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A Leviton

Publications and source records attributed to A Leviton.

At least 37 records · Page 2Linked to original sources
PubMed2000

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.

Black or African American↗
PubMed2000

New research directions in neuroepidemiology.

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.

Aged↗
PubMed2000

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

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 cord blood vessel walls be viewed as a morphologic expression of the fetal inflammatory response. We discuss the evidence supporting the hypothesis that the fetal inflammatory response contributes to neonatal brain injury and later developmental disability. Little support has been found for a maternal contribution. Intervention should be designed with the fetus in mind.

Amniotic Fluid↗
PubMed2000

Do clinical markers of barotrauma and oxygen toxicity explain interhospital variation in rates of chronic lung disease? The Neonatology Committee for the Developmental Network.

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 (Babies' and Children's Hospital [Babies']) and 2 in Boston (Beth Israel Hospital and Brigham and Women's 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 weeks' postmenstrual age. RESULTS: The prevalence rates of CLD differed substantially between the centers: 4% at Babies' and 22% at the 2 Boston hospitals, despite similar mortality rates. Initial respiratory management at Boston was more likely than at Babies' to include mechanical ventilation (75% vs 29%) and surfactant treatment (45% vs 10%). Case and control infants at Babies' 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 <8 K on days 4 to 7. Even after adjusting for white blood count <8 K and the 4 respiratory care variables, infants in Boston continued to be at increased risk of CLD, compared with premature infants at Babies' Hospital. 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 Babies' Hospital, was explained simply by the initiation of mechanical ventilation.

Barotrauma↗
PubMed1999

Labor and delivery characteristics and risks of cranial ultrasonographic abnormalities among very-low-birth-weight infants. The Developmental Epidemiology Network Investigators.

OBJECTIVE: The objective of this study was to evaluate the relationships between 3 labor and delivery characteristics (duration of labor, interval between membrane rupture and delivery, and route of delivery) and 4 neonatal cranial ultrasonographic abnormalities (intraventricular hemorrhage, ventriculomegaly, echodensity of cerebral white matter, and periventricular leukomalacia). STUDY DESIGN: We prospectively gathered data on 1588 very low birth weight infants including neonatal cranial ultrasonographic studies, maternal interview, and maternal and infant chart reviews. We performed univariate and multivariate analyses. RESULTS: In univariate analysis vaginal delivery was associated with an increased risk of all 4 cranial ultrasonographic abnormalities. In multivariate analysis, however, vaginal delivery was no longer associated with periventricular leukomalacia. Moreover, the risks of intraventricular hemorrhage, ventriculomegaly, and echodensity attributable to vaginal delivery were no longer elevated when the sample was limited to infants born within 1 hour after membrane rupture and adjustment was made for fetal vasculitis and for other potential confounders. CONCLUSION: Vaginal delivery was the only obstetric characteristic consistently associated with intracranial hemorrhage and white matter disease in these preterm infants. Because its relationship to brain lesions was markedly reduced when placental inflammation was accounted for, however, vaginal delivery may simply have acted as a marker for antecedent inflammation or infection and not as a direct contributor to brain disorders.

Brain↗
PubMed1999

Antenatal corticosteroids and cranial ultrasonographic abnormalities.

OBJECTIVE: This study was undertaken to determine whether very-low-birth-weight infants whose mothers received a course of antenatal corticosteroids were at decreased risk for 3 cranial ultrasonographic entities that predict neurodevelopmental dysfunction. STUDY DESIGN: This retrospective cohort study evaluated 1604 infants weighing 500 to 1500 g who underwent >/=1 of 3 cranial ultrasonographic scans required by design at specified postnatal intervals and whose own and mother's hospital charts were reviewed. Infants were classified according to mother's course of antenatal corticosteroids (none, partial, or complete). RESULTS: In the total sample the risks of intraventricular hemorrhage and of an echolucent image in the cerebral white matter were only modestly (and not statistically significantly) reduced after a full course of antenatal corticosteroids, whereas antenatal corticosteroids appeared to significantly reduce the risk of ventriculomegaly after even a partial course. Antenatal corticosteroids appeared to halve the risk of ventriculomegaly and echolucent image among the gestationally youngest infants and those with intraventricular hemorrhage, hypothyroxinemia, or vasculitis of the umbilical cord or chorionic plate of the placenta. CONCLUSION: These observations are consistent with the hypothesis that antenatal corticosteroids protect very-low-birth-weight infants, especially those who are most vulnerable, against the risk of cranial ultrasonographic abnormalities.

Adrenal Cortex Hormones↗
PubMed1999

White matter disorders of prematurity: association with intraventricular hemorrhage and ventriculomegaly. The Developmental Epidemiology Network.

OBJECTIVES: Because intraventricular hemorrhage (IVH) often precedes the development of sonographically defined white matter damage (WMD) in very preterm infants, we sought to identify the IVH characteristics that predict WMD. HYPOTHESES: We evaluated variations on the null hypothesis that infants with IVH are no more likely than infants without IVH to have WMD. These variations dealt with characteristics of the IVH (presence or absence of ventriculomegaly) or characteristics of the WMD (size, localization, and laterality). METHODS: A total of 1605 infants weighing 500 to 1500 g at birth between January 1991 and December 1993 underwent standardized cranial ultrasound studies with 6 standard coronal and 5 sagittal views at postnatal days 1 to 3, 7 to 10, and at 3 to 8 weeks. RESULTS: A total of 129 (8%) infants had WMD, either an echodensity alone (n = 59), an echolucency alone (n = 18), or both (n = 52). In analyses that controlled for gestational age, IVH was associated with a fivefold to ninefold increased risk of WMD regardless of size, laterality, or extent of lesions (P </=.0005). Compared with infants with neither IVH nor ventriculomegaly, infants with both were at 18- to 29-fold greater risk of WMD (P </=.0005). CONCLUSIONS: In this study IVH and ventriculomegaly were powerful predictors of WMD occurrence, whether small or large, unilateral or bilateral, localized or diffuse.

Brain Diseases↗
PubMed1999

Hypothyroxinemia of prematurity and the risk of cerebral white matter damage.

OBJECTIVE: Infants with hypothyroxinemia of prematurity (HOP) are at increased risk for neurodevelopmental dysfunction. Infants born near the end of the middle trimester are also at increased risk for an echolucency (EL) in the cerebral white matter, which reflects white matter damage and is the cranial ultrasound abnormality that best predicts neurodevelopmental dysfunction. We postulated that some of the increased risk of neurodevelopmental problems associated with HOP reflects an increased risk of EL. STUDY DESIGN: We studied 1414 infants weighing 500 to 1500 g who were born at 4 medical centers between 1991 and 1993. The infants had thyroxine blood levels measured during the first weeks of life, at least 1 of 3 cranial ultrasound scans performed at specified postnatal intervals, and their own and their mother's hospital charts reviewed. Infants were classified by whether or not their first thyroxine level placed them in the lowest quartile among all infants in this sample (ie, <67.8 nmol/L, our definition of HOP, equivalent to <5.3 micrograms/dL). RESULTS: After adjusting for such potential confounders as low gestational age and measures of illness severity, infants with HOP had twice the risk of EL as their peers with higher thyroxine levels. CONCLUSION: Our findings are consistent with the hypothesis that a "normal" blood thyroxine level protects infants born near the end of the middle trimester against the risk of cerebral white matter damage.

Brain↗
PubMed1999

Maternal infection, fetal inflammatory response, and brain damage in very low birth weight infants. Developmental Epidemiology Network Investigators.

Echolucent images (EL) of cerebral white matter, seen on cranial ultrasonographic scans of very low birth weight newborns, predict motor and cognitive limitations. We tested the hypothesis that markers of maternal and feto-placental infection were associated with risks of both early (diagnosed at a median age of 7 d) and late (median age = 21 d) EL in a multi-center cohort of 1078 infants <1500 x g. Maternal infection was indicated by fever, leukocytosis, and receipt of antibiotic; fetoplacental inflammation was indicated by the presence of fetal vasculitis (i.e. of the placental chorionic plate or the umbilical cord). The effect of membrane inflammation was also assessed. All analyses were performed separately in infants born within 1 h of membrane rupture (n = 537), or after a longer interval (n = 541), to determine whether infection markers have different effects in infants who are unlikely to have experienced ascending amniotic sac infection as a consequence of membrane rupture. Placental membrane inflammation by itself was not associated with risk of EL at any time. The risks of both early and late EL were substantially increased in infants with fetal vasculitis, but the association with early EL was found only in infants born > or =1 after membrane rupture and who had membrane inflammation (adjusted OR not calculable), whereas the association of fetal vasculitis with late EL was seen only in infants born <1 h after membrane rupture (OR = 10.8; p = 0.05). Maternal receipt of antibiotic in the 24 h just before delivery was associated with late EL only if delivery occurred <1 h after membrane rupture (OR = 6.9; p = 0.01). Indicators of maternal infection and of a fetal inflammatory response are strongly and independently associated with EL, particularly late EL.

Brain Damage, Chronic↗
PubMed1999

Brain damage in preterm newborns: might enhancement of developmentally regulated endogenous protection open a door for prevention?

We present a two-component model of brain white matter damage in preterm neonates. The insult component comprises infection and hypoxia-ischemia, which are both associated with inflammation-related abnormalities in the white matter. The developmental component comprises at least three factors, ie, immaturity of the ependymal/endothelial, oligodendroglial, and endogenous protection systems. All three factors are likely contributors to an increased vulnerability of the preterm newborn's white matter. In this article, we focus on recent developments in oligodendrocyte biology that support the view of certain cytokines and growth factors as oligotrophins based on their capability to enhance oligodendrocyte development or survival. We suggest that research into networks of developmentally regulated endogenous protectors (such as oligotrophins) is necessary to broaden our perspectives in brain injury prevention in preterm newborns.

Brain Damage, Chronic↗
PubMed1998

Infection remote from the brain, neonatal white matter damage, and cerebral palsy in the preterm infant.

This review synthesizes the literature supporting the hypothesis that infection during or even before pregnancy remote from the fetal brain leads to neonatal white matter damage (NWMD) and its long-term sequelae, including cerebral palsy. First, a framework of five dimensions is presented, including the spectrum of NWMD, its relationship with gestational age, its clinical spectrum, the expressions and correlates of infection, and the mother/child dyad. Second, a summary of the plethora of support for the remote infection/NWMD-hypothesis is presented by drawing on studies published over the past three decades. Although an epidemiological perspective is prominent, we invoke molecular explanations (especially the cytokine hypothesis) for observed associations. Third, the article concludes with a section on future studies needed to characterize and eliminate (pre-) pregnancy infections in the mother and to identify and evaluate potentially neuroprotective strategies in the fetus.

Brain Injuries↗
PubMed1998

Clusters of histologic characteristics in children with infratentorial neuroglial tumors. The Childhood Brain Tumor Consortium.

Five quantitative histologic factors, differing linear combinations of 26 reliably recognized histologic features, account for much of the histologic variance in 1068 children with infratentorial neuroglial tumors in the Childhood Brain Tumor Consortium (CBTC) database. In this study, we used the scores on the Spongy, Proliferative, Ring, Fibrillary, and Nuclear factors in cluster analyses and identified 11 clusters of children's tumors. Each had statistically significant differences in histology and relative histologic homogeneity. Three clusters had ependymoma-like histologic features; 4 had astrocytoma-like features; and 4 had primitive neuroectodermal-like (PNET or medulloblastoma) features. Each cluster had a unique high/low mean factor score pattern. Multiple operative and other clinical features characterized the three groups of clusters. We used Kaplan-Meier survival models to test for differences in survival among clusters and proportional hazards survival models to adjust for associated covariates. Among the 'ependymoma' clusters the 5 year survival probability ranged from 0.25 to 0.54. Among the 4 'astrocytoma' clusters, 5 year survival probability ranged from 0.59 to 0.94. The 5 year survival probability for the 'medulloblastoma' clusters ranged from 0.20 to 0.44. Within the three groups, clusters had differing covariates associated with survival. The tumor clusters identified in this study ensure relatively homogeneous histologic subsets. The five factor scores of a child's tumor provide the basis for finding the cluster nearest to that tumor. We propose that this tumor clustering strategy be employed for selection of children and for analyses of therapeutic clinical trials.

Astrocytoma↗
PubMed1998

Groups of histopathologic abnormalities in brains of very low birthweight infants.

The neuropathologic changes in brains of very premature infants are well recognized but relatively few studies have attempted to identify if specific neuropathologic features cluster together. These data could assist in determining pathogenetic mechanisms of immature brain injury. The goal of this study is to identify which, if any, combinations of histologic features occur together. We identified the presence or absence of 19 histologic features in the brains of 67 infants from a multicenter study of 1,665 prematurely born infants whose birthweight was 500-1,500 grams. We used clustering algorithms and factor analysis to group pathologic features that occurred together. Our results indicate that certain histopathologic features do cluster. For example, telencephalic white matter astrocytosis occurs in 2 groups: 1) associated with amphophilic globules, and, 2) in an uncorrelated group, associated with focal macrophage deposits and coagulative necroses. Parenchymal hemorrhage was not found to be associated with any telencephalic leukoencephalopathy, regardless of whether characterized by rarefaction, astrocytosis, focal coagulative necroses, or foci of macrophages in the white matter. Intraventricular hemorrhage and germinal matrix hemorrhage were not seen together more often than by chance expectation. Intraventricular hemorrhage was only marginally associated with parenchymal hemorrhage. Our data indicate that specific histopathologic features tend to preferentially cluster with each other in groups. This clustering may represent the manifestation of a common mechanism for each. These data should be valuable indicators for future research attempting to establish pathogenesis.

Algorithms↗
PubMed1998

Prognostic limitations of the Daumas-Duport grading scheme in childhood supratentorial astroglial tumors.

The Daumas-Duport grading scheme (DDGS) is a commonly used method for determining the grade of a tumor. It scores 4 histologic features and is used as a prognostic tool in adult astroglial tumors. This system of assigning children to prognostically homogeneous groups has not been evaluated. The Childhood Brain Tumor Consortium (CBTC) database includes 327 children with a CBTC assigned World Health Organization (WHO) diagnosis of supratentorial astroglial tumor and histologic features necessary for Daumas-Duport grading. We compared survival estimates for tumors within and between DDGS grades using a slightly broadened definition of endothelial prominence. The DDGS yielded only 3 histologic groups in children and only 2 prognostically differing groups. Subgroups within DDGS grades had significantly different survival distributions. The summing of 4 disparate histologic features in the DDGS is inadequate for the assessment of childhood supratentorial astroglial tumors. A classification system more fully summarizing the complete histologic content of tumors is most likely to provide diagnoses useful for clinical purposes.

Adolescent↗