimated that indefinitely long exposure to 1.88 μM dissolved Cu in the environment reduces hatching enzyme activity by 50%. The complexity arising from CuO ENP dissolution and CuO ENP assisted bioaccumulation of Cu has led to apparently contradictory findings about ion versus "nano" effects on hatching. Model-mediated data analyses indicate that, relative to copper salts, CuO ENPs increase the uptake rates of Cu into the perivitelline space up to 8 times. The toxicity assessment framework in this study can be adapted to accommodate other types of toxicant, environmental samples and other aquatic oviparous species. PMID:26378804

  9. Delay of Treatment Initiation Does Not Adversely Affect Survival Outcome in Breast Cancer

    PubMed Central

    Yoo, Tae-Kyung; Han, Wonshik; Moon, Hyeong-Gon; Kim, Jisun; Lee, Jun Woo; Kim, Min Kyoon; Lee, Eunshin; Kim, Jongjin; Noh, Dong-Young

    2016-01-01

    Purpose Previous studies examining the relationship between time to treatment and survival outcome in breast cancer have shown inconsistent results. The aim of this study was to analyze the overall impact of delay of treatment initiation on patient survival and to determine whether certain subgroups require more prompt initiation of treatment. Materials and Methods This study is a retrospective analysis of stage I-III patients who were treated in a single tertiary institution between 2005 and 2008. Kaplan-Meier survival analysis and Cox proportional hazards regression model were used to evaluate the impact of interval between diagnosis and treatment initiation in breast cancer and various subgroups. Results A total of 1,702 patients were included. Factors associated with longer delay of treatment initiation were diagnosis at another hospital, medical comorbidities, and procedures performed before admission for surgery. An interval between diagnosis and treatment initiation as a continuous variable or with a cutoff value of 15, 30, 45, and 60 days had no impact on disease-free survival (DFS). Subgroup analyses for hormone-responsiveness, triple-negative breast cancer, young age, clinical stage, and type of initial treatment showed no significant association between longer delay of treatment initiation and DFS. Conclusion Our results show that an interval between diagnosis and treatment initiation of 60 days or shorter does not appear to adversely affect DFS in breast cancer. PMID:26511801

  10. Fetal Heart Rate and Variability: Stability and Prediction to Developmental Outcomes in Early Childhood

    PubMed Central

    DiPietro, Janet A.; Bornstein, Marc H.; Hahn, Chun-Shin; Costigan, Kathleen; Achy-Brou, Aristide

    2008-01-01

    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 was demonstrated. Fetal heart rate variability at or after 28 weeks gestation and steeper developmental trajectories were significantly associated with mental and psychomotor development at 2 years (n = 82) and language ability at 2.5 years (n = 61). These data suggest that the foundations of individual differences in autonomic control originate during gestation and the developmental momentum of the fetal period continues after birth. PMID:17988321

  11. 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

  12. 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 ...

  13. 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 ...

  14. 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...

  15. 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...

  16. 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 ...

  17. 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...

  18. 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...

  19. 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

  20. Risk of adverse birth outcomes in populations living near landfill sites

    PubMed Central

    Elliott, Paul; Briggs, David; Morris, Sara; de Hoogh, Cornelis; Hurt, Christopher; Jensen, Tina Kold; Maitland, Ian; Richardson, Sylvia; Wakefield, Jon; Jarup, Lars

    2001-01-01

    Objective To investigate the risk of adverse birth outcomes associated with residence near landfill sites in Great Britain. Design Geographical study of risks of adverse birth outcomes in populations living within 2 km of 9565 landfill sites operational at some time between 1982 and 1997 (from a total of 19 196 sites) compared with those living further away. Setting Great Britain. Subjects Over 8.2 million live births, 43 471 stillbirths, and 124 597 congenital anomalies (including terminations). Main outcome measures All congenital anomalies combined, some specific anomalies, and prevalence of low and very low birth weight (<2500 g and <1500 g). Results For all anomalies combined, relative risk of residence near landfill sites (all waste types) was 0.92 (99% confidence interval 0.907 to 0.923) unadjusted, and 1.01 (1.005 to 1.023) adjusted for confounders. Adjusted risks were 1.05 (1.01 to 1.10) for neural tube defects, 0.96 (0.93 to 0.99) for cardiovascular defects, 1.07 (1.04 to 1.10) for hypospadias and epispadias (with no excess of surgical correction), 1.08 (1.01 to 1.15) for abdominal wall defects, 1.19 (1.05 to 1.34) for surgical correction of gastroschisis and exomphalos, and 1.05 (1.047 to 1.055) and 1.04 (1.03 to 1.05) for low and very low birth weight respectively. There was no excess risk of stillbirth. Findings for special (hazardous) waste sites did not differ systematically from those for non-special sites. For some specific anomalies, higher risks were found in the period before opening compared with after opening of a landfill site, especially hospital admissions for abdominal wall defects. Conclusions We found small excess risks of congenital anomalies and low and very low birth weight in populations living near landfill sites. No causal mechanisms are available to explain these findings, and alternative explanations include data artefacts and residual confounding. Further studies are needed to help differentiate between the various

  1. Fetal outcome of trisomy 18 diagnosed after 22 weeks of gestation: Experience of 123 cases at a single perinatal center.

    PubMed

    Nagase, Hiromi; Ishikawa, Hiroshi; Toyoshima, Katsuaki; Itani, Yasufumi; Furuya, Noritaka; Kurosawa, Kenji; Hirahara, Fumiki; Yamanaka, Michiko

    2016-01-01

    To investigate the pregnancy outcome of the fetuses with trisomy 18, we studied 123 cases of trisomy 18 who were born at our hospital from 1993 to 2009. Among them, 95.9% were diagnosed with trisomy 18 prenatally. Prenatal ultrasound findings showed fetal growth restriction in 77.2%, polyhydramnios in 63.4% and congenital heart defects in 95.1%. For 18 cases, cesarean section (C-section) was chosen, and for 75 cases, transvaginal delivery was chosen. Premature delivery occurred in 35.5%. Stillbirths occurred in 50 cases (40.7%). Fetal demise before onset of labor occurred in 30 cases and fetal demise during labor occurred in 20 cases which was 26.7% of vaginal deliveries. Among the 73 live-born infants, the survival rate for 24 h, 1 week, 1 month and 1 year were 63%, 43%, 33% and 3%. The median survival time was 3.5 days. There was no significant difference between the survival time of C-section and that of vaginal delivery. However, for the births involving breech presentation, the survival time of C-section was significantly longer than that of vaginal delivery. When the fetus is diagnosed with trisomy 18, the parents have to make many choices. These findings constitute critical information in prenatal counseling to the couples whose fetuses have been found to have trisomy 18, especially when they choose palliative approaches in the perinatal management. PMID:26104883

  2. An Outcome-based Approach for the Creation of Fetal Growth Standards: Do Singletons and Twins Need Separate Standards?

    PubMed Central

    Fahey, John; Platt, Robert W.; Liston, Robert M.; Lee, Shoo K.; Sauve, Reg; Liu, Shiliang; Allen, Alexander C.; Kramer, Michael S.

    2009-01-01

    Contemporary fetal growth standards are created by using theoretical properties (percentiles) of birth weight (for gestational age) distributions. The authors used a clinically relevant, outcome-based methodology to determine if separate fetal growth standards are required for singletons and twins. All singleton and twin livebirths between 36 and 42 weeks’ gestation in the United States (1995–2002) were included, after exclusions for missing information and other factors (n = 17,811,922). A birth weight range was identified, at each gestational age, over which serious neonatal morbidity and neonatal mortality rates were lowest. Among singleton males at 40 weeks, serious neonatal morbidity/mortality rates were lowest between 3,012 g (95% confidence interval (CI): 3,008, 3,018) and 3,978 g (95% CI: 3,976, 3,980). The low end of this optimal birth weight range for females was 37 g (95% CI: 21, 53) less. The low optimal birth weight was 152 g (95% CI: 121, 183) less for twins compared with singletons. No differences were observed in low optimal birth weight by period (1999–2002 vs. 1995–1998), but small differences were observed for maternal education, race, parity, age, and smoking status. Patterns of birth weight-specific serious neonatal morbidity/neonatal mortality support the need for plurality-specific fetal growth standards. PMID:19126584

  3. 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.

  4. Impact of Different Childhood Adversities on 1-Year Outcomes of Psychotic Disorder in the Genetics and Psychosis Study.

    PubMed

    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

    2016-03-01

    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

  5. 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

  6. 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

  7. 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…

  8. 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

  9. A meta-analysis of exposure to particulate matter and adverse birth outcomes

    PubMed Central

    2015-01-01

    Objectives The objective of this study was to conduct a systematic review to provide summarized evidence on the association between maternal exposure to particulate air pollution and birth weight (BW) and preterm birth (PTB) after taking into consideration the potential confounding effect of maternal smoking. Methods We systematically searched all published cohort and case-control studies examining BW and PTB association with particulate matter (PM, less than or equal to 2.5μm and 10.0 μm in diameter, PM2.5 and PM10, respectively) from PubMed and Web of Science, from January 1980 to April 2015. We extracted coefficients for continuous BW and odds ratio (OR) for PTB from each individual study, and meta-analysis was used to combine the coefficient and OR of individual studies. The methodological quality of individual study was assessed using a standard protocol proposed by Downs and Black. Forty-four studies met the inclusion criteria. Results In random effects meta-analyses, BW as a continuous outcome was negativelyassociated with 10 μg/m3 increase in PM10 (-10.31 g; 95% confidence interval [CI], -13.57 to -3.13 g; I-squared=0%, p=0.947) and PM2.5 (-22.17 g; 95% CI, -37.93 to -6.41 g; I-squared=92.3%, p <0.001) exposure during entire pregnancy, adjusted for maternal smoking. A significantly increased risk of PTB per 10 μg/m3 increase in PM10 (OR, 1.23; 95% CI, 1.04 to 1.41; I-squared=0%, p =0.977) and PM2.5 (OR, 1.14; 95% CI, 1.06 to 1.22; I-squared=92.5%, p <0.001) exposure during entire pregnancy was observed. Effect size of change in BW per 10 μg/m3 increase in PM tended to report stronger associations after adjustment for maternal smoking. Conclusions While this systematic review supports an adverse impact of maternal exposure to particulate air pollution on birth outcomes, variation in effects by exposure period and sources of heterogeneity between studies should be further explored. PMID:26796890

  10. 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

  11. LUPUS ANTICOAGULANT, BUT NOT ANTICARDIOLIPIN ANTIBODY, PREDICTS ADVERSE PREGNANCY OUTCOME IN PATIENTS WITH ANTIPHOSPHOLIPID ANTIBODIES

    PubMed Central

    Lockshin, Michael D.; Kim, Mimi; Laskin, Carl A.; Guerra, Marta; Branch, D. Ware; Merrill, Joan; Petri, Michelle; Porter, Flint; Sammaritano, Lisa; Stephenson, Mary D.; Buyon, Jill; Salmon, Jane E.

    2012-01-01

    BACKGROUND Which serologic and clinical findings predict adverse pregnancy outcome (APO) in patients with antiphospholipid antibody (aPL) is controversial. METHODS PROMISSE is a multicenter, prospective observational study of risk factors for APO in patients with aPL (lupus anticoagulant [LAC], anticardiolipin antibody [aCL] and/or antibody to β2 glycoprotein I [anti-β2-GP-I]). We tested the hypothesis that a pattern of clinical and serological variables can identify women at highest risk for APO. RESULTS Between 2003 and 2011 we enrolled 144 pregnant patients, of whom 28 had APO. Thirty-nine percent of patients with LAC had APO, compared to 3% who did not have LAC (p < 0.0001). Only 8% of women with IgG aCL ≥40 u/mL but not LAC suffered APO, compared to 43% of those with LAC (p = 0.002). IgM aCL or IgG or IgM anti-β2-GP-I did not predict APO. In bivariate analysis, APO occurred in 52% of patients with and 13% of patients without prior thrombosis (p = 0.00005), and in 23% with SLE compared to 17% without SLE (not significant); SLE was a predictor in multivariate analysis. Prior pregnancy loss did not predict APO, nor did maternal race. Simultaneous aCL, anti-β2-GP-I, and LAC did not predict APO better than did LAC alone. CONCLUSIONS LAC is the primary predictor of APO after 12 weeks gestation in aPL-associated pregnancies. ACL and anti-β2-GP-I, if LAC is not also present, do not predict APO. PMID:22275304

  12. 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

  13. 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

  14. 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

  15. Quality of community drinking water and the occurrence of late adverse pregnancy outcomes.

    PubMed

    Aschengrau, A; Zierler, S; Cohen, A

    1993-01-01

    The relationship between community drinking water quality and the occurrence of late adverse pregnancy outcomes was investigated by conducting a case-control study among women who delivered infants during August 1977 through March 1980 at Brigham and Women's Hospital in Massachusetts. The water quality indices were compared among 1,039 congenital anomaly cases, 77 stillbirth cases, 55 neonatal death cases, and 1,177 controls. Trace element levels were gathered from routine analyses of public water supplies from the communities in which the women resided during pregnancy. It was observed that, after adjustment for confounding, the frequency of stillbirths was increased for women exposed to chlorinated surface water (OR 2.6 95% CI 0.9-7.5) and for women exposed to detectable lead levels (OR 2.1; 95% CI 0.6-7.2); the frequency of cardiovascular defects was increased relative to detectable lead levels (OR 2.2, 95% CI 0.9-5.7); and the frequency of central nervous system defects was increased relative to the highest tertile of potassium (OR 6.3, 95% CI 1.1-37.3). The frequency of ear, face, and neck anomalies was increased in relation to detectable silver levels (OR 3.3, 95% CI 0.9-12.2), but the frequency decreased relative to high potassium levels (OR 0.2, 95% CI 0.1-0.7). The frequency of neonatal deaths was decreased relative to detectable fluoride levels (OR 0.4, 95% CI 0.2-1.0), and the frequency of musculoskeletal defects was decreased relative to detectable chromium levels (OR 0.4, 95% CI 0.2-1.0). The majority of these associations were not stable statistically. Further research is needed to corroborate these findings. PMID:8476301

  16. Birth malformations and other adverse perinatal outcomes in four U.S. Wheat-producing states.

    PubMed Central

    Schreinemachers, Dina M

    2003-01-01

    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

  17. 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

  18. 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

  19. Chronic fluoxetine treatment and maternal adversity differentially alter neurobehavioral outcomes in the rat dam.

    PubMed

    Pawluski, Jodi L; Charlier, Thierry D; Fillet, Marianne; Houbart, Virginie; Crispin, Hilda T; Steinbusch, Harry W; van den Hove, Daniël L

    2012-03-01

    The incidence of stress and stress-related disorders with the transition to motherhood, such as postpartum depression, is estimated to be 20%. Selective serotonin reuptake inhibitor (SSRI) medications are currently the antidepressant of choice to treat maternal mood disorders. However, little is known about the effects of these medications on the maternal brain and behavior. Therefore, the present study investigated how a commonly used SSRI, fluoxetine, affects neurobehavioral outcomes in the mother using a model of maternal adversity. To do this, gestationally stressed and non-stressed Sprague-Dawley rat dams were treated with either fluoxetine (5 mg/kg/day) or vehicle. Dams were divided into four groups: (1) Control + Vehicle, (2) Control + Fluoxetine, (3) Stress + Vehicle and (4) Stress + Fluoxetine. Fluoxetine or vehicle was administered to the dam during the postpartum period via osmotic minipump implants (Alzet) for 28 days. Results show that chronic fluoxetine treatment, after exposure to gestational stress, significantly decreased serum levels of corticosteroid binding globulin and increased hippocampal neurogenesis. In the absence of maternal stress, fluoxetine treatment alone significantly increased maternal arched-back nursing of pups, increased anxiety-related behavior, and decreased serum levels of corticosterone and corticosteroid binding globulin in the dam. This research provides important information on how SSRIs may act on the behavior, physiology, and neural plasticity of the mother. Although this is a first step in investigating the role of antidepressant treatment on the mother, much more work is needed before we can understand and improve the efficacy of these medications to treat mood disorders in pregnant and postpartum women. PMID:22173000

  20. 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

  1. Maternal pre-pregnancy BMI and adverse pregnancy outcomes among Chinese women: Results from the C-ABCS.

    PubMed

    Ding, X-X; Xu, S-J; Hao, J-H; Huang, K; Su, P-Y; Tao, F-B

    2016-04-01

    The aim of this study was to investigate associations between pre-pregnancy body mass index (BMI) and adverse pregnancy outcomes among Chinese pregnant women. A prospective population-based cohort study was performed using data collected as part of the China-Anhui Birth Cohort Study or C-ABCS. A total of 13,121 pregnant women who received the first prenatal visit were enrolled from November 2008 to October 2010. Logistic regression analysis was used to calculate associations between pre-pregnancy BMI and pregnancy outcomes. Results indicated that the increased pre-pregnancy BMI was associated with a number of adverse pregnancy outcomes such as hypertensive disorder (adjusted relative risk (ARR) 2.3, 95% confidence interval [CI] 1.5-3.6), gestational diabetes (ARR 3.5, 95% CI 2.3-5.2), caesarean delivery (ARR 2.0, 95% CI 1.6-2.4), and medically indicated preterm delivery (ARR 1.8, 95% CI 1.1-2.9). Women with pre-pregnancy BMI above the normal range pose an increased risk of adverse pregnancy outcomes. PMID:26492517

  2. APCR, factor V gene known and novel SNPs and adverse pregnancy outcomes in an Irish cohort of pregnant women

    PubMed Central

    2010-01-01

    Background Activated Protein C Resistance (APCR), a poor anticoagulant response of APC in haemostasis, is the commonest heritable thrombophilia. Adverse outcomes during pregnancy have been linked to APCR. This study determined the frequency of APCR, factor V gene known and novel SNPs and adverse outcomes in a group of pregnant women. Methods Blood samples collected from 907 pregnant women were tested using the Coatest® Classic and Modified functional haematological tests to establish the frequency of APCR. PCR-Restriction Enzyme Analysis (PCR-REA), PCR-DNA probe hybridisation analysis and DNA sequencing were used for molecular screening of known mutations in the factor V gene in subjects determined to have APCR based on the Coatest® Classic and/or Modified functional haematological tests. Glycosylase Mediated Polymorphism Detection (GMPD), a SNP screening technique and DNA sequencing, were used to identify SNPs in the factor V gene of 5 APCR subjects. Results Sixteen percent of the study group had an APCR phenotype. Factor V Leiden (FVL), FV Cambridge, and haplotype (H) R2 alleles were identified in this group. Thirty-three SNPs; 9 silent SNPs and 24 missense SNPs, of which 20 SNPs were novel, were identified in the 5 APCR subjects. Adverse pregnancy outcomes were found at a frequency of 35% in the group with APCR based on Classic Coatest® test only and at 45% in the group with APCR based on the Modified Coatest® test. Forty-eight percent of subjects with FVL had adverse outcomes while in the group of subjects with no FVL, adverse outcomes occurred at a frequency of 37%. Conclusions Known mutations and novel SNPs in the factor V gene were identified in the study cohort determined to have APCR in pregnancy. Further studies are required to investigate the contribution of these novel SNPs to the APCR phenotype. Adverse outcomes including early pregnancy loss (EPL), preeclampsia (PET) and intrauterine growth restriction (IGUR) were not significantly more frequent

  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. Socioeconomic Disparities in Ectopic Pregnancy: Predictors of Adverse Outcomes from Illinois Hospital-Based Care, 2000–2006

    PubMed Central

    Zhang, James X.; Lindau, Stacy Tessler

    2010-01-01

    This study aimed to identify the incidence of adverse outcomes from ectopic pregnancy hospital care in Illinois (2000–2006), and assess patient, neighborhood, hospital and time factors associated with these outcomes. Discharge data from Illinois hospitals were retrospectively analyzed and ectopic pregnancies were identified using DRG and ICD-9 diagnosis codes. The primary outcome was any complication identified by ICD-9 procedure codes. Secondary outcomes were length of stay and discharge status. Residential zip codes were linked to 2000 U.S. Census data to identify patients’ neighborhood demographics. Logistic regression was used to identify risk factors for adverse outcomes. Independent variables were insurance status, age, co-morbidities, neighborhood demographics, hospital type, hospital ectopic pregnancy service volume, and year of discharge. Of 13,007 ectopic pregnancy hospitalizations, 7.4% involved at least one complication identified by procedure codes. Hospitalizations covered by Medicare (for women with chronic disabilities) were more likely than those with other source or without insurance to result in surgical sterilization (OR 4.7, P = 0.012). Hospitalization longer than 2 days was more likely with Medicaid (OR 1.46, P<0.0005) or no insurance (OR 1.35, P<0.0005) versus other payers, and among church-operated versus secular hospitals (OR 1.21, P<0.0005). Compared to public hospitals, private hospitals had lower rates of complications (OR 0.39, P< 0.0005) and of hospitalization longer than 2 days (OR 0.57, P<0.0005). With time, hospitalizations became shorter (OR 0.53, P<0.0005) and complication rates higher (OR 1.33, P = 0.024). Ectopic pregnancy patients with Medicaid, Medicare or no insurance, and those admitted to public or religious hospitals, were more likely to experience adverse outcomes. PMID:20177756

  5. Socioeconomic disparities in ectopic pregnancy: predictors of adverse outcomes from Illinois hospital-based care, 2000-2006.

    PubMed

    Stulberg, Debra B; Zhang, James X; Lindau, Stacy Tessler

    2011-02-01

    This study aimed to identify the incidence of adverse outcomes from ectopic pregnancy hospital care in Illinois (2000-2006), and assess patient, neighborhood, hospital and time factors associated with these outcomes. Discharge data from Illinois hospitals were retrospectively analyzed and ectopic pregnancies were identified using DRG and ICD-9 diagnosis codes. The primary outcome was any complication identified by ICD-9 procedure codes. Secondary outcomes were length of stay and discharge status. Residential zip codes were linked to 2000 U.S. Census data to identify patients' neighborhood demographics. Logistic regression was used to identify risk factors for adverse outcomes. Independent variables were insurance status, age, co-morbidities, neighborhood demographics, hospital type, hospital ectopic pregnancy service volume, and year of discharge. Of 13,007 ectopic pregnancy hospitalizations, 7.4% involved at least one complication identified by procedure codes. Hospitalizations covered by Medicare (for women with chronic disabilities) were more likely than those with other source or without insurance to result in surgical sterilization (OR 4.7, P = 0.012). Hospitalization longer than 2 days was more likely with Medicaid (OR 1.46, P < 0.0005) or no insurance (OR 1.35, P < 0.0005) versus other payers, and among church-operated versus secular hospitals (OR 1.21, P < 0.0005). Compared to public hospitals, private hospitals had lower rates of complications (OR 0.39, P < 0.0005) and of hospitalization longer than 2 days (OR 0.57, P < 0.0005). With time, hospitalizations became shorter (OR 0.53, P < 0.0005) and complication rates higher (OR 1.33, P = 0.024). Ectopic pregnancy patients with Medicaid, Medicare or no insurance, and those admitted to public or religious hospitals, were more likely to experience adverse outcomes. PMID:20177756

  6. 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.

  7. 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...

  8. 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...

  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. Intrapartum fetal monitoring.

    PubMed

    Cahill, Alison G; Spain, Janine

    2015-06-01

    Intrapartum fetal monitoring to assess fetal well-being during the labor and delivery process has been a central component of intrapartum care for decades. Today, electronic fetal monitoring (EFM) is the most common method used to assess the fetus during labor without substantial evidence to suggest a benefit. A Cochrane review of 13 trials, which included over 37,000 women, found that continuous EFM provided no significant improvement in perinatal death rate [risk ratio (RR) 0.86; 95% confidence interval (CI), 0.59-1.23] or cerebral palsy rate (RR 1.75; 95% CI, 0.84-3.63) as compared with intermittent auscultation; however, there was a significant decrease in neonatal seizures (RR 0.50; 95% CI, 0.31-0.80). In addition, there was a significant increase in cesarean delivery (RR 1.63; 95% CI, 1.29-2.07) and operative vaginal delivery (RR 1.15; 95% CI, 1.01-1.33). Despite the lack of scientific support to suggest that EFM reduces adverse neonatal outcomes, its use is almost universal in the hospital setting and very likely has contributed to the rise in cesarean rate. PMID:25811127

  11. 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. PMID:25365504

  12. Antepartum fetal death following a yellow scorpion sting.

    PubMed

    Leibenson, Lilach; Leibenson, M; Silberstein, T

    2010-02-01

    Scorpion envenomation in pregnant victims has been scarcely studied. We would like to suggest an association between yellow scorpion sting during the third trimester of pregnancy and adverse fetal outcome. The particular deleterious mechanism of scorpion venom has not been elucidated yet. PMID:19466438

  13. Perioperative outcomes and adverse events of minimally invasive versus open posterior lumbar fusion: meta-analysis and systematic review.

    PubMed

    Goldstein, Christina L; Macwan, Kevin; Sundararajan, Kala; Rampersaud, Y Raja

    2016-03-01

    OBJECT The objective of this study was to determine the clinical comparative effectiveness and adverse event rates of posterior minimally invasive surgery (MIS) compared with open transforaminal or posterior lumbar interbody fusion (TLIF/PLIF). METHODS A systematic review of the Medline, EMBASE, PubMed, Web of Science, and Cochrane databases was performed. A hand search of reference lists was conducted. Studies were reviewed by 2 independent assessors to identify randomized controlled trials (RCTs) or comparative cohort studies including at least 10 patients undergoing MIS or open TLIF/PLIF for degenerative lumbar spinal disorders and reporting at least 1 of the following: clinical outcome measure, perioperative clinical or process measure, radiographic outcome, or adverse events. Study quality was assessed using the Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) protocol. When appropriate, a meta-analysis of outcomes data was conducted. RESULTS The systematic review and reference list search identified 3301 articles, with 26 meeting study inclusion criteria. All studies, including 1 RCT, were of low or very low quality. No significant difference regarding age, sex, surgical levels, or diagnosis was identified between the 2 cohorts (856 patients in the MIS cohort, 806 patients in the open cohort). The meta-analysis revealed changes in the perioperative outcomes of mean estimated blood loss, time to ambulation, and length of stay favoring an MIS approach by 260 ml (p < 0.00001), 3.5 days (p = 0.0006), and 2.9 days (p < 0.00001), respectively. Operative time was not significantly different between the surgical techniques (p = 0.78). There was no significant difference in surgical adverse events (p = 0.97), but MIS cases were significantly less likely to experience medical adverse events (risk ratio [MIS vs open] = 0.39, 95% confidence interval 0.23-0.69, p = 0.001). No difference in nonunion (p = 0.97) or reoperation rates (p = 0.97) was

  14. 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

  15. Prenatal Diagnosis and Pregnancy Outcome Analysis of Polyhydramnios.

    PubMed

    Liu, Li-Ling; Pang, Li-Hong; Deng, Bi-Ye

    2016-01-01

    The aim of the study was to investigate the etiology and pregnancy outcomes in mothers with polyhydramnios through prenatal diagnosis and pregnancy outcome analysis of pregnant women with polyhydramnios. One hundred and thirty women were enrolled. Fifty pregnant women with polyhydramnios were categorized as the case group, and 80 pregnant women with normal amniotic fluid were categorized as the control group. The causes of polyhydramnios and the pregnancy outcomes were analyzed. Two cases had chromosomal abnormalities, seven had severe α-thalassemia, 15 had fetal anomalies, four had maternal-fetal diseases and 22 had unexplained idiopathic polyhydramnios. Significantly, higher occurrences of cesarean section, preterm birth, fetal anomaly, fetal distress, fetal macrosomia and female fetuses occurred in patients with polyhydramnios than in patients without polyhydramnios. Polyhydramnios is associated with a higher occurrence of adverse perinatal outcomes. Intensive monitoring of the maternal-fetal condition and prenatal diagnosis is important in patients with polyhydramnios. PMID:26720631

  16. 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

  17. 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

  18. 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...

  19. 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. PMID:26234784

  20. 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 ...

  1. 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…

  2. Adverse Outcomes after Major Surgery in Patients with Pressure Ulcer: A Nationwide Population-Based Retrospective Cohort Study

    PubMed Central

    Chou, Chia-Lun; Lee, Woan-Ruoh; Yeh, Chun-Chieh; Shih, Chun-Chuan

    2015-01-01

    Background Postoperative adverse outcomes in patients with pressure ulcer are not completely understood. This study evaluated the association between preoperative pressure ulcer and adverse events after major surgeries. Methods Using reimbursement claims from Taiwan’s National Health Insurance Research Database, we conducted a nationwide retrospective cohort study of 17391 patients with preoperative pressure ulcer receiving major surgery in 2008-2010. With a propensity score matching procedure, 17391 surgical patients without pressure ulcer were selected for comparison. Eight major surgical postoperative complications and 30-day postoperative mortality were evaluated among patients with pressure ulcer of varying severity. Results Patients with preoperative pressure ulcer had significantly higher risk than controls for postoperative adverse outcomes, including septicemia, pneumonia, stroke, urinary tract infection, and acute renal failure. Surgical patients with pressure ulcer had approximately 1.83-fold risk (95% confidence interval 1.54-2.18) of 30-day postoperative mortality compared with control group. The most significant postoperative mortality was found in those with serious pressure ulcer, such as pressure ulcer with local infection, cellulitis, wound or treatment by change dressing, hospitalized care, debridement or antibiotics. Prolonged hospital or intensive care unit stay and increased medical expenditures were also associated with preoperative pressure ulcer. Conclusion This nationwide propensity score-matched retrospective cohort study showed increased postoperative complications and mortality in patients with preoperative pressure ulcer. Our findings suggest the urgency of preventing and managing preoperative pressure ulcer by a multidisciplinary medical team for this specific population. PMID:26000606

  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. An explanation of the pathophysiology of adverse neurodevelopmental outcomes in iron deficiency.

    PubMed

    Bakoyiannis, Ioannis; Gkioka, Eleana; Daskalopoulou, Afrodite; Korou, Laskarina-Maria; Perrea, Despina; Pergialiotis, Vasilios

    2015-01-01

    Iron deficiency (ID) is a major public health problem worldwide among children aged 0-12 months. Several factors seem to contribute to the iron-deficient state in infancy, including insufficient antenatal and neonatal iron supplementation, exclusive breastfeeding, and early umbilical cord clamping after birth. The most concerning complications of ID, except for anemia, are related to altered long-term neurodevelopment. Clinical studies have shown a negative impact of ID anemia on fetal and neonatal behavior including impairments of motor maturity, autonomic response, memory/learning, and mood. ID-induced defects during infancy seem to persist later in life, even after ID treatment. The underlying mechanisms involve dysfunctional myelination, neurotransmission alterations, and altered synaptogenesis and/or dendritogenesis. The purpose of the present review is to summarize these mechanisms and to provide recommendations for future clinical research in the field. PMID:25951130

  5. Lupus anticoagulant is the main predictor of adverse pregnancy outcomes in aPL-positive patients: validation of PROMISSE study results

    PubMed Central

    Yelnik, Cecile M; Laskin, Carl A; Porter, T Flint; Branch, D Ware; Buyon, Jill P; Guerra, Marta M; Lockshin, Michael D; Petri, Michelle; Merrill, Joan T; Sammaritano, Lisa R; Kim, Mimi Y; Salmon, Jane E

    2016-01-01

    Objective We previously reported that lupus anticoagulant (LAC) is the main predictor of poor pregnancy outcome in antiphospholipid antibody (aPL)-positive patients. We sought to confirm this finding in an independent group of patients who were subsequently recruited into the PROMISSE study. Methods The PROMISSE study is a multicentre, prospective, observational study of pregnancy outcomes in women with aPL and/or systemic lupus erythematosus (SLE) that enrolled patients from 2003 to 2015. All consecutive, aPL-positive patients from the PROMISSE study who completed their pregnancy between April 2011 and January 2015 (after the previous PROMISSE report) are included in the current report. Patients were followed monthly until delivery, and aPL was tested at first, second and third trimesters of pregnancy and at 12 weeks post partum. Adverse pregnancy outcomes (APOs) were defined as fetal death after 12 weeks of gestation, neonatal death, delivery prior to 36 weeks of gestation due to pre-eclampsia or placental insufficiency or small-for-gestational age (birth weight <5th percentile). Results Forty-four aPL-positive patients are included in this paper. Thirteen patients had APOs, which occurred in 80% of cases during the second trimester of pregnancy. LAC was present in 69% of patients with APOs compared with 27% of patients without APOs (p=0.01). No association was found between anticardiolipin antibodies (aCL) or anti-β2 glycoprotein I antibodies (aβ2GPI) IgG or IgM positivity and APOs. Definite antiphospholipid syndrome (history of thrombosis and/or pregnancy morbidity and aPL) was found in 92% of patients with any APOs compared with 45% of patients without APOs (p=0.004). Conversely, the frequency of SLE was not statistically different between those with and without APOs (30% vs 39%). Conclusions Our findings, in an independent group of aPL-positive patients from the PROMISSE study, confirm that LAC, but not aCL and aβ2GPI, is predictive of poor pregnancy

  6. 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

  7. The Effects of Chewing Betel Nut with Tobacco and Pre-pregnancy Obesity on Adverse Birth Outcomes Among Palauan Women.

    PubMed

    Berger, Katherine E; Masterson, James; Mascardo, Joy; Grapa, Jayvee; Appanaitis, Inger; Temengil, Everlynn; Watson, Berry Moon; Cash, Haley L

    2016-08-01

    The small Pacific Island nation of Palau has alarmingly high rates of betel nut with tobacco use and obesity among the entire population including pregnant women. This study aimed to determine the effects of betel nut with tobacco use and pre-pregnancy obesity on adverse birth outcomes. This study used retrospective cohort data on 1171 Palauan women who gave birth in Belau National Hospital in Meyuns, Republic of Palau between 2007 and 2013. The exposures of interest were pre-pregnancy obesity and reported betel nut with tobacco use during pregnancy. The primary outcomes measured were preterm birth and low birth weight among full-term infants. A significantly increased risk for low birth weight among full-term infants was demonstrated among those women who chewed betel nut with tobacco during pregnancy when other known risk factors were controlled for. Additionally, pre-pregnancy obesity was associated with a significantly increased risk for preterm birth when other known risk factors were controlled for. Both betel nut with tobacco use and pre-pregnancy obesity were associated with higher risks for adverse birth outcomes. These findings should be used to drive public health efforts in Palau, as well as in other Pacific Island nations where these studies are currently lacking. PMID:26994610

  8. [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

  9. 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

  10. 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

  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. 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

  13. 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

  14. 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

  15. Low-dose aspirin for prevention of adverse outcomes related to abnormal placentation.

    PubMed

    Bujold, Emmanuel; Roberge, Stéphanie; Nicolaides, Kypros H

    2014-07-01

    Meta-analysis of randomized studies on the use of low-dose aspirin in women at high risk of preeclampsia (PE) has demonstrated that if treatment is initiated at ≤16 weeks' gestation, there is significant reduction in the risk of PE [relative risk (RR) 0.47, 95% confidence interval (CI) 0.36-0.62], fetal growth restriction (RR 0.46, 95% CI 0.33-0.64), preterm birth (RR 0.35, 95% CI 0.22-0.57) and perinatal death (RR 0.41, 95% CI 0.19-0.92), whereas the effect of treatment after 16 weeks is substantially less (RR 0.78, 95% CI 0.61-0.99; RR 0.98, 95% CI 0.88-1.08; RR 0.90, 95% CI 0.83-0.97; and RR 0.93, 95% CI 0.73-1.19, respectively). Moreover, the decrease in the risk of PE from early onset treatment seems to be related to the dose of aspirin, and a dose of >80 mg daily should be considered for optimal benefits. PMID:24799357

  16. A prospective study of maternal and fetal outcome in acute Lassa fever infection during pregnancy.

    PubMed Central

    Price, M. E.; Fisher-Hoch, S. P.; Craven, R. B.; McCormick, J. B.

    1988-01-01

    Several viral infections have been reported to result in more severe disease in pregnant than non-pregnant women, but the relative risks have not been well characterised. This has now been done for Lassa fever in a prospective study of 68 pregnant and 79 non-pregnant women who were admitted to hospital in Sierra Leone with confirmed Lassa fever. Lassa fever was the main cause of maternal mortality in the hospital, accounting for 25% of maternal deaths. Twelve of 40 patients in the third trimester died, compared with two of 28 in the first two trimesters and 10 of 79 non-pregnant women. The odds ratio for death in the third trimester compared with the first two trimesters was 5.57 (95% confidence intervals 1.02 to 30.26). The condition of the mother improved rapidly after evacuation of the uterus, whether by spontaneous abortion, evacuation of retained products of conception, or normal delivery; 10 of 26 women without uterine evacuation died, but only four of 39 women with evacuation died (p = 0.0016). The odds ratio for death with pregnancy intact was 5.47 (95% confidence interval 1.35 to 22.16). Fetal and neonatal loss was 87%. The risk of death from Lassa fever in the third trimester is significantly higher than that in the first two trimesters and higher than that for non-pregnant women, but evacuation of the uterus can significantly improve the mother's chance of survival. PMID:3139220

  17. Using patient safety indicators to estimate the impact of potential adverse events on outcomes.

    PubMed

    Rivard, Peter E; Luther, Stephen L; Christiansen, Cindy L; Shibei Zhao; Loveland, Susan; Elixhauser, Anne; Romano, Patrick S; Rosen, Amy K

    2008-02-01

    The authors estimated the impact of potentially preventable patient safety events, identified by Agency for Healthcare Research and Quality (AHRQ) Patient Safety Indicators (PSIs), on patient outcomes: mortality, length of stay (LOS), and cost. The PSIs were applied to all acute inpatient hospitalizations at Veterans Health Administration (VA) facilities in fiscal 2001. Two methods-regression analysis and multivariable case matching- were used independently to control for patient and facility characteristics while predicting the effect of the PSI on each outcome. The authors found statistically significant (p < .0001) excess mortality, LOS, and cost in all groups with PSIs. The magnitude of the excess varied considerably across the PSIs. These VA findings are similar to those from a previously published study of nonfederal hospitals, despite differences between VA and non-VA systems. This study contributes to the literature measuring outcomes of medical errors and provides evidence that AHRQ PSIs may be useful indicators for comparison across delivery systems. PMID:18184870

  18. 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

  19. 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…

  20. 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. PMID:27087461

  1. 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

  2. Maternal Serum Analytes as Predictors of Fetal Growth Restriction with Different Degrees of Placental Vascular Dysfunction.

    PubMed

    Blitz, Matthew J; Rochelson, Burton; Vohra, Nidhi

    2016-06-01

    Abnormal levels of maternal serum analytes have been associated with fetal growth restriction (FGR) and preeclampsia secondary to placental vascular dysfunction. Accurately identifying the FGR fetuses at highest risk for adverse outcomes remains challenging. Placental function can be assessed by Doppler analysis of the maternal and fetal circulation. Although the combination of multiple abnormal maternal serum analytes and abnormal Doppler findings is strongly associated with adverse outcomes, the predictive value remains too low to be used as a screening test in a low-risk population. Stratification of cases based on the severity of Doppler abnormalities may improve predictive models. PMID:27235917

  3. 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

  4. Management of patients with chronic lymphocytic leukemia with a high risk of adverse outcome: the Mayo Clinic approach

    PubMed Central

    ZENT, CLIVE S.; KAY, NEIL E.

    2012-01-01

    Chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL) is usually an incidental diagnosis in patients with early–intermediate stage disease. However, most patients with a diagnosis of CLL will subsequently have significant morbidity and die from their disease and its complications. For these patients, CLL is not the ‘good leukemia’ with a predictably ‘benign’ outcome. Indeed, we can now identify a cohort of patients with high-risk CLL at diagnosis who will have rapid disease progression, poor response to treatment, and poor survival based on prognostic methods developed from an improved understanding of the biology of CLL. The concomitant development of improved treatments has led to risk-adjusted management approaches that could improve outcomes. We discuss the clinical and laboratory components of comprehensive risk evaluation of patients with CLL and our approach to the management of patients with a high to very high risk of disease progression and poor outcome. In addition, we review the challenges and prospects for improving prognostic precision and the development of new drugs to improve the treatment of patients with CLL with a high risk of adverse outcome. PMID:21649549

  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. PMID:26500288

  7. Effect of metformin on maternal and fetal outcomes in obese pregnant women (EMPOWaR): a randomised, double-blind, placebo-controlled trial

    PubMed Central

    Chiswick, Carolyn; Reynolds, Rebecca M; Denison, Fiona; Drake, Amanda J; Forbes, Shareen; Newby, David E; Walker, Brian R; Quenby, Siobhan; Wray, Susan; Weeks, Andrew; Lashen, Hany; Rodriguez, Aryelly; Murray, Gordon; Whyte, Sonia; Norman, Jane E

    2015-01-01

    Summary Background Maternal obesity is associated with increased birthweight, and obesity and premature mortality in adult offspring. The mechanism by which maternal obesity leads to these outcomes is not well understood, but maternal hyperglycaemia and insulin resistance are both implicated. We aimed to establish whether the insulin sensitising drug metformin improves maternal and fetal outcomes in obese pregnant women without diabetes. Methods We did this randomised, double-blind, placebo-controlled trial in antenatal clinics at 15 National Health Service hospitals in the UK. Pregnant women (aged ≥16 years) between 12 and 16 weeks' gestation who had a BMI of 30 kg/m2 or more and normal glucose tolerance were randomly assigned (1:1), via a web-based computer-generated block randomisation procedure (block size of two to four), to receive oral metformin 500 mg (increasing to a maximum of 2500 mg) or matched placebo daily from between 12 and 16 weeks' gestation until delivery of the baby. Randomisation was stratified by study site and BMI band (30–39 vs ≥40 kg/m2). Participants, caregivers, and study personnel were masked to treatment assignment. The primary outcome was Z score corresponding to the gestational age, parity, and sex-standardised birthweight percentile of liveborn babies delivered at 24 weeks or more of gestation. We did analysis by modified intention to treat. This trial is registered, ISRCTN number 51279843. Findings Between Feb 3, 2011, and Jan 16, 2014, inclusive, we randomly assigned 449 women to either placebo (n=223) or metformin (n=226), of whom 434 (97%) were included in the final modified intention-to-treat analysis. Mean birthweight at delivery was 3463 g (SD 660) in the placebo group and 3462 g (548) in the metformin group. The estimated effect size of metformin on the primary outcome was non-significant (adjusted mean difference −0·029, 95% CI −0·217 to 0·158; p=0·7597). The difference in the number of women reporting the

  8. How Does the Fast Track Intervention Prevent Adverse Outcomes in Young Adulthood?

    PubMed

    Sorensen, Lucy C; Dodge, Kenneth A

    2016-03-01

    Numerous studies have shown that childhood interventions can foster improved outcomes in adulthood. Less well understood is precisely how-that is, through which developmental pathways-these interventions work. This study assesses mechanisms by which the Fast Track project (n = 891), a randomized intervention in the early 1990s for high-risk children in four communities (Durham, NC; Nashville, TN; rural PA; and Seattle, WA), reduced delinquency, arrests, and general and mental health service utilization in adolescence through young adulthood (ages 12-20). A decomposition of treatment effects indicates that about a third of Fast Track's impact on later crime outcomes can be accounted for by improvements in social and self-regulation skills during childhood (ages 6-11), such as prosocial behavior, emotion regulation, and problem solving. These skills proved less valuable for the prevention of general and mental health problems. PMID:26670938

  9. A spatial bivariate probit model for correlated binary data with application to adverse birth outcomes.

    PubMed

    Neelon, Brian; Anthopolos, Rebecca; Miranda, Marie Lynn

    2014-04-01

    Motivated by a study examining geographic variation in birth outcomes, we develop a spatial bivariate probit model for the joint analysis of preterm birth and low birth weight. The model uses a hierarchical structure to incorporate individual and areal-level information, as well as spatially dependent random effects for each spatial unit. Because rates of preterm birth and low birth weight are likely to be correlated within geographic regions, we model the spatial random effects via a bivariate conditionally autoregressive prior, which induces regional dependence between the outcomes and provides spatial smoothing and sharing of information across neighboring areas. Under this general framework, one can obtain region-specific joint, conditional, and marginal inferences of interest. We adopt a Bayesian modeling approach and develop a practical Markov chain Monte Carlo computational algorithm that relies primarily on easily sampled Gibbs steps. We illustrate the model using data from the 2007-2008 North Carolina Detailed Birth Record. PMID:22599322

  10. 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

  11. 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

  12. 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

  13. 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

  14. Adverse Outcomes after Non-Chest Surgeries in Patients with Pulmonary Tuberculosis: A Nationwide Study

    PubMed Central

    Lin, Chao-Shun; Yeh, Chun-Chieh; Chung, Chi-Li; Hung, Chih-Jen; Chen, Ta-Liang

    2015-01-01

    Background The association between pulmonary tuberculosis (TB) and postoperative outcomes remains unknown. This study investigated outcomes following non-chest surgeries in patients with previous pulmonary TB. Methods Using Taiwan’s National Health Insurance Research Database, we analyzed 6911 patients (aged ≥ 20 years) with preoperative diagnosis of pulmonary TB and 6911 propensity score-matched controls receiving non-chest surgeries in 2008–2010. Postoperative outcomes were compared between patients with or without pulmonary TB by calculating adjusted odds ratios (ORs) and 95% confidence intervals (CIs) in the multivariate logistic regressions. Results Surgical patients with pulmonary TB had a significantly higher postoperative complication rates than controls, including septicemia, pneumonia, acute renal failure, deep wound infection, overall complications, and 30-day postoperative mortality (OR 1.41; 95% CI 1.07–1.86). The ORs of patients with low-income status were as high as 2.27 (95% CI 1.03–5.03). Preoperative use of TB drugs and TB-related medical expenditure also associated with higher postoperative mortality among surgical patients with pulmonary TB. Conclusions Surgical patients with pulmonary TB have significantly increased risks of postoperative complications and mortality after non-chest surgeries. This study suggests the need to improve postoperative care for surgical patients with pulmonary TB. PMID:26172153

  15. No adverse effects were identified on the perinatal outcomes after laser-assisted hatching treatment.

    PubMed

    Zhou, Hanying; Zao, Wanqiu; Zhang, Wei; Shi, Juanzi; Shi, Wenhao

    2014-12-01

    The aim of this study was to evaluate the safety of laser-assisted hatching (LAH) by comparing obstetric and neonatal outcomes between assisted hatching and control groups in cryopreserved embryo transfer cycles. A retrospective cohort analysis was carried out. A total of 699 women with 392 infants delivered were included. Laser- assisted hatching was carried out on D-3 thawed and warmed embryos before transfer in 480 cryopreserved embryos transfer cycles. Obstetric outcomes, neonatal outcomes, and congenital birth defects were recorded. A total of 815 cryopreserved embryo transfer cycles (480 in LAH group and 335 in control group) in 699 patients were analysed. Statistically significantly higher implantation (31.85% versus 16.95%), clinical pregnancy (53.96% versus 33.43%) and live delivery (44.58% versus 23.88%) rates were observed in the LAH group (all P < 0.001). For either singleton or multiple gestations, no statistically significant differences were found in mean gestational age, mean birth weight and mean Apgar score. Four major malformations occurred in the assisted hatching group and three malformations (one major and two minor) in the control group. This study did not identify any harmful effect of LAH on neonates, which suggested that LAH may be a safe treatment in cryopreserved embryo transfer cycles. PMID:25444502

  16. Trauma patient adverse outcomes are independently associated with rib cage fracture burden and severity of lung, head, and abdominal injuries

    PubMed Central

    Dunham, C Michael; Hileman, Barbara M; Ransom, Kenneth J; Malik, Rema J

    2015-01-01

    Objective: We hypothesized that lung injury and rib cage fracture quantification would be associated with adverse outcomes. Subjects and methods: Consecutive admissions to a trauma center with Injury Severity Score ≥ 9, age 18-75, and blunt trauma. CT scans were reviewed to score rib and sternal fractures and lung infiltrates. Sternum and each anterior, lateral, and posterior rib fracture was scored 1 = non-displaced and 2 = displaced. Rib cage fracture score (RCFS) = total rib fracture score + sternal fracture score + thoracic spine Abbreviated Injury Score (AIS). Four lung regions (right upper/middle, right lower, left upper, and left lower lobes) were each scored for % of infiltrate: 0% = 0; ≤ 20% = 1, ≤ 50% = 2, > 50% = 3; total of 4 scores = lung infiltrate score (LIS). Results: Of 599 patients, 193 (32%) had 854 rib fractures. Rib fracture patients had more abdominal injuries (p < 0.001), hemo/pneumothorax (p < 0.001), lung infiltrates (p < 0.001), thoracic spine injuries (p = 0.001), sternal fractures (p = 0.0028) and death or need for mechanical ventilation ≥ 3 days (Death/Vdays ≥ 3) (p < 0.001). Death/Vdays ≥ 3 was independently associated with RCFS (p < 0.001), LIS (p < 0.001), head AIS (p < 0.001) and abdominal AIS (p < 0.001). Of the 193 rib fracture patients, Glasgow Coma Score 3-12 or head AIS ≥ 2 occurred in 43%. A lung infiltrate or hemo/pneumothorax occurred in 55%. Thoracic spine injury occurred in 23%. RCFS was 6.3 ± 4.4 and Death/Vdays ≥ 3 occurred in 31%. Death/Vdays ≥ 3 rates correlated with RCFS values: 19% for 1-3; 24% for 4-6; 42% for 7-12 and 65% for ≥ 13 (p < 0.001). Death/Vdays ≥ 3 was independently associated with RCFS (p = 0.02), LIS (p = 0.001), head AIS (p < 0.001) and abdominal AIS (p < 0.001). Death/Vdays ≥ 3 association was better for RCFS (p = 0.005) than rib fracture score (p = 0.08) or number of fractured ribs (p = 0.80). Conclusion: Rib fracture patients have increased risk for truncal injuries and

  17. 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.

  18. 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

  19. 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

  20. 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

  1. Do adult men with untreated ventral penile curvature have adverse outcomes?

    PubMed Central

    Menon, Vani; Breyer, Benjamin; Copp, Hillary L.; Baskin, Laurence; Disandro, Michael; Schlomer, Bruce J.

    2016-01-01

    Summary Introduction Congenital ventral penile curvature without hypospadias is often treated surgically in childhood. The history of untreated ventral curvature is unknown. Objective This study’s aim was to examine the association of untreated ventral penile curvature with various sexual and psychosexual outcomes. Study design An electronic survey was advertised to men older than 18 years on Facebook. Men with possible ventral penile curvature identified themselves by choosing sketches that most closely represented their anatomy. Outcomes assessed included: Sexual Health Inventory for Men, difficulty of intercourse because of curvature, International Prostate Symptom Score, Penile Perception Score, psychosexual milestones, paternity, infertility, sitting to urinate, and the CDC HRQOL-4 module. Results Among participants, 81 out of 684 men (11.8%) reported untreated ventral penile curvature. Participants with self-reported curvature noted more difficulty with intercourse because of curvature (4.5 vs 4.9, p < 0.001), more unhealthy mental days (8.6 vs 6.2, p = 0.02), and increased dissatisfaction with penile self-perception compared with men without reported curvature (8.6 vs 9.5, p < 0.001). Discussion Men with possible untreated ventral curvature reported worse penile perception scores, more mentally unhealthy days, and increased difficulty with intercourse secondary to curvature compared with men without curvature. A limitation to this study is selection bias; responses collected were self-reported from survey volunteers. Additionally, the question identifying ventral penile curvature is not validated but performed well in pretesting. Most questions were from validated surveys, but some were modeled after validated surveys and/or contained high face validity types of questions. Conclusion Men with possible untreated ventral penile curvature reported more dissatisfaction with penile appearance, increased difficulty with intercourse, and more unhealthy mental

  2. Recent immigration and adverse pregnancy outcomes in an urban setting in Spain.

    PubMed

    Garcia-Subirats, Irene; Pérez, Glòria; Rodríguez-Sanz, Maica; Salvador, Joaquín; Jané, Mireia

    2011-07-01

    To describe social and economic inequalities in non-fatal pregnancy outcomes (low birth weight, preterm birth and small for gestational age births) in the neighbourhoods of the city of Barcelona (Spain), according to maternal age and maternal country of origin, between 1991 and 2005. A cross-sectional ecological study was carried out using the 38 neighbourhoods of Barcelona as the unit of analysis. The study population comprises the 192,921 live births to resident women aged 12-49 residing from 1991 to 2005. Information was gathered from births registry. Prevalence of low birth-weight, preterm birth and small for gestational age, was calculated for each of the 38 neighbourhoods of mothers' residence, stratifying results by maternal age and country of origin. The indicator of neighbourhood socio-economic level was the unemployment rate. Quartile maps along with Spearman correlation coefficients and linear regression were performed between indicators. The present study reports socio-economic inequalities in pregnancy outcomes among neighbourhoods in Barcelona (Spain): the more disadvantaged neighbourhoods have worse pregnancy outcomes (low birth weight, preterm birth and small for gestational age births) in all women age groups. These inequalities do not exist among immigrant women, and some groups of foreign mothers even have lower rates of low birth weight, preterm birth, and small for gestational age births than autochthonous women. The existing inequalities suggest that policy efforts to reduce these inequalities are not entirely successful and should focus on improving pregnancy and delivery care in less privileged women in a country with universal access to health care. PMID:20440546

  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. PMID:27582379

  4. Two pathways through adversity: Predicting well-being and housing outcomes among homeless service users.

    PubMed

    Walter, Zoe C; Jetten, Jolanda; Dingle, Genevieve A; Parsell, Cameron; Johnstone, Melissa

    2016-06-01

    People who experience homelessness face many challenges and disadvantages that negatively impact health and well-being and form barriers to achieving stable housing. Further, people who are homeless often have limited social connections and support. Building on previous research that has shown the beneficial effect of group identification on health and well-being, the current study explores the relationship between two social identity processes - multiple group memberships and service identification - and well-being and positive housing outcomes. Measures were collected from 76 participants while they were residing in a homeless accommodation service (T1) and again 2-4 weeks after leaving the service (or 3 months after T1 if participants had not left the service). Mediation analyses revealed that multiple group memberships and service identification at T1 independently predicted well-being at T2 indirectly, via social support. Further, both social identity processes also indirectly predicted housing outcomes via social support. The implications of these findings are twofold. First, while belonging to multiple social groups may provide a pathway to gaining social support and well-being, group belonging may not necessarily be beneficial to achieve stable housing. Second, fostering identification with homeless services may be particularly important as a source of support that contributes to well-being. PMID:26333919

  5. 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

  6. Role of genetic susceptibility in development of treatment-related adverse outcomes in cancer survivors.

    PubMed

    Bhatia, Smita

    2011-10-01

    Clear and unambiguous associations have been established between therapeutic exposures and specific complications. However, considerable interindividual variability is observed in the risk of developing an outcome for a given therapeutic exposure. Genetic predisposition and especially its interaction with therapeutic exposures can potentially exacerbate the toxic effect of treatment on normal tissues and organ systems, and can possibly explain the interindividual variability. This article provides a brief overview of the current knowledge about the role of genomic variation in the development of therapy-related complications. Relatively common outcomes with strong associations with therapeutic exposures, including cardiomyopathy, obesity, osteonecrosis, ototoxicity, and subsequent malignancies are discussed here. To develop a deeper understanding of the molecular underpinnings of therapy-related complications, comprehensive and near-complete collection of clinically annotated samples is critical. Methodologic issues such as study design, definition of the endpoints or phenotypes, identification of appropriate and adequately sized study population together with a reliable plan for collecting and maintaining high-quality DNA, and selection of an appropriate approach or platform for genotyping are also discussed. Understanding the etiopathogenetic pathways that lead to the morbidity is critical to developing targeted prevention and intervention strategies, optimizing risk-based health care of cancer survivors, thus minimizing chronic morbidities and improving quality of life. PMID:21980013

  7. An Elevated Glycemic Gap is Associated with Adverse Outcomes in Diabetic Patients with Acute Myocardial Infarction.

    PubMed

    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

  8. Periodontal bacteria in the genital tract: are they related to adverse pregnancy outcome?

    PubMed

    Cassini, M A; Pilloni, A; Condò, S G; Vitali, L A; Pasquantonio, G; Cerroni, L

    2013-01-01

    One of the most important factors implicated in preterm birth (PTB) is acute genitourinary tract infection. The bacteria causing chronic periodontal inflammation include Gram-negative rods and anaerobes similar to those found in women with bacterial vaginosis. The aim of this prospective study is to investigate the relationship between oral and vaginal microflora and preterm low birth weight. Real-time polymerase chain reaction was used to detect both the presence and level of six periodontitis-related species: Aggregatibacter actinomycetemcomitans (Aa), Porphyromonas gingivalis (Pg), Tannerella forsythia (Tf), Treponema denticola (Td), Fusobacterium nucleatum ssp(Fn), and Prevotella intermedia (Pi) for both oral samples of subgingival plaque and cervical samples, obtained from 80 patients, during gynaecological examinations. The more representative oral pathogen (less than 60 percent) species in oral samples of preterm and term group were Tf, Td, and Fn. 24.4 percent of pregnant women presented periodontal pathogens in vaginal swab; the most representative species with a percentage over 0.1 percent of total bacteria in genital tract of preterm group were Tf, Td, and Piwith a positive correlation (less than 0.5). The presence of the bacterium T. denticolain the vagina, regardless of the amount, adversely affects preterm delivery. PMID:24355228

  9. 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

  10. 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,...

  11. 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

  12. Prediction of Fetal Hypertrophic Cardiomyopathy in Diabetic Pregnancies Compared with Postnatal Outcome

    PubMed Central

    Elmekkawi, Sherif F.; Mansour, Ghada M.; Elsafty, Mohammed S.E.; Hassanin, Alaa S.; Laban, Mohamed; Elsayed, Heba M.

    2015-01-01

    neonatal distress due to HCM. In this study, 8 of the 10 fetuses with intrauterine demise and the 2 neonates who died within one week after delivery due to heart failure had a prenatal IVS thickness of ≥4.5 mm, while 7 of the 10 fetuses with intrauterine demise and the 2 neonates who died postnatal from heart failure had a prenatal IVS thickness to LMWT ratio of ≤1.18. CONCLUSION A prenatal IVS thickness of ≥4.5 mm or an IVS/LMWT ratio of ≤1.18 seems to be predictive of HCM and is associated with almost twofold higher risk of intrauterine fetal death and almost threefold higher risk of possibly relevant perinatal mortality. PMID:26664250

  13. Dynamical System Modeling of Immune Reconstitution after Allogeneic Stem Cell Transplantation Identifies Patients at Risk for Adverse Outcomes.

    PubMed

    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

    2015-07-01

    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

  14. 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

  15. 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

  16. The adverse outcome pathway for rodent liver tumor promotion by sustained activation of the aryl hydrocarbon receptor.

    PubMed

    Becker, Richard A; Patlewicz, Grace; Simon, Ted W; Rowlands, J Craig; Budinsky, Robert A

    2015-10-01

    An Adverse Outcome Pathway (AOP) represents the existing knowledge of a biological pathway leading from initial molecular interactions of a toxicant and progressing through a series of key events (KEs), culminating with an apical adverse outcome (AO) that has to be of regulatory relevance. An AOP based on the mode of action (MOA) of rodent liver tumor promotion by dioxin-like compounds (DLCs) has been developed and the weight of evidence (WoE) of key event relationships (KERs) evaluated using evolved Bradford Hill considerations. Dioxins and DLCs are potent aryl hydrocarbon receptor (AHR) ligands that cause a range of species-specific adverse outcomes. The occurrence of KEs is necessary for inducing downstream biological responses and KEs may occur at the molecular, cellular, tissue and organ levels. The common convention is that an AOP begins with the toxicant interaction with a biological response element; for this AOP, this initial event is binding of a DLC ligand to the AHR. Data from mechanistic studies, lifetime bioassays and approximately thirty initiation-promotion studies have established dioxin and DLCs as rat liver tumor promoters. Such studies clearly show that sustained AHR activation, weeks or months in duration, is necessary to induce rodent liver tumor promotion--hence, sustained AHR activation is deemed the molecular initiating event (MIE). After this MIE, subsequent KEs are 1) changes in cellular growth homeostasis likely associated with expression changes in a number of genes and observed as development of hepatic foci and decreases in apoptosis within foci; 2) extensive liver toxicity observed as the constellation of effects called toxic hepatopathy; 3) cellular proliferation and hyperplasia in several hepatic cell types. This progression of KEs culminates in the AO, the development of hepatocellular adenomas and carcinomas and cholangiolar carcinomas. A rich data set provides both qualitative and quantitative knowledge of the progression of

  17. 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…

  18. Oxygen desaturation in 6-min walk test is a risk factor for adverse outcomes in COPD.

    PubMed

    Waatevik, Marie; Johannessen, Ane; Gomez Real, Francisco; Aanerud, Marianne; Hardie, Jon Andrew; Bakke, Per Sigvald; Lind Eagan, Tomas Mikal

    2016-07-01

    The 6-min walk test (6MWT) is an exercise test that measures functional status in chronic obstructive pulmonary disease (COPD) patients and provides information on oxygen desaturation. We investigated oxygen desaturation during 6MWT as a risk factor for important COPD outcomes: mortality, frequency of exacerbations, decline in lung function and decline in lean body mass.433 COPD patients were included in the Bergen COPD Cohort Study 2006-2009, and followed-up for 3 years. Patients were characterised using spirometry, bioelectrical impedance measurements, Charlson comorbidity score, exacerbation history, smoking and arterial blood gases. 370 patients completed the 6MWT at the baseline of the study. Information on all-cause mortality was collected in 2011.Patients who experienced oxygen desaturation during the 6MWT had an approximately twofold increased risk of death (hazard ratio 2.4, 95% CI 1.2-5.1), a 50% increased risk for experiencing later COPD exacerbations (incidence rate ratio 1.6, 95% CI 1.1-2.2), double the yearly rate of decline in both forced vital capacity and forced expiratory volume in 1 s (3.2% and 1.7% versus 1.7% and 0.9%, respectively) and manifold increased yearly rate of loss of lean body mass (0.18 kg·m(-2) versus 0.03 kg·m(-2) among those who did not desaturate).Desaturating COPD patients had a significantly worse prognosis than non-desaturating COPD patients, for multiple important disease outcomes. PMID:27076586

  19. Low Plasma α-Tocopherol Concentrations and Adverse Clinical Outcomes in Diabetic Hemodialysis Patients

    PubMed Central

    Espe, Katharina M.; Raila, Jens; Henze, Andrea; Blouin, Katja; Schneider, Andreas; Schmiedeke, Daniel; Krane, Vera; Pilz, Stefan; Schweigert, Florian J.; Hocher, Berthold; Wanner, Christoph

    2013-01-01

    Summary Background and objectives Trials with the antioxidant vitamin E have failed to show benefit in the general population. Considering the different causes of death in ESRD, this study investigated the association between plasma concentrations of α-tocopherol and specific clinical outcomes in diabetic hemodialysis patients. Design, settings, participants, & measurements In 1046 diabetic hemodialysis patients (participants of the German Diabetes and Dialysis Study), α-tocopherol was measured in plasma by reversed-phase HPLC. By Cox regression analyses, hazard ratios were determined for prespecified end points according to baseline plasma α-tocopherol levels: sudden death (n=134), myocardial infarction (n=172), stroke (n=89), combined cardiovascular events (n=398), fatal infection (n=107), and all-cause mortality (n=508). Results Patients had a mean age of 66±8 years, and mean plasma α-tocopherol level was 22.8±9.6 µmol/L. Levels of α-tocopherol were highly correlated to triglycerides (r=0.63, P<0.001). Patients in the lowest α-tocopherol quartile had (in unadjusted analyses) a 79% higher risk of stroke and a 31% higher risk of all-cause mortality compared with patients in the highest quartile. The associations were attenuated after adjustment for confounders (hazard ratiostroke=1.56, 95% confidence interval=0.75–3.25; hazard ratiomortality=1.22, 95% confidence interval=0.89–1.69, respectively). There was no association between α-tocopherol and myocardial infarction, sudden death, or infectious death. Conclusions Plasma α-tocopherol concentrations were not independently associated with cardiovascular outcomes, infectious deaths, or all-cause mortality in diabetic hemodialysis patients. The lack of association can partly be explained by a confounding influence of malnutrition, which should be considered in the planning of trials to reduce cardiovascular risk in dialysis patients. PMID:23335039

  20. 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

  1. Outcomes and Adverse Events of Enlarged Tracheoesophageal Puncture after Total Laryngectomy

    PubMed Central

    Hutcheson, Katherine A.; Lewin, Jan S.; Sturgis, Erich M.; Risser, Jan

    2014-01-01

    Objective Enlargement of the tracheoesophageal puncture (TEP) results in aspiration around the voice prosthesis (VP) and may lead to pneumonia. The primary objective was to summarize control of leakage around the VP after conservative management of enlarged TEP. Study Design Retrospective cohort study. Methods This 5-year cohort included 194 patients who underwent total laryngectomy (± pharyngectomy) and TEP at the University of Texas MD Anderson Cancer Center. Control of leakage around the VP was analyzed at last follow-up after enlarged TEP. Adverse events were compared in patients with and without enlarged TEP. Results The incidence of enlarged TEP was 18.6% (36/194, 95% CI: 13.0%-24.1%). Conservative methods commonly attempted in lieu of complete TEP closure included placement of an enlarged-flange VP (34/36, 94%), temporary VP removal (14/36, 39%), and TEP-site injection (8/36, 22%). At last follow-up, conservative methods controlled leakage around the VP in 81% (29/36) of patients. Only 2 patients required complete TEP closure due to persistent leakage after enlarged TEP. Unresolved leakage was more common in patients with recurrent cancer after laryngectomy (p=0.081) and irregular TEP contour (p=0.003). Relative to controls without TEP enlargement, patients with enlarged TEP had 3-fold higher risk of pneumonia (RR: 3.4, 95% CI: 1.9-6.2) and aspiration of the prosthesis (RR: 3.3, 95% CI: 0.8-14.1). Conclusions Although the rate of enlarged TEP is relatively low, the complication significantly elevates risk of pneumonia. Prosthetic leakage related to TEP enlargement can often be managed conservatively to avoid complete closure of the TEP. Level of evidence: 2b PMID:21647906

  2. Maternal and fetal outcome in pre-eclampsia in a secondary care hospital in South India

    PubMed Central

    Aabidha, Parveen M.; Cherian, Anne G.; Paul, Emmanuel; Helan, Jasmin

    2015-01-01

    Background: Hypertensive disorders in pregnancy are one of the common causes for perinatal and maternal morbidity and mortality in developing countries. Pre-eclampsia is a condition which typically occurs after 20 weeks of gestation and has high blood pressure as the main contributing factor. The aim was to study the effects of pre-eclampsia on the mother and the fetus in rural South Indian population. Materials and Methods: This was a descriptive study conducted in a secondary level hospital in rural South India. A total of 1900 antenatal women were screened for pre-eclampsia during the period August 2010 to July 2011 to study the effects on the mother and fetus. Results: Of the 1900 women screened 93 were detected with pre-eclampsia in the study. Among these, 46.23% were primigravida, 30.1% belonged to socio-economic class 4 and 48.8% were among those with BMI 26–30. The incidence of severe pre-eclampsia was higher in the unregistered women. The most common maternal complication was antepartum hemorrhage (13.9%) and the most common neonatal complication was prematurity (23.65%). Conclusions: Treating anemia and improving socioeconomic status will improve maternal and neonatal outcome in pre-eclampsia. Antenatal care and educating women on significance of symptoms will markedly improve perinatal morbidity and mortality. Prematurity, growth restriction and low birth weight are neonatal complications to be anticipated and dealt with when the mother has pre-eclampsia. A good neonatal intensive care unit will help improve neonatal outcomes. PMID:25949977

  3. Left Atrial Volume and Adverse Cardiovascular Outcomes in Unselected Patients with and without CKD

    PubMed Central

    Hee, Leia; Nguyen, Tuan; Whatmough, Melinda; Descallar, Joseph; Chen, Jack; Kapila, Shruti; French, John K.

    2014-01-01

    Background and objectives Patients with CKD have increased cardiovascular morbidity and mortality. This study investigated the prognostic value of common clinical echocardiographic parameters. Design, setting, participants, & measurements There were 289 unselected consecutive patients who had a transthoracic echocardiogram between January and June 2003. Patients with stage 3 or 4 CKD (n=49) were compared with those with eGFR≥60 ml/min per 1.73 m2, n=240). Left ventricular volume, ejection fraction and mass, left atrial volume, and function parameters were measured. The primary endpoint, determined a priori, was a composite of cardiac death, myocardial infarction, and congestive cardiac failure. Results Patients were followed for a median 5.6 years. The incidence of the primary endpoint was higher in patients with CKD (29% versus 12%, P=0.001), who were older and had a higher prevalence of hypertension and ischemic heart disease. Indexed left ventricular mass (LVMI) and left atrial volume (LAVI) were higher in patients with CKD. Furthermore, patients with LAVI>32 ml/m2 had significantly lower event-free survival than patients with normal (<28 ml/m2) or mildly dilated LAVI (28–32 ml/m2) (P<0.001). Multivariate analysis showed that age (odds ratio [OR], 1.19; 95% confidence interval [95% CI], 1.08 to 1.31; P=0.001) and LVMI (OR, 3.66; 95% CI, 2.47 to 5.41; P<0.001) were independently associated with LAVI>32 ml/m2. Multivariate Cox regression analysis demonstrated that CKD (hazard ratio [HR], 1.13; 95% CI, 1.01 to 1.26; P=0.04), hypertension (HR, 2.18; 95% CI, 1.05 to 4.54; P=0.04), and a larger LAVI (HR, 1.35; 95% CI, 1.02 to 1.77; P=0.04) were independent predictors of the primary endpoint. Conclusions Patients with CKD were at higher risk for cardiovascular events. LAVI was significantly larger in the CKD group and was a predictor of adverse cardiac events. PMID:24923578

  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. Impact of single- vs double-layer closure on adverse outcomes and uterine scar defect: a systematic review and metaanalysis.

    PubMed

    Roberge, Stéphanie; Demers, Suzanne; Berghella, Vincenzo; Chaillet, Nils; Moore, Lynne; Bujold, Emmanuel

    2014-11-01

    A systematic review and metaanalysis were performed through electronic database searches to estimate the effect of uterine closure at cesarean on the risk of adverse maternal outcome and on uterine scar evaluated by ultrasound. Randomized controlled trials, which compared single vs double layers and locking vs unlocking sutures for uterine closure of low transverse cesarean, were included. Outcomes were short-term complications (endometritis, wound infection, maternal infectious morbidity, blood transfusion, duration of surgical procedure, length of hospital stay, mean blood loss), uterine rupture or dehiscence at next pregnancy, and uterine scar evaluation by ultrasound. Twenty of 1278 citations were included in the analysis. We found that all types of closure were comparable for short-term maternal outcomes, except for single-layer closure, which had shorter operative time (-6.1 minutes; 95% confidence interval [CI], -8.7 to -3.4; P < .001) than double-layer closure. Single layer (-2.6 mm; 95% CI, -3.1 to -2.1; P < .001) and locked first layer (mean difference, -2.5 mm; 95% CI, -3.2 to -1.8; P < .001) were associated with lower residual myometrial thickness. Two studies reported no significant difference between single- vs double-layer closure for uterine dehiscence (relative risk, 1.86; 95% CI, 0.44-7.90; P = .40) or uterine rupture (no case). In conclusion, current evidence based on randomized trials does not support a specific type of uterine closure for optimal maternal outcomes and is insufficient to conclude about the risk of uterine rupture. Single-layer closure and locked first layer are possibly coupled with thinner residual myometrium thickness. PMID:24912096

  6. Driving in young adults with attention deficit hyperactivity disorder: knowledge, performance, adverse outcomes, and the role of executive functioning.

    PubMed

    Barkley, Russell A; Murphy, Kevin R; Dupaul, George I; Bush, Tracie

    2002-07-01

    Past studies find that attention deficit hyperactivity disorder (ADHD) creates a higher risk for adverse driving outcomes. This study comprehensively evaluated driving in adults with ADHD by comparing 105 young adults with the disorder (age 17-28) to 64 community control (CC) adults on five domains of driving ability and a battery of executive function tasks. The ADHD group self-reported significantly more traffic citations, particularly for speeding, vehicular crashes, and license suspensions than the CC group, with most of these differences corroborated in the official DMV records. Cognitively, the ADHD group was less attentive and made more errors during a visual reaction task under rule-reversed conditions than the CC group. The ADHD group also obtained lower sceres on a test of driving rules and decision-making but not on a simple driving simulator. Both self- and other-ratings showed the CC group employed safer routine driving habits than the ADHD group. Relationships between the cognitive and driving measures and the adverse outcomes were limited or absent, calling into question their use in screening ADHD adults for driving risks. Several executive functions also were significantly yet modestly related to accident frequency and total traffic violations after controlling for severity of ADHD. These results are consistent with earlier studies showing significant driving problems are associated with ADHD. This study found that these driving difficulties were not a function of comorbid oppositional defiant disorder, depression, anxiety, or frequency of alcohol or illegal drug use. Findings to date argue for the development of interventions to reduce driving risks among adults with ADHD. PMID:12164675

  7. 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

  8. 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

  9. 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

  10. Regulation of Calcitriol Biosynthesis and Activity: Focus on Gestational Vitamin D Deficiency and Adverse Pregnancy Outcomes

    PubMed Central

    Olmos-Ortiz, Andrea; Avila, Euclides; Durand-Carbaja