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Biomedical subjects

Karin B Nelson

Publications and source records attributed to Karin B Nelson.

At least 19 recordsLinked to original sources
PubMed2006

Thrombophilias, perinatal stroke, and cerebral palsy.

Perinatal ischemic stroke has become recognized as a not-rare adverse outcome of pregnancy and a common cause of chronic neurologic disability in children. This review discusses the clinical entity, perinatal stroke, and its relationship to thrombophilias, inherited and acquired, and to maternal and pregnancy factors.

Brain Ischemia↗
PubMed2005

Selected neurotrophins, neuropeptides, and cytokines: developmental trajectory and concentrations in neonatal blood of children with autism or Down syndrome.

Using a double-antibody immunoaffinity assay (Luminex) and ELISA technology, we measured concentrations of certain neurotrophins, neuropeptides, and cytokines in pooled samples (one to three subjects per sample) eluted from archived neonatal blood of children with later-diagnosed autism, Down syndrome, very preterm birth, or term control infants. We also measured analytes in blood from healthy adult controls. Case or control status for infant subjects was ascertained by retrospective review of service agency medical records. We observed inhibitory substances in eluates from archived bloodspots, especially marked for measurement of BDNF. Concentrations in control subjects differed by age: BDNF rose markedly with age, while NT-3 and NT-4/5 concentrations were lower in adults than in newborn infants. IL-8 concentrations were higher in newborn infants, preterm and term, than in adults. Considered by diagnostic group, total protein was higher in Down syndrome than in either autism or control subjects. In infants with Down syndrome, concentrations of IL-8 levels were higher than in controls, whether or not corrected for total protein; NT-3 and CGRP were lower and VIP higher. In samples from autistic subjects, NT-3 levels were significantly lower than controls and an increase in VIP approached statistical significance. Concentrations of NT-4/5 and CGRP were correlated in infants with autism but not in Down syndrome or controls. Some of these results differ from earlier findings using a single-antibody recycling immunoaffinity chromatography (RIC) system. We discuss interrelationships of VIP, NT-3 and IL-8 and their potential relevance to features of the neuropathology of autism or Down syndrome.

Adult↗
PubMed2005

Genetic polymorphisms and cerebral palsy in very preterm infants.

In the present study, we examine whether selected genetic polymorphisms contribute to the development of cerebral palsy (CP) in very preterm infants. Subjects were 96 singleton infants with later-diagnosed CP and 119 control children, white non-Hispanic (n for CP=74, controls=88) or white Hispanic (CP=22, controls=31), born <32 wk gestation. Presence of CP was identified through state service agencies, with review of medical records. DNA extracted from archived neonatal blood was genotyped using multi-locus polymerase chain reaction amplification and immobilized sequence-specific oligonucleotide probes. Single nucleotide polymorphisms (SNPs) showing evidence of association with development of CP were endothelial nitric oxide synthase (eNOS) A(-922)G, factor 7 (F7) arg353gln and del(-323)10bp-ins, and lymphotoxin A (LTA) thr26asn. In white non-Hispanic children, beta-2 adrenergic receptor gln27glu was associated with CP risk; in Hispanic children, plasminogen activator inhibitor-1 (PAI-1) 4G(-675)5G and G11053T were associated with risk of CP. In a logistic regression considering these SNPs simultaneously in non-Hispanics, an association with CP was observed for heterozygotes of eNOS -922 (OR 3.0, CI 1.4-6.4), F7 (OR 2.7, CI 1.1-6.5), LTA (OR 2.1, CI 1.0-4.6), and PAI-1 (OR 3.2, CI 1.2-8.7). Factor 5, Factor 2, methylene tetrahydrofolate reductase, tumor necrosis factor-alpha, and other SNPs tested were not significantly associated with CP risk. We conclude that further study of genetic factors that may influence susceptibility to CP in very preterm infants is warranted.

Case-Control Studies↗
PubMed2005

Perinatal arterial stroke: understanding mechanisms and outcomes.

Arterial ischemic infarction occurring around the time of birth is an increasingly recognized cause of neurological disability in children. The rate of arterial infarction in neonates is as high as the annual incidence of large-vessel ischemic stroke in adults. Factors contributing to this increased risk of stroke among neonates include complications that occur before, during, and after delivery. Maternal conditions that have been associated with perinatal stroke in the fetus include prothrombotic disorders, cocaine abuse, and placental complications such as chorioamnionitis and placental vasculopathy. In many cases, the placenta is suspected to be the underlying embolic source for perinatal stroke, although data on placental pathology is often lacking. During the delivery process, an infant may develop a cervical arterial dissection that leads to stroke. Several conditions in the neonatal period predispose to perinatal stroke including prothrombotic disorders, congenital heart disease, meningitis, and systemic infection. Perinatal stroke may present with neonatal seizures during the first weeks of life or may be asymptomatic until months later when the infant is first noted to have pathological handedness. The outcome of perinatal stroke is variable and depends on severity, anatomic localization, and other factors not yet well characterized. As many as 50% of infants with documented stroke recognized in the newborn period do not develop a hemiparesis. The incidence, clinical presentation, pathogenesis, risk factors, and outcome of this increasingly recognized disorder are reviewed.

Cerebral Arterial Diseases↗
PubMed2005

Prothrombotic factors in children with stroke or porencephaly.

OBJECTIVE: This study compared the frequencies of genetic and functional coagulation abnormalities in children with arterial ischemic stroke or porencephaly with frequencies in previously published studies. METHODS: A series of 59 children (age 0-18 years) with arterial ischemic stroke or porencephaly were referred to the National Institutes of Health. A blood sample, buccal smear sample, questionnaire, and pedigree were requested for each child. Blood samples were analyzed for protein C (PC); protein S; antithrombin (AT); activated PC resistance (APCR); lipoprotein (a) [Lp(a)]; lupus anticoagulant; anticardiolipin antibodies; and the methylenetetrahydrofolate reductase C677T (MTHFR), factor V G1619A, factor II G20210A (PT), plasminogen activator inhibitor-1 4G6755G, and tissue factor pathway inhibitor C536T mutations. The frequency of each coagulation abnormality was compared with published international pediatric stroke case and control rates. RESULTS: At least 1 prothrombotic abnormality was identified in 63% (36 of 57) of children studied, including plasminogen activator inhibitor-1 4G6755G (15 of 56), MTHFR (12 of 56), elevated Lp(a) (12 of 59), APCR (11 of 58), factor V G1619A (5 of 57), PT (3 of 57), PC deficiency (1 of 59), and AT deficiency (1 of 59). The MTHFR mutation, elevated Lp(a), the PT mutation, and AT deficiency rates were similar to rates in cases and more common than control subjects in previously published studies. The rate of children with APCR or multiple abnormalities was higher than in previous pediatric stroke studies. A family history of early thrombosis was identified in one third of the children with a prothrombotic abnormality. CONCLUSIONS: Two thirds of children in this study had at least 1 of the prothrombotic risk factors tested, and several children had multiple risk factors. These results provide additional evidence that prothrombotic abnormalities are common among children with AIS or porencephaly.

Adolescent↗
PubMed2004

Expert medical testimony: Responsibilities of medical societies.

Expert witnesses for plaintiff and defense should be able to provide evidence-based literature to support their testimony in depositions and in the courtroom. Specialty societies, such as the American Academy of Neurology, should be willing to review complaints about unsubstantiated testimony and, at times, publicly discipline offending experts.

Expert Testimony↗
PubMed2004

Stroke in newborn infants.

The few days before and after birth are a time of special risk for stroke in both mother and infant, probably related to activation of coagulation mechanisms in this critical period. Arterial ischaemic stroke around the time of birth is recognised in about one in 4000 full-term infants, and may present with neurological and systemic signs in the newborn. Neonatal seizures are most commonly the clinical finding that triggers assessment. In other children, perinatal stroke is recognised only retrospectively, with emerging hemiparesis or seizures after the early months of life. Risk factors for perinatal stroke include hereditary or acquired thrombophilias and environmental factors. Perinatal stroke underlies an important share of congenital hemiplegic cerebral palsy, and probably some spastic quadriplegic cerebral palsy and seizure disorders. There is much to be learned about the natural history of perinatal stroke, and there are as yet no evidence-based strategies for prevention or treatment.

Brain Ischemia↗
PubMed2003

Neonatal cytokines and cerebral palsy in very preterm infants.

To examine the relationship of cytokines in blood of very preterm neonates with later diagnosis of spastic cerebral palsy (CP) compared with infants of similar gestational age without CP, we measured concentrations of inflammatory cytokines and other substances in archived neonatal blood by recycling immunoaffinity chromatography. Subjects were surviving children born before 32 wk gestational age (GA) to women without preeclampsia, 64 with later diagnoses of CP and 107 control children. The initial analyses were augmented by measurement of 11 cytokines by a bead-based flow analytic system (Luminex) in an additional 37 children with CP and 34 control children from the same cohort. Concentrations of examined substances did not differ by presence of indicators of infection in mother, infant, or placenta. On ANOVA, concentrations of a number of cytokines were significantly related to neonatal ultrasound abnormalities (periventricular leukomalacia, ventricular enlargement, or moderate or severe germinal matrix hemorrhage). None of the substances measured either by immunoaffinity chromatography or flow analytic methods, including IL-1, -6, and -8 and tumor necrosis factor-alpha, was related to later diagnosis of CP or its subtypes. Inflammatory cytokines in neonatal blood of very premature infants did not distinguish those with later diagnoses of CP from control children.

Adult↗
PubMed2003

Intrauterine exposure to infection and risk of cerebral palsy in very preterm infants.

OBJECTIVE: To evaluate exposure to intrauterine infection as an independent risk factor for spastic cerebral palsy (CP) among very prematurely born infants. STUDY DESIGN: Retrospective case-control study. METHODS: Singleton children with gestational ages less than 32 weeks and birth weights less than 1999 g who survived to age 2 years and were born from 1988 to 1994 in a level 2 or 3 hospital in California were included in the study. Cases were children with congenital spastic CP (n = 170). Controls were children randomly sampled within 250-g birth weight intervals (n = 270). Gestational age was controlled through multiple logistic models. Major analyses were controlled for preeclampsia and short time between admission and delivery. RESULTS: Neither clinical nor histologic indicators of intrauterine infection were associated with total spastic CP or spastic diplegia in these infants. Although not predicted by prior hypothesis, we observed an approximate doubling of risk for infants of infected mothers among children born to white women, whereas no association was noted among children born to women of other races/ethnicities. White controls had lower frequency of all measured infection indicators compared with white cases and cases and controls of other races/ethnicities. CONCLUSION: Exposure to intrauterine infection was not an independent risk factor for CP in very premature infants when gestational age and other confounders were tightly controlled.

Birth Weight↗
PubMed2003

How common are gastrointestinal disorders in children with autism?

We could identify no report that describes the prevalence of gastrointestinal disorders in a representative group of children with a diagnosis of autism compared with appropriate controls. Thus, we found no evidence upon which to base a confident conclusion as to whether gastrointestinal symptoms are more common in children with than without autism. However, the frequency of gastrointestinal symptoms observed in population-based samples of autistic children indicate that gastrointestinal problems are not nearly as common in children with autism as reports from pediatric gastroenterology clinics suggest.

Adolescent↗
PubMed2002

The epidemiology of cerebral palsy in term infants.

Half of cerebral palsy (CP) arises in infants of normal birthweight; yet, many fewer studies seek to identify risk factors for CP in term and near-term infants than in those born very prematurely. There has been no net decrease in the prevalence of CP in term and near-term infants over recent decades. Potentially asphyxiating birth complications account for a small minority of CP cases. Recent studies suggest that disorders of coagulation and intrauterine exposure to infection or inflammation are associated with risk of CP, and that both can be accompanied by signs of neonatal encephalopathy, the best available predictor of CP in term neonates. Therapeutic interventions directed at preventing interruption of oxygen supply have not been shown to reduce the occurrence of CP. There have not yet been studies examining whether medical interventions directed at infection or coagulation disorder can reduce the frequency of CP.

Blood Coagulation Disorders↗