Showing papers by "Alan Leviton published in 2000"

Do Clinical Markers of Barotrauma and Oxygen Toxicity Explain Interhospital Variation in Rates of Chronic Lung Disease

Abstract: Objective. To explore the hypothesis that variation in respiratory management among newborn intensive care units (NICUs) explains differences in chronic lung disease (CLD) rates. Design. Case–cohort study. Setting. NICUs at 1 medical center in New York (Babies9 and Children9s Hospital [Babies9]) and 2 in Boston (Beth Israel Hospital and Brigham and Women9s Hospital [Boston]). Study Population. Four hundred fifty-two infants born at 500 to 1500 g birth weight between January 1991 and December 1993, who were enrolled in an epidemiologic study of neonatal intracranial white matter disorders. Case Definition. Supplemental oxygen required at 36 weeks9 postmenstrual age. Results. The prevalence rates of CLD differed substantially between the centers: 4% at Babies9 and 22% at the 2 Boston hospitals, despite similar mortality rates. Initial respiratory management at Boston was more likely than at Babies9 to include mechanical ventilation (75% vs 29%) and surfactant treatment (45% vs 10%). Case and control infants at Babies9 were more likely than were those at Boston to have higher partial pressure of carbon dioxide and lower pH values on arterial blood gases. However, measures of oxygenation and ventilator settings among case and control infants were similar at the 2 medical centers in time-oriented logistic regression analyses. In multivariate logistic regression analyses, the initiation of mechanical ventilation was associated with increased risk of CLD: after adjusting for other potential confounding factors, the odds ratios for mechanical ventilation were 13.4 on day of birth, 9.6 on days 1 to 3, and 6.3 on days 4 to 7. Among ventilated infants, CLD risk was elevated for maximum peak inspiratory pressure >25 and maximum fraction of inspired oxygen = 1.0 on the day of birth, lowest peak inspiratory pressure >20 and maximum partial pressure of carbon dioxide >50 on days 1 to 3, and lowest white blood count Conclusion. In multivariate analyses, a number of specific measures of respiratory care practice during the first postnatal week were associated with the risk of a very low birth weight infant developing CLD. However, after adjusting for baseline risk, most of the increased risk of CLD among very low birth weight infants hospitalized at 2 Boston NICUs, compared with those at Babies9 Hospital, was explained simply by the initiation of mechanical ventilation.

Role of the fetus in perinatal infection and neonatal brain damage.

Abstract: Increasing evidence supports the view that infants exposed to perinatal infection are at increased risk for brain injury. We suggest that elevated cytokines in the amniotic fluid or in the fetal circulation be viewed as a humoral expression and that inflammatory cells in chorionic plate or umbilical

Limitations of the World Health Organization classification of childhood supratentorial astrocytic tumors

Abstract: BACKGROUND In the context of many implied but not rigorously stated histologic feature combinations, the World Health Organization (WHO) classification of astrocytic tumors specifies only the presence or absence of endothelial proliferation, necrosis, and mitosis to distinguish astrocytoma, anaplastic astrocytoma, and glioblastoma multiforme. METHODS The authors examined the effects of these and other reliably recognized histologic features on survival in the Childhood Brain Tumor Consortium (CBTC) sample of 340 children with supratentorial astrocytic tumors. RESULTS Overall, the WHO criteria distinguished only two prognostically distinct classes of astrocytomas. When the specific combinations of the three features were unambiguously designated, three diagnostic categories resulted. These revised diagnostic categories are consistent with WHO guidelines and have significantly different survival distributions. However, neither the original WHO diagnoses nor the revised categories adequately separated these tumors prognostically, because histologic features other than those specified by WHO were significantly associated with improved or worsened survival. CONCLUSIONS Classifications based on small numbers of specified histologic features may not be feasible because they inadequately separate childhood astrocytic tumors into prognostically homogeneous groups. Preferable classification techniques are those that simultaneously account for all reliably recognized histologic features. Cancer 2000;88:1477–83. © 2000 American Cancer Society.

Very Low Birthweight Infant’s Placenta and Its Relation to Pregnancy and Fetal Characteristics

Abstract: Our objective was to relate pathology of the very low birthweight (VLBW) infant's placenta to pregnancy and fetal characteristics. We correlated the pathologic features of 1146 placentas from infants with birth weights of 500-1500 g who were born between 1/1/91 and 12/31/93 to the number of gestations per pregnancy, initiator of preterm delivery, gestational age, birth weight Z score, and duration of rupture of membrane (ROM). Placental correlates of acute inflammation and villous edema were associated with preterm labor (PTL), prelabor premature rupture of membranes (PROM), lower gestational age, and higher birth weight Z score. In PTL pregnancies delivered within 1 h of membrane rupture, 61% of placentas already had membrane inflammation. Placental correlates of pregnancy-induced hypertension (PIH) were seen more commonly with PIH pregnancies, older gestational age, and lower birth weight Z score. We found a more prominent histopathologic signature for singleton than for multiple gestation placentas. The placental pathologic findings associated with the clinical diagnoses of infection, PIH, and low-birth weight Z scores in our VLBW/preterm population are similar to those in the literature regarding term pregnancies. The presence of multiple histologic findings consistent with inflammation in placentas of PTL pregnancies with duration of ROM lasting <1 h suggests that some cases of PTL are precipitated by a more long-standing infection than that previously suspected. Morphologic placental features appear to be correlates of the phenomena leading to premature delivery. Examination of the VLBW infant's placenta provides insight into the etiology and management of VLBW/preterm deliveries.

Very low birthweight placenta: clustering of morphologic characteristics.

Abstract: Our objective was to use factor analysis as a data reduction tool to organize a large number of placental pathologic features into useful aggregates. We examined 1146 placentas of live-born infants with a birth weight of 500-1500 g. We then conducted analyses of pairs of characteristics and multiple characteristics to identify "associated groups" and "factors," respectively. We found an associated group and factor that had placental features associated with acute inflammation and another associated group and factor that had features associated with vasculopathy. Acute umbilical vasculitis had the strongest correlation with other features of the acute inflammation associated group and factor. Gross evidence of acute inflammation (opacification and green appearance of membrane) was eliminated in the reduction from associated group to factor. Infarcts and syncytial knots were strongly dissociated with features of acute inflammation. The multiple pathologic features of the very low birthweight placenta can be aggregated into two associated groups or two factors. Lack of membrane opacification cannot be used as a criterion for declining microscopic examination. The absence of infarcts and syncytial knots should prompt a search for features of acute inflammation. If a placenta has two or more findings from the acute inflammation factor or the vasculopathy factor, it is unlikely to demonstrate features from the other factor.

What explains away the increased risk of histological chorioamnionitis in African-American mothers of very-low-birthweight infants?

Abstract: 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.

New Research Directions in Neuroepidemiology

Abstract: 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.

Definitive classes of childhood supratentorial neuroglial tumors. The Childhood Brain Tumor Consortium.

Abstract: Our objective in this study was to identify histologically homogenous classes of childhood supratentorial neuroglial tumors. Previously, we identified five quantitative histologic factors (differing linear combinations of 17 reliably recognized histologic features in neuroglial tumors). They account for much of the histologic variance in the 703 supratentorial tumors in the Childhood Brain Tumor Consortium (CBTC) database. In this study, we used the scores on the factors in cluster analyses and identified eight classes of neuroglial tumors. Each of these classes had significant differences in histology, allowing the separation of many of the conventional types of neuroglial tumors into two or more classes. For instance, fibrillary astrocytoma, pilocytic astrocytoma, subependymal giant cell astrocytoma, anaplastic astrocytoma, oligodendroglioma, and ependymoma were represented in two or more classes. Often these classes had statistically significant differences in survival distributions. For instance, the two classes of "anaplastic astrocytomas" have widely discrepant 5-year survival probabilities of 0.7 and 0.2. Use of the classes identified in this study ensures relatively homogeneous histologic subsets of tumors. We suggest that these classes will be useful for the selection of children for therapeutic clinical trials.

ORIGINAL ARTICLES: Definitive Classes of Childhood Supratentorial Neuroglial Tumors

Abstract: Our objective in this study was to identify histologically homogenous classes of childhood supratentorial neuroglial tumors. Previously, we identified five quantitative histologic factors (differing linear combinations of 17 reliably recognized histologic features in neuroglial tumors). They account for much of the histologic variance in the 703 supratentorial tumors in the Childhood Brain Tumor Consortium (CBTC) database. In this study, we used the scores on the factors in cluster analyses and identified eight classes of neuroglial tumors. Each of these classes had significant differences in histology, allowing the separation of many of the conventional types of neuroglial tumors into two or more classes. For instance, fibrillary astrocytoma, pilocytic astrocytoma, subependymal giant cell astrocytoma, anaplastic astrocytoma, oligodendroglioma, and ependymoma were represented in two or more classes. Often these classes had statistically significant differences in survival distributions. For instance, the two classes of “anaplastic astrocytomas” have widely discrepant 5-year survival probabilities of 0.7 and 0.2. Use of the classes identified in this study ensures relatively homogeneous histologic subsets of tumors. We suggest that these classes will be useful for the selection of children for therapeutic clinical trials.