bluuebunny/crossref_metadata_2025 huggingface dataset:
Phenotyping of congenic dipeptidyl peptidase 4 (DP4) deficient Dark Agouti (DA) rats suggests involvement of DP4 in neuro-, endocrine, and immune functions
Authors: Frerker Nadine , Raber Kerstin , Bode Felix , Skripuletz Thomas , Nave Heike , Klemann Christian , Pabst Reinhard , Stephan Michael , Schade Jutta , Brabant Georg , Wedekind Dirk , Jacobs Roland , Jörns Anne , Forssmann Ulf , Straub Rainer H. , Johannes Sigrid , Hoffmann Torsten , Wagner Leona , Demuth Hans-Ulrich , von Hörsten Stephan
Published: March 2009

: Treatment of diabetes type 2 using chronic pharmacological inhibition of dipeptidyl peptidase 4 (DP4) still requires an in-depth analysis of models for chronic DP4 deficiency, because adverse reactions induced by some DP4 inhibitors have been described.

: In the present study, a novel congenic rat model of DP4 deficiency on a “DP4-high” DA rat genetic background was generated (DA.F344-

: Similar to chronic pharmacological inhibition of DP4, DP4 deficient rats exhibited a phenotype involving reduced diet-induced body weight gain and improved glucose tolerance associated with increased levels of glucagon-like peptide-1 (GLP-1) and bound leptin as well as decreased aminotransferases and triglycerides. Additionally, DA.F344-

: While this animal model confirms a critical role of DP4 in GLP-1-dependent glucose regulation, genetically induced chronic DP4 deficiency apparently also affects stress-regulatory and immune-regulatory systems, indicating that the use of chronic DP4 inhibitors might have the potential to interfere with central nervous system and immune functions in vivo.

Clin Chem Lab Med 2009;47:275–87.
Association of polymorphisms of PTGS2 and CYP8A1 with myocardial infarction
Authors: Xie Xiang , Ma Yi-tong , Fu Zhen-yan , Yang Yi-ning , Ma Xiang , Chen Bang-dang , Wang Ying-hong , Liu Fen
Published: March 2009

: Cyclooxygenase-2 (COX-2) and prostacyclin synthase (PGIS) are enzymes involved in prostaglandin and prostacyclin synthesis, which have been linked to cardiovascular disease risk. We hypothesized that genetic variations altering the function of these enzymes would modify the risk of myocardial infarction (MI).

: In a Chinese case control study of MI patients (n=356) and healthy controls (n=350), we investigated the roles of polymorphisms in the PGIS gene (

: The CC genotype of

: The CC genotype of

Clin Chem Lab Med 2009;47:347–52.
Optimal Sensorimotor Control in Eye Movement Sequences
Authors: Munuera Jérôme , Morel Pierre , Duhamel Jean-René , Deneve Sophie
Published: March 2009

Fast and accurate motor behavior requires combining noisy and delayed sensory information with knowledge of self-generated body motion; much evidence indicates that humans do this in a near-optimal manner during arm movements. However, it is unclear whether this principle applies to eye movements. We measured the relative contributions of visual sensory feedback and the motor efference copy (and/or proprioceptive feedback) when humans perform two saccades in rapid succession, the first saccade to a visual target and the second to a memorized target. Unbeknownst to the subject, we introduced an artificial motor error by randomly “jumping” the visual target during the first saccade. The correction of the memory-guided saccade allowed us to measure the relative contributions of visual feedback and efferent copy (and/or proprioceptive feedback) to motor-plan updating. In a control experiment, we extinguished the target during the saccade rather than changing its location to measure the relative contribution of motor noise and target localization error to saccade variability without any visual feedback. The motor noise contribution increased with saccade amplitude, but remained <30% of the total variability. Subjects adjusted the gain of their visual feedback for different saccade amplitudes as a function of its reliability. Even during trials where subjects performed a corrective saccade to compensate for the target-jump, the correction by the visual feedback, while stronger, remained far below 100%. In all conditions, an optimal controller predicted the visual feedback gain well, suggesting that humans combine optimally their efferent copy and sensory feedback when performing eye movements.
Neurodevelopmental Outcomes of Infants Who Experience Intrauterine Growth Restriction
Authors: Rogers Elizabeth E. , Piecuch Robert E.
Published: March 2009

IUGR has been believed to lead to worse neurodevelopmental outcomes than if an infant had appropriate fetal growth. This is true at all gestational ages, although the literature supports a stronger association for late preterm and term infants than for preterm infants born at fewer than 32 weeks’ gestation. Recent evidence points to growth restriction as a risk factor for emotional and behavioral disorders as well. The specific cause of the growth restriction is an important factor in assessing risk for poor outcomes. Treatments to reduce the risk of adverse outcome include more advanced antenatal assessment to determine time of delivery, optimizing pre- and postnatal nutrition and growth, and the possible use of growth hormone as well as early intervention services.
Trends in Blood Lead Levels and Blood Lead Testing Among US Children Aged 1 to 5 Years, 1988–2004
Authors: Jones Robert L. , Homa David M. , Meyer Pamela A. , Brody Debra J. , Caldwell Kathleen L. , Pirkle James L. , Brown Mary Jean
Published: March 2009

OBJECTIVES. To evaluate trends in children's blood lead levels and the extent of blood lead testing of children at risk for lead poisoning from national surveys conducted during a 16-year period in the United States.

METHODS. Data for children aged 1 to 5 years from the National Health and Nutrition Examination Survey III Phase I, 1988–1991, and Phase II, 1991–1994 were compared to data from the survey period 1999–2004.

RESULTS. The prevalence of elevated blood lead levels, ≥10 μg/dL, among children decreased from 8.6% in 1988–1991 to 1.4% in 1999–2004, which is an 84% decline. From 1988–1991 and 1999–2004, children's geometric mean blood lead levels declined in non-Hispanic black (5.2–2.8 μg/dL), Mexican American (3.9–1.9 μg/dL), and non-Hispanic white children (3.1 μg/dL to 1.7 μg/dL). However, levels continue to be highest among non-Hispanic black children relative to Mexican American and non-Hispanic white children. Blood lead levels were distributed as follows: 14.0% were <1.0 μg/dL, 55.0% were 1.0 to <2.5 μg/dL, 23.6% were 2.5 to <5 μg/dL, 4.5% were 5 to <7.5 μg/dL, 1.5% were 7.5 to <10 μg/dL, and 1.4% were ≥10 μg/dL. Multivariable analysis indicated that residence in older housing, poverty, age, and being non-Hispanic black are still major risk factors for higher lead levels. Blood lead testing of Medicaid-enrolled children increased to 41.9% from 19.2% in 1988–1991. Only 43.0% of children with elevated blood lead levels had previously been tested.

CONCLUSIONS. Children's blood lead levels continue to decline in the United States, even in historically high-risk groups for lead poisoning. To maintain progress made and eliminate remaining disparities, efforts must continue to test children at high risk for lead poisoning, and identify and control sources of lead. Coordinated prevention strategies at national, state, and local levels will help achieve the goal of elimination of elevated blood lead levels.
Allergic Disease and Atopic Sensitization in Children in Relation to Measles Vaccination and Measles Infection
Authors: Rosenlund Helen , Bergström Anna , Alm Johan S. , Swartz Jackie , Scheynius Annika , van Hage Marianne , Johansen Kari , Brunekreef Bert , von Mutius Erika , Ege Markus J. , Riedler Josef , Braun-Fahrländer Charlotte , Waser Marco , Pershagen Göran ,   and the PARSIFAL Study Group
Published: March 2009

OBJECTIVE. Our aim was to investigate the role of measles vaccination and measles infection in the development of allergic disease and atopic sensitization.

METHODS. A total of 14 893 children were included from the cross-sectional, multicenter Prevention of Allergy–Risk Factors for Sensitization in Children Related to Farming and Anthroposophic Lifestyle study, conducted in 5 European countries (Austria, Germany, the Netherlands, Sweden, and Switzerland). The children were between 5 and 13 years of age and represented farm children, Steiner-school children, and 2 reference groups. Children attending Steiner schools often have an anthroposophic (holistic) lifestyle in which some immunizations are avoided or postponed. Parental questionnaires provided information on exposure and lifestyle factors as well as symptoms and diagnoses in the children. A sample of the children was invited for additional tests, and 4049 children provided a blood sample for immunoglobulin E analyses. Only children with complete information on measles vaccination and infection were included in the analyses (84%).

RESULTS. In the whole group of children, atopic sensitization was inversely associated with measles infection, and a similar tendency was seen for measles vaccination. To reduce risks of disease-related modification of exposure, children who reported symptoms of wheezing and/or eczema debuting during first year of life were excluded from some analyses. After this exclusion, inverse associations were observed between measles infection and “any allergic symptom” and “any diagnosis of allergy by a physician.” However, no associations were found between measles vaccination and allergic disease.

CONCLUSION. Our data suggest that measles infection may protect against allergic disease in children.
The Crying Infant: Diagnostic Testing and Frequency of Serious Underlying Disease
Authors: Freedman Stephen B. , Al-Harthy Nesrin , Thull-Freedman Jennifer
Published: March 2009

OBJECTIVE. To determine the proportion of children evaluated in an emergency department because of crying who have a serious underlying etiology. Secondary outcomes included the individual contributions of history, physical examination, and laboratory investigations in determining a diagnosis.

PATIENTS AND METHODS. We performed a retrospective review of all afebrile patients <1 year of age who presented with a chief complaint of crying, irritability, screaming, colic, or fussiness. All children with a serious underlying illness were identified by using a priori defined criteria. Chart review was conducted to determine if history, physical examination, or investigation data contributed to establishing the child's diagnosis.

RESULTS. Enrollment criteria were met by 237 patients, representing 0.6% of all visits. A total of 12 (5.1%) children had serious underlying etiologies with urinary tract infections being most prevalent (n = 3). Two (16.7%) of the serious diagnoses were only made on revisit. Of the 574 tests performed, 81 (14.1%) were positive. However, only 8 (1.4%) diagnoses were assigned on the basis of a positive investigation. History and/or examination suggested an etiology in 66.3% of cases. Unwell appearance was associated with serious etiologies. In only 2 (0.8%) children did investigations in the absence of a suggestive clinical picture contribute to the diagnosis. Both of these children were <4 months of age and had urinary tract infections. Among children <1 month of age, the positive rate of urine cultures performed was 10%. Ocular fluorescein staining and rectal examination with occult blood testing were performed infrequently, and results were negative in all cases. Successful follow-up was completed with 60% of caregivers, and no missed diagnoses were found.

CONCLUSIONS. History and physical examination remains the cornerstone of the evaluation of the crying infant and should drive investigation selection. Afebrile infants in the first few months of life should undergo urine evaluation. Other investigations should be performed on the basis of clinical findings.
Latent Tuberculosis Infection in Children: A Call for Revised Treatment Guidelines
Authors: Finnell S. Maria E. , Christenson John C. , Downs Stephen M.
Published: March 2009

BACKGROUND. Guidelines for latent tuberculosis infection do not consider drug-resistance patterns when recommending treatment for immigrant children.

OBJECTIVES. The purpose of this research was to decide at what rate of isoniazid resistance a different regimen other than isoniazid for 9 months should be considered.

METHODS. We constructed a decision tree by using published data. We studied 3 regimens considered to be effective for susceptible organisms: (1) isoniazid for 9 months, (2) rifampin for 6 months, and (3) isoniazid for 9 months plus rifampin for 6 months. In addition, we evaluated a regimen of isoniazid and rifampin for 3 months. Our base case was a 2-year-old child from Russia with a tuberculin skin test reaction of 12 mm. We assumed a societal perspective and expressed results as cost and cost per case of tuberculosis prevented. We conducted sensitivity analyses to test the stability of our model.

RESULTS. In our baseline analysis, rifampin was the least costly treatment regimen for any child arriving from an area with an isoniazid-resistance rate of ≥11%. Treatment with isoniazid plus rifampin was the most effective but would cost more than $1 million per reactivation case prevented. Isoniazid would become the least costly regimen if any of the following thresholds were met: rifampin resistance given isoniazid resistance of more than 82%; rifampin resistance given no isoniazid resistance of >9%; cost of rifampin more than $47/month; effectiveness of rifampin lower than 63%; effectiveness of isoniazid higher than 74%; and cost of pulmonary tuberculosis less than $7661. Isoniazid and rifampin for 3 months was the least costly for all cases from areas with isoniazid resistance of <80% as long as the regimen's effectiveness was >50% for susceptible bacteria. However, this assumption remains to be proven.

CONCLUSION. Because of the high prevalence of isoniazid resistance, rifampin should be considered for children with latent tuberculosis infection originating from countries with >11% isoniazid resistance.
Age and Violent-Content Labels Make Video Games Forbidden Fruits for Youth
Authors: Bijvank Marije Nije , Konijn Elly A. , Bushman Brad J. , Roelofsma Peter H. M. P.
Published: March 2009

OBJECTIVE. To protect minors from exposure to video games with objectionable content (eg, violence and sex), the Pan European Game Information developed a classification system for video games (eg, 18+). We tested the hypothesis that this classification system may actually increase the attractiveness of games for children younger than the age rating.

PARTICIPANTS AND METHODS. Participants were 310 Dutch youth. The design was a 3 (age group: 7–8, 12–13, and 16–17 years) × 2 (participant gender) × 7 (label: 7+, 12+, 16+, 18+, violence, no violence, or no label control) × 2 (game description: violent or nonviolent) mixed factorial. The first 2 factors were between subjects, whereas the last 2 factors were within subjects. Three personality traits (ie, reactance, trait aggressiveness, and sensation seeking) were also included in the analyses. Participants read fictitious video game descriptions and rated how much they wanted to play each game.

RESULTS. Results revealed that restrictive age labels and violent-content labels increased the attractiveness of video games for all of the age groups (even 7- to 8-year-olds and girls).

CONCLUSIONS. Although the Pan European Game Information system was developed to protect youth from objectionable content, this system actually makes such games forbidden fruits. Pediatricians should be aware of this forbidden-fruit effect, because video games with objectionable content can have harmful effects on children and adolescents.
Vitamin D Deficiency in Children With Chronic Kidney Disease: Uncovering an Epidemic
Authors: Ali Farah N. , Arguelles Lester M. , Langman Craig B. , Price Heather E.
Published: March 2009

BACKGROUND. Vitamin D deficiency in children adversely affects bone development by reducing mineralization. Children with chronic kidney disease are at risk for altered bone development from renal osteodystrophy and concomitant vitamin D deficiency. The pediatric Kidney Disease Outcomes Quality Initiative guidelines suggest measuring serum 25-hydroxyvitamin D (25[OH]D) levels if serum parathyroid hormone levels are above the target range for chronic kidney disease stages 2 and beyond, but the magnitude of vitamin D deficiency in children with chronic kidney disease is not well studied.

OBJECTIVES. The purpose of this work was to determine whether children with chronic kidney disease had vitamin D deficiency, to evaluate whether the prevalence of vitamin D deficiency changed over time, and to examine seasonal and ethnic differences in 25(OH)D levels.

METHODS. 25(OH)D levels in children with chronic kidney disease (stages 1–5) were measured over a 10-year period from 1987 to 1996. Data were also collected for a contemporary group of patients from 2005 to 2006.

RESULTS. The prevalence of vitamin D deficiency ranged from 20% to 75% in the decade studied. There was a significant trend for decreasing 25(OH)D levels over the decade, both at the group and individual levels. Seasonal variation was noted. In our contemporary population with chronic kidney disease, the mean 25(OH)D level was 21.8 ng/mL; we found a prevalence of vitamin D deficiency of 39%. Black and Hispanic patients had lower levels of 25(OH)D than white patients.

CONCLUSIONS. Children with chronic kidney disease have great risk for vitamin D deficiency, and its prevalence was increasing yearly in the studied decade. Contemporary data show that vitamin D deficiency remains a problem in these children. Sunlight exposure and ethnicity play a role in levels of 25(OH)D. Our data support the recent pediatric Kidney Disease Outcomes Quality Initiative guidelines for measurement of 25(OH)D levels in children with chronic kidney disease and secondary hyperparathyroidism.
Quality of Life in Pediatric Bipolar Disorder
Authors: Freeman Andrew J. , Youngstrom Eric A. , Michalak Erin , Siegel Rebecca , Meyers Oren I. , Findling Robert L.
Published: March 2009

OBJECTIVE. Bipolar disorder is a common mood disorder associated with significant disability and impairment in quality of life in adults. Little research has examined the impact of the disorder on quality of life in children and adolescents. The current study examines the quality of life in children and adolescents with bipolar disorder compared with other physical and psychiatric illnesses.

METHODS. This study included 529 youth and caregiver pairs who sought services at a community mental health center or an academic medical center. Diagnoses were based on semistructured interviews of caregivers and youths, and quality of life was determined by the parent-reported Revised Children Quality of Life Questioinnaire (KINDL) questionnaire and compared with published benchmarks for many medical illnesses.

RESULTS. Mean age of the youths was 12.0 years, 57% were boys, 72% were black, 22% were white, and 17% had received bipolar disorder diagnoses. Youths with bipolar disorder had significantly lower quality-of-life scores than youths with asthma, atopic dermatitis, obesity, arthritis, oxygen dependence, heart surgery during infancy, depression, behavior disorders, and nonmood and nonbehavior psychiatric diagnoses.

CONCLUSIONS. Youths with bipolar disorder reported lower quality of life than other youths encountered in pediatric practice. Pediatricians should attend not only to the child's mood symptoms but also to the overall impairment of the disorder.
Prevalence and Predictors of Perinatal Hemorrhagic Stroke: Results From the Kaiser Pediatric Stroke Study
Authors: Armstrong-Wells Jennifer , Johnston S. Claiborne , Wu Yvonne W. , Sidney Stephen , Fullerton Heather J.
Published: March 2009

OBJECTIVES. Predictors for perinatal arterial ischemic stroke include both maternal and intrapartum factors, but predictors of perinatal hemorrhagic stroke have not been studied. We sought to determine both the prevalence and predictors of perinatal hemorrhagic stroke within a large, multiethnic population.

PATIENTS AND METHODS. We performed a case-control study nested within the cohort of all infants born from 1993 to 2003 in the Northern California Kaiser Permanente Medical Care Program, a health maintenance organization providing care for >3 million members. Cases of symptomatic perinatal hemorrhagic stroke and perinatal arterial ischemic stroke in neonates (28 weeks' gestational age through 28 days of life) were identified through electronic searches of diagnosis and radiology databases and confirmed by medical chart review. Three controls per case were randomly selected and matched on birth year and facility. This analysis included cases of perinatal hemorrhagic stroke (intracerebral hemorrhage or subarachnoid hemorrhage, excluding pure intraventricular hemorrhage) and all controls. Predictors of perinatal hemorrhagic stroke were assessed by using logistic regression, adjusting for the matching criteria.

RESULTS. Among 323 532 live births, we identified 20 cases of perinatal hemorrhagic stroke (19 intracerebral hemorrhage and 1 subarachnoid hemorrhage), which yielded a population prevalence for perinatal hemorrhagic stroke of 6.2 in 100 000 live births. Cases presented with encephalopathy (100%) and seizures (65%). Perinatal hemorrhagic stroke was typically unifocal (74%) and unilateral (83%). Etiologies included thrombocytopenia (n = 4) and cavernous malformation (n = 1); 15 (75%) were idiopathic. Univariate predictors of perinatal hemorrhagic stroke included male gender, fetal distress, emergent cesarean delivery, prematurity, and postmaturity but not birth weight. When entered into a multivariate model, fetal distress and postmaturity continued to be independent predictors.

CONCLUSIONS. Fetal distress is an independent predictor of perinatal hemorrhagic stroke, perhaps suggesting a prenatal event. Postmaturity also predicts perinatal hemorrhagic stroke, an association not explained by large birth weight in our study.
Effectiveness of Educational Materials Designed to Change Knowledge and Behaviors Regarding Crying and Shaken-Baby Syndrome in Mothers of Newborns: A Randomized, Controlled Trial
Authors: Barr Ronald G. , Rivara Frederick P. , Barr Marilyn , Cummings Peter , Taylor James , Lengua Liliana J. , Meredith-Benitz Emily
Published: March 2009

BACKGROUND. Infant crying is an important precipitant for shaken-infant syndrome.

OBJECTIVE. To determine if parent education materials (The Period of PURPLE Crying [PURPLE]) change maternal knowledge and behavior relevant to infant shaking.

METHODS. This study was a randomized, controlled trial conducted in prenatal classes, maternity wards, and pediatric practices. There were 1374 mothers of newborns randomly assigned to the PURPLE intervention and 1364 mothers to the control group. Primary outcomes were measured by telephone 2 months after delivery. These included 2 knowledge scales about crying and the dangers of shaking; 3 scales about behavioral responses to crying generally and to unsoothable crying, and caregiver self-talk in response to unsoothable crying; and 3 questions concerning the behaviors of sharing of information with others about crying, walking away if frustrated, and the dangers of shaking.

RESULTS. The mean infant crying knowledge score was greater in the intervention group (69.5) compared with controls (63.3). Mean shaking knowledge was greater for intervention subjects (84.8) compared with controls (83.5). For reported maternal behavioral responses to crying generally, responses to unsoothable crying, and for self-talk responses, mean scores for intervention mothers were similar to those for controls. For the behaviors of information sharing, more intervention mothers reported sharing information about walking away if frustrated and the dangers of shaking, but there was little difference in sharing information about infant crying. Intervention mothers also reported increased infant distress.

CONCLUSIONS. Use of the PURPLE education materials seem to lead to higher scores in knowledge about early infant crying and the dangers of shaking, and in sharing of information behaviors considered to be important for the prevention of shaking.
Comparison of Enrollment in Interventional Therapies Between Late-Preterm and Very Preterm Infants at 12 Months’ Corrected Age
Authors: Kalia Jessica L. , Visintainer Paul , Brumberg Heather L. , Pici Maria , Kase Jordan
Published: March 2009

OBJECTIVE. To determine the requirement for therapeutic services of late-preterm infants (34 to 36 weeks' gestation) and morbidities associated with their developmental delays compared with their very preterm (<32 weeks' gestation) counterparts.

METHODS. We used a retrospective cohort study of former preterm children admitted to the neonatal unit who were evaluated at the Regional Neonatal Follow-up Program of Westchester Medical Center in New York at 12 ± 2 months' corrected age from January 2005 through October 2006. Logistic regression was used to compare odds ratios between late-preterm and very preterm children who qualified for early intervention services. Antenatal, demographic, and neonatal factors were compared between subgroups.

RESULTS. Of the 497 preterm infants evaluated at the Regional Neonatal Follow-up Program, 127 met inclusion criteria (77 very preterm and 50 late-preterm infants). Of the late-preterm infants, 30% qualified for and received early intervention services, 28% physical therapy, 16% occupational therapy, 10% speech therapy, and 6% special education. In the very preterm subgroup, 70% qualified for and received early intervention services, 66% physical therapy, 32% occupational therapy, 32% speech therapy, and 21% special education. Very preterm children were more likely to be enrolled in therapies than their late-preterm counterparts. However, when adjusting for neonatal comorbidities of prematurity, there was no difference in enrollment in early intervention services between the very preterm and late-preterm infants.

CONCLUSIONS. After controlling for comorbidities of prematurity, we found that late-preterm infants requiring admission to the neonatal unit have the same risk as very preterm infants of requiring interventional therapies. This would indicate that it is not only the degree of prematurity but also the morbidities experienced in the neonatal period in conjunction with the period of rapid brain growth that have a profound influence on neurodevelopmental outcomes. This should be considered when planning their hospital discharge and follow-up.
Longitudinal Trajectories of Postconcussive Symptoms in Children With Mild Traumatic Brain Injuries and Their Relationship to Acute Clinical Status
Authors: Yeates Keith Owen , Taylor H. Gerry , Rusin Jerome , Bangert Barbara , Dietrich Ann , Nuss Kathryn , Wright Martha , Nagin Daniel S. , Jones Bobby L.
Published: March 2009

OBJECTIVE. We examined whether mild traumatic brain injuries in children and adolescents, especially when associated with acute clinical features reflecting more severe injury, result in different postinjury trajectories of postconcussive symptoms compared with mild orthopedic injuries.

PARTICIPANTS AND METHODS. Participants in this prospective and longitudinal cohort study were 8- to 15-year-old children, 186 with mild traumatic brain injuries and 99 with mild orthopedic injuries, who were recruited from consecutive admissions to emergency departments in 2 large children's hospitals. Parents rated current postconcussive symptoms within 3 weeks of injury and at 1, 3, and 12 months after injury. At the initial assessment, parents also provided retrospective ratings of preinjury symptoms, and children with mild traumatic brain injuries received MRI of the brain. Clinical features examined as predictors of postconcussive symptoms included loss of consciousness, Glasgow Coma Scale score below 15, other injuries, acute symptoms of concussion, and intracranial abnormalities on the MRI.

RESULTS. Finite mixture modeling identified 4 longitudinal trajectories of postconcussive symptoms (ie, no postconcussive symptoms, moderate persistent postconcussive symptoms, high acute/resolved postconcussive symptoms, high acute/persistent postconcussive symptoms). The mild traumatic brain injuries and orthopedic injuries groups demonstrated a different distribution of trajectories. Children with mild traumatic brain injuries were more likely than those with orthopedic injuries to demonstrate high acute/resolved and high acute/persistent trajectories relative to the no postconcussive symptoms group. The 2 trajectories with high acute levels of postconcussive symptoms were especially likely among children with mild traumatic brain injuries whose acute clinical presentation reflected more severe injury.

CONCLUSIONS. Mild traumatic brain injuries, particularly those that are more severe, are more likely than orthopedic injuries to result in transient or persistent increases in postconcussive symptoms in the first year after injury. Additional research is needed to elucidate the range of factors, both injury related and non–injury related, that place some children with mild traumatic brain injuries at risk for postconcussive symptoms.
Antibiotic Use in Children Is Associated With Increased Risk of Asthma
Authors: Marra Fawziah , Marra Carlo A. , Richardson Kathryn , Lynd Larry D. , Kozyrskyj Anita , Patrick David M. , Bowie William R. , FitzGerald J. Mark
Published: March 2009

BACKGROUND. Antibiotic exposure in early childhood is a possible contributor to the increasing asthma prevalence in industrialized countries. Although a number of published studies have tested this hypothesis, the results have been conflicting.

OBJECTIVE. To explore the association between antibiotic exposure before 1 year of age and development of childhood asthma.

METHODS. Using administrative data, birth cohorts from 1997 to 2003 were evaluated (N = 251817). Antibiotic exposure was determined for the first year of life. After the first 24 months of life, the incidence of asthma was determined in both those exposed and not exposed to antibiotics in the first 12 months of life. Cox proportional hazards models were used to adjust for potential confounders and determine the hazard ratios associated with antibiotic exposure for the development of asthma.

RESULTS. Antibiotic exposure in the first year of life was associated with a small risk of developing asthma in early childhood after adjusting for gender, socioeconomic status at birth, urban or rural address at birth, birth weight, gestational age, delivery method, frequency of physician visits, hospital visit involving surgery, visits to an allergist, respirologist, or immunologist, congenital anomalies, and presence of otitis media, acute, or chronic bronchitis, and upper and lower respiratory tract infections during the first year of life. As the number of courses of antibiotics increased, this was associated with increased asthma risk, with the highest risk being in children who received >4 courses. All antibiotics were associated with an increased risk of developing asthma, with the exception of sulfonamides.

CONCLUSIONS. This study provides evidence that the use of antibiotics in the first year of life is associated with a small risk of developing asthma, and this risk increases with the number of courses of antibiotics prescribed.
A Prospective, Multicenter Study of Caspofungin for the Treatment of Documented Candida or Aspergillus Infections in Pediatric Patients
Authors: Zaoutis Theoklis E. , Jafri Hasan S. , Huang Li-Min , Locatelli Franco , Barzilai Asher , Ebell Wolfram , Steinbach William J. , Bradley John , Lieberman Jay M. , Hsiao Chih-Cheng , Seibel Nita , Laws Hans-Juergen , Gamba Melinda , Petrecz Maria , Taylor Arlene F. , Strohmaier Kim M. , Chow Joseph W. , Kartsonis Nicholas A. , Ngai Angela L.
Published: March 2009

OBJECTIVE. We evaluated the safety, tolerability, and efficacy of caspofungin in pediatric patients with invasive aspergillosis, invasive candidiasis, or esophageal candidiasis.

METHODS. This was a multicenter, prospective, open-label study in children 3 months to 17 years of age with proven or probable invasive aspergillosis, proven invasive candidiasis, or proven esophageal candidiasis. All of the patients received caspofungin 70 mg/m2 on day 1, followed by 50 mg/m2 per day (maximum: 70 mg/day), as primary or salvage monotherapy. Favorable response was defined as complete resolution of clinical findings and microbiologic (or radiographic/endoscopic) eradication (complete response) or significant improvement in these parameters (partial response). Efficacy was assessed at the end of caspofungin therapy in patients with a confirmed diagnosis who received ≥1 dose of caspofungin. The primary safety evaluation was the proportion of patients with clinical or laboratory drug-related adverse events.

RESULTS. Of the 49 patients enrolled, 3 were <2 years of age, 30 were 2 to 11 years of age, and 16 were 12 to 17 years of age. Forty-eight patients had confirmed disease: invasive aspergillosis (10), invasive candidiasis (37), and esophageal candidiasis (1). Eight of 10 patients with invasive aspergillosis had pulmonary involvement; 34 of 37 patients with invasive candidiasis had candidemia. Caspofungin was given for 2 to 87 days. Success at end of therapy was achieved in 5 of 10 patients with invasive aspergillosis, 30 of 37 with invasive candidiasis, and 1 of 1 with esophageal candidiasis. One patient (invasive candidiasis) relapsed during the 28-day follow-up period. Drug-related clinical or laboratory adverse events occurred in 27% and 35% of patients, respectively. There were no serious drug-related adverse events or discontinuations of caspofungin because of toxicity.

CONCLUSIONS. Caspofungin was generally well tolerated in pediatric patients aged 6 months through 17 years. Efficacy outcomes in patients with invasive aspergillosis or invasive candidiasis were consistent with previous adult studies in these indications.
Lasting Effects of Preterm Birth and Neonatal Brain Hemorrhage at 12 Years of Age
Authors: Luu Thuy Mai , Ment Laura R. , Schneider Karen C. , Katz Karol H. , Allan Walter C. , Vohr Betty R.
Published: March 2009

OBJECTIVES. Our goals were to compare cognitive, language, behavioral, and educational outcomes of preterm children to term controls and to evaluate the impact of neonatal brain injury, indomethacin, and environmental risk factors on intellectual function at 12 years of age.

METHODS. A total of 375 children born in 1989–1992 with birth weights of 600 to 1250 g enrolled in the Indomethacin Intraventricular Hemorrhage Prevention Trial and 111 controls were evaluated. Neuropsychometric testing, neurologic examination, and interviews on educational needs were completed. Severe brain injury was defined as the presence of grade 3 to 4 indomethacin intraventricular hemorrhage, periventricular leukomalacia, or severe ventriculomegaly on cranial ultrasound.

RESULTS. On the Wechsler Scales of Intelligence for Children, the preterm cohort obtained a full-scale IQ of 87.9 ± 18.3, verbal IQ of 90.8 ± 18.9, and performance IQ of 86.8 ± 17.9. Preterm children obtained scores 6 to 14 points lower than term controls on all psychometric tests after adjustment for sociodemographic factors. On the Clinical Evaluation of Language Fundamentals (test of basic language skills), 22% to 24% of preterm children scored in the abnormal ranges (<70) as opposed to 2% to 4% of controls. Preterm children with and without brain injury required more school services (76% and 44% vs 16%), and support in reading (44% and 28% vs 9%), writing (44% and 20% vs 4%), and mathematics (47% and 30% vs 6%) compared with controls. Preterm children also displayed more behavior problems than their term counterparts. Severe neonatal brain injury was the strongest predictor of poor intelligence. Antenatal steroids, higher maternal education, and 2-parent family were associated with better cognition, whereas minority status incurred a disadvantage. Indomethacin did not affect intellectual function among preterm children.

CONCLUSIONS. Preterm children born in the early 1990s, especially those with severe brain injury, demonstrate serious deficits in their neuropsychological profile, which translates into increased use of school services at 12 years.
Maternal Vitamin B12 Status and Risk of Neural Tube Defects in a Population With High Neural Tube Defect Prevalence and No Folic Acid Fortification
Authors: Molloy Anne M. , Kirke Peadar N. , Troendle James F. , Burke Helen , Sutton Marie , Brody Lawrence C. , Scott John M. , Mills James L.
Published: March 2009

OBJECTIVE. Folic acid fortification has reduced neural tube defect prevalence by 50% to 70%. It is unlikely that fortification levels will be increased to reduce neural tube defect prevalence further. Therefore, it is important to identify other modifiable risk factors. Vitamin B12 is metabolically related to folate; moreover, previous studies have found low B12 status in mothers of children affected by neural tube defect. Our objective was to quantify the effect of low B12 status on neural tube defect risk in a high-prevalence, unfortified population.

METHODS. We assessed pregnancy vitamin B12 status concentrations in blood samples taken at an average of 15 weeks’ gestation from 3 independent nested case-control groups of Irish women within population-based cohorts, at a time when vitamin supplementation or food fortification was rare. Group 1 blood samples were from 95 women during a neural tube defect–affected pregnancy and 265 control subjects. Group 2 included blood samples from 107 women who had a previous neural tube defect birth but whose current pregnancy was not affected and 414 control subjects. Group 3 samples were from 76 women during an affected pregnancy and 222 control subjects.

RESULTS. Mothers of children affected by neural tube defect had significantly lower B12 status. In all 3 groups those in the lowest B12 quartiles, compared with the highest, had between two and threefold higher adjusted odds ratios for being the mother of a child affected by neural tube defect. Pregnancy blood B12 concentrations of <250 ng/L were associated with the highest risks.

CONCLUSIONS. Deficient or inadequate maternal vitamin B12 status is associated with a significantly increased risk for neural tube defects. We suggest that women have vitamin B12 levels of >300 ng/L (221 pmol/L) before becoming pregnant. Improving B12 status beyond this level may afford a further reduction in risk, but this is uncertain.
Allogeneic Hematopoietic Stem-Cell Transplantation for Leukocyte Adhesion Deficiency
Authors: Qasim Waseem , Cavazzana-Calvo Marina , Davies E. Graham , Davis Jeffery , Duval Michel , Eames Gretchen , Farinha Nuno , Filopovich Alexandra , Fischer Alain , Friedrich Wilhelm , Gennery Andrew , Heilmann Carsten , Landais Paul , Horwitz Mitchell , Porta Fulvio , Sedlacek Petr , Seger Reinhard , Slatten Mary , Teague Lochie , Eapen Mary , Veys Paul
Published: March 2009

OBJECTIVES. Leukocyte adhesion deficiency is a rare primary immune disorder caused by defects of the CD18 β-integrin molecule on immune cells. The condition usually presents in early infancy and is characterized by deep tissue infections, leukocytosis with impaired formation of pus, and delayed wound healing. Allogeneic hematopoietic stem-cell transplantation offers the possibility of curative therapy, and with patient numbers at any individual center being limited, we surveyed the transplant experience at 14 centers worldwide.

METHODS. The course of 36 children with a confirmed diagnosis of leukocyte adhesion deficiency who underwent hematopoietic stem-cell transplantation between 1993 and 2007 was retrospectively analyzed. Data were collected by the registries of the European Society for Immunodeficiencies/European Group for Blood and Marrow Transplantation, and the Center for International Blood and Marrow Transplant Research.

RESULTS. At a median follow-up of 62 months (extending to 14 years), the overall survival rate was 75%. Myeloablative conditioning regimens were used in 28 patients, and reduced-intensity conditioning in 8 patients, with no deaths in this subgroup. Survival rates after matched family donor and unrelated donor transplants were similar, with 11 of 14 matched family donor and 12 of 14 unrelated donor recipients alive; mortality was greatest after haploidentical transplants, after which 4 of 8 children did not survive. Twenty-seven transplant recipients were alive, with full donor engraftment in 17 cases, mixed multilineage chimerism in 7 patients, and mononuclear cell-restricted chimerism in an additional 3 cases.

CONCLUSIONS. Hematopoietic stem-cell transplantation offers long-term benefit in leukocyte adhesion deficiency and should be considered as an early therapeutic option if a suitable HLA-matched stem-cell donation is available. Reduced-intensity conditioning was particularly safe, and mixed-donor chimerism seems sufficient to prevent significant symptoms, although careful long-term monitoring will be required for these patients.
Implications of a New Definition of Vitamin D Deficiency in a Multiracial US Adolescent Population: The National Health and Nutrition Examination Survey III
Authors: Saintonge Sandy , Bang Heejung , Gerber Linda M.
Published: March 2009

OBJECTIVE. In children, vitamin D deficiency can interfere with bone mineralization, leading to rickets. In adults, it is linked to cardiovascular disease, insulin resistance, and hypertension. Accurate estimates of the prevalence of vitamin D deficiency are complicated by the lack of consensus as to optimal vitamin D status. Currently, individuals with serum 25-hydroxyvitamin D levels of <11 ng/mL are classified as vitamin D deficient. Experts collectively have proposed that minimum levels be at least 20 ng/mL. Our objectives were to (1) determine the national prevalence of vitamin D deficiency in adolescents by using both the current and recommended cutoffs and (2) examine the implications of the new recommendation after adjustment for various factors.

METHODS. Data were obtained from National Health and Nutrition Examination Survey III, a cross-sectional survey administered to a nationally representative sample of noninstitutionalized civilians aged 2 months and older. Analyses were restricted to 2955 participants aged 12 to 19 with serum 25-hydroxyvitamin D levels. Relationships between serum 25-hydroxyvitamin D levels and sociodemographic variables were evaluated by using logistic regression.

RESULTS. Changing the definition of vitamin D deficiency from <11 to <20 ng/mL increased the prevalence from 2% to 14%. After adjustment for all covariates, non-Hispanic black adolescents had 20 times the risk of serum 25-hydroxyvitamin D <20 ng/mL compared with non-Hispanic white adolescents. The risk of deficiency was more than double for females compared with males. An inverse relationship between weight and serum 25-hydroxyvitamin D levels was found. Overweight adolescents had increased risk of deficiency compared with normal-weight adolescents.

CONCLUSIONS. There was a disproportionate burden of vitamin D deficiency in the non-Hispanic black adolescent population. Routine supplementation and monitoring of serum levels should be considered. Females and overweight adolescents are at increased risk. The consequences of chronic vitamin D deficiency in adolescents should be prospectively investigated.
Neonatal Watershed Brain Injury on Magnetic Resonance Imaging Correlates With Verbal IQ at 4 Years
Authors: Steinman Kyle J. , Gorno-Tempini Maria Luisa , Glidden David V. , Kramer Joel H. , Miller Steven P. , Barkovich A. James , Ferriero Donna M.
Published: March 2009

OBJECTIVE. We have previously described patterns of neonatal brain injury that correlate with global cognitive and motor outcomes. We now examine, in survivors of neonatal encephalopathy (presumed secondary to hypoxia-ischemia) without functional motor deficits, whether the severity and neuroanatomical involvement on neonatal MRI are associated with domain-specific cognitive outcomes, verbal and performance IQ, at 4 years of age.

METHODS. In this prospective study, neonatal MRIs of 81 term infants with neonatal encephalopathy were scored for degree of injury in 2 common patterns: watershed distribution and basal ganglia distribution. Follow-up evaluation at 4 years of age by examiners blinded to clinical history and MRIs included a 5-point neuromotor score and the Wechsler Preschool and Primary Scale of Intelligence–Revised. In 64 subjects with no functional motor impairment, test of trend was used to examine the association of ordered watershed-distribution and basal ganglia-distribution MRI scores with mean verbal and performance IQ.

RESULTS. Lower verbal and performance IQs were seen with increasing degree of injury on both watershed-distribution and basal ganglia–distribution scales in univariate analyses. When each MRI pattern score was adjusted for the other, only the association of decreasing verbal IQ with increasing watershed-distribution injury remained significant. A suggestion of decreasing verbal IQ with increasing basal ganglia–distribution injury was also seen in the multivariate model, whereas no association was seen between performance IQ and severity of injury in either MRI pattern.

CONCLUSIONS. In survivors of neonatal encephalopathy without functional motor deficits at 4 years of age, an increasing severity of watershed-distribution injury is associated with more impaired language-related abilities.
Impact of Disclosure of HIV Infection on Health-Related Quality of Life Among Children and Adolescents With HIV Infection
Authors: Butler Anne M. , Williams Paige L. , Howland Lois C. , Storm Deborah , Hutton Nancy , Seage George R. ,   for the Pediatric AIDS Clinical Trials Group 219C Study Team
Published: March 2009

BACKGROUND. Little is known concerning the impact of HIV status disclosure on quality of life, leaving clinicians and families to rely on research of children with other terminal illnesses.

OBJECTIVES. The purpose of this work was to examine the impact of HIV disclosure on pediatric quality of life and to describe the distribution of age at disclosure in a perinatally infected pediatric population.

METHODS. A longitudinal analysis was conducted of perinatally HIV-infected youth ≥5 years of age enrolled in a prospective cohort study, Pediatric AIDS Clinical Trials Group 219C, with ≥1 study visit before and after HIV disclosure. Age-specific quality-of-life instruments were completed by primary caregivers at routine study visits. The distribution of age at disclosure was summarized. Six quality-of-life domains were assessed, including general health perception, symptom distress, psychological status, health care utilization, physical functioning, and social/role functioning. For each domain, mixed-effects models were fit to estimate the effect of disclosure on quality of life.

RESULTS. A total of 395 children with 2423 study visits were analyzed (1317 predisclosure visits and 1106 postdisclosure visits). The median age at disclosure was estimated to be 11 years. Older age at disclosure was associated with earlier year of birth. Mean domain scores were not significantly different at the last undisclosed visit compared with the first disclosed visit, with the exception of general health perception. When all of the visits were considered, 5 of 6 mean domain scores were lower after disclosure, although the differences were not significant. In mixed-effects models, disclosure did not significantly impact quality of life for any domain.

CONCLUSIONS. Age at disclosure decreased significantly over time. There were no statistically significant differences between predisclosure and postdisclosure quality of life; therefore, disclosure should be encouraged at an appropriate time.