To describe the 5-year cumulative incidence of cardiac dysfunction in human immunodeficiency virus (HIV)-infected children.
We used a prospective cohort design, enrolling children at 10 hospitals. Group I included 205 vertically HIV-infected children enrolled at a median age of 1.9 years. Group II consisted of 600 HIV-exposed children enrolled prenatally or as neonates, of whom 93 were ultimately HIV-infected. The main outcome measures were echocardiographic indexes of left ventricular dysfunction.
In group I, the 5-year cumulative incidence of left ventricular fractional shortening ≤25% was 28.0%. The 5-year incidence of left ventricular end-diastolic dilatation was 21.7%, and heart failure and/or the use of cardiac medications 28.8%. The mortality rate 1 year after the diagnosis of heart failure was 52.5% [95% CI, 30.5-74.5]. Within group II, the 5-year cumulative incidence of decreased fractional shortening was 10.7% in the HIV-infected compared with 3.1% in the HIV-uninfected children (P = .01). Left ventricular dilation, heart failure, and/or the use of cardiac medications were more common in infected compared with uninfected children.
During 5 years of follow-up, cardiac dysfunction occurred in 18% to 39% of HIV-infected children and was associated with an increased risk of death. We recommend that HIV-infected children undergo routine echocardiographic surveillance for cardiac abnormalities.
We studied gene expression in nine sets of paired newborn blood spots stored for 8–10 years in either the frozen or unfrozen state. Fewer genes were expressed in unfrozen spots, but the average correlation coefficient for overall gene expression comparing the frozen and unfrozen state was 0.771 (95% CI: [0.700–0.828]).
To evaluate lipidomic differences between breast- and formula-fed infants.
We utilized high-resolution mass-spectrometry methods to analyze 3.2 mm dried blood spot samples collected at ages 3 months (n = 241) and 12 months (n = 144) from a representative birth cohort study. Lipidomic profiles were compared between infants exclusively breast-fed, formula-fed, or mixed-fed, and related to 12-month infancy weight. Data analysis included supervised multivariate statistics (partial least squares discriminant analysis), and univariate analysis with correction for multiple testing.
Distinct differences in 3-month lipidomic profiles were observed between exclusively breast-fed and formula-fed infants; mixed-fed infants showed intermediate profiles. Principle lipidomic characteristics of breast-fed infants were lower total phosphatidylcholines (PCs), with specifically lower short chain unsaturated PC but higher long chain polyunsaturated PC; higher cholesterol esters; and variable differences in sphingomyelins. At 12 months, lipidomic profiles were markedly different to those at 3 months, and differences between the earlier breast/formula/mixed-feeding groups were no longer evident. However, several specific lipid species, associated with breast-feeding at 3 months, also correlated with differences in 3- to 12-month weight.
State-of-the-art dried blood spot sample lipidomic profiling demonstrated striking differences between breast-fed and formula-fed infants. Although these changes diminished with age, breast-fed lipidomic profiles at 3 months were associated with infancy weight and could potentially represent biomarkers of infant nutrition.
CBGS, Cambridge Baby Growth Study; CE, Cholesterol ester; DBS, Dried blood spot; LC-PUFA, Long chain polyunsaturated fatty acid; PC, Phosphatidylcholine; PC-O, 1-alkyl,2-acylglycerophosphocholine; PC-P, 1-(alkenyl),2-acylglycerophosphocholin; PLS-DA, Partial least squares-discriminant analysis; SM, Sphingomyelin; TG, Triglyceride
To determine the prevalence and nature of residual cognitive disability after inpatient rehabilitation for children aged 7-18 years with traumatic injuries.
This retrospective cohort study included children aged 7-18 years in the Uniform Data System for Medical Rehabilitation who underwent inpatient rehabilitation for traumatic injuries in 523 facilities from 2002-2011. Traumatic injuries were identified by standardized Medicare Inpatient Rehabilitation Facility–Patient Assessment Instrument codes. Cognitive outcomes were measured by the Functional Independence Measure instrument. A validated, categorical staging system derived from responses to the items in the cognitive domain of the functional independence measure was used and consisted of clinically relevant levels of cognitive achievement from stage 1 (total cognitive disability) to stage 7 (completely independent cognitive function).
There were 13 798 injured children who completed inpatient rehabilitation during the 10-year period. On admission to inpatient rehabilitation, patients with traumatic brain injury (TBI) had more cognitive disability (median stage 2) than those with spinal cord injury or other injuries (median stage 5). Cognitive functioning improved for all patients, but children with TBI still tended to have significant residual cognitive disability (median stage on discharge, 4).
Injured children gained cognitive functionality throughout inpatient rehabilitation. Those with TBI had more severe cognitive disability on admission and more residual disability on discharge. This is important not only for patient and family expectation setting but also for resource and service planning, as discharge from inpatient rehabilitation is a critical milestone for reintegration into society for children with serious injury.
To determine the effect of psychosocial deprivation early in life on motor development and assess the impact of a foster care intervention on improving motor development.
In a randomized controlled trial, children living in Romanian institutions were randomly assigned to care as usual in the institution, or placed in family centered foster care as part of the Bucharest Early Intervention Project (BEIP). The average age of placement into foster care was 23 months. At 8 years of age, the Bruininks-Oseretsky 2nd edition, short form (BOT2-SF) assessed the motor proficiency of children in both groups, as well as a never-institutionalized group from the Romanian community.
Children in the never-institutionalized group did significantly better on the BOT2-SF than children who had ever been institutionalized. (p < .001). There was no significant difference in performance between children in the care as usual group and foster care group. This finding also held true for all individual items on the BOT2-SF, except sit-ups. Regression analyses revealed that the between-group and within-group differences in BOT2-SF scores were largely mediated by IQ.
Early deprivation had a negative effect on motor development which was not resolved by placement in foster care. This effect was predominantly mediated by IQ. This study highlights the importance of monitoring for and addressing motor delays in children with a history of institutionalization, particularly those children with low IQ.
institutional care; foster care; development; Bruininks-Oseretsky; BEIP
To evaluate the incidence of death or neurodevelopmental impairment (NDI) at 18 to 22 months corrected age in subjects enrolled in a trial of early dexamethasone treatment to prevent death or chronic lung disease in extremely low birth weight infants.
Evaluation of infants at 18 to 22 months corrected age included anthropomorphic measurements, a standard neurological examination, and the Bayley Scales of Infant Development-II, including the Mental Developmental Index (MDI) and the Psychomotor Developmental Index (PDI). NDI was defined as moderate or severe cerebral palsy, MDI or PDI less than 70, blindness, or hearing impairment.
Death or NDI at 18 to 22 months corrected age was similar in the dexamethasone and placebo groups (65 vs 66 percent, p= 0.99 among those with known outcome). The proportion of survivors with NDI was also similar, as were mean values for weight, length, and head circumference and the proportion of infants with poor growth (50 vs 41 percent, p=0.42 for weight less than 10th percentile). Forty nine percent of infants in the placebo group received treatment with corticosteroid compared to 32% in the dexamethasone group (p=0.02).
The risk of death or NDI and rate of poor growth were high but similar in the dexamethasone and placebo groups. The lack of a discernible effect of early dexamethasone on neurodevelopmental outcome may be due to frequent clinical corticosteroid use in the placebo group.
neurodevelopmental outcome; growth; bronchopulmonary dysplasia; cerebral palsy; neonatal follow-up
To evaluate associations between neonatal intensive care unit (NICU) room type (open ward and private room) and medical outcomes; neurobehavior, electrophysiology and brain structure at hospital discharge; and developmental outcomes at two years of age.
In this prospective longitudinal cohort study, we enrolled 136 preterm infants born <30 weeks gestation from an urban, 75-bed level III NICU from 2007-2010. Upon admission, each participant was assigned to a bedspace in an open ward or private room within the same hospital, based on space and staffing availability, where they remained for the duration of hospitalization. The primary outcome was developmental performance at two years of age (n=86 infants returned for testing, which was 83% of survivors) measured using the Bayley Scales of Infant and Toddler Development, 3rd Edition. Secondary outcomes were 1) medical factors throughout the hospitalization, 2) neurobehavior, and 3) cerebral injury and maturation (determined by magnetic resonance imaging and electroencephalography).
At term equivalent age, infants in private rooms were characterized by a diminution of normal hemispheric asymmetry and a trend toward having lower amplitude integrated electroencephalography cerebral maturation scores [p= 0.02; β=−0.52 (CI −0.95, −0.10)]. At age two years, infants from private rooms had lower language scores [p= 0.006; β=−8.3 (CI −14.2, −2.4)] and a trend toward lower motor scores [p= 0.02; β=−6.3 (CI −11.7, −0.99)], which persisted after adjustment for potential confounders.
These findings raise concerns that highlight the need for further research into the potential adverse effects of different amounts of sensory exposure in the NICU environment.
Single Patient Room; Single Family Ward; Open Bay; Open Ward; Development; Outcome; MRI; Room Type; Sensory Deprivation; Motor; Language; Cerebral Maturation; Sensory Exposure; Surface Based Morphometry; Hemispheric Asymmetry; Sound Abatement
To examine the association between 25-hydroxyvitamin D (25[OH]D) deficiency and anemia in a cohort of otherwise healthy children, and to determine whether race modifies the association between 25(OH)D status and hemoglobin (Hgb).
Cross-sectional study of 10,410 children and adolescents aged 1-21 years from the 2001-2006 National Health and Nutrition Examination Survey. Anemia was defined as hemoglobin less than the 5th percentile for age and sex based on NHANES III data.
Lower 25(OH)D levels were associated with increased risk for anemia; < 30 ng/mL, adjusted odds ratio (OR) 1.93, 95% confidence interval (CI) 1.21, 3.08, p=0.006, and < 20 ng/mL, OR 1.47, 95%CI 1.14-1.89, p=0.004. In linear regression, small but significant increases in Hgb were noted in the upper quartiles of 25(OH)D compared with the lowest quartile (< 20 ng/mL) in the full cohort. Results of race-stratified linear regression by 25(OH)D quartile in white children were similar to those observed in the full cohort, but in black children, increase in Hgb in the upper 25(OH)D quartiles was only apparent compared with the lowest black race specific quartile (<12 ng/mL).
25(OH)D deficiency is associated with increased risk of anemia in a healthy U.S. children, but the 25(OH)D threshold levels for lower Hgb are lower in black children in comparison with white children.
Management of pediatric chronic liver disease is limited by lack of validated noninvasive biomarkers of histological severity. We demonstrate that magnetic resonance elastography (MRE) is feasible and accurate in detecting significant hepatic fibrosis in a case series of 35 children with chronic liver disease, including severely obese children.
nonalcoholic fatty liver disease; nonalcoholic steatohepatitis; noninvasive biomarker; pediatric liver disease
Although colonization traditionally is considered a risk factor for Staphylococcus aureus infection, the relationship between contemporary S. aureus colonization and infection is not well characterized. We aimed to relate colonizing and disease-causing strains of S. aureus within individuals and households.
In a prospective study in St. Louis, Missouri of 163 pediatric outpatients (cases) with community-associated S. aureus skin and soft tissue infections (SSTI), infection isolates were obtained from cases along with colonization cultures from cases and their household contacts (n=562). Molecular typing by repetitive sequence-based PCR was employed to compare infecting and colonizing isolates within each case; the infecting strain from each case was compared with S. aureus strains colonizing household contacts. Colonization status of cases was followed for 12 months.
Among 1299 S. aureus isolates evaluated, 27 distinct strain types were identified. The range of distinct strain types per household was 1-6. One hundred ten cases (67%) were colonized at ≥1 body site with their infecting strain. Of the 53 cases whose infecting strain did not match a colonizing strain, 15 (28%) had ≥1 household contact whose colonizing strain matched the case’s infecting strain. Intrafamilial strain-relatedness was observed in 105 (64%) families.
One-third of cases were colonized with a different strain-type than the strain causing their SSTI. For cases with discordant SSTI/colonizing isolates, less than one-third could be linked to the strain from another household contact, suggesting acquisition from sources external to the household.
repetitive sequence-based polymerase chain reaction
Alveolar capillary dysplasia with misalignment of pulmonary veins (ACD/MPV) is a lethal neonatal lung disease. Although death is caused by hypoxia, the role of MPV is unknown. Using three-dimensional-reconstruction of ACD/MPV lung tissue, we report that MPV are intrapulmonary shunt vessels and speculate that MPV contributes to poor prognosis.
lung development; vascular remodeling; neonatal lung disorders; developmental aspects of the pulmonary circulation; blood flow; hypoxia; persistent pulmonary hypertension of the newborn
To determine the extent to which known pre- and perinatal predictors of childhood obesity also predict weight gain in early infancy.
We studied 690 infants participating in the prospective cohort Project Viva. We measured length and weight at birth and at 6 months. Using multivariable linear regression, we examined relationships of selected maternal and infant factors with change in weight-for-length z-score (WFL-z) from 0 to 6 months.
Mean (SD) change in WFL-z from 0 to 6 months was 0.23 (1.11), which translates to 4500 grams gained from birth to 6 months of life in an infant with average birth weight and length. After adjustment for confounding variables and birth weight-for-gestational age z-score (-0.28 [95% C.I. -0.37, -0.19] per unit), cord blood leptin (-0.40 [95% C.I. -0.61, -0.19] per 10 ng/ml) and gestational diabetes (-0.50 [95% C.I. -0.88, -0.11] versus normal glucose tolerance) were each associated with slower gain in WFL-z from 0 to 6 months.
Higher neonatal leptin and gestational diabetes predicted slower weight gain in the first 6 months of life. The hormonal milieu of the intrauterine environment may determine growth patterns in early infancy and thus later obesity.
To determine the prevalence of potential intracardiac shunts, including patent foramen ovale (PFO), in children with sickle cell disease (SCD) and stroke.
We performed a transthoracic echocardiogram (TTE) on 40 children with SCD (39 with hemoglobin SS and 1 with sickle-beta0 thalassemia) and earlier stroke (overt stroke in 30, silent infarction in 10). We compared 3 TTE techniques: conventional 2-dimensional imaging, color Doppler ultrasound, and intravenous agitated saline contrast injection for the detection of intracardiac shunts. We also evaluated the clinical, laboratory, and radio-graphic findings of the children with and without shunts.
We identified PFO or other potential intracardiac shunts in 10 of 40 children with SCD and earlier stroke (25%; 95% CI, 11.6-38.4). With contrasted TTE, we failed to detect potential shunts in 2 children. In a comparison group of 60 children with stroke but without SCD, retrospective review of clinical echocardiograms identified PFO in 7 of 60 (11.7%; 95% CI, 3.6-19.8). Clinical features significantly associated with the presence of intracardiac shunts were stroke in the setting of vaso-occlusive crisis (P = .026) and headache at stroke onset (P = .014).
One-quarter of children with SCD and stroke have potential intracardiac shunts. A combination of echocardiographic techniques is required for optimal shunt detection. Intracardiac shunting could be a risk factor for stroke in children with SCD because they are predisposed to thrombosis and elevations of right heart pressure, which could promote paradoxical embolization across an intracardiac shunt.
Among preterm infants, to examine tradeoffs between cognitive outcome and overweight/obesity at school age and in young adulthood in relation to infancy weight gain and linear growth.
We studied 945 participants in the Infant Health and Development Program, an 8-center study of preterm (≤37 weeks), low birth weight (≤2500 grams) infants from birth to 18 years. Adjusting for maternal and child factors in logistic regression, we estimated the odds of overweight/obesity (BMI ≥85th percentile at age 8 or ≥25 kg/m2 at age 18) and in separate models, low IQ (<85) per z-score change in infant length and BMI from term to 4 months, 4-12 months, and 12-18 months.
More rapid linear growth from term to 4 months was associated with lower odds of IQ<85 at age 8 (OR 0.82, 95% CI 0.70, 0.96), but a higher odds of overweight/obesity (OR 1.27, 95% CI 1.05, 1.53). More rapid BMI gain in all 3 infant time intervals was also associated with a higher odds of overweight/obesity, and from 4-12 months with a lower odds of IQ <85 at age 8. Results at age 18 were similar.
In preterm, low birth weight infants born in the 1980’s, faster linear growth soon after term was associated with better cognition but also with a higher risk of overweight/obesity at 8 and 18 years of age. BMI gain over the entire 18 months after term was associated with later risk of overweight/obesity, with less evidence for a benefit to IQ.
To compare the occurrence of injuries in adolescents with childhood-onset epilepsy and matched sibling controls.
Retrospective case-control lifetime injury assessments were obtained from a community-based cohort of adolescents with childhood-onset epilepsy diagnosed 9-years earlier, and their siblings. Children with epilepsy (n=501; mean age 15.3 years) included children with complicated (abnormal neurological exam or IQ<80; n=133) and uncomplicated (normal neurological exam and IQ≥80; n=368) epilepsy. Children with uncomplicated epilepsy were matched to sibling controls (n=210 pairs). Children reported whether they had ever (before and after epilepsy diagnosis) experienced injuries, “serious enough to require medical attention” and the type of treatment required.
49.1% of children with epilepsy experienced any injury, of whom 8.9% required surgery/hospitalization and 17.1% had an injury due to a seizure; fewer children with uncomplicated epilepsy had seizure-related injuries versus those with complicated epilepsy (13.6% vs. 27.4%; p≤0.01). The proportion of children with epilepsy with any injury by types (not mutually exclusive) were: 25.2% (n=126) fractures, 24.4% (n=122) head, 10.2% (n=51) other, 8.4% (n=42) dental and 8% (n=40) burns/scalds. A similar proportion of children with uncomplicated epilepsy experienced any injury (overall and by type) compared with matched sibling controls, with the exception that more children with uncomplicated epilepsy had head injuries (30.0% vs. 19.5%; p<0.02).
With the exception of head injuries, in a representative cohort of children with epilepsy compared with siblings there was no evidence of an increased risk of injury. This may reflect that the sample was not biased to more severe cases or that safety precautions to prevent injury were widely employed.
children; adolescents; epilepsy; injury; sibling controls
To determine the prevalence of specific micronutrient (iron, zinc, magnesium, phosphorus, selenium, copper, folate, vitamins A, D, E and B12) deficiencies in children with intestinal failure (IF), and identify risk factors associated with developing these deficiencies.
A retrospective review of prospectively collected data from 178 children with IF managed by the intestinal rehabilitation program at Cincinnati Children’s Hospital Medical Center, Ohio, USA between August1st 2007 and July 31st 2012. Transition to full enteral nutrition (FEN) was defined as the period during which the patient received between 20%–100% of estimated required nutrition enterally. FEN was defined as the patient tolerating all of the estimated required nutrition (100%) enterally for > 2 weeks.
Necrotizing enterocolitis (NEC) was the most common cause of IF (27.5 %). Iron was the most common micronutrient deficiency identified during (83.9%) and after (61%) successful transition to FEN with significant reduction in the percentage of patients with iron deficiency between the two periods (P=0.003). Predictors of micronutrient deficiency after successful transition to FEN include birth weight (P=0.03), weight percentiles (P=0.02), height percentiles (P=0.04) and PN duration (P=0.013). After multivariate adjustments, only PN duration remained statistically significant (P=0.03).
Micronutrient deficiencies persist in patients with IF during and after transition to enteral nutrition. These data support the need for routine monitoring and supplementation of these patients especially those on prolonged PN.
Prevalence; Micronutrient deficiency; Intestinal failure