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Showing papers by "Alan Leviton published in 2014"


Journal ArticleDOI
TL;DR: Evidence is discussed in support of the contention that the preterm newborn is capable of intermittent or sustained systemic inflammation (ISSI), which appears to contribute more to adverse neurodevelopmental outcomes in preterm infants than does shorter duration inflammation.
Abstract: Exposure to perinatal infection and inflammation is associated with an increased risk for neonatal brain damage and developmental disabilities. In this integrated mechanism review, we discuss evidence in support of the contention that the preterm newborn is capable of intermittent or sustained systemic inflammation (ISSI), which appears to contribute more to adverse neurodevelopmental outcomes in preterm infants than does shorter duration inflammation.

118 citations


Journal ArticleDOI
TL;DR: Among children born extremely prematurely, recurrent, or persistent elevations of inflammation-related proteins in blood during in the first two postnatal weeks are associated with an attention problem at age 2 y.
Abstract: Elevated blood levels of inflammation-related proteins are associated with an attention problem at age 24 mo in extremely preterm infants

96 citations


Journal ArticleDOI
TL;DR: D Diparesis and hemiparesis were more likely among infants who had at least 4 of 9 protein elevations that previously have been associated with cognitive impairment and microcephaly.
Abstract: The authors hypothesized that among extremely preterm infants, elevated concentrations of inflammation-related proteins in neonatal blood are associated with cerebral palsy at 24 months. In 939 infants born before 28 weeks gestation, the authors measured blood concentrations of 25 proteins on postnatal days 1, 7, and 14 and evaluated associations between elevated protein concentrations and cerebral palsy diagnosis. Protein elevations within 3 days of birth were not associated with cerebral palsy. Elevations of tumor necrosis factor-α, tumor necrosis factor-α-receptor-1, interleukin-8, and intercellular adhesion molecule-1 on at least 2 days were associated with diparesis. Recurrent-persistent elevations of interleukin-6, E-selectin, or insulin-like growth factor binding protein-1 were associated with hemiparesis. Diparesis and hemiparesis were more likely among infants who had at least 4 of 9 protein elevations that previously have been associated with cognitive impairment and microcephaly. Repeated eleva...

73 citations


Journal ArticleDOI
TL;DR: Why very preterm newborns who develop retinopathy of prematurity (ROP) appear to be at increased risk of abnormalities of both brain structure and function is explained.
Abstract: Purpose To explain why very preterm newborns who develop retinopathy of prematurity (ROP) appear to be at increased risk of abnormalities of both brain structure and function. Methods A total of 1,085 children born at Results The 173 children who had severe ROP, defined as prethreshold ROP (n = 146) or worse (n = 27) were somewhat more likely than their peers without ROP to have brain ultrasound lesions or cerebral palsy. They were approximately twice as likely to have very low Bayley Scales scores. After adjusting for risk factors common to both ROP and brain disorders, infants who developed severe ROP were at increased risk of low Bayley Scales only. Among children with prethreshold ROP, exposure to anesthesia was not associated with low Bayley Scales. Conclusions Some but not all of the association of ROP with brain disorders can be explained by common risk factors. Most of the increased risks of very low Bayley Scales associated with ROP are probably not a consequence of exposure to anesthetic agents.

34 citations


Journal ArticleDOI
TL;DR: This work encourages the creation of computational simulation models that integrate information about disease etiology, pathogenetic data, and the expertise of investigators from different disciplines to help epidemiologists identify contributors to disease at multiple levels as well as their interactions.
Abstract: 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.

29 citations


Journal ArticleDOI
01 Sep 2014-Cytokine
TL;DR: In very preterm newborns, circulating levels of endogenous erythropoietin vary significantly with circulate levels of inflammation-related proteins, and these findings suggest that Elevation of endogenous ______ might not be an epiphenomenon, but instead might contribute to subsequent events, by either promoting or reducing inflammation, or by promoting an anti-injury or repair capability.

20 citations


Journal ArticleDOI
TL;DR: The association of HTT with increased or decreased risk of indicators of brain damage depends on the presence or absence of ISSI, and Elevated risk of a very low mental development score was associated with both ISSI only and HTT+ISSI, whereas a veryLow motor development score and microcephaly were associated with HTT+.
Abstract: Background We sought to disentangle the contributions of hyperthyrotropinemia (an indicator of thyroid dysfunction) (HTT) and intermittent or sustained systemic inflammation (ISSI) to structural and functional indicators of brain damage.

13 citations


Journal ArticleDOI
TL;DR: A quality improvement curriculum that provides mentorship for resident quality improvement projects and is clinically relevant to pediatric neurologists is developed and its potential to meet the Accreditation Council for Graduate Medical Education's Next Accreditation System requirements is discussed.

12 citations


Journal ArticleDOI
TL;DR: In this paper, gene expression in 9 sets of paired newborn blood spots stored for 8-10 years in either the frozen state or the unfrozen state was studied, and the average correlation coefficient for overall gene expression comparing the frozen and unfrozen states was 0.771 (95% CI, 0.700-0.828).

9 citations


Journal ArticleDOI
TL;DR: Among ELGANs, recurrent/persistent blood gas abnormalities in the first three postnatal days convey information about the risk of severe and very severe BPD.
Abstract: Aim. To determine among infants born before the 28th week of gestation to what extent blood gas abnormalities during the first three postnatal days provide information about the risk of bronchopulmonary dysplasia (BPD). Methods. We studied the association of extreme quartiles of blood gas measurements (hypoxemia, hyperoxemia, hypocapnea, and hypercapnea) in the first three postnatal days, with bronchopulmonary dysplasia, among 906 newborns, using multivariable models adjusting for potential confounders. We approximated NIH criteria by classifying severity of BPD on the basis of the receipt of any O2 on postnatal day 28 and at 36 weeks PMA and assisted ventilation. Results. In models that did not adjust for ventilation, hypoxemia was associated with increased risk of severe BPD and very severe BPD, while infants who had hypercapnea were at increased risk of very severe BPD only. In contrast, infants who had hypocapnea were at reduced risk of severe BPD. Including ventilation for 14 or more days eliminated the associations with hypoxemia and with hypercapnea and made the decreased risk of very severe BPD statistically significant. Conclusions. Among ELGANs, recurrent/persistent blood gas abnormalities in the first three postnatal days convey information about the risk of severe and very severe BPD.

5 citations


Journal ArticleDOI
TL;DR: In this article, the prevalence, antecedents, and correlates of impaired visual fixation in former very preterm newborns were found to be much more likely to have been born after the shortest of gestations (odds ratio, 3.2; 99% confidence interval, 1.4-7.5).