Tufts Children's Hospital

OBJECTIVE: This report presents data from the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network on care of and morbidity and mortality rates for very low birth weight infants, according to gestational age (GA). METHODS: Perinatal/neonatal data were collected for 9575 infants of extremely low GA (22-28 weeks) and very low birth weight (401-1500 g) who were born at network centers between January 1, 2003, and December 31, 2007. RESULTS: Rates of survival to discharge increased with increasing GA (6% at 22 weeks and 92% at 28 weeks); 1060 infants died at <or=12 hours, with most early deaths occurring at 22 and 23 weeks (85% and 43%, respectively). Rates of prenatal steroid use (13% and 53%, respectively), cesarean section (7% and 24%, respectively), and delivery room intubation (19% and 68%, respectively) increased markedly between 22 and 23 weeks. Infants at the lowest GAs were at greatest risk for morbidities. Overall, 93% had respiratory distress syndrome, 46% patent ductus arteriosus, 16% severe intraventricular hemorrhage, 11% necrotizing enterocolitis, and 36% late-onset sepsis. The new severity-based definition of bronchopulmonary dysplasia classified more infants as having bronchopulmonary dysplasia than did the traditional definition of supplemental oxygen use at 36 weeks (68%, compared with 42%). More than one-half of infants with extremely low GAs had undetermined retinopathy status at the time of discharge. Center differences in management and outcomes were identified. CONCLUSION: Although the majority of infants with GAs of >or=24 weeks survive, high rates of morbidity among survivors continue to be observed.

Obesity now affects one in five children in the United States. Discrimination against overweight children begins early in childhood and becomes progressively institutionalized. Because obese children tend to be taller than their nonoverweight peers, they are apt to be viewed as more mature. The inappropriate expectations that result may have an adverse effect on their socialization. Many of the cardiovascular consequences that characterize adult-onset obesity are preceded by abnormalities that begin in childhood. Hyperlipidemia, hypertension, and abnormal glucose tolerance occur with increased frequency in obese children and adolescents. The relationship of cardiovascular risk factors to visceral fat independent of total body fat remains unclear. Sleep apnea, pseudotumor cerebri, and Blount's disease represent major sources of morbidity for which rapid and sustained weight reduction is essential. Although several periods of increased risk appear in childhood, it is not clear whether obesity with onset early in childhood carries a greater risk of adult morbidity and mortality. Obesity is now the most prevalent nutritional disease of children and adolescents in the United States. Although obesity-associated morbidities occur more frequently in adults, significant consequences of obesity as well as the antecedents of adult disease occur in obese children and adolescents. In this review, I consider the adverse effects of obesity in children and adolescents and attempt to outline areas for future research. I refer to obesity as a body mass index greater than the 95th percentile for children of the same age and gender.

BACKGROUND: Guidelines for prevention of group B streptococcal (GBS) infection have successfully reduced early onset (EO) GBS disease. Study results suggest that Escherichia coli is an important EO pathogen. OBJECTIVE: To determine EO infection rates, pathogens, morbidity, and mortality in a national network of neonatal centers. METHODS: Infants with EO infection were identified by prospective surveillance at Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Network centers. Infection was defined by positive culture results for blood and cerebrospinal fluid obtained from infants aged ≤72 hours plus treatment with antibiotic therapy for ≥5 days. Mother and infant characteristics, treatments, and outcomes were studied. Numbers of cases and total live births (LBs) were used to calculate incidence. RESULTS: Among 396 586 LBs (2006-2009), 389 infants developed EO infection (0.98 cases per 1000 LBs). Infection rates increased with decreasing birth weight. GBS (43%, 0.41 per 1000 LBs) and E coli (29%, 0.28 per 1000 LBs) were most frequently isolated. Most infants with GBS were term (73%); 81% with E coli were preterm. Mothers of 67% of infected term and 58% of infected preterm infants were screened for GBS, and results were positive for 25% of those mothers. Only 76% of mothers with GBS colonization received intrapartum chemoprophylaxis. Although 77% of infected infants required intensive care, 20% of term infants were treated in the normal newborn nursery. Sixteen percent of infected infants died, most commonly with E coli infection (33%). CONCLUSION: In the era of intrapartum chemoprophylaxis to reduce GBS, rates of EO infection have declined but reflect a continued burden of disease. GBS remains the most frequent pathogen in term infants, and E coli the most significant pathogen in preterm infants. Missed opportunities for GBS prevention continue. Prevention of E coli sepsis, especially among preterm infants, remains a challenge.

BACKGROUND: Infants with cardiac disease or prematurity are at risk for severe illness caused by respiratory syncytial virus. Immune globulin with a high titer of antibodies against respiratory syncytial virus may offer infants and young children at risk protection from this serious, common respiratory illness. METHODS: We studied 249 infants and young children (mean age, eight months) who had bronchopulmonary dysplasia due to prematurity (n = 102), congenital heart disease (n = 87), or prematurity alone (n = 60). Respiratory syncytial virus immune globulin was given monthly to some of these children in either a high dose (750 mg per kilogram of body weight; n = 81) or low dose (150 mg per kilogram; n = 79); 89 controls received no immune globulin. Group assignments were random. Assessments of respiratory illness and management were conducted without knowledge of the children's group assignments. RESULTS: There were 64 episodes of respiratory syncytial virus infection: 19 in the high-dose group, 16 in the low-dose group, and 29 in the control group. In the high-dose group there were fewer lower respiratory tract infections (7, vs. 20 in the control group; P = 0.01), fewer hospitalizations (6, vs. 18 in the control group; P = 0.02), fewer hospital days (43, vs. 128 in the control group; P = 0.02), fewer days in the intensive care unit (P = 0.05), and less use of ribavirin (P = 0.05). In the low-dose group there was a significant reduction only in the number of days in the intensive care unit (P = 0.03). Adverse events during the 580 infusions were generally mild and included fluid overload (in five children), oxygen desaturation (eight), and fever (six). Six children died: three in the high-dose group, three in the low-dose group, and none in the control group (P = 0.15), but no death was attributed to the use of immune globulin or to illness caused by respiratory syncytial virus. CONCLUSIONS: Administration of high doses of respiratory syncytial virus immune globulin is a safe and effective means of preventing lower respiratory tract infection in infants and young children at high risk for this disease.

Transcatheter closure of secundum atrial septal defect (ASD) using clamshell or buttoned devices is accompanied by a high incidence of residual shunt. Recently, a new self-centering device, the Amplatzer septal occluder (ASO), has been evaluated in an animal model with very good results. Therefore, our purpose is to report on our initial clinical experience with this device. Thirty patients underwent an attempt at catheter closure of their ASDs at a median age of 6.1 yr (range, 2.9-62.4 yr) and median weight of 22 kg (range, 13-69 kg) using the ASO. The median ASD diameter measured by transesophageal echocardiography (TEE) was 12.5 mm (range, 5-21 mm), and the median ASD balloon stretched diameter was 14 mm (range, 7-19 mm). All patients had right atrial and ventricular volume overload with a mean +/- SD Qp/Qs of 2.3 +/- 0.6. A 7F catheter was used for delivery of the device in all patients. The device was placed correctly in all patients. There was immediate and complete closure (C) in 17/30 patients, 10 patients had trivial residual shunt (TS), and 3 had moderate residual shunt (MS). The median fluoroscopy time was 15 min (range, 8-35 min), and the median total procedure time was 92.5 min (range, 40-135 min). There was no episode of device embolization or any other complication. Follow-up was performed using transthoracic echocardiography (TTE) 1 day, 1 mo, 3 mo, and yearly thereafter. At 1 day, there was C of the ASD in 24/30 patients, 3 had TS, 1 had small shunt (SS), and 2 had MS. At a median follow-up interval of 6 mo, there have been no episodes of endocarditis, thromboembolism, or wire fracture. We conclude that the use of the new ASO is safe and effective in complete closure of secundum ASDs up to a diameter of 21 mm in the majority of patients. Further clinical trials are underway.

OBJECTIVE: Perinatal inflammation is a major risk factor for neurological deficits in preterm infants. Several experimental studies have shown that systemic inflammation can alter the programming of the developing brain. However, these studies do not offer detailed pathophysiological mechanisms, and they rely on relatively severe infectious or inflammatory stimuli that most likely do not reflect the levels of systemic inflammation observed in many human preterm infants. The goal of the present study was to test the hypothesis that moderate systemic inflammation is sufficient to alter white matter development. METHODS: Newborn mice received twice-daily intraperitoneal injections of interleukin-1β (IL-1β) over 5 days and were studied for myelination, oligodendrogenesis, and behavior and with magnetic resonance imaging (MRI). RESULTS: Mice exposed to IL-1β had a long-lasting myelination defect that was characterized by an increased number of nonmyelinated axons. They also displayed a reduction of the diameter of the myelinated axons. In addition, IL-1β induced a significant reduction of the density of myelinating oligodendrocytes accompanied by an increased density of oligodendrocyte progenitors, suggesting a partial blockade in the oligodendrocyte maturation process. Accordingly, IL-1β disrupted the coordinated expression of several transcription factors known to control oligodendrocyte maturation. These cellular and molecular abnormalities were correlated with a reduced white matter fractional anisotropy on diffusion tensor imaging and with memory deficits. INTERPRETATION: Moderate perinatal systemic inflammation alters the developmental program of the white matter. This insult induces a long-lasting myelination deficit accompanied by cognitive defects and MRI abnormalities, further supporting the clinical relevance of the present data.

This study examines the differences which may distinguish systemic lupus erythematosus (SLE) presenting in adult life or childhood. A common database was established, with analysis of clinical, serological and outcome features of a cohort of patients with SLE, with disease diagnosed before the age of 16 (n = 39) or after the age of 16 (n = 165). Disease onset was generally more severe in the childhood-onset patients. Cardiopulmonary disease was more common in the older-onset group, but major haematological manifestations were more frequent in the childhood-onset group. Serologically, anti-DNA, anti-Sm and anti-RNP antibodies and a low C3 were all found more frequently in the younger patients. Twice as many adult-onset cases had died at the time of the last follow-up (10 vs 5%), but this group had been followed for a longer period (average 7.5 yr, S.D. 3.9 for adults vs average 4.8 yr, S.D. 3.2 for children). However, the younger patients were twice as likely (82 vs 40%) to require high-dose prednisone, although the requirement for immunosuppressive agents was similar in the two groups. Clinicians should anticipate that children with SLE have a more severe disease onset than adults in general.

BACKGROUND: Multiple lines of evidence indicate a strong genetic contribution to autism spectrum disorders (ASDs). Current guidelines for clinical genetic testing recommend a G-banded karyotype to detect chromosomal abnormalities and fragile X DNA testing, but guidelines for chromosomal microarray analysis have not been established. PATIENTS AND METHODS: A cohort of 933 patients received clinical genetic testing for a diagnosis of ASD between January 2006 and December 2008. Clinical genetic testing included G-banded karyotype, fragile X testing, and chromosomal microarray (CMA) to test for submicroscopic genomic deletions and duplications. Diagnostic yield of clinically significant genetic changes was compared. RESULTS: Karyotype yielded abnormal results in 19 of 852 patients (2.23% [95% confidence interval (CI): 1.73%-2.73%]), fragile X testing was abnormal in 4 of 861 (0.46% [95% CI: 0.36%-0.56%]), and CMA identified deletions or duplications in 154 of 848 patients (18.2% [95% CI: 14.76%-21.64%]). CMA results for 59 of 848 patients (7.0% [95% CI: 5.5%-8.5%]) were considered abnormal, which includes variants associated with known genomic disorders or variants of possible significance. CMA results were normal in 10 of 852 patients (1.2%) with abnormal karyotype due to balanced rearrangements or unidentified marker chromosome. CMA with whole-genome coverage and CMA with targeted genomic regions detected clinically relevant copy-number changes in 7.3% (51 of 697) and 5.3% (8 of 151) of patients, respectively, both higher than karyotype. With the exception of recurrent deletion and duplication of chromosome 16p11.2 and 15q13.2q13.3, most copy-number changes were unique or identified in only a small subset of patients. CONCLUSIONS: CMA had the highest detection rate among clinically available genetic tests for patients with ASD. Interpretation of microarray data is complicated by the presence of both novel and recurrent copy-number variants of unknown significance. Despite these limitations, CMA should be considered as part of the initial diagnostic evaluation of patients with ASD.

1. Human myeloid cells in the peripheral blood and bone marrow contain a very strong esterase activity which can be demonstrated histochemically by the use of naphthol AS-D chloroacetate as substrate. 2. As first pointed out by Gomori, this esterase activity is found not only in segmented but also immature myeloid cells. However, stem cells, cosinophilic and basophilic granulocytes, lymphocytes, monocytes, plasma cells, megakaryocytes, adult red cells and red cell precursors do not stain with this method. 3. Histocytes and mast cells are strongly positive for this esterase activity. 4. No differences in esterase activity have been noted thus far between neutrophilic leukocytes in normal individuals and in patients with chronic myclogenous leukemia or other diseases. 5. The leukocyte esterase activity is abolished by various well known inhibiting agents. Activity in young myeloid cells in non-leukemic bone marrow smears and in the peripheral blood of patients with myeloid leukemia is inhibited less than that in adult segmented neutrophils. 6. The functions of this esterase in leukocytes are unknown, but further studies of this enzyme seem warranted.

OBJECTIVES: To determine the relative incidence of accidental and abusive causes of head injuries in children younger than 6.5 years, to identify the types of craniocerebral damage resulting from reported mechanisms of injury, and to assess the likelihood of injuries being accidental or inflicted. METHODS: Retrospective review of medical records of 287 children with head injuries aged 1 week to 6.5 years admitted to a metropolitan children's hospital from January 1986 through December 1991. Those patients with diagnoses of skull fracture; concussion; subarachnoid hemorrhage (SAH); subgaleal, epidural, or subdural hematoma (SDH); parenchymal contusion or laceration; and closed head injury were included. Criteria were used for inclusion in categories of definite abuse or accident. RESULTS: Accidents accounted for 81% of cases and definite abuse for 19%. The mean age of the accident group was 2.5 years and for the definite abuse group, 0.7 years. Major differences were seen in the incidence of the following: SDH, 10% in the the accident group and 46% in the the definite abuse group; SAH, 8% in accident group and 31% in the definite abuse abuse; and retinal hemorrhages, 2% in the accident group and 33% in the definite abuse group. Associated cutaneous injuries consistent with inflicted injury were seen in 16% of the accident group and 50% of the definite abuse group. Twenty-three percent of those in the accident group were injured in motor vehicle crashes (MVCs), 58% by falls, 2% in play activities, and the rest had insufficient medical record information. In 56% of those in the definite abuse group, there was no history to account for the injuries and no history of MVC. In 17%, a fall was said to have been the mechanism of injury. In 24%, inflicted injury was admitted. Mortality rates were 13% in the definite abuse group and 2% in the accident group. Median hospital stay was 9.5 days for the definite abuse group and 3 days for the accident group. In falls less than 4 feet in the accident group, 8% had SDH, 2% had SAH, and none had retinal hemorrhages; among those in the definite abuse group reportedly falling less than 4 feet, 38% had SDH, 38% had SAH, and 25% had retinal hemorrhages. CONCLUSIONS: A substantial percentage of head injuries requiring hospitalization in children younger than 6.5 years are attributable to inflicted injury. Subdural hematoma, subarachnoid hemorrhage, retinal hemorrhages, and associated cutaneous, skeletal, and visceral injuries are significantly more common in inflicted head injury than in accidental injury.

BACKGROUND AND OBJECTIVES: Longitudinal assessment of disease activity is necessary for studies of therapeutic intervention in children with Crohn disease. The Pediatric Crohn Disease Activity Index (PCDAI) was developed a decade ago for such a purpose, but it function has only been examined in a small number of studies with a limited number of patients. The primary objectives of the present study were to develop cut scores reflecting disease activity as determined by physician global assessment (PGA) and to evaluate the responsiveness of the PCDAI to changes in patient condition after therapeutic interventions. METHODS: Data were derived from a prospective database of newly diagnosed children with inflammatory bowel disease established in 2002 at 18 pediatric gastroenterology centers in the United States and Canada. At diagnosis, at 30 days and 3 months after diagnosis, and quarterly thereafter, children (<16 years of age) with Crohn disease had disease assessment performed by PGA and PCDAI. Disease management was provided according to the dictates of the attending gastroenterologist and not by predetermined protocol. RESULTS: 181 patients had concomitant PGA and PCDAI performed at diagnosis, and 95 of these had similar assessment at short-term follow up. Mean +/- SD PCDAI scores for mild, moderate, and severe disease by PGA at diagnosis were 19.5 +/- 10.4, 32.2 +/- 12.7, and 47.8 +/- 14.9, respectively (P < 0.001 for all comparisons). Mean +/- SD PCDAI for inactive disease after treatment was 5.2 +/- 5.4. Receiver operating characteristic (ROC) curve analysis suggested that: 1) activity of moderate/severe disease was best reflected by a PCDAI of > or = 30 points, 2) clinical response (moderate/severe disease improving to mild/inactive) was best reflected by a decrease in PCDAI of > or = 12.5 points, and 3) a PCDAI < 10 best reflected inactive disease. CONCLUSIONS: PCDAI scores accurately reflect disease activity as assessed by physician global assessment. A PCDAI score of > or = 30 has acceptable sensitivity and specificity to indicate disease of moderate/severe activity. A PCDAI decrease of 12.5 points or greater following therapeutic intervention accurately reflects a clinically significant response. The PCDAI is an appropriate tool for intervention trials in Crohn disease in children.

Importance: Hypothermia initiated at less than 6 hours after birth reduces death or disability for infants with hypoxic-ischemic encephalopathy at 36 weeks' or later gestation. To our knowledge, hypothermia trials have not been performed in infants presenting after 6 hours. Objective: To estimate the probability that hypothermia initiated at 6 to 24 hours after birth reduces the risk of death or disability at 18 months among infants with hypoxic-ischemic encephalopathy. Design, Setting, and Participants: A randomized clinical trial was conducted between April 2008 and June 2016 among infants at 36 weeks' or later gestation with moderate or severe hypoxic-ischemic encephalopathy enrolled at 6 to 24 hours after birth. Twenty-one US Neonatal Research Network centers participated. Bayesian analyses were prespecified given the anticipated limited sample size. Interventions: Targeted esophageal temperature was used in 168 infants. Eighty-three hypothermic infants were maintained at 33.5°C (acceptable range, 33°C-34°C) for 96 hours and then rewarmed. Eighty-five noncooled infants were maintained at 37.0°C (acceptable range, 36.5°C-37.3°C). Main Outcomes and Measures: The composite of death or disability (moderate or severe) at 18 to 22 months adjusted for level of encephalopathy and age at randomization. Results: Hypothermic and noncooled infants were term (mean [SD], 39 [2] and 39 [1] weeks' gestation, respectively), and 47 of 83 (57%) and 55 of 85 (65%) were male, respectively. Both groups were acidemic at birth, predominantly transferred to the treating center with moderate encephalopathy, and were randomized at a mean (SD) of 16 (5) and 15 (5) hours for hypothermic and noncooled groups, respectively. The primary outcome occurred in 19 of 78 hypothermic infants (24.4%) and 22 of 79 noncooled infants (27.9%) (absolute difference, 3.5%; 95% CI, -1% to 17%). Bayesian analysis using a neutral prior indicated a 76% posterior probability of reduced death or disability with hypothermia relative to the noncooled group (adjusted posterior risk ratio, 0.86; 95% credible interval, 0.58-1.29). The probability that death or disability in cooled infants was at least 1%, 2%, or 3% less than noncooled infants was 71%, 64%, and 56%, respectively. Conclusions and Relevance: Among term infants with hypoxic-ischemic encephalopathy, hypothermia initiated at 6 to 24 hours after birth compared with noncooling resulted in a 76% probability of any reduction in death or disability, and a 64% probability of at least 2% less death or disability at 18 to 22 months. Hypothermia initiated at 6 to 24 hours after birth may have benefit but there is uncertainty in its effectiveness. Trial Registration: clinicaltrials.gov Identifier: NCT00614744.

Family-focused prevention programs have been shown to effectively reduce a range of negative behavioral health outcomes but have had limited reach. Three key barriers must be overcome to expand the reach of family-focused prevention programs and thereby achieve a significant public health impact. These barriers are (1) current social norms and perceptions of parenting programs; (2) concerns about the expertise and legitimacy of sponsoring organizations to offer parenting advice; and (3) a paucity of stable, sustainable funding mechanisms. Primary healthcare settings are well positioned to overcome these barriers. Recent changes within health care make primary care settings an increasingly favorable home for family-focused prevention and suggest possibilities for sustainable funding of family-focused prevention programs. This paper discusses the existing advantages of primary care settings and lays out a plan to move toward realizing the potential public health impact of family-focused prevention through widespread implementation in primary healthcare settings. Family-focused prevention programs have been shown to effectively reduce a range of negative behavioral health outcomes but have had limited reach. Three key barriers must be overcome to expand the reach of family-focused prevention programs and thereby achieve a significant public health impact. These barriers are (1) current social norms and perceptions of parenting programs; (2) concerns about the expertise and legitimacy of sponsoring organizations to offer parenting advice; and (3) a paucity of stable, sustainable funding mechanisms. Primary healthcare settings are well positioned to overcome these barriers. Recent changes within health care make primary care settings an increasingly favorable home for family-focused prevention and suggest possibilities for sustainable funding of family-focused prevention programs. This paper discusses the existing advantages of primary care settings and lays out a plan to move toward realizing the potential public health impact of family-focused prevention through widespread implementation in primary healthcare settings.

BACKGROUND: Although the numbers of women in training and in entry-level academic positions in medicine have increased substantially in recent years, the proportion of women in senior faculty positions has not changed. We conducted a study to determine the contributions of background and training, academic productivity, distribution of work time, institutional support, career attitudes, and family responsibilities to sex differences in academic rank and salary among faculty members of academic pediatric departments. METHODS: We conducted a cross-sectional survey of all salaried physicians in 126 academic departments of pediatrics in the United States in January 1992. Of the 6441 questionnaires distributed, 4285 (67 percent) were returned. The sample was representative of U.S. pediatric faculty members. Multivariate models were used to relate academic rank and salary to 16 independent variables. RESULTS: Significantly fewer women than men achieved the rank of associate professor or higher. For both men and women, higher salaries and ranks were related to greater academic productivity (more publications and grants), more hours worked, more institutional support of research, greater overall career satisfaction, and fewer career problems. Less time spent in teaching and patient care was related to greater academic productivity for both sexes. Women in the low ranks were less academically productive and spent significantly more time in teaching and patient care than men in those ranks. Adjustment for all independent variables eliminated sex differences in academic rank but not in salary. CONCLUSIONS: Lower rates of academic productivity, more time spent in teaching and patient care and less time spent in research, less institutional support for research, and lower rates of specialization in highly paid subspecialties contributed to the lower ranks and salaries of female faculty members.

BACKGROUND: Extremely preterm infants are at risk for neurodevelopmental impairment (NDI). Early cranial ultrasound (CUS) is usual practice, but near-term brain MRI has been reported to better predict outcomes. We prospectively evaluated MRI white matter abnormality (WMA) and cerebellar lesions, and serial CUS adverse findings as predictors of outcomes at 18 to 22 months' corrected age. METHODS: Early and late CUS, and brain MRI were read by masked central readers, in a large cohort (n = 480) of infants <28 weeks' gestation surviving to near term in the Neonatal Research Network. Outcomes included NDI or death after neuroimaging, and significant gross motor impairment or death, with NDI defined as cognitive composite score <70, significant gross motor impairment, and severe hearing or visual impairment. Multivariable models evaluated the relative predictive value of neuroimaging while controlling for other factors. RESULTS: Of 480 infants, 15 died and 20 were lost. Increasing severity of WMA and significant cerebellar lesions on MRI were associated with adverse outcomes. Cerebellar lesions were rarely identified by CUS. In full multivariable models, both late CUS and MRI, but not early CUS, remained independently associated with NDI or death (MRI cerebellar lesions: odds ratio, 3.0 [95% confidence interval: 1.3-6.8]; late CUS: odds ratio, 9.8 [95% confidence interval: 2.8-35]), and significant gross motor impairment or death. In models that did not include late CUS, MRI moderate-severe WMA was independently associated with adverse outcomes. CONCLUSIONS: Both late CUS and near-term MRI abnormalities were associated with outcomes, independent of early CUS and other factors, underscoring the relative prognostic value of near-term neuroimaging.

Preterm birth can be caused by intrauterine infection and maternal/fetal inflammatory responses. Maternal inflammation (chorioamnionitis) is often followed by a systemic fetal inflammatory response characterized by elevated levels of proinflammatory cytokines in the fetal circulation. The inflammation signal is likely transmitted across the blood-brain barrier and initiates a neuroinflammatory response. Microglial activation has a central role in this process and triggers excitotoxic, inflammatory, and oxidative damage in the developing brain. Neuroinflammation can persist over a period of time and sensitize the brain to subinjurious insults in early and chronic phases but may offer relative tolerance in the intermediate period through activation of endogenous anti-inflammatory, protective, and repair mechanisms. Neuroinflammatory injury not only destroys what exists but also changes what develops.

OBJECTIVE: The objective of this study was to document pulse oximeter saturation levels achieved in the first 4 weeks of life in infants who were born at < 28 weeks' gestation, compared with the levels that were targeted by local policy, and examine factors that are associated with compliance with the target range. METHODS: Infants who were < 28 weeks' gestation and < or = 96 hours of age were enrolled in a prospective, multicenter cohort study. Oximetry data were collected with masked signal-extraction oximeters for a 72-hour period in each of the first 4 weeks of life. Data were compared with the pulse oximeter saturation target range prescribed by local institutional policy. Factors that were associated with intended range compliance were identified with hierarchical modeling. RESULTS: Fourteen centers from 3 countries enrolled 84 infants with mean +/- SD birth weight of 863 +/- 208 g and gestational age of 26 +/- 1.4 weeks. Oxygen saturation policy limits ranged between 83% and 92% for lower limits and 92% and 98% for upper limits. For infants who received respiratory support, median pulse oximeter saturation level achieved was 95%. Center-specific medial levels were within the intended range at 12 centers. Centers maintained infants within their intended range 16% to 64% of the time but were above range 20% to 73% of the time. In hierarchical modeling, wider target ranges, higher target range upper limits, presence of a policy of setting oximeter alarms close to the target range limits, and lower gestational age were associated with improved target range compliance. CONCLUSIONS: Success with maintaining the intended pulse oximeter saturation range varied substantially among centers, among patients within centers, and for individual patients over time. Most noncompliance was above the intended range. Methods for improving compliance and the effect of improved compliance on neonatal outcomes require additional research.

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

BACKGROUND: Factor analyses suggest that the structure underlying metabolic syndrome is similar in adolescents and adults. However, adolescence is a period of intense physiological change, and therefore stability of the underlying metabolic structure and clinical categorization based on metabolic risk is uncertain. METHODS AND RESULTS: We analyzed data from 1098 participants in the Princeton School District Study, a school-based study begun in 2001-2002, who were followed up for 3 years. We performed factor analyses of 8 metabolic risks at baseline and follow-up to assess stability of factor patterns and clinical categorization of metabolic syndrome. Metabolic syndrome was defined using the current American Heart Association/National Heart, Lung, and Blood Institute definition for adults (AHA), a modified AHA definition used in prior pediatric metabolic syndrome studies (pediatric AHA), and the International Diabetes Federation (IDF) guidelines. We found that factor structures were essentially identical at both time points. However, clinical categorization was not stable. Approximately half of adolescents with baseline metabolic syndrome lost the diagnosis at follow-up regardless of the definitions used: pediatric AHA=56% (95% confidence interval [CI], 42% to 69%), AHA=49% (95% CI, 32% to 66%), IDF=53% (95% CI, 38% to 68%). In addition to loss of the diagnosis, new cases were identified. Cumulative incidence rates were as follows: pediatric AHA=3.8% (95% CI, 2.8% to 5.2%); AHA=4.4% (95% CI, 3.3% to 5.9%); IDF=5.2% (95% CI, 4.0% to 6.8%). CONCLUSIONS: During adolescence, metabolic risk factor clustering is consistent. However, marked instability exists in the categorical diagnosis of metabolic syndrome. This instability, which includes both gain and loss of the diagnosis, suggests that the syndrome has reduced clinical utility in adolescence and that metabolic syndrome-specific pharmacotherapy for youth may be premature.

PURPOSE: To determine the survival of infants and young children with non-metastatic medulloblastoma using intensive myeloablative chemotherapy and autologous hematopoietic progenitor cell rescue (AuHCR). METHODS: Twenty-one children less than 3 years old at diagnosis with non-metastatic medulloblastoma were enrolled on two identical serial studies, "Head Start" I and "Head Start" II. After surgery, patients received five cycles of induction chemotherapy consisting of vincristine, cisplatin, cyclophosphamide and etoposide. Following induction, all patients underwent myeloablative chemotherapy using carboplatin, thiotepa and etoposide with AuHCR. Irradiation was used only at relapse. RESULTS: The 5-year event-free (EFS) and overall survival (OS) rates (+/-SE) for all patients, patients with gross total resection, and patients with residual tumor were 52 +/- 11% and 70 +/- 10%, 64 +/- 13% and 79 +/- 11%, and 29 +/- 17% and 57 +/- 19%, respectively. The 5-year EFS and OS ( +/- SE) for patients with desmoplastic and classical medulloblastoma were 67 +/- 16% and 78 +/- 14%, and 42 +/- 14 and 67 +/- 14%, respectively. There were four treatment related deaths. The majority of survivors (71%) avoided irradiation completely. Mean intellectual functioning and quality of life (QoL) for children surviving without irradiation was within average range for a majority of survivors tested. CONCLUSION: This strategy of brief intensive chemotherapy for young children with non-metastatic medulloblastoma eliminated the need for craniospinal irradiation 52% of the patients, and may preserve QoL and intellectual functioning. The excellent survival rates are somewhat dampened by high toxic mortality.