Objective:
Our study investigated body image representations in female patients with anorexia nervosa and healthy controls using a size estimation with pictures of their own body. We also explored a method to reduce body image distortions through right hemispheric activation.
Method:
Pictures of participants' own bodies were shown on the left or right visual fields for 130 ms after presentation of neutral, positive, or negative word primes, which could be self-relevant or not, with the task of classifying the picture as "thinner than", "equal to", or "fatter than" one's own body. Subsequently, activation of the left- or right hemispheric through right- or left-hand muscle contractions for 3 min., respectively. Finally, participants completed the size estimation task again.
Results:
The distorted "fatter than" body image was found only in patients and only when a picture of their own body appeared on the right visual field (left hemisphere) and was preceded by negative self-relevant words. This distorted perception of the patients' body image was reduced after left-hand muscle contractions (right hemispheric activation).
Discussion:
To reduce body image distortions it is advisable to find methods that help anorexia nervosa patients to increase their self-esteem. The body image distortions were ameliorated after right hemispheric activation. A related method to prevent distorted body-image representations in these patients may be Eye Movement Desensitization and Reprocessing (EMDR) therapy.
2018
American Journal of Epidemiology
Hill's Heuristics and Explanatory Coherentism in Epidemiology.
In this essay, I argue that Ted Poston's theory of explanatory coherentism is well-suited as a tool for causal explanation in the health sciences, particularly in epidemiology. Coherence has not only played a role in epidemiology for more than half a century as one of Hill's viewpoints, it can also provide background theory for the development of explanatory systems by integrating epidemiologic evidence with a diversity of other error-independent data. I propose that computational formalization of Hill's viewpoints in an explanatory coherentist framework would provide an excellent starting point for a formal epistemological (knowledge-theoretical) project designed to improve causal explanation in the health sciences. As an example, I briefly introduce Paul Thagard's ECHO system and offer my responses to possible objections to my proposal.
Developmental Medicine and Child Neurology
Hypoxia–ischemia is not an antecedent of most preterm brain damage: the illusion of validity.
Gilles, F., Gressens, P., Dammann, O., Leviton, A.
Brain injury in preterm newborn infants is often attributed to hypoxia–ischemia even when neither hypoxia nor ischemia is documented, and many causative speculations are based on the same assumption. We review human and animal study contributions with their strengths and limitations, and conclude that – despite all the work done in human fetal neuropathology and developmental models in animals – the evidence remains unconvincing that hypoxemia, in the fetus or newborn infant, contributes appreciably to any encephalopathy of prematurity. Giving an inappropriate causal name to a disorder potentially limits the options for change, should our understanding of the etiologies advance. The only observationally‐based title we think appropriate is ‘encephalopathy of prematurity’. Future pathophysiological research should probably include appropriately designed epidemiology studies, highly active developmental processes, infection and other inflammatory stimuli, the immature immune system, long chain fatty acids and their transporters, and growth (neurotrophic) factors.
2017
Pediatric Research
Both antenatal and postnatal inflammation contribute information about the risk of brain damage in extremely preterm newborns.
Yanni, D., Korzeniewski, S. J., Allred, E. N., Fichorova, R. N., O’Shea, T. M., Kuban, K., Dammann, O., Leviton, A.
Background:
Preterm newborns exposed to intrauterine inflammation are at an increased risk of neurodevelopmental disorders. We hypothesized that adverse outcomes are more strongly associated with a combination of antenatal and postnatal inflammation than with either of them alone.
Methods:
We defined antenatal inflammation as histologic inflammation in the placenta. We measured the concentrations of seven inflammation-related proteins in blood obtained on postnatal days 1, 7, and 14 from 763 infants born before 28 weeks of gestation. We defined postnatal inflammation as a protein concentration in the highest quartile on at least 2 days. We used logistic regression models to evaluate the contribution of antenatal and postnatal inflammation to the risk of neurodevelopmental disorders.
Results:
The risk of white matter damage was increased when placental inflammation was followed by sustained elevation of C-reactive protein or ICAM-1. We found the same for spastic cerebral palsy when placental inflammation was followed by elevation of TNF-α or IL-8. The presence of both placental inflammation and elevated levels of IL-6, TNF-α, or ICAM-1 was associated with an increased risk for microcephaly.
Conclusion:
Compared with a single hit, two inflammatory hits are associated with stronger risk for abnormal cranial ultrasound, spastic cerebral palsy, and microcephaly at 2 years.
Perspectives in Biology and Medicine
The Etiological Stance: Explaining Illness Occurrence.
Kelly, Kelly, and Russo (2014) recently proposed to integrate biological, behavioral, and social mechanisms into "mixed mechanisms" situated in the individual's "lifeworld" when considering illness causation. This article suggests considering terminological discrepancies, replacing the pathogenetic with an etiological perspective (that includes, but is not limited to pathogenesis), and rethinking whether the lifeworld concept adds to what we consider an individual's "environment." It also proposes replacing the notion of "mixed mechanisms" with the concept of "combined contributions" of factors in etiological explanations of illness.
2016
Archives of disease in childhood
Fetal and neonatal edition. Systemic endogenous erythropoietin and associated disorders in extremely preterm newborns.
Holm, M., Skranes, J., Dammann, O., Fichorova, R. N., Allred, E. N., Leviton, A.
OBJECTIVE:
To explore the association between concentrations of endogenous erythropoietin (EPO) in blood the first 2 weeks of life and neonatal disorders in extremely low gestational age newborns (ELGANs).
DESIGN:
Prospective cohort study.
SETTING:
Neonatal care units at 14 participating hospitals in the USA.
PATIENTS:
867 children born before the 28th week of gestation from the ELGAN study cohort.
MAIN OUTCOME MEASURES:
EPO blood concentrations were measured on postnatal days 1, 7 and 14. The following neonatal characteristics and disorders were registered: blood gases, early and late respiratory dysfunction, pulmonary deterioration, retinopathy of prematurity (ROP), necrotising enterocolitis (NEC) and bronchopulmonary dysplasia (BPD). We calculated the gestational age-adjusted ORs for having each disorder associated with an EPO blood concentration in the highest or lowest quartile, compared with infants whose EPO concentration was in the middle two quartiles on the corresponding day.
RESULTS:
Newborns whose day-1 EPO was in the highest quartile were at increased risk for early and persistent respiratory dysfunction during the first 2 weeks of life, and NEC requiring surgery. The lowest EPO quartile on day 1 was associated with a decreased risk of moderate BPD. The association between low EPO and decreased risk of respiratory complications persisted on day 7. On day 14, being in the highest EPO quartile was associated with increased risk of ROP, and BPD not requiring ventilation assistance.
CONCLUSIONS:
EPO blood concentrations in extremely preterm newborns during the first 2 weeks of life convey information about increased risks of bowel, lung and retinal diseases.
Journal of Behavioral Addictions
Do I feel ill because I crave for work or do I crave for work because I feel ill? A longitudinal analysis of work craving and health.
Background:
The theory of work craving defines workaholism as a pathological work addiction which comprises: (a) obsessive-compulsive desire to work, (b) anticipation of self-worth compensatory incentives from working, (c) anticipation of reduction of negative emotions or withdrawal symptoms from working, and (d) neurotic perfectionism. Research has shown that workaholism is associated with adverse health outcomes. However, the antecedents of workaholism and the causal direction of the relationship with health have been largely neglected.
Aims:
In the present longitudinal study, we expect that work craving is predicted by deficits in emotional self-regulation (i.e., low action orientation) and mediates the relationship between self-regulation deficits and symptoms of psychological distress. We expected work craving to have an effect on later psychological distress symptoms, but not psychological distress symptoms to have an effect on later work craving. Methods In a sample of 170 German employees, a half-longitudinal design using two times of measurement was implemented to specify the paths of two different structural equation models of mediation: (a) action orientation to later work craving and work craving to later psychological distress, and alternatively, (b) the temporal order of action orientation to later distress and distress to later work craving.
Results:
Our data indicated that work craving partially mediated the relationship between self-regulation deficits and psychological distress, but psychological distress symptoms were not found to increase later work craving.
Conclusions:
The presented longitudinal study indicates important mechanisms of work craving, especially by highlighting the influence of self-regulation deficits on work craving and, in turn, psychological distress.
Motivation and Emotion
Enjoying influence on others: Congruently high implicit and explicit power motives are related to teachers’ well-being.
The present study examined the associations of implicit and explicit power motives with the well-being of teachers. Teachers (N = 170) participated in an online assessment, which included measures for implicit motives (assessed by the operant motive test), explicit motives, and well-being. We expected congruently high power motives to be linked with the highest levels of well-being. We tested this assumption using polynomial regressions with response surface analysis. Results were consistent with our hypothesis. Additionally, there was an effect of directional motive incongruence (a combination of a low implicit and a high explicit power motive was associated with higher well-being than a high implicit/low explicit combination), which did not hold when controlling for emotional stability. Results for achievement were comparable, but weaker, and there was no effect for motive incongruence. No significant associations were found for motive (in)congruence in the affiliation domain. Our findings underline the importance of the power motive in understanding individual differences in teachers’ well-being.
Pediatric Research
Everything is connected: social determinants of pediatric health and disease.
Tarazi, C., Skeer, M., Fiscella, K., Dean, S., Dammann, O.
Carine Tarazi, MA, is an Assistant Editor for Pediatric Research in Boston, Massachusetts, USA. Margie Skeer, ScD, MPH, MSW, served as a Guest Editor for this special issue. Dr. Skeer is Assistant Professor of Public Health and Community Medicine at Tufts University. Her research focuses on adolescent substance misuse and sexual risk prevention, both from epidemiologic and intervention-development perspectives. Kevin Fiscella, MD, MPH, served as a Guest Editor for this special issue. Dr. Fiscella is Tenured Professor of Family Medicine, Public Health Sciences and Community Health at the University of Rochester Medical Center. Dr. Fiscella's research focuses on health and health care disparities, particularly practical strategies to improve health equity. Stephanie Dean, MBA, is Managing Editor of Pediatric Research and is based out of editorial office in The Woodlands, Texas. Olaf Dammann, MD, served as a Guest Editor for this special issue. Dr. Dammann is a Professor of Public Health and Community Medicine, Pediatrics, and Ophthalmology at Tufts University School of Medicine in Boston, Massachusetts, USA, as well as Professor of Perinatal Neuroepidemiology at Hannover Medical School, Hannover, Germany. His research interests include the elucidation of risk factors for brain damage and retinopathy in preterm newborns, the theory of risk and causation in biomedical and public health research, and the development of computational chronic disease models.
Thinking about illness causation has a long and rich history in medicine [1, 2, 3, 4]. After a hiatus in the 1990s, the last one-and-a-half decades have seen a surge of publications on causality in the biomedical sciences. Interestingly, this surge is visible not only in the medical [5], epidemiological [6], bioinformatics [7], and public health [8] literatures, but also among philosophical publications [9, 10, 11, 12, 13, 14, 15]. In this essay, I review and discuss one most recent addition to the literature, Causality: Philosophical Theory Meets Scientific Practice, written by philosophers Phyllis Illari and Federica Russo about causality in the sciences, and particularly about the health sciences.
2015
Online Journal of Public Health Informatics
Agent-based computational model of the prevalence of gonococcal infections after the implementation of HIV pre-exposure prophylaxis guidelines.
Escobar, E., Durgham, R., Dammann, O., & Stopka, T. J.
Recently, the first comprehensive guidelines were published for pre-exposure prophylaxis (PrEP) for the prevention of HIV infection in populations with substantial risk of infection. Guidelines include a daily regimen of emtricitabine/tenofovir disoproxil fumarate (TDF/FTC) as well as condom usage during sexual activity. The relationship between the TDF/FTC intake regimen and condom usage is not yet fully understood. If men who have sex with men (MSM,) engage in high-risk sexual activities without using condoms when prescribed TDF/FTC they might be at an increased risk for other sexually transmitted diseases (STD). Our study focuses on the possible occurrence of behavioral changes among MSM in the United States over time with regard to condom usage. In particular, we were interested in creating a model of how increased uptake of TDF/FTC might cause a decline in condom usage, causing significant increases in non-HIV STD incidence, using gonococcal infection incidence as a biological endpoint. We used the agent-based modeling software NetLogo, building upon an existing model of HIV infection. We found no significant evidence for increased gonorrhea prevalence due to increased PrEP usage at any level of sample-wide usage, with a range of 0-90% PrEP usage. However, we did find significant evidence for decreased prevalence of HIV, with a maximal effect being reached when 5% to 10% of the MSM population used PrEP. Our findings appear to indicate that attitudes of aversion, within the medical community, toward the promotion of PrEP due to the potential risk of increased STD transmission are unfounded.
Five years ago, Chief Editors Sherin Devaskar and Petra Hüppi were looking back at their 7 years of work on the Journal and the foundational changes we take for granted today. Most importantly, they had moved Pediatric Research from a paper-based submission and review process to a web-based one. They had also divided the Table of Contents into Basic, Translational, and Clinical articles, and had introduced both the monthly Focus Page and the annual Review Issue. After this tremendous work, they turned the Journal over to our care. A few other big changes were occurring at that point in time. The shift to Nature Publishing Group extended our capabilities and expanded our audience. We went from designing our own covers the first year to having our pick of images in NPG’s stock. We now have a bimonthly podcast, Pediapod, for which authors are interviewed regarding their work. Stephanie Dean came on board as an efficient and very talented Managing Editor, always ready to hear ideas, field questions, run communications, make contributions, and ensure that the Journal was running smoothly. During that time, we also transitioned to a new manuscript submission system, eJournal Press, which meant that we all—editors, reviewers, and publisher—had our work cut out for us.
Studies in History and Philosophy of Science Part C: Studies in History and Philosophy of Biological and Biomedical Sciences.
Evidence, illness, and causation: An epidemiological perspective on the Russo–Williamson Thesis.
According to the Russo–Williamson Thesis, causal claims in the health sciences need to be supported by both difference-making and mechanistic evidence. In this article, we attempt to determine whether Evidence-based Medicine (EBM) can be improved through the consideration of mechanistic evidence. We discuss the practical composition and function of each RWT evidence type and propose that exposure–outcome evidence (previously known as difference-making evidence) provides associations that can be explained through a hypothesis of causation, while mechanistic evidence provides finer-grained associations and knowledge of entities that ultimately explains a causal hypothesis. We suggest that mechanistic evidence holds untapped potential to add value to the assessment of evidence quality in EBM and propose initial recommendations for the integration of mechanistic and exposure–outcome evidence to improve EBM by robustly leveraging available evidence in support of good medical decisions.
2014
Online Journal of Public Health Informatics
Systems Epidemiology: What’s in a Name?
Dammann, O., Gray, P., Gressens, P., Wolkenhauer, O., Leviton, A.
Systems biology is an interdisciplinary effort to integrate molecular, cellular, tissue, organ, and organism levels of function into computational models that facilitate the identification of general principles. Systems medicine adds a disease focus. Systems epidemiology adds yet another level consisting of antecedents that might contribute to the disease process in populations. In etiologic and prevention research, systems-type thinking about multiple levels of causation will allow epidemiologists to identify contributors to disease at multiple levels as well as their interactions. In public health, systems epidemiology will contribute to the improvement of syndromic surveillance methods. We encourage the creation of computational simulation models that integrate information about disease etiology, pathogenetic data, and the expertise of investigators from different disciplines.
PLOS ONE
Live to work or love to work: Work craving and work engagement.
Wojdylo, K., Baumann, N., Fischbach, L., & Engeser, S.
According to the theory of work craving, a workaholic has a craving for self-worth compensatory incentives and an expectation of relief from negative affect experienced through neurotic perfectionism and an obsessive-compulsive style of working. Research has shown that workaholism and work engagement should be considered as two distinct work styles with different health consequences. However, the mechanisms underlying the adoption of these work styles have been neglected. The present study proposes that work craving and work engagement are differentially associated with self-regulatory competencies and health. In particular, we expected that the working styles mediate the relationships between emotional self-regulation and health.
Methods:
In the cross-sectional study, 469 teachers from German schools completed online administered questionnaires. By means of structural equation modeling, we tested two indirect paths: a) from self-relaxation deficits via work craving to poor health and b) from self-motivation competencies via work engagement to good health.
Results:
As expected, we found evidence that a) the negative relationship of self-relaxation deficits on health was partially mediated by work craving and b) the positive relationship of self-motivation competencies on health was partially mediated by work engagement.
Conclusions:
The present study emphasizes the importance of self-regulation competencies for healthy or unhealthy work styles. Whereas work craving was associated with a low ability to down-regulate negative emotions and poor health, work engagement was associated with a high ability to up-regulate positive emotions and good health.
Zeitschrift für Klinische Psychologie und Psychotherapie
Selbstregulation von Emotionen als Schutzfaktor gegen gesundheitliche Auswirkungen von Mobbing.
Wojdylo, K., Baumann, N., Kuhl, J., & Horstmann, J.
Although several studies have already addressed the relationship between bullying and health effects, little is known about the meaning of self-regulative mechanisms for the health of bullying victims. Objective: Do low action-oriented victims of bullying differ from high action-oriented victims of bullying in the intensity of their health symptoms? Method: Thirty five inpatients from a psychosomatic rehabilitation center who were victims of bullying participated in our study. Variables were assessed using standardized diagnostic procedures (Bullying Questionnaire, ACS, SCL-90-R). Results: For patients with low self-regulatory ability (i.e., state orientation) stronger bullying was associated with higher psychosomatic symptoms. In contrast, patients with high self-regulatory ability (i.e., action orientation) had relatively low psychosomatic symptoms, irrespective of the multiplicity of specific bullying behaviors. Conclusion: The ability to self-regulate emotions seems to buffer adverse health effects associated with a severe social stressor like bullying.
2013
Brain, Behaviour, Immunity
Inflammation-initiating illnesses, inflammation-related proteins, and cognitive impairment in extremely preterm infants.
O’Shea, T. M., Shah, B., Allred, E. N., Fichorova, R. N., Kuban, K. C. K., Dammann, O., Leviton, A., ELGAN Study Investigators
Neonatal inflammation is associated with perinatal brain damage. We evaluated to what extent elevated blood levels of inflammation-related proteins supplement information about the risk of impaired early cognitive function provided by inflammation-related illnesses. From 800 infants born before the 28th week of gestation, we collected blood spots on days 1, 7 and 14, for analysis of 25 inflammation-related proteins, and data about culture-positive bacteremia, necrotizing enterocolitis (Bell stage IIIb), and isolated perforation of the intestine, during the first two weeks, and whether they were ventilated on postnatal day 14. We considered a protein to be persistently or recurrently elevated if its concentration was in the top quartile (for gestational age and day blood was collected) on two separate days one week apart. We assessed the children at 2 years of age with the Bayley Mental Development Index (MDI). The combinations of NEC and ventilation on day 14, and of bacteremia and ventilation on day 14 consistently provided information about elevated risk of MDI <55, regardless of whether or not a variable for an elevated protein concentration was included in the model. A variable for a persistently or recurrently elevated concentration of each of the following proteins provided additional information about an increased risk of MDI <55: CRP, SAA, IL-6, TNF-alpha, IL-8, MIP-1beta, ICAM-1, E-SEL, and IGFBP-1. We conclude that elevated blood concentrations of inflammation-related proteins provide information about the risk of impaired cognitive function at age 2 years that supplements information provided by inflammation-associated illnesses.
Journal of Child Neurology
Systemic inflammation, intraventricular hemorrhage, and white matter injury.
Leviton, A., Allred, E. N., Dammann, O., Engelke, S., Fichorova, R. N., Hirtz, D., Kuban, K. C. K., Ment, L. R., O’Shea, T. M., Paneth, N., Shah, B., Schreiber, M. D., & ELGAN Study Investigators
To see if the systemic inflammation profile of 123 infants born before the 28th week of gestation who had intraventricular hemorrhage without white matter injury differed from that of 68 peers who had both lesions, we compared both groups to 677 peers who had neither. Cranial ultrasound scans were read independently by multiple readers until concordance. The concentrations of 25 proteins were measured with multiplex arrays using an electrochemiluminescence system. Infants who had both hemorrhage and white matter injury were more likely than others to have elevated concentrations of C-reactive protein and interleukin 8 on days 1, 7, and 14, and elevated concentrations of serum amyloid A and tumor necrosis factor-α on 2 of these days. Intraventricular hemorrhage should probably be viewed as 2 entities: hemorrhage alone and hemorrhage with white matter injury. Each entity is associated with inflammation, but the combination has a stronger inflammatory signal than hemorrhage alone.
Pediatric Research
The road from systems biology to systems medicine.
Wolkenhauer, O., Auffray, C., Jaster, R., Steinhoff, G., Dammann, O.
As research institutions prepare roadmaps for "systems medicine," we ask how this differs from applications of systems biology approaches in medicine and what we (should) have learned from about one decade of funding in systems biology. After surveying the area, we conclude that systems medicine is the logical next step and necessary extension of systems biology, and we focus on clinically relevant applications. We specifically discuss three related notions. First, more interdisciplinary collaborations are needed to face the challenges of integrating basic research and clinical practice: integration, analysis, and interpretation of clinical and nonclinical data for diagnosis, prognosis, and therapy require advanced statistical, computational, and mathematical tools. Second, strategies are required to (i) develop and maintain computational platforms for the integration of clinical and nonclinical data, (ii) further develop technologies for quantitative and time-resolved tracking of changes in gene expression, cell signaling, and metabolism in relation to environmental and lifestyle influences, and (iii) develop methodologies for mathematical and statistical analyses of integrated data sets and multilevel models. Third, interdisciplinary collaborations represent a major challenge and are difficult to implement. For an efficient and successful initiation of interdisciplinary systems medicine programs, we argue that epistemological, ontological, and sociological aspects require attention.
Personality and Social Psychology Bulletin
You are not alone: Relatedness reduces adverse effects of state orientation on well-being under stress.
A low ability to self-regulate emotions (state orientation) is associated with reduced well-being—especially under stress. Until now, research has approached this topic from an asocial perspective that views the self as devoid from relatedness concerns. However, people are social creatures who benefit from their relationships with others. As such, we expected that personally valuing (Study 1) and experimentally priming (Study 2) a sense of relatedness with others would act as a buffer against stress-related impairments in state-oriented individuals. In Study 1, high (vs. low) benevolence values removed the adverse effect of state orientation on well-being found under stressful life circumstances. In Study 2, focusing on similarities (vs. differences) while comparing oneself with a friend removed the adverse effect of state orientation on recovery from a negative mood induction. Our findings suggest that individuals with low self-regulatory competencies may profit from valuing and directing their attention toward their relatedness with others.
2012
Pediatric Research
Schizophrenia and autism: both shared and disorder-specific pathogenesis via perinatal inflammation?
Prenatal exposure to infection and subsequent inflammatory responses have been implicated in the etiology of schizophrenia and autism. In this review, we summarize current evidence from human and animal studies supporting the hypothesis that the pathogenesis of these two disorders is linked via exposure to inflammation at early stages of development. Moreover, we propose a hypothetical model in which inflammatory mechanisms may account for multiple shared and disorder-specific pathological characteristics of both entities. In essence, our model suggests that acute neuroinflammation during early fetal development may be relevant for the induction of psychopathological and neuropathological features shared by schizophrenia and autism, while post-acute latent and persistent inflammation may contribute to schizophrenia- and autism-specific phenotypes, respectively.
2011
American Journal of Reproductive Immunology
Cluster analysis of placental inflammatory proteins can distinguish preeclampsia from preterm labor and premature membrane rupture in singleton deliveries less than 28 weeks of gestation.
Faupel-Badger, J. M., Fichorova, R. N., Allred, E. N., Hecht, J. L., Dammann, O., Leviton, A., McElrath, T. F.
Problem:
Inflammation within the preterm placenta is common and leads to adverse outcomes for premature infants. The risks of complications are different between iatrogenic (e.g. preeclampsia) and spontaneous (e.g. preterm labor and membrane rapture) causes of preterm delivery, suggesting different underlying biology contributes to these placental conditions.
Method of Study:
Thirty preterm singleton placentas from the following groups were analyzed: 1) severe preeclampsia (PE), 2) preterm premature membrane rupture (pPROM) and 3) preterm labor (PL). Proinflammatory and anti-inflammatory cytokines, adhesion and angiogenic molecules were measured in placental lysates using a multiplex assay. K-means cluster analysis was used to generate patterns of protein level intensity.
Results:
Three cluster patterns were apparent. Placentas from PE had high levels of VEGF combined with low levels of acute inflammatory proteins (IL-1β, IL-18, IL-6, TNF-α), low IL-1 RA and high TGF-β. PL and pPROM had higher anti-inflammatory IL-1 RA and thrombomodulin combined with lower VEGF, regardless of proinflammatory cytokines and adhesion molecules. Half of the PL and pPROM cases had clusters of heightened inflammatory responses (lower TGF-β clustered with higher intensity of inflammatory mediators).
Conclusions:
Discriminating protein patterns were elucidated and may serve as a foundation from which to understand the biological mechanisms underlying these pregnancy complications.
Journal of Reproductive Immunology
Persistence after birth of systemic inflammation associated with umbilical cord inflammation.
Leviton, A., Hecht, J. L., Allred, E. N., Yamamoto, H., Fichorova, R. N., Dammann, O., ELGAN Study Investigators
Intrauterine inflammation is followed by elevated concentrations of inflammation-related proteins in the newborn's blood. Many of these proteins have short half-lives. The persistence of this postnatal inflammation has not previously been investigated. In a sample of 834 infants born before the 28th week of gestation, 12% (103) had grade 1 or 2, and 17% (142) had grade 3, 4, or 5 umbilical cord inflammation. Concentrations of nine proteins previously shown to be associated with umbilical cord inflammation at birth were measured on the first postnatal day and at two weekly intervals after birth. We evaluated the hypothesis that children who had umbilical cord inflammation were no more likely than others to have elevated concentrations of inflammation-related proteins in postnatal blood. The concentrations of seven of the nine proteins [C-reactive protein (CRP), myeloperoxidase (MPO), IL1β, IL8, TNFα, intercellular adhesion molecule-1 (ICAM3), and matrix metalloproteinase (MMP9)] showed a tendency to be elevated on day 7 among infants with funisitis. Adjusting for gestational age, growth restriction, and three postnatal exposures (ventilation on day 7, presumed and definite early bacteremia, and Bell stage III necrotizing endocolitis) did not diminish the elevated odds ratios of concentrations in the top quartile (for gestational age and day the specimen was obtained) of MPO, IL1β, TNFα, IL8, ICAM3, and MMP9. The persistence of a relationship between umbilical cord inflammation and elevated blood concentrations of inflammation-related proteins on postnatal day 7 suggests the existence of phenomena that contribute to a reinforcement loop and thereby sustained systemic inflammation.
Motivation and Emotion
Directional discrepancy between implicit and explicit power motives is related to well-being among managers.
This study investigates explicit –implicit motive discrepancies and their effect on well-being. Participants were 382 executive managers (107 females and 275 males). Female managers had higher explicit affiliation scores than males, whereas male managers had marginally significant higher explicit power scores than females. Males and females did not differ in their implicit motives. We expected a directional discrepancy on the power motive (explicit vs. implicit: “Striving for goals without gaining pleasure from doing so”) to predict impaired well-being. Results were consistent with this hypothesis, using polynomial regression analysis with response surface methods, instead of calculating motive difference scores. Discrepancies in the achievement and affiliation motives were not related to well-being. Results are discussed considering the specificity of motive discrepancies for selected groups, such as managers, and the importance of distinguishing between absolute versus directional motive discrepancy scores in motivation research.
Pediatric Research
Neonatal encephalopathy or hypoxic-ischemic encephalopathy? Appropriate terminology matters.
In 1976, Sarnat and Sarnat (1) published a proposed staging system for neonatal encephalopathy. They carefully used the term “neonatal encephalopathy” in the title. However, in the abstract, they wrote about “postanoxic encephalopathy” and about “ischemic-anoxic encephalopathy” in the article itself. Infants were >36wks GA, and all had “a well-defined episode of fetal distress or an Apgar score of 5 or less at one or five minutes after delivery” (1). Apparently, much of the evidence that hypoxia and/or ischemia were indeed the causes of the encephalopathy was indirect and far from solid. Today, 35 y later, the term “hypoxic-ischemic encephalopathy” is widely used standard terminology, and we and others (2, 3) strongly believe that it should not be.
2010
Acta Paediatrica
Policy benchmarking report on neonatal health and social policies in 13 European countries.
Keller, M., Felderhoff-Mueser, U., Lagercrantz, H., Dammann, O., Marlow, N., Hüppi, P., Buonocore, G., Poets, C.,Simbruner, G., Guimaraes, H.,Mader, S., Merialdi, M.,Saugstad, O. D.
BACKGROUND AND AIM:
Preterm birth is the major cause of infant mortality and morbidity in both developed and developing countries. In Europe, the prevalence rate of premature birth ranges from 5.5 to 11.4% - an average of 7.1% of all live births. In this report, we aim to compare the current health and social policies, as well as practices in 13 EU member states.
MATERIALS AND METHODS:
Using desk research, relevant information was gathered from each of the 13 European countries with regard to the prevalence of preterm birth, the cost of preterm birth to healthcare budgets, and the relevant policies, guidelines and practices in place at the national and, in some cases, regional level. The information comes from a range of sources, including government and parent association websites, published scientific literature and media reports.
RESULTS: Despite the growing prevalence and increasing costs, neonatal and preterm infant health rank low on the policy agendas of EU member states.
CONCLUSION:
Based on the findings, there are a number of recommendations that should be considered. The European Union should (i) recognize the growing challenge of prematurity in Europe and its significant impact on infant morbidity and mortality, (ii) improve neonatal health through the development and implementation of coordinated EU health and social policies, (iii) address the lack of comparable European data on prematurity, including prevalence, mortality, acute morbidity and long-term impairment, (iv) also increase the standard of neonatal care across Europe by supporting the development and implementation of European medical guidelines and quality standards, (v) support the development of European postgraduate training programmes in Peri- and Neonatology in order to increase the quality and availability of trained healthcare professionals.
Acta Paediatrica
The clustering of disorders in infants born before the 28th week of gestation.
Leviton, A., Dammann, O., Engelke, S., Allred, E., Kuban, K. C. K., O’Shea, T. M., Paneth, N., ELGAN Study Investigators
AIM: To see whether disorders prevalent in infants born extremely preterm cluster.
DESIGN: Observational cohort study.
SETTING:University-affiliated newborn intensive care nurseries.
SUBJECTS: One thousand two hundred and twenty-three infants born before the 28th week of gestation who survived until 36 weeks postmenstrual age when the diagnosis of bronchopulmonary dysplasia (BPD) could be made.
INTERVENTIONS: None.
MAIN OUTCOME MEASURES: Cerebral white matter damage (an echolucent lesion, or moderate or severe ventriculomegaly on a protocol cranial ultrasound scan), BPD, retinopathy of prematurity (ROP), necrotizing enterocolitis (NEC) and early and late bacteremia.
RESULTS: After adjustment for gestational age, children who had severe NEC (Bell stage IIIb) were at increased risk of cerebral white matter damage, severe ROP (stage 3+), and severe BPD (defined as both oxygen and ventilator dependent). Children who had early bacteremia were at increased risk of late bacteremia and severe ROP. Those who had severe ROP were at increased risk of severe BPD and both early and late bacteremia.
CONCLUSIONS: Necrotizing enterocolitis is the disorder common to most of the clusters, but we do not know if its onset occurred before the others. Organ-damage-promoting substances, however, have been found in the circulation of newborn animals with bowel inflammation, supporting the view that NEC contributes to the damage of other organs.
We have read with great interest the article by Henderson and colleagues in a recent issue of the Annals, in which the authors describe early loss of oligodendrocytes, without concomitant T-cell and B-cell infiltration or macrophage activity in tissue that borders a small sedection of acute multiple sclerosis (MS) lesions. Neighboring areas with degenerate myelin were found to be infiltrated with macrophages, and fully demyelinated white matter areas contained lipid-laden macrophages, T-cells and B-cells, and immunoglobulin G deposits. These results are certainly interesting and thought-provoking. The authors’ findings further strengthen the notion that MS is not so much, as has classically been argued, a primary autoimmune disease, but rather a disease starting within the central nervous system, with response of the immune system only in later stages.
International Journal of Developmental Neuroscience
NEUROBID—an EU-funded project to study the developing brain barriers.
Bueter, W., Saunders, N. R., Mallard, C., Bauer, H.-C., Stolp, H. B., Kavelaars, A., & Dammann, O.
Brain diseases are one of the most prevalent groups of diseases in Europe with estimated annual costs amounting to €386 billion. Data collected by the WHO suggest that brain diseases are responsible for 35% of Europe's total disease burden. In the treatment of neurological disease, the blood brain barrier (BBB) still represents an obstacle for the delivery of drugs to the brain and thus a major challenge for the development of therapeutic regimens. Understanding the molecular basis and functioning of the BBB in health and disease, including transport mechanisms across the BBB, therefore holds significant potential for future strategies to prevent and ameliorate neurological disease.
Recent research indicates that some neurological disorders have a developmental etiologic component. The major goal of the NEUROBID project is thus to understand the molecular mechanisms and function of the BBB in health and disease both in the developing brain and the adult central nervous system. With an interdisciplinary consortium from the fields of developmental neurobiology and BBB research, NEUROBID aims to (i) understand the involvement of normal and disturbed BBB function in normal and abnormal brain development and (ii) to develop novel strategies for drug delivery to the brain. Unique transport mechanisms across the BBB will be used to target potential therapeutic macromolecular and cellular agents specifically to the brain barriers and transport them into the brain. The main target disorders of NEUROBID are non-inherited neurodevelopmental disorders arising from perinatal adverse exposure, such as cerebral palsy, and classic adult neurological disorders such as multiple sclerosis and stroke.
In the long term, NEUROBID hopes to pave the way for new treatment strategies and thus reduce the economic and social burden of neurological disease.
The Journal of Maternal - Fetal & Neonatal Medicine
Maternal obesity and neonatal Apgar scores.
Chen, M., McNiff, C., Madan, J., Goodman, E:, Davis, J. M., Dammann, O.
OBJECTIVE:
To determine whether maternal obesity in early pregnancy is associated with low neonatal 5-min Apgar scores while adjusting for confounders.
METHODS:
Data were obtained from Maine State Birth Records Database. Analyses were restricted to information on 58,089 white women and their newborns. Maternal weight status was defined using the recorded early second trimester maternal body mass index (BMI) and defined as normal weight (BMI <25), overweight (BMI 25 to <30), obese (BMI 30 to <40), and morbidly obese (BMI >or=40). Logistic regression analysis was used to assess the association of maternal weight status with low Apgar score while adjusting for confounders.
RESULTS:
Compared with newborns of normal weight women, the risk to receive low Apgar scores (4-6) is increased in newborns of obese (OR 1.4, 95% CI 1.1-1.7) and morbidly obese mothers (OR 2.0, 95% CI 1.5-2.7). The association did not achieve significance for newborns of overweight mothers (OR 1.2, 95% CI 0.99-1.4). No association was identified between maternal weight status and very low Apgar scores (0-3).
CONCLUSIONS:
Maternal obesity is associated with a significantly increased risk for decreased Apgar scores at birth. Further studies are needed to clarify the relationships among maternal obesity, complications of pregnancy, and neonatal outcome.
2009
Cytokine
Maternal obesity and markers of inflammation in pregnancy.
Madan, J. C., Davis, J. M., Craig, W. Y., Collins, M., Allan, W., Quinn, R., Dammann, O.
OBJECTIVES:
To evaluate whether obesity is associated with changes in pro-inflammatory and immunomodulatory cytokines in pregnancy.
METHODS: We performed a cross-sectional study using maternal serum from the early second trimester to examine biomarkers associated with inflammation in relation to maternal body mass index (n=80 total).
RESULTS:
Leptin and high sensitivity C-reactive protein were significantly different between groups and increased with increasing body mass index. MCP-1 was significantly increased in the morbidly obese mothers. Interleukin-2 exhibited a U-shaped relationship with body mass index; transforming growth factor-beta1 demonstrated a nonsignificant negative trend with body mass index; and the levels of hepatocyte growth factor and tumor necrosis factor-alpha did not differ appreciably between groups.
CONCLUSIONS:
Maternal obesity in pregnancy is associated with changes in cytokines, protein hormones and acute phase proteins in the second trimester, with an increase in MCP-1 in the morbid obesity category, and an increase in Leptin and hsCRP with increasing BMI category.
Journal of Child Neurology
''Intraventricular'' hemorrhage and cystic periventricular leukomalacia in preterm infants: how are they related?
Kusters, C. D., Chen, M. L., Follett, P. L., & Dammann, O.
Intraventricular hemorrhage and cystic periventricular leukomalacia are often co-occurring characteristics of brain damage in preterm infants. Using data from 1016 infants born before 30 completed weeks' gestational age, we sought to clarify the relationship between severe intraventricular hemorrhage and cystic periventricular leukomalacia, with special emphasis on common antecedents and potential confounding. After comparing risk factors for intraventricular hemorrhage grades 1 through 4 and cystic periventricular leukomalacia, it appears the risk patterns for intraventricular hemorrhage grade 3, intraventricular hemorrhage grade 4, and cystic periventricular leukomalacia differ. The association between intraventricular hemorrhage grade 3 and cystic periventricular leukomalacia differs appreciably from the association between intraventricular hemorrhage grade 4 and cystic periventricular leukomalacia, supporting the notion that intraventricular hemorrhage grade 3 and intraventricular hemorrhage grade 4 are different entities. The presence of intraventricular hemorrhage grade 3 and intraventricular hemorrhage grade 4 increases the risk of cystic periventricular leukomalacia, even after adjusting for potential confounders. This raises the possibility that intraventricular hemorrhage grade 3 and intraventricular hemorrhage grade 4 cause cystic periventricular leukomalacia.
Pediatric Research
Endoplasmic reticulum stress, inflammation, and perinatal brain damage.
Inflammation seems to play a role in the pathogenesis of perinatal brain damage in fetuses/infants born much before term. We raise the possibility that noninflammatory phenomena induce endoplasmic reticulum stress, which, in turn, leads to the unfolded protein response, which is followed by apoptosis-promoting processes and inflammation. Perhaps by these events, noninflammatory stimuli lead to perinatal brain damage.
2008
American Journal of Epidemiology
Pregnancy Disorders That Lead to Delivery Before the 28th Week of Gestation: An Epidemiologic Approach to Classification.
McElrath, T. F., Hecht, J. L., Dammann, O., Boggess, K., Onderdonk, A., Markenson, G., Harper, M., Delpapa, E., Allred, E. N., Leviton, A., & ELGAN Study Investigators
Epidemiologists have grouped the multiple disorders that lead to preterm delivery before the 28th week of gestation in a variety of ways. The authors sought to identify characteristics that would help guide how to classify disorders that lead to such preterm delivery. They enrolled 1,006 women who delivered a liveborn singleton infant of less than 28 weeks' gestation at 14 centers in the United States between 2002 and 2004. Each delivery was classified by presentation: preterm labor (40%), prelabor premature rupture of membranes (23%), preeclampsia (18%), placental abruption (11%), cervical incompetence (5%), and fetal indication/intrauterine growth restriction (3%). Using factor analysis (eigenvalue = 1.73) to compare characteristics identified by standardized interview, chart review, placental histology, and placental microbiology among the presentation groups, the authors found 2 broad patterns. One pattern, characterized by histologic chorioamnionitis and placental microbe recovery, was associated with preterm labor, prelabor premature rupture of membranes, placental abruption, and cervical insufficiency. The other, characterized by a paucity of organisms and inflammation but the presence of histologic features of dysfunctional placentation, was associated with preeclampsia and fetal indication/intrauterine growth restriction. Disorders leading to preterm delivery may be separated into two groups: those associated with intrauterine inflammation and those associated with aberrations of placentation.
British Journal of Psychology
Work-Life Balance and Subjective Well-Being: The Mediating Role of Need Fulfillment.
The relationship between work-life balance (WLB) (i.e. the perceived sufficiency of the time available for work and social life) and well-being is well-documented. However, previous research failed to sufficiently explain why this relationship exists. In this research, the hypothesis was tested that a sufficient amount of the time available increases well-being because it facilitates satisfaction of personal needs. Using two separate samples (students and employees), the mediating role of need fulfilment in the relationship between WLB and well-being was supported. The results suggest that perceived sufficiency of the time available for work and social life predicts the level of well-being only if the individual's needs are fulfilled within that time.
Based on the framework of Personality Systems Interactions theory, this article addresses the functional mechanisms by which positive affect influences motivational and self-regulatory determinants of health-relevant behavior on an elementary level of processing. Research encompassing experimental procedures such as the Stroop task will be presented which suggest that positive affect is necessary not only to facilitate self-regulation of negative emotions but also to facilitate self-motivation, i.e., the enactment of difficult intentions that entail the risk of procrastination. We also highlight the role of state and trait accessibility of self-referential information (”self-access”) in generating such positive affect. The relevance of the findings for health maintenance is addressed.
2007
International Journal of Cancer
Nijmegen Breakage Syndrome mutations and risk of breast cancer.
Bogdanova, N., Feshchenko,S., Schürmann, P., Waltes, R., Wieland, B., Hillemanns, P., Rogov, Y. I., Dammann, O., Bremer,M., Karstens, J. H., Sohn, C., Varon, R., & Dörk, T.
Mutations in the NBS1 gene have been identified as disease‐causing mutations in patients with Nijmegen Breakage Syndrome (NBS), but their clinical impact on breast cancer susceptibility has remained uncertain. We determined the frequency of 2 NBS mutations, 657del5 and R215W, in two large series of breast cancer cases and controls from Northern Germany and from the Republic of Belarus. The 5‐bp‐deletion 657del5 was identified in 15/1,588 cases (0.9%) from Belarus and in 1/1,076 cases (0.1%) from Germany but in only 1/1,014 population controls from Belarus and 0/1017 German controls (p < 0.01). The missense substitution R215W was observed in 9/1,588 Byelorussian and 9/1,076 German patients (0.6% and 0.8%, respectively) but was also present in 5/1,014 Byelorussian and 2/1,017 German control individuals (adjusted OR = 1.9, 95%CI 0.8–4.6, p = 0.18). Studies of lymphoblastoid cell lines revealed that NBS1/p95 protein levels were reduced to 70% in cells from a heterozygous breast cancer patient carrying R215W and to 15% in cells from a NBS patient compound heterozygous for 657del5/R215W suggesting that the R215W substitution may be associated with protein instability. Levels of radiation‐induced phosphorylation of Nbs1/p95(Ser343) were reduced to 60% and 35% of wildtype, respectively. Neither age at diagnosis nor family history of breast cancer differed significantly between carriers and noncarriers of NBS mutations. The combined data are in line with an about 3‐fold increase in breast cancer risk for female NBS heterozygotes (OR 3.1; 95%CI 1.4–6.6) and indicate that the 657del5 deletion and perhaps the R215W substitution contribute to inherited breast cancer susceptibility in Central and Eastern Europe.
Lancet
Happiness reconsidered in children with cerebral palsy.
Health researchers measure happiness, or quality of life, with standardised interviews or questionnaires to learn about participants' perceptions of wellbeing and life satisfaction. Thus quality of life (sometimes also called patient-reported outcomes) is inherently subjective—eg, walking the dog for 2 h might increase your neighbour's quality of life but decrease your own. Objectively evaluated health, or functional, status is but one of many factors that influence subjectively perceived quality of life.
Neonatology
NEOBRAIN – an EU-funded project committed to protect the newborn train.
Brain damage and its adverse neurodevelopmental sequelae are among the most devastating correlates of preterm birth. Clinical and scientific efforts have not led to an appreciable reduction of either preterm delivery or brain damage among preterm infants. With improved neonatal care over the past decades and the concomitant increasing survival of the most immature, the prevalence of long-term neurodevelopmental disability among preterm children will probably increase. In light of these troublesome data, the glaring absence of neuroprotective strategies from the neonatologists’ armamentarium seems even more striking. While recent studies suggest a protective effect of hypothermia in neonatal encephalopathy of term infants, the most feasible interventions in preterm children are the administration of 1 course of antenatal steroids to the mother and the careful limitation of postnatal intervention to the lowest possible level of invasiveness. Moreover, the natural history of brain damage in preterm newborns is still a matter of debate, incorporating multiple possible pathways, such as inflammation, ischaemia, free radicals or multiple insults.
Seminars in Fetal & Neonatal
Anti-inflammatory and immunomodulatory strategies to protect the perinatal brain.
Infection and inflammation contribute to perinatal brain damage, particularly to the white matter. Although combating perinatal inflammation can be dangerous, because inflammation might have beneficial effects for mother and fetus, it is worthwhile reviewing potential anti-inflammatory neuroprotective compounds, along with their potential adverse effects. Further research on the possible neuroprotective roles of existing medications and substances is necessary.
2006
Pediatrics
Hospital volume and neonatal mortality among very low birth weight infants.
Bartels, D. B., Wypij, D., Wenzlaff, P., Dammann, O., & Poets, C. F.
BACKGROUND:
Very low birth weight infants (< 1500 g) are at increased mortality risk. Data on the impact of NICU volume are sparse, in comparison with those on the level of care. We hypothesized that neonatal mortality would be higher in small NICUs (< 36 very low birth weight admissions per year) than in large NICUs, with adjustment for volume of the delivery unit.
METHODS:
We analyzed population-based data from a quality assurance program in Lower Saxony (Germany). Perinatal data for almost all very low birth weight infants born in 1991 to 1999 (n = 7745) were available. Analyses were restricted to infants born at 24 to 30 weeks (n = 4379). Data validation procedures, univariate data analyses, and logistic regression models based on general estimating equations were performed.
RESULTS:
Neonatal mortality among infants admitted to NICUs was 12.2% in small NICUs and 10.2% in large NICUs. The mortality rate in small NICUs was increased significantly. Compared with infants from large delivery hospitals (> 1000 births per year) and large NICUs, the adjusted odds ratio was 1.94 for neonates for whom both units were small, 1.75 for those from large delivery units but small neonatal units, and 1.16 for those for whom only the NICU was large. Stratification according to gestational age revealed the greatest impact on mortality for infants of < 29 weeks.
CONCLUSIONS:
Results suggest that creating larger perinatal centers may improve perinatal health care. The volume of the NICU was associated more strongly with 28-day mortality than was the volume of the delivery hospital, and it had the largest impact on survival for infants of < 29 weeks.
Pediatrics
Incidence and clinical presentation of invasive neonatal group B streptococcal infections in Germany.
Fluegge, K., Siedler, A., Heinrich, B., Schule-Moenting, J., Moenning, M. J., Bartels, D. B., Dammann, O., von Kries, R., Berner, R., German Pediatric Surveillance Unit Study Group
OBJECTIVE:
Streptococcus agalactiae (group B Streptococcus) is an important cause of morbidity and mortality in newborn infants. So far, there have been no published data on the incidence, morbidity, and mortality of invasive neonatal group B Streptococcus infections in Germany.
METHODS:
A prospective active surveillance study involving all of the pediatric hospitals, which reported their cases to the German Pediatric Surveillance Unit, and all of the microbiological laboratories serving pediatric hospitals, which reported their cases to the Laboratory Sentinel Group at Robert Koch Institute Berlin, was conducted between 2001 and 2003. Capture-recapture analysis was used to evaluate the completeness of reported neonatal invasive group B Streptococcus infections.
RESULTS:
We collected and analyzed data from 347 and 360 infants with invasive group B Streptococcus infection during the first 3 months of life, as reported by pediatricians to the German Pediatric Surveillance Unit and microbiologists to the Robert Koch Institute Berlin, respectively. Using capture-recapture analysis, we calculated an incidence of 0.47 per 1000 live births. Nearly 60% of the infants suffered from early-onset disease, and 16% of these presented with meningitis. In contrast, 61.8% of infants with late-onset disease presented with meningitis. Prematurity was present in 22.4% of early-onset disease and 39.7% of late-onset disease cases, respectively. A high proportion of infants suffered from sequelae because of group B Streptococcus infection at the time of discharge from the hospital. Most common sequelae were hydrocephalus and cerebral seizure. Case fatality rate was 4.3%.
CONCLUSIONS:
This study, which is the first to provide information on the current national incidence and morbidity of invasive group B Streptococcus infection in Germany, demonstrates remarkable country-specific variation in comparison with other European countries, which gather data in a similar fashion. Therefore, the importance of country-specific prevention guidelines has to be stressed.
Balance in life is an important predictor of well-being and health. This pilot research investigates the relationship between self-regulation and life balance, that is, the appropriate proportion of time spent across major life domains. In Study 1, time management was investigated as a self-regulatory competence. In contrast to expectations, time management showed only an indirect relationship to life balance through the perceived control over time. In Study 2, self-motivation, self-relaxation, and self-determination were studied as additional components of self-regulation. As expected, self-determination predicted life balance. Self-motivation and self-relaxation were linked to self-determination and showed an indirect relationship to life balance. In line with theoretical expectations, persons skilled in self-motivation and self-relaxation scored higher on self-determination, which, in turn, facilitated balance among life domains.
Those of us not addicted to querying PubMed for “synuclein” and “parkin” may consider news of two more mutations at one of the nine known Parkinson’s disease (PD)-related Mendelian gene loci a minor matter. But the reports of new α-synuclein mutations by Farrer et al and Zarranzet al in this issue of Annals reconfirm the central role of this protein in the pathologenesis of PD and the other “α-synucleinopathies” and shed light on the mechanism(s) by which α-synuclein dysfunction could lead to cell death. The former report demonstrates the toxicity of excessive α-synuclein expression in the human brain. The latter provides a new example of a qualitative defect in that protein. The existence of two very different kinds of PD-causing, dominantly-acting α-synuclein mutation helps us understand PD in its common, “sporadic” form.
2001
Lancet
Broad-spectrum antibiotics in ORACLE.
Leviton, A., Allred, E. N., Dammann, O., Kuban, K. C. K.,& Martin, C. R.
Unlike workers in previous clinical trials of antibiotics for preterm and prelabour fetal membrane rupture, S L Kenyon and colleagues, in their study of broad-spectrum antibiotics for preterm and prelabour rupture of fetal membranes (March 31, p 979), and that of antibiotics for spontaneous preterm labour (March 31, p 989) do not have delay until delivery as the primary outcome. They chose an innovative approach that emphasises neonatal disorders. We commend them for this.
Unfortunately, their main outcome was a composite variable that included any of the following phenomena: death before discharge, oxygen supplementation at 36 weeks after conception, and major cerebral abnormality on cranial ultrasonography (not otherwise defined). Are they equivalent? Fortunately, Kenyon and colleagues did separate analyses to look at each of these components.
We wonder about the inferences they draw from their inability to show that erythromycin and co-amoxiclav, alone or in combination, reduced the frequency of the primary composite outcome among infants born to women who presented with spontaneous preterm labour with intact
membranes. Kenyon and colleagues conclude that their results suggest that the part played by subclinical infection in the cause of spontaneous preterm labour has been overestimated. Because they do not report assessments of amniotic fluid or placenta microbiology, or indicators of an inflammatory response, it seems inappropriate to draw this inference.
Did they take into account that infectious or inflammatory phenomena that arise days to weeks before delivery can potentially lead to spontaneous preterm labour with intact membranes? Did they look into whether such phenomena might contribute to only some of the neonatal morbidities they assessed, but not all, or that such phenomena contribute to the onset of these morbidities long before the antibiotics are administered?
Many of the risk factors previously identified for disorders such as Alzheimer's disease, periventricular leukomalacia, multiple sclerosis, stroke, cerebral palsy, mental retardation, and acquired learning and attention disorders ultimately may be shown to damage the central and peripheral nervous systems through activation of inflammatory mediators. The challenge to epidemiologists in the future is to expand use of epidemiologic methods to explore how immune-mediated insults produce CNS disorders in human populations. Studies of the association of use of nonsteroidal anti-inflammatory drugs with risk of Alzheimer's disease and those of the association of immune parameters with risk of cerebral palsy are excellent examples of how epidemiology can contribute to our understanding of the causes of neurologic and/or neurodevelopmental disorders. Many of the immune parameters of interest have short half-lives and are difficult to measure outside of the laboratory setting. Questions also remain as to the proper timing of measurements in relation to the initial insult and, in some cases, which tissue is the most appropriate to sample. These measurement issues will need to be resolved before use of immune biomarkers in epidemiologic studies of the etiologies of neurologic disorders can be fully realized. Epidemiologists are most likely to help identify ways to prevent neurologic disorders if they are knowledgeable about the molecular biology of inflammation, modulators of CNS vulnerability, and genetic polymorphisms that influence both inflammation and CNS vulnerability and are prepared to become adept at biomarker epidemiology. This does not necessarily compel them to gain extensive knowledge of neurobiology. Rather, neuroepidemiology in the 21st century will require increased collaboration between epidemiologists, neurologists, and neurobiologists.
Paediatric and Perinatal Epidemiology
What explains away the increased risk of histological chorioamnionitis in African-American mothers of very-low-birthweight infants? Developmental Epidemiology Network Investigators.
We sought explanations for African-American mothers' increased risk of chorioamnionitis by sequentially adjusting for confounder variables both individually and in groups. We searched for a subset of covariates that had the most influence on the chorioamnionitis odds ratio (OR) of these women. The sample consisted of 305 African-American and 520 White mothers who gave birth to a very-low-birthweight (< or = 1500 g) infant between 1991 and 1993, whose placenta was examined according to protocol and whose hospital chart was reviewed. Histologically proven chorioamnionitis was present in 43% of the placentas from African-American women and in 27% of those from Whites (crude OR 2.1, 95% confidence interval 1.5, 2.8). Singleton status appeared to be the most important effect modifier, with significant crude ORs of 1.5 among singletons and 3.4 among non-singletons. Using logistic regression models in the whole sample and in subgroups, we sought to 'explain away' this increased risk. Indeed, addition of information about confounder variables resulted in considerable reduction in the ORs to 1.1 among singletons and 1.9 among non-singletons. Particularly important among the confounders were singleton birth, Medicaid insurance, duration of ruptured membranes and gestational age. We discuss the possibility that this set of confounding variables conveys, in part, the same information as the variable African-American, and also perhaps information about the availability and/or utilisation of prenatal health care.
