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1.  A randomized, masked study of weekly erythropoietin dosing in preterm infants 
The Journal of pediatrics  2011;160(5):790-5.e1.
Background
Erythropoietin (Epo) increases and maintains hematocrit using once weekly dosing in adults with anemia due to end stage renal disease. Epo is used in preterm infants to treat the anemia of prematurity, but has not been studied using once weekly dosing, a schedule which might offer neuroprotection in addition to increasing red cell mass. We compared reticulocyte responses of once weekly Epo dosing with thrice weekly dosing in preterm infants.
Methods
Infants ≤1,500 grams and ≥7 days of age were randomized to once weekly Epo, 1,200 units/kg/dose, or thrice weekly Epo, 400 units/kg/dose, subcutaneously for 4 weeks, along with iron and vitamin supplementation. Complete blood counts, absolute reticulocyte counts (ARC), transfusions, phlebotomy losses, and adverse events were recorded.
Results
Twenty preterm infants (962±55 grams, 27.9±0.4 weeks, 17±3 days of age) were enrolled. Groups were similar at baseline. Infants in both groups increased ARC (p<0.01, thrice weekly Epo group). ARC were similar between treatment groups at the start and end of 4 weeks. Hematocrit remained stable, and similar numbers of transfusions were administered. No adverse effects of either dosing schedule were noted.
Conclusions
Preterm infants respond to weekly Epo by increasing ARC and maintaining hematocrit. We speculate that once weekly Epo dosing might be beneficial to preterm infants requiring increased erythropoiesis.
doi:10.1016/j.jpeds.2011.10.026
PMCID: PMC3598609  PMID: 22137666
erythropoietin; transfusions; dosing schedule; anemia of prematurity; neuroprotection
2.  Adrenal Insufficiency in Newborns with Congenital Diaphragmatic Hernia 
The Journal of pediatrics  2010;156(3):495-497.e1.
Newborns with congenital diaphragmatic hernia frequently have catecholamine-unresponsive systemic hypotension and respiratory failure. We found that adrenal insufficiency frequently complicates the clinical course of infants with congenital diaphragmatic hernia and was associated with increased severity of illness.
doi:10.1016/j.jpeds.2009.10.044
PMCID: PMC3594092  PMID: 20056240
3.  Vitamin D Deficiency, Adiposity, and Cardiometabolic Risk in Urban Schoolchildren 
The Journal of pediatrics  2011;159(6):945-950.
Objective
To determine the relationship between serum vitamin D levels and cardiometabolic risk factors independent of adiposity in urban schoolchildren.
Study design
We assessed the relationships among serum 25-hydroxyvitamin D [25(OH)D], adiposity measured by body mass index (BMI) z-score (BMIz), and 6 cardiometabolic risk factors (total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides, interleukin-6, and C-reactive protein [CRP]) in a cross-sectional sample of 263 racially and ethnically diverse schoolchildren from the Boston area during late winter. Multivariate regression analyses adjusting for sociodemographic characteristics and BMIz examined associations of 25(OH)D and cardiometabolic risk factors.
Results
Overall, 74.6% of the children were vitamin D deficient [25(OH)D <50 nmol/L; mean, 41.8 ± 13.7 nmol/L]; 45% were overweight or obese (20%and 25%, respectively; BMIz = 0.75 ± 1.1). The 25(OH)D level was not associated with BMIz, but was positively associated with the cardiometabolic risk factor CRP (β = 0.03; P < .05). BMIz was associated with elevated triglycerides (β = 0.13), CRP (β = 0.58), and interleukin-6 (β= 0.14) and low high-density lipoprotein cholesterol (β = −0.09; all P < .01).
Conclusions
Vitamin D deficiency is highly prevalent during the late winter months in urban schoolchildren living in the northeastern United States. This widespread deficiency may contribute to the lack of associations between 25(OH)D and both BMIz and cardiometabolic risk factors. The association between 25(OH)D and CRP warrants further study.
doi:10.1016/j.jpeds.2011.06.001
PMCID: PMC3586426  PMID: 21784451
4.  Child Mental Health Problems and Obesity in Early Adulthood 
The Journal of pediatrics  2010;156(1):93-97.
Objective
To examine whether mental health problems in childhood increase the likelihood of overweight or obesity during early adulthood among male subjects.
Study design
In a national prospective population-based study conducted in Finland, child mental health, including depression, emotional problems, conduct problems, and hyperactivity (determined on the basis of child, parent, and teacher information), was assessed at age 8 years. Body mass index (BMI) was obtained from military examination records (n = 2209) conducted in early adulthood (age range, 18–23 years).
Results
Both moderate (50th–90th percentile) and high (>90th percentile) levels of conduct problems at age 8 years were prospectively associated with a young adult being obese (BMI ≥ 30; odds ratio [OR], 2.0; 95% CI, 1.2–3.2; and OR, 2.9; 95% Confidence interval [CI], 1.5–5.9; respectively). Conduct problems were also prospectively associated with a young adult being overweight (25 ≤ BMI < 30; OR, 1.5; 95% CI, 1.1–1.9 for moderate levels of conduct problems, and OR, 1.9; 95% CI, 1.2–2.8 for high levels), after controlling for hyperactive problems and sociodemographic factors.
Conclusions
Conduct problems in childhood are prospectively associated with overweight and obese in young adulthood. Future studies should address the potential for interventions to reduce obesity risk in young adulthood for boys who manifest conduct problems early in life.
doi:10.1016/j.jpeds.2009.06.066
PMCID: PMC3586427  PMID: 19783001
5.  Cardiovascular Risk and Insulin Resistance in Childhood Cancer Survivors 
The Journal of Pediatrics  2011;160(3):494-499.
Objective
Increased cardiovascular (CV) risk has been reported in adults who are childhood cancer survivors (CCS). We sought to determine the emergence of CV risk factors in CCS while still children.
Study design
CCS in remission ≥5 years from cancer diagnosis (n=319, age=14.5yrs), and their siblings (controls, n=208, age=13.6yrs) participated in this cross-sectional study of CV risk, which included physiologic assessment of insulin sensitivity/resistance (hyperinsulinemic euglycemic clamp). Adjusted comparisons between CCS major diagnoses (leukemia [n=110], central nervous system tumors [n=82], solid tumors [n=127]) and controls were performed using linear regression for CV risk factors and insulin sensitivity.
Results
Despite no significant differences in weight and body mass index, CCS had greater adiposity (waist [73.1 vs. 71.1cm, p=0.02]; percent fat [28.1vs.25.9%, p=0.007]), lower lean body mass (38.4vs.39.9 kg, p=0.01) than controls. After adjustment for adiposity, CCS had higher total cholesterol (154.7vs.148.3mg/dl, p=0.004), LDL-cholesterol (89.4vs.83.7mg/dl, p=0.002), triglycerides (91.8 vs. 84mg/dl, p=0.03) and were less insulin sensitive (Mlbm 12.1vs.13.4mg/kg/min, p=0.002) than controls.
Conclusions
CCS have greater CV risk than healthy children. Because CV risk factors track from childhood into adulthood, early development of altered body composition and decreased insulin sensitivity in CCS may contribute significantly to their risk of early CV morbidity and mortality.
doi:10.1016/j.jpeds.2011.08.018
PMCID: PMC3246569  PMID: 21920542
cardiometabolic risk; metabolic syndrome; children; cholesterol; adiposity
6.  Reliability of resting blood pressure measurement and classification using an oscillometric device in children with chronic kidney disease 
The Journal of Pediatrics  2011;160(3):434-440.e1.
Objective
To compare the reliability of blood pressure (BP) readings obtained by an oscillometric device to those obtained by auscultation and assess for differences in BP status classification based upon the two techniques.
Study design
Resting BP was measured by auscultation and with an oscillometric device at the same encounter in 235 subjects enrolled in the Chronic Kidney Disease in Children study. Resting auscultatory BP’s were averaged and compared with averaged oscillometric readings. BP agreement by the two methods was assessed using Bland-Altman plots, and BP status classification agreement was assessed by calculation of Kappa statistics.
Results
Oscillometric BP readings were higher than auscultatory readings, with a median paired difference of 9 mmHg for systolic BP (SBP) and 6 mmHg for diastolic BP (DBP). Correlation for mean SBP was 0.624 and for mean DBP was 0.491. The bias for oscillometric BP measurement was 8.7 mmHg for SBP (P<0.01) and 5.7 mmHg for DBP (P<0.01). BP status classification agreement was 61% for SBP and 63% for DBP, with Kappas of 0.31 for SBP and 0.20 for DBP.
Conclusions
Compared with auscultation, the oscillometric device significantly overestimated both systolic and diastolic BP, leading to frequent misclassification of BP status.
doi:10.1016/j.jpeds.2011.08.071
PMCID: PMC3274610  PMID: 22048052
7.  Correlation of N-terminal fragment of B-type natriuretic peptide levels with clinical, laboratory, and echocardiographic abnormalities in children with sickle cell disease 
The Journal of Pediatrics  2011;160(3):428-433.e1.
Objective
To determine whether or not the N-terminal fragment of B-type natriuretic peptide (NTproBNP) was a biomarker of clinical, laboratory, and echocardiographic abnormalities in children with homozygous sickle cell disease (SCD).
Study design
A single-center retrospective study consisted of analysis of data from November, 2007 to December, 2010. We correlated serum NTproBNP with clinical and laboratory findings, echocardiographic data, and New York Heart Association (NYHA) functional class.
Results
NTproBNP levels from 42 children (median age 9 years, 52% female) had significant correlations with hemoglobin (r= −0.63, p<0.05), and echocardiographic measurements including tricuspid regurgitant velocity (r=0.46, p<0.05), lateral E’ (r=−0.52, p<0.05) and lateral E/E’ ratio (r=0.60, p<0.05) suggesting diastolic dysfunction. In addition, NTproBNP levels increased from NYHA functional class I to class III and had a significant linear correlation with the NYHA functional class (r=0.69, p <0.05).
Conclusions
NTproBNP correlated with low hemoglobin and tissue Doppler data as indicators of diastolic dysfunction. Elevated NTproBNP may be a prognostic biomarker for the presence of diastolic dysfunction related to anemia in children with SCD.
doi:10.1016/j.jpeds.2011.09.015
PMCID: PMC3274616  PMID: 22048047
8.  Elevated concentrations of inflammation-related proteins in postnatal blood predict severe developmental delay at two years in extremely premature infants 
The Journal of Pediatrics  2011;160(3):395-401.e4.
Objective
To evaluate the hypothesis that elevated levels of inflammation-related proteins in early postnatal blood predict impaired mental and motor development among extremely preterm infants.
Study design
We measured concentrations of 25 inflammation-related proteins in blood collected on postnatal days 1, 7, and 14 from 939 infants born before 28 weeks gestation. An elevated level was defined as a concentration in the highest quartile for gestational age and day of blood collection. We identified impaired development at 24 months of age using the Bayley Scales of Infant Development. The primary outcomes were scores on the Mental or Motor Scale below 55 (more than 3 standard deviations below the mean).
Results
For 17 of the 25 inflammation-related proteins, one or more statistically significant association (p < 0.01) was found between an elevated blood level of the protein and a developmental impairment. Elevations on multiple days were more often associated with developmental impairment than elevations present for only one day. The highest number of elevations was found in day-14 blood.
Conclusions
In extremely preterm infants, elevated levels of inflammation-related proteins in blood collected on postnatal days 7 and 14, especially when sustained, are associated with impaired mental and motor development at age two years.
doi:10.1016/j.jpeds.2011.08.069
PMCID: PMC3279610  PMID: 22000304
cytokines; developmental disability; prematurity; Bayley Scales of Infant Development; neurodevelopmental outcome
9.  Ciliopathies: the central role of cilia in a spectrum of pediatric disorders 
The Journal of Pediatrics  2011;160(3):366-371.
doi:10.1016/j.jpeds.2011.11.024
PMCID: PMC3282141  PMID: 22177992
cilia; basal body; centrosome; primary ciliary dyskinesia; polycystic kidney disease
10.  Abatacept and Sodium Thiosulfate for Treatment of Recalcitrant Juvenile Dermatomyositis Complicated by Ulceration and Calcinosis 
The Journal of Pediatrics  2012;160(3):520-522.
We report the successful use of abatacept and sodium thiosulfate in a patient with severe recalcitrant juvenile dermatomyositis complicated by ulcerative skin disease and progressive calcinosis. This combination therapy resulted in significant reduction in muscle and skin inflammation, decreased corticosteroid dependence, and halted the progression of calcinosis.
doi:10.1016/j.jpeds.2011.11.057
PMCID: PMC3306811  PMID: 22244459
11.  Effects of Immediate Telephone Follow-Up with Providers on Sweat Chloride Test Timing after Cystic Fibrosis Newborn Screening Identifies a Single Mutation 
The Journal of pediatrics  2012;162(3):522-529.
Objectives
To assess whether reporting “possible cystic fibrosis (CF)” newborn screening (NBS) results via fax plus simultaneous telephone contact with primary care providers (PCPs), versus fax alone, influenced three outcomes: getting a sweat chloride test, age at sweat chloride test, and sweat-testing before 8 weeks old.
Study Design
Retrospective cohort comparison of infants born in Wisconsin whose PCPs received telephone intervention (n=301), versus recent historical controls whose PCP did not (n=355). Intervention data were collected during a longitudinal research and quality improvement effort; de-identified comparison data were constructed from auxiliary NBS tracking information. Parametric and nonparametric statistical analyses tested for group differences.
Results
Most infants (92%) with “possible CF” NBS results whose PCPs lacked telephone intervention ultimately underwent sweat-testing, underlining efficacy for fax-only reporting. Telephone intervention was significantly associated with improvements in infants undergoing sweat-testing at both ≤6 and <8 weeks and a slight, but non-significant, 3.5-day reduction in infants’ age at sweat-testing. The effect of telephone intervention was greater for PCPs whose patients underwent sweat-testing at community-affiliated medical centers versus academic medical centers (p=0.008).
Conclusion
Reporting “possible CF” NBS results via fax plus simultaneous telephone follow-up with PCPs increases the number of infants who have sweat chloride tests before 8 weeks of age, when affected infants are more likely to receive full benefits of early diagnosis and treatment.
doi:10.1016/j.jpeds.2012.08.055
PMCID: PMC3582754  PMID: 23102590
Neonatal screening; sweat chloride testing; heterozygote; genetic carrier detection; genetic testing; public health genetics; parent-provider communication
12.  Clinical Factors Associated with PANDAS 
The Journal of Pediatrics  2011;160(2):314-319.
Objective
To explore associated clinical factors in children with pediatric autoimmune neuropsychiatric disorders associated with streptococcus (PANDAS).
Study design
Children with tics and/or OCD (n = 109) were examined by personal and family history, diagnostic interview, physical examination, medical record review, and measurement of baseline levels of streptococcal antibodies.
Results
Significant group differences were found on several variables, such that those diagnosed with PANDAS (versus without PANDAS) were more likely to have had dramatic onset; definite remissions; remission of neuropsychiatric symptoms during antibiotic therapy; a history of tonsillectomies/adenoidectomies; evidence of GAS infection, and clumsiness.
Conclusion
The identification of clinical features associated with PANDAS should assist in delineating risks for this subtype of OCD/tics.
doi:10.1016/j.jpeds.2011.07.012
PMCID: PMC3227761  PMID: 21868033
Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections; PANDAS; Obsessive-Compulsive Disorder; Tic disorder; Children
13.  Psychiatric Disorders in Youth with Medically Unexplained Chest Pain vs. Innocent Heart Murmur 
The Journal of Pediatrics  2011;160(2):320-324.
Objective
To examine prevalence of DSM-IV psychiatric disorders in youth with chest pain compared with a control sample with innocent heart murmur.
Study design
We assessed youth ages 8–17 years who were evaluated in cardiology settings for medically unexplained chest pain (N=100) or innocent heart murmur (N=80). We conducted semi-structured interviews and assessed medical history, quality of life, and disability.
Results
Youth with chest pain had a higher prevalence of psychiatric disorders compared with those with murmur (74% vs. 47%, X2 = 13.3; p<.001). Anxiety disorders predominated, although major depression was also more common in the chest pain group (9% vs. 0%; FET; p<.01). Onset of psychiatric disorders generally preceded chest pain. Patterns were similar for boys and girls and for children and adolescents. Chest pain was associated with poorer quality of life and with pain-related disability for youth with comorbid psychiatric disorder.
Conclusions
In childhood and adolescence, medically unexplained chest pain is associated with a high prevalence of psychiatric disorders. Systematic mental health screening may improve detection and enhance management of these patients.
doi:10.1016/j.jpeds.2011.07.011
PMCID: PMC3227786  PMID: 21868030
Children; adolescents; cardiology; anxiety
14.  Inhaled NO therapy increases blood nitrite, nitrate and S-nitrosohemoglobin concentrations in infants with pulmonary hypertension 
The Journal of Pediatrics  2011;160(2):245-251.
Objective
To measure the circulating concentrations of nitric oxide (NO) adducts with NO bioactivity following inhaled NO therapy in infants with pulmonary hypertension.
Study design
In this single center study five sequential blood samples were collected from infants with pulmonary hypertension before, during and after therapy with iNO (n=17). Samples were collected from a control group of hospitalized infants without pulmonary hypertension (n=16) and from healthy adults for comparison (n=12).
Results
After beginning iNO (20 ppm) whole blood nitrite increased about two-fold within two hours (P<0.01). Whole blood nitrate increased to four-fold higher than baseline during treatment with 20ppm iNO (P<0.01). S-nitrosohemoglobin (SNO-Hb) increased measurably after beginning iNO (P<0.01) whereas iron nitrosyl hemoglobin and total Hb-bound NO-species compounds did not change.
Conclusion
Treatment of pulmonary hypertensive infants with iNO results in increases in nitrite, nitrate, and SNO-Hb in circulating blood. We speculate that these compounds may be carriers of NO bioactivity throughout the body and account for peripheral effects of iNO in the brain, heart and other organs.
doi:10.1016/j.jpeds.2011.07.040
PMCID: PMC3237823  PMID: 21907348
newborn; nitric oxide
15.  Effects of Chronic Transfusions on Abdominal Sonographic Abnormalities in Children with Sickle Cell Anemia 
The Journal of Pediatrics  2011;160(2):281-285.e1.
Objective
To assess the effects of chronic erythrocyte transfusions on prevalence of sonographic incidence of organ damage in children with sickle cell anemia (SCA).
Study design
Children (n=148; mean age, 13.0 years) with SCA, receiving chronic transfusions (average, 7 years) underwent abdominal sonography at 25 institutions. After central imaging review, spleen, liver and kidney measurements were compared with published normal values. Potential relations between ultrasound, clinical and laboratory data were explored via Analysis of Variance, Student t-test and Cochran Mantel Haenzel tests of non-zero correlation.
Results
Average spleen length was similar to normal children, but over one-third had spleen volumes > 300mL, 15 had previous splenectomy for splenomegaly and 24 had abnormal splenic echotexture. Two-thirds had hepatobiliary disease; 37 had prior cholecystectomy, 46 had gallstones, 16 had gallbladder sludge. Gallbladder disease correlated with older age (p = 0.002), longer liver length (p < 0.001), longer duration of transfusions (p = 0.034) and higher total bilirubin (p < 0.001). Liver (p < 0.001) and renal lengths (p ≤ 0.005) were larger than published norms.
Conclusions
In children with SCA, long-term transfusion therapy may not prevent development or progression of abdominal organ dysfunction.
doi:10.1016/j.jpeds.2011.07.050
PMCID: PMC3237893  PMID: 21907352
sickle cell anemia; iron overload; splenomegaly; gallstones; hepatomegaly; nephromegaly
16.  Dog Bite Prevention: A New Screening Tool 
The Journal of Pediatrics  2011;160(2):337-341.e2.
Objectives
To determine what children know about preventing dog bites and parental desires for dog bite prevention education.
Study design
This cross-sectional study sampled 5-15 year olds and their parents/guardians presenting to a pediatric emergency department with non-urgent complaints or dog bites. Pairs completed surveys and knowledge-based simulated scenario tests developed from American Academy of Pediatrics (AAP) and Center for Disease Control and Prevention (CDC) dog bite prevention recommendations. Regression analyses modeled knowledge test scores and probability of passing; a passing score was ≥11/14 questions.
Results
Of 300 parent/child pairs, 43% of children failed the knowledge test. Older children had higher odds of passing the knowledge test than younger children, as did children with white parents versus non-white parents. No associations were found between knowledge scores and other sociodemographic or experiential factors. Over 70% of children had never received dog bite prevention education, although 88% of parents desired it.
Conclusion
Dog bites are preventable injures disproportionately affecting children. Dog bite prevention knowledge in our sample was poor, particularly among younger children and children with non-white parents. Formal dog bite prevention education is warranted and welcomed by a majority of parents.
doi:10.1016/j.jpeds.2011.07.016
PMCID: PMC3258302  PMID: 21885057
dog bite; injury prevention; education; knowledge; emergency department
17.  POSTURAL TACHYCARDIA IN CHILDREN AND ADOLESCENTS – WHAT IS ABNORMAL? 
The Journal of Pediatrics  2011;160(2):222-226.
Objectives To evaluate whether the use of adult heart rate (HR) criteria is appropriate for diagnosing Postural Tachycardia Syndrome (POTS) and orthostatic intolerance (OI) in children and adolescents and to establish normative data and diagnostic criteria for pediatric POTS and OI.
Study design 106 normal controls between the ages 8 and 19 years (14.5±3.3 years) underwent standardized autonomic testing, including 5 minutes of 70 degree head-up tilt. The orthostatic HR increment and absolute orthostatic HR were assessed and retrospectively compared with 654 pediatric patients of similar age (15.5±2.3 years), who were referred to our Clinical Autonomic Laboratory with symptoms of OI.
Results The HR increment was mildly higher in patients referred for POTS/OI but there was considerable overlap between patient and control group. 42% of normal controls had a HR increment of 30bpm or more. The 95th percentile for the orthostatic HR increment in normal controls was 42.9bpm. Absolute orthostatic HR showed a greater and more consistent difference between groups, although there was still considerable overlap.
Conclusions The diagnostic criteria for OI/POTS in adults are inadequate for children and adolescents. Based on our normative data, new criteria are proposed for the diagnosis of OI and POTS in children and adolescents.
doi:10.1016/j.jpeds.2011.08.054
PMCID: PMC3258321  PMID: 21996154
nervous system; autonomic; orthostatic intolerance; postural tachycardia; adolescent autonomic dysfunction
18.  Disease Activity, Proteinuria, and Vitamin D Status in Children with Systemic Lupus Erythematosus and Juvenile Dermatomyositis 
The Journal of Pediatrics  2011;160(2):297-302.
Objective
To evaluate relationships between vitamin D, proteinuria, and disease activity in pediatric systemic lupus erythematosus (SLE) and juvenile dermatomyositis (JDM).
Study design
Multiple linear regression was used to associate subject-reported race, sunscreen use, and vitamin D intake with physician-assessed disease activity and serum 25-hydroxyvitamin D [25(OH)D] in subjects with pediatric SLE (n = 37) or JDM (n = 21). Serum 25(OH)D was correlated with urinary vitamin D binding protein/creatinine ratio (DBP/C) and other indicators of proteinuria.
Results
Serum 25(OH)D levels in subjects with SLE were inversely associated with the natural log of urinary DBP/C (r = −0.63, p < 0.001) and urine protein to creatinine ratio (r = −0.60, p<0.001), with an adjusted mean 10.9 (95% CI 5.1, 16.8) ng/mL decrease in 25(OH)D for those with proteinuria. Excluding subjects with proteinuria, serum 25(OH)D levels were inversely associated with disease activity in JDM, but not in SLE. Overall, 66% of all subjects were taking concurrent corticosteroids, but this was not associated with 25(OH)D levels.
Conclusions
Low serum 25(OH)D in patients with SLE is associated with proteinuria and urinary DBP. Vitamin D deficiency is associated with disease activity in patients with JDM and SLE; this relationship in SLE may be confounded by proteinuria.
doi:10.1016/j.jpeds.2011.08.011
PMCID: PMC3258326  PMID: 21924736
25-hydroxyvitamin D; vitamin D binding protein
19.  Markers of severe vaso-occlusive painful episode frequency in children and adolescents with sickle cell anemia 
The Journal of Pediatrics  2011;160(2):286-290.
Objective
To identify factors associated with frequent severe vaso-occlusive pain crises in a contemporary pediatric cohort of sickle cell anemia (SCA)enrolled in a prospective study of pulmonary hypertension and the hypoxic response in sickle cell disease (SCD).
Study design
Clinical and laboratory characteristics of children with SCA who had ≥3 severe pain crises requiring health care in the preceding year were compared with subjects with <3 such episodes.
Results
Seventy-five children (20%) reported ≥3 severe pain episodes in the preceding year, and 232 (61%) had none. Frequent pain episodes were associated with older age (OR 1.2; 95% CI 1.1–1.3; P<0.0001), α-thalassemia trait (OR 3.5; 1.6–6.7; P=0.002), higher median hemoglobin (OR 1.7; 95% CI: 1.2–2.4; P<0.003) and lower lactate dehydrogenase (LDH) concentration (OR 1.82; 95% CI: 1.07–3.11; P = 0.027). Children with high pain frequency also had an increased iron burden (serum ferritin 480 vs. 198 μg/L; P=0.006) and higher median tricuspid regurgitation jet velocity (2.41 vs. 2.31 m/s; P=0.001). Neither hydroxy urea use nor fetal hemoglobin levels were significantly different according to severe pain history.
Conclusions
In our cohort of children with SCA increasing age was associated with higher frequency of severe pain episodes as were α-thalassemia, iron overload, higher hemoglobin and lower LDH concentration and higher tricuspid regurgitation velocity.
doi:10.1016/j.jpeds.2011.07.018
PMCID: PMC3258348  PMID: 21890147
Sickle cell anemia; vaso-occlusive crisis; pain
20.  Outcome of Extremely Low Birth Weight Infants Who Received Delivery Room Cardiopulmonary Resuscitation 
The Journal of Pediatrics  2011;160(2):239-244.e2.
Objective
To determine whether delivery room cardiopulmonary resuscitation (DR-CPR) independently predicts morbidities and neurodevelopmental impairment (NI) in extremely low birth weight (ELBW) infants.
Study design
Cohort study of infants born with birth weight (BW) 401-1000g and gestational age (GA) 23-30wks. DR-CPR was defined as chest compressions and/or drugs. Logistic regression was used to determine associations between DR-CPR and morbidities, mortality and NI at 18-24 months (Bayley II mental or psychomotor index < 70, cerebral palsy, blindness or deafness). Data are adjusted Odds Ratio (OR) with 95% confidence interval.
Results
Of 8685 infants, 1333(15%) received DR-CPR. DR-CPR infants had lower BW (708±141vs 764±146g, p<0.0001) and GA (25±2 vs 26±2 wks, p<0.0001). DR-CPR infants had more pneumothoraces (OR 1.28, 1.48-2.99), Grade 3-4 intraventricular hemorrhage (OR 1.47, 1.23-1.74), bronchopulmonary dysplasia (OR 1.34, 1.13-1.59), death by 12 hours (OR 3.69, 2.98-4.57) and by 120 days after birth (OR 2.22, 1.93-2.57). NI among survivors (OR 1.23, 1.02-1.49), and death or NI (OR 1.70, 1.46-1.99) were higher for DR-CPR infants. Only 14% of DR-CPR recipients with 5-minute Apgar score<2 survived without NI.
Conclusions
DR-CPR is a prognostic marker for higher mortality and NI for ELBW survivors. New DR-CPR strategies are needed for this population.
doi:10.1016/j.jpeds.2011.07.041
PMCID: PMC3258355  PMID: 21930284
cardiac compressions; epinephrine; neurodevelopmental outcomes
21.  Correlates of Resistin in Children with Chronic Kidney Disease: The Chronic Kidney Disease in Children Cohort 
The Journal of pediatrics  2012;161(2):276-280.
Objective
To test the hypothesis that resistin is associated with insulin resistance and inflammation in pediatric patients with chronic kidney disease (CKD).
Study design
This study is a cross-sectional analysis of 319 children in the Chronic Kidney Disease in Children cohort, a large cohort of children with stage II–IV CKD. Univariate and multivariate regression modeling was used to evaluate the association of serum resistin level with glomerular filtration rate (GFR), demographic data, and cardiovascular risk factors, including inflammatory cytokines, insulin resistance, and serum lipids.
Results
In univariate analyses, serum resistin level was negatively correlated with GFR (P < .01). Increased serum resistin was associated with elevated inflammatory cytokines, including interleukin (IL)-6 (P < .01), IL-10 (P < .01), and tumor necrosis factor-α (P < .01). Resistin level was not associated with insulin resistance, although it was positively correlated with serum triglycerides (P < .01) and negatively correlated with high-density lipoprotein cholesterol (P < .01). In multivariate analysis, GFR (β = −0.01; P < .001), IL-6 (β = 0.18; P < .001), IL-10 (β = 0.09; P = .01), and pubertal status (β = 0.18; P < .01) were significantly associated with serum resistin level.
Conclusion
These results indicate that serum resistin level increases with GFR decline and is involved in the inflammatory milieu present in CKD.
doi:10.1016/j.jpeds.2012.01.055
PMCID: PMC3553545  PMID: 22421264
22.  Computed Tomography for Minor Head Injury: Variation and Trends Among Major U.S. Pediatric Emergency Departments 
The Journal of pediatrics  2011;160(1):136-139.e1.
Objectives
To investigate the variation and trends in neuroimaging among children evaluated for minor head injury at major U.S. pediatric emergency departments (ED).
Study design
We conducted a retrospective study of children < 19 years of age with mild head injury who were evaluated and discharged home from the ED at 40 pediatric hospitals from 2005–2009 using the Pediatric Health Information Systems™ database. Variation in CT rates between hospitals was assessed for correlation with hospital specific rates of intracranial hemorrhage, admission and return visits. Age adjusted trends in CT utilization were calculated over the 5 years.
Results
Over the 5 years, the median rate of imaging for minor head injured patients was 36% [IQR 29–42%, range 19–58%]. There was no correlation between institution-specific rates of CT imaging and intracranial hemorrhage, admission or return visit rates. Age-adjusted rates of CT utilization decreased over the 5-year period on CT rates (OR 0.94 [95% CI 0.92, 0.97], p<0.001).
Conclusions
In this study, we found significant practice variation in CT utilization at pediatric hospitals evaluating children with minor head injury. These data may help guide national benchmarks for the appropriate use of CT imaging in pediatric minor head injury patients.
doi:10.1016/j.jpeds.2011.06.024
PMCID: PMC3209487  PMID: 21813133
Trauma; Radiology; Computed Tomography
23.  A sensitive diffusion tensor imaging quantification method to identify language pathway abnormalities in children with developmental delay 
The Journal of pediatrics  2011;160(1):147-151.
Objective
To investigate whether abnormal regional white matter architecture in the perisylvian region could be used as an easy and sensitive quantitative method to demonstrate language pathway abnormalities in children with developmental delay (DD).
Study design
We performed diffusion tensor imaging (DTI) in 15 DD subjects (age: 61.1± 20.9 months) and 15 age-matched typically developing (TD) children (age: 68.4± 19.2). Using DTI color-coded orientation maps, we quantified the fraction of fibers in the perisylvian region that are oriented in anteroposterior (AP) and mediolateral (ML) directions and their ratio(AP/ML) was calculated.
Results
The AP/ML ratio was more sensitive than tractography in characterizing perisylvian regional abnormalities in DD children. The AP/ML ratio of the left perisylvian region was significantly lower in DD children compared with TD children (p = 0.03). The ML component of bilateral perisylvian regions was significantly higher in DD children compared with TD children (p=0.01 (left) and p=0.004(right)). No significant difference was found in the AP component between the two groups. A significant negative correlation of the left ML component with Vineland communication skills was observed (r = −0.657, p=0.011).
Conclusions
The AP/ML ratio appears to be a sensitive indicator of regional white matter architectural abnormalities in the perisylvian region of DD children.
doi:10.1016/j.jpeds.2011.06.036
PMCID: PMC3218229  PMID: 21839473
Developmental delay; Arcuate Fasciculus; Diffusion tensor imaging; Mental retardation; perisylvian language pathways
24.  Body Composition Abnormalities in Long-Term Survivors of Pediatric Hematopoietic Stem Cell Transplantation 
The Journal of pediatrics  2011;160(1):122-128.
Objective
To quantify lean mass (LM) and fat mass (FM) in survivors of childhood allogeneic hematopoietic stem-cell transplantation (alloHSCT) compared with healthy reference participants, and identify risk factors for body composition abnormalities.
Study design
Whole body LM and FM were measured bydual energy x-ray absorptiometry in 54 survivors (ages 5–25 yr) and 894 healthy reference participants in a cross-sectional study. Multivariate regression models were used to compare sex-and race- specific Z-scores for LM (LM-Ht-Z) and FM (FM-Ht-Z) relative to height in survivors and reference participants, and to identify correlates of LM-Ht-Z and FM-Ht-Z in alloHSCT.
Results
Height-Z was significantly lower in alloHSCT (P<0.001) vs. reference participants; BMI-Z did not differ (P=0.13). Survivors had significantly lower mean LM-Ht-Z [−0.72 (95% CI:−1.02, −0.42);P<0.001] and greater FM-Ht-Z[1.10 (95% CI:0.84, 1.39;P<0.001], compared with reference participants. LM-Ht-Z deficits in alloHSCTwere larger [−1.26(95% CI:−1.53, −0.99;P<0.001] after adjustment for FM-Ht-Z. Endocrinopathies and alloHSCT characteristics were not associated with LM-Ht-Z or FM-Ht-Z.
Conclusions
Survivors of childhood alloHSCT have significant LM deficits and FM excess. Future studies should identify the mechanism and consequences of these abnormalities.
doi:10.1016/j.jpeds.2011.06.041
PMCID: PMC3218257  PMID: 21839468
Allogeneic hematopoietic stem cell transplantation; growth failure; body composition; LM; fat mass
25.  Randomized Controlled Trial of Restrictive Fluid Management in Transient Tachypnea of the Newborn 
The Journal of pediatrics  2011;160(1):38-43.e1.
Objective
To determine the effect of mild fluid restriction on the hospital course of neonates with transient tachypnea of the newborn (TTN).
Study design
This is a pilot prospective randomized controlled trial of 64 late preterm and term neonates diagnosed with TTN at a single tertiary-care hospital in the United States. Patients were randomized to receive standard fluid management or mild fluid restriction. Primary outcome was duration of respiratory support. Secondary outcomes were duration of admission to the ICU, time to first enteral feed, and total and composite hospital charges. Results were analyzed by t-test, chi-square, Kaplan-Meier estimation and proportional hazards regression.
Results
Fluid restriction did not cause adverse events or unsafe dehydration. Fluid management strategy did not affect primary or secondary outcomes in the broad study population. Fluid restriction significantly reduced duration of respiratory support (p=0.008) and hospitalization costs (p=0.017) for neonates with severe TTN.
Conclusions
Mild fluid restriction appears safe in late preterm and term neonates with uncomplicated TTN. Fluid restriction may be of benefit in decreasing duration of respiratory support and hospitalization charges in term and late preterm neonates with uncomplicated severe TTN.
doi:10.1016/j.jpeds.2011.06.027
PMCID: PMC3219819  PMID: 21839467

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