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Alan Leviton

Publications and source records attributed to Alan Leviton.

At least 19 recordsLinked to original sources
PubMed2006

Inflammation, brain damage and visual dysfunction in preterm infants.

Antenatal intrauterine infection and the fetal inflammatory response appear to be important pathogenetic factors in preterm birth and subsequent neonatal disorders of the lung and brain. In this paper, we expand this concept to include visual dysfunction. Although present data tend to support our notion, we suggest that more experimental and epidemiological research is needed to elucidate mechanisms of infection/inflammation-induced damage to the eye and visual brain pathways of preterm infants.

Brain Injuries↗
PubMed2005

Antenatal glucocorticoids increase early total thyroxine levels in premature infants.

BACKGROUND: Hypothyroxinemia is associated with adverse neonatal outcomes including white matter damage, cerebral palsy, poor neurodevelopment and death. It has become increasingly important to understand the natural history and modifiers of thyroid function in the premature infant. It is standard obstetrical practice to offer antenatal glucocorticoids to pregnant women with threatened preterm delivery. Few studies have investigated the effect of antenatal glucocorticoids on neonatal thyroid function. OBJECTIVE: To examine the association between antenatal exposure to glucocorticoids and early total thyroxine (T4) levels among extremely premature infants. METHODS: We studied 521 infants born at 4 medical centers. Entry criteria included a gestational age of 23-28 weeks and a serum thyroxine level obtained in the first postnatal week. Receipt of antenatal glucocorticoids was recorded as none, partial, or complete. A complete course consisted of two doses of betamethasone or four doses of dexamethasone within a 48-hour period between 2 and 7 days of delivery. Early total T4 levels were obtained from state-mandated newborn screening programs. RESULTS: Controlling for potential maternal, perinatal and neonatal confounding variables, infants exposed to a complete course of antenatal glucocorticoids had total T4 levels 0.8 microg/dl higher than their peers who were not exposed to a complete course of antenatal glucocorticoids (p = 0.03). CONCLUSIONS: Extremely premature infants who received a complete course of antenatal glucocorticoids had significantly higher total thyroxine levels in the first postnatal week. Maternal, perinatal, and early neonatal variables did not completely explain this association. We speculate that antenatal glucocorticoids influence early neonatal thyroid function.

Adult↗
PubMed2005

The adaptive immune response in neonatal cerebral white matter damage.

Hypotheses that inflammation contributes to neonatal cerebral white matter damage have evolved over the last three decades. The latest, expanded here, suggests that the adaptive immune system contributes to the intensity and duration of the processes that result in damage to cerebral white matter in the fetus and newborn. We propose several mechanisms by which fetal T lymphocytes could be activated during fetal exposure to infection. These include specific recognition of bacterial antigens, specific recognition of autoantigens, polyclonal activation by Toll-like receptors, and bystander activation by cytokines.

Adaptation, Physiological↗
PubMed2005

Proposed definition and classification of cerebral palsy, April 2005.

Because of the availability of new knowledge about the neurobiology of developmental brain injury, information that epidemiology and modern brain imaging is providing, the availability of more precise measuring instruments of patient performance, and the increase in studies evaluating the efficacy of therapy for the consequences of injury, the need for reconsideration of the definition and classification of cerebral palsy (CP) has become evident. Pertinent material was reviewed at an international symposium participated in by selected leaders in the preclinical and clinical sciences. Suggestions were made about the content of a revised definition and classification of CP that would meet the needs of clinicians, investigators, and health officials, and provide a common language for improved communication. With leadership and direction from an Executive Committee, panels utilized this information and have generated a revised Definition and Classification of Cerebral Palsy. The Executive Committee presents this revision and welcomes substantive comments about it.

Cerebral Palsy↗
PubMed2005

Lung and brain damage in preterm newborns, and their association with gestational age, prematurity subgroup, infection/inflammation and long term outcome.

Compared with those born at term, preterm newborns are at an increased risk of short term disorders of the lung (bronchopulmonary dysplasia; BPD) and the brain (white matter damage; WMD), and of long term developmental and pulmonary dysfunctions. Although all of these adverse outcomes are associated with low gestational age, brain, but not lung, damage appears to be associated with the prematurity subgroup [spontaneous preterm labour and/or preterm prelabour rupture of membranes (PPROM) vs pregnancy-induced hypertension (PIH)]. Part of the association between brain damage and prematurity subgroup might be due to a differential exposure of members of these subgroups to perinatal infection/inflammation. There is a lack of studies evaluating the association of antenatal and perinatal risk factors with late childhood pulmonary dysfunction among those born during the second trimester. In this paper we discuss the complexities that paediatricians, perinatologists and perinatal epidemiologists face as they try to understand the contributions of factors associated with preterm birth to neonatal and childhood disorders.

Brain Diseases↗
PubMed2005

Video and CD-ROM as a training tool for performing neurologic examinations of 1-year-old children in a multicenter epidemiologic study.

In lieu of traditional training of examiners to identify cerebral palsy on a neurologic examination at age 1 year, we proposed an alternative approach using a multimedia training video and CD-ROM we developed after a two-step validation process. We hypothesized that use of CD-ROM interactive training will lead to reliable and valid performance of the neurologic examination by both pediatric neurologists and nonpediatric neurologists. All examiners were asked to take one of six interobserver variability tests found on the CD-ROM on two occasions. In the first interobserver variability evaluation, 89% (531 of 594) of the responses agreed with the gold standard responses. Following annotated feedback to the examiners about the two items that had a 60% correct rate, the correct response rate rose to 93% (114 of 123). In the second interobserver variability evaluation, 88% (493 of 560) of the responses agreed with the gold standard responses. Following annotated feedback to the examiners about the four items that had a 70% correct rate, the correct response rate rose to 96% (104 of 108). Interactive CD-ROM examination training is an efficient and cost-effective means of training both neurologists and non-neurologists to perform structured neurologic examinations in 1-year-old children. It provides an effective means to evaluate interobserver variability, offers a route for feedback, and creates an opportunity to reevaluate variability, both immediately and at periodic intervals.

CD-ROM↗
PubMed2004

Lung and brain damage in preterm newborns. Are they related? How? Why?

The relationships among bronchopulmonary dysplasia (BPD), brain white matter damage (WMD) and cerebral palsy (CP) are far from simple. Apparently, BPD and WMD are not associated, while BPD and CP are. The most likely explanation for this paradox is that ultrasound imaging does not identify all the WMD that might lead to CP ('tip-of-the-iceberg effect'). We discuss further methodological inconsistencies, etiological peculiarities related to antenatal infection/inflammation, and intervention-related issues. In particular, we expand on the multiple-hit scenario in the etiology of BPD and offer support for the hypothesis that it is not lung disease, but factors associated with lung disease (e.g. postnatal steroid exposure) that increase the risk for developmental disability in childhood.

Brain Diseases↗
PubMed2004

Prognostic limitations of the Daumas-Duport grading scheme in infratentorial neuroglial tumors in children.

The Daumas-Duport grading scheme (DDGS) utilizes four histologic features in an additive method (grade 1 if none present, grade 2 if only one is present, etc.). Its efficacy in achieving prognostically homogeneous groups of childhood infratentorial neuroglial tumors and its concordance with World Health Organization (WHO) diagnoses has not been evaluated. We investigated these questions using the Childhood Brain Tumor Consortium (CBTC) database of 1241 neuroglial tumors limited to the infratentorial compartment. We calculated survival function estimates for various DDGS grades as well as the histologic features within each grade. The feature of endothelial prominence improved survival expectation, whereas the remaining three features of nuclear atypia, mitoses, and necrosis were associated with worsened survival. Survival estimates for tumors with DDGS grades 2 and 3 did not differ. Some grades contained feature subsets with significantly different survival distributions. The survival distributions of DDGS grade 1, DDGS grade 2 with only endothelial prominence, and DDGS grade 3 with nuclear atypia and endothelial prominence were not significantly different. DDGS grade within WHO diagnoses had no significant effect on survival expectation. We conclude that grading by summation of only four histologic features, as in the DDGS, is inappropriate for assessment of childhood neuroglial tumors. A classification scheme considering the complete histologic content is more likely to provide clinically useful diagnoses. Such a scheme, based on the CBTC database is available. This scheme uses 26 histologic features identified as reliable in read-reread studies.

Child↗
PubMed2004

Coagulation, inflammation, and the risk of neonatal white matter damage.

Indicators of coagulation activation are sometimes increased in the blood of newborns and adults who have a systemic inflammatory response. These coagulation factors have the ability to exacerbate inflammation, which in turn can promote coagulation. Therapies directed solely at coagulation factors and therapies directed solely at inflammation factors have not proved effective in reducing mortality in adults with a systemic inflammatory response syndrome and multi-organ dysfunction (SIRS/MOD). On the other hand, the only therapy that has reduced mortality in SIRS/MOD is activated protein C, which has both anti-coagulation and anti-inflammatory effects. This and other observations support the view that activated coagulation factors enhance inflammation. Since newborns at risk of cerebral white matter damage and cerebral palsy are more likely than their peers to have a systemic inflammatory response, which is sometimes accompanied by elevated blood levels of coagulation factors, we suggest that activated coagulation factors contribute to the occurrence of cerebral white matter damage by exacerbating inflammatory phenomena, rather than by occluding cerebral blood vessels.

Adult↗
PubMed2004

Inflammatory brain damage in preterm newborns--dry numbers, wet lab, and causal inferences.

Epidemiologic observations support the contention that infection, inflammation, and neonatal white matter damage (WMD) are associated. We also have documentation from multiple experimental models that infection/inflammation can damage developing white matter. Based on these observations in humans and animals, we offer causal inferences using widely accepted causal criteria and the multivariable model of causation. As much as we want to, however, we are reluctant to state unequivocally that inflammation causes WMD in humans born much before term. The main reason is that we lack convincing evidence that inflammation precedes WMD (temporal evidence). We also need more (and more detailed) observational studies clarifying the presumed infection --> inflammation --> WMD sequence before we can initiate intervention trials to reduce the risk of WMD.

Analysis of Variance↗
PubMed2004

Preconditioning and the developing brain.

Preconditioning occurs when a subinjurious exposure renders the brain less vulnerable to a subsequent damaging exposure. In this essay, various models of preconditioning in the immature brain are discussed. Adenosine, excitatory amino acids, nitric oxide, hypoxia-inducible factor, ATP-sensitive K+ channels, caspases, heat shock proteins, inflammatory mediators and gene expression all seem to be involved in sensing, transducing and executing preconditioning resistance. Also reviewed in this essay is evidence that some subinjurious exposures render the brain more vulnerable to a subsequent damaging exposure. We believe that unraveling the mechanisms of how the developing brain becomes inherently resilient or vulnerable will offer important insights into the pathogenesis of injury. Preconditioning of the brain or induction of tolerance of the immune system might be utilized in the future to decrease CNS vulnerability and the occurrence of perinatal brain injury.

Animals↗
PubMed2003

Bronchopulmonary dysplasia is not associated with ultrasound-defined cerebral white matter damage in preterm newborns.

Bronchopulmonary dysplasia (BPD) and cerebral white matter damage (WMD) are neonatal disorders that occur most commonly in those who are born much before term. In a large multicenter database, we sought to determine whether the two disorders occur together more frequently than expected and whether BPD and other neonatal respiratory characteristics are more common among infants who develop ultrasound-defined WMD than among those who do not. In a sample of 904 infants who were born before the 30th week of gestation and survived until 36 wk postmenstrual age, we did not find a co-occurrence of BPD and WMD above what would be expected by chance. Confounding does not seem to account for this lack of association between WMD and BPD. In conclusion, our findings do not support the hypothesis that BPD contributes to the occurrence of sonographically defined WMD.

Brain Diseases↗
PubMed2003

Antenatal mycoplasma infection, the fetal inflammatory response and cerebral white matter damage in very-low-birthweight infants.

We address the question as to whether Ureaplasma urealyticum or Mycoplasma hominis, cultured from the placenta of very-low-birthweight (VLBW) infants, are associated with an increased risk of (a) fetal vasculitis and (b) ultrasonographic cerebral white matter echolucency. The sample consisted of 464 VLBW infants for whom (i) the surface of the chorion was cultured for U. urealyticum and M. hominis; (ii) the placenta was examined histologically; and (iii) a cranial ultrasound scan was obtained close to days 1, 7 or 21. Infants with echolucency were compared with controls in univariable and stratified analyses and in multivariable logistic regressions. Fifty-three per cent of placentas from infants with fetal vasculitis harboured U. urealyticum compared with 18% of controls (P </= 0.001). M. hominis was present in 14% of cases of fetal vasculitis and in 2% of controls (P </= 0.001). Among cases of echolucency, 22% had U. urealyticum compared with 30% of controls (P = 0.33), whereas 17% of these cases and 5% of controls had M. hominis (P = 0.08). Our findings support the hypothesis that U. urealyticum in the placenta of VLBW infants contributes to the fetal inflammatory response without contributing to white matter damage. Our finding that M. hominis in the placenta was associated with a not quite significant threefold risk increase for echolucency deserves further investigation.

Brain↗
PubMed2003

Prolonged latency after preterm premature rupture of membranes: an evaluation of histologic condition and intracranial ultrasonic abnormality in the neonate born at <28 weeks of gestation.

OBJECTIVE: The purpose of this study was to evaluate whether infants who were delivered at <28 weeks of gestation after prolonged latency in pregnancies that were complicated by preterm premature rupture of membranes are at increased risk of histologic chorioamnionitis and intracranial ultrasound abnormalities. STUDY DESIGN: A retrospective cohort analysis of 430 singleton infants born at <28 weeks of gestation in five hospitals (January 1991 through December 1993) with at least one of three protocol cranial scans read by a consensus committee and with placental pathologic evidence. Outcome variables were placental (histologic chorioamnionitis, fetal vasculitis) and neonatal (intraventricular hemorrhage, echolucencies, ventriculomegaly). Latency was divided into five intervals, and outcomes in the longer four intervals were compared with those in infants who were delivered at <1 hour after membrane rupture. Each outcome-latency relationship was evaluated in a logistic model that was controlled for confounders. RESULTS: Odds ratios and CIs for each latency interval that was controlled for confounders that included gestational age, maternal race, antenatal steroid and antibiotic administration, and delivery mode show a statistically significant increase in the risk of histologic chorioamnionitis and fetal vasculitis. Models for intraventricular hemorrhage, ventriculomegaly, and echolucencies failed to demonstrate significant differences with increasing latency. CONCLUSIONS: Ascending transcervical infection after preterm premature rupture of membranes is documented by the increasing odds ratios of placental inflammation. The odds of ultrasonically detectable brain abnormalities, however, did not increase with increasing latency.

Adult↗
PubMed2002

Clinical and survival covariates of eight classes of childhood supratentorial neuroglial tumors.

BACKGROUND: In the current study, the authors investigated clinical, surgical, and histologic characteristics (covariates) and their interactions in eight previously identified classes of childhood supratentorial neuroglial tumors. The classes resulted from 5 factor score profiles on 703 supratentorial neuroglial tumors in the Childhood Brain Tumor Consortium database. METHODS: The Cox proportional models were used to identify class survival covariates. RESULTS: Age was found to be a survival covariate only in Class 1, in which older age increased the 5-year survival rate 73% from the first year (0.49) to the tenth year (0.85). A greater amount of tumor removed improved survival in Classes 2 and 4 only. Rosenthal fibers improved survival in Class 2 and overrode the negative effects of high Proliferative factor scores and pleomorphic nuclei. Survival for Class 3 children with high Proliferative factor scores improved from 0.60 to 0.95 as the Spongy factor scores increased. Survival in Class 4 increased from 0.17 to 0.39 with total tumor removal. Irregular nuclei and glomeruloid capillaries improved survival in Class 5 patients. Class 6 survival improved with low cell density. Macrocysts in tumors in Classes 1 and 5 were found to improve survival. CONCLUSIONS: As a result of the current study, the authors conclude that survival covariates differ with tumor class and may modify prognosis considerably.

Astrocytoma↗