Karl C K Kuban

Bio: Karl C K Kuban is an academic researcher from Tufts Medical Center. The author has contributed to research in topics: Periventricular leukomalacia & Population. The author has an hindex of 12, co-authored 12 publications receiving 1017 citations. Previous affiliations of Karl C K Kuban include Floating Hospital for Children & Tufts University.

Maternal infection, fetal inflammatory response, and brain damage in very low birth weight infants

Abstract: 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 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.

Perinatal infection, fetal inflammatory response, white matter damage, and cognitive limitations in children born preterm.

Abstract: Only sparse information is available about a possible association between antenatal infection outside the brain and subsequent cognitive limitations among preterm infants. Based on published studies, we provide a theoretical schema that links them via the fetal inflammatory response and neonatal white matter damage. We conclude that the relationship between antenatal infection and cognitive limitations deserves much further attention by researchers interested in the prevention of this undesirable outcome of prematurity.

Intraoperative Hyperglycemia during Infant Cardiac Surgery Is Not Associated with Adverse Neurodevelopmental Outcomes at 1, 4, and 8 Years

Abstract: Background: It is unknown whether intraoperative hyperglycemia in infants is associated with worse neurodevelopmental outcomes after low-flow cardiopulmonary bypass (LF), deep hypothermic circulatory arrest (CA), or both. Methods: In a database review of a prospective trial of 171 infants undergoing arterial switch for D-transposition of the great arteries who were randomly assigned to predominately LF or CA, glucose was measured after induction (T1), 5 min after cardiopulmonary bypass onset (T2), at the onset of CA or LF (T3), 5 min after CPB resumption (T4), at rewarming to 32°C (T5), 10 min after cardiopulmonary bypass weaning (T6), and 90 min after CA or LF (T7). Outcomes included seizures, electroencephalographic findings, and neurodevelopmental evaluation at 1, 4, and 8 yr. Results: Glucose concentrations were affected by support strategy and age at surgery. Lower glucose in the entire group at T6 ‐T7 tended to predict electroencephalographic seizures (P 0.06 and P 0.007) but was not related to clinical seizures. Within the predominantly CA group, higher glucose did not correlate with worse outcomes. Rather, it was associated with more rapid electroencephalographic normalization of “close burst” and “relative continuous” activity at all times except T2 (P < 0.03), a finding more pronounced in infants aged 7 days old or younger. Intraoperative serum glucose concentrations were unrelated to neurodevelopmental outcomes at ages 1, 4, and 8 yr. Conclusions: Low glucose after cardiopulmonary bypass tended to relate to electroencephalographic seizures and slower electroencephalogram recovery, independent of CA duration. High glucose concentrations were not associated with worse neurodevelopmental outcomes. Avoiding hypoglycemia may be

Hypocarbia during the First 24 Postnatal Hours and White Matter Echolucencies in Newborns <28 Weeks Gestation

Abstract: The purpose of the present study was to test the hypothesis that newborns ≤28 wk gestation who have a Pco2 measurement in the lowest gestational age-specific quartile (hypocarbia) on the first day of life are not at increased risk for ultrasonographic white matter echolucency (EL) after adjustment for confounders. The sample consisted of 799 infants ≤28 wk gestation born during 1991–1993. Forty-eight infants with EL were classified as cases and compared with 751 controls, i.e. those without EL. We performed univariable comparisons, stratified analyses, and multivariable logistic regression. In the univariable analyses, hypocarbia on the first day of life was associated with an increased EL risk. The odds ratios for the hypocarbia-EL relationship were prominently elevated in the strata of infants who did not have other major risk factors for EL (e.g. gestational age 26–28 wk, normothyroxinemia, no characteristics of antenatal infection). In the multivariable analyses, the association diminished after adjustment with a hypocarbia propensity score (odds ratio = 1.7; 95% confidence interval, 0.8–3.2) or with potential confounders.

Systemic hypotension and white‐matter damage in preterm infants

Abstract: This study was designed to test the hypothesis that systemic hypotension during the first postnatal week increases the risk of ultrasonographic echolucency in the white matter of preterm infants (< or = 28 weeks' gestation) while adjusting for confounders. From a study base of 1607 very-low-birthweight neonates (500 to 1500 g), a subsample of 243 preterm infants (122 females; < or = 28 weeks' gestation) was selected for echolucency and data collection prospectively for the entire first postnatal week. Data analyses were performed separately for the first 24 hours of life, for the interval from the end of the first 24 hours to the end of the fourth postnatal day, and for days 5, 6, and 7. Systemic hypotension was defined as the mean arterial blood pressure in the lowest quartile for the infant's week of gestational age. Protocol cranial ultrasounds were those obtained closest to days 1, 7, and 21. A committee of sonologists classified the infants as having either echolucency (echolucency group) or not (control group). Systemic hypotension during the first week of life appeared to be associated with echolucency in univariable analyses but the association did not persist after adjustment for potential confounders. Detailed summaries of 13 previous studies, the majority of which did not show an association between systemic hypotension and white-matter damage, are presented. In sum, these results do not support the hypothesis that systemic hypotension contributes to echolucency among preterm infants.

Neurodevelopmental and growth impairment among extremely low-birth-weight infants with neonatal infection.

Abstract: ContextNeonatal infections are frequent complications of extremely low-birth-weight (ELBW) infants receiving intensive care.ObjectiveTo determine if neonatal infections in ELBW infants are associated with increased risks of adverse neurodevelopmental and growth sequelae in early childhood.Design, Setting, and ParticipantsInfants weighing 401 to 1000 g at birth (born in 1993-2001) were enrolled in a prospectively collected very low-birth-weight registry at academic medical centers participating in the National Institute of Child Health and Human Development Neonatal Research Network. Neurodevelopmental and growth outcomes were assessed at a comprehensive follow-up visit at 18 to 22 months of corrected gestational age and compared by infection group. Eighty percent of survivors completed the follow-up visit and 6093 infants were studied. Registry data were used to classify infants by type of infection: uninfected (n = 2161), clinical infection alone (n = 1538), sepsis (n = 1922), sepsis and necrotizing enterocolitis (n = 279), or meningitis with or without sepsis (n = 193).Main Outcome MeasuresCognitive and neuromotor development, neurologic status, vision and hearing, and growth (weight, length, and head circumference) were assessed at follow-up.ResultsThe majority of ELBW survivors (65%) had at least 1 infection during their hospitalization after birth. Compared with uninfected infants, those in each of the 4 infection groups were significantly more likely to have adverse neurodevelopmental outcomes at follow-up, including cerebral palsy (range of significant odds ratios [ORs], 1.4-1.7), low Bayley Scales of Infant Development II scores on the mental development index (ORs, 1.3-1.6) and psychomotor development index (ORs, 1.5-2.4), and vision impairment (ORs, 1.3-2.2). Infection in the neonatal period was also associated with impaired head growth, a known predictor of poor neurodevelopmental outcome.ConclusionsThis large cohort study suggests that neonatal infections among ELBW infants are associated with poor neurodevelopmental and growth outcomes in early childhood. Additional studies are needed to elucidate the pathogenesis of brain injury in infants with infection so that novel interventions to improve these outcomes can be explored.

Neonatal brain injury.

Abstract: More than 95 percent of infants who have neonatal stroke survive to adulthood, and many have residual motor or cognitive disabilities. This article makes the point that recognition of at-risk newborns by means of advanced methods of neuroimaging, combined with a plan for rational intervention, may result in the prevention or the reduction in the incidence of lifelong disabilities such as cerebral palsy, epilepsy, and behavioral and learning disorders.

Neurobiology of Periventricular Leukomalacia in the Premature Infant

Abstract: Brain injury in the premature infant is a problem of enormous importance. Periventricular leukomalacia (PVL) is the major neuropathologic form of this brain injury and underlies most of the neurologic morbidity encountered in survivors of premature birth. Prevention of PVL now seems ultimately achievable because of recent neurobiologic insights into pathogenesis. The pathogenesis of this lesion relates to three major interacting factors. The first two of these, an incomplete state of development of the vascular supply to the cerebral white matter, and a maturation-dependent impairment in regulation of cerebral blood flow underlie a propensity for ischemic injury to cerebral white matter. The third major pathogenetic factor is the maturation-dependent vulnerability of the oligodendroglial (OL) precursor cell that represents the major cellular target in PVL. Recent neurobiologic studies show that these cells are exquisitely vulnerable to attack by free radicals, known to be generated in abundance with ischemia-reperfusion. This vulnerability of OLs is maturation-dependent, with the OL precursor cell highly vulnerable and the mature OL resistant, and appears to relate to a developmental window characterized by a combination of deficient antioxidant defenses and active acquisition of iron during OL differentiation. The result is generation of deadly reactive oxygen species and apoptotic OL death. Important contributory factors in pathogenesis interact with this central theme of vulnerability to free radical attack. Thus, the increased likelihood of PVL in the presence of intraventricular hemorrhage could relate to increases in local iron concentrations derived from the hemorrhage. The important contributory role of maternal/fetal infection or inflammation and cytokines in the pathogenesis of PVL could be related to effects on the cerebral vasculature and cerebral hemodynamics, to generation of reactive oxygen species, or to direct toxic effects on vulnerable OL precursors. A key role for elevations in extracellular glutamate, caused by ischemia-reperfusion, is suggested by demonstrations that glutamate causes toxicity to OL precursors by both nonreceptor- and receptor-mediated mechanisms. The former involves an exacerbation of the impairment in antioxidant defenses, and the latter, an alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid/kainate receptor-mediated cell death. Most importantly, these new insights into the pathogenesis of PVL suggest potential preventive interventions. These include avoidance of cerebral ischemia by detection of infants with impaired cerebrovascular autoregulation, e.g. through the use of in vivo near-infrared spectroscopy, the use of free radical scavengers to prevent toxicity by reactive oxygen species, the administration of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid/kainate receptor antagonists to prevent glutamate-mediated injury, or the use of maternal antibiotics or anticytokine agents to prevent toxicity from maternal/fetal infection or inflammation and cytokines.

Chorioamnionitis as a risk factor for cerebral palsy: A meta-analysis.

Abstract: ContextChorioamnionitis has been implicated in the pathogenesis of cerebral palsy, but most studies have not reported a significant association. Cystic periventricular leukomalacia (cPVL) is believed to be a precursor of cerebral palsy in preterm infants.ObjectivesTo determine whether chorioamnionitis is associated with cerebral palsy or cPVL and to examine factors that may explain differences in study results.Data SourcesSearches of MEDLINE (1966-1999), Index Medicus (1960-1965), Doctoral Dissertation Abstracts On-Line (1861-1999), bibliographies, and online conference proceedings (1999) were performed for English-language studies with titles or abstracts that discussed prenatal risk factors for cerebral palsy or cPVL.Study SelectionOf 229 initially identified publications, meta-analyses were performed on studies that addressed the association between clinical (n = 19) or histologic (n = 7) chorioamnionitis and cerebral palsy or cPVL in both preterm and full-term infants. Inclusion criteria were: presence of appropriate exposure and outcome measures, case-control or cohort study design, and provision of sufficient data to calculate relative risks (RRs) or odds ratios with 95% confidence intervals (CIs). Studies evaluating risk of cerebral palsy following maternal fever, urinary tract infection, or other maternal infection were collected, but not included in the meta-analysis.Data ExtractionInformation from individual studies was abstracted using standardized forms by 2 independent observers blinded to authors' names, journal titles, and funding sources.Data SynthesisUsing a random effects model, clinical chorioamnionitis was significantly associated with both cerebral palsy (RR, 1.9; 95% CI, 1.4-2.5) and cPVL (RR, 3.0; 95% CI, 2.2-4.0) in preterm infants. The RR of histologic chorioamnionitis and cerebral palsy was 1.6 (95% CI, 0.9-2.7) in preterm infants, and histologic chorioamnionitis was significantly associated with cPVL (RR, 2.1; 95% CI, 1.5-2.9). Among full-term infants, a positive association was found between clinical chorioamnionitis and cerebral palsy (RR, 4.7; 95% CI, 1.3-16.2). Factors explaining differences in study results included varying definitions of clinical chorioamnionitis, extent of blinding in determining exposure status, and whether individual studies adjusted for potential confounders.ConclusionOur meta-analysis indicates that chorioamnionitis is a risk factor for both cerebral palsy and cPVL.