Sulfadoxine-Pyrimethamine Exhibits Dose-Response Protection Against Adverse Birth Outcomes Related to Malaria and Sexually Transmitted and Reproductive Tract Infections.

PubMed

Chico, R Matthew; Chaponda, Enesia Banda; Ariti, Cono; Chandramohan, Daniel

2017-04-15

We conducted a prospective cohort study in Zambia among pregnant women who received intermittent preventive treatment using sulfadoxine-pyrimethamine (IPTp-SP). We calculated the odds ratios (ORs) of adverse birth outcomes by IPTp-SP exposure, 0-1 dose (n = 126) vs ≥2 doses (n = 590) and ≥2 doses (n = 310) vs ≥3 doses (n = 280) in 7 categories of malaria infection and sexually transmitted and reproductive tract infections (STIs/RTIs). We found no significant differences in baseline prevalence of infection across IPTp-SP exposure groups. However, among women given 2 doses compared to 0-1 dose, the odds of any adverse birth outcome were reduced 45% (OR, 0.55; 95% confidence interval [CI], 0.36, 0.86) and 13% further with ≥3 doses (OR, 0.43; 95% CI, 0.27, 0.68). Two or more doses compared to 0-1 dose reduced preterm delivery by 58% (OR, 0.42; 95% CI, 0.27, 0.67) and 21% further with ≥3 doses (OR, 0.21; 95% CI, 0.13, 0.35). Women with malaria at enrollment who received ≥2 doses vs 0-1 had 76% lower odds of any adverse birth outcome (OR, 0.24; 95% 0.09, 0.66), and Neisseria gonorrhoeae and/or Chlamydia trachomatis had 92% lower odds of any adverse birth outcome (OR, 0.08; 95% CI, 0.01, 0.64). Women with neither a malaria infection nor STIs/RTIs who received ≥2 doses had 73% fewer adverse birth outcomes (OR, 0.27; 95% CI, 0.11, 0.68). IPTp-SP appears to protect against malaria, STIs/RTIs, and other unspecified causes of adverse birth outcome. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America.

PUTATIVE ADVERSE OUTCOME PATHWAY FOR INHIBITON ...

EPA Pesticide Factsheets

The adverse outcome pathway (AOP) provides a framework for organizing knowledge to define links between a molecular initiating event (MIE) and an adverse outcome (AO) occurring at a higher level of biological organization, such as the individual or population. The AOP framework proceeds from a general (e.g., not chemical specific) molecular mode of action, designated as a MIE, through stepwise changes in biological status, defined as key events (KEs), to a final AO that can be used in risk assessment. Because aromatase-inhibiting pharmaceuticals are widely used to treat breast cancer patients, we explored the unintended consequences that might occur in fish exposed to these chemicals through wastewater discharge into the aquatic environment. Unlike mammals, fish have two isoforms of aromatase, one that predominates in the ovary (cyp19a1a) and a second (cyp19a1b) that prevails in the brain. Aromatase activity in fish brain can be 100 to 1000 times that in mammals and is associated with reproduction. We have developed a putative AOP for inhibition of brain aromatase in fish leading to reproductive dysfunction based on review of relevant literature and reproductive experiments with the marine fish cunner (Tautogolabrus adspersus) exposed to aromatase-inhibiting pharmaceuticals in the laboratory. The first KE in this AOP is a decrease in brain aromatase activity due to exposure to an aromatase inhibitor. KEs then progress through subsequent steps including decreas

Effects of noise and electromagnetic fields on reproductive outcomes.

PubMed Central

Meyer, R E; Aldrich, T E; Easterly, C E

1989-01-01

Much public health research has been directed to studies of cancer risks due to chemical agents. Recently, increasing attention has been given to adverse reproductive outcomes as another, shorter-term biologic indicator of public health impact. Further, several low-level ubiquitous physical agents have been implicated recently as possibly affecting human health. These physical factors (noise and electromagnetic fields) represent difficult topics for research with epidemiologic study methods. This paper provides a brief review of the published data related to the risk of adverse reproductive outcomes and exposure to noise or electromagnetic fields. The discussion includes ideas for possible biologic mechanisms, considerations for exposure assessment, and suggestions for epidemiologic research. PMID:2667980

ADVERSE PREGNANCY OUTCOMES ASSOCIATED WITH MATERNAL ENALAPRIL ANTIHYPERTENSIVE TREATMENT

EPA Science Inventory

Enalapril, one of several antihypertensive drugs that act as angiotensin-converting enzyme (ACE) inhibitors, is often used for treatment of hypertension in women of reproductive age. Adverse birth outcomes following the use of ACE inhibitors, including enalapril, during pregnanc...

Adverse pregnancy and birth outcomes associated with underlying diagnosis with and without assisted reproductive technology treatment.

PubMed

Stern, Judy E; Luke, Barbara; Tobias, Michael; Gopal, Daksha; Hornstein, Mark D; Diop, Hafsatou

2015-06-01

To compare the risks for adverse pregnancy and birth outcomes by diagnoses with and without assisted reproductive technology (ART) treatment to non-ART pregnancies in fertile women. Historical cohort of Massachusetts vital records linked to ART clinic data from Society for Assisted Reproductive Technology Clinic Outcome Reporting System. Not applicable. Diagnoses included male factor (ART only), endometriosis, ovulation disorders, tubal (ART only), and reproductive inflammatory disorders (non-ART only). Pregnancies resulting in singleton and twin live births from 2004 to 2008 were linked to hospital discharges in women who had ART treatment (n = 3,689), women with no ART treatment in the current pregnancy (n = 4,098), and non-ART pregnancies in fertile women (n = 297,987). None. Risks of gestational diabetes, prenatal hospitalizations, prematurity, low birth weight, and small for gestational age were modeled using multivariate logistic regression with fertile deliveries as the reference group adjusted for maternal age, race/ethnicity, education, chronic hypertension, diabetes mellitus, and plurality (adjusted odds ratios [AORs] and 95% confidence intervals [CIs]). Risk of prenatal hospital admissions was increased for endometriosis (ART: 1.97, 1.38-2.80; non-ART: 3.34, 2.59-4.31), ovulation disorders (ART: 2.31, 1.81-2.96; non-ART: 2.56, 2.05-3.21), tubal factor (ART: 1.51, 1.14-2.01), and reproductive inflammation (non-ART: 2.79, 2.47-3.15). Gestational diabetes was increased for women with ovulation disorders (ART: 2.17, 1.72-2.73; non-ART: 1.94, 1.52-2.48). Preterm delivery (AORs, 1.24-1.93) and low birth weight (AORs, 1.27-1.60) were increased in all groups except in endometriosis with ART. The findings indicate substantial excess perinatal morbidities associated with underlying infertility-related diagnoses in both ART-treated and non-ART-treated women. Copyright © 2015 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

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...

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...

Adverse Outcome Pathways: From Research to Regulation ...

EPA Pesticide Factsheets

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 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 co-sponsored by NICEATM and PCRM 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. This manuscript provides a

Reproductive outcomes in DDT applicators.

PubMed

Cocco, Pierluigi; Fadda, Domenica; Ibba, Antonio; Melis, Massimo; Tocco, Maria Giuseppina; Atzeri, Sergio; Avataneo, Giuseppe; Meloni, Michele; Monni, Filippo; Flore, Costantino

2005-05-01

To explore reproductive outcomes in relation to occupational exposure to DDT. We inquired into the reproductive history, including total number of children, sex distribution in the offspring, time-to-pregnancy, and number of spontaneous abortions and stillbirths, of the spouses of 105 men first exposed to DDT in a 1946-1950 anti-malarial campaign in Sardinia, Italy. The time-to-pregnancy in months at the first successful conception was estimated from population Registrars. Cumulative DDT exposure during the anti-malarial campaign was retrospectively estimated. The stillbirth rate was elevated and the male/female ratio in the offspring was reversed among DDT-exposed workers, and particularly among DDT applicators, compared to the unexposed subjects. Among DDT applicators, the stillbirth rate increased and the male/female ratio decreased by the tertile of cumulative DDT exposure. The fecundity ratio among spouses of DDT applicators was 0.72 (95% CI, 0.41,1.21) compared to the unexposed. The average number of children and abortion rate were unaffected by DDT exposure. The low statistical power of our study does not allow definitive conclusions. However, the results prompt further in-depth research into adverse reproductive outcomes and reduced fertility among men heavily exposed to DDT.

Endometriosis, assisted reproduction technology, and risk of adverse pregnancy outcome.

PubMed

Stephansson, Olof; Kieler, Helle; Granath, Fredrik; Falconer, Henrik

2009-09-01

Endometriosis, a common gynaecological disease, is characterized by local and systemic inflammation, which may cause infertility and consequently, increased utilization of assisted reproduction technology (ART). We aimed to estimate the risk for preterm birth, small-for-gestational-age (SGA) birth, stillbirth, Caesarean section, pre-eclampsia and antepartal haemorrhage among women with a previous diagnosis of endometriosis compared with women with no previous diagnosis of endometriosis. In a nationwide Swedish study including 1,442,675 singleton births we assessed the association between adverse pregnancy outcome, ART and a previous diagnosis of endometriosis. Information was obtained by linkage of data between 1992 and 2006 in the Medical Birth Register with the Patient Register between 1964 and 2006. There were 13,090 singleton births among 8922 women diagnosed with endometriosis. Compared with women without endometriosis, women with endometriosis had higher risks of preterm birth [adjusted odds ratio 1.33, 95% confidence interval (CI), 1.23-1.44]. Among women with endometriosis 11.9% conceived after ART compared with 1.4% of women without endometriosis. The risk of preterm birth associated with endometriosis among women with ART was 1.24 (95% CI, 0.99-1.57), and among women without ART 1.37 (95% CI, 1.25-1.50). Women with endometriosis had higher risks of antepartal bleeding/placental complications, pre-eclampsia and Caesarean section. There was no association between endometriosis and risk of SGA-birth or stillbirth. Endometriosis appears to be a risk factor for preterm birth, irrespective of ART. Women with endometriosis may be more likely to be delivered by Caesarean section and to suffer from antepartal haemorrhage/placental complications and pre-eclampsia.

PUTATIVE ADVERSE OUTCOME PATHWAY FOR INHIBITON OF BRAIN AROMATASE IN FISH LEADING TO REPRODUCTIVE IMPAIRMENT

EPA Science Inventory

The adverse outcome pathway (AOP) provides a framework for organizing knowledge to define links between a molecular initiating event (MIE) and an adverse outcome (AO) occurring at a higher level of biological organization, such as the individual or population. The AOP framework p...

Prevalence of abortion and adverse pregnancy outcomes among working women in Korea: A cross-sectional study

PubMed Central

Park, Chulyong; Kang, Mo-Yeol; Kim, Dohyung; Park, Jaechan; Eom, Huisu

2017-01-01

Objectives To investigate incidence and distribution of major adverse reproductive health problems related to various kinds of industries in Korea and to compare risks for major reproductive outcomes to assess maternal health in working and non-working women. Methods We requested claim data from the Korean National Health Insurance. We defined reference groups as (1) non-working women and (2) workers in the education field. Women working in each industry were compared with reference groups regarding rates of miscarriage, threatened abortion, preterm labor, and intrauterine growth restriction. Logistic regression was used for multivariate analysis, and age and income adjustment was performed. Results The percentages of all adverse obstetric outcomes were higher in working women than in non-working women. Working women had higher and statistically significant adjusted odds ratios (ORs) for miscarriage in 18 of the 21 industries. The age and income-adjusted OR for miscarriage for all working women was 1.26 (95% confidence interval, 1.23–1.28). Business facilities management and business support services, manufacturing, human health and social work activities, wholesale and retail trade, and professional, scientific, and technical activities were major industries with higher adjusted ORs for adverse obstetric outcomes. Conclusions We confirmed that compared to non-working women, working women have a higher risk for adverse pregnancy outcomes. Thus, adverse pregnancy outcomes such as threatened abortion, preterm labor, and intrauterine growth restriction may be associated with working status. This exploratory study identified several industries where in-depth studies are required in future to improve occupational safety in women of reproductive age. PMID:28850585

Prevalence of abortion and adverse pregnancy outcomes among working women in Korea: A cross-sectional study.

PubMed

Park, Chulyong; Kang, Mo-Yeol; Kim, Dohyung; Park, Jaechan; Eom, Huisu; Kim, Eun-A

2017-01-01

To investigate incidence and distribution of major adverse reproductive health problems related to various kinds of industries in Korea and to compare risks for major reproductive outcomes to assess maternal health in working and non-working women. We requested claim data from the Korean National Health Insurance. We defined reference groups as (1) non-working women and (2) workers in the education field. Women working in each industry were compared with reference groups regarding rates of miscarriage, threatened abortion, preterm labor, and intrauterine growth restriction. Logistic regression was used for multivariate analysis, and age and income adjustment was performed. The percentages of all adverse obstetric outcomes were higher in working women than in non-working women. Working women had higher and statistically significant adjusted odds ratios (ORs) for miscarriage in 18 of the 21 industries. The age and income-adjusted OR for miscarriage for all working women was 1.26 (95% confidence interval, 1.23-1.28). Business facilities management and business support services, manufacturing, human health and social work activities, wholesale and retail trade, and professional, scientific, and technical activities were major industries with higher adjusted ORs for adverse obstetric outcomes. We confirmed that compared to non-working women, working women have a higher risk for adverse pregnancy outcomes. Thus, adverse pregnancy outcomes such as threatened abortion, preterm labor, and intrauterine growth restriction may be associated with working status. This exploratory study identified several industries where in-depth studies are required in future to improve occupational safety in women of reproductive age.

Childhood psychosocial adversity and female reproductive timing: a cohort study of the ALSPAC mothers

PubMed Central

Magnus, Maria C; Anderson, Emma L; Howe, Laura D; Joinson, Carol J; Penton-Voak, Ian S; Fraser, Abigail

2018-01-01

Background Previous studies of childhood psychosocial adversity and age at menarche mostly evaluated single or a few measures of adversity, and therefore could not quantify total psychosocial adversity. Limited knowledge is currently available regarding childhood psychosocial adversity in relation to age at menopause and reproductive lifespan. Methods We examined the associations of total and specific components of childhood psychosocial adversity with age at menarche (n=8984), age at menopause (n=945), and length of reproductive lifespan (n=841), in mothers participating in the Avon Longitudinal Study of Parents and Children. We used confirmatory factor analysis to characterise lack of care, maladaptive family functioning, non-sexual abuse, overprotective parenting, parental mental illness and sexual abuse. These specific components of childhood psychosocial adversity were combined into a total psychosocial adversity score using a second-order factor analysis. We used structural equation models to simultaneously conduct the factor analysis and estimate the association with the continuous outcomes of interest. Results Total childhood psychosocial adversity was not associated with age at menarche, age at menopause or length of reproductive lifespan. When we examined the separate psychosocial adversity constructs, sexual abuse was inversely associated with age at menarche, with a mean difference of −0.17 (95% CI −0.23 to −0.12) years per SD higher factor score, and with age at menopause, with a mean difference of −0.17 (95% CI −0.52 to 0.18) per SD higher factor score. Conclusion Childhood sexual abuse was associated with lower age at menarche and menopause, but the latter needs to be confirmed in larger samples. PMID:29122994

Developing confidence in adverse outcome pathway-based ...

EPA Pesticide Factsheets

An adverse outcome pathway (AOP) description linking inhibition of aromatase (cytochrome P450 [cyp] 19) to reproductive dysfunction was reviewed for scientific and technical quality and endorsed by the OECD. An intended application of the AOP framework is to support the use of mechanistic or pathway-based data to infer or predict chemical hazards and apical adverse outcomes. As part of this work, ToxCast high throughput screening data were used to identify a chemicals’ ability to inhibit aromatase activity in vitro. Twenty-four hour in vivo exposures, focused on effects on production and circulating concentrations of 17β-estradiol (E2), key events in the AOP, were conducted to verify in vivo activity. Based on these results, imazalil was selected as a case study chemical to test an AOP-based hazard prediction. A computational model of the fish hypothalamic-pituitary-gonadal-liver axis and a statistically-based model of oocyte growth dynamics were used to predict impacts of different concentrations of imazalil on multiple key events along the AOP, assuming continuous exposure for 21 d. Results of the model simulations were used to select test concentrations and design a fathead minnow reproduction study in which fish were exposed to 20, 60, or 200 µg imazalil/L for durations of 2.5, 10, or 21d. Within 60 h of exposure, female fathead minnows showed significant reductions in ex vivo production of E2, circulating E2 concentrations, and significant increases in

Developing confidence in adverse outcome pathway-based ...

EPA Pesticide Factsheets

An adverse outcome pathway (AOP) description linking inhibition of aromatase (cytochrome P450 [cyp] 19) to reproductive dysfunction was reviewed for scientific and technical quality and endorsed by the OECD (https://aopwiki.org/wiki/index.php/Aop:25). An intended application of the AOP framework is to support the use of mechanistic or pathway-based data to infer or predict chemical hazards and apical adverse outcomes. As part of this work, ToxCast high throughput screening data were used to identify a chemicals’ ability to inhibit aromatase activity in vitro. Twenty-four hour in vivo exposures, focused on effects on production and circulating concentrations of 17â-estradiol (E2), key events in the AOP, were conducted to verify in vivo activity. Based on these results, imazalil was selected as a case study chemical to test an AOP-based hazard prediction. A computational model of the fish hypothalamic-pituitary-gonadal-liver axis and a statistically-based model of oocyte growth dynamics were used to predict impacts of different concentrations of imazalil on multiple key events along the AOP, assuming continuous exposure for 21 d. Results of the model simulations were used to select test concentrations and design a fathead minnow reproduction study in which fish were exposed to 20, 60, or 200 µg imazalil/L for durations of 2.5, 10, or 21d. Within 60 h of exposure, female fathead minnows showed significant reductions in ex vivo production of E2, circulating E2 c

Department of Defense Birth and Infant Health Registry: select reproductive health outcomes, 2003-2014.

PubMed

Bukowinski, Anna T; Conlin, Ava Marie S; Gumbs, Gia R; Khodr, Zeina G; Chang, Richard N; Faix, Dennis J

2017-11-01

Established following a 1998 directive, the Department of Defense Birth and Infant Health Registry (Registry) team conducts surveillance of select reproductive health outcomes among military families. Data are compiled from the Military Health System Data Repository and Defense Manpower Data Center to define the Registry cohort and outcomes of interest. Outcomes are defined using ICD-9/ICD-10 and Current Procedural Terminology codes, and include: pregnancy outcomes (e.g., live births, losses), birth defects, preterm births, and male:female infant sex ratio. This report includes data from 2003-2014 on 1,304,406 infants among military families and 258,332 pregnancies among active duty women. Rates of common adverse infant and pregnancy outcomes were comparable to or lower than those in the general US population. These observations, along with prior Registry analyses, provide reassurance that military service is not independently associated with increased risks for select adverse reproductive health outcomes. The Registry's diverse research portfolio demonstrates its unique capabilities to answer a wide range of questions related to reproductive health. These data provide the military community with information to identify successes and areas for improvement in prevention and care.

Childhood psychosocial adversity and female reproductive timing: a cohort study of the ALSPAC mothers.

PubMed

Magnus, Maria C; Anderson, Emma L; Howe, Laura D; Joinson, Carol J; Penton-Voak, Ian S; Fraser, Abigail

2018-01-01

Previous studies of childhood psychosocial adversity and age at menarche mostly evaluated single or a few measures of adversity, and therefore could not quantify total psychosocial adversity. Limited knowledge is currently available regarding childhood psychosocial adversity in relation to age at menopause and reproductive lifespan. We examined the associations of total and specific components of childhood psychosocial adversity with age at menarche (n=8984), age at menopause (n=945), and length of reproductive lifespan (n=841), in mothers participating in the Avon Longitudinal Study of Parents and Children. We used confirmatory factor analysis to characterise lack of care, maladaptive family functioning, non-sexual abuse, overprotective parenting, parental mental illness and sexual abuse. These specific components of childhood psychosocial adversity were combined into a total psychosocial adversity score using a second-order factor analysis. We used structural equation models to simultaneously conduct the factor analysis and estimate the association with the continuous outcomes of interest. Total childhood psychosocial adversity was not associated with age at menarche, age at menopause or length of reproductive lifespan. When we examined the separate psychosocial adversity constructs, sexual abuse was inversely associated with age at menarche, with a mean difference of -0.17 (95% CI -0.23 to -0.12) years per SD higher factor score, and with age at menopause, with a mean difference of -0.17 (95% CI -0.52 to 0.18) per SD higher factor score. Childhood sexual abuse was associated with lower age at menarche and menopause, but the latter needs to be confirmed in larger samples. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Adverse Reproductive and Developmental Health Outcomes Following Prenatal Exposure to a Hydraulic Fracturing Chemical Mixture in Female C57Bl/6 Mice.

PubMed

Kassotis, Christopher D; Bromfield, John J; Klemp, Kara C; Meng, Chun-Xia; Wolfe, Andrew; Zoeller, R Thomas; Balise, Victoria D; Isiguzo, Chiamaka J; Tillitt, Donald E; Nagel, Susan C

2016-09-01

Unconventional oil and gas operations using hydraulic fracturing can contaminate surface and groundwater with endocrine-disrupting chemicals. We have previously shown that 23 of 24 commonly used hydraulic fracturing chemicals can activate or inhibit the estrogen, androgen, glucocorticoid, progesterone, and/or thyroid receptors in a human endometrial cancer cell reporter gene assay and that mixtures can behave synergistically, additively, or antagonistically on these receptors. In the current study, pregnant female C57Bl/6 dams were exposed to a mixture of 23 commonly used unconventional oil and gas chemicals at approximately 3, 30, 300, and 3000 μg/kg·d, flutamide at 50 mg/kg·d, or a 0.2% ethanol control vehicle via their drinking water from gestational day 11 through birth. This prenatal exposure to oil and gas operation chemicals suppressed pituitary hormone concentrations across experimental groups (prolactin, LH, FSH, and others), increased body weights, altered uterine and ovary weights, increased heart weights and collagen deposition, disrupted folliculogenesis, and other adverse health effects. This work suggests potential adverse developmental and reproductive health outcomes in humans and animals exposed to these oil and gas operation chemicals, with adverse outcomes observed even in the lowest dose group tested, equivalent to concentrations reported in drinking water sources. These endpoints suggest potential impacts on fertility, as previously observed in the male siblings, which require careful assessment in future studies.

Adverse Reproductive and Developmental Health Outcomes Following Prenatal Exposure to a Hydraulic Fracturing Chemical Mixture in Female C57Bl/6 Mice

PubMed Central

Kassotis, Christopher D.; Bromfield, John J.; Klemp, Kara C.; Meng, Chun-Xia; Wolfe, Andrew; Zoeller, R. Thomas; Balise, Victoria D.; Isiguzo, Chiamaka J.; Tillitt, Donald E.

2016-01-01

Unconventional oil and gas operations using hydraulic fracturing can contaminate surface and groundwater with endocrine-disrupting chemicals. We have previously shown that 23 of 24 commonly used hydraulic fracturing chemicals can activate or inhibit the estrogen, androgen, glucocorticoid, progesterone, and/or thyroid receptors in a human endometrial cancer cell reporter gene assay and that mixtures can behave synergistically, additively, or antagonistically on these receptors. In the current study, pregnant female C57Bl/6 dams were exposed to a mixture of 23 commonly used unconventional oil and gas chemicals at approximately 3, 30, 300, and 3000 μg/kg·d, flutamide at 50 mg/kg·d, or a 0.2% ethanol control vehicle via their drinking water from gestational day 11 through birth. This prenatal exposure to oil and gas operation chemicals suppressed pituitary hormone concentrations across experimental groups (prolactin, LH, FSH, and others), increased body weights, altered uterine and ovary weights, increased heart weights and collagen deposition, disrupted folliculogenesis, and other adverse health effects. This work suggests potential adverse developmental and reproductive health outcomes in humans and animals exposed to these oil and gas operation chemicals, with adverse outcomes observed even in the lowest dose group tested, equivalent to concentrations reported in drinking water sources. These endpoints suggest potential impacts on fertility, as previously observed in the male siblings, which require careful assessment in future studies. PMID:27560547

Effects of the workplace on fertility and related reproductive outcomes.

PubMed Central

Baranski, B

1993-01-01

This report reviews the recent literature on the adverse effects of occupational factors on fertility and related reproductive outcomes. Few studies fulfill the criteria of good study design because of small sample size, insensitive measures of effect, selection, recall, and observation bias, weak if any control of confounding factors, bad definition of exposure, inability to analyze a dose-response relationship, and inadequate statistical analysis. The high prevalence of unsuccessful reproductive outcomes in the general population makes the design of human fertility studies difficult. Although a number of publications indicate that certain occupational factors and settings adversely affect both male and female fertility, it is virtually impossible to estimate the proportion of infertility due to occupational factors in the general population. The collected data suggest that the exposure to the following substances or occupational settings may affect a function of male genital system, leading to sperm abnormalities, hyperestrogenism, impotence, infertility, and/or increased spontaneous abortion rate in wives of exposed workers: alkylmercury, antimonide, anesthetic gases, boron, carbon disulfide, chlorodecone, chloroprene, some carbamates (carbaryl), diaminostilbene, 1,2-dibromo-3-chloropropane, ethylene glycol ethers, ethylene dibromide, inorganic lead, manganese, methyl chloride, organic solvents, synthetic estrogens and progestins, tetraethyllead, combined exposure to styrene and acetone, welding operations, and heat. The majority of reviewed papers on female fertility concerns the alterations of menstrual cycle and pregnancy complications rather than occupational exposure-induced female infertility. The literature supports the hypothesis that, in general, working women have a tendency of higher risk of unsuccessful reproductive outcomes, although the existing data are not sufficient. PMID:8243410

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...

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...

Position of the American Dietetic Association and American Society for Nutrition: obesity, reproduction, and pregnancy outcomes.

PubMed

Siega-Riz, Anna Maria; King, Janet C

2009-05-01

Given the detrimental influence of maternal overweight and obesity on reproductive and pregnancy outcomes for the mother and child, it is the position of the American Dietetic Association and the American Society for Nutrition that all overweight and obese women of reproductive age should receive counseling on the roles of diet and physical activity in reproductive health prior to pregnancy,during pregnancy, and in the inter conceptional period, in order to ameliorate these adverse outcomes. The effect of maternal nutritional status prior to pregnancy on reproduction and pregnancy outcomes is of great public health importance. Obesity in the United States and worldwide has grown to epidemic proportions, with an estimated 33% of US women classified as obese. This position paper has two objectives: (a) to help nutrition professionals become aware of the risks and possible complications of overweight and obesity for fertility,the course of pregnancy, birth outcomes, and short- and long-term maternal and child health outcomes;and (b) related to the commitment to research by the American Dietetic Association and the American Society for Nutrition, to identify the gaps in research to improve our knowledge of the risks and complications associated with being overweight and obese before and during pregnancy.Only with an increased knowledge of these risks and complications can health care professionals develop effective strategies that can be implemented before and during pregnancy as well as during the inter conceptional period to ameliorate adverse outcomes.

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

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)...

No increased risk of major congenital anomalies or adverse pregnancy or neonatal outcomes following letrozole use in assisted reproductive technology.

PubMed

Tatsumi, T; Jwa, S C; Kuwahara, A; Irahara, M; Kubota, T; Saito, H

2017-01-01

rule out the possibility that letrozole might cause large increases in birth-defect risks in ART patients. The results suggest that letrozole stimulation reduces the risk of miscarriage, with no increase in the risk of major congenital anomalies or adverse pregnancy or neonatal outcomes compared with natural cycles in women undergoing ART. Letrozole may thus be a safe option for mild ovarian stimulation. None. Not applicable. © The Author 2016. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Review: Toxicants in reproductive fluid and in vitro fertilization (IVF) outcome.

PubMed

Kumar, Sunil; Mishra, Vineet V

2010-09-01

Some of the physical, chemical, dietary, occupational and environmental factors are having adverse effect on human reproduction. Increasing trend in reproductive disorders in recent years at least in part might be associated with these factors. The data available suggests less success rate of in vitro fertilization (IVF) outcome of parents exposed to some of the reproductive toxic chemicals as compared to parents who were not exposed to such chemicals. However, data are very meager and require more studies as some debatable data also exists. But existing positive findings encourage in advising that sub-fertile subjects, who are planning to go for the IVF, should reduce toxic exposure well in advance by adopting positive life style and work environment. Further, clinician ought to be aware of occupational and environmental exposure history of the participating couple.

Adverse reproductive and developmental health outcomes following prenatal exposure to a 2 hydraulic fracturing chemical mixture in female C57Bl/6 mice

USGS Publications Warehouse

Kassotis, Christopher D.; Bromfield, John J.; Klemp, Kara C.; Meng, Chun-Xia; Wolfe, Andrew R.; Zoeller, Thomas; Balise, Victoria D.; Isiguzo, Chiamaka J.; Tillitt, Donald E.; Nagel, Susan C.

2016-01-01

Unconventional oil and gas operations using hydraulic fracturing can contaminate surface and groundwater with endocrine-disrupting chemicals. We have previously shown that 23 of 24 commonly used hydraulic fracturing chemicals can activate or inhibit the estrogen, androgen, glucocorticoid, progesterone, and/or thyroid receptors in a human endometrial cancer cell reporter gene assay and that mixtures can behave synergistically, additively, or antagonistically on these receptors. In the current study, pregnant female C57Bl/6 dams were exposed to a mixture of 23 commonly used unconventional oil and gas chemicals at approximately 3, 30, 300, and 3000 μg/kg·d, flutamide at 50 mg/kg·d, or a 0.2% ethanol control vehicle via their drinking water from gestational day 11 through birth. This prenatal exposure to oil and gas operation chemicals suppressed pituitary hormone concentrations across experimental groups (prolactin, LH, FSH, and others), increased body weights, altered uterine and ovary weights, increased heart weights and collagen deposition, disrupted folliculogenesis, and other adverse health effects. This work suggests potential adverse developmental and reproductive health outcomes in humans and animals exposed to these oil and gas operation chemicals, with adverse outcomes observed even in the lowest dose group tested, equivalent to concentrations reported in drinking water sources. These endpoints suggest potential impacts on fertility, as previously observed in the male siblings, which require careful assessment in future studies. - See more at: http://press.endocrine.org/doi/10.1210/en.2016-1242#sthash.9kqfLvXg.dpuf

Non-cigarette tobacco use among women and adverse pregnancy outcomes

PubMed Central

ENGLAND, LUCINDA J.; KIM, SHIN Y.; TOMAR, SCOTT L; RAY, CECILY S; GUPTA, PRAKASH C.; EISSENBERG, THOMAS; CNATTINGIUS, SVEN; BERNERT, JOHN T.; TITA, ALAN THEVENET N.; WINN, DEBORAH M.; DJORDJEVIC, MIRJANA V.; LAMBE, MATS; STAMILIO, DAVID; CHIPATO, TSUNGAI; TOLOSA, JORGE E.

2017-01-01

Although cigarette smoking remains the most prevalent form of tobacco use in girls and in women of reproductive age globally, use of non-cigarette forms of tobacco is prevalent or gaining in popularity in many parts of the world, especially in low- and middle-income countries. Sparse but growing evidence suggests that the use of some non-cigarette tobacco products during pregnancy increases the risk of adverse pregnancy outcomes. In this paper we review the literature on the prevalence of non-cigarette tobacco product use in pregnant women and in women of reproductive age in high-, middle-, and low-income countries and the evidence that maternal use of these products during pregnancy has adverse health effects. In addition, we communicate findings from an international group of perinatal and tobacco experts that was convened to establish research priorities concerning the use of non-cigarette tobacco products during pregnancy. The working group concluded that attempts to develop a public health response to non-cigarette tobacco use in women are hindered by a lack of data on the epidemiology of use in many parts of the world and by our limited understanding of the type and magnitude of the health effects of these products. We highlight research gaps and provide recommendations for a global research agenda. PMID:20225987

Reproductive Outcomes Associated with Noise Exposure — A Systematic Review of the Literature

PubMed Central

Ristovska, Gordana; Laszlo, Helga Elvira; Hansell, Anna L.

2014-01-01

Introduction: High noise exposure during critical periods in gestation is a potential stressor that may result in increased risk of implantation failure, dysregulation of placentation or decrease of uterine blood flow. This paper systematically reviews published evidence on associations between reproductive outcomes and occupational and environmental noise exposure. Methods: The Web of Science, PubMed and Embase electronic databases were searched for papers published between 1970 to June 2014 and via colleagues. We included 14 epidemiological studies related to occupational noise exposure and nine epidemiological studies related to environmental noise exposure. There was some evidence for associations between occupational noise exposure and low birthweight, preterm birth and small for gestational age, either independently or together with other occupational risk factors. Five of six epidemiologic studies, including the two largest studies, found significant associations between lower birthweight and higher noise exposure. There were few studies on other outcomes and study design issues may have led to bias in assessments in some studies. Conclusions: There is evidence for associations between noise exposure and adverse reproductive outcomes from animal studies. Few studies in have been conducted in humans but there is some suggestive evidence of adverse associations with environmental noise from both occupational and epidemiological studies, especially for low birthweight. PMID:25101773

Arsenic in drinking water and adverse birth outcomes in Ohio.

PubMed

Almberg, Kirsten S; Turyk, Mary E; Jones, Rachael M; Rankin, Kristin; Freels, Sally; Graber, Judith M; Stayner, Leslie T

2017-08-01

Arsenic in drinking water has been associated with adverse reproductive outcomes in areas with high levels of naturally occurring arsenic. Less is known about the reproductive effects of arsenic at lower levels. This research examined the association between low-level arsenic in drinking water and small for gestational age (SGA), term low birth weight (term LBW), very low birth weight (VLBW), preterm birth (PTB), and very preterm birth (VPTB) in the state of Ohio. Exposure was defined as the mean annual arsenic concentration in drinking water in each county in Ohio from 2006 to 2008 using Safe Drinking Water Information System data. Birth outcomes were ascertained from the birth certificate records of 428,804 births in Ohio from the same time period. Multivariable generalized estimating equation logistic regression models were used to assess the relationship between arsenic and each birth outcome separately. Sensitivity analyses were performed to examine the roles of private well use and prenatal care utilization in these associations. Arsenic in drinking water was associated with increased odds of VLBW (AOR 1.14 per µg/L increase; 95% CI 1.04, 1.24) and PTB (AOR 1.10; 95% CI 1.06, 1.15) among singleton births in counties where <10% of the population used private wells. No significant association was observed between arsenic and SGA, or VPTB, but a suggestive association was observed between arsenic and term LBW. Arsenic in drinking water was positively associated with VLBW and PTB in a population where nearly all (>99%) of the population was exposed under the current maximum contaminant level of 10µg/L. Current regulatory standards may not be protective against reproductive effects of prenatal exposure to arsenic. Copyright © 2017 Elsevier Inc. All rights reserved.

Can Drosophila melanogaster represent a model system for the detection of reproductive adverse drug reactions?

PubMed

Avanesian, Agnesa; Semnani, Sahar; Jafari, Mahtab

2009-08-01

Once a molecule is identified as a potential drug, the detection of adverse drug reactions is one of the key components of its development and the FDA approval process. We propose using Drosophila melanogaster to screen for reproductive adverse drug reactions in the early stages of drug development. Compared with other non-mammalian models, D. melanogaster has many similarities to the mammalian reproductive system, including putative sex hormones and conserved proteins involved in genitourinary development. Furthermore, the D. melanogaster model would present significant advantages in time efficiency and cost-effectiveness compared with mammalian models. We present data on methotrexate (MTX) reproductive adverse events in multiple animal models, including fruit flies, as proof-of-concept for the use of the D. melanogaster model.

Adverse outcome pathways: a concise introduction for toxicologists

PubMed Central

Vergauwen, Lucia; Hengstler, Jan G.; Angrish, Michelle; Whelan, Maurice

2018-01-01

Adverse outcome pathways are designed to provide a clear-cut mechanistic representation of critical toxicological effects that propagate over different layers of biological organization from the initial interaction of a chemical with a molecular target to an adverse outcome at the individual or population level. Adverse outcome pathways are currently gaining momentum, especially in view of their many potential applications as pragmatic tools in the fields of human toxicology, ecotoxicology and risk assessment. A number of guidance documents, issued by the Organization for Economic Cooperation and Development, as well as landmark papers, outlining best practices to develop, assess and use adverse outcome pathways, have been published in the last few years. The present paper provides a synopsis of the main principles related to the adverse outcome pathway framework for the toxicologist less familiar with this area, followed by two case studies relevant for human toxicology and ecotoxicology. PMID:28660287

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...

Systems Toxicology of Male Reproductive Development ...

EPA Pesticide Factsheets

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 reproductive developmental defects. The present study established the links between environmental chemicals, molecular targets, and adverse outcomes using U.S. EPA animal study (ToxRefDB) and high-throughput screening (ToxCast) databases. This systems-based approach revealed a phenotypic hierarchy across 63 chemicals and a pleiotropic in vitro bioactivity profile. Although estrogenic and anti-androgenic activities have been extensively studied in male reproductive developmental toxicity, the present study showed these receptor targets to be only a subset of the potential landscape of molecular targets. A variety of chemical (e.g. phthalates, conazoles, carbamates, and phenol compounds) and bioactivity (e.g. nuclear receptors, vascular remodeling proteins, and cytochrome-P450 reductases) clusters further suggested multiple pathways leading to the adverse outcomes. This points to the need for multi-scale systems models to predict whether the occurrence of one adverse outcome may predict the risk of another. Imbalances in androgen and estrogen signaling have been a general focus in male reproductive toxicology research. While a number of recent studies have demonstrated that both hormonal

The health outcomes of human offspring conceived by assisted reproductive technologies (ART).

PubMed

Chen, M; Heilbronn, L K

2017-08-01

Concerns have been raised about the health and development of children conceived by assisted reproductive technologies (ART) since 1978. Controversially, ART has been linked with adverse obstetric and perinatal outcomes, an increased risk of birth defects, cancers, and growth and development disorders. Emerging evidence suggests that ART treatment may also predispose individuals to an increased risk of chronic ageing related diseases such as obesity, type 2 diabetes and cardiovascular disease. This review will summarize the available evidence on the short-term and long-term health outcomes of ART singletons, as multiple pregnancies after multiple embryos transfer, are associated with low birth weight and preterm delivery, which can separately increase risk of adverse postnatal outcomes, and impact long-term health. We will also examine the potential factors that may contribute to these health risks, and discuss underlying mechanisms, including epigenetic changes that may occur during the preimplantation period and reprogram development in utero, and adult health, later in life. Lastly, this review will consider the future directions with the view to optimize the long-term health of ART children.

The Complement System and Adverse Pregnancy Outcomes

PubMed Central

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

2015-01-01

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

Exposure to phthalates: reproductive outcome and children health. A review of epidemiological studies.

PubMed

Jurewicz, Joanna; Hanke, Wojciech

2011-06-01

Phthalates are a family of industrial chemicals that have been used for a variety of purposes. As the potential consequences of human exposure to phthalates have raised concerns in the general population, they have been studied in susceptible subjects such as pregnant women, infants and children. This article aims at evaluating the impact of exposure to phthalates on reproductive outcomes and children health by reviewing most recent published literature. Epidemiological studies focusing on exposure to phthalates and pregnancy outcome, genital development, semen quality, precocious puberty, thyroid function, respiratory symptoms and neurodevelopment in children for the last ten years were identified by a search of the PubMed, Medline, Ebsco, Agricola and Toxnet literature bases. The results from the presented studies suggest that there are strong and rather consistent indications that phthalates increase the risk of allergy and asthma and have an adverse impact on children's neurodevelopment reflected by quality of alertness among girls, decreased (less masculine) composite score in boys and attention deficit hyperactivity disorder. Results of few studies demonstrate negative associations between phthalate levels commonly experienced by the public and impaired sperm quality (concentration, morphology, motility). Phthalates negatively impact also on gestational age and head circumference; however, the results of the studies were not consistent. In all the reviewed studies, exposure to phthalates adversely affected the level of reproductive hormones (luteinizing hormone, free testosterone, sex hormone-binding globulin), anogenital distance and thyroid function. The urinary levels of phthalates were significantly higher in the pubertal gynecomastia group, in serum in girls with premature thelarche and in girls with precocious puberty. Epidemiological studies, in spite of their limitations, suggest that phthalates may affect reproductive outcome and children health

[Effect of air pollution on pregnancy outcome of women at reproductive age in Xi'an, 2010-2013].

PubMed

Wang, L L; Bai, R H; Zhang, Q; Yan, H

2016-11-10

Objective: To compare the differences in the incidence of adverse pregnancy outcome in different area, and confirm if the incidence of adverse pregnancy outcomes is closely associated with air pollution. Methods: A cross-sectional study was conducted in the central urban area and the rural-urban area of Xi'an through a questionnaire survey conducted among the local reproductive women selected through multistage stratified random sampling during 2010-2013, all the reproductive women surveyed were in pregnancy or had definite pregnancy outcomes. Results: The annual average of SO 2 concentration in the central urban area was 38-54 μg/m 3 , higher than that in the rural-urban area (29-43 μg/m 3 ). The annual average NO 2 concentration in the central urban area was 29-87 μg/m 3 , higher than that in the rural-urban area (22-42 μg/m 3 ). The incidence of birth defects was higher in the central urban area than in the rural-urban area (2.1% vs. 1.0%), the difference was significant ( P <0.05). After adjusting for confounding factors, logistic regression analysis showed the incidence of birth defects in the central urban area was still significantly higher than that in the rural-urban area, the difference was significant ( P <0.05). Conclusion: The incidence of adverse pregnancy was closely associated with the level of air pollution.

Gastroschisis: antenatal sonographic predictors of adverse neonatal outcome.

PubMed

Page, Rachael; Ferraro, Zachary Michael; Moretti, Felipe; Fung, Karen Fung Kee

2014-01-01

The aim of this review was to identify clinically significant ultrasound predictors of adverse neonatal outcome in fetal gastroschisis. A quasi-systematic review was conducted in PubMed and Ovid using the key terms "gastroschisis," "predictors," "outcome," and "ultrasound." A total of 18 papers were included. The most common sonographic predictors were intra-abdominal bowel dilatation (IABD), intrauterine growth restriction (IUGR), and bowel dilatation not otherwise specified (NOS). Three ultrasound markers were consistently found to be statistically insignificant with respect to predicting adverse outcome including abdominal circumference, stomach herniation and dilatation, and extra-abdominal bowel dilatation (EABD). Gastroschisis is associated with several comorbidities, yet there is much discrepancy in the literature regarding which specific ultrasound markers best predict adverse neonatal outcomes. Future research should include prospective trials with larger sample sizes and use well-defined and consistent definitions of the adverse outcomes investigated with consideration given to IABD.

Putative adverse outcome pathways relevant to neurotoxicity

PubMed Central

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

2016-01-01

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

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...

1991 Gulf War exposures and adverse birth outcomes.

PubMed

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

2013-01-01

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.

Developing and applying the adverse outcome pathway ...

EPA Pesticide Factsheets

To support a paradigm shift in regulatory toxicology testing and risk assessment, the Adverse Outcome Pathway (AOP) concept has recently been proposed. This concept is similar to that for Mode of Action (MOA), describing a sequence of measurable key events triggered by a molecular initiating event in which a stressor interacts with a biological target. The resulting cascade of key events includes molecular, cellular, structural and functional changes in biological systems, resulting in a measurable adverse outcome. Thereby, an AOP ideally provides information relevant to chemical structure-activity relationships as a basis to predict effects for structurally similar compounds. AOPs could potentially also form the basis for qualitative and quantitative predictive modeling of the human adverse outcome resulting from molecular initiating or other key events for which higher-throughput testing methods are available or can be developed.A variety of cellular and molecular processes are known to be critical to normal function of the central (CNS) and peripheral nervous systems (PNS). Because of the biological and functional complexity of the CNS and PNS, it has been challenging to establish causative links and quantitative relationships between key events that comprise the pathways leading from chemical exposure to an adverse outcome in the nervous system. Following introduction of principles of the description and assessment of MOA and AOPs, examples of adverse out

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

Waste incineration and adverse birth and neonatal outcomes: a systematic review.

PubMed

Ashworth, Danielle C; Elliott, Paul; Toledano, Mireille B

2014-08-01

Public concern about potential health risks associated with incineration has prompted studies to investigate the relationship between incineration and risk of cancer, and more recently, birth outcomes. We conducted a systematic review of epidemiologic studies evaluating the relationship between waste incineration and the risk of adverse birth and neonatal outcomes. Literature searches were performed within the MEDLINE database, through PubMed and Ovid interfaces, for the search terms; incineration, birth, reproduction, neonatal, congenital anomalies and all related terms. Here we discuss and critically evaluate the findings of these studies. A comprehensive literature search yielded fourteen studies, encompassing a range of outcomes (including congenital anomalies, birth weight, twinning, stillbirths, sex ratio and infant death), exposure assessment methods and study designs. For congenital anomalies most studies reported no association with proximity to or emissions from waste incinerators and "all anomalies", but weak associations for neural tube and heart defects and stronger associations with facial clefts and urinary tract defects. There is limited evidence for an association between incineration and twinning and no evidence of an association with birth weight, stillbirths or sex ratio, but this may reflect the sparsity of studies exploring these outcomes. The current evidence-base is inconclusive and often limited by problems of exposure assessment, possible residual confounding, lack of statistical power with variability in study design and outcomes. However, we identified a number of higher quality studies reporting significant positive relationships with broad groups of congenital anomalies, warranting further investigation. Future studies should address the identified limitations in order to help improve our understanding of any potential adverse birth outcomes associated with incineration, particularly focussing on broad groups of anomalies, to inform

Conceptualizing adverse outcome pathways for ...

EPA Pesticide Factsheets

Cyclooxygenase (COX) inhibition is of concern in fish because COX inhibitors (e.g., ibuprofen) are ubiquitous in aquatic systems/fish tissues, and can disrupt synthesis of prostaglandins that modulate a variety of essential biological functions (e.g., reproduction). This study utilized newly generated high content (transcriptomic and metabolomic) empirical data in combination with existing high throughput (ACTOR, epa.gov) toxicity data to facilitate development of adverse outcome pathways (AOPs) for molecular initiating event (MIE) of COX inhibition. We examined effects of a waterborne, 96h exposure to three COX inhibitors (indomethacin (IN; 100 µg/L), ibuprofen (IB; 200 µg/L) and celecoxib (CX; 20 µg/L) on the liver metabolome and ovarian gene expression (using oligonucleotide microarray 4 x15K platform) in sexually mature fathead minnows (n=8). Differentially expressed genes were identified (t-test, p < 0.01), and functional analyses performed to determine enriched Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways (p < 0.05). Principal component analysis indicated that liver metabolomics profiles of IN, IB and CX were not significantly different from control or one another. When compared to control, exposure to IB and CX resulted in differential expression of comparable numbers of genes (IB = 433, CX= 545). In contrast, 2558 genes were differentially expressed in IN-treated fish. KEGG pathway analyses show that IN had extensive effects on oocyte meios

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…

Adverse health outcomes in women exposed in utero to diethylstilbestrol.

PubMed

Hoover, Robert N; Hyer, Marianne; Pfeiffer, Ruth M; Adam, Ervin; Bond, Brian; Cheville, Andrea L; Colton, Theodore; Hartge, Patricia; Hatch, Elizabeth E; Herbst, Arthur L; Karlan, Beth Y; Kaufman, Raymond; Noller, Kenneth L; Palmer, Julie R; Robboy, Stanley J; Saal, Robert C; Strohsnitter, William; Titus-Ernstoff, Linda; Troisi, Rebecca

2011-10-06

Before 1971, several million women were exposed in utero to diethylstilbestrol (DES) given to their mothers to prevent pregnancy complications. Several adverse outcomes have been linked to such exposure, but their cumulative effects are not well understood. We combined data from three studies initiated in the 1970s with continued long-term follow-up of 4653 women exposed in utero to DES and 1927 unexposed controls. We assessed the risks of 12 adverse outcomes linked to DES exposure, including cumulative risks to 45 years of age for reproductive outcomes and to 55 years of age for other outcomes, and their relationships to the baseline presence or absence of vaginal epithelial changes, which are correlated with a higher dose of, and earlier exposure to, DES in utero. Cumulative risks in women exposed to DES, as compared with those not exposed, were as follows: for infertility, 33.3% vs. 15.5% (hazard ratio, 2.37; 95% confidence interval [CI], 2.05 to 2.75); spontaneous abortion, 50.3% vs. 38.6% (hazard ratio, 1.64; 95% CI, 1.42 to 1.88); preterm delivery, 53.3% vs. 17.8% (hazard ratio, 4.68; 95% CI, 3.74 to 5.86); loss of second-trimester pregnancy, 16.4% vs. 1.7% (hazard ratio, 3.77; 95% CI, 2.56 to 5.54); ectopic pregnancy, 14.6% vs. 2.9% (hazard ratio, 3.72; 95% CI, 2.58 to 5.38); preeclampsia, 26.4% vs. 13.7% (hazard ratio 1.42; 95% CI, 1.07 to 1.89); stillbirth, 8.9% vs. 2.6% (hazard ratio, 2.45; 95% CI, 1.33 to 4.54); early menopause, 5.1% vs. 1.7% (hazard ratio, 2.35; 95% CI, 1.67 to 3.31); grade 2 or higher cervical intraepithelial neoplasia, 6.9% vs. 3.4% (hazard ratio, 2.28; 95% CI, 1.59 to 3.27); and breast cancer at 40 years of age or older, 3.9% vs. 2.2% (hazard ratio, 1.82; 95% CI, 1.04 to 3.18). For most outcomes, the risks among exposed women were higher for those with vaginal epithelial changes than for those without such changes. In utero exposure of women to DES is associated with a high lifetime risk of a broad spectrum of adverse health outcomes

Significant Adverse Events and Outcomes After Medical Abortion

PubMed Central

Cleland, Kelly; Creinin, Mitchell D.; Nucatola, Deborah; Nshom, Montsine; Trussell, James

2013-01-01

Objective To analyze rates of significant adverse events and outcomes in women having a medical abortion at Planned Parenthood health centers in 2009 and 2010, and to identify changes in the rates of adverse events and outcomes between the 2 years. Methods In this database review we analyzed data from Planned Parenthood affiliates that provided medical abortion in 2009 and 2010, almost exclusively using an evidence-based buccal misoprostol regimen. We evaluated the incidence of six clinically significant adverse events (hospital admission, blood transfusion, emergency room treatment, intravenous antibiotics administration, infection, and death) and two significant outcomes (ongoing pregnancy and ectopic pregnancy diagnosed after medical abortion treatment was initiated). We calculated an overall rate as well as rates for each event and identified changes between the 2 years. Results Amongst 233,805 medical abortions provided in 2009 and 2010, significant adverse events or outcomes were reported in 1,530 cases (0.65%). There was no statistically significant difference in overall rates between years. The most common significant outcome was ongoing intrauterine pregnancy (0.50%); significant adverse events occurred in 0.16% of cases. One patient death occurred due to an undiagnosed ectopic pregnancy. Only rates for emergency room treatment and blood transfusion differed by year, and were slightly higher in 2010. Conclusion Review of this large dataset reinforces the safety of the evidence-based medical abortion regimen. PMID:23262942

Department of Defense Birth and Infant Health Registry: Select Reproductive Health Outcomes, 2003-2014 (Open Access Publisher’s Version)

DTIC Science & Technology

2017-11-01

November 2017 Vol. 24 No. 11 MSMR Page 39 Established following a 1998 directive, the Department of Defense Birth and Infant Health Registry...Registry) team conducts surveillance of select repro- ductive health outcomes among military families. Data are compiled from the Military Health System...adverse reproductive health outcomes. The Regis- try’s diverse research portfolio demonstrates its unique capabilities to answer a wide range of

Soy Intake Modifies the Relation Between Urinary Bisphenol A Concentrations and Pregnancy Outcomes Among Women Undergoing Assisted Reproduction

PubMed Central

Mínguez-Alarcón, Lidia; Chiu, Yu-Han; Gaskins, Audrey J.; Souter, Irene; Williams, Paige L.; Calafat, Antonia M.; Hauser, Russ

2016-01-01

Context: Experimental data in rodents suggest that the adverse reproductive health effects of bisphenol A (BPA) can be modified by intake of soy phytoestrogens. Whether the same is true in humans is not known. Objective: The purpose of this study was to evaluate whether soy consumption modifies the relation between urinary BPA levels and infertility treatment outcomes among women undergoing assisted reproduction. Setting: The study was conducted in a fertility center in a teaching hospital. Design: We evaluated 239 women enrolled between 2007 and 2012 in the Environment and Reproductive Health (EARTH) Study, a prospective cohort study, who underwent 347 in vitro fertilization (IVF) cycles. Participants completed a baseline questionnaire and provided up to 2 urine samples in each treatment cycle before oocyte retrieval. IVF outcomes were abstracted from electronic medical records. We used generalized linear mixed models with interaction terms to evaluate whether the association between urinary BPA concentrations and IVF outcomes was modified by soy intake. Main Outcome Measure: Live birth rates per initiated treatment cycle were measured. Results: Soy food consumption modified the association of urinary BPA concentration with live birth rates (P for interaction = .01). Among women who did not consume soy foods, the adjusted live birth rates per initiated cycle in increasing quartiles of cycle-specific urinary BPA concentrations were 54%, 35%, 31%, and 17% (P for trend = .03). The corresponding live birth rates among women reporting pretreatment consumption of soy foods were 38%, 42%, 47%, and 49% (P for trend = 0.35). A similar pattern was found for implantation (P for interaction = .02) and clinical pregnancy rates (P for interaction = .03) per initiated cycle, where urinary BPA was inversely related to these outcomes among women not consuming soy foods but unrelated to them among soy consumers. Conclusion: Soy food intake may protect against the adverse

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

Direct effects of leptin and adiponectin on peripheral reproductive tissues: a critical review

PubMed Central

Kawwass, Jennifer F.; Summer, Ross; Kallen, Caleb B.

2015-01-01

Obesity is a risk factor for infertility and adverse reproductive outcomes. Adipose tissue is an important endocrine gland that secretes a host of endocrine factors, called adipokines, which modulate diverse physiologic processes including appetite, metabolism, cardiovascular function, immunity and reproduction. Altered adipokine expression in obese individuals has been implicated in the pathogenesis of a host of health disorders including diabetes and cardiovascular disease. It remains unclear whether adipokines play a significant role in the pathogenesis of adverse reproductive outcomes in obese individuals and, if so, whether the adipokines are acting directly or indirectly on the peripheral reproductive tissues. Many groups have demonstrated that receptors for the adipokines leptin and adiponectin are expressed in peripheral reproductive tissues and that these adipokines are likely, therefore, to exert direct effects on these tissues. Many groups have tested for direct effects of leptin and adiponectin on reproductive tissues including the testis, ovary, uterus, placenta and egg/embryo. The hypothesis that decreased fertility potential or adverse reproductive outcomes may result, at least in part, from defects in adipokine signaling within reproductive tissues has also been tested. Here, we present a critical analysis of published studies with respect to two adipokines, leptin and adiponectin, for which significant data have been generated. Our evaluation reveals significant inconsistencies and methodological limitations regarding the direct effects of these adipokines on peripheral reproductive tissues. We also observe a pervasive failure to account for in vivo data that challenge observations made in vitro. Overall, while leptin and adiponectin may directly modulate peripheral reproductive tissues, existing data suggest that these effects are minor and non-essential to human or mouse reproductive function. Current evidence suggests that direct effects of

Computational Approaches for Identifying Adverse Outcome Pathways

EPA Science Inventory

Adverse Outcome Pathways (AOPs) provide a framework for organizing toxicity information to improve predictions of the potential adverse impact of environment stressors on humans or wildlife populations, but these benefits are currently limited by the small number of AOPs currentl...

Preventable health and cost burden of adverse birth outcomes associated with pregestational diabetes in the United States.

PubMed

Peterson, Cora; Grosse, Scott D; Li, Rui; Sharma, Andrea J; Razzaghi, Hilda; Herman, William H; Gilboa, Suzanne M

2015-01-01

Preconception care for women with diabetes can reduce the occurrence of adverse birth outcomes. We aimed to estimate the preconception care (PCC)-preventable health and cost burden of adverse birth outcomes associated with diagnosed and undiagnosed pregestational diabetes mellitus (PGDM) in the United States. Among women of reproductive age (15-44 years), we estimated age- and race/ethnicity-specific prevalence of diagnosed and undiagnosed diabetes. We applied age and race/ethnicity-specific pregnancy rates, estimates of the risk reduction from PCC for 3 adverse birth outcomes (preterm birth, major birth defects, and perinatal mortality), and lifetime medical and lost productivity costs for children with those outcomes. Using a probabilistic model, we estimated the reduction in adverse birth outcomes and costs associated with universal PCC compared with no PCC among women with PGDM. We did not assess maternal outcomes and associated costs. We estimated 2.2% of US births are to women with PGDM. Among women with diagnosed diabetes, universal PCC might avert 8397 (90% prediction interval [PI], 5252-11,449) preterm deliveries, 3725 (90% PI, 3259-4126) birth defects, and 1872 (90% PI, 1239-2415) perinatal deaths annually. Associated discounted lifetime costs averted for the affected cohort of children could be as high as $4.3 billion (90% PI, 3.4-5.1 billion) (2012 US dollars). PCC among women with undiagnosed diabetes could yield an additional $1.2 billion (90% PI, 951 million-1.4 billion) in averted cost. Results suggest a substantial health and cost burden associated with PGDM that could be prevented by universal PCC, which might offset the cost of providing such care. Published by Elsevier Inc.

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,...

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...

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...

Impact of Hurricane Exposure on Reproductive Health Outcomes, Florida, 2004.

PubMed

Grabich, Shannon C; Robinson, Whitney R; Konrad, Charles E; Horney, Jennifer A

2017-08-01

Prenatal hurricane exposure may be an increasingly important contributor to poor reproductive health outcomes. In the current literature, mixed associations have been suggested between hurricane exposure and reproductive health outcomes. This may be due, in part, to residual confounding. We assessed the association between hurricane exposure and reproductive health outcomes by using a difference-in-difference analysis technique to control for confounding in a cohort of Florida pregnancies. We implemented a difference-in-difference analysis to evaluate hurricane weather and reproductive health outcomes including low birth weight, fetal death, and birth rate. The study population for analysis included all Florida pregnancies conceived before or during the 2003 and 2004 hurricane season. Reproductive health data were extracted from vital statistics records from the Florida Department of Health. In 2004, 4 hurricanes (Charley, Frances, Ivan, and Jeanne) made landfall in rapid succession; whereas in 2003, no hurricanes made landfall in Florida. Overall models using the difference-in-difference analysis showed no association between exposure to hurricane weather and reproductive health. The inconsistency of the literature on hurricane exposure and reproductive health may be in part due to biases inherent in pre-post or regression-based county-level comparisons. We found no associations between hurricane exposure and reproductive health. (Disaster Med Public Health Preparedness. 2017;11:407-411).

Advanced maternal age and adverse pregnancy outcomes: A systematic review and meta-analysis

PubMed Central

Derricott, Hayley; Jones, Rebecca L.; Heazell, Alexander E. P.

2017-01-01

Background Advanced maternal age (AMA; ≥35 years) is an increasing trend and is reported to be associated with various pregnancy complications. Objective To determine the risk of stillbirth and other adverse pregnancy outcomes in women of AMA. Search strategy Embase, Medline (Ovid), Cochrane Database of Systematic Reviews, ClinicalTrials.gov, LILACS and conference proceedings were searched from ≥2000. Selection criteria Cohort and case-control studies reporting data on one or more co-primary outcomes (stillbirth or fetal growth restriction (FGR)) and/or secondary outcomes in mothers ≥35 years and <35 years. Data collection and analysis The effect of age on pregnancy outcome was investigated by random effects meta-analysis and meta-regression. Stillbirth rates were correlated to rates of maternal diabetes, obesity, hypertension and use of assisted reproductive therapies (ART). Main results Out of 1940 identified titles; 63 cohort studies and 12 case-control studies were included in the meta-analysis. AMA increased the risk of stillbirth (OR 1.75, 95%CI 1.62 to 1.89) with a population attributable risk of 4.7%. Similar trends were seen for risks of FGR, neonatal death, NICU unit admission restriction and GDM. The relationship between AMA and stillbirth was not related to maternal morbidity or ART. Conclusions Stillbirth risk increases with increasing maternal age. This is not wholly explained by maternal co-morbidities and use of ART. We propose that placental dysfunction may mediate adverse pregnancy outcome in AMA. Further prospective studies are needed to directly test this hypothesis. PMID:29040334

Does age of the sperm donor influence live birth outcome in assisted reproduction?

PubMed

Ghuman, N K; Mair, E; Pearce, K; Choudhary, M

2016-03-01

Does age of the sperm donor have an effect on reproductive outcomes (live birth rate and miscarriage occurrence) of donor insemination or in vitro fertilization treatment using donated sperm? Live birth and miscarriage occurrence in assisted reproduction treatment using donor sperms was not found to be affected by the age of sperm donors up to 45 years old. Literature on the effect of sperm donor age on outcome of medically assisted reproduction is scarce. Most researchers agree that semen parameters deteriorate with increasing paternal age. However, there is no substantial evidence to suggest that this deterioration adversely affects the reproductive outcomes in couples undergoing medically assisted reproduction. This retrospective cohort study analysed 46 078 first donor insemination treatments and fresh in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) cycles using donated sperm from 1991 to 2012. The first fresh donor insemination and IVF/ICSI treatment cycles (46 078 treatment cycles) using donated sperm from the long-term anonymized data registry from 1991 to 2012 of the HFEA, the UK regulator, were analysed by the binary logistic modelling technique for association between sperm donor age and reproductive outcomes (live birth occurrence and miscarriage occurrence). The statistical package SPSS (version 21) was used for analysis and results were considered to be statistically significant if the P-value was <0.05. Of 46 078 women, 84.6% (N = 38 974) underwent donor insemination treatment and the remainder, 15.4% (N = 7104), had IVF/ICSI treatment with donor sperm. The live birth occurrence decreased with increasing female age in both treatment groups; In the donor insemination treatment group, it was 11.1% in 18-34 year old women, 8.3% in 35-37 year old women and 4.7% in 38-50 year old women. The corresponding figures in the IVF/ICSI treatment group were 28.9, 22.0 and 12.9% respectively. In each of these subgroups, no evidence of declining

Availability of reproductive healthcare services at schools and subsequent birth outcomes among adolescent mothers

PubMed Central

Madkour, Aubrey Spriggs; Xie, Yiqiong; Harville, Emily Wheeler

2016-01-01

BACKGROUND Adverse birth outcomes are more common among adolescent versus adult mothers, but little is known about school-based services that may improve birth outcomes in this group. METHODS Data from Waves I and IV of the National Longitudinal Study of Adolescent Health were analyzed. Girls and women who gave birth to singleton live infants after Wave I and before age 20, were still in secondary school while pregnant, and had complete data (N=402) were included. Mothers reported infants’ birthweight and gestational age. School administrators reported whether family planning counseling, diagnostic screening (including sexually transmitted diseases [STDs]), STD treatment, and prenatal/postpartum healthcare were provided on-site at school at Wave I. Multilevel models adjusted for individual and school characteristics were conducted. RESULTS Few schools offered reproductive healthcare services on-site. In multilevel analyses, availability of family planning counseling (Est. β=0.21, 95% confidence interval [CI] 0.04, 0.38) and prenatal/postpartum healthcare (Est. β=0.21, 95% CI 0.02, 0.40) were significantly associated with increased infant birthweight. No services examined were significantly associated with increased gestational age. CONCLUSIONS Some school-based reproductive health services may improve subsequent birth outcomes among adolescent mothers. Future analyses should examine the mechanisms by which services impact birth outcomes. PMID:27246673

[Relationship between pesticide exposure and adverse pregnancy outcomes among reproductive couples in rural areas of China].

PubMed

Qu, Y M; Chen, S; Li, J J; Jin, R R; Pan, H; Jiang, Y

2017-06-10

Objective: To analyze the association between pesticide exposure and adverse pregnancy outcomes in women from the rural areas of China. Methods: Data of "National Free Preconception Health Examination Project (NFPHEP)" from January 2010 to December 2012 was used for analysis. A total of 248 501 families that were planning to deliver a baby in the next 6 months were enrolled. Data on paternal exposure to pesticides before or during pregnancy was collected through questionnaires, with related outcomes on pregnancy recorded by doctors. Results: Among all the 248 501 participants, 1 806 (0.74 % ) women and 2 653 (1.09 % ) men reported to have been exposed to pesticide before pregnancy, with 505 (0.21 % ) reported of having been exposed to pesticide during the period of pregnancy. Maternal exposure to pesticide was found a risk factor related to stillbirth ( OR =3.37, 95 %CI : 2.05-5.55), peculiar smell pregnancy ( OR =3.17, 95 %CI :1.18-8.55) and low birth weight ( OR =7.56, 95 % CI : 5.36-10.66). Paternal exposure to pesticide was also found related to miscarriage ( OR =1.37, 95 % CI : 1.03-1.80), low birth weight ( OR =3.65, 95 % CI :1.51-8.84), or giant infant ( OR =0.64, 95 %CI : 0.44-0.93). Maternal exposure to pesticide during pregnancy appeared a risk factor on miscarriage ( OR =4.65, 95 % CI : 3.47-6.24). Other adverse outcomes on pregnancy would include premature birth and high birth weight. Conclusion: Parental pesticide exposure appeared a risk factor on stillbirth, peculiar smell pregnancy, low birth weight and miscarriage.

Obesity and reproductive function: a review of the evidence.

PubMed

Klenov, Violet E; Jungheim, Emily S

2014-12-01

Over the last decade, the evidence linking obesity to impaired reproductive function has grown. In this article, we review this evidence and discuss the underlying pathophysiology. Obese women are less likely than normal-weight women to achieve pregnancy. Female obesity adversely affects reproductive function through alterations in the hypothalamic-pituitary-ovarian axis, oocyte quality, and endometrial receptivity. It is unclear which mechanism contributes the most to subfecundity, and it is likely a cumulative process. Emerging data highlight the contribution of male obesity to impaired reproductive function and that couple obesity has synergistic adverse effects. Once pregnant, obese women are at higher risk for adverse pregnancy outcomes. Weight loss improves reproductive potential in obese patients. As obese women surpass 35 years of age, age may be more important than body mass index in determining reproductive potential. Obstetrician gynecologists need to be aware of the negative impact of obesity on reproductive function so that they appropriately counsel their patients. Further work is needed to clarify the underlying pathophysiology responsible for adverse effects of obesity on reproduction so that novel treatment approaches may be developed.

Soy Intake Modifies the Relation Between Urinary Bisphenol A Concentrations and Pregnancy Outcomes Among Women Undergoing Assisted Reproduction.

PubMed

Chavarro, Jorge E; Mínguez-Alarcón, Lidia; Chiu, Yu-Han; Gaskins, Audrey J; Souter, Irene; Williams, Paige L; Calafat, Antonia M; Hauser, Russ

2016-03-01

Experimental data in rodents suggest that the adverse reproductive health effects of bisphenol A (BPA) can be modified by intake of soy phytoestrogens. Whether the same is true in humans is not known. The purpose of this study was to evaluate whether soy consumption modifies the relation between urinary BPA levels and infertility treatment outcomes among women undergoing assisted reproduction. The study was conducted in a fertility center in a teaching hospital. We evaluated 239 women enrolled between 2007 and 2012 in the Environment and Reproductive Health (EARTH) Study, a prospective cohort study, who underwent 347 in vitro fertilization (IVF) cycles. Participants completed a baseline questionnaire and provided up to 2 urine samples in each treatment cycle before oocyte retrieval. IVF outcomes were abstracted from electronic medical records. We used generalized linear mixed models with interaction terms to evaluate whether the association between urinary BPA concentrations and IVF outcomes was modified by soy intake. Live birth rates per initiated treatment cycle were measured. Soy food consumption modified the association of urinary BPA concentration with live birth rates (P for interaction = .01). Among women who did not consume soy foods, the adjusted live birth rates per initiated cycle in increasing quartiles of cycle-specific urinary BPA concentrations were 54%, 35%, 31%, and 17% (P for trend = .03). The corresponding live birth rates among women reporting pretreatment consumption of soy foods were 38%, 42%, 47%, and 49% (P for trend = 0.35). A similar pattern was found for implantation (P for interaction = .02) and clinical pregnancy rates (P for interaction = .03) per initiated cycle, where urinary BPA was inversely related to these outcomes among women not consuming soy foods but unrelated to them among soy consumers. Soy food intake may protect against the adverse reproductive effects of BPA. As these findings represent the first report suggesting a

Smoking and Adverse Maternal and Child Health Outcomes in Brazil

PubMed Central

2013-01-01

Introduction: Numerous studies from high-income countries document the causal relationship between cigarette smoking during pregnancy and adverse maternal and child health (MCH) outcomes. Less research has been conducted in low and middle income countries, but a burgeoning literature can be found for Brazil. Methods: We review Brazilian studies of the prevalence of maternal smoking, the relative risk of smoking-attributable adverse MCH outcomes, and present new estimates for these outcomes, using the attributable fraction method. Results: We found that Brazilian studies of the relative risks of smoking-attributable adverse MCH outcomes were broadly consistent with previous reviews. Based on a comparison of maternal smoking over time, smoking during pregnancy has declined by about 50% over the last 20 years in Brazil. For 2008, we estimate that 5,352 cases of spontaneous abortion, 10,929 cases of preterm birth, 20,717 cases of low birth weight, and 29 cases of sudden infant death syndrome are attributable to maternal smoking. Between 1989 and 2008, the percent of smoking-attributable adverse MCH outcomes in Brazil was at least halved. Conclusions: The results show that over a 20-year period, during which Brazil implemented numerous effective tobacco control measures, the country experienced a dramatic decrease in both maternal smoking prevalence and smoking-attributable adverse MCH outcomes. Countries that implement effective tobacco control measures can expect to reduce both maternal smoking and adverse MCH outcomes, thereby improving the public health. PMID:23873977

Interpregnancy interval following miscarriage and adverse pregnancy outcomes: systematic review and meta-analysis.

PubMed

Kangatharan, Chrishny; Labram, Saffi; Bhattacharya, Sohinee

2017-03-01

.88, 1.02) were not affected by IPI. Similar findings were obtained in subgroup analyses when IPI of <6 months was compared with IPI of 6-12 months and >12 months. This is the first systematic review and meta-analysis providing clear evidence that an IPI of less than 6 months following miscarriage is not associated with adverse outcomes in the next pregnancy. This information may be used to revise current guidance. © The Author 2016. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com

Paternal Urinary Concentrations of Parabens and Other Phenols in Relation to Reproductive Outcomes among Couples from a Fertility Clinic

PubMed Central

Dodge, Laura E.; Williams, Paige L.; Williams, Michelle A.; Missmer, Stacey A.; Toth, Thomas L.; Calafat, Antonia M.

2015-01-01

Background Human exposure to phenols, including bisphenol A and parabens, is widespread. Evidence suggests that paternal exposure to environmental chemicals may adversely affect reproductive outcomes. Objectives We evaluated associations of paternal phenol urinary concentrations with fertilization rate, embryo quality, implantation, and live birth. Methods Male–female couples who underwent in vitro fertilization (IVF) and/or intrauterine insemination (IUI) cycles in a prospective study of environmental determinants of fertility and pregnancy outcomes were included. The geometric mean of males’ specific gravity–adjusted urinary phenol concentrations measured before females’ cycle was quantified. Associations between male urinary phenol concentrations and fertilization rate, embryo quality, implantation, and live birth were investigated using generalized linear mixed models to account for multiple cycles per couple. Results Couples (n = 218) underwent 195 IUI and 211 IVF cycles. Paternal phenol concentrations were not associated with fertilization or live birth following IVF. In adjusted models, compared with the lowest quartile of methyl paraben, paternal concentrations in the second quartile were associated with decreased odds of live birth following IUI (adjusted odds ratio = 0.19; 95% CI: 0.04, 0.82). Conclusions To our knowledge, these are some of the first data on the association of paternal urinary phenol concentrations with reproduction and pregnancy outcomes. Although these results do not preclude possible adverse effects of paternal paraben exposures on such outcomes, given the modest sample size, further understanding could result from confirmation using a larger and more diverse population. Citation Dodge LE, Williams PL, Williams MA, Missmer SA, Toth TL, Calafat AM, Hauser R. 2015. Paternal urinary concentrations of parabens and other phenols in relation to reproductive outcomes among couples from a fertility clinic. Environ Health Perspect 123

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

The use of missing birth record data as a marker for adverse reproductive outcomes: a geocoded analysis of birth record data.

PubMed Central

Headley, Adrienne J.; Fulcomer, Mark C.; Bastardi, Matthew M.; Im, Wansoo; Sass, Marcia M.; Chung, Katherine

2006-01-01

Adverse reproductive outcomes (AROs) disproportionately affect black American infants and significantly contribute to the U.S. infant mortality rate. Without accurate understanding of AROs, there remains little hope of ameliorating infant mortality rates or eliminating infant health disparities. However, despite the importance of monitoring infant mortality rates and health disparities, birth record data quality is not assured. Racial disparities in the reporting of birth record data have been documented, and missing birth record data for AROs appears to be disproportionate. Due to the extent of missing birth record data, innovative strategies have been developed to evaluate relationships between maternal socioeconomic status (SES) and community-based ARO rates. Because addresses convey aggregate information about income level, education and occupation, ZIP codes, census tracts and census block-groups have been applied to geocoding efforts. The goals of this study are to: 1) analyze the extent of missing birth record data for New Jersey areas with high rates of an ARO (preterm birth), 2) evaluate associations between the extent of missing birth record data and other AROs, and 3) consider how geocoding strategies could be applied to provide a basis for understanding maternal SES risk factors and ARO resource allocation for at-risk communities. PMID:16895276

Authentic leadership and nurse-assessed adverse patient outcomes.

PubMed

Wong, Carol A; Giallonardo, Lisa M

2013-07-01

Our purpose was to test a model examining relationships among authentic leadership, nurses' trust in their manager, areas of work life and nurse-assessed adverse patient outcomes. Although several work environment factors have been cited as critical to patient outcomes, studies linking nursing leadership styles with patient outcomes are limited suggesting the need for additional research to investigate the mechanisms by which leadership may influence patient outcomes. Secondary analysis of data collected in a cross-sectional survey of 280 (48% response rate) registered nurses working in acute care hospitals in Ontario was conducted using structural equation modelling. The final model fit the data acceptably (χ(2) = 1.30, df = 2, P = 0.52, IFI = 0.99, CFI = 1.00, RMSEA = 0.00). Authentic leadership was significantly associated with decreased adverse patient outcomes through trust in the manager and areas of work life. The findings suggest that nurses who see their managers as demonstrating high levels of authentic leadership report increased trust, greater congruence in the areas of work life and lower frequencies of adverse patient outcomes. Managers who emphasize transparency, balanced processing, self-awareness and high ethical standards in their interactions with nurses may contribute to safer work environments for patients and nurses. © 2013 John Wiley & Sons Ltd.

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...

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...

Adverse Outcome Pathway Network Analyses: Techniques and benchmarking the AOPwiki

EPA Science Inventory

Abstract: As the community of toxicological researchers, risk assessors, and risk managers adopt the adverse outcome pathway (AOP) paradigm for organizing toxicological knowledge, the number and diversity of adverse outcome pathways and AOP networks are continuing to grow. This ...

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...

Quantitative Adverse Outcome Pathways and Their Application to Predictive Toxicology

EPA Science Inventory

A quantitative adverse outcome pathway (qAOP) consists of one or more biologically based, computational models describing key event relationships linking a molecular initiating event (MIE) to an adverse outcome. A qAOP provides quantitative, dose–response, and time-course p...

Adverse psychological outcomes following colposcopy and related procedures: a systematic review.

PubMed

O'Connor, M; Gallagher, P; Waller, J; Martin, C M; O'Leary, J J; Sharp, L

2016-01-01

Although colposcopy is the leading follow-up option for women with abnormal cervical cytology, little is known about its psychological consequences. We performed a systematic review to examine: (1) what, if any, are the adverse psychological outcomes following colposcopy and related procedures; (2) what are the predictors of adverse psychological outcomes post-colposcopy; and (3) what happens to these outcomes over time. Five electronic databases (PubMed, PsychINFO, CINAHL, Web of Science, Scopus) were searched for studies published in English between January 1986 and February 2014. Eligible studies assessed psychological wellbeing at one or more time-points post-colposcopy. Two reviewers independently screened titles and abstracts. Full texts of potentially eligible papers were reviewed. Data were abstracted from, and a quality appraisal performed of, eligible papers. Twenty-three papers reporting 16 studies were eligible. Colposcopy and related procedures can lead to adverse psychological outcomes, particularly anxiety. Ten studies investigated predictors of adverse psychological outcomes; management type and treatment had no impact on this. Seven studies investigated temporal trends in psychological outcomes post-colposcopy; findings were mixed, especially in relation to anxiety and distress. Studies were methodologically heterogeneous. Follow-up investigations and procedures for abnormal cervical cytology can cause adverse psychological outcomes among women. However, little is known about the predictors of these outcomes or how long they persist. There is a need for a more standardised approach to the examination of the psychological impact of colposcopy, especially longer-term outcomes. Follow-up investigations for abnormal cervical cytology can cause adverse psychological outcome among women. © 2015 Royal College of Obstetricians and Gynaecologists.

Adverse Outcome Pathway (AOP) Network Development for ...

EPA Pesticide Factsheets

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 research. According to the Organization for Economic Co-operation and Development guidelines, AOPs are pathways with one MIE anchored to an adverse outcome (AO) by key events (KEs) and key event relationships (KERs). However, this approach does not always capture the cumulative impacts of multiple MIEs on the AO. For example, hepatic lipid flux due to chemical-induced toxicity initiates from multiple ligand-activated receptors and signaling pathways that cascade across biology to converge upon a common fatty liver (FL, also known as steatosis) outcome. To capture this complexity, a top-down strategy was used to develop a FL AOP network (AOPnet). Literature was queried based on the terms steatosis, fatty liver, cirrhosis, and hepatocellular carcinoma. Search results were analyzed for physiological and pathophysiological organ level, cellular and molecular processes, as well as pathway intermediates, to identify potential KEs and MIEs that are key for hepatic lipid metabolism, maintenance, and dysregulation. The analysis identified four apical KE nodes (hepatic fatty acid uptake, de novo fatty acid and lipid synthesis, fatty acid oxidation, and lipid efflux) juxtaposed to the FL AO. The apic

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...

Effect of Paternal Age on Reproductive Outcomes of In Vitro Fertilization

PubMed Central

Zheng, Haiyan; Liu, Haiying; Liu, Jianqiao

2015-01-01

Although the adverse effects of maternal aging on reproductive outcomes have been investigated widely, there is no consensus on the impact of paternal age. Therefore, we investigated the effect of paternal age on reproductive outcomes in a retrospective analysis of 9,991 in vitro fertilization (IVF) cycles performed at the Reproductive Medicine Center of the Third Affiliated Hospital of Guangzhou Medical University (China) between January 2007 and October 2013. Samples were grouped according to maternal age [<30 (3,327 cycles), 30–34 (4,587 cycles), and 35–38 (2,077 cycles)] and then subgrouped according to paternal age (<30, 30–32, 33–35, 36–38, 39–41, and ≥42). The groups did not differ in terms of fertilization rate, numbers of viable and high-quality embryos and miscarriage rate when controlling maternal age (P >0.05). Chi-squared analysis revealed that there were no differences in implantation and pregnancy rates among the different paternal age groups when maternal age was <30 and 35–38 years (P >0.05). However, implantation and pregnancy rates decreased with paternal age in the 31–34 y maternal age group (P <0.05). Our study indicates that paternal age has no impact on fertilization rate, embryo quality at the cleavage stage and miscarriage rate. For the 30–34 y maternal age group, the implantation rate decreased with increased paternal age, with the pregnancy rate in this group being significantly higher in the paternal <30 y and 30–32 y age groups, compared with those in the 36–38 y and 39–41 y groups. PMID:26352861

Adverse pregnancy outcomes following syphilis treatment in pregnancy in the UK.

PubMed

Wallace, Harriet E; Isitt, Catherine E; Broomhall, Harriet M; Perry, Alison E; Wilson, Janet D

2016-10-01

Syphilis infection in pregnancy is known to cause a number of severe adverse pregnancy outcomes, including second-trimester miscarriage, stillbirth, very pre-term delivery and neonatal death, in addition to congenital syphilis. A retrospective review of women with positive syphilis serology and a pregnancy outcome between 2005 and 2012 in Leeds, UK, was performed. In all, 57 cases of positive syphilis serology in pregnancy were identified: 24 with untreated syphilis treated in the current pregnancy (Group 1); seven with reported but unconfirmed prior treatment who were retreated (Group 2); and 26 adequately treated prior to pregnancy (Group 3). The rate of severe adverse pregnancy outcomes in Group 1 at 21% was significantly higher than the 0% outcome of Group 3 (p = 0.02). The severe adverse pregnancy outcomes were two second-trimester miscarriages, two pre-term births at 25 and 28 weeks and one stillbirth at 32 weeks. There were no cases of term congenital syphilis or term neonatal death, but we observed high rates of other adverse pregnancy outcomes despite treatment during pregnancy. Rapid referral for treatment is needed before 18 weeks in order to minimise adverse pregnancy outcomes. © The Author(s) 2016.

Systematic review of pediatric health outcomes associated with childhood adversity.

PubMed

Oh, Debora Lee; Jerman, Petra; Silvério Marques, Sara; Koita, Kadiatou; Purewal Boparai, Sukhdip Kaur; Burke Harris, Nadine; Bucci, Monica

2018-02-23

Early detection of and intervention in childhood adversity has powerful potential to improve the health and well-being of children. A systematic review was conducted to better understand the pediatric health outcomes associated with childhood adversity. PubMed, PsycArticles, and CINAHL were searched for relevant articles. Longitudinal studies examining various adverse childhood experiences and biological health outcomes occurring prior to age 20 were selected. Mental and behavioral health outcomes were excluded, as were physical health outcomes that were a direct result of adversity (i.e. abusive head trauma). Data were extracted and risk of bias was assessed by 2 independent reviewers. After identifying 15940 records, 35 studies were included in this review. Selected studies indicated that exposure to childhood adversity was associated with delays in cognitive development, asthma, infection, somatic complaints, and sleep disruption. Studies on household dysfunction reported an effect on weight during early childhood, and studies on maltreatment reported an effect on weight during adolescence. Maternal mental health issues were associated with elevated cortisol levels, and maltreatment was associated with blunted cortisol levels in childhood. Furthermore, exposure to childhood adversity was associated with alterations of immune and inflammatory response and stress-related accelerated telomere erosion. Childhood adversity affects brain development and multiple body systems, and the physiologic manifestations can be detectable in childhood. A history of childhood adversity should be considered in the differential diagnosis of developmental delay, asthma, recurrent infections requiring hospitalization, somatic complaints, and sleep disruption. The variability in children's response to adversity suggests complex underlying mechanisms and poses a challenge in the development of uniform diagnostic guidelines. More large longitudinal studies are needed to better

Feasibility, Process, and Outcomes of Cardiovascular Clinical Trial Data Sharing: A Reproduction Analysis of the SMART-AF Trial.

PubMed

Gay, Hawkins C; Baldridge, Abigail S; Huffman, Mark D

2017-12-01

Data sharing is as an expanding initiative for enhancing trust in the clinical research enterprise. To evaluate the feasibility, process, and outcomes of a reproduction analysis of the THERMOCOOL SMARTTOUCH Catheter for the Treatment of Symptomatic Paroxysmal Atrial Fibrillation (SMART-AF) trial using shared clinical trial data. A reproduction analysis of the SMART-AF trial was performed using the data sets, data dictionary, case report file, and statistical analysis plan from the original trial accessed through the Yale Open Data Access Project using the SAS Clinical Trials Data Transparency platform. SMART-AF was a multicenter, single-arm trial evaluating the effectiveness and safety of an irrigated, contact force-sensing catheter for ablation of drug refractory, symptomatic paroxysmal atrial fibrillation in 172 participants recruited from 21 sites between June 2011 and December 2011. Analysis of the data was conducted between December 2016 and April 2017. Effectiveness outcomes included freedom from atrial arrhythmias after ablation and proportion of participants without any arrhythmia recurrence over the 12 months of follow-up after a 3-month blanking period. Safety outcomes included major adverse device- or procedure-related events. The SMART AF trial participants' mean age was 58.7 (10.8) years, and 72% were men. The time from initial proposal submission to final analysis was 11 months. Freedom from atrial arrhythmias at 12 months postprocedure was similar compared with the primary study report (74.0%; 95% CI, 66.0-82.0 vs 76.4%; 95% CI, 68.7-84.1). The reproduction analysis success rate was higher than the primary study report (65.8%; 95% CI 56.5-74.2 vs 75.6%; 95% CI, 67.2-82.5). Adverse events were minimal and similar between the 2 analyses, but contact force range or regression models could not be reproduced. The feasibility of a reproduction analysis of the SMART-AF trial was demonstrated through an academic data-sharing platform. Data sharing can be

.Network analytics for adverse outcome pathways

EPA Science Inventory

Adverse Outcome Pathways (AOPs) organize toxicological knowledge from the molecular level up to the population level, providing evidence-based causal linkages at each step. The AOPWiki serves as a repository of AOPs. With the international adoption of the AOP framework, the AOPw...

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...

Applying Aggregate Exposure Pathway and Adverse Outcome ...

EPA Pesticide Factsheets

Hazard assessment for nanomaterials often involves applying in vitro dose-response data to estimate potential health risks that arise from exposure to products that contain nanomaterials. However, much uncertainty is inherent in relating bioactivities observed in an in vitro system to the perturbations of biological mechanisms that lead to apical adverse health outcomes in living organisms. The Adverse Outcome Pathway (AOP) framework addresses this uncertainty by acting as a scaffold onto which in vitro toxicity testing and other data can be arranged to aid in the interpretation of these results in terms of biologically-relevant responses, as an AOP connects an upstream molecular initiating event (MIE) to a downstream adverse outcome. In addition to hazard assessment, risk estimation also requires reconciling in vitro concentrations sufficient to produce bioactivity with in vivo concentrations that can trigger a MIE at the relevant biological target. Such target site exposures (TSEs) can be estimated by integrating pharmacokinetic considerations with environmental and exposure factors. Environmental and exposure data have been historically scattered in various resources, such as monitoring data for air pollutants or exposure models for specific chemicals. The Aggregate Exposure Pathway (AEP) framework is introduced to organize existing knowledge concerning biologically, chemically, and physically plausible, as well as empirically supported, links between the i

Reproductive adverse outcome pathways for chemical inhibitors of steroid synthesis in fish

EPA Science Inventory

A key physiological process controlling reproductive success of oviparous vertebrates (fish, amphibian, reptiles, birds) involves production of the egg yolk protein precursor vitellogenin (VTG). VTG production is an estrogen receptor (ER)-mediated process that, in females, is con...

Impact of a labor and delivery safety bundle on a modified adverse outcomes index.

PubMed

Tolcher, Mary Catherine; Torbenson, Vanessa E; Weaver, Amy L; McGree, Michaela E; El-Nashar, Sherif A; Nesbitt, Katharine M; Gostout, Bobbie S; Famuyide, Abimbola O

2016-03-01

The Obstetrics Adverse Outcomes Index was designed to measure the quality of perinatal care and includes 10 adverse events that may occur at or around the time of delivery. We hypothesized that adverse outcomes in the labor and delivery suite, including hypoxic ischemic encephalopathy, could be decreased with a combination of interventions, even among high-risk pregnancies. The objective of the study was to evaluate the impact of a labor and delivery care bundle on adverse obstetrics outcomes as measured by a modified Obstetrics Adverse Outcomes Index, Weighted Adverse Outcomes Index, and Severity Index. This is a retrospective cohort study including all women who delivered at our academic, tertiary care institution over a 3 year period of time, before and after the implementation of an intervention to decrease adverse outcomes. Outcome measures consisted of previously reported indices that were modified including the addition of hypoxic ischemic encephalopathy. The adverse outcomes index is a percentage of deliveries with 1 or more adverse events, the weighted adverse outcomes index is the sum of the points assigned to cases with adverse outcomes divided by the number of deliveries, and the severity index is the sum of the adverse outcome scores divided by the number of deliveries with an identified adverse outcome. A segmented regression analysis was utilized to evaluate the differences in the level and trend of each index before and after our intervention using calendar month as the unit of analysis. During the study period, 5826 deliveries met inclusion criteria. Comparing the pre- and postintervention periods, high-risk pregnancy was more common in the postintervention period (73.5% vs 79.4%, P < .001). Overall, there was a decrease in both the Modified Weighted Adverse Outcomes Index (P = .0497) and the Modified Severity Index (P = 0.01) comparing the pre- and postintervention periods; there was no difference in the Modified Adverse Outcomes Index (P = .43

Adverse pregnancy outcomes after in vitro fertilization: effect of number of embryos transferred and plurality at conception.

PubMed

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

2015-07-01

To evaluate risks for adverse pregnancy outcomes by number of embryos transferred (ET) and fetal heartbeats (FHB) in assisted reproductive technology-conceived singleton live births. Longitudinal cohort using cycles reported to the Society for Assisted Reproductive Technology Clinic Outcomes Reporting System between 2004 and 2008 among women who were treated and gave birth in Massachusetts. Not applicable. Assisted reproductive technology data on 6,073 births between 2004 and 2008 were linked to vital records and hospital data. Likelihood of ET ≥3 vs. 1-2, FHB >1 vs. 1, and risks of preterm birth (PTB, <37 weeks' gestation), low birth weight (LBW, <2,500 g), and small-for-gestational-age birth weight (SGA, <10th percentile) with FHB >1 were modeled with binary logistic regression using a backward-stepping algorithm, and presented as adjusted odds ratios (95% confidence intervals). None. ET ≥3, FHB >1, PTB, LBW, and SGA. Higher ET was significantly more likely with older maternal age, intracytoplasmic sperm injection, assisted hatching, cleavage-stage embryos, and thawed embryos. The likelihood of FHB >1 with ≥3 ET vs. 1-2 ET was 2.04 (1.68-2.48). Risks of PTB and LBW with FHB >1 were 1.63 (1.27-2.09) and 1.81 (1.36-2.39), respectively; the risk of SGA was not significant. Nulliparity was associated with higher risks of PTB (1.34 [1.12-1.59]), LBW (1.48 [1.20-1.83]), and SGA (2.17 [1.69-2.78]). Number of embryos transferred was strongly associated with FHBs, with twice the risk of FHB >1 with ≥3 ET vs. 1-2 ET. Increasing FHBs were associated with significantly greater risks for PTB and LBW outcomes. Copyright © 2015 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Effect of maternal age on maternal and neonatal outcomes after assisted reproductive technology.

PubMed

Wennberg, Anna Lena; Opdahl, Signe; Bergh, Christina; Aaris Henningsen, Anna-Karina; Gissler, Mika; Romundstad, Liv Bente; Pinborg, Anja; Tiitinen, Aila; Skjærven, Rolv; Wennerholm, Ulla-Britt

2016-10-01

To compare the effect of maternal age on assisted reproductive technology (ART) and spontaneous conception (SC) pregnancies regarding maternal and neonatal complications. Nordic retrospective population-based cohort study. Data from national ART registries were cross-linked with national medical birth registries. Not applicable. A total of 300,085 singleton deliveries: 39,919 after ART and 260,166 after SC. None. Hypertensive disorders in pregnancy (HDP), placenta previa, cesarean delivery, preterm birth (PTB; <37 weeks), low birth weight (LBW; <2,500 g), small for gestational age (SGA), and perinatal mortality (≥28 weeks). Adjusted odds ratios (AORs) were calculated. Associations between maternal age and outcomes were analyzed. The risk of placenta previa (AOR 4.11-6.05), cesarean delivery (AOR 1.18-1.50), PTB (AOR 1.23-2.19), and LBW (AOR 1.44-2.35) was significantly higher in ART than in SC pregnancies for most maternal ages. In both ART and SC pregnancies, the risk of HDP, placenta previa, cesarean delivery, PTB, LBW, and SGA changed significantly with age. The AORs for adverse neonatal outcomes at advanced maternal age (>35 years) showed a greater increase in SC than in ART. The change in risk with age did not differ between ART and SC for maternal outcomes at advanced maternal age. Having singleton conceptions after ART results in higher maternal and neonatal outcome risks overall, but the impact of age seems to be more pronounced in couples conceiving spontaneously. Copyright © 2016 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Derivation and evaluation of putative adverse outcome ...

EPA Pesticide Factsheets

Cyclooxygenase (COX) inhibition is of concern in fish because COX inhibitors (e.g., ibuprofen) are ubiquitous in aquatic systems/fish tissues, and can disrupt synthesis of prostaglandins that modulate a variety of essential biological functions including reproduction. High content (transcriptomic) empirical data and publicly available high throughput toxicity data (actor.epa.gov) were utilized to develop putative adverse outcome pathways (AOPs) for molecular initiating event (MIE) of COX inhibition. Effects of a waterborne, 96h exposure to indomethacin (IN; 100 µg/L), ibuprofen (IB; 200 µg/L) and celecoxib (CX; 20 µg/L) on liver metabolome and ovarian gene expression (using oligonucleotide microarrays) in sexually mature fathead minnows (n=8) were examined. Metabolomic profiles of IN, IB and CX were not significantly different from control or one another. Exposure to IB and CX resulted in differential expression of comparable numbers of genes (IB = 433, CX= 545). In contrast, 2558 genes were differentially expressed in IN-treated fish. Functional analyses (canonical pathway and gene set enrichment) indicated extensive effects of IN on prostaglandin synthesis pathway, oocyte meiosis and several other processes consistent with physiological roles of prostaglandins. Transcriptomic data was congruent with apical endpoint data - IN reduced plasma prostaglandin F2 alpha concentrations, and ovarian COX activity, whereas IB and CX did not. Putative AOPs pathways for

Influence of Study Design on Developmental and Reproductive Toxicology Study Outcomes.

PubMed

Foster, Paul M D

2017-01-01

Regulatory studies of developmental and reproductive toxicity (DART) studies have remained largely unchanged for decades, with exposures occurring at various phases of the reproductive cycle and toxicity evaluations at different ages/times depending on the study purpose. The National Toxicology Program has conducted studies examining the power to detect adverse effects where there is a prenatal exposure, but evaluations occur postnatally. In these studies, examination is required of only 1 male and female pup from each litter beyond weaning. This provides poor resolving power to detect rare events (e.g., reproductive tract malformations). If an adverse effect is detected, there is little confidence in the shape of the dose-response curve (and the Benchmark Dose or No Observed Adverse Effect Level [NOAEL]). We have developed a new protocol to evaluate DART, the modified one generation study, with exposure commencing with pregnant animals and retention of 4 males and females from each litter beyond weaning to improve statistical power. These animals can be allocated to specific cohorts that examine subchronic toxicity, teratology, littering, and neurobehavioral toxicity in the same study. This approach also results in a reduction in animal numbers used, compared with individual stand-alone studies, and offers increased numbers of end points evaluated compared with recent Organization for Economic Cooperation and Development proposals.

Assisted reproductive technology with donor sperm: national trends and perinatal outcomes.

PubMed

Gerkowicz, Sabrina A; Crawford, Sara B; Hipp, Heather S; Boulet, Sheree L; Kissin, Dmitry M; Kawwass, Jennifer F

2018-04-01

Information regarding the use of donor sperm in assisted reproductive technology, as well as subsequent treatment and perinatal outcomes, remains limited. Outcome data would aid patient counseling and clinical decision making. The objectives of the study were to report national trends in donor sperm utilization and live birth rates of donor sperm-assisted reproductive technology cycles in the United States and to compare assisted reproductive technology treatment and perinatal outcomes between cycles using donor and nondonor sperm. We hypothesize these outcomes to be comparable between donor and nondonor sperm cycles. This was a retrospective cohort study using data from all US fertility centers reporting to the Centers for Disease Control and Prevention's National Assisted Reproductive Technology Surveillance System, accounting for ∼98% of assisted reproductive technology cycles (definition excludes intrauterine insemination). The number and percentage of assisted reproductive technology cycles using donor sperm and rates of pregnancy, live birth, preterm birth (<37 weeks), and low birthweight (<2500 g) were the primary outcomes measured. Treatments assessed include use of donor vs nondonor sperm. The trends analysis included all banking and fresh assisted reproductive technology cycles using donor and autologous oocytes performed between 1996 and 2014 (n = 1,710,034). The outcomes analysis was restricted to include only fresh autologous cycles performed between 2010 and 2014 (n = 437,569) to focus on cycles with a potential outcome and cycles reflective of current practice, thereby improving the clinical relevance. Cycles canceled prior to retrieval were excluded. Statistical analysis included linear regression to explore polynomial trends and log-binomial regression to estimate relative risk for outcomes among cycles using donor and nondonor sperm. Of all banking and fresh donor and autologous oocyte assisted reproductive technology cycles performed between

The adverse effects of tobacco smoking on reproduction and health: a review from the literature.

PubMed

Tuormaa, T E

1995-01-01

This paper compromises a short literary review of the adverse consequences of tobacco smoking on reproduction, as well as on infant and adult health. Furthermore, attention is drawn to the bad effects of smoking on the nutritional status.

Reproductive and Developmental Toxicity of Formaldehyde: A Systematic Review

PubMed Central

Duong, Anh; Steinmaus, Craig; McHale, Cliona M.; Vaughan, Charles P.; Zhang, Luoping

2011-01-01

Formaldehyde, the recently classified carcinogen and ubiquitous environmental contaminant, has long been suspected of causing adverse reproductive and developmental effects, but previous reviews were inconclusive, due in part, to limitations in the design of many of the human population studies. In the current review, we systematically evaluated evidence of an association between formaldehyde exposure and adverse reproductive and developmental effects, in human populations and in vivo animal studies, in the peer-reviewed literature. The mostly retrospective human studies provided evidence of an association of maternal exposure with adverse reproductive and developmental effects. Further assessment of this association by meta-analysis revealed an increased risk of spontaneous abortion (1.76, 95% CI 1.20–2.59, p=0.002) and of all adverse pregnancy outcomes combined (1.54, 95% CI 1.27–1.88, p<0.001), in formaldehyde-exposed women, although differential recall, selection bias, or confounding cannot be ruled out. Evaluation of the animal studies including all routes of exposure, doses and dosing regimens studied, suggested positive associations between formaldehyde exposure and reproductive toxicity, mostly in males. Potential mechanisms underlying formaldehyde-induced reproductive and developmental toxicities, including chromosome and DNA damage (genotoxicity), oxidative stress, altered level and/or function of enzymes, hormones and proteins, apoptosis, toxicogenomic and epigenomic effects (such as DNA methylation), were identified. To clarify these associations, well-designed molecular epidemiologic studies, that include quantitative exposure assessment and diminish confounding factors, should examine both reproductive and developmental outcomes associated with exposure in males and females. Together with mechanistic and animal studies, this will allow us to better understand the systemic effect of formaldehyde exposure. PMID:21787879

[Severe Adverse Pregnancy Outcomes in Placenta Previa and Prior Cesarean Delivery].

PubMed

Zhou, Mi; Chen, Meng; Zhang, Li; He, Guo-Lin; He, Lei; Wei, Qiang; Li, Tao; Liu, Xing-Hui

2017-09-01

To investigate the severe adverse pregnancy outcomes in pregnancies with placenta previa and prior cesarean delivery and its risk factors. This retrospective casecontrol study reviewed all pregnancies with placenta previa and prior cesarean delivery delivered by repeat cesarean section in our institution between January 2005 and June 2015,and investigated the incidence of severe adverse pregnancy outcome. A composite of severe adverse pregnancy outcomes (including transfusion of 10 units or more red blood cells,maternal ICU admission,unanticipated injuries,repeat operation,hysterectomy,and maternal death) and other maternal and neonatal outcomes were described. Univariate and multivariable logistic regression analysis were used to quantify the effects of risk factors on severe adverse pregnancy outcomes. There were 478 women with placenta previa and prior cesarean delivery in our hospital over the last decade. The average age of them was 32.5±4.8 years old,most women were beyond 30 years old,the average gravidity and parity were 4 and 1,131 cases (27.4%) had severe adverse pregnancy outcomes. Transfusion of 10 units or more red blood cells happened in 75 cases (15.7%,75/478); 44 cases (9.2%,44/478) necessitated maternal ICU admission; unanticipated bladder injury occurred in 11 cases,but non ureter or bowel injury happened; All 4 repeat operations were due to delayed hemorrhage after conservative management during cesarean delivery,and an emergent hysterectomy was performed for all of the 4 cases. Hysterectomy (107 cases,22.4%) was the most common severe adverse pregnancy outcome. Among all 311 morbidly adherent placenta cases finally confirmed by pathological or surgical findings or both,only 172 (55.3%) were suspected before delivery. Multivariable logistic regression analysis showed that the risk of severe adverse pregnancy outcomes was significantly increased by pernicious placenta previa (i.e. anterior placenta overlying the prior cesarean scar),suspicion of

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

Assisted reproductive technologies: a hierarchy of risks for conception, pregnancy outcomes and treatment decisions.

PubMed

Davies, M J; Rumbold, A R; Moore, V M

2017-08-01

The use of assisted reproductive technologies (ART) for the treatment of infertility has grown exponentially over the last 20 years, and now accounts for 4% of all births in Australia, and over 1 m births annually around the globe. There is consistent reporting of increased risk of adverse perinatal outcomes and birth defects following infertility treatment. However, change in practice has been stymied by critical knowledge gaps with regards to (a) the relative contribution of patient and treatment factors to adverse outcomes, (b) the independent contribution of specific contemporary treatments and treatment combinations to outcomes, (c) the impact of innovations in laboratory and clinical practice on treatment success and observed risk and (d) changes over time in patient characteristics. Here we summarize key findings from the South Australian Birth Cohort, which is a whole-of-population cohort of over 300,000 births from 1986 to 2002. Relative to spontaneous conceptions, singletons from assisted conception were more likely to be stillborn [odds ratio (OR)=1.82; 95% confidence interval (CI) 1.34-2.48], while survivors as a group were comprehensively disadvantaged at birth, including lower birth weight (OR=2109 g; 95% CI 2129-289), very low birth weight (OR=2.74; 95% CI 2.19-3.43), very preterm birth (OR=2.30; 95% CI 1.82-2.90) and neonatal death (OR=2.04; 95% CI 1.27-3.26). Major birth defects, including cardiac, urogenital and musculoskeletal defects are doubled after fresh ICSI cycles, which is a particular concern as ICSI now accounts for 70% of all treatment cycles globally. Future study is needed to provide contemporary, precise evidence to inform patient and clinic decision making, and generate knowledge for future innovation in ART laboratory methods and clinical practice, thereby optimizing treatment and health outcomes while reducing adverse events.

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...

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). ...

Maternal veterinary occupation and adverse birth outcomes in Washington State, 1992-2014: a population-based retrospective cohort study.

PubMed

Meisner, Julianne; Vora, Manali V; Fuller, Mackenzie S; Phipps, Amanda I; Rabinowitz, Peter M

2018-05-01

Women in veterinary occupations are routinely exposed to potential reproductive hazards, yet research into their birth outcomes is limited. We conducted a population-based retrospective cohort study of the association between maternal veterinary occupation and adverse birth outcomes. Using Washington State birth certificate, fetal death certificate and hospital discharge data from 1992 to 2014, we compared birth outcomes of mothers in veterinary professions (n=2662) with those in mothers in dental professions (n=10 653) and other employed mothers (n=8082). Relative risks (RRs) and 95% CIs were estimated using log binomial regression. Outcomes studied were premature birth (<37 weeks), small for gestational age (SGA), malformations and fetal death (death at ≥20 weeks gestation). Subgroup analyses evaluated risk of these outcomes among veterinarians and veterinary support staff separately. While no statistically significant associations were found, we noted a trend for SGA births in all veterinary mothers compared with dental mothers (RR=1.16, 95% CI 0.99 to 1.36) and in veterinarians compared with other employed mothers (RR=1.37, 95% CI 0.96 to 1.96). Positive but non-significant association was found for malformations among children of veterinary support staff. These results support the need for further study of the association between veterinary occupation and adverse birth outcomes. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

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

Adverse pregnancy outcomes in women with nausea and vomiting of pregnancy.

PubMed

Temming, Lorene; Franco, Albert; Istwan, Niki; Rhea, Debbie; Desch, Cheryl; Stanziano, Gary; Joy, Saju

2014-01-01

To examine the influence of nausea and vomiting of pregnancy (NVP) on pregnancy outcomes. Outcomes were compared for primigravidas with a current singleton gestation enrolled at <20 weeks' gestation in a maternity risk screening and education program (n = 81 486). Patient-reported maternal characteristics and pregnancy outcomes were compared for women with and without NVP and within the NVP group for those with and without poor weight gain. 6.4% of women reported NVP as a pregnancy complication. Women reporting NVP were more likely to be younger, obese, single and smoke. They had higher rates of preterm delivery, pregnancy-induced hypertension and low birth weight <2500 g. Almost one-quarter of women with NVP had lower than recommended weight gain. Poor weight gain was associated with a higher incidence of adverse outcomes. Obesity, tobacco use and poor pregnancy weight gain independently increased the odds of an adverse outcome. NVP and subsequent poor weight gain may be associated with adverse pregnancy outcomes.

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...

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...

Glyphosate and adverse pregnancy outcomes, a systematic review of observational studies.

PubMed

de Araujo, Jessica S A; Delgado, Isabella F; Paumgartten, Francisco J R

2016-06-06

A study in frog and chicken embryos, and reports of a high incidence of birth defects in regions of intensive GM-soy planting have raised concerns on the teratogenic potential of glyphosate-based herbicides. These public concerns prompted us to conduct a systematic review of the epidemiological studies testing hypotheses of associations between glyphosate exposure and adverse pregnancy outcomes including birth defects. A systematic and comprehensive literature search was performed in MEDLINE, TOXLINE, Bireme-BVS and SCOPUS databases using different combinations of exposure and outcome terms. A case-control study on the association between pesticides and congenital malformations in areas of extensive GM soy crops in South America, and reports on the occurrence of birth defects in these regions were reviewed as well. The search found ten studies testing associations between glyphosate and birth defects, abortions, pre-term deliveries, small for gestational date births, childhood diseases or altered sex ratios. Two additional studies examined changes of time-to-pregnancy in glyphosate-exposed populations. Except for an excess of Attention Deficit Hyperactivity Disorder - ADHD (OR = 3.6, 1.3-9.6) among children born to glyphosate appliers, no significant associations between this herbicide and adverse pregnancy outcomes were described. Evidence that in South American regions of intensive GM-soy planting incidence of birth defects is high remains elusive. Current epidemiological evidence, albeit limited to a few studies using non-quantitative and indirect estimates and dichotomous analysis of exposures, does not lend support to public concerns that glyphosate-based pesticides might pose developmental risks to the unborn child. Nonetheless, owing to methodological limitations of existing analytical observational studies, and particularly to a lack of a direct measurement (urine and/or blood levels), or an indirect estimation of exposure that has proven valid, these

Co-occurring obesity and smoking among U.S. women of reproductive age: Associations with educational attainment and health biomarkers and outcomes.

PubMed

Vurbic, Drina; Harder, Valerie S; Redner, Ryan R; Lopez, Alexa A; Phillips, Julie K; Higgins, Stephen T

2015-11-01

Obesity and smoking are independently associated with socioeconomic disadvantage and adverse health effects in women of reproductive age and their children, but little is known about co-occurring obesity and smoking. The purpose of this study was to investigate relationships between co-occurring obesity and smoking, socioeconomic status, and health biomarkers and outcomes in a nationally representative sample. Data from non-pregnant women of reproductive age were obtained from the U.S. National Health and Nutrition Examination Surveys reported between 2007 and 2010. Linear and logistic regressions were used to examine associations between obesity and smoking alone and in combination with educational attainment and a range of health biomarkers and outcomes. Prevalence of co-occurring obesity and smoking was 8.1% (~4.1 million U.S. women of reproductive age) and increased as an inverse function of educational attainment, with the least educated women being 11.6 times more likely to be obese smokers than the most educated. Compared to women with neither condition, obese smokers had significantly poorer cardiovascular and glycemic biomarker profiles, and higher rates of menstrual irregularity, hysterectomy, oophorectomy, physical limitations, and depression. Obese smokers also had significantly worse high-density lipoprotein (HDL) cholesterol levels, physical mobility, and depression scores than those with obesity or smoking alone. Co-occurring obesity and smoking is highly associated with low educational attainment, a marker of socioeconomic disadvantage, and a broad range of adverse health biomarkers and outcomes. Interventions specifically targeting co-occurring obesity and smoking are likely necessary in efforts to reduce health disparities among disadvantaged women and their children. Copyright © 2015 Elsevier Inc. All rights reserved.

Paternal education and adverse birth outcomes in Canada.

PubMed

Shapiro, Gabriel D; Bushnik, Tracey; Sheppard, Amanda J; Kramer, Michael S; Kaufman, Jay S; Yang, Seungmi

2017-01-01

Research on predictors of adverse birth outcomes has focused on maternal characteristics. Much less is known about the role of paternal factors. Paternal education is an important socioeconomic marker that may predict birth outcomes over and above maternal socioeconomic indicators. Using data from the 2006 Canadian Birth-Census Cohort, we estimated the associations between paternal education and preterm birth, small-for-gestational-age (SGA) birth, stillbirth and infant mortality in Canada, controlling for maternal characteristics. Binomial regression was used to estimate risk ratios and risk differences for adverse birth outcomes associated with paternal education, after controlling for maternal education, age, marital status, parity, ethnicity and nativity. A total of 131 285 singleton births were included in the present study. Comparing the lowest to the highest paternal education category, adjusted risk ratios (95% CIs) were 1.22 (1.10 to 1.35) for preterm birth, 1.13 (1.03 to 1.23) for SGA birth, 1.92 (1.28 to 2.86) for stillbirth and 1.67 (1.01 to 2.75) for infant mortality. Consistent patterns of associations were observed for absolute risk differences. Our study suggests that low paternal education increases the risk of adverse birth outcomes, and especially of fetal and infant mortality, independently from maternal characteristics. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Accelerating Adverse Outcome Pathway (AOP) development ...

EPA Pesticide Factsheets

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. However, the conventional process for assembly of these AOPs is time and resource intensive, and has been a rate limiting step for AOP use and development. Therefore computational approaches to accelerate the process need to be developed. We previously developed a method for generating computationally predicted AOPs (cpAOPs) by association mining and integration of data from publicly available databases. In this work, a cpAOP network of ~21,000 associations was established between 105 phenotypes from TG-GATEs rat liver data from different time points (including microarray, pathological effects and clinical chemistry data), 994 REACTOME pathways, 688 High-throughput assays from ToxCast and 194 chemicals. A second network of 128,536 associations was generated by connecting 255 biological target genes from ToxCast to 4,980 diseases from CTD using either HT screening activity from ToxCast for 286 chemicals or CTD gene expression changes in response to 2,330 chemicals. Both networks were separately evaluated through manual extraction of disease-specific cpAOPs and comparison with expert curation of the relevant literature. By employing data integration strategies that involve the weighting of n

Trends in adverse maternal outcomes during childbirth: a population-based study of severe maternal morbidity.

PubMed

Roberts, Christine L; Ford, Jane B; Algert, Charles S; Bell, Jane C; Simpson, Judy M; Morris, Jonathan M

2009-02-25

Maternal mortality is too rare in high income countries to be used as a marker of the quality of maternity care. Consequently severe maternal morbidity has been suggested as a better indicator. Using the maternal morbidity outcome indicator (MMOI) developed and validated for use in routinely collected population health data, we aimed to determine trends in severe adverse maternal outcomes during the birth admission and in particular to examine the contribution of postpartum haemorrhage (PPH). We applied the MMOI to the linked birth-hospital discharge records for all women who gave birth in New South Wales, Australia from 1999 to 2004 and determined rates of severe adverse maternal outcomes. We used frequency distributions and contingency table analyses to examine the association between adverse outcomes and maternal, pregnancy and birth characteristics, among all women and among only those with PPH. Using logistic regression, we modelled the effects of these characteristics on adverse maternal outcomes. The impact of adverse outcomes on duration of hospital admission was also examined. Of 500,603 women with linked birth and hospital records, 6242 (12.5 per 1,000) suffered an adverse outcome, including 22 who died. The rate of adverse maternal outcomes increased from 11.5 in 1999 to 13.8 per 1000 deliveries in 2004, an annual increase of 3.8% (95%CI 2.3-5.3%). This increase occurred almost entirely among women with a PPH. Changes in pregnancy and birth factors during the study period did not account for increases in adverse outcomes either overall, or among the subgroup of women with PPH. Among women with severe adverse outcomes there was a 12% decrease in hospital days over the study period, whereas women with no severe adverse outcome occupied 23% fewer hospital days in 2004 than in 1999. Severe adverse maternal outcomes associated with childbirth have increased in Australia and the increase was entirely among women who experienced a PPH. Reducing or stabilising

An Integrative data mining approach to identifying Adverse Outcome Pathway (AOP) Signatures

EPA Science Inventory

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 populatio...

Area-level risk factors for adverse birth outcomes: trends in urban and rural settings.

PubMed

Kent, Shia T; McClure, Leslie A; Zaitchik, Ben F; Gohlke, Julia M

2013-06-10

Significant and persistent racial and income disparities in birth outcomes exist in the US. The analyses in this manuscript examine whether adverse birth outcome time trends and associations between area-level variables and adverse birth outcomes differ by urban-rural status. Alabama births records were merged with ZIP code-level census measures of race, poverty, and rurality. B-splines were used to determine long-term preterm birth (PTB) and low birth weight (LBW) trends by rurality. Logistic regression models were used to examine differences in the relationships between ZIP code-level percent poverty or percent African-American with either PTB or LBW. Interactions with rurality were examined. Population dense areas had higher adverse birth outcome rates compared to other regions. For LBW, the disparity between population dense and other regions increased during the 1991-2005 time period, and the magnitude of the disparity was maintained through 2010. Overall PTB and LBW rates have decreased since 2006, except within isolated rural regions. The addition of individual-level socioeconomic or race risk factors greatly attenuated these geographical disparities, but isolated rural regions maintained increased odds of adverse birth outcomes. ZIP code-level percent poverty and percent African American both had significant relationships with adverse birth outcomes. Poverty associations remained significant in the most population-dense regions when models were adjusted for individual-level risk factors. Population dense urban areas have heightened rates of adverse birth outcomes. High-poverty African American areas have higher odds of adverse birth outcomes in urban versus rural regions. These results suggest there are urban-specific social or environmental factors increasing risk for adverse birth outcomes in underserved communities. On the other hand, trends in PTBs and LBWs suggest interventions that have decreased adverse birth outcomes elsewhere may not be reaching

Area-level risk factors for adverse birth outcomes: trends in urban and rural settings

PubMed Central

2013-01-01

Background Significant and persistent racial and income disparities in birth outcomes exist in the US. The analyses in this manuscript examine whether adverse birth outcome time trends and associations between area-level variables and adverse birth outcomes differ by urban–rural status. Methods Alabama births records were merged with ZIP code-level census measures of race, poverty, and rurality. B-splines were used to determine long-term preterm birth (PTB) and low birth weight (LBW) trends by rurality. Logistic regression models were used to examine differences in the relationships between ZIP code-level percent poverty or percent African-American with either PTB or LBW. Interactions with rurality were examined. Results Population dense areas had higher adverse birth outcome rates compared to other regions. For LBW, the disparity between population dense and other regions increased during the 1991–2005 time period, and the magnitude of the disparity was maintained through 2010. Overall PTB and LBW rates have decreased since 2006, except within isolated rural regions. The addition of individual-level socioeconomic or race risk factors greatly attenuated these geographical disparities, but isolated rural regions maintained increased odds of adverse birth outcomes. ZIP code-level percent poverty and percent African American both had significant relationships with adverse birth outcomes. Poverty associations remained significant in the most population-dense regions when models were adjusted for individual-level risk factors. Conclusions Population dense urban areas have heightened rates of adverse birth outcomes. High-poverty African American areas have higher odds of adverse birth outcomes in urban versus rural regions. These results suggest there are urban-specific social or environmental factors increasing risk for adverse birth outcomes in underserved communities. On the other hand, trends in PTBs and LBWs suggest interventions that have decreased adverse

Differences in reproductive toxicology between alopecia drugs: an analysis on adverse events among female and male cases

PubMed Central

Li, Qingfeng

2016-01-01

Alopecia is a dermatological condition with limited therapeutic options. Only two drugs, finasteride and minoxidil, are approved by FDA for alopecia treatment. However, little is known about the differences in adverse effects between these two drugs. We examined the clinical reports submitted to the FDA Adverse Event Reporting System (FAERS) from 2004 to 2014. For both female and males, finasteride was found to be more associated with reproductive toxicity as compared to minoxidil. Among male alopecia cases, finasteride was significantly more concurrent with several forms of sexual dysfunction. Among female alopecia cases, finasteride was significantly more concurrent with harm to fetus and disorder of uterus. In addition, drug-gene network analysis indicated that finasteride could profoundly disturb pathways related to sex hormone signaling and oocyte maturation. These findings could provide clues for subsequent toxicological research. Taken together, this analysis suggested that finasteride could be more liable to various reproductive adverse effects. Some of these adverse effects have yet to be warned in FDA-approved drug label. This information can help improve the treatment regimen of alopecia and post-marketing regulation of drug products. PMID:27738338

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

The effect of paternal age on assisted reproduction outcome.

PubMed

Dain, Lena; Auslander, Ron; Dirnfeld, Martha

2011-01-01

To summarize the current knowledge about the association between paternal age and assisted reproductive technology (ART) outcomes. In contrast to the extensive investigation of the relationship between maternal age and the success of ART, there are few studies examining the effect of paternal age on ART outcomes. Systematic review of the literature. By means of a PubMed literature search using the phrases "paternal age", "male age", and "assisted reproductive technology", we identified articles that investigated the role of male age in in vitro reproduction techniques. The 10 studies included in this review did not show a clear correlation between advanced paternal age and rates of fertilization, implantation, pregnancy, miscarriage, and live birth. Paternal age was not found to affect embryo quality at the cleavage stage (days 2-3). However, a significant decrease in blastocyst embryo formation was associated with increased paternal age, probably reflecting male genomic activation within the embryo. Except for volume, characteristics of semen such as motility, concentration, and morphology did not decrease with age. There is insufficient evidence to demonstrate an unfavorable effect of paternal age on ART outcomes. Further study with well-defined entry criteria and uniform reporting of outcomes is needed to investigate the subject. Copyright © 2011. Published by Elsevier Inc.

Adverse outcome pathways (AOPs) to enhance EDC ...

EPA Pesticide Factsheets

Screening and testing for endocrine active chemicals was mandated under 1996 amendments to the Safe Drinking Water Act and Food Quality Protection Act. Efficiencies can be gained in the endocrine disruptor screening program by using available biological and toxicological knowledge to facilitate greater use of high throughput screening data and other data sources to inform endocrine disruptor assessments. Likewise, existing knowledge, when properly organized, can help aid interpretation of test results. The adverse outcome pathway (AOP) framework, which organizes information concerning measureable changes that link initial biological interactions with a chemical to adverse effects that are meaningful to risk assessment and management, can aid this process. This presentation outlines the ways in which the AOP framework has already been employed to support EDSP and how it may further enhance endocrine disruptor assessments in the future. Screening and testing for endocrine active chemicals was mandated under 1996 amendments to the Safe Drinking Water Act and Food Quality Protection Act. Efficiencies can be gained in the endocrine disruptor screening program by using available biological and toxicological knowledge to facilitate greater use of high throughput screening data and other data sources to inform endocrine disruptor assessments. Likewise, existing knowledge, when properly organized, can help aid interpretation of test results. The adverse outcome pathway

Circulating Angiogenic Factors and the Risk of Adverse Outcomes among Haitian Women with Preeclampsia.

PubMed

March, Melissa I; Geahchan, Carl; Wenger, Julia; Raghuraman, Nandini; Berg, Anders; Haddow, Hamish; Mckeon, Bri Ann; Narcisse, Rulx; David, Jean Louis; Scott, Jennifer; Thadhani, Ravi; Karumanchi, S Ananth; Rana, Sarosh

2015-01-01

Angiogenic factors are strongly associated with adverse maternal and fetal outcomes among women with preterm preeclampsia (PE) in developed countries. We evaluated the role of angiogenic factors and their relationship to adverse outcomes among Haitian women with PE. We measured plasma antiangiogenic soluble fms-like tyrosine kinase 1 (sFlt1) and proangiogenic placental growth factor (PlGF) levels in women with PE (n=35) compared to controls with no hypertensive disorders (NHD) (n=43) among subjects with singleton pregnancies that delivered at Hospital Albert Schweitzer (HAS) in Haiti. We divided the preeclamptic women into two groups, early onset (≤ 34 weeks) and late onset (>34 weeks) and examined relationships between sFlt1/PlGF ratios on admission and adverse outcomes (abruption, respiratory complications, stroke, renal insufficiency, eclampsia, maternal death, birth weight <2500 grams, or fetal/neonatal death) in women with PE subgroups as compared to NHD groups separated by week of admission. Data are presented as median (25th-75th centile), n (%), and proportions. Among patients with PE, most (24/35) were admitted at term. Adverse outcome rates in PE were much higher among the early onset group compared to the late onset group (100.0% vs. 54.2%, P=0.007). Plasma angiogenic factors were dramatically altered in both subtypes of PE. Angiogenic factors also correlated with adverse outcomes in both subtypes of PE. The median sFlt1/PlGF ratios for subjects with early onset PE with any adverse outcome vs. NHD <=34 weeks with no adverse outcome were 703.1 (146.6, 1614.9) and 9.6 (3.5, 58.6); P<0.001). Among late onset group the median sFlt1/PlGF ratio for women with any adverse outcome was 130.7 (56.1, 242.6) versus 22.4 (10.2, 58.7; P=0.005) in NHD >34 weeks with no adverse outcome. PE-related adverse outcomes are common in women in Haiti and are associated with profound angiogenic imbalance regardless of gestational age at presentation.

HIGH-THROUGHPUT CELLULAR ASSAYS FOR MODELING TOXICITY IN THE FISH REPRODUCTIVE SYSTEM

EPA Science Inventory

The most important benefit of this project is the experimental evaluation of all essential steps in the development and testing of adverse outcome pathways (AOP) for a diverse set of reproductive and non-reproductive toxicants. In contrast to human testing and the toxicity pat...

Application of Adverse Outcome Pathways (AOPs) in Human ...

EPA Pesticide Factsheets

The adverse outcome pathway (AOP) framework was developed to help organize and disseminate existing knowledge concerning the means through which specific perturbations of biological pathways can lead to adverse outcomes considered relevant to risk-based regulatory decision-making. Because many fundamental molecular and cellular pathways are conserved across taxa, data from assays that screen chemicals for their ability to interact with specific biomolecular targets can often be credibly applied to a broad range of species, even if the apical outcomes of those perturbations may differ. Information concerning the different trajectories of adversity that molecular initiating events may take in different taxa, life stages, and sexes of organisms can be captured in the form of an AOP network. As an example, AOPs documenting divergent consequences of thyroid peroxidase (TPO) and deiodinase (DIO) inhibition in mammals, amphibians, and fish have been developed. These AOPs provide the foundation for using data from common in vitro assays for TPO or DIO activity to inform both human health and ecological risk assessments. They also provide the foundation for an integrated approach to testing and assessment, where available information and biological understanding can be integrated in order to formulate plausible and testable hypotheses which can be used to target in vivo testing on the endpoints of greatest concern. Application of this AOP knowledge in several different r

Application of adverse outcome pathways (AOPs) in human ...

EPA Pesticide Factsheets

The adverse outcome pathway (AOP) framework was developed to help organize and disseminate existing knowledge concerning the means through which specific perturbations of biological pathways can lead to adverse outcomes considered relevant to risk-based regulatory decision-making. Because many fundamental molecular and cellular pathways are conserved across taxa, data from assays that screen chemicals for their ability to interact with specific biomolecular targets can often be credibly applied to a broad range of species, even if the apical outcomes of those perturbations may differ. Information concerning the different trajectories of adversity that molecular initiating events may take in different taxa, life stages, and sexes of organisms can be captured in the form of an AOP network. As an example, AOPs documenting divergent consequences of thyroid peroxidase (TPO) and deiodinase (DIO) inhibition in mammals, amphibians, and fish have been developed. These AOPs provide the foundation for using data from common in vitro assays for TPO or DIO activity to inform both human health and ecological risk assessments. They also provide the foundation for an integrated approach to testing and assessment, where available information and biological understanding can be integrated in order to formulate plausible and testable hypotheses which can be used to target in vivo testing on the endpoints of greatest concern. Application of this AOP knowledge in several different r

Early Elevations of the Complement Activation Fragment C3a and Adverse Pregnancy Outcomes

PubMed Central

Lynch, Anne M.; Gibbs, Ronald S.; Murphy, James R.; Giclas, Patricia C.; Salmon, Jane E.; Holers, V. Michael

2016-01-01

OBJECTIVE To estimate whether elevations of complement C3a early in pregnancy are predictive of the subsequent development of adverse pregnancy outcomes. METHODS A plasma sample was obtained from each enrolled pregnant woman before 20 weeks of gestation. The cohort (n=1,002) was evaluated for the development of adverse pregnancy outcomes defined as hypertensive diseases of pregnancy (gestational hypertension or preeclampsia), preterm birth (before 37 weeks of gestation), premature rupture of the membranes, pregnancy loss (during the embryonic and fetal period), intrauterine growth restriction, and the composite outcome of any adverse outcome. RESULTS One or more adverse pregnancy outcomes occurred in 211 (21%) of the cohort. The mean levels (ng/mL) of C3a in early pregnancy were significantly (P=<.001) higher among women with one or more adverse outcomes (858±435) compared with women with an uncomplicated pregnancy (741±407). Adjusted for parity and prepregnancy body mass index, women with levels of C3a in the upper quartile in early pregnancy were three times more likely to have an adverse outcome later in pregnancy compared with women in the lowest quartile (95% confidence interval, 1.8–4.8; P<.001). The link between early elevated C3a levels and adverse pregnancy outcomes was driven primarily by individual significant (P<.05) associations of C3a with hypertensive diseases of pregnancy, preterm birth, and premature rupture of the membranes. CONCLUSION Elevated C3a as early as the first trimester of pregnancy is an independent predictive factor for adverse pregnancy outcomes, suggesting that complement-related inflammatory events in pregnancy contribute to the subsequent development of poor outcomes at later stages of pregnancy. PMID:21173647

A review and rationale for studying the cardiovascular effects of drinking water arsenic in women of reproductive age

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kwok, Richard K., E-mail: rkwok@rti.org

2007-08-01

Drinking water arsenic has been shown to be associated with a host of adverse health outcomes at exposure levels > 300 {mu}g of As/L. However, the results are not consistent at exposures below this level. We have reviewed selected articles that examine the effects of drinking water arsenic on cardiovascular outcomes and present a rationale for studying these effects on women of reproductive age, and also over the course of pregnancy when they would potentially be more susceptible to adverse cardiovascular and reproductive outcomes. It is only recently that reproductive effects have been linked to drinking water arsenic. However, theremore » is a paucity of information about the cardiovascular effects of drinking water arsenic on women of reproductive age. Under the cardiovascular challenge of pregnancy, we hypothesize that women with a slightly elevated exposure to drinking water arsenic may exhibit adverse cardiovascular outcomes at higher rates than in the general population. Studying sensitive clinical and sub-clinical indicators of disease in susceptible sub-populations may yield important information about the potentially enormous burden of disease related to low-level drinking water arsenic exposure.« less

Obesity and Outcome of Assisted Reproduction in Patients With Polycystic Ovary Syndrome

PubMed Central

Tziomalos, Konstantinos; Dinas, Konstantinos

2018-01-01

Assisted reproduction, including in vitro fertilization and intracytoplasmic sperm injection, is increasingly being used for the management of infertility in patients with polycystic ovary syndrome (PCOS). However, there are limited data regarding the association between obesity and the outcome of assisted reproduction in this specific population as well as on the effects of weight loss. The aim of the present review is to summarize the existing evidence on the association between obesity and the outcome of assisted reproduction in patients with PCOS. Accumulating data suggest that obesity is associated with lower pregnancy and live birth rates in patients with PCOS who are undergoing assisted reproduction therapy. However, it remains unclear whether weight loss improves the outcome of this therapy. Notably, recent guidelines state that the health benefits of postponing pregnancy to achieve weight loss must be balanced against the risk of declining fertility with advancing age. Therefore, if weight loss is not achieved within a reasonable time period, assisted reproduction therapy should be offered in adequately selected patients with PCOS, regardless of the presence of obesity. PMID:29670581

The influence of the built environment on adverse birth outcomes.

PubMed

Woods, N; Gilliland, J; Seabrook, J A

2017-01-01

Adverse birth outcomes are associated with neonatal morbidity and mortality, and higher risk for coronary heart disease, non-insulin-dependent diabetes and hypertension in adulthood. Although there has been considerable research investigating the association between maternal and environmental factors on adverse birth outcomes, one risk factor, not fully understood, is the influence of the built environment. A search of MEDLINE, Scopus, and Cochrane was conducted to find articles assessing the influence of the built environment on preterm birth (PTB), low birth weight (LBW), and small-for-gestational-age (SGA). In total, 41 studies met our inclusion criteria, and were organized into nine categories: Roadways, Greenness, Power Plants, Gas Stations/Wells, Waste Management, Power Lines, Neighborhood Conditions, Food Environment, and Industry. The most common built environmental variable was roads/traffic, encompassing 17/41 (41%) of the articles reviewed, of which 12/17 (71%) found a significant small to moderate association between high traffic exposure and adverse birth outcomes.

Workgroup report: Implementing a national occupational reproductive research agenda--decade one and beyond.

PubMed

Lawson, Christina C; Grajewski, Barbara; Daston, George P; Frazier, Linda M; Lynch, Dennis; McDiarmid, Melissa; Murono, Eisuke; Perreault, Sally D; Robbins, Wendie A; Ryan, Megan A K; Shelby, Michael; Whelan, Elizabeth A

2006-03-01

The initial goal of occupational reproductive health research is to effectively study the many toxicants, physical agents, and biomechanical and psychosocial stressors that may constitute reproductive hazards in the workplace. Although the main objective of occupational reproductive researchers and clinicians is to prevent recognized adverse reproductive outcomes, research has expanded to include a broader spectrum of chronic health outcomes potentially affected by reproductive toxicants. To aid in achieving these goals, the National Institute for Occupational Safety and Health, along with its university, federal, industry, and labor colleagues, formed the National Occupational Research Agenda (NORA) in 1996. NORA resulted in 21 research teams, including the Reproductive Health Research Team (RHRT). In this report, we describe progress made in the last decade by the RHRT and by others in this field, including prioritizing reproductive toxicants for further study; facilitating collaboration among epidemiologists, biologists, and toxicologists; promoting quality exposure assessment in field studies and surveillance; and encouraging the design and conduct of priority occupational reproductive studies. We also describe new tools for screening reproductive toxicants and for analyzing mode of action. We recommend considering outcomes such as menopause and latent adverse effects for further study, as well as including exposures such as shift work and nanomaterials. We describe a broad domain of scholarship activities where a cohesive system of organized and aligned work activities integrates 10 years of team efforts and provides guidance for future research.

Workgroup Report: Implementing a National Occupational Reproductive Research Agenda—Decade One and Beyond

PubMed Central

Lawson, Christina C.; Grajewski, Barbara; Daston, George P.; Frazier, Linda M.; Lynch, Dennis; McDiarmid, Melissa; Murono, Eisuke; Perreault, Sally D.; Robbins, Wendie A.; Ryan, Megan A.K.; Shelby, Michael; Whelan, Elizabeth A.

2006-01-01

The initial goal of occupational reproductive health research is to effectively study the many toxicants, physical agents, and biomechanical and psychosocial stressors that may constitute reproductive hazards in the workplace. Although the main objective of occupational reproductive researchers and clinicians is to prevent recognized adverse reproductive outcomes, research has expanded to include a broader spectrum of chronic health outcomes potentially affected by reproductive toxicants. To aid in achieving these goals, the National Institute for Occupational Safety and Health, along with its university, federal, industry, and labor colleagues, formed the National Occupational Research Agenda (NORA) in 1996. NORA resulted in 21 research teams, including the Reproductive Health Research Team (RHRT). In this report, we describe progress made in the last decade by the RHRT and by others in this field, including prioritizing reproductive toxicants for further study; facilitating collaboration among epidemiologists, biologists, and toxicologists; promoting quality exposure assessment in field studies and surveillance; and encouraging the design and conduct of priority occupational reproductive studies. We also describe new tools for screening reproductive toxicants and for analyzing mode of action. We recommend considering outcomes such as menopause and latent adverse effects for further study, as well as including exposures such as shift work and nanomaterials. We describe a broad domain of scholarship activities where a cohesive system of organized and aligned work activities integrates 10 years of team efforts and provides guidance for future research. PMID:16507468

The impact of endometriosis on the outcome of Assisted Reproductive Technology.

PubMed

González-Comadran, Mireia; Schwarze, Juan Enrique; Zegers-Hochschild, Fernando; Souza, Maria do Carmo B; Carreras, Ramon; Checa, Miguel Ángel

2017-01-24

Endometriosis has been described to impair fertility through various mechanisms. However, studies evaluating the reproductive outcomes of women undergoing assisted reproductive technologies show controversial results. The aim of this study is to assess whether the reproductive outcome is impaired among women with endometriosis-associated infertility undergoing IVF. A retrospective cohort study was performed, including women undergoing IVF reported by the Red Latinoamericana de Reproduccion Asistida (Redlara) registry, between January 2010 and December 2012. The study group included women with endometriosis-associated infertility, and the control group women with tubal factor, endocrine disorders or unexplained infertility. Women above 40 years, severe male factor and premature ovarian failure were excluded. The reproductive outcomes of between both groups were compared. The primary outcome was live birth. Secondary outcomes included clinical pregnancy, miscarriage, number of oocytes retrieved and number of fertilized oocytes. Outcomes were assessed after the first fresh IVF cycle, and were adjusted for age and number of embryos transferred. A total of 22.416 women were included (3.583 with endometriosis and 18.833 in the control group). Mean age of patients in the endometriosis group and control group was 34.86 (3.47) and 34.61 (3.91) respectively, p = 0.000. The mean number of oocytes retrieved were 8.89 (6.23) and 9.86 (7.02) respectively, p = 0.000. No significant differences were observed between groups in terms of live birth (odds ratio (OR) 1.032, p = 0.556), clinical pregnancy (OR 1.044, p = 0.428) and miscarriage rates (OR 1.049, p = 0.623). Women with endometriosis had significantly lower number of oocytes retrieved (incidence risk ratio (IRR) 0.917, 95% CI 0.895-0.940), however, the number of fertilized oocytes did not differ among the two groups when adjusting for the number of oocytes retrieved (IRR 1.003, p = 0.794). An age

Perinatal outcomes among singletons after assisted reproductive technology with single-embryo or double-embryo transfer versus no assisted reproductive technology.

PubMed

Martin, Angela S; Chang, Jeani; Zhang, Yujia; Kawwass, Jennifer F; Boulet, Sheree L; McKane, Patricia; Bernson, Dana; Kissin, Dmitry M; Jamieson, Denise J

2017-04-01

To examine outcomes of singleton pregnancies conceived without assisted reproductive technology (non-ART) compared with singletons conceived with ART by elective single-embryo transfer (eSET), nonelective single-embryo transfer (non-eSET), and double-embryo transfer with the establishment of 1 (DET -1) or ≥2 (DET ≥2) early fetal heartbeats. Retrospective cohort using linked ART surveillance data and vital records from Florida, Massachusetts, Michigan, and Connecticut. Not applicable. Singleton live-born infants. None. Preterm birth (PTB <37 weeks), very preterm birth (VPTB <32 weeks), small for gestational age birth weight (<10th percentile), low birth weight (LBW <2,500 g), very low birth weight (VLBW <1,500 g), 5-minute Apgar score <7, and neonatal intensive care unit (NICU) admission. After controlling for maternal characteristics and employing a weighted propensity score approach, we found that singletons conceived after eSET were less likely to have a 5-minute Apgar <7 (adjusted odds ratio [aOR] 0.33; 95% CI, 0.15-0.69) compared with non-ART singletons. There were no differences among outcomes between non-ART and non-eSET infants. We found that PTB, VPTB, LBW, and VLBW were more likely among DET -1 and DET ≥2 compared with non-ART infants, with the odds being higher for DET ≥2 (PTB aOR 1.58; 95% CI, 1.09-2.29; VPTB aOR 2.46; 95% CI, 1.20-5.04; LBW aOR 2.17; 95% CI, 1.24-3.79; VLBW aOR 3.67; 95% CI, 1.38-9.77). Compared with non-ART singletons, singletons born after eSET and non-eSET did not have increased risks whereas DET -1 and DET ≥2 singletons were more likely to have adverse perinatal outcomes. Copyright © 2017 American Society for Reproductive Medicine. All rights reserved.

The Relationship of Assisted Reproductive Technology on Perinatal Outcomes in Triplet Gestations.

PubMed

Shah, Jaimin S; Roman, Tania; Viteri, Oscar A; Haidar, Ziad A; Ontiveros, Alejandra; Sibai, Baha M

2018-06-08

 To assess whether assisted reproductive technology (ART) is associated with increased risk of adverse perinatal outcomes in triplet gestations compared with spontaneous conception.  Secondary analysis of a multicenter randomized trial for the prevention of preterm birth in multiple gestations. Triplets delivered at ≥ 24 weeks were studied. The primary outcome was the rate of composite neonatal morbidity (CNM) that included one or more of the following: bronchopulmonary dysplasia, respiratory distress syndrome, necrotizing enterocolitis, culture proven sepsis, pneumonia, retinopathy of prematurity, intraventricular hemorrhage, periventricular leukomalacia, or perinatal death.  There were 381 triplets (127 women) of which 89 patients conceived via ART and 38 patients spontaneously. Women with ART were more likely to be older, Caucasian, married, nulliparous, have higher level of education, and develop pre-eclampsia. Spontaneously conceived triplets were more likely to delivery at an earlier gestation (31.2 ± 3.5 vs 32.8 ± 2.7 weeks) ( p  = 0.009) with a lower birth weight ( p  < 0.001). After adjusting for confounders, no differences were noted in culture proven sepsis, perinatal death, CNM, respiratory distress syndrome, or Apgar score < 7 at 5 minutes. All remaining perinatal outcomes were similar.  Triplets conceived by ART had similar perinatal outcomes compared with spontaneously conceived triplets. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

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....

Social capital and adverse treatment outcomes of tuberculosis: a case-control study.

PubMed

Deshmukh, P R; Mundra, A; Dawale, A

2017-08-01

'Social capital' refers to social norms, relationships, networks and values that affect the functioning and development of society. Social capital influences health positively, but its role in the treatment outcomes of tuberculosis (TB) is not known. To study the role of social capital in determining adverse TB treatment outcomes. Of 516 patients registered under the Revised National Tuberculosis Control Programme in 2014 in Wardha Tuberculosis Unit, Wardha, India, we included 88 patients with adverse treatment outcomes as cases and 187 controls from among those without adverse outcomes. Multiple logistic regression was used to compare standardised Z-scores. A greater proportion of controls than cases belonged to higher quartiles of social capital and its domains than cases, and the mean standardised Z-score was also consistently higher among controls than cases. Respectively 47% and 15% of cases and controls were in the poorest quartile of social capital, whereas respectively 10% and 33% of cases and controls were in the richest quartile. Each unit increase in Z-score of overall social capital reduced the odds of adverse treatment outcomes by 63.1%. Appropriate interventions for building social capital for TB patients and linking them with the programme would improve programme performance.

The future of preconception care in the United States: multigenerational impact on reproductive outcomes.

PubMed

St Fleur, Michelle; Damus, Karla; Jack, Brian

2016-07-19

The future of preconception care will require an innovative multigenerational approach to health promotion for women and men to achieve optimal reproductive health outcomes. In this paper we provide a summary of historical trends in perinatal interventions in the United States that have effectively reduced adverse perinatal outcomes but have not improved disparities among ethnic/racial groups. We describe evidence pointing to an enhanced preconception care paradigm that spans the time periods before, during, and between pregnancies and across generations for all women and men. We describe how the weathering, Barker, and life course theories point to stress and non-chromosomal inheritance as key mediators in racial disparities. Finally, we provide evidence that indicates that humans exposed to toxic stress can be impacted in future generations and that these phenomena are potentially related to epigenetic inheritance, resulting in perinatal disparities. We believe that this expanded view will define preconception care as a critical area for research in the years ahead.

Adverse Outcome Pathways – Organizing Toxicological ...

EPA Pesticide Factsheets

The number of chemicals for which environmental regulatory decisions are required far exceeds the current capacity for toxicity testing. High throughput screening (HTS) commonly used for drug discovery has the potential to increase this capacity. The adverse outcome pathway (AOP) concept has emerged as a natural framework for connecting high throughput toxicity testing (HTT) results to potential impacts on humans and wildlife populations. An AOP consists of two main components that describe the biological mechanisms driving toxicity. Key events represent biological processes essential for causing the adverse outcome that are also measurable experimentally. Key event relationships capture the biological processes connecting the key events. Evidence documented for each KER based on measurements of the KEs can provide the confidence needed for extrapolating HTT from early key events to overt toxicity represented by later key events based on the AOP. The IPCS mode of action (MOA) framework incorporates information required for making a chemical-specific toxicity determination. Given the close relationship between the AOP and MOA frameworks, it is possible to assemble an MOA by incorporating HTT results, chemical properties including absorption, distribution, metabolism, and excretion (ADME), and an AOP describing the biological basis of toxicity thereby streamlining the process. While current applications focus on the assessment of risk for environmental chemicals,

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...

A thick placenta: a predictor of adverse pregnancy outcomes.

PubMed

Miwa, Ichiro; Sase, Masakatsu; Torii, Mayumi; Sanai, Hiromi; Nakamura, Yasuhiko; Ueda, Kazuyuki

2014-01-01

The aim of this study is to evaluate the efficacy of an ultrasonographic measurement of placental thickness and the correlation of a thick placenta with adverse perinatal outcome. Placental thickness was measured in single gravidas, 16 to 40 weeks of gestation, between 2005 and 2009. Placentas were considered to be thick if their measured thickness were above the 95th percentile for gestational age. The incidence of thick placentas was 4.3% (138/3,183). Perinatal morbidity and neonatal conditions were worse in cases with thick placenta rather than without thick placenta. Ultrasonographic measurement of placental thickness is a simple method to estimate placental size. Thick placenta may be a useful predictor of adverse pregnancy outcomes.

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 ...

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...

Integrating toxicogenomics data into cancer adverse outcome pathways

EPA Science Inventory

Integrating toxicogenomics data into adverse outcome pathways for cancer.J. Christopher CortonNHEERL/ORD, EPA, Research Triangle Park, NCAs the toxicology field continues to move towards a new paradigm in toxicity testing and safety assessment, there is the expectation that model...

Informatics approaches in the Biological Characterization of Adverse Outcome Pathways

EPA Science Inventory

Adverse Outcome Pathways (AOPs) are a conceptual framework to characterize toxicity pathways by a series of mechanistic steps from a molecular initiating event to population outcomes. This framework helps to direct risk assessment research, for example by aiding in computational ...

Continued Statin Prescriptions After Adverse Reactions and Patient Outcomes: A Cohort Study.

PubMed

Zhang, Huabing; Plutzky, Jorge; Shubina, Maria; Turchin, Alexander

2017-08-15

Many patients discontinue statin treatment, often after having a possible adverse reaction. The risks and benefits of continued statin therapy after an adverse reaction are not known. To examine the relationship between continuation of statin therapy (any prescription within 12 months after an adverse reaction) and clinical outcomes. Retrospective cohort study. Primary care practices affiliated with 2 academic medical centers. Patients with a presumed adverse reaction to a statin between 2000 and 2011. Information on adverse reactions to statins was obtained from structured electronic medical record data or natural-language processing of narrative provider notes. The primary composite outcome was time to a cardiovascular event (myocardial infarction or stroke) or death. Most (81%) of the adverse reactions to statins were identified from the text of electronic provider notes. Among 28 266 study patients, 19 989 (70.7%) continued receiving statin prescriptions after the adverse reaction. Four years after the presumed adverse event, the cumulative incidence of the composite primary outcome was 12.2% for patients with continued statin prescriptions, compared with 13.9% for those without them (difference, 1.7% [95% CI, 0.8% to 2.7%]; P < 0.001). In a secondary analysis of 7604 patients for whom a different statin was prescribed after the adverse reaction, 2014 (26.5%) had a documented adverse reaction to the second statin, but 1696 (84.2%) of those patients continued receiving statin prescriptions. The risk for recurrent adverse reactions to statins could not be established for the entire sample. It was also not possible to determine whether patients actually took the statins. Continued statin prescriptions after an adverse reaction were associated with a lower incidence of death and cardiovascular events. Chinese National Key Program of Clinical Science, National Natural Science Foundation of China, and Young Scientific Research Fund of Peking Union Medical College

The Associations Between Air Pollution and Adverse Pregnancy Outcomes in China.

PubMed

Tan, Yafei; Yang, Rong; Zhao, Jinzhu; Cao, Zhongqiang; Chen, Yawen; Zhang, Bin

2017-01-01

Research on the potential impact of air pollution on the human's health has increased rapidly in recent years. Several studies have suggested that exposure to air pollutants during period of pregnancy which is a crucial time point of mother-fetus development may have long-term and serious impact on adverse pregnancy outcomes. There is lack of review to evaluate the existed epidemiologic evidence on the associations between air pollutants and adverse pregnancy outcomes in China, so we conducted a review to explore the current epidemiological evidence on the effects of air pollutants to pregnancy outcomes and possible mechanisms during the pregnancy process. We used keywords to systematically search all the English and Chinese literatures on studies that were conducted in China. Exposure to air pollutants during pregnancy had shown there were harmful effects for different birth outcomes: preterm birth, low birth weight, stillbirth, birth defects, infertility, and macrosomia fetus. Results on the effects of air pollutants on adverse pregnancy outcomes are small and inconsistent because they vary in their design and methodology. The existed available evidence is compatible with either a small negative effect of air pollutants on pregnancy outcomes or with no effect; therefore, further studies are needed to confirm and quantify the possible associations and potential biologic mechanisms between air pollutants and pregnancy outcomes.

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.

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

An antenatal prediction model for adverse birth outcomes in an urban population: The contribution of medical and non-medical risks.

PubMed

Posthumus, A G; Birnie, E; van Veen, M J; Steegers, E A P; Bonsel, G J

2016-07-01

in the Netherlands the perinatal mortality rate is high compared to other European countries. Around eighty percent of perinatal mortality cases is preceded by being small for gestational age (SGA), preterm birth and/or having a low Apgar-score at 5 minutes after birth. Current risk detection in pregnancy focusses primarily on medical risks. However, non-medical risk factors may be relevant too. Both non-medical and medical risk factors are incorporated in the Rotterdam Reproductive Risk Reduction (R4U) scorecard. We investigated the associations between R4U risk factors and preterm birth, SGA and a low Apgar score. a prospective cohort study under routine practice conditions. six midwifery practices and two hospitals in Rotterdam, the Netherlands. 836 pregnant women. the R4U scorecard was filled out at the booking visit. after birth, the follow-up data on pregnancy outcomes were collected. Multivariate logistic regression was used to fit models for the prediction of any adverse outcome (preterm birth, SGA and/or a low Apgar score), stratified for ethnicity and socio-economic status (SES). factors predicting any adverse outcome for Western women were smoking during the first trimester and over-the-counter medication. For non-Western women risk factors were teenage pregnancy, advanced maternal age and an obstetric history of SGA. Risk factors for high SES women were low family income, no daily intake of vegetables and a history of preterm birth. For low SES women risk factors appeared to be low family income, non-Western ethnicity, smoking during the first trimester and a history of SGA. the presence of both medical and non-medical risk factors early in pregnancy predict the occurrence of adverse outcomes at birth. Furthermore the risk profiles for adverse outcomes differed according to SES and ethnicity. to optimise effective risk selection, both medical and non-medical risk factors should be taken into account in midwifery and obstetric care at the booking visit

Elevated risk of adverse obstetric outcomes in pregnant women with depression.

PubMed

Kim, Deborah R; Sockol, Laura E; Sammel, Mary D; Kelly, Caroline; Moseley, Marian; Epperson, C Neill

2013-12-01

In this study, we evaluated the association between prenatal depression symptoms adverse birth outcomes in African-American women. We conducted a retrospective cohort study of 261 pregnant African-American women who were screened with the Edinburgh Postnatal Depression Scale (EPDS) at their initial prenatal visit. Medical records were reviewed to assess pregnancy and neonatal outcomes, specifically preeclampsia, preterm birth, intrauterine growth retardation, and low birth weight. Using multivariable logistic regression models, an EPDS score ≥10 was associated with increased risk for preeclampsia, preterm birth, and low birth weight. An EPDS score ≥10 was associated with increased risk for intrauterine growth retardation, but after controlling for behavioral risk factors, this association was no longer significant. Patients who screen positive for depression symptoms during pregnancy are at increased risk for multiple adverse birth outcomes. In a positive, patient-rated depression screening at the initial obstetrics visit, depression is associated with increased risk for multiple adverse birth outcomes. Given the retrospective study design and small sample size, these findings should be confirmed in a prospective cohort study.

Urinary Phthalate Metabolite Concentrations and Reproductive Outcomes among Women Undergoing in Vitro Fertilization: Results from the EARTH Study.

PubMed

Hauser, Russ; Gaskins, Audrey J; Souter, Irene; Smith, Kristen W; Dodge, Laura E; Ehrlich, Shelley; Meeker, John D; Calafat, Antonia M; Williams, Paige L

2016-06-01

Evidence from both animal and human studies suggests that exposure to phthalates may be associated with adverse female reproductive outcomes. We evaluated the associations between urinary concentrations of phthalate metabolites and outcomes of assisted reproductive technologies (ART). This analysis included 256 women enrolled in the Environment and Reproductive Health (EARTH) prospective cohort study (2004-2012) who provided one to two urine samples per cycle before oocyte retrieval. We measured 11 urinary phthalate metabolites [mono(2-ethylhexyl) phthalate (MEHP), mono(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), mono(2-ethyl-5-oxohexyl) phthalate (MEOHP), mono(2-ethyl-5-carboxypentyl) phthalate (MECPP), mono-isobutyl phthalate (MiBP), mono-n-butyl phthalate (MBP), monobenzyl phthalate (MBzP), monoethyl phthalate (MEP), monocarboxyisooctyl phthalate (MCOP), monocarboxyisononyl phthalate (MCNP), and mono(3-carboxypropyl) phthalate (MCPP)]. We used generalized linear mixed models to evaluate the association of urinary phthalate metabolites with in vitro fertilization (IVF) outcomes, accounting for multiple IVF cycles per woman. In multivariate models, women in the highest as compared with lowest quartile of MEHP, MEHHP, MEOHP, MECPP, ΣDEHP (MEHP + MEHHP + MEOHP + MECPP), and MCNP had lower oocyte yield. Similarly, the number of mature (MII) oocytes retrieved was lower in the highest versus lowest quartile for these same phthalate metabolites. The adjusted differences (95% CI) in proportion of cycles resulting in clinical pregnancy and live birth between women in the fourth versus first quartile of ΣDEHP were -0.19 (-0.29, -0.08) and -0.19 (-0.28, -0.08), respectively, and there was also a lower proportion of cycles resulting in clinical pregnancy and live birth for individual DEHP metabolites. Urinary concentrations of DEHP metabolites were inversely associated with oocyte yield, clinical pregnancy, and live birth following ART. Hauser R, Gaskins AJ, Souter I, Smith

Modeling adverse environmental impacts on the reproductive system.

PubMed

Sussman, N B; Mazumdar, S; Mattison, D R

1999-03-01

When priority topics are being established for the study of women's health, it is generally agreed that one important area on which to focus research is reproduction. For example, increasing attention has been directed to environmental exposures that disrupt the endocrine system and alter reproduction. These concerns also suggest the need to give greater attention to the use of animal toxicologic testing to draw inferences about human reproductive risks. Successful reproduction requires multiple simultaneous and sequential processes in both the male and female, and the effect of toxicity on reproduction-related processes is time dependent. Currently, however, the risk assessment approach does not allow for the use of multiple processes or for considering the reproductive process response as a function of time. We discuss several issues in modeling exposure effects on reproductive function for risk assessment and present an overview of approaches for reproductive risk assessment. Recommendations are provided for an effective animal study design for determining reproductive risk that addresses optimization of the duration of dosing, observation of the effects of exposure on validated biomarkers, analysis of several biomarkers for complete characterization of the exposure on the underlying biologic processes, the need for longitudinally observed exposure effects, and a procedure for estimating human reproductive risk from the animal findings. An approach to characterizing reproductive toxicity to estimate the increased fertility risks in a dibromochloropropane (DBCP)-exposed human population is illustrated, using several reproductive biomarkers simultaneously from a longitudinal rabbit inhalation study of DBCP and an interspecies extrapolation method.

Endocrine-disrupting activity of hydraulic fracturing chemicals and adverse health outcomes after prenatal exposure in male mice

USGS Publications Warehouse

Kassotis, Christopher D.; Klemp, Kara C.; Vu, Danh C.; Lin, Chung-Ho; Meng, Chun-Xia; Besch-Williford, Cynthia L.; Pinatti, Lisa; Zoeller, R. Thomas; Drobnis, Erma Z.; Balise, Victoria D.; Isiguzo, Chiamaka J.; Williams, Michelle A.; Tillitt, Donald E.; Nagel, Susan C.

2015-01-01

Oil and natural gas operations have been shown to contaminate surface and ground water with endocrine-disrupting chemicals. In the current study, we fill several gaps in our understanding of the potential environmental impacts related to this process. We measured the endocrine-disrupting activities of 24 chemicals used and/or produced by oil and gas operations for five nuclear receptors using a reporter gene assay in human endometrial cancer cells. We also quantified the concentration of 16 of these chemicals in oil and gas wastewater samples. Finally, we assessed reproductive and developmental outcomes in male C57BL/6J mice after the prenatal exposure to a mixture of these chemicals. We found that 23 commonly used oil and natural gas operation chemicals can activate or inhibit the estrogen, androgen, glucocorticoid, progesterone, and/or thyroid receptors, and mixtures of these chemicals can behave synergistically, additively, or antagonistically in vitro. Prenatal exposure to a mixture of 23 oil and gas operation chemicals at 3, 30, and 300 μg/kg · d caused decreased sperm counts and increased testes, body, heart, and thymus weights and increased serum testosterone in male mice, suggesting multiple organ system impacts. Our results suggest possible adverse developmental and reproductive health outcomes in humans and animals exposed to potential environmentally relevant levels of oil and gas operation chemicals.

Endocrine-Disrupting Activity of Hydraulic Fracturing Chemicals and Adverse Health Outcomes After Prenatal Exposure in Male Mice.

PubMed

Kassotis, Christopher D; Klemp, Kara C; Vu, Danh C; Lin, Chung-Ho; Meng, Chun-Xia; Besch-Williford, Cynthia L; Pinatti, Lisa; Zoeller, R Thomas; Drobnis, Erma Z; Balise, Victoria D; Isiguzo, Chiamaka J; Williams, Michelle A; Tillitt, Donald E; Nagel, Susan C

2015-12-01

Oil and natural gas operations have been shown to contaminate surface and ground water with endocrine-disrupting chemicals. In the current study, we fill several gaps in our understanding of the potential environmental impacts related to this process. We measured the endocrine-disrupting activities of 24 chemicals used and/or produced by oil and gas operations for five nuclear receptors using a reporter gene assay in human endometrial cancer cells. We also quantified the concentration of 16 of these chemicals in oil and gas wastewater samples. Finally, we assessed reproductive and developmental outcomes in male C57BL/6J mice after the prenatal exposure to a mixture of these chemicals. We found that 23 commonly used oil and natural gas operation chemicals can activate or inhibit the estrogen, androgen, glucocorticoid, progesterone, and/or thyroid receptors, and mixtures of these chemicals can behave synergistically, additively, or antagonistically in vitro. Prenatal exposure to a mixture of 23 oil and gas operation chemicals at 3, 30, and 300 μg/kg · d caused decreased sperm counts and increased testes, body, heart, and thymus weights and increased serum testosterone in male mice, suggesting multiple organ system impacts. Our results suggest possible adverse developmental and reproductive health outcomes in humans and animals exposed to potential environmentally relevant levels of oil and gas operation chemicals.

Pregnancy loss history at first parity and selected adverse pregnancy outcomes.

PubMed

Ahrens, Katherine A; Rossen, Lauren M; Branum, Amy M

2016-07-01

To evaluate the association between pregnancy loss history and adverse pregnancy outcomes. Pregnancy history was captured during a computer-assisted personal interview for 21,277 women surveyed in the National Survey of Family Growth (1995-2013). History of pregnancy loss (<20 weeks) at first parity was categorized in three ways: number of losses, maximum gestational age of loss(es), and recency of last pregnancy loss. We estimated risk ratios for a composite measure of selected adverse pregnancy outcomes (preterm, stillbirth, or low birthweight) at first parity and in any future pregnancy, separately, using predicted margins from adjusted logistic regression models. At first parity, compared with having no loss, having 3+ previous pregnancy losses (adjusted risk ratio (aRR) = 1.66 [95% CI = 1.13, 2.43]), a maximum gestational age of loss(es) at ≥10 weeks (aRR = 1.28 [1.04, 1.56]) or having experienced a loss 24+ months ago (aRR = 1.36 [1.10, 1.68]) were associated with increased risks of adverse pregnancy outcomes. For future pregnancies, only having a history of 3+ previous pregnancy losses at first parity was associated with increased risks (aRR = 1.97 [1.08, 3.60]). Number, gestational age, and recency of pregnancy loss at first parity were associated with adverse pregnancy outcomes in U.S. women. Published by Elsevier Inc.

Adverse Perinatal Outcomes among Immigrant Women from Ethiopia in Israel.

PubMed

Calderon-Margalit, Ronit; Sherman, Dan; Manor, Orly; Kurzweil, Yaffa

2015-06-01

Immigration from Ethiopia to Israel started about 30 years ago. We aimed to compare birth outcomes between Israeli women of Ethiopian origin and Israeli-born, non-Ethiopian women. We hypothesized a higher frequency of adverse birth outcomes among Ethiopian women and a trend of improvement among those who were raised in Israel since early childhood. This is a descriptive study, comparing birth outcomes of Ethiopian (n = 1,319) and non-Ethiopian women (n = 27,307) who gave birth in a medical center in Central Israel in 2002 to 2009. Ethiopian women were further categorized by age at immigration. Logistic regressions were constructed to compare the incidence of adverse birth outcomes between Ethiopian and non-Ethiopian women, controlling for potential confounders. Ethiopian women had about twice the incidence of very and extremely preterm births, compared with non-Ethiopians. Ethiopian women had twice the odds for neonates who were either small for gestational age or had low 5-minute Apgar scores. Ethiopian women had about threefold increased risk of stillbirths (OR 2.9 [95% CI 1.87-4.49]). No trend of improvement was noted for women who were raised in Israel from early childhood. Ethiopian women are at increased risk of adverse birth outcomes. Future research is needed to investigate the underlying causes for the increased risks and lack of improvement among those who were raised in Israel that will lead to effective interventions. © 2015 Wiley Periodicals, Inc.

Quantitative Adverse Outcome Pathways and Their ...

EPA Pesticide Factsheets

A quantitative adverse outcome pathway (qAOP) consists of one or more biologically based, computational models describing key event relationships linking a molecular initiating event (MIE) to an adverse outcome. A qAOP provides quantitative, dose–response, and time-course predictions that can support regulatory decision-making. Herein we describe several facets of qAOPs, including (a) motivation for development, (b) technical considerations, (c) evaluation of confidence, and (d) potential applications. The qAOP used as an illustrative example for these points describes the linkage between inhibition of cytochrome P450 19A aromatase (the MIE) and population-level decreases in the fathead minnow (FHM; Pimephales promelas). The qAOP consists of three linked computational models for the following: (a) the hypothalamic-pitutitary-gonadal axis in female FHMs, where aromatase inhibition decreases the conversion of testosterone to 17β-estradiol (E2), thereby reducing E2-dependent vitellogenin (VTG; egg yolk protein precursor) synthesis, (b) VTG-dependent egg development and spawning (fecundity), and (c) fecundity-dependent population trajectory. While development of the example qAOP was based on experiments with FHMs exposed to the aromatase inhibitor fadrozole, we also show how a toxic equivalence (TEQ) calculation allows use of the qAOP to predict effects of another, untested aromatase inhibitor, iprodione. While qAOP development can be resource-intensive, the quan

Reproductive Health Risks Associated with Occupational Exposures to Antineoplastic Drugs in Health Care Settings: A Review of the Evidence

PubMed Central

Connor, Thomas H.; Lawson, Christina C.; Polovich, Martha; McDiarmid, Melissa A.

2015-01-01

Objectives Antineoplastic drugs are known reproductive and developmental toxicants. Our objective was to review the existing literature of reproductive health risks to workers who handle antineoplastic drugs. Methods A structured literature review of 18 peer-reviewed, English language publications of occupational exposure and reproductive outcomes was performed. Results While effect sizes varied with study size and population, occupational exposure to antineoplastic drugs appears to raise the risk of both congenital malformations and miscarriage. Studies of infertility and time-to-pregnancy also suggested an increased risk for sub-fertility. Conclusions Antineoplastic drugs are highly toxic in patients receiving treatment and adverse reproductive effects have been well documented in these patients. Healthcare workers with chronic, low level occupational exposure to these drugs also appear to have an increased risk of adverse reproductive outcomes. Additional precautions to prevent exposure should be considered. PMID:25153300

Setting the stage to advance the adverse outcome pathway (AOP) framework through horizon scanning

EPA Science Inventory

Recognizing the international interest surrounding the adverse outcome pathway framework, which captures existing information describing causal linkages between a molecular initiating event through levels of biological organization to an adverse outcome of regulatory significance...

Dental neglect and adverse birth outcomes: a validation and observational study.

PubMed

Acharya, S; Pentapati, K C; Bhat, P V

2013-05-01

The objectives of this study were to validate the Indian translation of the Dental Neglect Scale (DNS) among a sample of parturient Indian women and to investigate dental neglect as a possible risk indicator in adverse birth outcomes. Three hundred and sixteen parturient women were administered the DNS and the Modified Dental Beliefs Scale (MDBS) and were also clinically examined for oral health status. Information regarding socio-economic status, weeks of gestation and birth weight was also collected. A gestation period of less than 37 weeks was considered as preterm and a birth weight of less than 2500 gm as 'low birth weight'. The Indian version of the DNS was found to be reliable (Cronbach's Alpha = 0.72) and valid for assessing dental neglect among the women. Factor analysis of the DNS revealed a two-factor structure accounting for 56% variance. Dental neglect was higher among those with poorer oral health status, lower socio-economic and educational status. Multinomial logistic regression showed high dental neglect and negative dental beliefs and not poor oral health, as significant risk indicators for occurrence of adverse birth outcomes. The finding of an association of adverse birth outcomes with dental neglect and beliefs, but not with poor oral health could be due to the influence of other more important general factors which had a direct bearing on birth outcomes. There is a need for further research to assess the role of behavioural factors like dental neglect as risk indicators for adverse birth outcomes. © 2012 John Wiley & Sons A/S.

Risk Factors and Risk Stratification for Adverse Obstetrical Outcomes After Appendectomy or Cholecystectomy During Pregnancy.

PubMed

Sachs, Adam; Guglielminotti, Jean; Miller, Russell; Landau, Ruth; Smiley, Richard; Li, Guohua

2017-05-01

Identification of risk factors for adverse obstetrical outcomes after appendectomy and cholecystectomy during pregnancy is necessary for evidence-based risk reduction and adequate patient counseling. To identify risk factors for adverse obstetrical outcomes after appendectomy and cholecystectomy during pregnancy and stratify the risk of such outcomes. A cohort study was conducted using the Nationwide Inpatient Sample, a nationally representative sample of patients discharged from community hospitals in the United States, from January 1, 2003, to December 31, 2012. Multivariable analysis of risk factors for adverse obstetric outcomes was performed for 19 926 women undergoing appendectomy or cholecystectomy during pregnancy and a scoring system for such risk factors was developed. Data analysis was conducted from January 1, 2015, to July 31, 2016. A composite measure including 7 adverse obstetrical outcomes throughout pregnancy and occurring before hospital discharge. Of the 19 926 women (mean [SD] age, 26 [6] years) in the study, 1018 adverse obstetrical events were recorded in 953 pregnant women (4.8%). The 3 most frequent adverse events were preterm delivery (360 [35.4%]), preterm labor without preterm delivery (269 [26.4%]), and miscarriage (262 [25.7%]). The risk factors associated most strongly with an adverse obstetrical outcome included cervical incompetence (adjusted odds ratio, 24.29; 95% CI, 7.48-78.81), preterm labor during current pregnancy (adjusted odds ratio, 18.34; 95% CI, 4.95-67.96), vaginitis or vulvovaginitis (adjusted odds ratio, 5.17; 95% CI, 2.19-12.23), and sepsis (adjusted odds ratio, 3.39; 95% CI, 2.08-5.51). A scoring system based on statistically significant variables classified the study sample into 3 risk groups corresponding to predicted probabilities of adverse obstetrical outcomes of 2.5% (≤4 points), 8.2% (5-8 points), and 21.8% (≥9 points). Approximately 5% of women experience adverse obstetrical outcomes after appendectomy

Maternal psychological distress during pregnancy does not increase the risk for adverse birth outcomes.

PubMed

Staneva, Aleksandra A; Morawska, Alina; Bogossian, Fiona; Wittkowski, Anja

2018-01-01

Maternal psychological distress during pregnancy is a potential risk factor for various birth complications. This study aimed to explore psychological factors associated with adverse birth outcomes. Symptoms of psychological distress, individual characteristics, and medical complications were assessed at two time points antenatally in 285 women from Australia and New Zealand; birth outcomes were assessed postpartum, between January 2014 and September 2015. Hierarchical multiple regression analyses were conducted to examine the relation of psychological distress to adverse birth outcomes. Medical complications during pregnancy, such as serious infections, placental problems and preeclampsia, and antenatal cannabis use, were the factors most strongly associated with adverse birth outcomes, accounting for 22 percent of the total variance (p < .001). Symptoms of depression and/or anxiety, low social support, and low sense of coherence were not associated with birth complications. In unadjusted analyses, self-reported diagnosis of anxiety disorder during pregnancy and an orientation toward a Regulator mothering style were associated with adverse birth outcomes; however, after controlling for medical complications, these were no longer associated. Our study results indicate that antenatal depressive and/or anxiety symptoms were not independently associated with adverse birth outcomes, a reassuring finding for women who are already psychologically vulnerable during pregnancy.

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

mHealth to promote pregnancy and interconception health among African-American women at risk for adverse birth outcomes: a pilot study.

PubMed

Foster, Jennifer; Miller, Lindsey; Isbell, Sheila; Shields, Tekesia; Worthy, Natasha; Dunlop, Anne Lang

2015-01-01

The use of mobile phone applications (mHealth) to provide health education and behavioral prompts is 1 of the 12 common mHealth functions identified by the World Health Organization as innovations to strengthen health systems. Among low-income pregnant and parenting women, health education is widely recognized as a way to improve maternal and infant health outcomes, but the efficacy of written health education materials to change knowledge and behavior for this population is questionable. mHealth prompts, in contrast, is a promising alternative. A team of researchers in medicine/epidemiology, anthropology/midwifery, computer science/sensors, and community-based case management created and pilot tested a mHealth application (mHealth app) for African-American women at high risk for adverse birth outcomes. We tested the acceptability and feasibility of the interactive application among women during the reproductive stages of early and late pregnancy, postpartum, and interconception. Interview data from 14 women in the various reproductive stages revealed that most women found the mHealth messages helpful. Also, 62 Ob-Gyn physicians and nurses and 19 Family Medicine residents provided feedback. Women's responses to specific messages trended down over time. Women in the postpartum phase had the highest response rate to particular text messages, followed by those in the pregnancy phase. Responses dropped off dramatically during the interconception period. About 21% of women lost their phones. Unexpected findings were that all participants already had smartphones, women wanted messages about depression, and clinicians wanted the app to link to case management for individualized medical care. Logistical challenges to app management were limitations but are useful for consideration before scale-up. This study corroborates findings in the health literacy literature that women most at risk for adverse birth outcomes need additional face-to-face support with m

mHealth to promote pregnancy and interconception health among African-American women at risk for adverse birth outcomes: a pilot study

PubMed Central

Miller, Lindsey; Isbell, Sheila; Shields, Tekesia; Worthy, Natasha; Dunlop, Anne Lang

2015-01-01

Background The use of mobile phone applications (mHealth) to provide health education and behavioral prompts is 1 of the 12 common mHealth functions identified by the World Health Organization as innovations to strengthen health systems. Among low-income pregnant and parenting women, health education is widely recognized as a way to improve maternal and infant health outcomes, but the efficacy of written health education materials to change knowledge and behavior for this population is questionable. mHealth prompts, in contrast, is a promising alternative. Methods A team of researchers in medicine/epidemiology, anthropology/midwifery, computer science/sensors, and community-based case management created and pilot tested a mHealth application (mHealth app) for African-American women at high risk for adverse birth outcomes. We tested the acceptability and feasibility of the interactive application among women during the reproductive stages of early and late pregnancy, postpartum, and interconception. Results Interview data from 14 women in the various reproductive stages revealed that most women found the mHealth messages helpful. Also, 62 Ob-Gyn physicians and nurses and 19 Family Medicine residents provided feedback. Women’s responses to specific messages trended down over time. Women in the postpartum phase had the highest response rate to particular text messages, followed by those in the pregnancy phase. Responses dropped off dramatically during the interconception period. About 21% of women lost their phones. Unexpected findings were that all participants already had smartphones, women wanted messages about depression, and clinicians wanted the app to link to case management for individualized medical care. Conclusions Logistical challenges to app management were limitations but are useful for consideration before scale-up. This study corroborates findings in the health literacy literature that women most at risk for adverse birth outcomes need additional

Risk Factors and Risk Stratification for Adverse Obstetrical Outcomes After Appendectomy or Cholecystectomy During Pregnancy

PubMed Central

Guglielminotti, Jean; Miller, Russell; Landau, Ruth; Smiley, Richard; Li, Guohua

2017-01-01

Importance Identification of risk factors for adverse obstetrical outcomes after appendectomy and cholecystectomy during pregnancy is necessary for evidence-based risk reduction and adequate patient counseling. Objectives To identify risk factors for adverse obstetrical outcomes after appendectomy and cholecystectomy during pregnancy and stratify the risk of such outcomes. Design, Setting, and Participants A cohort study was conducted using the Nationwide Inpatient Sample, a nationally representative sample of patients discharged from community hospitals in the United States, from January 1, 2003, to December 31, 2012. Multivariable analysis of risk factors for adverse obstetric outcomes was performed for 19 926 women undergoing appendectomy or cholecystectomy during pregnancy and a scoring system for such risk factors was developed. Data analysis was conducted from January 1, 2015, to July 31, 2016. Main Outcomes and Measures A composite measure including 7 adverse obstetrical outcomes throughout pregnancy and occurring before hospital discharge. Results Of the 19 926 women (mean [SD] age, 26 [6] years) in the study, 1018 adverse obstetrical events were recorded in 953 pregnant women (4.8%). The 3 most frequent adverse events were preterm delivery (360 [35.4%]), preterm labor without preterm delivery (269 [26.4%]), and miscarriage (262 [25.7%]). The risk factors associated most strongly with an adverse obstetrical outcome included cervical incompetence (adjusted odds ratio, 24.29; 95% CI, 7.48-78.81), preterm labor during current pregnancy (adjusted odds ratio, 18.34; 95% CI, 4.95-67.96), vaginitis or vulvovaginitis (adjusted odds ratio, 5.17; 95% CI, 2.19-12.23), and sepsis (adjusted odds ratio, 3.39; 95% CI, 2.08-5.51). A scoring system based on statistically significant variables classified the study sample into 3 risk groups corresponding to predicted probabilities of adverse obstetrical outcomes of 2.5% (≤4 points), 8.2% (5-8 points), and 21.8% (≥9

Tobacco and areca nut chewing--reproductive impairments: an overview.

PubMed

Kumar, Sunil

2013-04-01

A large number of people are using smokeless tobacco and areca nut worldwide. Sufficient data on tobacco smoking have harmful effect on human health and reproduction is available. However, data on the smokeless tobacco and areca nut use on human reproduction is scanty. This overview is an attempt to compose on the consumption of smokeless tobacco and areca nut on human reproduction and some relevant experimental data were also included. The existing studies suggest that tobacco and areca nut chewing alone, together or with other ingredients had reproductive toxic potential. Pregnant women using smokeless tobacco during pregnancy also had adverse effect on pregnancy and its outcome. Thus pregnant women must avoid consumption of any mixture containing areca nut and tobacco in order to protect the pregnancy and outcome. The data suggest that smokeless tobacco use is also harmful as smoking for reproduction and use of areca nut might have further compounded the problem. Copyright © 2012 Elsevier Inc. All rights reserved.

Time-to-pregnancy and pregnancy outcomes in a South African population

PubMed Central

2010-01-01

Background Time-to-pregnancy (TTP) has never been studied in an African setting and there are no data on the rates of adverse pregnancy outcomes in South Africa. The study objectives were to measure TTP and the rates of adverse pregnancy outcomes in South Africa, and to determine the reliability of the questionnaire tool. Methods The study was cross-sectional and applied systematic stratified sampling to obtain a representative sample of reproductive age women for a South African population. Data on socio-demographic, work, health and reproductive variables were collected on 1121 women using a standardized questionnaire. A small number (n = 73) of randomly selected questionnaires was repeated to determine reliability of the questionnaire. Data was described using simple summary statistics while Kappa and intra-class correlation statistics were calculated for reliability. Results Of the 1121 women, 47 (4.2%) had never been pregnant. Mean gravidity was 2.3 while mean parity was 2.0 There were a total of 2467 pregnancies; most (87%) resulted in live births, 9.5% in spontaneous abortion and 2.2% in still births. The proportion of planned pregnancies was 39% and the median TTP was 6 months. The reliability of the questionnaire for TTP data was good; 63% for all participants and 97% when censored at 14 months. Overall reliability of reporting adverse pregnancy outcomes was very high, ranging from 90 - 98% for most outcomes. Conclusion This is the first comprehensive population-based reproductive health study in South Africa, to describe the biologic fertility of the population, and provides rates for planned pregnancies and adverse pregnancy outcomes. The reliability of the study questionnaire was substantial, with most outcomes within 70 - 100% reliability index. The study provides important public information for health practitioners and researchers in reproductive health. It also highlights the need for public health intervention programmes and epidemiological

The Role of Gender Empowerment on Reproductive Health Outcomes in Urban Nigeria

PubMed Central

Speizer, Ilene S.; Fotso, Jean-Christophe; Akiode, Akinsewa; Saad, Abdulmumin; Calhoun, Lisa; Irani, Laili

2014-01-01

Objectives To date, limited evidence is available for urban populations in sub-Saharan Africa, specifically research into the association between urban women’s empowerment and reproductive health outcomes. The objective of this study is to investigate whether women’s empowerment in urban Nigerian settings is associated with family planning use and maternal health behaviors. Moreover, we examine whether different effects of empowerment exist by region of residence. Methods This study uses baseline household survey data from the Measurement, Learning & Evaluation Project (MLE) for the Nigerian Urban Reproductive Health Initiative (NURHI) being implemented in six major cities. We examine four dimensions of empowerment: economic freedom, attitudes towards domestic violence, partner prohibitions and decision-making. We determine if the empowerment dimensions have different effects on reproductive health outcomes by region of residence using multivariate analyses. Results Results indicate that more empowered women are more likely to use modern contraception, deliver in a health facility and have a skilled attendant at birth. These trends vary by empowerment dimension and by city/region in Nigeria. Conclusions We conclude by discussing the implications of these findings on future programs seeking to improve reproductive health outcomes in urban Nigeria and beyond. PMID:23576403

THE ADVERSE OUTCOME PATHWAY (AOP) FRAMEWORK ...

EPA Pesticide Factsheets

An Adverse Outcome Pathway (AOP) represents the organization of current and newly acquired knowledge of biological pathways. These pathways contain a series of nodes (Key Events, KEs) that when sufficiently altered influence the next node on the pathway, beginning from an Molecular Initiating Event (MIE), through intermediate KEs, ending in an Adverse Outcome (AO) which may be used as a basis for decision making. A KE is a measurable biological change, and is linked with other KEs via Key Event Relationships (KERs). A given KE may be involved in several AOPs, leading to a plausible network of biological changes that are involved in an organism’s response to an external stressor. When describing an AOP, five guiding principles have been proposed [1]: 1) an AOP is not specific to a single external stressor, 2) AOPs are modular, with KEs and KERs that can be used in several AOPs, 3) a single AOP is the unit of development, 4) most biological responses will be the result of networks of AOPs, and 5) AOPs will be modified as more biological knowledge becomes available. The collaborative development of AOPs is recommended to be performed using the AOP-Wiki (https://aopwiki.org), which is an effort between the European Commission – DG Joint Research Centre (JRC) and U.S. Environmental Protection Agency (EPA). The Wiki is one part of a larger OECD-sponsored AOP Knowledgebase effort, which is a repository for all AOPs developed as part of the Organization for Economic

Racial Discrimination and Adverse Birth Outcomes: An Integrative Review.

PubMed

Alhusen, Jeanne L; Bower, Kelly M; Epstein, Elizabeth; Sharps, Phyllis

2016-11-01

This article presents an integrative review of the literature examining the relationship between racial discrimination and adverse birth outcomes. Searches for research studies published from 2009 to 2015 were conducted using PubMed, CINAHL, Scopus, PsycINFO, Web of Science, and Embase. Articles were assessed for potential inclusion using the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) 2009 framework. Fifteen studies met criteria for review. The majority of the studies found a significant relationship between racial discrimination and low birth weight, preterm birth, and small for gestational age. Each of the studies that examined more proximal variables related to birth outcomes such as entry into prenatal care, employment opportunities, neighborhood characteristics, or inflammatory markers found significant associations between the specific variables examined and racial discrimination. Participants in qualitative studies discussed experiences of institutional racism with regard to several components of prenatal care including access and quality of care. Racial discrimination is a significant risk factor for adverse birth outcomes. To best understand the mechanisms by which racial discrimination impacts birth outcomes, and to inform the development of effective interventions that eliminate its harmful effects on health, longitudinal research that incorporates comprehensive measures of racial discrimination is needed. Health care providers must fully acknowledge and address the psychosocial factors that impact health outcomes in minority racial/ethnic women. © 2016 by the American College of Nurse-Midwives.

Racial Discrimination and Adverse Birth Outcomes: An Integrative Review

PubMed Central

Alhusen, Jeanne L.; Bower, Kelly; Epstein, Elizabeth; Sharps, Phyllis

2016-01-01

Introduction This article presents an integrative review of the literature examining the relationship between racial discrimination and adverse birth outcomes. Methods Searches for research studies published from 2009 to 2015 were conducted using PubMed, CINAHL, Scopus, PsycINFO, Web of Science, and Embase. Articles were assessed for potential inclusion using the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) 2009 framework. Results Fifteen studies met criteria for review. The majority of the studies found a significant relationship between racial discrimination and low birth weight, preterm birth, and small for gestational age. Each of the studies that examined more proximal variables related to birth outcomes such as entry into prenatal care, employment opportunities, neighborhood characteristics, or inflammatory markers found significant associations between the specific variables examined and racial discrimination. Participants in qualitative studies discussed experiences of institutional racism with regard to several components of prenatal care including access and quality of care. Discussion Racial discrimination is a significant risk factor for adverse birth outcomes. To best understand the mechanisms by which racial discrimination impacts birth outcomes, and to inform the development of effective interventions that eliminate its harmful effects on health, longitudinal research that incorporates comprehensive measures of racial discrimination is needed. Health care providers must fully acknowledge and address the psychosocial factors that impact health outcomes in minority racial/ethnic women. PMID:27737504

[Chorionicity and adverse perinatal outcome].

PubMed

Ferreira, Isabel; Laureano, Carla; Branco, Miguel; Nordeste, Ana; Fonseca, Margarida; Pinheiro, Adelaide; Silva, Maria Isabel; Almeida, Maria Céu

2005-01-01

Considering the highest rate of morbidity and mortality in diamniotic monochorionic twins, the authors evaluated and compared the adverse obstetric and perinatal outcome in twin pregnancies according to chorionicity. A retrospective study was conducted in all twin deliveries that occurred in the Obstetric Unit of Maternidade Bissaya-Barreto, for a period of tree years (from the 1st of January 1999 until the 31st of December 2001). From de 140 diamniotic twin pregnancies studied, we considered two groups according to the chorionicity: monochorionic and dichorionic. We compared multiple parameters as, epidemiologic data, adverse obstetric outcome, gestacional delivery age, type of delivery and the morbidity, the mortality and the follow-up of the newborn. The statistic tests used were the X2 and the t student. From the 140 twin pregnancies included in the study, 66% (92 cases) presented dichorionic placentation and 34% (48 cases) were monochorionic. In the group of monochorionic pregnancies, we observed highly difference related to pathology of amniotic fluid (14.5% vs 2.2%), discordant fetal growth (41.6% vs 22.8%) and rate of preterm delivery (66.6% vs 32.6%). Related to the newborn we verified that they had a lower average birth weight (1988g vs 2295g), a highly rate of weight discordancy (23% vs 15.3%), intraventricular haemorrhage (2.2% vs 0%) and IUGR (6.6% vs 1.6%), statistically significant in the monochorionic group. Also the perinatal mortality rate was significantly higher in the monochorionic pregnancies (93.7 per thousand vs 21.7 per thousand). The high rate of morbidity and mortality related to the monochorionic twin pregnancies, implies the need of a correct identification of the type of chorionicity and also a high standard of prenatal surveillance in prenatal specialised health centers.

Religion, Poverty, and Politics: Their Impact on Women's Reproductive Health Outcomes.

PubMed

Kimball, Richard; Wissner, Michael

2015-01-01

This study sought to explore the relationship(s) between U.S. states of selected social determinants of health (SDH) and three women's reproductive health outcomes including abortion, teen births, and infant mortality rates (IMR). The data from multiple population surveys were used to establish on a state-by-state basis, the interactions between selected SDH (religion, voting patterns, child poverty, and GINI) and their policy effects on three women's reproductive health outcomes (abortion, teen births, and IMRs) using publicly available national databases. Child poverty rates and the GINI coefficient were analyzed. Religiosity information was obtained from the Pew Forum's surveys. Voting results were collected from the 2008 congressional and presidential races and were used as proxy measures for conservative- versus liberal-leaning policies and policy makers. Using multiple regression analysis, higher IMRs were associated with higher religiosity scores. Lower abortion rates were associated with voting conservatively and higher income inequality. Higher teen birth rates were associated with higher child poverty rates and voting conservatively. This study shows that selected SDH may have substantial impacts on women's reproductive health outcomes at the state level. Significant inequalities exist between liberal and conservative states that affect women's health outcomes. © 2015 Wiley Periodicals, Inc.

Validation of birth outcomes from the Society for Assisted Reproductive Technology Clinic Outcome Reporting System (SART CORS): population-based analysis from the Massachusetts Outcome Study of Assisted Reproductive Technology (MOSART).

PubMed

Stern, Judy E; Gopal, Daksha; Liberman, Rebecca F; Anderka, Marlene; Kotelchuck, Milton; Luke, Barbara

2016-09-01

To assess the validity of outcome data reported to the Society for Assisted Reproductive Technology Clinic Outcome Reporting System (SART CORS) compared with data from vital records and the birth defects registry in Massachusetts. Longitudinal cohort. Not applicable. A total of 342,035 live births and fetal deaths from Massachusetts mothers giving birth in the state from July 1, 2004, to December 31, 2008; 9,092 births and fetal deaths were from mothers who had conceived with the use of assisted reproductive technology (ART) and whose cycle data had been reported to the SART CORS. Not applicable. Percentage agreement between maternal race and ethnicity, delivery outcome (live birth or fetal death), plurality (singleton, twin, or triplet+), delivery date, and singleton birth weight reported in the SART CORS versus vital records; sensitivity and specificity for birth defects among singletons as reported in the SART CORS versus the Massachusetts Birth Defects Monitoring Program (BDMP). There was >95% agreement between the SART CORS and vital records for fields of maternal race/ethnicity, live birth/fetal death, and plurality; birth outcome date was within 1 day with 94.9% agreement and birth weight was within 100 g with 89.6% agreement. In contrast, sensitivity for report of any birth defect was 38.6%, with a range of 18.4%-50.0%, for specific birth defect categories. Although most SART CORS outcome fields are accurately reported, birth defect variables showed poor sensitivity compared with the gold standard data from the BDMP. We suggest that reporting of birth defects be discontinued. Copyright © 2016 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Antihistamines and other prognostic factors for adverse outcome in hyperemesis gravidarum

PubMed Central

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

2014-01-01

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

Enhanced bio-concentration of tris(1,3-dichloro-2-propyl) phosphate in the presence of nano-TiO2 can lead to adverse reproductive outcomes in zebrafish.

PubMed

Ren, Xin; Zhao, Xuesong; Duan, Xiaoyue; Fang, Ziwei

2018-02-01

Interactions between organic toxicants and nano-particles in the aquatic environment may modify toxicant bioavailability and consequently the toxicant's fate and toxicity. To evaluate the potential impact of nano-titanium dioxide (TiO 2 ) on the bio-concentration and reproductive endocrine disruption of tris(1,3-dichloro-2-propyl) phosphate (TDCIPP) in fish, a comparative bioaccumulation study was conducted on zebrafish (Danio rerio, AB strain) treated with 0, 5.74, 23.6, or 90.7 μg L -1 TDCIPP alone or co-exposed to TDCIPP and 0.09 mg L -1 nano-TiO 2 for 21 days. Nano-TiO 2 can absorb TDCIPP and nano-TiO 2 is taken up into zebrafish. Chemical measurements showed that TDCIPP was bio-concentrated in zebrafish, and the highest level was detected in the liver, followed by the brain and gonads. Compared with TDCIPP treatment, increased tissue burdens of both TDCIPP were observed in the liver, brain, and gonads suggesting that nano-TiO 2 adsorbed TDCIPP and acted as a carrier facilitating the uptake and translocation of TDCIPP in tissues. Higher bio-concentration in the presence of nano-TiO 2 resulted in a significant decrease in the hepatic-somatic index, gonad-somatic index and brain-somatic index in F0 females but not F0 males. Moreover, a further gender-dependent reduction in testosterone (T), estradiol (E2), follicle-stimulating hormone (FSH) and luteinizing hormone (LH), and induction of plasma vitellogenin (VTG) concentrations in adults were observed following co-exposure. Co-exposure also inhibited egg production and caused significant developmental toxicity in F1 larvae. The results obtained using this multi-marker approach suggested that nano-TiO 2 is a carrier of TDCIPP and accelerated its bio-concentration in adult zebrafish, resulting in adverse reproduction outcomes. Copyright © 2017 Elsevier Ltd. All rights reserved.

Linking Adverse Outcome Pathways to Dynamic Energy Budgets: A Conceptual Model

DOE Office of Scientific and Technical Information (OSTI.GOV)

Murphy, Cheryl; Nisbet, Roger; Antczak, Philipp

Ecological risk assessment quantifies the likelihood of undesirable impacts of stressors, primarily at high levels of biological organization. Data used to inform ecological risk assessments come primarily from tests on individual organisms or from suborganismal studies, indicating a disconnect between primary data and protection goals. We know how to relate individual responses to population dynamics using individual-based models, and there are emerging ideas on how to make connections to ecosystem services. However, there is no established methodology to connect effects seen at higher levels of biological organization with suborganismal dynamics, despite progress made in identifying Adverse Outcome Pathways (AOPs) thatmore » link molecular initiating events to ecologically relevant key events. This chapter is a product of a working group at the National Center for Mathematical and Biological Synthesis (NIMBioS) that assessed the feasibility of using dynamic energy budget (DEB) models of individual organisms as a “pivot” connecting suborganismal processes to higher level ecological processes. AOP models quantify explicit molecular, cellular or organ-level processes, but do not offer a route to linking sub-organismal damage to adverse effects on individual growth, reproduction, and survival, which can be propagated to the population level through individual-based models. DEB models describe these processes, but use abstract variables with undetermined connections to suborganismal biology. We propose linking DEB and quantitative AOP models by interpreting AOP key events as measures of damage-inducing processes in a DEB model. Here, we present a conceptual model for linking AOPs to DEB models and review existing modeling tools available for both AOP and DEB.« less

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...

20170312 - Adverse Outcome Pathway (AOP) framework for ...

EPA Pesticide Factsheets

Vascular development commences with de novo assembly of a primary capillary plexus (vasculogenesis) followed by its expansion (angiogenesis) and maturation (angio-adaptation) into a hierarchical system of arteries and veins. These processes are tightly regulated by genetic signals and environmental factors linked to morphogenesis and microphysiology. Gestational exposure to some chemicals disrupts vascular development leading to adverse outcomes. To broadly assess consequences of gestational toxicant exposure on vascular development, an Adverse Outcome Pathway (AOP) framework was constructed that integrates data from ToxCast high-throughput screening (HTS) assays with pathway-level information from the literature and public databases. The AOP-based model resolved the ToxCast library (1065 compounds) into a matrix based on several dozen molecular functions critical for developmental angiogenesis. A sample of 38 ToxCast chemicals selected across the matrix tested model performance. Putative vascular disrupting chemical (pVDC) bioactivity was assessed by multiple laboratories utilizing diverse angiogenesis assays, including: transgenic zebrafish, complex human cell co-cultures, engineered microscale systems, and human-synthetic models. The ToxCast pVDC signature predicted vascular disruption in a manner that was chemical-specific and assay-dependent. An AOP for developmental vascular toxicity was constructed that focuses on inhibition of VEGF receptor (VEGFR2). Thi

Adverse Outcome Pathway (AOP) framework for embryonic ...

EPA Pesticide Factsheets

Vascular development commences with de novo assembly of a primary capillary plexus (vasculogenesis) followed by its expansion (angiogenesis) and maturation (angio-adaptation) into a hierarchical system of arteries and veins. These processes are tightly regulated by genetic signals and environmental factors linked to morphogenesis and microphysiology. Gestational exposure to some chemicals disrupts vascular development leading to adverse outcomes. To broadly assess consequences of gestational toxicant exposure on vascular development, an Adverse Outcome Pathway (AOP) framework was constructed that integrates data from ToxCast high-throughput screening (HTS) assays with pathway-level information from the literature and public databases. The AOP-based model resolved the ToxCast library (1065 compounds) into a matrix based on several dozen molecular functions critical for developmental angiogenesis. A sample of 38 ToxCast chemicals selected across the matrix tested model performance. Putative vascular disrupting chemical (pVDC) bioactivity was assessed by multiple laboratories utilizing diverse angiogenesis assays, including: transgenic zebrafish, complex human cell co-cultures, engineered microscale systems, and human-synthetic models. The ToxCast pVDC signature predicted vascular disruption in a manner that was chemical-specific and assay-dependent. An AOP for developmental vascular toxicity was constructed that focuses on inhibition of VEGF receptor (VEGFR2). Thi

Predicting adverse neonatal outcomes in fetuses with abdominal wall defects using prenatal risk factors.

PubMed

Nicholas, Sara S; Stamilio, David M; Dicke, Jeffery M; Gray, Diana L; Macones, George A; Odibo, Anthony O

2009-10-01

The aim of this study was to determine whether prenatal variables can predict adverse neonatal outcomes in fetuses with abdominal wall defects. A retrospective cohort study that used ultrasound and neonatal records for all cases of gastroschisis and omphalocele seen over a 16-year period. Cases with adverse neonatal outcomes were compared with noncases for multiple candidate predictive factors. Univariable and multivariable statistical methods were used to develop the prediction models, and effectiveness was evaluated using the area under the receiver operating characteristic curve. Of 80 fetuses with gastroschisis, 29 (36%) had the composite adverse outcome, compared with 15 of 33 (47%) live neonates with omphalocele. Intrauterine growth restriction was the only significant variable in gastroschisis, whereas exteriorized liver was the only predictor in omphalocele. The areas under the curve for the prediction models with gastroschisis and omphalocele are 0.67 and 0.74, respectively. Intrauterine growth restriction and exteriorization of the liver are significant predictors of adverse neonatal outcome with gastroschisis and omphalocele.

Occupational exposure associated with reproductive dysfunction.

PubMed

Kumar, Sunil

2004-01-01

Evidence suggestive of harmful effects of occupational exposure on the reproductive system and related outcomes has gradually accumulated in recent decades, and is further compounded by persistent environmental endocrine disruptive chemicals. These chemicals have been found to interfere with the function of the endocrine system, which is responsible for growth, sexual development and many other essential physiological functions. A number of occupations are being reported to be associated with reproductive dysfunction in males as well as in females. Generally, occupations involving the manufacture/or application of some of the persistent chemicals that are not easily degradable as well as bio-accumulative chemicals, occupations involving intensive exposure to heat and radiation, occupations involving the use of toxic solvents as well as toxic fumes are reported to be associated with reproductive dysfunction. Occupational exposure of males to various persistent chemicals have been reported to have male mediated adverse reproductive outcomes in the form of abortion, reduction in fertility etc. with inconclusive or limited evidence. Nevertheless, there is a need for more well designed studies in order to implicate any individual chemical having such effects as in most occupations workers are exposed to raw, intermediate and finished products and there are also several confounding factors associated with lifestyles responsible for reproductive dysfunction. There is an urgent need to look at indiscriminate use of persistent chemicals especially pesticides and persistent organic pollutants (POP's) as these chemicals enter the food chain also and could be potential for exposure during the critical period of development. It is also necessary to impart information, and to educate about the safe use of these chemicals, as a very sensitive reproduction issue is involved with exposure to these chemicals. Occupational exposures often are higher than environmental exposures, so

Propiconazole inhibits steroidogenesis and reproduction in the fathead minnow (Pimephales promelas)

EPA Science Inventory

This study assessed effects of the conazole-fungicide propiconazole on endocrine function and reproductive success of the fathead minnow, using an experimental approach based on previously defined adverse outcome pathways (AOPs) for chemicals that inhibit steroidogenesis in fish...

Does early second-trimester sonography predict adverse perinatal outcomes in monochorionic diamniotic twin pregnancies?

PubMed

Allaf, M Baraa; Campbell, Winston A; Vintzileos, Anthony M; Haeri, Sina; Javadian, Pouya; Shamshirsaz, Amir A; Ogburn, Paul; Figueroa, Reinaldo; Wax, Joseph; Markenson, Glenn; Chavez, Martin R; Ravangard, Samadh F; Ruano, Rodrigo; Sangi-Haghpeykar, Haleh; Salmanian, Bahram; Meyer, Marjorie; Johnson, Jeffery; Ozhand, Ali; Davis, Sarah; Borgida, Adam; Belfort, Michael A; Shamshirsaz, Alireza A

2014-09-01

To determine whether intertwin discordant abdominal circumference, femur length, head circumference, and estimated fetal weight sonographic measurements in early second-trimester monochorionic diamniotic twins predict adverse obstetric and neonatal outcomes. We conducted a multicenter retrospective cohort study involving 9 regional perinatal centers in the United States. We examined the records of all monochorionic diamniotic twin pregnancies with two live fetuses at the 16- to 18-week sonographic examination who had serial follow-up sonography until delivery. The intertwin discordance in abdominal circumference, femur length, head circumference, and estimated fetal weight was calculated as the difference between the two fetuses, expressed as a percentage of the larger using the 16- to 18-week sonographic measurements. An adverse composite obstetric outcome was defined as the occurrence of 1 or more of the following in either fetus: intrauterine growth restriction, twin-twin transfusion syndrome, intrauterine fetal death, abnormal growth discordance (≥20% difference), and very preterm birth at or before 28 weeks. An adverse composite neonatal outcome was defined as the occurrence of 1 or more of the following: respiratory distress syndrome, any stage of intraventricular hemorrhage, 5-minute Apgar score less than 7, necrotizing enterocolitis, culture-proven early-onset sepsis, and neonatal death. Receiver operating characteristic and logistic regression-with-generalized estimating equation analyses were constructed. Among the 177 monochorionic diamniotic twin pregnancies analyzed, intertwin abdominal circumference and estimated fetal weight discordances were only predictive of adverse composite obstetric outcomes (areas under the curve, 79% and 80%, respectively). Receiver operating characteristic curves showed that intertwin discordances in abdominal circumference, femur length, head circumference, and estimated fetal weight were not acceptable predictors of twin

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...

Effects of psychosocial characteristics of work on pregnancy outcomes: a critical review.

PubMed

Mutambudzi, Miriam; Meyer, John D; Warren, Nicholas; Reisine, Susan

2011-05-01

Birth outcomes may influence subsequent susceptibility to chronic diseases. With the increased number of women who continue to work during pregnancy, occupational stress has been hypothesized to be a potential contributor to adverse reproductive health outcomes. The Job Demand and Control model has been primarily used in investigating associations between work-related stress and outcomes such as preterm delivery, low birth weight, and spontaneous abortion. A literature review of occupational factors that have been associated with adverse reproductive outcomes was conducted. In studies assessing preterm delivery and low birth weight, some evidence has suggested a modest association with work-related stress but has not been conclusive. In the literature on psychosocial characteristics of work and spontaneous abortion, job strain alone was often not associated with adverse outcomes. However the presence of other risk factors resulted in a synergistic effect which strengthened the odds of an adverse outcome. Future studies should use a prospective design with a large study sample, in which work-related stress exposure data are collected before or in the early stages of the pregnancy. In addition, future research should measure psychosocial characteristics of work both objectively and subjectively.

Review of hazards to female reproductive health in veterinary practice.

PubMed

Scheftel, Joni M; Elchos, Brigid L; Rubin, Carol S; Decker, John A

2017-04-15

OBJECTIVE To review publications that address female reproductive health hazards in veterinary practice, summarize best practices to mitigate reproductive risks, and identify current knowledge gaps. DESIGN Systematized review. SAMPLE English-language articles describing chemical, biological, and physical hazards present in the veterinary workplace and associations with adverse reproductive outcomes or recommendations for minimizing risks to female reproductive health. PROCEDURES Searches of the CAB abstracts database were performed in July 2012 and in May 2015 with the following search terms: veterinarians AND occupational hazards and vets.id AND occupational hazards.sh. Searches of the PubMed database were conducted in November 2012 and in May 2015 with the following medical subject heading terms: occupational exposure AND veterinarians; anesthetics, inhalation/adverse effects AND veterinarians; risk factors AND pregnancy AND veterinarians; pregnancy outcome AND veterinarians; and animal technicians AND occupational exposure. Two additional PubMed searches were completed in January 2016 with the terms disinfectants/toxicity AND female AND fertility/drug effects and veterinarians/psychology AND stress, psychological. No date limits were applied to searches. RESULTS 4 sources supporting demographic trends in veterinary medicine and 118 resources reporting potential hazards to female reproductive health were identified. Reported hazards included exposure to anesthetic gases, radiation, antineoplastic drugs, and reproductive hormones; physically demanding work; prolonged standing; and zoonoses. CONCLUSIONS AND CLINICAL RELEVANCE Demographic information suggested that an increasing number of women of reproductive age will be exposed to chemical, biological, and physical hazards in veterinary practice. Information on reproductive health hazards and minimizing risk, with emphasis on developing a safety-focused work culture for all personnel, should be discussed starting

Review of hazards to female reproductive health in veterinary practice

PubMed Central

Scheftel, Joni M.; Elchos, Brigid L.; Rubin, Carol S.; Decker, John A.

2017-01-01

OBJECTIVE To review publications that address female reproductive health hazards in veterinary practice, summarize best practices to mitigate reproductive risks, and identify current knowledge gaps. DESIGN Systematized review. SAMPLE English-language articles describing chemical, biological, and physical hazards present in the veterinary workplace and associations with adverse reproductive outcomes or recommendations for minimizing risks to female reproductive health. PROCEDURES Searches of the CAB abstracts database were performed in July 2012 and in May 2015 with the following search terms: veterinarians AND occupational hazards and vets.id AND occupational hazards.sh. Searches of the PubMed database were conducted in November 2012 and in May 2015 with the following medical subject heading terms: occupational exposure AND veterinarians; anesthetics, inhalation/adverse effects AND veterinarians; risk factors AND pregnancy AND veterinarians; pregnancy outcome AND veterinarians; and animal technicians AND occupational exposure. Two additional PubMed searches were completed in January 2016 with the terms disinfectants/toxicity AND female AND fertility/drug effects and veterinarians/psychology AND stress, psychological. No date limits were applied to searches. RESULTS 4 sources supporting demographic trends in veterinary medicine and 118 resources reporting potential hazards to female reproductive health were identified. Reported hazards included exposure to anesthetic gases, radiation, antineoplastic drugs, and reproductive hormones; physically demanding work; prolonged standing; and zoonoses. CONCLUSIONS AND CLINICAL RELEVANCE Demographic information suggested that an increasing number of women of reproductive age will be exposed to chemical, biological, and physical hazards in veterinary practice. Information on reproductive health hazards and minimizing risk, with emphasis on developing a safety-focused work culture for all personnel, should be discussed starting

Developing and applying the adverse outcome pathway concept for understanding and predicting neurotoxicity

PubMed Central

Bal-Price, Anna; Lein, Pamela J.; Keil, Kimberly P.; Sethi, Sunjay; Shafer, Timothy; Barenys, Marta; Fritsche, Ellen; Sachana, Magdalini; Meek, M.E. (Bette)

2016-01-01

The Adverse Outcome Pathway (AOP) concept has recently been proposed to support a paradigm shift in regulatory toxicology testing and risk assessment. This concept is similar to the Mode of Action (MOA), in that it describes a sequence of measurable key events triggered by a molecular initiating event in which a stressor interacts with a biological target. The resulting cascade of key events includes molecular, cellular, structural and functional changes in biological systems, resulting in a measurable adverse outcome. Thereby, an AOP ideally provides information relevant to chemical structure-activity relationships as a basis for predicting effects of structurally similar compounds. AOPs could potentially also form the basis for qualitative and quantitative predictive modeling of the human adverse outcome resulting from molecular initiating or other key events for which higher-throughput testing methods are available or can be developed. A variety of cellular and molecular processes are known to be critical for normal function of the central (CNS) and peripheral nervous systems (PNS). Because of the biological and functional complexity of the CNS and PNS, it has been challenging to establish causative links and quantitative relationships between key events that comprise the pathways leading from chemical exposure to an adverse outcome in the nervous system. Following introduction of the principles of MOA and AOPs, examples of potential or putative adverse outcome pathways specific for developmental or adult neurotoxicity are summarized and aspects of their assessment considered. Their possible application in developing mechanistically informed Integrated Approaches to Testing and Assessment (IATA) is also discussed. PMID:27212452

Urinary Phthalate Metabolite Concentrations and Reproductive Outcomes among Women Undergoing in Vitro Fertilization: Results from the EARTH Study

PubMed Central

Hauser, Russ; Gaskins, Audrey J.; Souter, Irene; Smith, Kristen W.; Dodge, Laura E.; Ehrlich, Shelley; Meeker, John D.; Calafat, Antonia M.; Williams, Paige L.

2015-01-01

Background: Evidence from both animal and human studies suggests that exposure to phthalates may be associated with adverse female reproductive outcomes. Objective: We evaluated the associations between urinary concentrations of phthalate metabolites and outcomes of assisted reproductive technologies (ART). Methods: This analysis included 256 women enrolled in the Environment and Reproductive Health (EARTH) prospective cohort study (2004–2012) who provided one to two urine samples per cycle before oocyte retrieval. We measured 11 urinary phthalate metabolites [mono(2-ethylhexyl) phthalate (MEHP), mono(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), mono(2-ethyl-5-oxohexyl) phthalate (MEOHP), mono(2-ethyl-5-carboxypentyl) phthalate (MECPP), mono-isobutyl phthalate (MiBP), mono-n-butyl phthalate (MBP), monobenzyl phthalate (MBzP), monoethyl phthalate (MEP), monocarboxyisooctyl phthalate (MCOP), monocarboxyisononyl phthalate (MCNP), and mono(3-carboxypropyl) phthalate (MCPP)]. We used generalized linear mixed models to evaluate the association of urinary phthalate metabolites with in vitro fertilization (IVF) outcomes, accounting for multiple IVF cycles per woman. Results: In multivariate models, women in the highest as compared with lowest quartile of MEHP, MEHHP, MEOHP, MECPP, ΣDEHP (MEHP + MEHHP + MEOHP + MECPP), and MCNP had lower oocyte yield. Similarly, the number of mature (MII) oocytes retrieved was lower in the highest versus lowest quartile for these same phthalate metabolites. The adjusted differences (95% CI) in proportion of cycles resulting in clinical pregnancy and live birth between women in the fourth versus first quartile of ΣDEHP were –0.19 (–0.29, –0.08) and –0.19 (–0.28, –0.08), respectively, and there was also a lower proportion of cycles resulting in clinical pregnancy and live birth for individual DEHP metabolites. Conclusions: Urinary concentrations of DEHP metabolites were inversely associated with oocyte yield, clinical pregnancy

Association of maternal periodontal health with adverse pregnancy outcome.

PubMed

Kumar, Ashok; Basra, Minu; Begum, Nargis; Rani, Vigya; Prasad, Sudha; Lamba, Arundeep Kaur; Verma, Mahesh; Agarwal, Sarita; Sharma, Shashi

2013-01-01

The present study aims to determine the association of periodontal disease (identified early in pregnancy) and adverse pregnancy outcomes in a North Indian population.   A total of 340 primigravida women, aged 20-35 years with single live pregnancy were recruited at 14-20 weeks period of gestation from the antenatal clinic. These women had undergone periodontal examination at time of recruitment. The pregnancy outcomes were recorded. Out of 340 primigravida women, 147 (43.23%) women had gingivitis and 61 (17.94%) women had periodontitis. Periodontitis was found to be significantly associated with pre-eclampsia, intrauterine growth restriction, preterm delivery, and low birthweight with odds ratios (95% confidence interval) of 7.48 (2.72-22.42), 3.35 (1.20-9.55), 2.72 (1.30-5.68) and 3.03 (1.53-5.97), respectively. The study shows a significant association between periodontitis (but not with gingivitis) and adverse pregnancy outcomes. Maternal periodontitis is associated with an increased risk of pre-eclampsia, intrauterine growth restriction, preterm delivery and low birthweight infants. © 2012 The Authors. Journal of Obstetrics and Gynaecology Research © 2012 Japan Society of Obstetrics and Gynecology.

Maternal language and adverse birth outcomes in a statewide analysis.

PubMed

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

2016-01-01

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

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

PubMed

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

2008-05-01

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

Cytomegalovirus seroprevalence in pregnant women and association with adverse pregnancy/neonatal outcomes in Jiangsu Province, China.

PubMed

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

2014-01-01

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. 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. 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. 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.

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

Aflatoxin Exposure During Pregnancy, Maternal Anemia, and Adverse Birth Outcomes

PubMed Central

Smith, Laura E.; Prendergast, Andrew J.; Turner, Paul C.; Humphrey, Jean H.; Stoltzfus, Rebecca J.

2017-01-01

Pregnant women and their developing fetuses are vulnerable to multiple environmental insults, including exposure to aflatoxin, a mycotoxin that may contaminate as much as 25% of the world food supply. We reviewed and integrated findings from studies of aflatoxin exposure during pregnancy and evaluated potential links to adverse pregnancy outcomes. We identified 27 studies (10 human cross-sectional studies and 17 animal studies) assessing the relationship between aflatoxin exposure and adverse birth outcomes or anemia. Findings suggest that aflatoxin exposure during pregnancy may impair fetal growth. Only one human study investigated aflatoxin exposure and prematurity, and no studies investigated its relationship with pregnancy loss, but animal studies suggest aflatoxin exposure may increase risk for prematurity and pregnancy loss. The fetus could be affected by maternal aflatoxin exposure through direct toxicity as well as indirect toxicity, via maternal systemic inflammation, impaired placental growth, or elevation of placental cytokines. The cytotoxic and systemic effects of aflatoxin could plausibly mediate maternal anemia, intrauterine growth restriction, fetal loss, and preterm birth. Given the widespread exposure to this toxin in developing countries, longitudinal studies in pregnant women are needed to provide stronger evidence for the role of aflatoxin in adverse pregnancy outcomes, and to explore biological mechanisms. Potential pathways for intervention to reduce aflatoxin exposure are urgently needed, and this might reduce the global burden of stillbirth, preterm birth, and low birthweight. PMID:28500823

Aflatoxin Exposure During Pregnancy, Maternal Anemia, and Adverse Birth Outcomes.

PubMed

Smith, Laura E; Prendergast, Andrew J; Turner, Paul C; Humphrey, Jean H; Stoltzfus, Rebecca J

2017-04-01

AbstractPregnant women and their developing fetuses are vulnerable to multiple environmental insults, including exposure to aflatoxin, a mycotoxin that may contaminate as much as 25% of the world food supply. We reviewed and integrated findings from studies of aflatoxin exposure during pregnancy and evaluated potential links to adverse pregnancy outcomes. We identified 27 studies (10 human cross-sectional studies and 17 animal studies) assessing the relationship between aflatoxin exposure and adverse birth outcomes or anemia. Findings suggest that aflatoxin exposure during pregnancy may impair fetal growth. Only one human study investigated aflatoxin exposure and prematurity, and no studies investigated its relationship with pregnancy loss, but animal studies suggest aflatoxin exposure may increase risk for prematurity and pregnancy loss. The fetus could be affected by maternal aflatoxin exposure through direct toxicity as well as indirect toxicity, via maternal systemic inflammation, impaired placental growth, or elevation of placental cytokines. The cytotoxic and systemic effects of aflatoxin could plausibly mediate maternal anemia, intrauterine growth restriction, fetal loss, and preterm birth. Given the widespread exposure to this toxin in developing countries, longitudinal studies in pregnant women are needed to provide stronger evidence for the role of aflatoxin in adverse pregnancy outcomes, and to explore biological mechanisms. Potential pathways for intervention to reduce aflatoxin exposure are urgently needed, and this might reduce the global burden of stillbirth, preterm birth, and low birthweight.

Adverse Pregnancy Outcomes Among Women with Prior Spontaneous or Induced Abortions

PubMed Central

Makhlouf, Michel A; Clifton, Rebecca G.; Roberts, James M.; Myatt, Leslie; Hauth, John C.; Leveno, Kenneth J.; Varner, Michael W.; Thorp, John M.; Mercer, Brian M.; Peaceman, Alan M.; Ramin, Susan M.; Iams, Jay D.; Sciscione, Anthony; Tolosa, Jorge E.; Sorokin, Yoram

2014-01-01

OBJECTIVE To determine whether prior spontaneous (SAB) or induced (IAB) abortions, or the inter-pregnancy interval are associated with subsequent adverse pregnancy outcomes in nulliparous women. METHODS We performed a secondary analysis of data collected from nulliparous women enrolled in a completed trial of vitamins C and E or placebo for preeclampsia prevention. Adjusted odds ratios for maternal and fetal outcomes were determined for nulliparous women with prior SABs and IABs as compared to primigravid participants. RESULTS Compared with primigravidas, women with one prior SAB were at increased risk for perinatal death (OR 1.5; 95% CI 1.1–2.3) in subsequent pregnancies. Two or more SABs were associated with an increased risk for spontaneous preterm birth (OR 2.6, 95% CI 1.7–4.0), preterm PROM (OR 2.9, 95% CI 1.6–5.3) and perinatal death (OR 2.8, 95% CI 1.5–5.3). Women with one previous IAB had higher rates of spontaneous preterm birth (OR 1.4, 95% CI 1.0–1.9) and preterm PROM (OR 2.0, 95% CI 1.4–3.0). An inter-pregnancy interval less than 6 months after SAB was not associated with adverse outcomes. CONCLUSION Nulliparous women with a history of SAB or IAB, especially multiple SABs, are at increased risk for adverse pregnancy outcomes. PMID:24347257

Alcohol, drugs, caffeine, tobacco, and environmental contaminant exposure: reproductive health consequences and clinical implications.

PubMed

Sadeu, J C; Hughes, Claude L; Agarwal, Sanjay; Foster, Warren G

2010-08-01

Reproductive function and fertility are thought to be compromised by behaviors such as cigarette smoking, substance abuse, and alcohol consumption; however, the strength of these associations are uncertain. Furthermore, the reproductive system is thought to be under attack from exposure to environmental contaminants, particularly those chemicals shown to affect endocrine homeostasis. The relationship between exposure to environmental contaminants and adverse effects on human reproductive health are frequently debated in the scientific literature and these controversies have spread into the lay press drawing increased public and regulatory attention. Therefore, the objective of the present review was to critically evaluate the literature concerning the relationship between lifestyle exposures and adverse effects on fertility as well as examining the evidence for a role of environmental contaminants in the purported decline of semen quality and the pathophysiology of subfertility, polycystic ovarian syndrome, and endometriosis. The authors conclude that whereas cigarette smoking is strongly associated with adverse reproductive outcomes, high-level exposures to other lifestyle factors are only weakly linked with negative fertility impacts. Finally, there is no compelling evidence that environmental contaminants, at concentrations representative of the levels measured in contemporary biomonitoring studies, have any effect, positive or negative, on reproductive health in the general population. Further research using prospective study designs with robust sample sizes are needed to evaluate testable hypotheses that address the relationship between exposure and adverse reproductive health effects.

Adverse outcome pathway (AOP) development and evaluation ...

EPA Pesticide Factsheets

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 measured in high throughput toxicity testing and the organism or population-level events that are commonly relevant in defining risk. Recognizing the importance of this emerging framework, the Organisation for Economic Co-operation and Development (OECD) launched a program to support the development, documentation and consideration of AOPs by the international community in 2012 (http://www.oecd.org/chemicalsafety/testing/adverse-outcome-pathways-molecular-screening-and-toxicogenomics.htm). In 2014, a handbook (https://aopkb.org/common/AOP_Handbook.pdf) was developed to guide users in the documentation and evaluation of AOPs and their entry into an official knowledgebase. The handbook draws on longstanding experience in consideration of mechanistic data (e.g., mode of action analysis) to inform risk assessment. To further assist users, a training program was developed by members of the OECD Extended Advisory Group to teach users the basic principles of AOP development and the best practices as outlined in the OECD AOP handbook. Training sessions began in early 2015, and this course will provide training for interested SOT scientists. Following this course, all participants will be familiar w

Frequency, Risk Factors, and Adverse Fetomaternal Outcomes of Placenta Previa in Northern Tanzania

PubMed Central

Senkoro, Elizabeth Eliet; Mwanamsangu, Amasha H.; Chuwa, Fransisca Seraphin; Msuya, Sia Emmanuel; Mnali, Oresta Peter

2017-01-01

Background and Objective. Placenta previa (PP) is a potential risk factor for obstetric hemorrhage, which is a major cause of fetomaternal morbidity and mortality in developing countries. This study aimed to determine frequency, risk factors, and adverse fetomaternal outcomes of placenta previa in Northern Tanzania. Methodology. A retrospective cohort study was conducted using maternally-linked data from Kilimanjaro Christian Medical Centre birth registry spanning 2000 to 2015. All women who gave birth to singleton infants were studied. Adjusted odds ratios (ORs) with 95% confidence intervals for risk factors and adverse fetomaternal outcomes associated with PP were estimated in multivariable logistic regression models. Result. A total of 47,686 singleton deliveries were analyzed. Of these, the frequency of PP was 0.6%. Notable significant risk factors for PP included gynecological diseases, alcohol consumption during pregnancy, malpresentation, and gravidity ≥5. Adverse maternal outcomes were postpartum haemorrhage, antepartum haemorrhage, and Caesarean delivery. PP increased odds of fetal Malpresentation and early neonatal death. Conclusion. The prevalence of PP was comparable to that found in past research. Multiple independent risk factors were identified. PP was found to have associations with several adverse fetomaternal outcomes. Early identification of women at risk of PP may help clinicians prevent such complications. PMID:28321338

Inflammatory Bowel Disease: Influence and Implications in Reproduction

PubMed Central

Glover, Louise E.; Fennimore, Blair; Wingfield, Mary

2016-01-01

The incidence and prevalence of inflammatory bowel disease (IBD) continues to rise with time, signifying its emergence as a global disease. Clinical onset of IBD, comprising Crohn’s disease and ulcerative colitis, typically occurs prior to or at peak reproductive age. Although active disease in female patients is associated with reduced fertility and adverse obstetric outcomes in pregnancy, the molecular mechanisms underlying this altered reproductive course, as well as its impact on IBD transmission to offspring, remain poorly understood. Clinical and experimental studies have now begun to elucidate the hormonal, environmental and microbial factors that modulate immune-reproductive crosstalk in IBD, and define their impact on maternal health, fetal development and heritability of disease risk. Evolving insight into maternal-fetal imprinting in IBD has important implications for patient counseling and disease management during pregnancy, and may help predict clinical outcomes for both mother and child. PMID:27537054

Urinary tract infection and adverse outcome of pregnancy.

PubMed

Dimetry, Shaira R; El-Tokhy, Hanan M; Abdo, Nagla M; Ebrahim, Moustafa A; Eissa, Mohammed

2007-01-01

Urinary tract infections (UTIs) during pregnancy are among the commonest health problems world wide, specially in developing countries, including Egypt. It has several adverse outcomes not only on the mother but also on the fetus as well.. The aim of this study is to determine the incidence of UTIs during pregnancy, study the main risk factors associated with such infections and find the impact of these infections on some pregnancy outcomes namely the gestational age and birth weight. A follow-up study on 249 pregnant women attending the ante natal care clinic at Zagazig university hospital. They were recruited over a period from 1st of September to 30th of or November, 2005. The outcome could be recorded for 201 of them. Data were collected through a pretested questionnaire, repeated urine analyses and recording of outcome of pregnancy. The study revealed that the incidence of UTIs during pregnancy was 31.3%. The commonest organisms were Klebsiella and E-coli. Several socio-demographic characteristics were found significantly associated with UTIs, age being 30 years and more, illiterates and low educational level, low socio-economic level and those with unsatisfactory personal hygiene and those using underwear clothes other than cotton. Significant associations with UTIs were also found in multigravidae 4th and more, those having more than one child and those who previously suffered UTIs. The only predicting variable with UTIs was low socio-economic level. The study revealed that the probability of delivering premature infants and low birth weights was significantly higher among those who experienced UTIs during pregnancy. Multivariate analysis revealed that UTI was one of the main contributors to pre-mature deliveries. Urinary tract infections with pregnancy still constitute a big problem with high incidence. It has a great impact on pregnancy outcome mainly pre-mature labor. So, the study recommends health education about personal hygiene, repeated urine

The future trajectory of adverse outcome pathways: a commentary.

PubMed

Sewell, Fiona; Gellatly, Nichola; Beaumont, Maria; Burden, Natalie; Currie, Richard; de Haan, Lolke; Hutchinson, Thomas H; Jacobs, Miriam; Mahony, Catherine; Malcomber, Ian; Mehta, Jyotigna; Whale, Graham; Kimber, Ian

2018-04-01

The advent of adverse outcome pathways (AOPs) has provided a new lexicon for description of mechanistic toxicology, and a renewed enthusiasm for exploring modes of action resulting in adverse health and environmental effects. In addition, AOPs have been used successfully as a framework for the design and development of non-animal approaches to toxicity testing. Although the value of AOPs is widely recognised, there remain challenges and opportunities associated with their use in practise. The purpose of this article is to consider specifically how the future trajectory of AOPs may provide a basis for addressing some of those challenges and opportunities.

Early Imaging and Adverse Neurodevelopmental Outcome in Asphyxiated Newborns Treated With Hypothermia.

PubMed

Al Amrani, Fatema; Kwan, Saskia; Gilbert, Guillaume; Saint-Martin, Christine; Shevell, Michael; Wintermark, Pia

2017-08-01

Brain injury can be identified as early as day two of life in asphyxiated newborns treated with hypothermia, when using diffusion magnetic resonance imaging (MRI). However, it remains unclear whether these diffusion changes can predict future neurodevelopment. This study aimed to determine whether abnormal early diffusion changes in newborns treated with hypothermia are associated with adverse neurodevelopmental outcome at age two years. Asphyxiated newborns treated with hypothermia were enrolled prospectively. They underwent magnetic resonance imaging (MRI) at specific time points over the first month of life, including diffusion-weighted imaging and diffusion-tensor imaging. Apparent diffusion coefficient (ADC) and fractional anisotropy (FA) values were measured in different regions of interest. Adverse neurodevelopmental outcome was defined as cerebral palsy, global developmental delay, and/or seizure disorder around age two years. ADC and FA values were compared between the newborns developing or not developing adverse outcome. Twenty-nine asphyxiated newborns treated with hypothermia were included. Among the newborns developing adverse outcome, ADC values were significantly decreased on days two to three of life and increased around day ten of life in the thalamus, posterior limb of the internal capsule, and the lentiform nucleus. FA values decreased in the same regions around day 30 of life. These newborns also had increased ADC around day ten of life and around day 30 of life, and decreased FA around day 30 of life in the anterior and posterior white matter. Diffusion changes that were evident as early as day two of life, when the asphyxiated newborns were still treated with hypothermia, were associated with later abnormal neurodevelopmental outcome. Copyright © 2017 Elsevier Inc. All rights reserved.

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

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Peterson, David; Truong, Pauline T.; Parpia, Sameer

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 assessmore » 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

Adverse effects of the anabolic steroid, boldenone undecylenate, on reproductive functions of male rabbits

PubMed Central

Oda, Samah S; El-Ashmawy, Ibrahim M

2012-01-01

Summary This study was conducted to evaluate the adverse effects of the anabolic steroid, boldenone undecylenate (BOL) on reproductive functions of male rabbits. Thirty white New Zealand mature male rabbits were divided into three groups (10 rabbits each). Group A rabbits served as a control group. Group B rabbits received 4.4 mg/kg body weight (bwt) BOL 5% oily solution. Group C rabbits received 8.8 mg/kg bwt BOL. Rabbits were injected intramuscularly twice weekly for two months. BOL had no significant effect on the bwt and bwt gain. Testes and epididymis weights were decreased significantly in the BOL-treated groups. BOL caused significant reduction in serum testosterone level, seminal volume, sperm motility, and sperm count. No abnormalities were detected in the sperm morphology of the BOL-treated groups. Histopathological alterations in the testes and epididymis were marked in the group C rabbits. These results indicate that administration of BOL exerts a significant harmful effect on the reproductive functions of male rabbits. PMID:22583130

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

Reproductive outcomes after multiagent chemotherapy for high-risk gestational trophoblastic neoplasia.

PubMed

Wong, Jacqueline M K; Liu, Dachao; Lurain, John R

2014-01-01

To analyze the reproductive outcomes of women with high-risk gestational trophoblastic neoplasia (GTN) treated with multiagent EMA-CO chemotherapy. Of 212 patients treated with chemotherapy for GTN between 1986 and 2012, 65 (31%) could be contacted by telephone or mail and consented to participate in a questionnaire designed to assess their menstrual and reproduction outcomes. Twenty-four high-risk (HR) and 41 low-risk (LR) patients consented to the study. Fifteen (63%) HR and 34 (83%) LR women had not undergone hysterectomy (p = 0.08). Of the 12 HR and 33 LR women who could recall their menstrual history, all 12 (100%) HR and 32 (97%) LR women resumed menses after chemotherapy. Both groups also had a similar age of menopause (HR, 43.8 years; LR, 48.5 years) (p = 0.19). Although fewer women in the HR group desired to become pregnant after chemotherapy (HR 5/15 [33%] vs. LR 25/34 [74%]) (p = 0.01), 8 HR women (53%) and 29 LR women (85%) eventually became pregnant (p = 0.03), with equivalent live birth rates of 74% and 76%, respectively. Multiagent EMA-CO chemotherapy did not significantly alter menstrual or reproductive outcomes compared to single-agent methotrexate chemotherapy for GTN.

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...

Maternal Language and Adverse Birth Outcomes in a Statewide Analysis

PubMed Central

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

2016-01-01

Background Limited English proficiency is associated with disparities across diverse health outcomes. However, evidence regarding adverse birth outcomes across languages is limited, particularly among US Asian and Pacific Islander populations. The study goal was to consider the relationship of maternal language to birth outcomes using statewide hospitalization data. Methods Detailed discharge data from Hawai‘i childbirth hospitalizations from 2012 (n=11,419) were compared by maternal language (English language or not) for adverse outcomes using descriptive and multivariable log-binomial regression models, controlling for race/ethnicity, age group, and payer. Results Ten percent of mothers spoke a language other than English; 93% of these spoke an Asian or Pacific Islander language. In multivariable models, compared to English speakers non-English speakers had significantly higher risk (adjusted relative risk [ARR]: 2.02; 95% Confidence Interval [CI]: 1.34–3.04) of obstetric trauma in vaginal deliveries without instrumentation. Some significant variation was seen by language for other birth outcomes, including an increased rate of primary Caesarean sections and vaginal births after Caesarean among non-English speakers. Conclusions Non-English speakers had approximately two times higher risk of having an obstetric trauma during a vaginal birth when other factors, including race/ethnicity, were controlled. Non-English speakers also had higher rates of potentially high-risk deliveries. PMID:26361937

Urinary bisphenol A concentrations and early reproductive health outcomes among women undergoing IVF.

PubMed

Ehrlich, Shelley; Williams, Paige L; Missmer, Stacey A; Flaws, Jodi A; Ye, Xiaoyun; Calafat, Antonia M; Petrozza, John C; Wright, Diane; Hauser, Russ

2012-12-01

In women undergoing IVF, are urinary bisphenol A (BPA) concentrations associated with ovarian response and early reproductive outcomes, including oocyte maturation and fertilization, Day 3 embryo quality and blastocyst formation? Higher urinary BPA concentrations were found to be associated with decreased ovarian response, number of fertilized oocytes and decreased blastocyst formation. Experimental animal and in vitro studies have reported associations between BPA exposure and adverse reproductive outcomes. We previously reported an association between urinary BPA and decreased ovarian response [peak serum estradiol (E(2)) and oocyte count at the time of retrieval] in women undergoing IVF; however, there are limited human data on reproductive health outcomes, such as fertilization and embryo development. Prospective preconception cohort study. One hundred and seventy-four women aged 18-45 years and undergoing 237 IVF cycles were recruited at the Massachusetts General Hospital Fertility Center, Boston, MA, USA, between November 2004 and August 2010. These women were followed until they either had a live birth or discontinued treatment. Cryothaw and donor egg cycles were not included in the analysis. Urinary BPA concentrations were measured by online solid-phase extraction-high-performance liquid chromatography-isotope dilution-tandem mass spectrometry. Mixed effect models, poisson regression and multivariate logistic regression models were used wherever appropriate to evaluate the association between cycle-specific urinary BPA concentrations and measures of ovarian response, oocyte maturation (metaphase II), fertilization, embryo quality and cleavage rate. We accounted for correlation among multiple IVF cycles in the same woman using generalized estimating equations. The geometric mean (SD) for urinary BPA concentrations was 1.50 (2.22) µg/l. After adjustment for age and other potential confounders (Day 3 serum FSH, smoking, BMI), there was a significant linear

Ionotropic GABA receptor antagonism-induced adverse outcome pathways for potential neurotoxicity biomarkers.

PubMed

Gong, Ping; Hong, Huixiao; Perkins, Edward J

2015-01-01

Antagonism of ionotropic GABA receptors (iGABARs) can occur at three distinct types of receptor binding sites causing chemically induced epileptic seizures. Here we review three adverse outcome pathways, each characterized by a specific molecular initiating event where an antagonist competitively binds to active sites, negatively modulates allosteric sites or noncompetitively blocks ion channel on the iGABAR. This leads to decreased chloride conductance, followed by depolarization of affected neurons, epilepsy-related death and ultimately decreased population. Supporting evidence for causal linkages from the molecular to population levels is presented and differential sensitivity to iGABAR antagonists in different GABA receptors and organisms discussed. Adverse outcome pathways are poised to become important tools for linking mechanism-based biomarkers to regulated outcomes in next-generation risk assessment.

Metabolic control of oocyte development: linking maternal nutrition and reproductive outcomes

PubMed Central

Liu, Honglin; Gu, Xi; Boots, Christina; Moley, Kelle H.

2015-01-01

Obesity, diabetes, and related metabolic disorders are major health issues worldwide. As the epidemic of metabolic disorders continues, the associated medical comorbidities, including the detrimental impact on reproduction, increase as well. Emerging evidence suggests that the effects of maternal nutrition on reproductive outcomes are likely to be mediated, at least in part, by oocyte metabolism. Well-balanced and timed energy metabolism is critical for optimal development of oocytes. To date, much of our understanding of oocyte metabolism comes from the effects of extrinsic nutrients on oocyte maturation. In contrast, intrinsic regulation of oocyte development by metabolic enzymes, intracellular mediators, and transport systems is less characterized. Specifically, decreased acid transport proteins levels, increased glucose/lipid content and elevated reactive oxygen species in oocytes have been implicated in meiotic defects, organelle dysfunction and epigenetic alteration. Therefore, metabolic disturbances in oocytes may contribute to the diminished reproductive potential experienced by women with metabolic disorders. In-depth research is needed to further explore the underlying mechanisms. This review also discusses several approaches for metabolic analysis. Metabolomic profiling of oocytes, the surrounding granulosa cells, and follicular fluid will uncover the metabolic networks regulating oocyte development, potentially leading to the identification of oocyte quality markers and prevention of reproductive disease and poor outcomes in offspring. PMID:25280482

Adverse pregnancy outcomes among women with prior spontaneous or induced abortions.

PubMed

Makhlouf, Michel A; Clifton, Rebecca G; Roberts, James M; Myatt, Leslie; Hauth, John C; Leveno, Kenneth J; Varner, Michael W; Thorp, John M; Mercer, Brian M; Peaceman, Alan M; Ramin, Susan M; Iams, Jay D; Sciscione, Anthony; Tolosa, Jorge E; Sorokin, Yoram

2014-10-01

The aim of the article is to determine whether prior spontaneous abortion (SAB) or induced abortion (IAB), or the interpregnancy interval are associated with subsequent adverse pregnancy outcomes in nulliparous women. We performed a secondary analysis of data collected from nulliparous women enrolled in a completed trial of vitamins C and E or placebo for preeclampsia prevention. Adjusted odds ratios (ORs) for maternal and fetal outcomes were determined for nulliparous women with prior SABs and IABs as compared with primigravid participants. Compared with primigravidas, women with one prior SAB were at increased risk for perinatal death (adj. OR, 1.5; 95% CI, 1.1-2.3) in subsequent pregnancies. Two or more SABs were associated with an increased risk for spontaneous preterm birth (PTB) (adj. OR, 2.6, 95% CI, 1.7-4.0), preterm premature rupture of membranes (PROM) (adj. OR, 2.9; 95% CI, 1.6-5.3), and perinatal death (adj. OR, 2.8; 95% CI, 1.5-5.3). Women with one previous IAB had higher rates of spontaneous PTB (adj. OR, 1.4; 95% CI, 1.0-1.9) and preterm PROM (OR, 2.0; 95% CI, 1.4-3.0). An interpregnancy interval less than 6 months after SAB was not associated with adverse outcomes. Nulliparous women with a history of SAB or IAB, especially multiple SABs, are at increased risk for adverse pregnancy outcomes. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Magnitude of income-related disparities in adverse perinatal outcomes.

PubMed

Shankardass, Ketan; O'Campo, Patricia; Dodds, Linda; Fahey, John; Joseph, Ks; Morinis, Julia; Allen, Victoria M

2014-03-04

To assess and compare multiple measurements of socioeconomic position (SEP) in order to determine the relationship with adverse perinatal outcomes across various contexts. 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. 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. 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.

Experience of violence and adverse reproductive health outcomes, HIV risks among mobile female sex workers in India

PubMed Central

2011-01-01

Background Female sex workers (FSWs) are a population sub-group most affected by the HIV epidemic in India and elsewhere. Despite research and programmatic attention to FSWs, little is known regarding sex workers' reproductive health and HIV risk in relation to their experiences of violence. This paper therefore aims to understand the linkages between violence and the reproductive health and HIV risks among a group of mobile FSWs in India. Methods Data are drawn from a cross-sectional behavioural survey conducted in 22 districts from four high HIV prevalence states (Andhra Pradesh, Karnataka, Maharashtra, Tamil Nadu) in India between September 2007 and July 2008. The survey sample included 5,498 FSWs who had moved to at least two different places for sex work in the past two years, and are classified as mobile FSWs in the current study. Analyses calculated the prevalence of past year experiences of violence; and adjusted logistic regression models examined the association between violence and reproductive health and HIV risks after controlling for background characteristics and program exposure. Results Approximately one-third of the total mobile FSWs (30.5%, n = 1,676) reported experiencing violence at least once in the past year; 11% reported experiencing physical violence, and 19.5% reported experiencing sexual violence. Results indicate that FSWs who had experienced any violence (physical or sexual) were significantly more likely to be vulnerable to both reproductive health and HIV risks. For example, FSWs who experienced violence were more likely than those who did not experience violence to have experienced a higher number of pregnancies (adjusted odds ratio [OR] = 1.2, 95% confidence interval [CI] = 1.0-1.6), ever experienced pregnancy loss (adjusted OR = 1.4, 95% CI = 1.2-1.6), ever experienced forced termination of pregnancy (adjusted OR = 2.4, 95% CI = 2.0-2.7), experienced multiple forced termination of pregnancies (adjusted OR = 2.2, 95% CI = 1

Experience of violence and adverse reproductive health outcomes, HIV risks among mobile female sex workers in India.

PubMed

Swain, Suvakanta N; Saggurti, Niranjan; Battala, Madhusudana; Verma, Ravi K; Jain, Anrudh K

2011-05-20

Female sex workers (FSWs) are a population sub-group most affected by the HIV epidemic in India and elsewhere. Despite research and programmatic attention to FSWs, little is known regarding sex workers' reproductive health and HIV risk in relation to their experiences of violence. This paper therefore aims to understand the linkages between violence and the reproductive health and HIV risks among a group of mobile FSWs in India. Data are drawn from a cross-sectional behavioural survey conducted in 22 districts from four high HIV prevalence states (Andhra Pradesh, Karnataka, Maharashtra, Tamil Nadu) in India between September 2007 and July 2008. The survey sample included 5,498 FSWs who had moved to at least two different places for sex work in the past two years, and are classified as mobile FSWs in the current study. Analyses calculated the prevalence of past year experiences of violence; and adjusted logistic regression models examined the association between violence and reproductive health and HIV risks after controlling for background characteristics and program exposure. Approximately one-third of the total mobile FSWs (30.5%, n = 1,676) reported experiencing violence at least once in the past year; 11% reported experiencing physical violence, and 19.5% reported experiencing sexual violence. Results indicate that FSWs who had experienced any violence (physical or sexual) were significantly more likely to be vulnerable to both reproductive health and HIV risks. For example, FSWs who experienced violence were more likely than those who did not experience violence to have experienced a higher number of pregnancies (adjusted odds ratio [OR] = 1.2, 95% confidence interval [CI] = 1.0-1.6), ever experienced pregnancy loss (adjusted OR = 1.4, 95% CI = 1.2-1.6), ever experienced forced termination of pregnancy (adjusted OR = 2.4, 95% CI = 2.0-2.7), experienced multiple forced termination of pregnancies (adjusted OR = 2.2, 95% CI = 1.7-2.8), and practice inconsistent

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.

Adverse pregnancy outcomes in women with systemic lupus erythematosus from a multiethnic US cohort: LUMINA (LVI) [corrected].

PubMed

Andrade, R; Sanchez, M L; Alarcón, G S; Fessler, B J; Fernández, M; Bertoli, A M; Apte, M; Vilá, L M; Arango, A M; Reveille, J D

2008-01-01

To study the factors associated with an adverse pregnancy outcome in women with systemic lupus erythematosus (SLE). SLE women from LUMINA of Hispanic, African American and Caucasian ethnicity were studied. Adverse pregnancy outcome was a miscarriage or abortion (<20 weeks), a stillbirth (> or = 20) and/or a moderate to severe preterm-baby (<34 weeks); good outcome was either a mild preterm-baby (> or = 34 weeks) or a full-term baby [C-section or vaginal delivery (38-42 weeks)]. Pregnancies occurring after SLE diagnosis (TD) were included; pregnancy outcome was the unit of analyses. The relationship between selected variables and pregnancy outcomes was examined by univariable and multivariable analyses. Adverse outcomes occurred in 63.7% of 102 pregnancies. In the univariable analyses, Texan Hispanic and African American ethnicities, fewer years of education, higher number of ACR criteria, renal involvement, glucocorticoid exposure and the maximum dose of glucocorticoids used prior to the pregnancy outcome were associated with an adverse pregnancy outcome. Renal involvement was independently associated with an adverse pregnancy outcome [Odds ratio (OR)=5.219 (95% Confidence Interval (CI) 1.416-19.239, p=0.0131] as were the maximum dose of glucocorticoids used prior to the pregnancy outcome (OR=1.028; CI:1.002-1.054; p=0.0315) and fewer years of education (OR=1.204; CI:1.006-1.472; p=0.0437). Ethnicity was not retained in the multivariable model. Renal involvement, the maximum dose of glucocorticoids used prior to pregnancy and fewer years of education were associated with adverse pregnancy outcomes. These data have implications for the management of women with lupus planning to become pregnant.

Associations of neighborhood-level racial residential segregation with adverse pregnancy outcomes.

PubMed

Salow, Arturo D; Pool, Lindsay R; Grobman, William A; Kershaw, Kiarri N

2018-03-01

Previous analyses utilizing birth certificate data have shown environmental factors such as racial residential segregation may contribute to disparities in adverse pregnancy outcomes. However, birth certificate data are ill equipped to reliably differentiate among small for gestational age, spontaneous preterm birth, and medically indicated preterm birth. We sought to utilize data from electronic medical records to determine whether residential segregation among Black women is associated with an increased risk of adverse pregnancy outcomes. The study population was composed of 4770 non-Hispanic Black women who delivered during the years 2009 through 2013 at a single urban medical center. Addresses were geocoded at the level of census tract, and this tract was used to determine the degree of residential segregation for an individual's neighborhood. Residential segregation was measured using the Gi* statistic, a z-score that measures the extent to which the neighborhood racial composition deviates from the composition of the larger surrounding area. The Gi* statistic z-scores were categorized as follows: low (z < 0), medium (z = 0-1.96), and high (z > 1.96). Adverse pregnancy outcomes included overall preterm birth, spontaneous preterm birth, medically indicated preterm birth, and small for gestational age. Hierarchical logistic regression models accounting for clustering by census tract and repeated births among mothers were used to estimate odds ratios of adverse pregnancy outcomes associated with segregation. In high segregation areas, the prevalence of overall preterm birth was significantly higher than that in low segregation areas (15.5% vs 10.7%, respectively; P < .001). Likewise, the prevalence of spontaneous preterm birth and medically indicated preterm birth were higher in high (9.5% and 6.0%) vs low (6.2% and 4.6%) segregation neighborhoods (P < .001 and P = .046, respectively). The associations of high segregation with overall preterm birth (odds

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:…

The Association Between Learning Climate and Adverse Obstetrical Outcomes in 16 Nontertiary Obstetrics-Gynecology Departments in the Netherlands.

PubMed

Smirnova, Alina; Ravelli, Anita C J; Stalmeijer, Renée E; Arah, Onyebuchi A; Heineman, Maas Jan; van der Vleuten, Cees P M; van der Post, Joris A M; Lombarts, Kiki M J M H

2017-12-01

To investigate the association between learning climate and adverse perinatal and maternal outcomes in obstetrics-gynecology departments. The authors analyzed 23,629 births and 103 learning climate evaluations from 16 nontertiary obstetrics-gynecology departments in the Netherlands in 2013. Multilevel logistic regressions were used to calculate the odds of adverse perinatal and maternal outcomes, by learning climate score tertile, adjusting for maternal and department characteristics. Adverse perinatal outcomes included fetal or early neonatal mortality, five-minute Apgar score < 7, or neonatal intensive care unit admission for ≥ 24 hours. Adverse maternal outcomes included postpartum hemorrhage and/or transfusion, death, uterine rupture, or third- or fourth-degree perineal laceration. Bias analyses were conducted to quantify the sensitivity of the results to uncontrolled confounding and selection bias. Learning climate scores were significantly associated with increased odds of adverse perinatal outcomes (aOR 2.06, 95% CI 1.14-3.72). Compared with the lowest tertile, departments in the middle tertile had 46% greater odds of adverse perinatal outcomes (aOR 1.46, 95% CI 1.09-1.94); departments in the highest tertile had 69% greater odds (aOR 1.69, 95% CI 1.24-2.30). Learning climate was not associated with adverse maternal outcomes (middle vs. lowest tertile: OR 1.04, 95% CI 0.93-1.16; highest vs. lowest tertile: OR 0.98, 95% CI 0.88-1.10). Learning climate was associated with significantly increased odds of adverse perinatal, but not maternal, outcomes. Research in similar clinical contexts is needed to replicate these findings and explore potential mechanisms behind these associations.

Adverse Reproductive Health Outcomes and Exposure to Gaseous and Particulate-Matter Air Pollution in Pregnant Women.

PubMed

Wu, Jun; Laurent, Olivier; Li, Lianfa; Hu, Jianlin; Kleeman, Michael

2016-07-01

There is growing epidemiologic evidence of associations between maternal exposure to ambient air pollution and adverse birth outcomes, such as preterm birth (PTB). Recently, a few studies have also reported that exposure to ambient air pollution may also increase the risk of some common pregnancy complications, such as preeclampsia and gestational diabetes mellitus (GDM). Research findings, however, have been mixed. These inconsistent results could reflect genuine differences in the study populations, the study locations, the specific pollutants considered, the designs of the study, its methods of analysis, or random variation. Dr. Jun Wu of the University of California– Irvine, a recipient of HEI’s Walter A. Rosenblith New Investigator Award, and colleagues have examined the association between air pollution and adverse birth and pregnancy outcomes in California women. In addition, they examined the effect modification by socioeconomic status (SES) and other factors. A retrospective nested case–control study was conducted using birth certificate data from about 4.4 million birth records in California from 2001 to 2008. Wu and colleagues analyzed data on low birth weight (LBW) at term (infants born between 37 and 43 weeks of gestation and weighing less than 2500 g), PTB (infants born before 37 weeks of gestation), and preeclampsia (including eclampsia) of the mother during the pregnancy. In addition, they obtained data on GDM for the years 2006– 2008. In the analyses, all outcomes were included as binary variables. Maternal residential addresses at the time of delivery were geocoded, and a large suite of air pollution exposure metrics was considered, such as (1) regulatory monitoring data on concentrations of criteria pollutants NO2, PM2.5 (particulate matter ≤ 2.5 μm in aerodynamic diameter), and ozone (O3) estimated by empirical Bayesian kriging; (2) concentrations of primary and secondary PM2.5 and PM0.1 components and sources estimated by the

Use of Putative Adverse Outcome Pathways for Chemical Hazard Identification

EPA Science Inventory

The Adverse Outcome Pathway (AOP) framework provides a knowledge infrastructure for evaluating health effects of environmental chemicals. In this work we are examining proof-of-concept issues in the development and prospective application of AOPs in chemical safety. Key outputs i...

Practical approaches to adverse outcome pathway (AOP) ...

EPA Pesticide Factsheets

Adverse Outcome Pathways (AOPs) describe toxicant effects as a sequential chain of causally linked events beginning with a molecular perturbation and culminating in an adverse outcome at an individual or population level. Strategies for developing AOPs are still evolving and depend largely on the intended use or motivation for development. Four ecological AOP case studies, which were developed for different purposes, are described herein. In each situation, creation of the AOP began in a manner determined by the initial motivation for its creation, and expanded either to include additional components of the pathway, or to address the domains of applicability in terms of chemical initiators, susceptible species, life stages, etc. From these case studies, some general strategies can be gleaned which a developer may find useful for supporting an existing AOP or creating a new one. Several web-based tools which can aid in AOP assembly, as well as evaluation of weight of evidence for scientific robustness of AOP components are highlighted. The need for AOP development and greater population of AOPs in the online knowledgebase has been widely recognized (e.g., OECD Project 1.29, Knapen et al 2015, Escher et al 2016; Groh et al 2015), but currently there are few AOP developers. To promote broader development of AOPs, and the inclusion of potential developers across various types of institutes and fields of study, this manuscript outlines strategies for initiating

The potential of AOP networks for reproductive and developmental toxicity assay development

EPA Science Inventory

Historically, the prediction of reproductive and early developmental toxicity has largely relied on the use of animals. The Adverse Outcome Pathway (AOP) framework forms a basis for the development of new non-animal test methods. It also provides biological context for mechanisti...

Adverse surgical outcomes in screen-detected ductal carcinoma in situ of the breast.

PubMed

Thomas, Jeremy; Hanby, Andrew; Pinder, Sarah E; Ball, Graham; Lawrence, Gill; Maxwell, Anthony; Wallis, Matthew; Evans, Andrew; Dobson, Hilary; Clements, Karen; Thompson, Alastair

2014-07-01

The Sloane Project is the largest prospective audit of ductal carcinoma in situ (DCIS) worldwide, with over 12,000 patients registered between 2003 and 2012, accounting for 50% of screen-detected DCIS diagnosed in the United Kingdom (UK) over the period of accrual. Complete multidisciplinary data from 8313 patients with screen-detected DCIS were analysed for surgical outcome in relation to key radiological and pathological parameters for the cohort and also by hospital of treatment. Adverse surgical outcomes were defined as either failed breast conservation surgery (BCS) or mastectomy for small lesions (<20mm) (MFSL). Inter-hospital variation was analysed by grouping hospitals into high, medium and low frequency subgroups for these two adverse outcomes. Patients with failed BCS or MFSL together accounted for 49% of all mastectomies. Of 6633 patients embarking on BCS, 799 (12.0%) required mastectomy. MFSL accounted for 510 (21%) of 2479 mastectomy patients. Failed BCS was associated with significant radiological under-estimation of disease extent and MFSL significant radiological over-estimation of disease extent. There was considerable and significant inter-hospital variation in failed BCS (range 3-32%) and MFSL (0-60%) of a hospital's BCS/mastectomy workload respectively. Conversely, there were no differences between the key radiological and pathological parameters in high, medium and low frequency adverse-outcome hospitals. This evidence suggests significant practice variation, not patient factors, is responsible for these adverse surgical outcomes in screen-detected DCIS. The Sloane Project provides an evidence base for future practice benchmarking. Copyright © 2014 Elsevier Ltd. All rights reserved.

Infertility treatment use in relation to selected adverse birth outcomes.

PubMed

Welmerink, Diana B; Voigt, Lynda F; Daling, Janet R; Mueller, Beth A

2010-12-01

To determine whether maternal infertility treatment is associated with adverse outcomes. Population-based cohort study using linked birth certificate-hospital discharge data. Washington State. Live-born singleton infants conceived with infertility treatment between 2003 and 2006 (n = 2,182) and a random sample of live-born singleton infants conceived spontaneously, frequency matched by birth year (n = 10,989). None. Mantel-Haenszel adjusted relative risks (RRs) and 95% confidence intervals (CIs) were computed for low birth weight, delivery at <37 weeks, small for gestational age infants, any malformation, placenta previa, and placenta abruptio. Women with infertility treatment were at increased risk of placental abnormalities, including placenta abruptio (RR, 1.6; 95% CI, 1.1-2.5) and placenta previa (RR, 3.0; 95% CI, 2.0-4.7). Their infants were more likely to be delivered at <37 weeks (RR, 1.7; 95% CI, 1.4-1.9) or weigh <2500 g (RR, 1.4; 95% CI, 1.1-1.7); however, they were not at increased risk of being small for gestational age. An increased risk of malformations was observed in infants born to older women with infertility treatment, but not to younger women. Women using infertility treatment are at increased risk for delivering preterm, placenta previa, and placenta abruptio. Studies with measurement of specific infertility treatments will help identify the mechanisms. Copyright © 2010 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Prenatal exposure to bisphenol a at environmentally relevant doses adversely affects the murine female reproductive tract later in life.

PubMed

Newbold, Retha R; Jefferson, Wendy N; Padilla-Banks, Elizabeth

2009-06-01

Exposure to endocrine-disrupting chemicals during critical developmental periods causes adverse consequences later in life; an example is prenatal exposure to the pharmaceutical diethylstilbestrol (DES). Bisphenol A (BPA), an environmental estrogen used in the synthesis of plastics, is of concern because its chemical structure resembles that of DES, and it is a "high-volume production" chemical with widespread human exposure. In this study we investigated whether prenatal BPA causes long-term adverse effects in female reproductive tissues in an experimental animal model previously shown useful in studying effects of prenatal DES. Timed pregnant CD-1 mice were treated on days 9-16 of gestation with BPA (0.1, 1, 10, 100, or 1,000 mug/kg/day). After delivery, pups were held for 18 months; reproductive tissues were then evaluated. Ovarian cysts were significantly increased in the 1-mug/kg BPA group; ovarian cyst-adenomas were seen in the other three BPA-treated groups but not in corn-oil controls. We observed increased progressive proliferative lesions of the oviduct after BPA treatment, similar to those described in response to DES. Further, although not statistically different from the controls, prominent mesonephric (Wolffian) remnants and squamous metaplasia of the uterus, as well as vaginal adenosis, were present in BPA-treated mice, similar to lesions reported following DES treatment. More severe pathologies observed in some BPA-treated animals included atypical hyperplasia and stromal polyps of the uterus; sarcoma of the uterine cervix; and mammary adenocarcinoma. We did not observe these lesions in controls. These data suggest that BPA causes long-term adverse reproductive and carcinogenic effects if exposure occurs during critical periods of differentiation.

Adverse perinatal outcomes in borderline amniotic fluid index.

PubMed

Jamal, Ashraf; Kazemi, Maryam; Marsoosi, Vajiheh; Eslamian, Laleh

2016-11-01

Normal amniotic fluid predicts normal placental function, fetal growth and fetal well-being. To determine adverse pregnancy outcomes in borderline amniotic fluid index (AFI). Pregnant women (37-40 wks) with diagnosis of borderline AFI between December 2012 and August 2014 were identified. Antepartum, intrapartum and neonatal data were collected and compared with those of pregnant women with normal AFI. An AFI less than 8 and more than 5 cm was defined for borderline AFI. Pregnancy outcomes included Cesarean section for non-reassuring fetal heart rate, meconium stained amniotic fluid, 5-min Apgar score <7, low birth weight, umbilical cord blood pH at term and NICU admission. Gestational age at delivery in pregnancies with borderline AFI was significantly lower than normal AFI. Cesarean section rate for non-reassuring fetal heart rate in women of borderline AFI was significantly higher and there was an increased incidence of birth weight less than 10 th percentile for gestation age in borderline AFI group. Incidence of low Apgar score and low umbilical artery pH in pregnancies with borderline AFI was significantly higher than women with normal AFI. There were no significant difference in the rate of NICU admission and meconium staining in both groups. There are significant differences for adverse pregnancy outcomes , such as Cesarean section due to non-reassuring fetal heart rate, birth weight less than 10 th percentile for gestation age, low 5 min Apgar score and low umbilical artery pH between pregnancies with borderline and normal AFI.

Untreated maternal syphilis and adverse outcomes of pregnancy: a systematic review and meta-analysis

PubMed Central

Kamb, Mary L; Newman, Lori M; Mark, Jennifer; Broutet, Nathalie; Hawkes, Sarah J

2013-01-01

Abstract Objective To perform a systematic review and meta-analysis of reported estimates of adverse pregnancy outcomes among untreated women with syphilis and women without syphilis. Methods PubMed, EMBASE and Cochrane Libraries were searched for literature assessing adverse pregnancy outcomes among untreated women with seroreactivity for Treponema pallidum infection and non-seroreactive women. Adverse pregnancy outcomes were fetal loss or stillbirth, neonatal death, prematurity or low birth weight, clinical evidence of syphilis and infant death. Random-effects meta-analyses were used to calculate pooled estimates of adverse pregnancy outcomes and, where appropriate, heterogeneity was explored in group-specific analyses. Findings Of the 3258 citations identified, only six, all case-control studies, were included in the analysis. Pooled estimates showed that among untreated pregnant women with syphilis, fetal loss and stillbirth were 21% more frequent, neonatal deaths were 9.3% more frequent and prematurity or low birth weight were 5.8% more frequent than among women without syphilis. Of the infants of mothers with untreated syphilis, 15% had clinical evidence of congenital syphilis. The single study that estimated infant death showed a 10% higher frequency among infants of mothers with syphilis. Substantial heterogeneity was found across studies in the estimates of all adverse outcomes for both women with syphilis (66.5% [95% confidence interval, CI: 58.0–74.1]; I2 = 91.8%; P < 0.001) and women without syphilis (14.3% [95% CI: 11.8–17.2]; I2 = 95.9%; P < 0.001). Conclusion Untreated maternal syphilis is associated with adverse pregnancy outcomes. These findings can inform policy decisions on resource allocation for the detection of syphilis and its timely treatment in pregnant women. PMID:23476094

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...

Weight-of-evidence evaluation of an adverse outcome ...

EPA Pesticide Factsheets

Ongoing honey bee colony losses are of significant international concern because of the essential role these insects play in pollinating staple food crops. Chemical and non-chemical stressors both have been implicated as possible contributors to colony failure, however, the potential role of commonly-used neonicotinoid insecticides has emerged as particularly concerning. Neonicotinoids act on the nicotinic acetylcholine receptor (nAChR) to eliminate target pest insects, however, mounting evidence indicates that these chemicals may adversely affect beneficial pollinators, such as the honey bee, via impacts on learning and memory thereby affecting foraging success. However, the mechanisms linking activation of the nAChR to adverse effects on learning and memory are uncertain. Additionally, clear connections between observed impacts on individual bees and colony level effects are lacking. Therefore, the objective of this work was to develop adverse outcome pathways (AOPs) as a means to evaluate the biological plausibility and empirical evidence supporting (or refuting) the linkage between the nAChR and colony level impacts. Development of these AOPs has led to the identification of research gaps which, for example, may be of high priority in understanding how perturbation of pathways involved in neurotransmission can adversely affect honey bee health, causing colony instability and further failure. From this effort, an AOP network also was developed, laying the f

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...

Decreased first trimester PAPP-A is a predictor of adverse pregnancy outcome.

PubMed

Yaron, Yuval; Heifetz, Sigal; Ochshorn, Yifat; Lehavi, Ofer; Orr-Urtreger, Avi

2002-09-01

Low levels of maternal serum pregnancy associated plasma protein-A (PAPP-A) have been linked to chromosome anomalies such as trisomy 21, 13 and 18, triploidy and sex chromosome aneuploidy. Low levels of PAPP-A have also been implicated in spontaneous miscarriage. The purpose of this study was to evaluate whether low levels of first trimester PAPP-A are predictive of other adverse pregnancy outcomes. The study included patients with singleton pregnancies who underwent combined first trimester screening using nuchal translucency (NT) and maternal serum free beta-human chorionic gonadotrophin (free beta-hCG) and PAPP-A at 10-13 weeks' gestation. Patients with chromosome aberrations or fetal anomalies were excluded. Serum marker levels were expressed as gestational age-specific multiples of the median (MoMs). The incidences of various adverse pregnancy outcomes (spontaneous preterm labor, fetal growth restriction (FGR), proteinuric and non-proteinuric pregnancy induced hypertension (PIH), intrauterine fetal demise, oligohydramnios, spontaneous miscarriage and placental abruption) were evaluated, according to maternal PAPP-A MoM levels. Of the 1622 patients in the study, pregnancy complications were observed in 184 (11.3%). Patients with PAPP-A < or =0.25 MoM had significantly higher rates of FGR (RR = 3.12), proteinuric PIH (RR = 6.09), spontaneous miscarriage (RR = 8.76). No statistically significant differences were noted for other adverse outcomes evaluated Women with PAPP-A < or =0.50 MoM also had significantly higher rates of FGR (RR = 3.30) and spontaneous miscarriage (RR = 3.78). We conclude that decreased levels of first trimester maternal serum PAPP-A are predictive not only of chromosome anomalies but also of adverse pregnancy outcome. Copyright 2002 John Wiley & Sons, Ltd.

Parameters Associated with Adverse Fetal Outcomes in Parvovirus B19 Congenital Infection.

PubMed

Agra, Isabela Karine Rodrigues; Amorim Filho, Antonio Gomes; Lin, Lawrence Hsu; Biancolin, Sckarlet Ernandes; Francisco, Rossana Pulcineli Vieira; Brizot, Maria de Lourdes

2017-11-01

Objective  To investigate the clinical and sonographic parameters associated with adverse fetal outcomes in patients with congenital parvovirus B19 infection managed by intrauterine transfusion. Methods  This was a single-center retrospective study conducted from January 2005 to December 2016 that assessed patients with singleton pregnancies with fetal parvovirus infection confirmed by a polymerase chain reaction of the amniotic fluid or fetal blood samples who underwent at least one intrauterine transfusion. The maternal characteristics, sonographic findings and parameters related to intrauterine transfusion were compared between the two groups (recovery/non-recovery), who were categorized based on fetal response after in-utero transfusions. Progression to fetal death or delivery without fetal recovery after the transfusions was considered non-recovery and categorized as an adverse outcome. Results  The final analysis included ten singleton pregnancies: seven of which were categorized into the recovery group and three of which into the non-recovery group. The baseline characteristics were similar between the groups. All fetuses were hydropic at the time of diagnosis. No significant differences related to sonographic or intrauterine transfusion parameters were identified between the groups; however, the non-recovery group tended to have an increased number of sonographic markers and lower fetal hemoglobin and platelet levels before the transfusion. Conclusion  We were unable to firmly establish the clinical or sonographic parameters associated with adverse fetal outcomes in patients with parvovirus infection managed with intrauterine transfusions; however, edema, placental thickening and oligohydramnios may indicate greater fetal compromise and, subsequently, adverse outcomes. However, further studies are necessary, mainly due to the small number of cases analyzed in the present study. Thieme Revinter Publicações Ltda Rio de Janeiro, Brazil.

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

Meningitis With a Negative Cerebrospinal Fluid Gram Stain in Adults: Risk Classification for an Adverse Clinical Outcome

PubMed Central

Khoury, Nabil T.; Hossain, Md Monir; Wootton, Susan H.; Salazar, Lucrecia; Hasbun, Rodrigo

2012-01-01

Objective To derive and validate a risk score for an adverse clinical outcome in adults with meningitis and a negative cerebrospinal fluid (CSF) Gram stain. Patients and Methods We conducted a retrospective study of 567 adults from Houston, Texas, with meningitis evaluated between January 1, 2005, and January 1, 2010. The patients were divided into derivation (N=292) and validation (N=275) cohorts. An adverse clinical outcome was defined as a Glasgow Outcome Scale score of 4 or less. Results Of the 567 patients, 62 (11%) had an adverse clinical outcome. A predictive model was created using 3 baseline variables that were independently associated with an adverse clinical outcome (P<.05): age greater than 60 years, abnormal findings on neurologic examination (altered mental status, focal neurologic deficits, or seizures), and CSF glucose level of less than 2.4975 mmol/L (to convert CSF glucose to mmol/L, multiply by 0.05551). The model classified patients into 2 categories of risk for an adverse clinical outcome—derivation sample: low risk, 0.6% and high risk, 32.8%; P<.001; and validation sample: low risk, 0.5% and high risk, 21.1%; P<.001. Conclusion Adults with meningitis and a negative CSF Gram stain can be accurately stratified for the risk of an adverse clinical outcome using clinical variables available at presentation. PMID:23218086

Effect of Paternal Age on Reproductive Outcomes of Intracytoplasmic Sperm Injection

PubMed Central

Zheng, Haiyan; Liu, Haiying; Huang, Qing; Liu, Jianqiao

2016-01-01

The impact of paternal age on reproduction, especially using assisted reproductive technologies, has not been well studied to date. To investigate the effect of paternal age on reproductive outcomes, here we performed a retrospective analysis of 2,627 intracytoplasmic sperm injection (ICSI) cycles performed at the Reproductive Medicine Center of the Third Affiliated Hospital of Guangzhou Medical University (China) between January 2007 and May 2015. Effect of paternal age on embryo quality [number of fertilized oocytes, 2 pronucleus zygotes (2PNs), viable embryos, and high-quality embryos] was analyzed by multiple linear regression. Relationships between paternal age and pregnancy outcomes were analyzed by binary logistic regression. After adjusting for female age, no association between paternal age and the following parameters of embryo quality was observed: number of fertilized oocytes (B = -0.032; 95% CI -0.069–0.005; P = 0.088), number of 2PNs (B = -0.005; 95% CI -0.044–0.034; P = 0.806), and number of viable embryos (B = -0.025; 95% CI -0.052–0.001; P = 0.062). However, paternal age negatively influenced the number of high-quality embryos (B = -0.020; 95% CI -0.040–0.000; P = 0.045). Moreover, paternal age had no effect on pregnancy outcomes (OR for a 5-year interval), including the rates of clinical pregnancy (OR 0.919; 95% CI 0.839–1.006; P = 0.067), ongoing pregnancy (OR 0.914; 95% CI 0.833–1.003; P = 0.058), early pregnancy loss (OR 1.019; 95% CI 0.823–1.263; P = 0.861), live births (OR 0.916; 95% CI 0.833–1.007; P = 0.070), and preterm births (OR 1.061; 95% CI 0.898–1.254; P = 0.485). Therefore, increased paternal age negatively influences the number of high-quality embryos, but has no effect on pregnancy outcomes in couples undergoing ICSI cycles. However, more studies including men aged over 60 years with a longer-term follow-up are needed. PMID:26901529

[Maternal hemoglobin in Peru: regional differences and its association with adverse perinatal outcomes].

PubMed

Gonzales, Gustavo F; Tapia, Vilma; Gasco, Manuel; Carrillo, Carlos

2011-01-01

To evaluate hemoglobin (Hb) levels in pregnant women from different geographical regions from Peru; to establish anemia and erythrocytocis rates and to establish the role of Hb on adverse perinatal outcomes using the Perinatal Information System (PIS) database of Peruvian Ministry of Health. Data were obtained from 379,816 births of 43 maternity care units between 2000 and 2010. Anemia and erythrocytocis rates were determined in each geographical region as well as rates of adverse perinatal outcomes. To analyze data the STATA program (versión 10.0,Texas, USA) was used. The results were considered significant at p<0.01. Mild anemia rate was higher in the coast (25.8%) and low forest (26.2%). Moderate/severe anemia rate in low forest was 2.6% and at the coast was 1.0%. In the highland, the highest rate of moderate/severe anemia was in the southern highlands (0.6%). The highest rate of erythrocytocis was found in the central highland (23.7%), 11.9% in the southern highland and 9.5% in the north highland. Severe anemia and erythrocytocis were associated with adverse perinatal outcomes. There are differences by Peruvian geographical region in anemia rates. In the central highlands were found the highest rates of erythrocytocis due to hypoxia effect in the high altitudes; however in the southern highlands, erythrocytocis was lower. Severe anemia and erythrocytosis were associated with increased adverse perinatal outcomes.

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...

PRELIMINARY SCREENING FOR THE POTENTIAL OF DRINKING WATER DISINFECTION BYPRODUCTS TO ALTER MALE REPRODUCTION

EPA Science Inventory

There is increasing epidemiologic interest in the role drinking water disinfection byproducts (DBPS) may play in adverse reproductive outcomes such as inability to conceive, spontaneous abortion, and low birth weight. nfortunately, few studies have attempted to determine whether ...

Risk factors for adverse outcomes in older adults with blunt chest trauma: A systematic review.

PubMed

Sawa, Jake; Green, Robert S; Thoma, Brent; Erdogan, Mete; Davis, Philip J

2017-08-11

The objective of this study was to systematically review the published literature for risk factors associated with adverse outcomes in older adults sustaining blunt chest trauma. EMBASE and MEDLINE were searched from inception until March 2017 for prognostic factors associated with adverse outcomes in older adults sustaining blunt chest trauma using a pre-specified search strategy. References were independently screened for inclusion by two reviewers. Study quality was assessed using the Quality in Prognostic Studies tool. Where appropriate, descriptive statistics were used to evaluate study characteristics and predictors of adverse outcomes. Thirteen cohort studies representing 79,313 patients satisfied our selection criteria. Overall, 26 prognostic factors were examined across studies and were reported for morbidity (8 studies), length of stay (7 studies), mortality (6 studies), and loss of independence (1 study). No studies examined patient quality of life or emergency department recidivism. Prognostic factors associated with morbidity and mortality included age, number of rib fractures, and injury severity score. Although age and rib fractures were found to be associated with adverse outcomes in more than 3 studies, meta-analysis was not performed due to heterogeneity amongst included studies in how these variables were measured. While blunt chest wall trauma in older adults is relatively common, the literature on prognostic factors for adverse outcomes in this patient population remains inadequate due to a paucity of high quality studies and lack of consistent reporting standards.

Is polypharmacy an independent risk factor for adverse outcomes after an emergency department visit?

PubMed

Salvi, Fabio; Rossi, Lorena; Lattanzio, Fabrizia; Cherubini, Antonio

2017-03-01

This study aimed at verifying the role of polypharmacy as an independent risk factor for adverse health outcomes in older emergency department (ED) patients. This was a large (n = 2057) sample of older ED patients (≥65 years) participating in an observational cohort study. Polypharmacy and excessive polypharmacy were defined as having 6-9 drug prescriptions and 10 or more drug prescriptions in the last 3 months, respectively. The total number of medication prescriptions was also available. Outcome measures were in-hospital mortality; 30-day ED return; ED revisit, hospital admission, and mortality at 6 months. Logistic and Cox regression models as well as receiver operating characteristic curves using the Youden index and the area under the curve were calculated. Polypharmacy and excessive polypharmacy were present in 624 (30.3 %) and 367 (17.8 %) subjects, respectively. The mean number of prescriptions in the last 3 months was 5.7 (range 0-25) drugs. Polypharmacy and, particularly, excessive polypharmacy were constantly and independently associated with worse outcomes. A cut-off of 6 had the highest value of the Youden Index in predicting the majority of the adverse outcomes considered. Polypharmacy and excessive polypharmacy are independent risk factors for adverse health outcomes after an ED visit. Further studies are needed to clarify whether drug related issues (such as non-compliance, inappropriate or suboptimal prescribing, adverse drug reactions, and drug-drug or drug-disease interactions) or underlying multimorbidity and disease severity, as well as clinical complexity and frailty, are responsible for the negative outcomes associated with polypharmacy.

Risk of poor neonatal outcome at term after medically assisted reproduction: a propensity score-matched study.

PubMed

Ensing, Sabine; Abu-Hanna, Ameen; Roseboom, Tessa J; Repping, Sjoerd; van der Veen, Fulco; Mol, Ben Willem J; Ravelli, Anita C J

2015-08-01

To study risk of birth asphyxia and related morbidity among term singletons born after medically assisted reproduction (MAR). Population cohort study. Not applicable. A total of 1,953,932 term singleton pregnancies selected from a national registry for 1999-2011. None. Primary outcome Apgar score <4; secondary outcomes Apgar score <7, intrauterine fetal death, perinatal mortality, congenital anomalies, small for gestational age, asphyxia related morbidity, and cesarean delivery. The risks of birth asphyxia and related morbidity were calculated in women who conceived either through MAR or spontaneously (SC), with a subgroup analysis for in vitro fertilization (IVF). An additional propensity score matching analysis was performed with matching on multiple maternal baseline covariates (maternal age, ethnicity, socioeconomic status, parity, year of birth, and preexistent diseases). Each MAR pregnancy was matched to three SC controls. Relative to SC, the MAR singletons had an increased risk of adverse neonatal outcomes including Apgar score <4 (adjusted odds ratio [OR] 1.29; 95% CI, 1.14-1.46) and intrauterine fetal death (adjusted OR 1.61; 95% CI, 1.35-1.91). After propensity score matching, the risk of an Apgar score <4 was comparable between MAR and SC singletons (OR 0.99; 95% CI, 0.87-1.14). Cesarean delivery for both fetal distress and nonprogressive labor occurred more among MAR pregnancies compared with SC pregnancies. Term singletons conceived after MAR have an increased risk of morbidity related to birth asphyxia. Because this is mainly due to maternal characteristics, obstetric caregivers should be aware that the increased rates of cesareans reflect the behavior of women and physicians rather than increased perinatal complications. Copyright © 2015 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Doping with anabolic androgenic steroids (AAS): Adverse effects on non-reproductive organs and functions.

PubMed

Nieschlag, Eberhard; Vorona, Elena

2015-09-01

Since the 1970s anabolic androgenic steroids (AAS) have been abused at ever increasing rates in competitive athletics, in recreational sports and in bodybuilding. Exceedingly high doses are often consumed over long periods, in particular by bodybuilders, causing acute or chronic adverse side effects frequently complicated by additional polypharmacy. This review summarizes side effects on non-reproductive organs and functions; effects on male and female reproduction have been recently reviewed in a parallel paper. Among the most striking AAS side effects are increases in haematocrit and coagulation causing thromboembolism, intracardiac thrombosis and stroke as well as other cardiac disturbances including arrhythmias, cardiomyopathies and possibly sudden death. 17α-alkylated AAS are liver toxic leading to cholestasis, peliosis, adenomas and carcinomas. Hyperbilirubinaemia can cause cholemic nephrosis and kidney failure. AAS abuse may induce exaggerated self-confidence, reckless behavior, aggressiveness and psychotic symptoms. AAS withdrawal may be accompanied by depression and suicidal intentions. Since AAS abuse is not or only reluctantly admitted physicians should be aware of the multitude of serious side effects when confronted with unclear symptoms.

Adverse effects of the anabolic steroid, boldenone undecylenate, on reproductive functions of male rabbits.

PubMed

Oda, Samah S; El-Ashmawy, Ibrahim M

2012-06-01

This study was conducted to evaluate the adverse effects of the anabolic steroid, boldenone undecylenate (BOL) on reproductive functions of male rabbits. Thirty white New Zealand mature male rabbits were divided into three groups (10 rabbits each). Group A rabbits served as a control group. Group B rabbits received 4.4 mg/kg body weight (bwt) BOL 5% oily solution. Group C rabbits received 8.8 mg/kg bwt BOL. Rabbits were injected intramuscularly twice weekly for two months. BOL had no significant effect on the bwt and bwt gain. Testes and epididymis weights were decreased significantly in the BOL-treated groups. BOL caused significant reduction in serum testosterone level, seminal volume, sperm motility, and sperm count. No abnormalities were detected in the sperm morphology of the BOL-treated groups. Histopathological alterations in the testes and epididymis were marked in the group C rabbits. These results indicate that administration of BOL exerts a significant harmful effect on the reproductive functions of male rabbits. © 2012 The Authors. International Journal of Experimental Pathology © 2012 International Journal of Experimental Pathology.

Further evidence for periodontal disease as a risk indicator for adverse pregnancy outcomes.

PubMed

Turton, Mervyn; Africa, Charlene W J

2017-06-01

Although there is increasing evidence to suggest an association between periodontal disease and adverse pregnancy outcomes, the issue remains controversial. This study tested the hypothesis that periodontal disease is a risk indicator for preterm delivery of low-birthweight infants. The study sample comprised 443 pregnant women with a mean (± standard deviation) age of 24.13 (±5.30) years. At first visit, maternal oral health status was assessed by the measurement of probing pocket depth and clinical attachment loss, and periodontal status was graded as absent, mild, moderate or severe. An association was sought between pregnancy outcomes and maternal periodontal status. While controlling for other factors, significant associations were found between pregnancy outcomes and maternal periodontal index scores. This study provides further evidence that periodontal disease is a risk indicator for adverse pregnancy outcomes. © 2016 FDI World Dental Federation.

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

PubMed

Vinken, Mathieu

2013-10-04

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. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

A Review of the Effects of Chronic Arsenic Exposure on Adverse Pregnancy Outcomes.

PubMed

Milton, Abul H; Hussain, Sumaira; Akter, Shahnaz; Rahman, Mijanur; Mouly, Tafzila A; Mitchell, Kane

2017-05-23

Exposure to arsenic has a number of known detrimental health effects but impact on pregnancy outcomes is not as widely recognized. This narrative review examines existing epidemiological evidence investigating the association between arsenic exposure via drinking water and adverse pregnancy outcomes. We reviewed published epidemiological studies from around the world on impact of chronic arsenic exposure on spontaneous abortion, stillbirth, neonatal death, post neonatal death, low birth weight and preterm baby. Plausible mechanisms of arsenic toxicity causing adverse pregnancy outcomes were also determined through literature review. There is convincing evidence to support the association between high inorganic arsenic exposure (>50 ppb) and spontaneous abortion, stillbirth and low birth weight. Limitations of certain studies include study design, small sample size, recall constraints and exposure assessment. There needs to be further research investigating the dose metered impact of arsenic exposure on pregnancy outcomes. Further research on impact of low-moderate arsenic concentration exposure on pregnancy outcomes will allow for appropriate public health policy recommendations.

A Review of the Effects of Chronic Arsenic Exposure on Adverse Pregnancy Outcomes

PubMed Central

Milton, Abul H.; Hussain, Sumaira; Akter, Shahnaz; Rahman, Mijanur; Mouly, Tafzila A.; Mitchell, Kane

2017-01-01

Exposure to arsenic has a number of known detrimental health effects but impact on pregnancy outcomes is not as widely recognized. This narrative review examines existing epidemiological evidence investigating the association between arsenic exposure via drinking water and adverse pregnancy outcomes. We reviewed published epidemiological studies from around the world on impact of chronic arsenic exposure on spontaneous abortion, stillbirth, neonatal death, post neonatal death, low birth weight and preterm baby. Plausible mechanisms of arsenic toxicity causing adverse pregnancy outcomes were also determined through literature review. There is convincing evidence to support the association between high inorganic arsenic exposure (>50 ppb) and spontaneous abortion, stillbirth and low birth weight. Limitations of certain studies include study design, small sample size, recall constraints and exposure assessment. There needs to be further research investigating the dose metered impact of arsenic exposure on pregnancy outcomes. Further research on impact of low–moderate arsenic concentration exposure on pregnancy outcomes will allow for appropriate public health policy recommendations. PMID:28545256

Childhood and Adolescent Adversity and Cardiometabolic Outcomes: A Scientific Statement From the American Heart Association.

PubMed

Suglia, Shakira F; Koenen, Karestan C; Boynton-Jarrett, Renée; Chan, Paul S; Clark, Cari J; Danese, Andrea; Faith, Myles S; Goldstein, Benjamin I; Hayman, Laura L; Isasi, Carmen R; Pratt, Charlotte A; Slopen, Natalie; Sumner, Jennifer A; Turer, Aslan; Turer, Christy B; Zachariah, Justin P

2018-01-30

Adverse experiences in childhood and adolescence, defined as subjectively perceived threats to the safety or security of the child's bodily integrity, family, or social structures, are known to be associated with cardiometabolic outcomes over the life course into adulthood. This American Heart Association scientific statement reviews the scientific literature on the influence of childhood adversity on cardiometabolic outcomes that constitute the greatest public health burden in the United States, including obesity, hypertension, type 2 diabetes mellitus, and cardiovascular disease. This statement also conceptually outlines pathways linking adversity to cardiometabolic health, identifies evidence gaps, and provides suggestions for future research to inform practice and policy. We note that, despite a lack of objective agreement on what subjectively qualifies as exposure to childhood adversity and a dearth of prospective studies, substantial evidence documents an association between childhood adversity and cardiometabolic outcomes across the life course. Future studies that focus on mechanisms, resiliency, and vulnerability factors would further strengthen the evidence and provide much-needed information on targets for effective interventions. Given that childhood adversities affect cardiometabolic health and multiple health domains across the life course, interventions that ameliorate these initial upstream exposures may be more appropriate than interventions remediating downstream cardiovascular disease risk factor effects later in life. © 2017 American Heart Association, Inc.

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...

Decline in Child Marriage and Changes in Its Effect on Reproductive Outcomes in Bangladesh

PubMed Central

2012-01-01

This paper explores the decline in child marriage and changes in its effect on reproductive outcomes of Bangladeshi women, using the 2007 Bangladesh Demographic and Health Survey data. Chi-square tests, negative binomial Poisson regression and binary logistic regression were performed in analyzing the data. Overall, 82% of women aged 20-49 years were married-off before 18 years of age, and 63% of the marriages took place before 16 years of age. The incidence of child marriage was significantly less among the young women aged 20-24 years compared to their older counterparts. Among others, women's education appeared as the most significant single determinant of child marriage as well as decline in child marriage. Findings revealed that, after being adjusted for sociodemographic factors, child marriage compared to adult marriage appeared to be significantly associated with lower age at first birth (OR=0.81, 95% CI=76-0.86), higher fertility (IRR=1.45, 95% WCI=1.35-1.55), increased risk of child mortality (IRR=1.64, 95% WCI=1.44-1.87), decreased risk of contraceptive-use before any childbirths (OR=0.56, 95% CI=0.50-0.63), higher risk of giving three or more childbirth (OR=3.94, 95% CI=3.38-4.58), elevated risk of unplanned pregnancies (OR=1.21, 95% CI=1.02-1.45), increased risk of pregnancy termination (OR=1.16, 95% CI=1.00-1.34), and higher risk of the use of any current contraceptive method (OR=1.20, 95% CI=1.06-1.35). Increased enforcement of existing policies is crucial for the prevention of child marriage. Special programmes should be undertaken to keep girls in school for longer period to raise the age of females at first marriage in Bangladesh and thereby reduce the adverse reproductive outcomes. PMID:23082634

Prenatal Exposure to Bisphenol A at Environmentally Relevant Doses Adversely Affects the Murine Female Reproductive Tract Later in Life

PubMed Central

Newbold, Retha R.; Jefferson, Wendy N.; Padilla-Banks, Elizabeth

2009-01-01

Background Exposure to endocrine-disrupting chemicals during critical developmental periods causes adverse consequences later in life; an example is prenatal exposure to the pharmaceutical diethylstilbestrol (DES). Bisphenol A (BPA), an environmental estrogen used in the synthesis of plastics, is of concern because its chemical structure resembles that of DES, and it is a “high-volume production” chemical with widespread human exposure. Objectives In this study we investigated whether prenatal BPA causes long-term adverse effects in female reproductive tissues in an experimental animal model previously shown useful in studying effects of prenatal DES. Methods Timed pregnant CD-1 mice were treated on days 9–16 of gestation with BPA (0.1, 1, 10, 100, or 1,000 μg/kg/day). After delivery, pups were held for 18 months; reproductive tissues were then evaluated. Results Ovarian cysts were significantly increased in the 1-μg/kg BPA group; ovarian cyst-adenomas were seen in the other three BPA-treated groups but not in corn-oil controls. We observed increased progressive proliferative lesions of the oviduct after BPA treatment, similar to those described in response to DES. Further, although not statistically different from the controls, prominent mesonephric (Wolffian) remnants and squamous metaplasia of the uterus, as well as vaginal adenosis, were present in BPA-treated mice, similar to lesions reported following DES treatment. More severe pathologies observed in some BPA-treated animals included atypical hyperplasia and stromal polyps of the uterus; sarcoma of the uterine cervix; and mammary adenocarcinoma. We did not observe these lesions in controls. Conclusions These data suggest that BPA causes long-term adverse reproductive and carcinogenic effects if exposure occurs during critical periods of differentiation. PMID:19590677

Adverse Experiences in Early Childhood and Kindergarten Outcomes.

PubMed

Jimenez, Manuel E; Wade, Roy; Lin, Yong; Morrow, Lesley M; Reichman, Nancy E

2016-02-01

To examine associations between adverse childhood experiences (ACEs) in early childhood and teacher-reported academic and behavioral problems in kindergarten. We conducted a secondary analysis of data from the Fragile Families and Child Wellbeing Study, a national urban birth cohort. Subjects with primary caregiver-reported information on ACE exposures ascertained at 5 years and teacher-reported outcomes at the end of the child's kindergarten year were included. Outcomes included teacher ratings of academic skills, emergent literacy skills, and behavior. We included 8 ACE exposures on the basis of the original Centers for Disease Control and Prevention Kaiser study and created an ACE score by summing individual adversities. We examined the associations between teacher-reported academic and behavioral outcomes and ACE scores by using logistic regression. In the study sample, 1007 children were included. Fifty-five percent had experienced 1 ACE and 12% had experienced ≥ 3. Adjusting for potential confounders, experiencing ≥ 3 ACEs was associated with below-average language and literacy skills (adjusted odds ratio [AORs]: 1.8; 95% confidence interval [CI]: 1.1-2.9) and math skills (AOR: 1.8, 95% CI: 1.1-2.9), poor emergent literacy skills, attention problems (AOR: 3.5, 95% CI: 1.8-6.5), social problems (AOR: 2.7, 95% CI: 1.4-5.0), and aggression (AOR: 2.3, 95% CI: 1.2-4.6). In this study of urban children, experiencing ACEs in early childhood was associated with below-average, teacher-reported academic and literacy skills and behavior problems in kindergarten. These findings underscore the importance of integrated approaches that promote optimal development among vulnerable children. Copyright © 2016 by the American Academy of Pediatrics.

Women's health: periodontitis and its relation to hormonal changes, adverse pregnancy outcomes and osteoporosis.

PubMed

Krejci, Charlene B; Bissada, Nabil F

2012-01-01

To examine the literature with respect to periodontitis and issues specific to women's health, namely, hormonal changes, adverse pregnancy outcomes and osteoporosis. The literature was evaluated to review reported associations between periodontitis and genderspecific issues, namely, hormonal changes, adverse pregnancy outcomes and osteoporosis. Collectively, the literature provided a large body of evidence that supports various associations between periodontitis and hormonal changes, adverse pregnancy outcomes and osteoporosis; however, certain shortcomings were noted with respect to biases involving definitions, sample sizes and confounding variables. Specific cause and effect relationships could not be delineated at this time and neither could definitive treatment interventions. Future research must include randomised controlled trials with consistent definitions, adequate controls and sufficiently large sample sizes in order to clarify specific associations, identify cause and effect relationships, define treatment options and determine treatment interventions which will lessen the untoward effects on the at-risk populations.

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

PubMed

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

2009-01-01

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

Chlamydia trachomatis and Neisseria gonorrhoeae in HIV-infected Pregnant Women and Adverse Infant Outcomes.

PubMed

Adachi, Kristina; Klausner, Jeffrey D; Xu, Jiahong; Ank, Bonnie; Bristow, Claire C; Morgado, Mariza G; Watts, D Heather; Weir, Fred; Persing, David; Mofenson, Lynne M; Veloso, Valdilea G; Pilotto, Jose Henrique; Joao, Esau; Gray, Glenda; Theron, Gerhard; Santos, Breno; Fonseca, Rosana; Kreitchmann, Regis; Pinto, Jorge; Mussi-Pinhata, Marisa M; Ceriotto, Mariana; Machado, Daisy Maria; Bryson, Yvonne J; Grinsztejn, Beatriz; Bastos, Francisco I; Siberry, George; Nielsen-Saines, Karin

2016-08-01

Sexually transmitted infections (STIs) in pregnancy such as Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) may lead to adverse infant outcomes. Individual urine specimens from HIV-infected pregnant women diagnosed with HIV during labor were collected at the time of infant birth and tested by polymerase chain reaction for CT and NG. Infant HIV infection was determined at 3 months with morbidity/mortality assessed through 6 months. Of 1373 maternal urine samples, 277 (20.2%) were positive for CT and/or NG; 249 (18.1%) for CT, 63 (4.6%) for NG and 35 (2.5%) for both CT and NG. HIV infection was diagnosed in 117 (8.5%) infants. Highest rates of adverse outcomes (sepsis, pneumonia, congenital syphilis, septic arthritis, conjunctivitis, low birth weight, preterm delivery and death) were noted in infants of women with CT and NG (23/35, 65.7%) compared with NG (16/28, 57.1%), CT (84/214, 39.3%) and no STI (405/1096, 37%, P = 0.001). Death (11.4% vs. 3%, P = 0.02), low birth weight (42.9% vs. 16.9%, P = 0.001) and preterm delivery (28.6% vs. 10.2%, P = 0.008) were higher among infants of CT and NG-coinfected women. Infants who had any adverse outcome and were born to women with CT and/or NG were 3.5 times more likely to be HIV infected after controlling for maternal syphilis (odds ratio: 3.5, 95% confidence interval: 1.4-8.3). By adjusted multivariate logistic regression, infants born to mothers with any CT and/or NG were 1.35 times more likely to have an adverse outcome (odds ratio, 1.35; 95% confidence interval, 1.03-1.76). STIs in HIV-infected pregnant women are associated with adverse outcomes in HIV-exposed infected and uninfected infants.

Chlamydia trachomatis and Neisseria gonorrhoeae in HIV-infected Pregnant Women and Adverse Infant Outcomes

PubMed Central

Adachi, Kristina; Klausner, Jeffrey D.; Xu, Jiahong; Ank, Bonnie; Bristow, Claire C.; Morgado, Mariza G.; Watts, D. Heather; Weir, Fred; Persing, David; Mofenson, Lynne M.; Veloso, Valdilea G.; Pilotto, Jose Henrique; Joao, Esau; Gray, Glenda; Theron, Gerhard; Santos, Breno; Fonseca, Rosana; Kreitchmann, Regis; Pinto, Jorge; Mussi-Pinhata, Marisa M.; Ceriotto, Mariana; Machado, Daisy Maria; Bryson, Yvonne J.; Grinsztejn, Beatriz; Bastos, Francisco I.; Siberry, George; Nielsen-Saines, Karin

2016-01-01

BACKGROUND Sexually transmitted infections (STIs) in pregnancy such as Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) may lead to adverse infant outcomes. METHODOLOGY Individual urine specimens from HIV-infected pregnant women diagnosed with HIV during labor were collected at the time of infant birth and tested by polymerase chain reaction for CT and NG. Infant HIV infection was determined at 3 months with morbidity/mortality assessed through 6 months. RESULTS Of 1373 maternal urines, 277 (20.2%) were positive for CT and/or NG; 249 (18.1%) for CT, 63 (4.6%) for NG, and 35 (2.5%) for both CT and NG. HIV infection was diagnosed in 117 (8.5%) infants. Highest rates of adverse outcomes (sepsis, pneumonia, congenital syphilis, septic arthritis, conjunctivitis, low birth weight, preterm delivery, death) were noted in infants of women with CT and NG (23/35, 65.7%) compared to NG (16/28, 57.1%), CT (84/214, 39.3%), and no STI (405/1096, 37%, p=0.001). Death (11.4% vs. 3%, p=0.02), low birth weight (42.9% vs. 16.9%, p=0.001), and preterm delivery (28.6% vs. 10.2%, p=0.008) were higher among infants of CT and NG co-infected women. Infants who had any adverse outcome and were born to women with CT and/or NG were 3.5 times more likely to be HIV-infected after controlling for maternal syphilis (OR 3.5, 95% CI 1.4-8.3). By adjusted multivariate logistic regression, infants born to mothers with any CT and/or NG were 1.35 times more likely to have an adverse outcome (OR 1.35, 95% CI 1.03-1.76). CONCLUSION STIs in HIV-infected pregnant women are associated with adverse outcomes in HIV-exposed infected and uninfected infants. PMID:27164464

Treating periodontal disease for preventing adverse birth outcomes in pregnant women.

PubMed

Iheozor-Ejiofor, Zipporah; Middleton, Philippa; Esposito, Marco; Glenny, Anne-Marie

2017-06-12

Periodontal disease has been linked with a number of conditions, such as cardiovascular disease, stroke, diabetes and adverse pregnancy outcomes, all likely through systemic inflammatory pathways. It is common in women of reproductive age and gum conditions tend to worsen during pregnancy. Some evidence from observational studies suggests that periodontal intervention may reduce adverse pregnancy outcomes. There is need for a comprehensive Cochrane review of randomised trials to assess the effect of periodontal treatment on perinatal and maternal health. To assess the effects of treating periodontal disease in pregnant women in order to prevent or reduce perinatal and maternal morbidity and mortality. Cochrane Oral Health's Information Specialist searched the following databases: Cochrane Oral Health's Trials Register (to 6 October 2016), Cochrane Pregnancy and Childbirth's Trials Register (to 7 October 2016), the Cochrane Central Register of Controlled Trials (CENTRAL; 2016, Issue 9) in the Cochrane Library, MEDLINE Ovid (1946 to 6 October 2016), Embase Ovid (1980 to 6 October 2016), and LILACS BIREME Virtual Health Library (Latin American and Caribbean Health Science Information database; 1982 to 6 October 2016). ClinicalTrials.gov and the World Health Organization International Clinical Trials Registry Platform were searched for ongoing trials on 6 October 2016. We placed no restrictions on the language or date of publication when searching the electronic databases. We included all randomised controlled trials (RCTs) investigating the effects of periodontal treatment in preventing or reducing perinatal and maternal morbidity and mortality. We excluded studies where obstetric outcomes were not reported. Two review authors independently screened titles and abstracts and extracted data using a prepiloted data extraction form. Missing data were obtained by contacting authors and risk of bias was assessed using Cochrane's 'Risk of bias' tool. Where appropriate

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

Partner Disengagement from Pregnancy and Adverse Maternal and Infant Outcomes.

PubMed

Urquia, Marcelo L; Pulver, Ariel; Heaman, Maureen I; Ray, Joel G; Daoud, Nihaya; O'Campo, Patricia

2017-03-01

To assess whether partner disengagement from pregnancy is associated with adverse maternal and infant outcomes. We analyzed data from the 2006-2007 Canadian Maternity Experiences Survey, comprising a cross-sectional representative sample of 6,421 childbearing women. Multiple logistic regression assessed the association between adverse outcomes and three indicators of partner disengagement: (1) partner did not want the pregnancy, (2) partner argued more than usual in the year prior to the baby's birth, and (3) partner was absent at the delivery. Of all respondents, 3.8% had partners who did not want the pregnancy, 16.1% argued more than usual with their partner in the past year, and 7.6% had partners who were absent at the delivery. Women whose partner did not want the pregnancy were more likely to report intimate partner violence (IPV) (adjusted odds ratio [AOR] 3.55; 95% confidence interval [95% CI] 2.36-5.14), elevated depressive symptoms in the extended postpartum period (AOR 2.56, 95% CI 1.70-3.83), and nonroutine child healthcare visits after birth (AOR 1.54, 95% CI 1.13-2.11). Women whose partner argued more in the past year had higher odds of IPV (AOR 4.82, 95% CI 3.69-6.30), elevated depressive symptoms in the extended postpartum period (AOR 3.63; 95% CI 2.84-4.64), and nonroutine child healthcare visits (AOR 1.49, 95% CI 1.26-1.77), after adjustment for potential confounders. Partner disengagement is common and is associated with adverse maternal and infant outcomes. Affected women may benefit from special assistance during pregnancy and after delivery.

Anti-prothrombin antibodies are associated with adverse pregnancy outcome.

PubMed

Marozio, Luca; Curti, Antonella; Botta, Giovanni; Canuto, Emilie M; Salton, Loredana; Tavella, Anna Maria; Benedetto, Chiara

2011-11-01

Women with antiphospholipid antibodies (aPL) such as lupus anticoagulant, anticardiolipin antibodies, and anti-β(2) glycoprotein-1 antibodies are at high risk of late pregnancy complications, such as severe pre-eclampsia, placental insufficiency, and fetal loss. It has been observed that aPL consists of a heterogeneous group of antibodies targeting several phospholipid-binding plasma proteins, including also anti-prothrombin (anti-PT), anti-protein S (anti-PS), and anti-protein C (anti-PC) antibodies. Their potential role in late pregnancy complications is not known. The aim of this work was to investigate the association between those autoantibodies and histories for adverse pregnancy outcome. Anti-PT, anti-PS, and anti-PC antibodies were evaluated in 163 patients with previous severe pre-eclampsia, fetal death, and/or placental abruption and in as many women with previous uneventful pregnancies, negative for aPL. The prevalence of anti-PT antibodies was higher in cases than in controls (OR, 95% CI: 10.92, 4.52-26.38). The highest prevalence was observed in subjects with fetal death. Anti-PT antibodies appear to be associated with adverse pregnancy outcome, irrespectively of aPL. © 2011 John Wiley & Sons A/S.

Relationship between paternal somatic health and assisted reproductive technology outcomes.

PubMed

Eisenberg, Michael L; Li, Shufeng; Wise, Lauren A; Lynch, Courtney D; Nakajima, Steven; Meyers, Stuart A; Behr, Barry; Baker, Valerie L

2016-09-01

To study the association between paternal medical comorbidities and the outcomes of assisted reproductive technology (ART). Retrospective cohort study. Academic reproductive medicine center. We analyzed fresh ART cycles uszing freshly ejaculated sperm from the male partner of couples undergoing ART cycles from 2004 until 2014. We recorded patient and partner demographic characteristics. The cohort was linked to hospital billing data to obtain information on selected male partners' comorbidities identified using ICD-9-CM codes. None. Fertilization, clinical pregnancy, miscarriage, implantation, and live-birth rates as well as birth weights and gestational ages. In all, we identified 2,690 men who underwent 5,037 fresh ART cycles. Twenty-seven percent of men had at least one medical diagnosis. Men with nervous system diseases had on average lower pregnancy rates (23% vs. 30%) and live-birth rates (15% vs. 23%) than men without nervous system diseases. Lower fertilization rates were also observed among men with respiratory diseases (61% vs. 64%) and musculoskeletal diseases (61% vs. 64%) relative to those without these diseases. In addition, men with diseases of the endocrine system had smaller children (2,970 vs. 3,210 g) than men without such diseases. Finally, men with mental disorders had children born at an earlier gestational age (36.5 vs. 38.0 weeks). The current report identified a possible relationship between a man's health history and IVF outcomes. As these are potentially modifiable factors, further research should determine whether treatment for men's health conditions may improve or impair IVF outcomes. Copyright © 2016 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Effects of a group-based reproductive management extension programme on key management outcomes affecting reproductive performance.

PubMed

Brownlie, Tom S; Morton, John M; Heuer, Cord; McDougall, Scott

2015-02-01

A group-based reproductive management extension programme has been designed to help managers of dairy herds improve herd reproductive performance. The aims of this study were, firstly, to assess effects of participation by key decision makers (KDMs) in a farmer action group programme in 2009 and 2010 on six key management outcomes (KMOs) that affect reproductive performance over 2 years (2009-2010 and 2010-2011), and secondly, to describe KDM intentions to change management behaviour(s) affecting each management outcome after participation in the programme. Seasonal calving dairy herds from four regions of New Zealand were enrolled in the study. Intentions to modify management behaviour were recorded using the formal written action plans developed during the extension programme. KMOs assessed were calving pattern of the herd, pre-calving heifer liveweight, pre-calving and premating body condition score (BCS), oestrus detection, anoestrus cow management and bull management. Participation was associated with improvements in heifer liveweight, more heifers calving in the first 6 weeks of the seasonal calving period, premating BCS and oestrus detection. No significant effects were observed on anoestrus cow management or bull management. KDMs with greater numbers of proposed actions had lower 6 week in-calf rates in the second study year than KDMs who proposed fewer actions. A more effective strategy to ensure more appropriate objectives is proposed. Strategies to help KDMs to implement proposed actions more successfully should be investigated to improve the programme further. Copyright © 2014 Elsevier Ltd. All rights reserved.

Patient-Reported Disease Activity and Adverse Pregnancy Outcomes in Systemic Lupus Erythematosus and Rheumatoid Arthritis.

PubMed

Harris, Nathaniel; Eudy, Amanda; Clowse, Megan

2018-06-15

While increased rheumatic disease activity during pregnancy has been associated with adverse pregnancy outcomes, this activity is typically assessed by the physician. Little is known, however, about the association between patient-reported measures of disease activity and pregnancy outcomes. Univariate and multivariable regression models were used to assess the relationship between patient and physician-reported measures of disease activity and adverse pregnancy outcomes in 225 patients with lupus or rheumatoid arthritis (RA) enrolled in a prospective registry at a single academic center from 2008-2016. In women with RA, patient-reported disease activity is associated with preterm birth (OR 5.9 (1.5-23.9)), and gestational age (beta -1.5 weeks (-2.6, -0.4 weeks)). The physician assessment of disease activity also predicted preterm (OR 2.1 (1.2-3.5)), small for gestational age births (OR 1.8 (1.03-3.1), and gestational age in weeks (beta -0.6 weeks (-0.9, -0.02 weeks)). On the other hand, SLE patient-reported disease activity measures, including the HAQ, pain or global health measures, are not associated with adverse pregnancy outcomes. However, physician measures of SLE disease activity are associated with preterm birth (OR 2.9 (1.-6.3)), cesarean delivery (OR 2.3 (1.0-5.3)), and preeclampsia (OR 2.8 (1.3-6.3)). The results do not appear to be driven by lupus nephritis or antiphospholipid syndrome. For women with RA, patient-reported measures of disease activity may be useful adjuncts to physician-reported measures in identifying pregnancies at greater risk. In contrast, in SLE, no patient-reported measures were associated with adverse outcomes while physician measures of disease activity helped predict several adverse pregnancy outcomes. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

An Integrative Data Mining Approach to Identify Adverse Outcome Pathway Signatures

EPA Science Inventory

Adverse Outcome Pathways (AOPs) provide a formal framework for describing the mechanisms underlying the toxicity of chemicals in our environment. This process improves our ability to incorporate high-throughput toxicity testing (HTT) results and biomarker information on early key...

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

PubMed

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

2013-04-01

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

Surgical Adverse Events, Risk Management, and Malpractice Outcome: Morbidity and Mortality Review Is Not Enough

PubMed Central

Morris, John A.; Carrillo, Ysela; Jenkins, Judith M.; Smith, Philip W.; Bledsoe, Sandy; Pichert, James; White, Andrew

2003-01-01

Objective To review all admissions (age > 13) to three surgical patient care centers at a single academic medical center between January 1, 1995, and December 6, 1999, for significant surgical adverse events. Summary Background Data Little data exist on the interrelationships between surgical adverse events, risk management, malpractice claims, and resulting indemnity payments to plaintiffs. The authors hypothesized that examination of this process would identify performance improvement opportunities overlooked by standard medical peer review; the risk of litigation would be constant across the three homogeneous patient care centers; and the risk management process would exceed the performance improvement process. Methods Data collected included patient demographics (age, gender, and employment status), hospital financials (hospital charges, costs, and financial class), and outcome. Outcome categories were medical (disability: <1 month, 1–6 months, permanent/death), legal (no legal action, settlement, summary judgment), financial (indemnity payments, legal fees, write-offs), and cause and effect analysis. Cause and effect analysis attempts to identify system failures contributing to adverse outcomes. This was determined by two independent analysts using the 17 Harvard criteria and subdividing these into subsystem causative factors. Results The study group consisted of 130 patients with surgical adverse events resulting in total liabilities of $8.2 million. The incidence of adverse events per 1,000 admissions across the three patient care centers was similar, but indemnity payments per 1,000 admissions varied (cardiothoracic = $30, women’s health = $90, trauma = $520). Patient demographics were not predictive of high-risk subgroups for adverse events or litigation. In terms of medical outcome, 51 patients had permanent disability or death, accounting for 98% of the indemnity payments. In terms of legal outcome, 103 patients received no indemnity payments, 15

Health, equity, and reproductive risks in the workplace.

PubMed

Daniels, C R; Paul, M; Rosofsky, R

1990-01-01

Potential exposure to occupational reproductive hazards raises complex questions regarding health and gender discrimination in the workplace. On the one hand, growing scientific evidence suggests that workplace exposures to either sex can cause a wide range of disorders ranging from infertility to adverse pregnancy outcomes. On the other hand, policies alleging to protect workers from reproductive risks have often reinforced gender inequalities in the workplace. This article sheds new light on this continuing debate through an examination of the policy insights suggested by a recent study of reproductive hazard policies in Massachusetts. In what ways do policies evidenced in this study reflect or differ from historical patterns of protectionism? The article presents a political-legal review of reproductive hazard policies in the workplace, then examines the policy implications of the Massachusetts study, and finally presents the prescriptions for change that are implied by both the historical and contemporary evidence.

Advancing adolescent sexual and reproductive health by promoting healthy relationships.

PubMed

Tharp, Andra Teten; Carter, Marion; Fasula, Amy M; Hatfield-Timajchy, Kendra; Jayne, Paula E; Latzman, Natasha E; Kinsey, Jennine

2013-11-01

The field of public health faces a challenge in preventing adverse sexual and reproductive health outcomes such as sexually transmitted diseases, unintended pregnancy, and dating and sexual violence among adolescents. Innovative approaches are needed to better address these issues. Focusing on healthy relationships is an emerging approach that may be used to promote adolescent sexual and reproductive health. In this report, we discuss the need for innovative and efficient strategies for adolescent sexual and reproductive health, the benefits of a healthy relationships approach, describe the need for a science-based conceptual framework on healthy relationships, and provide some considerations for developing a conceptual framework of healthy relationships in order to move the field of public health forward.

Adverse Outcome Pathways – Organizing Toxicological Information to Improve Decision Making

EPA Science Inventory

The number of chemicals for which environmental regulatory decisions are required far exceeds the current capacity for toxicity testing. High throughput screening (HTS) commonly used for drug discovery has the potential to increase this capacity. The adverse outcome pathway (AOP)...

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.

Intimate partner violence among Egyptian pregnant women: incidence, risk factors, and adverse maternal and fetal outcomes.

PubMed

Ibrahim, Z M; Sayed Ahmed, W A; El-Hamid, S A; Hagras, A M

2015-01-01

To assess incidence and risk factors of intimate partner violence (IPV) during pregnancy among a sample of women from Egypt and to evaluate its impact on maternal and fetal adverse health outcomes. After obtaining ethical approval, a total of 1,857 women aged 18 - 43 years completed the study and were investigated using an interview questionnaire. The questionnaire contains five main items: demographic characteristics of women, intimate partner characteristics, assessment of IPV during current pregnancy, and assessment of maternal as well as fetal/neonatal adverse outcomes. Women were also examined to detect signs of violence and identify injuries. Exposure to IPV during pregnancy was reported among 44.1% of the studied women. Emotional violence was the most common form. Women exposed to violence were of younger age, higher parity, and lower educational level. Their partners were older, less educated, and more likely to be addicted to drugs and alcohol. Women were also found to have significantly higher incidence of adverse pregnancy outcomes (miscarriage, preterm labor, and premature rupture of membrane), and fetal/neonatal adverse outcomes (fetal distress, fetal death, and low birth weight). A total of 297 cases had been exposed to physical violence (15.9%) vs 32.6% and 10% exposed to emotional and sexual violence, respectively. The most common form of physical violence was kicking. Violence during pregnancy is prevalent among Egyptian women. Exposure to violence was a significant risk factor for multiple adverse maternal and fetal health outcomes.

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.

Evaluating PTSD on Reproductive Outcomes: Women Deployed in Iraq and Afghanistan

DTIC Science & Technology

2009-10-01

Center attacks and its effect on pregnancy outcome . Paediatric and Perinatal Epidemiology, 2005. 19(5): p. 334-41. 6. Xiong, X., et al., Exposure ...health system. Thus, the effect of women’s military service on reproductive outcomes is a key concern. Due to the unique situation of women in the... exposure to PTSD as a consequence of deployment is one example of recent concern. A recent study found women who had deployed to Iraq/Afghanistan

The clinical content of preconception care: reproductive history.

PubMed

Stubblefield, Phillip G; Coonrod, Dean V; Reddy, Uma M; Sayegh, Raja; Nicholson, Wanda; Rychlik, Daniel F; Jack, Brian W

2008-12-01

A history of previous birth of a low birthweight infant, previous cesarean sections, multiple previous spontaneous abortions, prior stillbirth, or uterine anomaly identifies women at increased risk for recurrent abortion, preterm birth, or stillbirth. We review the evidence for the potential benefit of reproductive history in identifying strategies for evaluation and treatment to prevent recurrent adverse pregnancy outcome. We offer evidence-based recommendations for management of women with these histories.

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...

Linking mode of action of the model respiratory and photosynthesis uncoupler 3,5-dichlorophenol to adverse outcomes in Lemna minor.

PubMed

Xie, Li; Gomes, Tânia; Solhaug, Knut Asbjørn; Song, You; Tollefsen, Knut Erik

2018-04-01

Standard chemical toxicity testing guidelines using aquatic plant Lemna minor have been developed by several international standardisation organisations. Although being highly useful for regulatory purposes by focusing on traditional adverse endpoints, these tests provide limited information about the toxic mechanisms and modes of action (MoA). The present study aimed to use selected functional assays in L. minor after exposure to 3,5-dichlorophenol (3,5-DCP) as a model to characterise the toxic mechanisms causing growth inhibition and lethality in primary producers. The results demonstrated that 3,5-DCP caused concentration-dependent effects in chloroplasts and mitochondria. Uncoupling of oxidative phosphorylation (OXPHOS), reduction in chlorophyll (Chlorophyll a and b) content, reproduction rate and frond size were the most sensitive endpoints, followed by formation of reactive oxygen species (ROS), lipid peroxidation (LPO), reduction of carotenoid content and impairment of photosynthesis efficiency. Suppression of photosystem II (PSII) efficiency, electron transport rate (ETR), chlorophyll (a and b) contents and oxidative phosphorylation (OXPHOS) were closely correlated while ROS production and LPO were negative correlated with ETR, carotenoid content and growth parameters. A network of conceptual Adverse Outcome Pathways (AOPs) was developed to decipher the causal relationships between molecular, cellular, and apical adverse effects occurring in L. minor to form a basis for future studies with similar compounds. Copyright © 2018 Elsevier B.V. All rights reserved.

Incidence and Predictors of Long-Term Adverse Outcomes in Patients with Rheumatic Mitral Stenosis in Sinus Rhythm.

PubMed

Nachom, Patsadee; Ratanasit, Nithima

2016-04-01

Rheumatic fever and rheumatic heart disease remain important health problems in developing countries. Mitral stenosis (MS) is the most common form of rheumatic heart disease. The aim of this study was to investigate incidence and echocardiographic predictors of long-term adverse outcomes in patients with rheumatic mitral stenosis in sinus rhythm. We retrospectively reviewed medical records of patients diagnosed with isolated rheumatic MS of any severity at Siriraj Hospital between 1996 and 2013. Demographic data, echocardiographic data, and long-term adverse outcomes were collected. Long-term adverse outcomes included all-cause mortality, hospitalization due to heart failure, new-onset atrial fibrillation, and/or embolic stroke during follow-up. One hundred eighty five patients (aged 41.9 ± 13.2 years, 81.1% female) were included during the median follow-up period of 12.6 years (95% CI: 11.2-14.0). MS was classified as mild, moderate, and severe in 8.6%, 2 7.6%, and 63.8% of patients, respectively. Average mitral valve score was 8.25 ± 1.5. Most patients (61.6%) underwent percutaneous balloon mitral valvulotomy. Incidence of long-term adverse outcome was 43.2% (95% CI: 36.0-50.7%) and included mortality in two patients (1.1%, 95% CI: 0.13-3.9%), hospitalization due to heart failure in 20 patients (10.8%, 95% CI: 6.7-16.2%), new-onset atrial fibrillation in 71 patients (38.4%, 95% CI: 31.3-45.8%), and embolic stroke in 14 patients (7.6%, 95% CI: 4.2-12.4%). Echocardiographic parameters associated with long-term adverse outcomes were left atrial dimension greater than 50 mm (HR 2.61, 95% CI: 1.08-6.30; p = 0.03) and left ventricular end-systolic dimension less than 28 mm (HR 3.06, 95% CI: 1.25-7.49; p = 0.01). Long-term adverse outcomes are common in patients with rheumatic MS in sinus rhythm. Long-term adverse outcomes were found to correlate with left atrial dimension and left ventricular end-systolic dimension.

Associations between prenatal arsenic exposure with adverse pregnancy outcome and child mortality.

PubMed

Shih, Yu-Hsuan; Islam, Tariqul; Hore, Samar Kumar; Sarwar, Golam; Shahriar, Mohammad Hasan; Yunus, Mohammad; Graziano, Joseph H; Harjes, Judith; Baron, John A; Parvez, Faruque; Ahsan, Habibul; Argos, Maria

2017-10-01

Chronic arsenic exposure is a public health concern in many parts of the world, with elevated concentrations in groundwater posing a threat to millions of people. Arsenic is associated with various cancers and an array of chronic diseases; however, the relationship with adverse pregnancy outcomes and child mortality is less established. We evaluated associations between individual-level prenatal arsenic exposure with adverse pregnancy outcomes and child mortality in a pregnancy study among 498 women nested in a larger population-based cohort in rural Bangladesh. Creatinine-adjusted urinary total arsenic concentration, a comprehensive measure of exposure from water, food, and air sources, reflective of the prenatal period was available for participants. Self-reported pregnancy outcomes (livebirth, stillbirth, spontaneous/elective abortion) were ascertained. Generalized estimating equations, accounting for multiple pregnancies of participants, were used to estimate odds ratios and 95% confidence intervals in relation to adverse pregnancy outcomes. Vital status of livebirths was subsequently ascertained through November 2015. Cox proportional hazards models were used to estimate hazard ratios and 95% confidence intervals in relation to child mortality. We observed a significant association between prenatal arsenic exposure and the risk of stillbirth (greater than median; adjusted OR = 2.50; 95% CI = 1.04, 6.01). We also observed elevated risk of child mortality (greater than median; adjusted HR = 1.92; 95% CI = 0.78, 4.68) in relation to prenatal arsenic exposure. Prospective studies should continue to evaluate prenatal and early life health effects of arsenic exposure and arsenic remediation strategies for women of child-bearing age. Copyright © 2017 Elsevier Inc. All rights reserved.

Prenatal hazardous substance use and adverse birth outcomes

PubMed Central

Quesada, Odayme; Gotman, Nathan; Howell, Heather B.; Funai, Edmund F.; Rounsaville, Bruce J.; Yonkers, Kimberly A.

2012-01-01

Objective Assess the relative effects of a variety of illicit and licit drugs on risk for adverse birth outcomes. Methods We used data from two large prospective investigations, and a novel analytic method, recursive partitioning class analysis to identify risk factors associated with preterm birth and delivering a small for gestational age infant. Results Compared to cocaine and opiate non-users, cocaine users were 3.53 times as likely (95% Cl: 1.65–7.56; p=0.001) and opiate users 2.86 times as likely (95% Cl: 1.11–7.36; p=0.03) to deliver preterm. The odds of delivering a small for gestational age infant for women who smoked more than two cigarettes daily was 3.74, (95% Cl: 2.47–5.65; p<0.0001) compared to women who smoked two or less cigarettes daily and had one previous child. Similarly, less educated, nulliparous women who smoked two or fewer cigarettes daily were 4.12 times as likely (95% Cl: 2.04–8.34; p<0.0001) to have a small for gestational age infant. Conclusions Among our covariates, prenatal cocaine and opiate use are the predominant risk factors for preterm birth; while tobacco use was the primary risk factor predicting small for gestational age at delivery. Multi-substance use did not substantially increase risk of adverse birth outcomes over these risk factors. PMID:22489543

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

PubMed Central

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

2013-01-01

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

Influence of median surgeon operative duration on adverse outcomes in bariatric surgery.

PubMed

Reames, Bradley N; Bacal, Daniel; Krell, Robert W; Birkmeyer, John D; Birkmeyer, Nancy J O; Finks, Jonathan F

2015-01-01

Evidence suggests that prolonged operative time adversely affects surgical outcomes. However, whether faster surgeons have better outcomes is unclear, as a surgeon׳s speed could reflect skill and efficiency, but may alternatively reflect haste. This study evaluates whether median surgeon operative time is associated with adverse surgical outcomes after laparoscopic Roux-en-Y gastric bypass. We performed a retrospective cohort study using statewide clinical registry data from the years 2006 to 2012. Surgeons were ranked by their median operative time and grouped into terciles. Multivariable logistic regression with robust standard errors was used to evaluate the influence of median surgeon operative time on 30-day surgical outcomes, adjusting for patient and surgeon characteristics, trainee involvement, concurrent procedures, and the complex interaction between these variables. A total of 16,344 patients underwent surgery during the study period. Compared to surgeons in the fastest tercile, slow surgeons required 53 additional minutes to complete a gastric bypass procedure (median [interquartile range] 139 [133-150] versus 86 [69-91], P<.001). After adjustment for patient characteristic only, slow surgeons had significantly higher adjusted rates of any complication, prolonged length of stay, emergency department visits or readmissions, and venous thromboembolism (VTE). After further adjustment for surgeon characteristics, resident involvement, and the interaction between these variables, slow surgeons had higher rates of any complication (10.5% versus 7.1%, P=.039), prolonged length of stay (14.0% versus 4.4%, P=.002), and VTE (0.39% versus .22%, P<.001). Median surgeon operative duration is independently associated with adjusted rates of certain adverse outcomes after laparoscopic Roux-en-Y gastric bypass. Improving surgeon efficiency while operating may reduce operative time and improve the safety of bariatric surgery. Copyright © 2015 American Society for

The association between adverse pregnancy outcomes and maternal human papillomavirus infection: a systematic review protocol.

PubMed

Niyibizi, Joseph; Zanré, Nadège; Mayrand, Marie-Hélène; Trottier, Helen

2017-03-11

Human papillomavirus (HPV) is the most prevalent genital infection, especially in young women of reproductive age. In vitro and animal model experiments provide compelling evidence of the harmful effect of HPV on pregnancy outcomes, but results from epidemiologic studies are inconclusive. We aim to determine the strength of the relationship between adverse pregnancy outcomes (APO) and HPV infection and assess its consistency across studies, by systematically reviewing the literature. The search strategy has been developed on the basis of the PICOS framework: Population (pregnant women); Exposure (HVP infection confirmed by HPV testing); Comparator (pregnant women without HPV infection); Outcomes (miscarriage, spontaneous preterm birth, low birth weight, preterm premature rupture of membranes, pregnancy-induced hypertensive disorders and intrauterine growth restriction) and Study design (observational studies). We will search three information sources: (1) electronic databases (MEDLINE, EMBASE, and EBM Reviews databases); (2) Grey literature (Google Scholar and Web of Science conference proceedings); and (3) citing and cited articles of included studies. Two reviewers (JN, NZ) will independently and in duplicate screen identified articles, select eligible studies, and extract data. Discrepancies will be resolved by consensus and otherwise by discussion with the other authors (MHM, HT). Quality of included studies will be assessed using the Effective Public Health Practice Project (EPHPP) Quality Assessment Tool for Quantitative Studies. We will narratively synthesize extracted data whether meta-analysis is conducted or not. Meta-analysis of each outcome will be performed, and where appropriate, an average measure of association will be computed. We will use the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach to assess and grade the strength of confidence in cumulative estimate. Comprehensive and high-quality evidence of a negative

Creating a Structured Adverse Outcome Pathway Knowledgebase via Ontology-Based Annotations

EPA Science Inventory

The Adverse Outcome Pathway (AOP) framework is increasingly used to integrate data based on traditional and emerging toxicity testing paradigms. As the number of AOP descriptions has increased, so has the need to define the AOP in computable terms. Herein, we present a comprehens...

Male gender and renal dysfunction are predictors of adverse outcome in nonpostoperative ischemic colitis patients.

PubMed

Lee, Tsung-Chun; Wang, Hsiu-Po; Chiu, Han-Mo; Lien, Wan-Ching; Chen, Mei-Jyh; Yu, Linda C H; Sun, Chia-Tung; Lin, Jaw-Town; Wu, Ming-Shiang

2010-01-01

Ischemic colitis (IC) spans a broad spectrum from self-limiting illness to intestinal gangrene and mortality. Prognostic factors specifically for nonpostoperative IC were not fully characterized. We aim to focus on nonpostoperative IC in patients with renal dysfunction and try to identify prognostic factors for adverse outcomes. We conducted a retrospective analysis at a university-affiliated tertiary medical center in Taiwan. From January 2003 to August 2008, 25 men and 52 women (mean age: 66 y) had colonoscopic biopsy-proven IC without prior culprit surgery. We estimated glomerular filtration rate with simplified Modification of Diet in Renal Disease equation. Nine patients with glomerular filtration rate below 30 mL per minute per 1.73 m were classified as renal dysfunction group (including 7 dialysis patients). Adverse outcomes were defined as need for surgery and mortality. Predictors for adverse outcomes were captured by univariate and multivariate analysis. Research ethical committee approved the study protocol. Patients with renal dysfunction more often had: diabetes mellitus (56% vs. 16%, P=0.02), prolonged symptoms (6.8 d vs. 3.5 d, P=0.01), lower hemoglobin (11.1 g/dL vs. 13.4 g/dL, P=0.01), and more often right colonic involvement (56% vs. 19%, P=0.03). Renal dysfunction patients also had longer hospitalization days (median 15 d vs. 4 d, P=0.045). However, there was no statistical significance in the rate of either surgery or mortality between these 2 groups (P>0.05). Univariate analysis showed that renal dysfunction, sex, emergency department referral, presentation with abdominal pain were significant for adverse outcome (P<0.1). Multivariate analysis revealed that male sex conveyed 9.5-fold risk (P=0.01) and renal dysfunction conveyed 8.5-fold risk (P=0.03) for adverse outcomes. Nonpostoperative IC patients with concurrent renal dysfunction had distinct clinical profiles. Multivariate analysis showed that male patients had 9.5-fold and renal

Integrating publicly-available data to generate computationally-predicted adverse outcome pathways for hepatic steatosis

EPA Science Inventory

The adverse outcome pathway (AOP) framework provides a way of organizing knowledge related to the key biological events that result in a particular health outcome. For the majority of environmental chemicals, the availability of curated pathways characterizing potential toxicity ...

Effects of bisphenol A on male and couple reproductive health: a review.

PubMed

Mínguez-Alarcón, Lidia; Hauser, Russ; Gaskins, Audrey J

2016-09-15

Bisphenol A (BPA) is a ubiquitous environmental toxicant with endocrine-disrupting properties and is suspected to affect human reproduction. The objective of this review was to summarize the potential effects of male exposure to BPA on markers of testicular function and couple reproductive outcomes. Five epidemiologic studies on BPA and reproductive hormones all found significant associations with at least one reproductive hormone; however, no consistent relationships were observed across studies. Six epidemiologic studies evaluated the relation between BPA and semen parameters, and although the majority reported negative associations with various parameters, there were few consistent trends across studies. Finally, three epidemiologic studies examined BPA and couple reproductive outcomes, and only one found an association. Overall, the evidence supporting an association between BPA exposure and adverse male reproductive health outcomes in humans remains limited and inconclusive. Reasons for the discrepancies in results could include, but are not limited to, differences in study populations (e.g., fertile vs. subfertile men), BPA urinary concentrations (occupationally vs. nonoccupationally exposed), misclassification of BPA exposure (e.g., using one urine sample to characterize exposure vs. multiple samples), sample sizes, study design (e.g., cross-sectional vs. prospective), and residual confounding (e.g., due to diet and lifestyle factors). It is also possible that some of the statistically significant findings were due to chance alone. Clearly, further studies are needed to further clarify the role of this ubiquitous endocrine-disrupting chemical on male reproductive health. Copyright © 2016. Published by Elsevier Inc.

Adverse outcome pathway networks II: Network analytics.

PubMed

Villeneuve, Daniel L; Angrish, Michelle M; Fortin, Marie C; Katsiadaki, Ioanna; Leonard, Marc; Margiotta-Casaluci, Luigi; Munn, Sharon; O'Brien, Jason M; Pollesch, Nathan L; Smith, L Cody; Zhang, Xiaowei; Knapen, Dries

2018-06-01

Toxicological responses to stressors are more complex than the simple one-biological-perturbation to one-adverse-outcome model portrayed by individual adverse outcome pathways (AOPs). Consequently, the AOP framework was designed to facilitate de facto development of AOP networks that can aid in the understanding and prediction of pleiotropic and interactive effects more common to environmentally realistic, complex exposure scenarios. The present study introduces nascent concepts related to the qualitative analysis of AOP networks. First, graph theory-based approaches for identifying important topological features are illustrated using 2 example AOP networks derived from existing AOP descriptions. Second, considerations for identifying the most significant path(s) through an AOP network from either a biological or risk assessment perspective are described. Finally, approaches for identifying interactions among AOPs that may result in additive, synergistic, or antagonistic responses (or previously undefined emergent patterns of response) are introduced. Along with a companion article (part I), these concepts set the stage for the development of tools and case studies that will facilitate more rigorous analysis of AOP networks, and the utility of AOP network-based predictions, for use in research and regulatory decision-making. The present study addresses one of the major themes identified through a Society of Environmental Toxicology and Chemistry Horizon Scanning effort focused on advancing the AOP framework. Environ Toxicol Chem 2018;37:1734-1748. © 2018 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals, Inc. on behalf of SETAC. This article is a US government work and, as such, is in the public domain in the United States of America. © 2018 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals, Inc. on behalf of SETAC. This article is a US government work and, as such, is in the public domain in the

Practical approaches to adverse outcome pathway development and weight‐of‐evidence evaluation as illustrated by ecotoxicological case studies

EPA Science Inventory

Adverse Outcome Pathways (AOPs) describe toxicant effects as a sequential chain of causally linked events beginning with a molecular perturbation and culminating in an adverse outcome at an individual or population level. Strategies for developing AOPs are still evolving and dep...

Frameworks for organizing exposure and toxicity data - the Aggregate Exposure Pathway (AEP) and the Adverse Outcome Pathway (AOP)

EPA Science Inventory

The Adverse Outcome Pathway (AOP) framework organizes existing knowledge regarding a series of biological events, starting with a molecular initiating event (MIE) and ending at an adverse outcome. The AOP framework provides a biological context to interpret in vitro toxicity dat...

Latino Adolescent Reproductive and Sexual Health Behaviors and Outcomes: Research Informed Guidance for Agency-based Practitioners

PubMed Central

Guilamo-Ramos, Vincent; Goldberg, Vincent; Lee, Jane; McCarthy, Katherine; Leavitt, Sarah

2011-01-01

Latinos are the largest and fastest growing minority youth group in the United States. Currently, Latino adolescents experience higher rates of teen pregnancy compared to any other racial or ethnic group and have disproportionately high levels of sexually transmitted infections and HIV. Latino teens are also affected by a number of social problems such as school dropout, poverty, depression and limited access to healthcare, which contributes to disparities in reproductive health outcomes for this population. Relatively few intervention research studies and programs have been dedicated to reducing sexual risk among Latino youth, despite their particular vulnerabilities in experiencing negative reproductive health outcomes. We provide recommendations for identifying the unique reproductive health needs of Latino youth and specific applied strategies so that agency-based social workers and other providers can develop family-based interventions that improve adolescent Latino sexual and reproductive health. PMID:23279981

Reproductive outcome after IVF following hysteroscopic division of incomplete uterine septum/arcuate uterine anomaly in women with primary infertility

PubMed Central

Abuzeid, M.; Ghourab, G.; Abuzeid, O.; Mitwally, M.; Ashraf, M.; Diamond, M.

2014-01-01

Objective: To determine reproductive outcome after in-vitro fertilization/embryo transfer (IVF-ET) in women with primary infertility following hysteroscopic septoplasty of incomplete uterine septum or arcuate uterine anomaly. Methods: This is a historical cohort study. The study group consisted of 156 consecutive patients who underwent a total of 221 cycles of IVF/ET following hysteroscopic septoplasty of an incomplete uterine septum or arcuate anomaly (Group 1). The control group included 196 consecutive patients with normal endometrial cavity on hysteroscopy who underwent a total of 369 cycles of IVF/ET (Group 2). The reproductive outcome after the first cycle of IVF-ET and the best reproductive outcome of all the cycles the patient underwent were calculated. In addition, we compared the reproductive outcome in the study group based on the type of the anomalies (septum versus arcuate). Results: In the first fresh cycle, following septoplasty, there were significantly higher clinical pregnancy and delivery rates in Group 1 (60.3% and 51.3% respectively) compared to Group 2 (38.8% and 33.2% respectively). However, there was no significant difference between the two groups in the clinical pregnancy (74.4% vs. 67.3%) or in the delivery (65.4% vs. 60.2%) rates per patient, respectively. There was no significant difference in the reproductive outcome after IVF-ET between patients who previously had arcuate uterine anomaly versus incomplete uterine septum. Conclusion: Reproductive outcome of IVF-ET after hysteroscopic correction of incomplete uterine septum/arcuate uterine anomaly in women with primary infertility is no different from women with normal uterine cavity. PMID:25593694

OS104. Are preeclampsia and adverse obstetrical outcomes predictors for longterm cardiovascular disease?

PubMed

Sia, W W; Tsuyuki, R; Pertman, S; Hui, W

2012-07-01

Epidemiologic studies suggest that pregnancy complications such as preeclampsia, gestational diabetes, preterm delivery and low birth weight independently increase maternal risk for future development of cardiovascular disease. To further investigate whether preeclampsia, gestational diabetes, and adverse obstetrical outcomes such as placental abruption, intrauterine growth restriction and preterm delivery, are independent risk factors for longterm cardiovascular disease. This was a case-control study where 252 parous women (cases) with coronary artery disease were matched with a parous woman within 5 years of age with no known coronary artery disease (controls). Participants were recruited from the Royal Alexandra Hospital in cardiac catheterization lab recovery room in Edmonton, Canada. Women with significant angiographic coronary artery stenosis were eligible as cases and those without were eligible as controls. Participants were interviewed on their pregnancy histories and traditional cardiovascular risk factors, such as hypertension, diabetes etc. Descriptive statistics, chi-square tests and conditional regression analysis were performed. We recruited 244 cases and 246 controls. The average age was 66.3 and 65.8 respectively. Cases were more likely obese, had more pregnancies as well as traditional cardiovascular risk factors than controls. Adverse pregnancy outcomes were similar between the two groups except gestational hypertension. However, it was not statistically significant in the conditional logistic regression model. Independent risk factors for future cardiovascular diseases were: dyslipidemia (OR 12.8), hypertension (3.0), and being a current (OR 7.4) or former smoker (1.8). Adverse pregnancy outcomes In this study, adverse pregnancy outcomes were not independently associated with cardiovascular disorders. Our study was limited by recall bias, and ascertainment of diagnosis.Our study supports that dyslipidemia, hypertensiion and smoking increase

Ovarian function and reproductive outcomes of female patients with systemic lupus erythematosus and the strategies to preserve their fertility.

PubMed

Oktem, Ozgur; Guzel, Yılmaz; Aksoy, Senai; Aydin, Elvin; Urman, Bulent

2015-03-01

Systemic lupus erythematosus (SLE) is a chronic autoimmune systemic disease that mainly affects women of reproductive age. Emerging data from recent molecular studies show us that estrogen hormone plays a central role in the development of this disease. By acting via its cognate receptors ERα and ERβ expressed on immune cells, estrogen can modulate immune function in both the innate and adaptive immune responses. Interestingly, estrogen may also evoke autoimmune responses after binding to B lymphocytes leading to the generation of high-affinity autoantibodies and proinflammatory cytokines (so-called estrogen-induced autoimmunity). Unfortunately, reproductive function of young female patients with this disease is commonly compromised by different pathophysiologic processes. First, ovarian reserve is diminished even in the presence of mild disease suggesting a direct impact of the disease itself on ovarian function possibly due to ovarian involvement in the form of autoimmune oophoritis. Second, SLE patients with severe manifestations of the disease are treated with alkylating chemotherapy agent cyclophosphamide. Cyclophosphamide and other drugs of alkylating category have the highest gonadotoxicity. Therefore, SLE patients exposed to cyclophosphamide have a much higher risk of developing infertility and premature ovarian failure than do the counterparts who are treated with other less toxic treatments. Third, the functions of the hypothalamic pituitary ovarian axis are perturbed by chronic inflammatory state. And finally adverse pregnancy outcomes are more commonly observed in SLE patients such as fetal loss, preterm birth, intrauterine fetal growth restriction, preeclampsia-eclampsia, and fetal congenital heart block. We aimed in this review article to provide the readers an update on how estrogen hormone closely interacts with and induces lupus-prone changes in the immune system. We also discuss ovarian function and other reproductive outcomes in SLE patients

Early warning score independently predicts adverse outcome and mortality in patients with acute pancreatitis.

PubMed

Jones, Michael J; Neal, Christopher P; Ngu, Wee Sing; Dennison, Ashley R; Garcea, Giuseppe

2017-08-01

The aim of this study was to compare the prognostic value of established scoring systems with early warning scores in a large cohort of patients with acute pancreatitis. In patients presenting with acute pancreatitis, age, sex, American Society of Anaesthesiologists (ASA) grade, Modified Glasgow Score, Ranson criteria, APACHE II scores and early warning score (EWS) were recorded for the first 72 h following admission. These variables were compared between survivors and non-survivors, between patients with mild/moderate and severe pancreatitis (based on the 2012 Atlanta Classification) and between patients with a favourable or adverse outcome. A total of 629 patients were identified. EWS was the best predictor of adverse outcome amongst all of the assessed variables (area under curve (AUC) values 0.81, 0.84 and 0.83 for days 1, 2 and 3, respectively) and was the most accurate predictor of mortality on both days 2 and 3 (AUC values of 0.88 and 0.89, respectively). Multivariable analysis revealed that an EWS ≥2 was independently associated with severity of pancreatitis, adverse outcome and mortality. This study confirms the usefulness of EWS in predicting the outcome of acute pancreatitis. It should become the mainstay of risk stratification in patients with acute pancreatitis.

Influence of paternal age on perinatal outcomes.

PubMed

Hurley, Emily G; DeFranco, Emily A

2017-11-01

There is an increasing trend to delay childbearing to advanced parental age. Increased risks of advanced maternal age and assisted reproductive technologies are widely accepted. There are limited data regarding advanced paternal age. To adequately counsel patients on risk, more research regarding advanced paternal age is necessary. We sought to determine the influence of paternal age on perinatal outcomes, and to assess whether this influence differs between pregnancies achieved spontaneously and those achieved with assisted reproductive technology. A population-based retrospective cohort study of all live births in Ohio from 2006 through 2012 was completed. Data were evaluated to determine if advanced paternal age is associated with an increased risk of adverse outcomes in pregnancies. The analysis was stratified by status of utilization of assisted reproductive technology. Generalized linear regression models assessed the association of paternal age on pregnancy complications in assisted reproductive technology and spontaneously conceived pregnancies, after adjusting for maternal age, race, multifetal gestation, and Medicaid status, using Stata software (Stata, Release 12; StataCorp, College Station, TX). Paternal age was documented in 82.2% of 1,034,552 live births in Ohio during the 7-year study period. Paternal age ranged from 12-87 years, with a median of 30 (interquartile range, 26-35) years. Maternal age ranged from 11-62 years, with a median of 27 (interquartile range, 22-31) years. The use of assisted reproductive technology in live births increased as paternal age increased: 0.1% <30 years vs 2.5% >60 years, P < .001. After accounting for maternal age and other confounding risk factors, increased paternal age was not associated with a significant increase in the rate of preeclampsia, preterm birth, fetal growth restriction, congenital anomaly, genetic disorder, or neonatal intensive care unit admission. The influence of paternal age on pregnancy outcomes

The Chernobyl accident, congenital anomalies and other reproductive outcomes.

PubMed

Little, J

1993-04-01

Studies of the association between the Chernobyl accident in April 1986 and reproductive outcome, with particular reference to congenital anomalies, are reviewed. All of the studies so far have been based on the detection of a change in frequency over time. An increased frequency of trisomy 21 in the former West Berlin in January 1987, and increases in the frequency of neural tube defects in several small hospital-based series in Turkey, are not confirmed in larger and more representative series in Europe. No clear changes in the prevalence at birth of anomalies which might be associated with the accident are apparent in Byelorussia or the Ukraine, the republics with the highest exposure to fallout. However, these data are difficult to interpret as the methods of acquisition have not been described and they have not yet been reported in full. Thus, there is no consistent evidence of a detrimental physical effect of the Chernobyl accident on congenital anomalies. This is also the case for other measured outcomes of pregnancy. There is evidence of indirect effects--an increase in induced abortions substantial enough to show as a reduction in total births, due to anxieties created. Data are not available on the reproductive outcomes of women pregnant at the time of the accident who were evacuated from the 30 km zone of immediate contamination, of workers in the plant at the time of the accident or of decontamination workers. Moreover, no data are available from several of the other countries closest to the Chernobyl area.

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. © The Author(s) 2015.

Adverse nurse outcomes: correlation to nurses' workload, staffing, and shift rotation in Kuwaiti hospitals.

PubMed

Al-Kandari, Fatimah; Thomas, Deepa

2008-08-01

This study was conducted to identify adverse outcomes to nurses in relation to their daily patient load, nursing care activities, staffing, and shift rotation. A structured questionnaire was used to collect data from medical and surgical nurses (N = 784). Skipping tea/coffee breaks (95%), feeling responsible for more patients than they could safely care for (87%), inadequate help available (86%), inadequate time to document care (80%), verbal abuse by a patient or a visitor (77%), and concern about quality of care (71%) were the major reported adverse outcomes related to short staffing, increased patient load, and increased nursing care activities.

Father absence and reproduction-related outcomes in Malaysia, a transitional fertility population.

PubMed

Sheppard, Paula; Snopkowski, Kristin; Sear, Rebecca

2014-06-01

Father absence is consistently associated with children's reproductive outcomes in industrialized countries. It has been suggested that father absence acts as a cue to particular environmental conditions that influence life history strategies. Much less is known, however, about the effects of father absence on such outcomes in lower-income countries. Using data from the 1988 Malaysian Family Life Survey (n = 567), we tested the effect of father absence on daughters' age at menarche, first marriage, and first birth; parity progression rates; and desired completed family size in Malaysia, a country undergoing an economic and fertility transition. Father absence during later childhood (ages 8 to 15), although not during earlier childhood, was associated with earlier progressions to first marriage and first birth, after controlling for other confounders. Father absence does not affect age at menarche, desired family size, or progression from first to second birth. The patterns found in this transitional population partly mirror those in developed societies, where father absence accelerates reproductive events. There is, however, a notable contrast between the acceleration in menarche for father-absent girls consistently found in developed societies and the lack of any association in our findings. The mechanisms through which father absence affects reproduction may differ in different ecological contexts. In lower-income contexts, direct paternal investment or influence may be of more importance in determining reproductive behavior than whether fathers act as a cue to environmental conditions.

Gestational dyslipidaemia and adverse birthweight outcomes: a systematic review and meta-analysis.

PubMed

Wang, J; Moore, D; Subramanian, A; Cheng, K K; Toulis, K A; Qiu, X; Saravanan, P; Price, M J; Nirantharakumar, K

2018-05-21

Low and high birthweight is known to increase the risk of acute and longer-term adverse outcomes, such as stillbirth, infant mortality, obesity, type 2 diabetes and cardiovascular diseases. Gestational dyslipidaemia is associated with a numbers of adverse birth outcomes, but evidence regarding birthweight is still inconsistent to reliably inform clinical practice and treatment recommendations. The aim of this study was to explore the relationship between maternal gestational dyslipidaemia and neonatal health outcomes, namely, birthweight, metabolic factors and inflammatory parameters. We searched systematically Embase, MEDLINE, PubMed, CINAHL Plus and Cochrane Library up to 1 August 2016 (with an updated search in MEDLINE at the end of July 2017) for longitudinal studies that assessed the association of maternal lipid levels during pregnancy with neonatal birthweight, or metabolic and inflammatory parameters up to 3 years old. Data from 46 publications including 31,402 pregnancies suggest that maternal high triglycerides and low high-density-lipoprotein cholesterol levels throughout pregnancy are associated with increased birthweight, higher risk of large for gestational age and macrosomia and lower risk of small-for-gestational age. The findings were consistent across the studied populations, but stronger associations were observed in women who were overweight or obese prior to pregnancy. This meta-analysis suggested that the potential under-recognized adverse effects of intrauterine exposure to maternal dyslipidaemia may warrant further investigation into the relationship between maternal dyslipidaemia and birthweight in large prospective cohorts or in randomized trials. © 2018 World Obesity Federation.

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...

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

EPA Pesticide Factsheets

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 framework is designed to be chemical agnostic, it is widely recognized that considering chemicals’ absorption, distribution, metabolism, and excretion (ADME) behaviors is critical in applying the AOP framework in chemical-specific risk assessment. Currently, information being generated as part of the Organisation for Economic Co-operation and Development (OECD) AOP Development Programme is being consolidated into an AOP Knowledgebase (http://aopwiki.org). To enhance the use of this Knowledgebase in risk assessment, an ADME Module has been developed to contain the ADME information needed to connect MIEs and other key events in an AOP for specific chemicals. The conceptual structure of this module characterizes the potential of a chemical to reach the target MIE based on either its structure-based features or relative rates of ADME. The key features of this module include (1) a framework for connecting biology-based AOP to biochemical-based ADME and chemical/human activity-based exposure pathways; (2) links to qualitative tools (e.g., structure-based cheminformatic model) that screen for chemicals that could potentially reach the target MIE; (3) links to quantitative tools (e.g., dose-r

Advancing the adverse outcome pathway framework - An international horizon scanning approach (presentation)

EPA Science Inventory

In preparation for a Society of Environmental Toxicology and Chemistry Pellston Workshop titled “Advancing the Adverse Outcome Pathway (AOP) Concept: An International Horizon Scanning Approach,” a horizon scanning effort was undertaken to gather input from the global ...

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...

Accelerating Adverse Outcome Pathway Development Using ...

EPA Pesticide Factsheets

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 knowledgebase, 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 twenty-first century toxicity testing strategies. This review article describes how effective knowledge management and automated approaches to AOP development can enhance and accelerate the development and use of AOPs. As the principles documented in this review are put into practice, we anticipate that the quality and quantity of AOPs available will increase substantially. This, in turn, will aid in the interpretation of ToxCast and other high-throughput tox

AOP-DB Frontend: A user interface for the Adverse Outcome Pathways Database.

EPA Science Inventory

The EPA Adverse Outcome Pathway Database (AOP-DB) is a database resource that aggregates association relationships between AOPs, genes, chemicals, diseases, pathways, species orthology information, ontologies. The AOP-DB frontend is a simple yet powerful AOP-DB user interface in...

AOP-DB Frontend: A user interface for the Adverse Outcome Pathways Database

EPA Science Inventory

The EPA Adverse Outcome Pathway Database (AOP-DB) is a database resource that aggregates association relationships between AOPs, genes, chemicals, diseases, pathways, species orthology information, ontologies. The AOP-DB frontend is a simple yet powerful user interface in the for...

The adverse outcome pathway: A multifaceted framework supporting 21st century toxicology

EPA Science Inventory

The adverse outcome pathway (AOP) framework serves as a knowledge assembly, interpretation, and communication tool designed to support the translation of pathway-specific mechanistic data into responses relevant to assessing and managing risks of chemicals to human health and the...

Frailty in community-dwelling older adults: association with adverse outcomes

PubMed Central

Sánchez-García, Sergio; García-Peña, Carmen; Salvà, Antoni; Sánchez-Arenas, Rosalinda; Granados-García, Víctor; Cuadros-Moreno, Juan; Velázquez-Olmedo, Laura Bárbara; Cárdenas-Bahena, Ángel

2017-01-01

Background The study of frailty is important to identify the additional needs of medical long-term care and prevent adverse outcomes in community dwelling older adults. This study aimed to determine the prevalence of frailty and its association with adverse outcomes in community dwelling older adults. Methods A cross-sectional study was carried out from April to September 2014. The population sample was 1,252 older adults (≥60 years) who were beneficiaries of the Mexican Institute of Social Security (IMSS) in Mexico City. Data were derived from the database of the “Cohort of Obesity, Sarcopenia and Frailty of Older Mexican Adults” (COSFOMA). Operationalization of the phenotype of frailty was performed using the criteria of Fried et al (weight loss, self-report of exhaustion, low physical activity, slow gait, and weakness). Adverse outcomes studied were limitation in basic activities of daily living (ADLs), falls and admission to emergency services in the previous year, and low quality of life (WHOQOL-OLD). Results Frailty was identified in 20.6% (n=258), pre-frailty in 57.6% (n=721), and not frail in 21.8% (n=273). The association between frailty and limitations in ADL was odds ratio (OR) =2.3 (95% confidence interval [CI] 1.7–3.2) and adjusted OR =1.7 (95% CI 1.2–2.4); falls OR =1.6 (95% CI 1.2–2.1) and adjusted OR =1.4 (95% CI 1.0–1.9); admission to emergency services OR =1.9 (95% CI 1.1–3.1) and adjusted OR =1.9 (95% CI 1.1–3.4); low quality of life OR =3.4 (95% CI 2.6–4.6) and adjusted OR =2.1 (95% CI 1.5–2.9). Conclusion Approximately 2 out of 10 older adults demonstrate frailty. This is associated with limitations in ADL, falls, and admission to emergency rooms during the previous year as well as low quality of life. PMID:28721028

Risk factors for adverse driving outcomes in Dutch adults with ADHD and controls.

PubMed

Bron, Tannetje I; Bijlenga, Denise; Breuk, Minda; Michielsen, Marieke; Beekman, Aartjan T F; Kooij, J J Sandra

2018-02-01

To identify risk factors for adverse driving outcomes and unsafe driving among adults with and without ADHD in a Dutch sample. In this cross-sectional study, validated self-report questionnaires were used to compare driving history and current driving behavior between 330 adults diagnosed with ADHD and 330 controls. Adults with ADHD had significantly more adverse driving outcomes when compared to controls. Having an ADHD diagnosis significantly increased the odds for having had 3 or more vehicular crashes (OR = 2.72; p = .001). Driving frequency, male gender, age, high anxiety levels, high hostility levels, and alcohol use all significantly influenced the odds for unsafe driving behavior, for having had 12 or more traffic citations, and/or for having had 3 or more vehicular crashes. Alcohol use, and high levels of anxiety and hostility are highly prevalent among adults with ADHD, and they mediate the risk for negative driving outcomes in this group. Copyright © 2017 Elsevier Ltd. All rights reserved.

An occupational reproductive research agenda for the third millennium.

PubMed Central

Lawson, Christina C; Schnorr, Teresa M; Daston, George P; Grajewski, Barbara; Marcus, Michele; McDiarmid, Melissa; Murono, Eisuke; Perreault, Sally D; Schrader, Steven M; Shelby, Michael

2003-01-01

There is a significant public health concern about the potential effects of occupational exposure to toxic substances on reproductive outcomes. Several toxicants with reported reproductive and developmental effects are still in regular commercial or therapeutic use and thus present potential exposure to workers. Examples of these include heavy metals, organic solvents, pesticides and herbicides, and sterilants, anesthetic gases, and anticancer drugs used in health care. Many other substances are suspected of producing reproductive or developmental toxicity but lack sufficient data. Progress has been limited in identifying hazards and quantifying their potencies and in separating the contribution of these hazards from other etiologic factors. Identifying the causative agents, mechanisms by which they act, and any potential target populations, present the opportunity to intervene and protect the reproductive health of workers. The pace of laboratory studies to identify hazards and to underpin the biologic plausibility of effects in humans has not matched the pace at which new chemicals are introduced into commerce. Though many research challenges exist today, recent technologic and methodologic advances have been made that allow researchers to overcome some of these obstacles. The objective of this article is to recommend future directions in occupational reproductive health research. By bridging interdisciplinary gaps, the scientific community can work together to improve health and reduce adverse outcomes. PMID:12676620

Agricultural pesticide use and adverse birth outcomes in the San Joaquin Valley of California.

PubMed

Larsen, Ashley E; Gaines, Steven D; Deschênes, Olivier

2017-08-29

Virtually all agricultural communities worldwide are exposed to agricultural pesticides. Yet, the health consequences of such exposure are poorly understood, and the scientific literature remains ambiguous. Using individual birth and demographic characteristics for over 500 000 birth observations between 1997-2011 in the agriculturally dominated San Joaquin Valley, California, we statistically investigate if residential agricultural pesticide exposure during gestation, by trimester, and by toxicity influences birth weight, gestational length, or birth abnormalities. Overall, our analysis indicates that agricultural pesticide exposure increases adverse birth outcomes by 5-9%, but only among the population exposed to very high quantities of pesticides (e.g., top 5th percentile, i.e., ~4200 kg applied over gestation). Thus, policies and interventions targeting the extreme right tail of the pesticide distribution near human habitation could largely eliminate the adverse birth outcomes associated with agricultural pesticide exposure documented in this study.The health consequences of exposure to pesticides are uncertain and subject to much debate. Here, the effect of exposure during pregnancy is investigated in an agriculturally dominated residential area, showing that an increase in adverse birth outcomes is observed with very high levels of pesticide exposure.

Can Erythrocytes Transmit Oxidative Stress Beyond the Lungs? An Adverse Outcome Pathway for the Cardiovascular Effects of Air Pollution.

EPA Science Inventory

Adverse outcome pathways (AOPs) are systems biology roadmaps with potential utility in xenobiotic exposure risk assessment. AOPs connect molecular initiating events (MIEs) to population-level adverse outcomes (AOs) via cellular, organ, and organism key events (KE) and KE relatio...

Association Between Pesticide Residue Intake From Consumption of Fruits and Vegetables and Pregnancy Outcomes Among Women Undergoing Infertility Treatment With Assisted Reproductive Technology.

PubMed

Chiu, Yu-Han; Williams, Paige L; Gillman, Matthew W; Gaskins, Audrey J; Mínguez-Alarcón, Lidia; Souter, Irene; Toth, Thomas L; Ford, Jennifer B; Hauser, Russ; Chavarro, Jorge E

2018-01-01

Animal experiments suggest that ingestion of pesticide mixtures at environmentally relevant concentrations decreases the number of live-born offspring. Whether the same is true in humans is unknown. To examine the association of preconception intake of pesticide residues in fruits and vegetables (FVs) with outcomes of infertility treatment with assisted reproductive technologies (ART). This analysis included 325 women who completed a diet assessment and subsequently underwent 541 ART cycles in the Environment and Reproductive Health (EARTH) prospective cohort study (2007-2016) at a fertility center at a teaching hospital. We categorized FVs as having high or low pesticide residues using a validated method based on surveillance data from the US Department of Agriculture. Cluster-weighted generalized estimating equations were used to analyze associations of high- and low-pesticide residue FV intake with ART outcomes. Adjusted probabilities of clinical pregnancy and live birth per treatment cycle. In the 325 participants (mean [SD] age, 35.1 [4.0] y; body mass index, 24.1 [4.3]), mean (SD) intakes of high- and low-pesticide residue FVs were 1.7 (1.0) and 2.8 (1.6) servings/d, respectively. Greater intake of high-pesticide residue FVs was associated with a lower probability of clinical pregnancy and live birth. Compared with women in the lowest quartile of high-pesticide FV intake (<1.0 servings/d), women in the highest quartile (≥2.3 servings/d) had 18% (95% CI, 5%-30%) lower probability of clinical pregnancy and 26% (95% CI, 13%-37%) lower probability of live birth. Intake of low-pesticide residue FVs was not significantly related to ART outcomes. Higher consumption of high-pesticide residue FVs was associated with lower probabilities of pregnancy and live birth following infertility treatment with ART. These data suggest that dietary pesticide exposure within the range of typical human exposure may be associated with adverse reproductive consequences.

The effects of competition on assisted reproductive technology outcomes.

PubMed

Henne, Melinda B; Bundorf, M Kate

2010-04-01

To evaluate the relationship between competition among fertility clinics and assisted reproductive technology (ART) treatment outcomes, particularly multiple births. Using clinic-level data from 1995 to 2001, we examined the relationship between competition and clinic-level ART outcomes and practice patterns. National database registry. Clinics performing ART. The number of clinics within a 20-mile (32.19-km) radius of a given clinic. Clinic-level births, singleton births, and multiple births per ART cycle; multiple births per ART birth; average number of embryos transferred per cycle; and the proportion of cycles for women under age 35 years. The number of competing clinics is not strongly associated with ART birth and multiple birth rates. Relative to clinics with no competitors, the rate of multiple births per cycle is lower (-0.03 percentage points) only for clinics with more than 15 competitors. Embryo transfer practices are not statistically significantly associated with the number of competitors. Clinic-level competition is strongly associated with patient mix. The proportion of cycles for patients under 35 years old is 6.4 percentage points lower for clinics with more than 15 competitors than for those with no competitors. Competition among fertility clinics does not appear to increase rates of multiple births from ART by promoting more aggressive embryo transfer decisions. Copyright 2010 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.Published by Elsevier Inc.

Long-term adverse effects of neonatal exposure to bisphenol A on the murine female reproductive tract.

PubMed

Newbold, Retha R; Jefferson, Wendy N; Padilla-Banks, Elizabeth

2007-01-01

The developing fetus is uniquely sensitive to perturbation by chemicals with hormone-like activity. The adverse effects of prenatal diethylstilbestrol (DES) exposure are a classic example. Since concern has been mounting regarding the human health and environmental effects of bisphenol A (BPA), a high-production-volume chemical with estrogenic activity used in the synthesis of plastics, we investigated its long-term effects in an experimental animal model that was previously shown useful in studying the adverse effects of developmental exposure to DES. Outbred female CD-1 mice were treated on days 1-5 with subcutaneous injections of BPA (10, 100 or 1000 microg/kg/day) dissolved in corn oil or corn oil alone (Control). At 18 months, ovaries and reproductive tract tissues were examined. There was a statistically significant increase in cystic ovaries and cystic endometrial hyperplasia (CEH) in the BPA-100 group as compared to Controls. Progressive proliferative lesion (PPL) of the oviduct and cystic mesonephric (Wolffian) duct remnants were also seen in all of the BPA groups. More severe pathologies of the uterus following neonatal BPA treatment included adenomyosis, leiomyomas, atypical hyperplasia, and stromal polyps. These data suggest that BPA causes long-term adverse effects if exposure occurs during critical periods of differentiation.

Long-term Adverse Effects of Neonatal Exposure to Bisphenol A on the Murine Female Reproductive Tract

PubMed Central

Newbold, Retha R.; Jefferson, Wendy N.; Banks, Elizabeth Padilla

2007-01-01

The developing fetus is uniquely sensitive to perturbation by chemicals with hormone-like activity. The adverse effects of prenatal diethylstilbestrol (DES) exposure are a classic example. Since concern has been mounting regarding the human health and environmental effects of bisphenol A (BPA), a high-production-volume chemical with estrogenic activity used in the synthesis of plastics, we investigated its long-term effects in an experimental animal model that was previously shown useful in studying the adverse effects of developmental exposure to DES. Outbred female CD-1 mice were treated on days 1-5 with subcutaneous injections of BPA (10, 100 or 1000 μg/kg/day) dissolved in corn oil or corn oil alone (Control). At 18 months, ovaries and reproductive tract tissues were examined. There was a statistically significant increase in cystic ovaries and cystic endometrial hyperplasia (CEH) in the BPA-100 group as compared to Controls. Progressive proliferative lesion (PPL) of the oviduct and cystic mesonephric (Wolffian) duct remnants were also seen in all of the BPA groups. More severe pathologies of the uterus following neonatal BPA treatment included adenomyosis, leiomyomas, atypical hyperplasia, and stromal polyps. These data suggest that BPA causes long-term adverse effects if exposure occurs during critical periods of differentiation. PMID:17804194

Global estimates of syphilis in pregnancy and associated adverse outcomes: analysis of multinational antenatal surveillance data.

PubMed

Newman, Lori; Kamb, Mary; Hawkes, Sarah; Gomez, Gabriela; Say, Lale; Seuc, Armando; Broutet, Nathalie

2013-01-01

The World Health Organization initiative to eliminate mother-to-child transmission of syphilis aims for ≥ 90% of pregnant women to be tested for syphilis and ≥ 90% to receive treatment by 2015. We calculated global and regional estimates of syphilis in pregnancy and associated adverse outcomes for 2008, as well as antenatal care (ANC) coverage for women with syphilis. Estimates were based upon a health service delivery model. National syphilis seropositivity data from 97 of 193 countries and ANC coverage from 147 countries were obtained from World Health Organization databases. Proportions of adverse outcomes and effectiveness of screening and treatment were from published literature. Regional estimates of ANC syphilis testing and treatment were examined through sensitivity analysis. In 2008, approximately 1.36 million (range: 1.16 to 1.56 million) pregnant women globally were estimated to have probable active syphilis; of these, 80% had attended ANC. Globally, 520,905 (best case: 425,847; worst case: 615,963) adverse outcomes were estimated to be caused by maternal syphilis, including approximately 212,327 (174,938; 249,716) stillbirths (>28 wk) or early fetal deaths (22 to 28 wk), 91,764 (76,141; 107,397) neonatal deaths, 65,267 (56,929; 73,605) preterm or low birth weight infants, and 151,547 (117,848; 185,245) infected newborns. Approximately 66% of adverse outcomes occurred in ANC attendees who were not tested or were not treated for syphilis. In 2008, based on the middle case scenario, clinical services likely averted 26% of all adverse outcomes. Limitations include missing syphilis seropositivity data for many countries in Europe, the Mediterranean, and North America, and use of estimates for the proportion of syphilis that was "probable active," and for testing and treatment coverage. Syphilis continues to affect large numbers of pregnant women, causing substantial perinatal morbidity and mortality that could be prevented by early testing and treatment

Prostate cancer outcomes in France: treatments, adverse effects and two-year mortality

PubMed Central

2014-01-01

Background This very large population-based study investigated outcomes after a diagnosis of prostate cancer (PCa) in terms of mortality rates, treatments and adverse effects. Methods Among the 11 million men aged 40 years and over covered by the general national health insurance scheme, those with newly managed PCa in 2009 were followed for two years based on data from the national health insurance information system (SNIIRAM). Patients were identified using hospitalisation diagnoses and specific refunds related to PCa and PCa treatments. Adverse effects of PCa treatments were identified by using hospital diagnoses, specific procedures and drug refunds. Results The age-standardised two-year all-cause mortality rate among the 43,460 men included in the study was 8.4%, twice that of all men aged 40 years and over. Among the 36,734 two-year survivors, 38% had undergone prostatectomy, 36% had been treated by hormone therapy, 29% by radiotherapy, 3% by brachytherapy and 20% were not treated. The frequency of treatment-related adverse effects varied according to age and type of treatment. Among men between 50 and 69 years of age treated by prostatectomy alone, 61% were treated for erectile dysfunction and 24% were treated for urinary disorders. The frequency of treatment for these disorders decreased during the second year compared to the first year (erectile dysfunction: 41% vs 53%, urinary disorders: 9% vs 20%). The frequencies of these treatments among men treated by external beam radiotherapy alone were 7% and 14%, respectively. Among men between 50 and 69 years with treated PCa, 46% received treatments for erectile dysfunction and 22% for urinary disorders. For controls without PCa but treated surgically for benign prostatic hyperplasia, these frequencies were 1.5% and 6.0%, respectively. Conclusions We report high survival rates two years after a diagnosis of PCa, but a high frequency of PCa treatment-related adverse effects. These frequencies remain

Comparison of Reproductive Outcomes following Retained Products of Conception after Vaginal Delivery versus First-Trimester Abortion.

PubMed

Melcer, Yaakov; Smorgick, Noam; Schneider, David; Pansky, Moty; Halperin, Reuvit; Ben-Ami, Ido

2015-01-01

To compare the reproductive outcomes of women with pathologically confirmed retained products of conception (RPOC) following spontaneous vaginal delivery versus first-trimester pregnancy termination. We retrospectively reviewed all cases of women who underwent uterine re-evacuation due to pathologically confirmed RPOC between January 1, 2000 and December 31, 2010. Reproductive outcomes were compared between women with RPOC following spontaneous vaginal delivery and those who underwent dilatation and curettage (D&C) due to first-trimester abortion. The study group consisted of 176 patients with pathologically confirmed RPOC. Of those, 83 (47.1%) were admitted after spontaneous vaginal delivery and 93 (52.9%) following D&C due to first-trimester abortion. There were no significant differences in the conception rate, the mean time to conception and the rate of a new infertility problem between women with RPOC after vaginal delivery compared to those following pregnancy termination (p > 0.05). Furthermore, there were no significant differences between the groups in pregnancy outcomes following RPOC. Pathologically confirmed RPOC harbors the same reproductive outcomes following spontaneous vaginal delivery and first-trimester pregnancy termination. © 2015 S. Karger AG, Basel.

Hyperglycemia and Adverse Pregnancy Outcome (HAPO) Study: associations of maternal A1C and glucose with pregnancy outcomes.

PubMed

Lowe, Lynn P; Metzger, Boyd E; Dyer, Alan R; Lowe, Julia; McCance, David R; Lappin, Terence R J; Trimble, Elisabeth R; Coustan, Donald R; Hadden, David R; Hod, Moshe; Oats, Jeremy J N; Persson, Bengt

2012-03-01

To compare associations of maternal glucose and A1C with adverse outcomes in the multinational Hyperglycemia and Adverse Pregnancy Outcome (HAPO) Study and determine, based on those comparisons, if A1C measurement can provide an alternative to an oral glucose tolerance test (OGTT) in pregnant women. Eligible pregnant women underwent a 75-g OGTT at 24-32 weeks' gestation. A sample for A1C was also collected. Neonatal anthropometrics and cord serum C-peptide were measured. Associations with outcomes were assessed using multiple logistic regression with adjustment for potential confounders. Among 23,316 HAPO Study participants with glucose levels blinded to caregivers, 21,064 had a nonvariant A1C result. The mean ± SD A1C was 4.79 ± 0.40%. Associations were significantly stronger with glucose measures than with A1C for birth weight, sum of skinfolds, and percent body fat >90th percentile and for fasting and 1-h glucose for cord C-peptide (all P < 0.01). For example, in fully adjusted models, odds ratios (ORs) for birth weight >90th percentile for each measure higher by 1 SD were 1.39, 1.45, and 1.38, respectively, for fasting, 1-, and 2-h plasma glucose and 1.15 for A1C. ORs for cord C-peptide >90th percentile were 1.56, 1.45, and 1.35 for glucose, respectively, and 1.32 for A1C. ORs were similar for glucose and A1C for primary cesarean section, preeclampsia, and preterm delivery. On the basis of associations with adverse outcomes, these findings suggest that A1C measurement is not a useful alternative to an OGTT in pregnant women.

Prediction of adverse pregnancy outcome in monochorionic- diamniotic twin pregnancies complicated by selective fetal growth restriction.

PubMed

Monaghan, Caitriona; Kalafat, Erkan; Binder, Julia; Thilaganathan, Baskaran; Khalil, Asma

2018-04-28

To identify key factors implicated in adverse perinatal outcome in monochorionic twin pregnancies complicated by selective fetal growth restriction. This is a retrospective cohort study conducted in a single tertiary referral centre included all monochorionic diamniotic (MCDA) twin pregnancies complicated by selective fetal growth restriction (sFGR). The presence of co-existing twin to twin transfusion syndrome (TTTS) was noted. Fetal biometry and Doppler indices, including the umbilical artery (UA) and ductus venosus (DV), were recorded at the time of diagnosis. The type of sFGR was diagnosed according to the pattern of end-diastolic flow (EDF) in the UA of the smaller twin. DV pulsatility indices were converted to z-scores and estimated fetal weight (EFW) values to centiles, to correct for gestational age (GA). Cox proportional hazards model was used to examine for independent predictors of adverse perinatal outcome. Adverse perinatal outcome was defined according to survival and included both intra-uterine fetal demise and neonatal death of the FGR twin. We analysed 104 pregnancies complicated by sFGR. Sixty-six (63.5%) were diagnosed with type I and 38 (36.5%) with type II at initial presentation. Pregnancies complicated by type II sFGR were diagnosed (median GA 19.6 weeks' vs 21.5 weeks, p=0.012) and delivered (median GA 30.4 weeks' vs 32.57 weeks; p=0.055) earlier and are associated with increased risk of adverse perinatal outcomes (intrauterine demise of the smaller twin 19.7% vs 10.6%, p=0.001), when compared to type I sFGR. Twin pregnancies complicated by sFGR, whether type I or II, resulting in intrauterine demise have a significantly earlier onset of diagnosis (p<0.001), earlier GA at delivery (p<0.05), higher DV pulsatility index (p<0.05), and lower birth weight (BW) centile of the smaller twin (p<0.01) when compared to pregnancies resulting in livebirth. Co-existing TTTS had no significant impact on the perinatal outcome of pregnancies diagnosed with

International Federation of Gynecology and Obstetrics opinion on reproductive health impacts of exposure to toxic environmental chemicals.

PubMed

Di Renzo, Gian Carlo; Conry, Jeanne A; Blake, Jennifer; DeFrancesco, Mark S; DeNicola, Nathaniel; Martin, James N; McCue, Kelly A; Richmond, David; Shah, Abid; Sutton, Patrice; Woodruff, Tracey J; van der Poel, Sheryl Ziemin; Giudice, Linda C

2015-12-01

Exposure to toxic environmental chemicals during pregnancy and breastfeeding is ubiquitous and is a threat to healthy human reproduction. There are tens of thousands of chemicals in global commerce, and even small exposures to toxic chemicals during pregnancy can trigger adverse health consequences. Exposure to toxic environmental chemicals and related health outcomes are inequitably distributed within and between countries; universally, the consequences of exposure are disproportionately borne by people with low incomes. Discrimination, other social factors, economic factors, and occupation impact risk of exposure and harm. Documented links between prenatal exposure to environmental chemicals and adverse health outcomes span the life course and include impacts on fertility and pregnancy, neurodevelopment, and cancer. The global health and economic burden related to toxic environmental chemicals is in excess of millions of deaths and billions of dollars every year. On the basis of accumulating robust evidence of exposures and adverse health impacts related to toxic environmental chemicals, the International Federation of Gynecology and Obstetrics (FIGO) joins other leading reproductive health professional societies in calling for timely action to prevent harm. FIGO recommends that reproductive and other health professionals advocate for policies to prevent exposure to toxic environmental chemicals, work to ensure a healthy food system for all, make environmental health part of health care, and champion environmental justice. Copyright © 2015 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

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...

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...

The impact of female reproductive function on outcomes after traumatic brain injury.

PubMed

Ripley, David L; Harrison-Felix, Cindy; Sendroy-Terrill, Melissa; Cusick, Christopher P; Dannels-McClure, Amy; Morey, Clare

2008-06-01

To determine the impact of traumatic brain injury (TBI) on female menstrual and reproductive functioning and to examine the relationships between severity of injury, duration of amenorrhea, and TBI outcomes. Retrospective cohort survey. Telephone interview. Women (N=30; age range, 18-45y), between 1 and 3 years postinjury, who had completed inpatient rehabilitation for TBI. Not applicable. Data collected included menstrual and reproductive functioning pre- and postinjury, demographic, and injury characteristics. Outcome measures included the Glasgow Outcome Scale-Extended (GOS-E), the Mayo-Portland Adaptability Inventory-4 (MPAI-4), and the Medical Outcome Study 12-Item Short-Form Health Survey, Version 2 (SF-12v2). The median duration of amenorrhea was 61 days (range, 20-344d). Many subjects' menstrual function changed after TBI, reporting a significant increase in skipped menses postinjury (P<.001) and a trend toward more painful menses (P=.061). More severe TBI, as measured by the duration of posttraumatic amnesia, was significantly predictive of a longer duration of amenorrhea (P=.004). Subjects with a shorter duration of amenorrhea scored significantly better on the SF-12 physical component subscale (P=.004), the GOS-E (P=.05), and the MPAI-4 participation subscale (P=.05) after controlling for age, injury severity, and time postinjury. The severity of TBI was predictive of duration of amenorrhea and a shorter duration of amenorrhea was predictive of better ratings of global outcome, community participation, and health-related quality of life postinjury.

Association Between Pesticide Residue Intake From Consumption of Fruits and Vegetables and Pregnancy Outcomes Among Women Undergoing Infertility Treatment With Assisted Reproductive Technology

PubMed Central

Chiu, Yu-Han; Williams, Paige L.; Gillman, Matthew W.; Gaskins, Audrey J.; Mínguez-Alarcón, Lidia; Souter, Irene; Toth, Thomas L.; Ford, Jennifer B.; Hauser, Russ; Chavarro, Jorge E.

2018-01-01

IMPORTANCE Animal experiments suggest that ingestion of pesticide mixtures at environmentally relevant concentrations decreases the number of live-born offspring. Whether the same is true in humans is unknown. OBJECTIVE To examine the association of preconception intake of pesticide residues in fruits and vegetables (FVs) with outcomes of infertility treatment with assisted reproductive technologies (ART). DESIGN, SETTING, AND PARTICIPANTS This analysis included 325 women who completed a diet assessment and subsequently underwent 541 ART cycles in the Environment and Reproductive Health (EARTH) prospective cohort study (2007–2016) at a fertility center at a teaching hospital. We categorized FVs as having high or low pesticide residues using a validated method based on surveillance data from the US Department of Agriculture. Cluster-weighted generalized estimating equations were used to analyze associations of high– and low–pesticide residue FV intake with ART outcomes. MAIN OUTCOMES AND MEASURES Adjusted probabilities of clinical pregnancy and live birth per treatment cycle. RESULTS In the 325 participants (mean [SD] age, 35.1 [4.0] y; body mass index, 24.1 [4.3]), mean (SD) intakes of high– and low–pesticide residue FVs were 1.7 (1.0) and 2.8 (1.6) servings/d, respectively. Greater intake of high–pesticide residue FVs was associated with a lower probability of clinical pregnancy and live birth. Compared with women in the lowest quartile of high-pesticide FV intake (<1.0 servings/d), women in the highest quartile (≥ 2.3 servings/d) had 18% (95% CI, 5%–30%) lower probability of clinical pregnancy and 26% (95% CI, 13%–37%) lower probability of live birth. Intake of low–pesticide residue FVs was not significantly related to ART outcomes. CONCLUSIONS AND RELEVANCE Higher consumption of high–pesticide residue FVs was associated with lower probabilities of pregnancy and live birth following infertility treatment with ART. These data suggest that

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. Published by Oxford University Press on behalf of the Society of Toxicology 2015. This work is written by US Government employees and is in the public domain in the US.

Biomarkers for Adverse Pregnancy Outcomes in Rheumatic Diseases.

PubMed

Soh, May Ching; Nelson-Piercy, Catherine

2017-05-01

Pregnancy is a delicate balance of angiogenic factors. Adverse pregnancy outcomes in the form of placental insufficiency occur when antiangiogenic factors predominate, which manifests as maternal-placental syndrome (MPS). Women with rheumatic disease are at increased risk of MPS. Endothelial damage from circulating antiangiogenic factors and other inflammatory molecules in combination with preexisting maternal vascular risk factors is the likely underlying pathophysiological process for MPS. It is likely that these changes persist, and additional "insults" from ongoing inflammation, medications, and disease damage contribute to the development of accelerated cardiovascular disease seen in young women with rheumatic disease. Copyright © 2017 Elsevier Inc. All rights reserved.

The adverse outcome pathway for skin sensitisation: Moving closer to replacing animal testing.

PubMed

Schultz, Terry W; Dimitrova, Gergana; Dimitrov, Sabcho; Mekenyan, Ovanes G

2016-10-01

This article outlines the work of the Organisation for Economic Co-operation and Development (OECD) that led to being jointly awarded the 2015 Lush Black Box Prize. The award-winning work centred on the development of 'The Adverse Outcome Pathway for Skin Sensitisation Initiated by Covalent Binding to Proteins'. This Adverse Outcome Pathway (AOP) has provided the mechanistic basis for the integration of skin sensitisation-related information. Recent developments in integrated approaches to testing and assessment, based on the AOP, are summarised. The impact of the AOP on regulatory policy and on the Three Rs are discussed. An overview of the next generation of the skin sensitisation AOP module in the OECD QSAR Toolbox, based on more-recent work at the Laboratory of Mathematical Chemistry, is also presented. 2016 FRAME.

Travel time from home to hospital and adverse perinatal outcomes in women at term in the Netherlands.

PubMed

Ravelli, A C J; Jager, K J; de Groot, M H; Erwich, J J H M; Rijninks-van Driel, G C; Tromp, M; Eskes, M; Abu-Hanna, A; Mol, B W J

2011-03-01

To study the effect of travel time, at the start or during labour, from home to hospital on mortality and adverse outcomes in pregnant women at term in primary and secondary care. Population-based cohort study from 2000 up to and including 2006. The Netherlands Perinatal Registry. A total of 751,926 singleton term hospital births. We assessed the impact of travel time by car, calculated from the postal code of the woman's residence to the 99 maternity units, on neonatal outcome. Logistic regression modelling with adjustments for gestational age, maternal age, parity, ethnicity, socio-economic status, urbanisation, tertiary care centres and volume of the hospital was used. Mortality (intrapartum, and early and late neonatal mortality) and adverse neonatal outcomes (mortality, Apgar <4 and/or admission to a neonatal intensive care unit). The mortality was 1.5 per 1000 births, and adverse outcomes occurred in 6.0 per 1000 births. There was a positive relationship between longer travel time (≥20 minutes) and total mortality (OR 1.17, 95% CI 1.002-1.36), neonatal mortality within 24 hours (OR 1.51, 95% CI 1.13-2.02) and with adverse outcomes (OR 1.27, 95% CI 1.17-1.38). In addition to travel time, both delivery at 37 weeks of gestation (OR 2.23, 95% CI 1.81-2.73) or 41 weeks of gestation (OR 1.52, 95% CI 1.29-1.80) increased the risk of mortality. A travel time from home to hospital of 20 minutes or more by car is associated with an increased risk of mortality and adverse outcomes in women at term in the Netherlands. These findings should be considered in plans for the centralisation of obstetric care. © 2010 The Authors Journal compilation © RCOG 2010 BJOG An International Journal of Obstetrics and Gynaecology.

Fetal sex modifies effects of prenatal stress exposure and adverse birth outcomes.

PubMed

Wainstock, Tamar; Shoham-Vardi, Ilana; Glasser, Saralee; Anteby, Eyal; Lerner-Geva, Liat

2015-01-01

Prenatal maternal stress is associated with pregnancy complications, poor fetal development and poor birth outcomes. Fetal sex has also been shown to affect the course of pregnancy and its outcomes. The aim of this study was to evaluate whether fetal sex modifies the association between continuous exposure to life-threatening rocket attack alarms and adverse pregnancy outcomes. A retrospective cohort study was conducted in which the exposed group was comprised of 1846 women exposed to rocket-attack alarms before and during pregnancy. The unexposed group, with similar sociodemographic characteristics, delivered during the same period of time at the same medical center, but resided out of rocket-attack range. Multivariable models for each gender separately, controlling for possible confounders, evaluated the risk associated with exposure for preterm births (PTB), low birthweight (LBW), small for gestational age and small head circumference (HC). In both univariable and multivariable analyses exposure status was a significant risk factor in female fetuses only: PTB (adj. OR = 1.43; 1.04-1.96), LBW (adj. OR = 1.41; 1.02-1.95) and HC < 31 cm (adj. OR = 1.78; 1.11-2.88). In addition, regarding all adverse outcomes, the male-to-female ratio was higher in the exposed group than in the unexposed group. The findings support the hypothesis that male and female fetuses respond differentially to chronic maternal stress.

Unmet reproductive health needs among women in some West African countries: a systematic review of outcome measures and determinants.

PubMed

Ayanore, Martin Amogre; Pavlova, Milena; Groot, Wim

2016-01-16

Identifying relevant measures of women's reproductive health needs is critical to improve women's chances of service utilization. The study aims to systematically review and analyze the adequacy of outcome measures and determinants applied in previous studies for assessing women reproductive health needs across West Africa. Evidence on outcomes and determinants of unmet reproductive health needs among women of childbearing age in diverse multicultural, religious, and ethnic settings in West African countries was systematically reviewed. The review included recent English language publications (from January 2009 - March 2014). Clinical studies particularly on obstetric care services and reproductive services in relation to HIV/AIDS were excluded. We acknowledge the possibility to have excluded non-English publications and yet-to-be-published articles related to the study aim and objectives. Outcomes and determinants were assessed and defined at three main levels; contraceptive use, obstetric care, and antenatal care utilization. Results show increasing unmet need for women's reproductive health needs. Socio-cultural norms and practices resulting in discontinuation of service use, economic constraints, travel distance to access services and low education levels of women were found to be key predictors of service utilization for contraception, antenatal and obstetric care services. Outcome measures were mainly assessed based on service utilization, satisfaction, cost, and quality of services available as core measures across the three levels assessed in this review. Evidence from this review indicates that currently applied measures of women's reproductive health needs might be inadequate in attaining best maternal outcomes since they appear rather broad. More support and research for developing and advancing context-related measures may help to improve women's maternal health.

Intersections of poverty, race/ethnicity, and sex: Alcohol consumption and adverse outcomes in the United States

PubMed Central

Glass, Joseph E.; Rathouz, Paul J.; Gattis, Maurice; Joo, Young Sun; Nelson, Jennifer C.; Williams, Emily C.

2017-01-01

We examine whether intersectionality theory—which formalizes the notion that adverse health outcomes owing to having a marginalized social status, identity, or characteristic, may be magnified for individuals with an additional marginalized social status, identity, or characteristic —can be applied using quantitative methods to describe the differential effects of poverty on alcohol consumption across sex and race/ethnicity. Using the National Epidemiologic Survey on Alcohol and Related Conditions, we analyze longitudinal data from Black, Hispanic, and White drinkers (n = 21,140) to assess multiplicative interactions between poverty, as defined by the U.S. Census Bureau, sex, and race/ethnicity, on adverse alcohol outcomes. Findings indicated that the effect of poverty on the past-year incidence of heavy episodic drinking was stronger among Black men and Black women in comparison to men and women of other racial/ethnic groups. Poverty reduction programs that are culturally informed may help reduce racial/ethnic disparities in the adverse outcomes of alcohol consumption. PMID:28349171

Intersections of poverty, race/ethnicity, and sex: alcohol consumption and adverse outcomes in the United States.

PubMed

Glass, Joseph E; Rathouz, Paul J; Gattis, Maurice; Joo, Young Sun; Nelson, Jennifer C; Williams, Emily C

2017-05-01

We examine whether intersectionality theory-which formalizes the notion that adverse health outcomes owing to having a marginalized social status, identity, or characteristic, may be magnified for individuals with an additional marginalized social status, identity, or characteristic-can be applied using quantitative methods to describe the differential effects of poverty on alcohol consumption across sex and race/ethnicity. Using the National Epidemiologic Survey on Alcohol and Related Conditions, we analyze longitudinal data from Black, Hispanic, and White drinkers (n = 21,140) to assess multiplicative interactions between poverty, as defined by the US Census Bureau, sex, and race/ethnicity, on adverse alcohol outcomes. Findings indicated that the effect of poverty on the past-year incidence of heavy episodic drinking was stronger among Black men and Black women in comparison to men and women of other racial/ethnic groups. Poverty reduction programs that are culturally informed may help reduce racial/ethnic disparities in the adverse outcomes of alcohol consumption.

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...

Managing patients with concerns about workplace reproductive hazards.

PubMed

Frazier, L M; Jones, T L

2000-01-01

To find out who uses an occupational reproductive consultation service, what proportion of patients have different types of workplace exposures, and what hypotheses can be generated about barriers to implementing medically necessary job modifications to promote reproductive health. A case series study was conducted by reviewing medical records at two occupational health clinics. 51 patients (1 man and 50 women) were seen, 10 of whom wished to discuss a future pregnancy and 41 of whom were pregnant. Pregnant women worked with a mean of 15.5 different chemicals, and patients were also concerned about ionizing radiation, biological hazards, electromagnetic fields, and ultraviolet light. Pregnant women made clinic visits at a mean gestational age of 10.9 weeks. Only one man used the service, suggesting a lack of knowledge about possible paternal contributions to adverse reproductive outcomes. Many pregnant women visited the clinic too late to prevent harm from exposure to some teratogens, so preconception counseling may be of benefit. Cases are presented that illustrate ways in which the primary care provider can assist the patient who may be exposed to reproductive hazards.

Maternal Smoking Among Women With and Without Use of Assisted Reproductive Technologies

PubMed Central

Tong, Van T.; Kissin, Dmitry M.; Bernson, Dana; Copeland, Glenn; Boulet, Sheree L.; Zhang, Yujia; Jamieson, Denise J.; England, Lucinda J.

2016-01-01

Objective To estimate smoking prevalence during the year before pregnancy and during pregnancy and adverse outcomes among women who delivered infants with and without assisted reproductive technology (ART) using linked birth certificates (BC) and National ART Surveillance System (NASS) data. Methods Data were analyzed for 384,390 women and 392,248 infants born in Massachusetts and Michigan during 2008–2009. Maternal smoking prevalence was estimated using smoking indicated from BC by ART status. For ART users, to evaluate underreporting, prepregnancy smoking was estimated from BC, NASS, or both sources. Effect of prenatal smoking on preterm and mean birthweight (term only) for singleton infants were examined by ART status. Results Maternal smoking prevalence estimates were significantly lower for ART users than nonusers (pre-pregnancy = 3.2% vs. 16.7%; prenatal = 1.0% vs. 11.1%, p < 0.05). When combining smoking information from BC and NASS, prepregnancy smoking prevalence estimates for ART users could be as high as 4.4% to 6.1%. Adverse effects of smoking on infant outcomes in ART pregnancies were consistent with the effects seen in non-ART pregnancies, specifically decline in infant birthweight and increase in preterm delivery, although association between smoking and preterm was not significant. Conclusion A low, but substantial proportion of ART users smoked before and during pregnancy. As ART users are highly motivated to get pregnant, it should be clearly communicated that smoking can decrease fertility and adversely affect pregnancy outcomes. Continued efforts are needed to encourage smoking cessation and maintain tobacco abstinence among all women of reproductive age. PMID:27243366

Derivation and evaluation of adverse outcome pathways for the effects of cyclooxygenase inhibitors on reproductive processes in fish

EPA Science Inventory

Cyclooxygenase (COX) inhibition is of concern in fish because COX inhibitors (e.g., ibuprofen) are ubiquitous in aquatic systems/fish tissues, and can disrupt synthesis of prostaglandins that modulate a variety of essential biological functions (e.g., reproduction). This study ut...

Allostatic load: A theoretical model for understanding the relationship between maternal posttraumatic stress disorder and adverse birth outcomes.

PubMed

Li, Yang; Rosemberg, Marie-Anne Sanon; Seng, Julia S

2018-07-01

Adverse birth outcomes such as preterm birth and low birth weight are significant public health concerns and contribute to neonatal morbidity and mortality. Studies have increasingly been exploring the predictive effects of maternal posttraumatic stress disorder (PTSD) on adverse birth outcomes. However, the biological mechanisms by which maternal PTSD affects birth outcomes are not well understood. Allostatic load refers to the cumulative dysregulations of the multiple physiological systems as a response to multiple social-ecological levels of chronic stress. Allostatic load has been well documented in relation to both chronic stress and adverse health outcomes in non-pregnant populations. However, the mediating role of allostatic load is less understood when it comes to maternal PTSD and adverse birth outcomes. To propose a theoretical model that depicts how allostatic load could mediate the impact of maternal PTSD on birth outcomes. We followed the procedures for theory synthesis approach described by Walker and Avant (2011), including specifying focal concepts, identifying related factors and relationships, and constructing an integrated representation. We first present a theoretical overview of the allostatic load theory and the other 4 relevant theoretical models. Then we provide a brief narrative review of literature that empirically supports the propositions of the integrated model. Finally, we describe our theoretical model. The theoretical model synthesized has the potential to advance perinatal research by delineating multiple biomarkers to be used in future. After it is well validated, it could be utilized as the theoretical basis for health care professionals to identify high-risk women by evaluating their experiences of psychosocial and traumatic stress and to develop and evaluate service delivery and clinical interventions that might modify maternal perceptions or experiences of stress and eliminate their impacts on adverse birth outcomes. Copyright

Adverse Effects of Common Drugs: Dietary Supplements.

PubMed

Felix, Todd Matthew; Karpa, Kelly Dowhower; Lewis, Peter R

2015-09-01

Dietary supplement-induced adverse effects often resolve quickly after discontinuation of the offending product, especially in younger patients. The potential for unwanted outcomes can be amplified in elderly patients or those taking multiple prescription drugs, especially where interactions exist with drugs metabolized by cytochrome P450 enzymes. Attributing injury or illness to a specific supplement can be challenging, especially in light of multi-ingredient products, product variability, and variability in reporting, as well as the vast underreporting of adverse drug reactions. Clinicians prescribing a new drug or evaluating a patient with a new symptom complex should inquire about use of herbal and dietary supplements as part of a comprehensive evaluation. Clinicians should report suspected supplement-related adverse effects to the local or state health department, as well as the Food and Drug Administration's MedWatch program (available at https://www.safetyreporting.hhs.gov). Clinicians should consider discussing suspected adverse effects involving drugs, herbal products, or dietary supplements with their community- and hospital-based pharmacists, and explore patient management options with medical or clinical toxicology subspecialists. Written permission from the American Academy of Family Physicians is required for reproduction of this material in whole or in part in any form or medium.

Adverse obstetric outcomes during delivery hospitalizations complicated by suicidal behavior among US pregnant women.

PubMed

Zhong, Qiu-Yue; Gelaye, Bizu; Smoller, Jordan W; Avillach, Paul; Cai, Tianxi; Williams, Michelle A

2018-01-01

The effects of suicidal behavior on obstetric outcomes remain dangerously unquantified. We sought to report on the risk of adverse obstetric outcomes for US women with suicidal behavior at the time of delivery. We performed a cross-sectional analysis of delivery hospitalizations from 2007-2012 National (Nationwide) Inpatient Sample. From the same hospitalization record, International Classification of Diseases codes were used to identify suicidal behavior and adverse obstetric outcomes. Adjusted odds ratios (aOR) and 95% confidence intervals (CI) were obtained using logistic regression. Of the 23,507,597 delivery hospitalizations, 2,180 were complicated by suicidal behavior. Women with suicidal behavior were at a heightened risk for outcomes including antepartum hemorrhage (aOR = 2.34; 95% CI: 1.47-3.74), placental abruption (aOR = 2.07; 95% CI: 1.17-3.66), postpartum hemorrhage (aOR = 2.33; 95% CI: 1.61-3.37), premature delivery (aOR = 3.08; 95% CI: 2.43-3.90), stillbirth (aOR = 10.73; 95% CI: 7.41-15.56), poor fetal growth (aOR = 1.70; 95% CI: 1.10-2.62), and fetal anomalies (aOR = 3.72; 95% CI: 2.57-5.40). No significant association was observed for maternal suicidal behavior with cesarean delivery, induction of labor, premature rupture of membranes, excessive fetal growth, and fetal distress. The mean length of stay was longer for women with suicidal behavior. During delivery hospitalization, women with suicidal behavior are at increased risk for many adverse obstetric outcomes, highlighting the importance of screening for and providing appropriate clinical care for women with suicidal behavior during pregnancy.

Four trace elements in pregnant women and their relationships with adverse pregnancy outcomes.

PubMed

Shen, P-J; Gong, B; Xu, F-Y; Luo, Y

2015-12-01

Lack of trace elements during pregnancy is detrimental to maternal and fetal health. Our aim is to study the changes in trace element levels in Chinese pregnant women and their association with adverse pregnancy outcomes. 1568 cases of Chinese pregnant women in remote areas were collected for a prospective cohort study. Serum copper, zinc, calcium and iron levels were measured at pre-pregnancy, 1st trimester (7w-12w), 2nd trimester (24w-28w) and 3rd trimester (35w-40w). (1) Serum copper levels was significantly higher after pregnancy than before, calcium and iron levels decreased, but zinc levels did not change significantly. (2) Copper and zinc deficiency in pregnant women was not a common finding, but lack of iron and calcium was frequently encountered; iron deficiency was especially common in the 3rd trimester (42.27%). (3) Serum zinc and iron levels in patients who either had a miscarriage or a preterm delivery were significantly lower than in the control group (p < 0.05). In patients with premature rupture of membranes, serum zinc levels were significantly lower (p < 0.05). In patients with intrauterine growth restriction (IUGR), serum copper, zinc, calcium and iron were significantly lower (p < 0.05). Trace elements is closely associated with fetal growth and development during pregnancy. Deficiency can lead to adverse pregnancy outcomes. Therefore, we should have a reasonable diet, replenish trace elements, therefore reducing the occurrence of adverse pregnancy outcomes.

EMBRYONIC VASCULAR DISRUPTION ADVERSE OUTCOMES: LINKING HIGH THROUGHPUT SIGNALING SIGNATURES WITH FUNCTIONAL CONSEQUENCES

EPA Science Inventory

Embryonic vascular disruption is an important adverse outcome pathway (AOP) given the knowledge that chemical disruption of early cardiovascular system development leads to broad prenatal defects. High throughput screening (HTS) assays provide potential building blocks for AOP d...

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...

Global Estimates of Syphilis in Pregnancy and Associated Adverse Outcomes: Analysis of Multinational Antenatal Surveillance Data

PubMed Central

Newman, Lori; Kamb, Mary; Hawkes, Sarah; Gomez, Gabriela; Say, Lale; Seuc, Armando; Broutet, Nathalie

2013-01-01

Background The World Health Organization initiative to eliminate mother-to-child transmission of syphilis aims for ≥90% of pregnant women to be tested for syphilis and ≥90% to receive treatment by 2015. We calculated global and regional estimates of syphilis in pregnancy and associated adverse outcomes for 2008, as well as antenatal care (ANC) coverage for women with syphilis. Methods and Findings Estimates were based upon a health service delivery model. National syphilis seropositivity data from 97 of 193 countries and ANC coverage from 147 countries were obtained from World Health Organization databases. Proportions of adverse outcomes and effectiveness of screening and treatment were from published literature. Regional estimates of ANC syphilis testing and treatment were examined through sensitivity analysis. In 2008, approximately 1.36 million (range: 1.16 to 1.56 million) pregnant women globally were estimated to have probable active syphilis; of these, 80% had attended ANC. Globally, 520,905 (best case: 425,847; worst case: 615,963) adverse outcomes were estimated to be caused by maternal syphilis, including approximately 212,327 (174,938; 249,716) stillbirths (>28 wk) or early fetal deaths (22 to 28 wk), 91,764 (76,141; 107,397) neonatal deaths, 65,267 (56,929; 73,605) preterm or low birth weight infants, and 151,547 (117,848; 185,245) infected newborns. Approximately 66% of adverse outcomes occurred in ANC attendees who were not tested or were not treated for syphilis. In 2008, based on the middle case scenario, clinical services likely averted 26% of all adverse outcomes. Limitations include missing syphilis seropositivity data for many countries in Europe, the Mediterranean, and North America, and use of estimates for the proportion of syphilis that was “probable active,” and for testing and treatment coverage. Conclusions Syphilis continues to affect large numbers of pregnant women, causing substantial perinatal morbidity and mortality that

Reproductive Outcomes Following Maternal Exposure to the Events of September 11, 2001, at the World Trade Center, in New York City.

PubMed

Maslow, Carey B; Caramanica, Kimberly; Li, Jiehui; Stellman, Steven D; Brackbill, Robert M

2016-10-01

To estimate associations between exposure to the events of September 11, 2001, (9/11) and low birth weight (LBW), preterm delivery (PD), and small size for gestational age (SGA). We matched birth certificates filed in New York City for singleton births between 9/11 and the end of 2010 to 9/11-related exposure data provided by mothers who were World Trade Center Health Registry enrollees. Generalized estimating equations estimated associations between exposures and LBW, PD, and SGA. Among 3360 births, 5.8% were LBW, 6.5% were PD, and 9% were SGA. Having incurred at least 2 of 4 exposures, having performed rescue or recovery work, and probable 9/11-related posttraumatic stress disorder 2 to 3 years after 9/11 were associated with PD and LBW during the early study period. Disasters on the magnitude of 9/11 may exert effects on reproductive outcomes for several years. Women who are pregnant during and after a disaster should be closely monitored for physical and psychological sequelae. In utero and maternal disaster exposure may affect birth outcomes. Researchers studying effects of individual disasters should identify commonalities that may inform postdisaster responses to minimize disaster-related adverse birth outcomes.

Use of an Adverse Outcome Pathway for Hepatic Steatosis to Build Chemical Groups

EPA Science Inventory

The Adverse Outcome Pathway (AOP) framework systematically documents the mechanisms underlying effects of chemicals starting with the initial interaction of chemicals with the biological system, i.e. the molecular initiating event (MIE). Chemical activity in assays designed to mo...

Effect of breeding protocols and reproductive tract score on reproductive performance of dairy heifers and economic outcome of breeding programs.

PubMed

Stevenson, J L; Rodrigues, J A; Braga, F A; Bitente, S; Dalton, J C; Santos, J E P; Chebel, R C

2008-09-01

The objectives of this study were to evaluate the effect of reproductive protocols and reproductive tract score on reproductive performance of dairy heifers and economic outcomes of breeding programs. Holstein heifers (n = 534), 13 +/- 1 mo of age, were randomly assigned to 1 of 4 reproductive protocols. On the day of enrollment (d 0), heifers were palpated per rectum and received a score according to the maturity of their reproductive tract (1 = prepubertal; 2 = peripubertal; and 3 = puber-tal). Estrous detection-control heifers (CON, n = 146) received no treatment and were inseminated on detection of estrus for 28 d. Prostaglandin F(2alpha)-treated heifers (PGED, n = 137) received 1 injection of PGF(2alpha) on d 0 and were inseminated on detection of estrus; heifers not in-seminated by d 14 received a second injection of PGF(2alpha) and were observed for estrus and artificial insemination (AI) for an additional 14 d. Heifers enrolled in the estrous detection-timed AI (EDTAI, n = 140) treatment received a controlled internal drug-release (CIDR) insert on d 0, and 7 d later, the CIDR was removed and all heifers received an injection of PGF(2alpha), heifers received AI on detection of estrus, and those not inseminated by 72 h after PGF(2alpha) received an injection of GnRH concurrent with AI. Heifers in the GnRH-timed AI (GTAI, n = 111) treatment received 1 injection of GnRH on d 0, on d 6 heifers received a CIDR insert and injections of GnRH and PGF(2alpha), on d 13 the CIDR was removed and heifers received an injection of PGF(2alpha), and 48 h later all heifers received an injection of GnRH and AI. Pregnancy was diagnosed at 32 +/- 3 and 62 +/- 3 d after AI. Cost of reproductive protocols and their economic outcomes were calculated for a 28 d period beginning at enrollment. Heifers in the PGED treatment were inseminated at a faster rate than CON heifers. A smaller proportion of prepubertal and peripubertal heifers were inseminated within 14 d of enrollment

Computationally predicted Adverse Outcome Pathway networks for liver-related diseases using publicly available data sources: Case studies and lessons learned

EPA Science Inventory

The Adverse Outcome Pathway (AOP) framework summarizes key information about mechanistic events leading to an adverse health or ecological outcome. In recent years computationally predicted AOPs (cpAOP) making use of publicly available data have been proposed as a means of accele...

Development of a Novel Quantitative Adverse Outcome Pathway Predictive Model for Lung Cancer

EPA Science Inventory

Traditional methods for carcinogenicity testing are resource-intensive, retrospective, and time consuming. An increasing testing burden has generated interest in the adverse outcome pathway (AOP) concept as a tool to evaluate chemical safety in a more efficient, rapid and effecti...

Use of Adverse Outcome Pathways to Inform Decisions on Chemical Innovation, Regulation & Stewardship

EPA Science Inventory

An invited group of scientists participated in a SETAC Pellston WorkshopTM, “Advancing the Adverse Outcome Pathway (AOP) Concept – An International Horizon Scanning Approach,” in April 2017. The workshop addressed key challenges or limitations of AOP constructs...

Constructing Adverse Outcome Pathways: a Demonstration of an Ontology-based Semantics Mapping Approach

EPA Science Inventory

Adverse outcome pathway (AOP) provides a conceptual framework to evaluate and integrate chemical toxicity and its effects across the levels of biological organization. As such, it is essential to develop a resource-efficient and effective approach to extend molecular initiating ...

Adverse perinatal outcomes associated with moderate or severe maternal anaemia based on parity in Finland during 2006-10.

PubMed

Räisänen, Sari; Kancherla, Vijaya; Gissler, Mika; Kramer, Michael R; Heinonen, Seppo

2014-09-01

Anaemia during pregnancy is an important public health problem. We investigated whether the association between maternal anaemia during pregnancy and adverse perinatal outcomes differed between nulliparous and multiparous women. A retrospective population-based cohort study was conducted using data on all singleton births (n = 290 662) recorded in the Finnish Medical Birth Register during 2006-10. Maternal anaemia was defined as a maternal haemoglobin level of <100 g/L). Adverse perinatal outcomes that were examined included preterm delivery (<37 weeks), small-for-gestational age (SGA, <2 standard deviation), admission to neonatal intensive care, stillbirth, early neonatal death, and major congenital anomalies. An association between anaemia and adverse outcomes was assessed by logistic regression analysis. The prevalence of anaemia during pregnancy was 2.5% among nulliparous women and 2.3% among multiparous women. Among nulliparous women, anaemia was not associated with adverse perinatal outcomes. Among multiparous women, anaemia was associated with preterm delivery (adjusted odds ratio [aOR] 1.32, [95% CI 1.14, 1.53]), SGA (aOR 1.27, [95% CI 1.04, 1.55]), and admission to neonatal intensive care (aOR 1.23, [95% CI 1.10, 1.38]); there was a trend towards increased odds of major congenital anomalies (aOR 1.15, [95% CI 0.99, 1.34]). These data underscore that maternal anaemia is associated with several adverse perinatal outcomes. This association was, however, confined to multiparous women. Future research should explore in detail the timing of anaemia in these associations. © 2014 John Wiley & Sons Ltd.

The impact of stress and psychosocial interventions on assisted reproductive technology outcome.

PubMed

Morreale, Mary; Balon, Richard; Tancer, Manuel; Diamond, Michael

2011-01-01

In natural cycles of attempted conception, stress has been shown to predict lower conception rates. The objective of this article is to determine whether stress affects the outcome of assisted reproductive technology (ART) as well. In addition, this article analyzes the effect that psychosocial interventions targeting the reduction of stress have on ART outcomes. This review examined available PubMed articles published in the past 15 years, and 28 articles were included. Looking specifically at numbers of women studied, stress appears to negatively affect ART outcome; interventions targeting stress reduction appear beneficial. Because stress appears to negatively affect ART outcome, and psychosocial interventions do not have detrimental effects, screening for stress should occur and some type of intervention considered during the ART process.

Evaluation of Follicular Synchronization Caused by Estrogen Administration and Its Reproductive Outcome

PubMed Central

Wu, Bi; Shi, Yan; Gong, Xia; Yu, Lin; Chen, Qiuju; Wang, Jian; Sun, Zhaogui

2015-01-01

To evaluate multiple follicular development synchronization after estrogen stimulation in prepubertal mice, follicular responsiveness to gonadotropin superovulation, the prospective reproductive potential and ovarian polycystic ovary syndrome (PCOS)-like symptoms at adulthood, prepubertal mice were intraperitoneally injected with estrogen to establish an animal model with solvent as control. When synchronized tertiary follicles in ovaries, in vitro oocyte maturation and fertilization rates, blastocyst formation rate, developmental potential into offspring by embryo transfer, adult fertility and PCOS-like symptoms, and involved molecular mechanisms were focused, it was found that estrogen stimulation (10μg/gBW) leads to follicular development synchronization at the early tertiary stage in prepubertal mice; reproduction from oocytes to offspring could be realized by means of the artificial reproductive technology though the model mice lost their natural fertility when they were reared to adulthood; and typical symptoms of PCOS, except changes in inflammatory pathways, were not remained up to adulthood. So in conclusion, estrogen can lead to synchronization in follicular development in prepubertal mice, but does not affect reproductive outcome of oocytes, and no typical symptoms of PCOS remained at adulthood despite changes related to inflammation. PMID:26010950

Childhood outcomes of assisted reproductive technology.

PubMed

Savage, Tim; Peek, John; Hofman, Paul L; Cutfield, Wayne S

2011-09-01

There is a large population of children conceived via assisted reproductive technology (ART), which continues to increase worldwide, without a clear understanding of associated long-term outcomes. ART children are more likely to be the result of multiple pregnancies, and thus to be born prematurely or low birthweight. There is growing evidence that ART children are phenotypically and biochemically different from naturally conceived children, but the mechanism(s) leading to these changes have not been elucidated. There is a possible increased risk of rare imprinted gene disorders in these children. However, it remains unclear whether more subtle changes in DNA methylation occur commonly, leading to differences in gene expression and phenotype in ART children. Although an increased risk of cancer among ART children has been reported, the role of ART in the development of cancer has not been demonstrated. Further research and ongoing surveillance of ART children is essential to better understand the possible effects of ART on the long-term health of this population.

Maternal nutritional status predicts adverse birth outcomes among HIV-infected rural Ugandan women receiving combination antiretroviral therapy.

PubMed

Young, Sera; Murray, Katherine; Mwesigwa, Julia; Natureeba, Paul; Osterbauer, Beth; Achan, Jane; Arinaitwe, Emmanuel; Clark, Tamara; Ades, Veronica; Plenty, Albert; Charlebois, Edwin; Ruel, Theodore; Kamya, Moses; Havlir, Diane; Cohan, Deborah

2012-01-01

Maternal nutritional status is an important predictor of birth outcomes, yet little is known about the nutritional status of HIV-infected pregnant women treated with combination antiretroviral therapy (cART). We therefore examined the relationship between maternal BMI at study enrollment, gestational weight gain (GWG), and hemoglobin concentration (Hb) among 166 women initiating cART in rural Uganda. Prospective cohort. HIV-infected, ART-naïve pregnant women were enrolled between 12 and 28 weeks gestation and treated with a protease inhibitor or non-nucleoside reverse transcriptase inhibitor-based combination regimen. Nutritional status was assessed monthly. Neonatal anthropometry was examined at birth. Outcomes were evaluated using multivariate analysis. Mean GWG was 0.17 kg/week, 14.6% of women experienced weight loss during pregnancy, and 44.9% were anemic. Adverse fetal outcomes included low birth weight (LBW) (19.6%), preterm delivery (17.7%), fetal death (3.9%), stunting (21.1%), small-for-gestational age (15.1%), and head-sparing growth restriction (26%). No infants were HIV-infected. Gaining <0.1 kg/week was associated with LBW, preterm delivery, and a composite adverse obstetric/fetal outcome. Maternal weight at 7 months gestation predicted LBW. For each g/dL higher mean Hb, the odds of small-for-gestational age decreased by 52%. In our cohort of HIV-infected women initiating cART during pregnancy, grossly inadequate GWG was common. Infants whose mothers gained <0.1 kg/week were at increased risk for LBW, preterm delivery, and composite adverse birth outcomes. cART by itself may not be sufficient for decreasing the burden of adverse birth outcomes among HIV-infected women. Clinicaltrials.gov NCT00993031.

AOP-DB: A database resource for the exploration of Adverse Outcome Pathways through integrated association networks.

EPA Science Inventory

The Adverse Outcome Pathway (AOP) framework describes the progression of a toxicity pathway from molecular perturbation to population-level outcome in a series of measurable, mechanistic responses. The controlled, computer-readable vocabulary that defines an AOP has the ability t...

Systematic review of adverse outcomes of external cephalic version and persisting breech presentation at term.

PubMed

Nassar, Natasha; Roberts, Christine L; Barratt, Alexandra; Bell, Jane C; Olive, Emily C; Peat, Brian

2006-03-01

The aim of this study was to determine the frequency of adverse maternal and fetal outcomes of both external cephalic version (ECV) and persisting breech presentation at term. We conducted a systematic review of the literature using Medline, Embase and All Evidence Based Medicine (EBM) Reviews databases. Data were extracted from studies that compared women who had an ECV from 36 weeks' gestation with a similar control group of women enrolled at the same gestational age, eligible for, but who did not have an ECV. Eleven studies with a total of 2503 women were included. Adverse outcomes related to ECV were rarely reported and in most studies there was no evidence that relevant outcomes were ascertained among similar women who did not have an ECV. There was no increased risk of antepartum fetal death associated with ECV, but numbers were small. There were no reported cases of uterine rupture, placental abruption, prelabour rupture of membranes or cord prolapse, but these outcomes were not examined among controls. Onset of labour within 24 h and nuchal cord was non-significantly higher among women who had an ECV compared with those with a persisting breech. Despite limited reporting and small numbers, the results of our review suggest that adverse maternal and fetal outcomes of both ECV and persisting breech presentation are rare. Only with improved reporting and collection of safety data on ECV and persisting breech presentation can we provide high-quality information to assist informed decision making by pregnant women with a breech presentation at term.

Adverse Childhood Experiences and Young Adult Health Outcomes among Youth Aging Out of Foster Care.

PubMed

Rebbe, Rebecca; Nurius, Paula S; Courtney, Mark E; Ahrens, Kym R

2018-04-27

Former youth in foster care (YFC) are at greater risk of chronic health conditions than their peers. Although research in general population samples has demonstrated a dose-response relationship between adverse childhood experiences (ACEs) and adult health outcomes, few studies have conducted similar analyses in highly stress-exposed populations such as YFC. This paper uses person-centered latent class analysis (LCA) methods to examine the relationship between different profiles of ACE exposures and divergent health trajectories amongst this high-risk population. Data are from longitudinal research that followed transition-age YFC from age 17-26 (N =732). Using three subgroups previously identified by their ACEs histories, Complex, Environmental, and Lower Adversity groups, we applied group mean statistics to test for differences between the groups for physical and sexual health outcomes in young adulthood. In contrast to prior research demonstrating that the Environmental group was at the highest risk of criminal behavior outcomes, for most of the physical and sexual health risk outcomes evaluated in this paper, the Complex Adversity group had the highest risk. This study demonstrates that there are subgroups of YFC which each have a distinct profile of risk in young adulthood, with the Complex group being at highest risk of the physical and sexual health risk outcomes evaluated. Findings strongly suggest the need for targeted strategies to promote screening for ACEs and chronic health conditions, linkage to adult healthcare, and continuity of care for adolescents and young adults in foster care to offset these trajectories. Copyright © 2018. Published by Elsevier Inc.

Adverse obstetric outcomes during delivery hospitalizations complicated by suicidal behavior among US pregnant women

PubMed Central

Gelaye, Bizu; Smoller, Jordan W.; Avillach, Paul; Cai, Tianxi; Williams, Michelle A.

2018-01-01

Objective The effects of suicidal behavior on obstetric outcomes remain dangerously unquantified. We sought to report on the risk of adverse obstetric outcomes for US women with suicidal behavior at the time of delivery. Methods We performed a cross-sectional analysis of delivery hospitalizations from 2007–2012 National (Nationwide) Inpatient Sample. From the same hospitalization record, International Classification of Diseases codes were used to identify suicidal behavior and adverse obstetric outcomes. Adjusted odds ratios (aOR) and 95% confidence intervals (CI) were obtained using logistic regression. Results Of the 23,507,597 delivery hospitalizations, 2,180 were complicated by suicidal behavior. Women with suicidal behavior were at a heightened risk for outcomes including antepartum hemorrhage (aOR = 2.34; 95% CI: 1.47–3.74), placental abruption (aOR = 2.07; 95% CI: 1.17–3.66), postpartum hemorrhage (aOR = 2.33; 95% CI: 1.61–3.37), premature delivery (aOR = 3.08; 95% CI: 2.43–3.90), stillbirth (aOR = 10.73; 95% CI: 7.41–15.56), poor fetal growth (aOR = 1.70; 95% CI: 1.10–2.62), and fetal anomalies (aOR = 3.72; 95% CI: 2.57–5.40). No significant association was observed for maternal suicidal behavior with cesarean delivery, induction of labor, premature rupture of membranes, excessive fetal growth, and fetal distress. The mean length of stay was longer for women with suicidal behavior. Conclusion During delivery hospitalization, women with suicidal behavior are at increased risk for many adverse obstetric outcomes, highlighting the importance of screening for and providing appropriate clinical care for women with suicidal behavior during pregnancy. PMID:29447245

Effects of Prior Contest Experience and Contest Outcome on Female Reproductive Decisions and Offspring Fitness.

PubMed

Pilakouta, Natalie; Halford, Cerian; Rácz, Rita; Smiseth, Per T

2016-09-01

Winning or losing a prior contest can influence the outcome of future contests, but it might also alter subsequent reproductive decisions. For example, losers may increase their investment in the current breeding attempt if losing a contest indicates limited prospects for future breeding. Using the burying beetle Nicrophorus vespilloides, we tested whether females adjust their prehatching and posthatching reproductive effort after winning or losing a contest with a same-sex conspecific. Burying beetles breed on carcasses of small vertebrates for which there is fierce intrasexual competition. We found no evidence that winning or losing a contest influenced reproductive investment decisions in this species. Instead, we show that a female's prior contest experience (regardless of its outcome) influenced the amount of posthatching care provided, with downstream consequences for the female's reproductive output; both winners and losers spent more time provisioning food to their offspring and produced larger broods than females with no contest experience. We discuss the wider implications of our findings and present a conceptual model linking contest-mediated adjustments in parental investment to population-level processes. We propose that the frequency of intraspecific contests could both influence and be influenced by population dynamics in species where contest experience influences the size and/or number of offspring produced.

Cigarette smoking and adverse health outcomes among adults receiving federal housing assistance☆

PubMed Central

Helms, Veronica E.; King, Brian A.; Ashley, Peter J.

2017-01-01

Cigarette smoking is higher among low-income adults and individuals who reside in federally assisted housing are particularly susceptible to the adverse effects of smoking and secondhand smoke exposure. This study assessed smoking-related behaviors and health outcomes among U.S. adults who received federal housing assistance during 2006–2012. National Health Interview Survey data linked with administrative data from the U.S. Department of Housing and Urban Development were analyzed; 5218 HUD-assisted adults were assessed. Demographic characteristics associated with smoking, including frequency and consumption, were assessed among adult cigarette smokers. Fourteen adverse health outcomes were examined among cigarette smoking and nonsmoking adults. One-third (33.6%) of HUD-assisted adults were current cigarette smokers. Smoking prevalence was highest among adults aged 25–44 (42.5%), non-Hispanic whites (39.5%), and adults who resided in households with children (37.5%). Half attempted to quit in the past year; 82.1% were daily smokers; and, 35.8% of daily smokers reported smoking 20+ cigarettes a day. Multivariable analyses revealed that compared to nonsmokers, cigarette smokers had increased likelihood of reporting fair or poor health (95% CI: 1.04–1.52), chronic obstructive pulmonary disease (CI: 1.87–3.06), disability (CI: 1.25–1.83), asthma (CI: 1.02–1.55), serious psychological distress (CI: 1.39–2.52), >1 emergency room visit in the past year (CI: 1.09–1.56), and ≥10 work loss days in the past year (CI: 1.15–3.06). Adults who receive housing assistance represent an at-risk population for adverse health outcomes associated with smoking and secondhand smoke. Housing assistance programs provide a valuable platform for the implementation of evidence-based tobacco prevention and control measures, including smokefree policies. PMID:28192095

Cellulitis in Obesity: Adverse Outcomes Affected by Increases in Body Mass Index.

PubMed

Theofiles, Meghan; Maxson, Julie; Herges, Lori; Marcelin, Alberto; Angstman, Kurt B

2015-10-01

Cellulitis in obese patients is associated with increased rates of treatment failure compared to those with normal body mass index (BMI); however, patients have not been extensively studied in the outpatient environment or stratified based on range of obesity and associated risk factors. This study looked at antibiotic dosing and treatment failure in the obese population from the primary care perspective and accounts for BMI range, weight, comorbid diabetes, and tobacco use. This study was a retrospective chart review of 637 adult primary care patients designed to evaluate rates of treatment failure of outpatient cellulitis among patients of varying BMI. Treatment failure was defined as (a) hospital admission for intravenous antibiotics, (b) prolonged antibiotic course, or (c) requiring a different antibiotic after initial course. Adverse outcomes were not statistically significant between normal BMI and those with BMI ≥40 kg/m(2). A subset of patients with a BMI ≥50 kg/m(2) was noted to have approximately twice the rate of adverse outcomes as the normal BMI group. While controlling for age, gender, race, diagnosis of diabetes mellitus, and tobacco use, a BMI of ≥50 kg/m(2) and a weight ≥120 kg was associated with adverse outcomes with an odds ratio of 2.440 (95% CI, 1.260-4.724; P = .008) and 2.246 (95% CI, 1.154-4.369; P = .017), respectively. Patients with cellulitis weighing >120kg or with a BMI ≥50 kg/m(2) were at greatest risk for treatment failure in the outpatient setting, even when controlling for comorbid diabetes and tobacco use. As morbid obesity continues to become more prevalent, it becomes imperative that primary care physicians have better antibiotic dosing guidelines to account for the physiologic effects of obesity to minimize the risk of increased morbidity, health care costs, and antibiotic resistance. © The Author(s) 2015.

Sensivity of Adult Reproduction and Reproductive Development in Japanese Medaka Exposed to 4-Tert-octylphenol

EPA Science Inventory

In response to legislation, the USEPA is developing assessment tools for identifying chemicals likely to cause sublethal effects on reproduction and reproductive development with ultimate adverse impacts on fish populations. While fecundity and fertility data from short-term adul...

Tiered Approaches to Incorporate the Adverse Outcome Pathway Framework into Chemical-Specific Risk-Based Decision Making

EPA Science Inventory

The concept of Adverse Outcome Pathways (AOPs) arose as a means of addressing the challenges associated with establishing relationships between high-throughout (HT) in vitro dose response data and in vivo biological outcomes. However, AOP development has also been met with challe...

The effect of fertility treatment on adverse perinatal outcomes in women aged at least 40 years.

PubMed

Harlev, Avi; Walfisch, Asnat; Oran, Eynan; Har-Vardi, Iris; Friger, Michael; Lunenfeld, Eitan; Levitas, Eliahu

2018-01-01

To compare perinatal outcomes between spontaneous conception and assisted reproductive technologies (ART) among patients of advanced maternal age. The present retrospective study included data from singleton pregnancies of women aged at least 40 years who delivered between January 1, 1991, and December 31, 2013, at Soroka University Medical Center, Beer Sheva, Israel. Demographic, obstetric, and perinatal data were compared between pregnancies conceived with ART (in vitro fertilization [IVF] or ovulation induction) and those conceived spontaneously. Multiple regression models were used to define independent predictors of adverse outcomes. A total of 8244 singleton pregnancies were included; 229 (2.8%) following IVF, 86 (1.0%) following ovulation induction, and 7929 (96.2%) were spontaneous. Preterm delivery (P<0.001), fetal growth restriction (FGR) (P<0.001), and cesarean delivery (P<0.001) demonstrated linear associations with the conception mode; the highest rates for each were observed for IVF, with decreased rates for ovulation induction and spontaneous conception. The incidence of gestational diabetes and hypertensive disorders were highest among pregnancies following ART. No association was observed between conception mode and perinatal mortality. Multivariate logistic regression demonstrated that IVF was independently associated with increased odds of preterm delivery (P<0.001) and FGR (P=0.027) compared with spontaneous conception. Among patients of advanced maternal age, ART were independently associated with increased FGR and preterm delivery rates compared with spontaneous pregnancies; perinatal mortality was comparable. © 2017 International Federation of Gynecology and Obstetrics.

The household food insecurity gradient and potential reductions in adverse population mental health outcomes in Canadian adults.

PubMed

Jessiman-Perreault, Geneviève; McIntyre, Lynn

2017-12-01

Household food insecurity is related to poor mental health. This study examines whether the level of household food insecurity is associated with a gradient in the risk of reporting six adverse mental health outcomes. This study further quantifies the mental health impact if severe food insecurity, the extreme of the risk continuum, were eliminated in Canada. Using a pooled sample of the Canadian Community Health Survey (N = 302,683), we examined the relationship between level of food insecurity, in adults 18-64 years, and reporting six adverse mental health outcomes. We conducted a probit analysis adjusted for multi-variable models, to calculate the reduction in the odds of reporting mental health outcomes that might accrue from the elimination of severe food insecurity. Controlling for various demographic and socioeconomic covariates, a food insecurity gradient was found in six mental health outcomes. We calculated that a decrease between 8.1% and 16.0% in the reporting of these mental health outcomes would accrue if those who are currently severely food insecure became food secure, after controlling for covariates. Household food insecurity has a pervasive graded negative effect on a variety of mental health outcomes, in which significantly higher levels of food insecurity are associated with a higher risk of adverse mental health outcomes. Reduction of food insecurity, particularly at the severe level, is a public health concern and a modifiable structural determinant of health worthy of macro-level policy intervention.

Developing and applying the adverse outcome pathway concept for understanding and predicting neurotoxicity

EPA Science Inventory

To support a paradigm shift in regulatory toxicology testing and risk assessment, the Adverse Outcome Pathway (AOP) concept has recently been proposed. This concept is similar to that for Mode of Action (MOA), describing a sequence of measurable key events triggered by a molecula...

Evaluation of normalization of cerebro-placental ratio as a potential predictor for adverse outcome in SGA fetuses.

PubMed

Monteith, Cathy; Flood, Karen; Mullers, Sieglinde; Unterscheider, Julia; Breathnach, Fionnuala; Daly, Sean; Geary, Michael P; Kennelly, Mairead M; McAuliffe, Fionnuala M; O'Donoghue, Keelin; Hunter, Alison; Morrison, John J; Burke, Gerald; Dicker, Patrick; Tully, Elizabeth C; Malone, Fergal D

2017-03-01

Intrauterine growth restriction accounts for a significant proportion of perinatal morbidity and mortality currently encountered in obstetric practice. The primary goal of antenatal care is the early recognition of such conditions to allow treatment and optimization of both maternal and fetal outcomes. Management of pregnancies complicated by intrauterine growth restriction remains one of the greatest challenges in obstetrics. Frequently, however, clinical evidence of underlying uteroplacental dysfunction may only emerge at a late stage in the disease process. With advanced disease the only therapeutic intervention is delivery of the fetus and placenta. The cerebroplacental ratio is gaining much interest as a useful tool in differentiating the at-risk fetus in both intrauterine growth restriction and the appropriate-for-gestational-age setting. The cerebroplacental ratio quantifies the redistribution of the cardiac output resulting in a brain-sparing effect. The Prospective Observational Trial to Optimize Pediatric Health in Intrauterine Growth Restriction group previously demonstrated that the presence of a brain-sparing effect is significantly associated with an adverse perinatal outcome in the intrauterine growth restriction cohort. The aim of the Prospective Observational Trial to Optimize Pediatric Health in Intrauterine Growth Restriction study was to evaluate the optimal management of fetuses with an estimated fetal weight <10th centile. The objective of this secondary analysis was to evaluate if normalizing cerebroplacental ratio predicts adverse perinatal outcome. In all, 1116 consecutive singleton pregnancies with intrauterine growth restriction completed the study protocol over 2 years at 7 centers, undergoing serial sonographic evaluation and multivessel Doppler measurement. Cerebroplacental ratio was calculated using the pulsatility and resistance indices of the middle cerebral and umbilical artery. Abnormal cerebroplacental ratio was defined as <1

Reproductive outcome in 3 families with a satellited chromosome 4 with review of the literature

DOE Office of Scientific and Technical Information (OSTI.GOV)

Arn, P.H.; Younie, L.; Russo, S.

We describe 3 families segregating for a translocation of the nucleolus organizer region (NOR) onto chromosome 4. Review of previously reported cases of translocations involving NOR and chromosome 4 shows that these translocations may be associated with variable reproductive outcomes. We provide evidence that imprinting is not the mechanism responsible for the variable reproductive outcomes in the case of satellited 4p chromosomes; this may offer indirect support for a ribosomal gene position effect. Translocated ribosomal genes may influence the expression of neighboring genes and could explain the variable phenotypes in individuals with satellited nonacrocentric chromosomes. We recommend that prenatal counselingmore » of individuals with satellited nonacrocentric chromosomes should be cautious. 23 refs., 2 figs., 1 tab.« less

Systemic oxidative stress could predict assisted reproductive technique outcome.

PubMed

Ahelik, A; Mändar, R; Korrovits, P; Karits, P; Talving, E; Rosenstein, K; Jaagura, M; Salumets, A; Kullisaar, T

2015-05-01

Previous studies have indicated that OxS (oxidative stress) may appear as a possible reason for poor ART outcome. Our aim was to study OxS levels in both partners of couples seeking Assisted reproduction Technology (ART). Altogether 79 couples were recruited. Oxidative DNA damage (8-OHdG) and lipid peroxidation (8-EPI) were measured, and clinical background and ART outcomes were recorded. Both OxS markers accurately reflected clinical conditions with prominent negative effects attributable to genital tract infections, endometriosis, uterine myoma and smoking. Furthermore, the level of OxS was also affected by partner's state of health. The highest 8-EPI levels were detected in both partners when biochemically detectable pregnancies did not develop into clinically detectable pregnancies (in women, 97,8 ± 16,7 vs 72.9 ± 22,9, p = 0.007; in men, 89.6 ± 20,4 vs 72,1 ± 22,6, p = 0.049). To conclude, high grade systemix OxS in both partners may negatively affect the maintenance and outcome of pregnancy. Applying the detection of OxS in ART patients may select patients with higher success rate and/or those who require antioxidant therapy. This would lead to improvement of ART outcome as well as natural fertility.

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

PubMed

Ge, Xing; Tao, Fangbiao; Huang, Kun; Mao, Leijing; Huang, Sanhuan; Niu, Ying; Hao, Jiahu; Sun, Yanli; Rutayisire, Erigene

2016-01-01

To examine the prevalence of snoring during pregnancy and its effects on key pregnancy outcomes. 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. 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. 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.

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

Intrahospital transfers and adverse patient outcomes: An analysis of administrative health data.

PubMed

Blay, Nicole; Roche, Michael; Duffield, Christine; Xu, Xiaoyue

2017-12-01

To determine whether there was an association between intra-hospital transfers and adverse outcomes. Transfers between clinical units and between beds on the same unit are routine aspects of an episode of care in acute hospitals. The rate of these transfers per episode has increased in response to high occupancy levels, a decline in bed numbers, and increased demand for hospital services. The impact of the number of transfers between both wards and beds on patient outcomes is not widely explored. Retrospective cross sectional design using hospital administrative data. Data were extracted from existing hospital administrative datasets for one large metropolitan hospital for the financial year 2008-09 in Australia (n = 14,133). Descriptive analyses and logistic regression models were developed for each of 3 selected patient outcomes. Nearly one-tenth of patients (9.2%) experienced a fall with injury, 3.8% of surgical patients a wound infection and 0.1% a complication from medication errors. For each bed or ward transfer, the odds of falls and wound infections increased. Medication errors were not associated with either bed or ward moves. Hospitals should minimise the number of bed and ward transfers per episode of care in order to reduce the likelihood of adverse patient outcomes. Current bed management policies and practices should be evaluated and further refined to address this need. Additional strategies include improving coordination and communication during and after transfer. Nurses must consider the potential cost of intrahospital transfers on patients, length of stay and bed availability. © 2017 John Wiley & Sons Ltd.

Maternal Nutritional Status Predicts Adverse Birth Outcomes among HIV-Infected Rural Ugandan Women Receiving Combination Antiretroviral Therapy

PubMed Central

Young, Sera; Murray, Katherine; Mwesigwa, Julia; Natureeba, Paul; Osterbauer, Beth; Achan, Jane; Arinaitwe, Emmanuel; Clark, Tamara; Ades, Veronica; Plenty, Albert; Charlebois, Edwin; Ruel, Theodore; Kamya, Moses; Havlir, Diane; Cohan, Deborah