METHODS. Data from waves I and III of the National Longitudinal Study of Adolescent Health were examined to determine the association between adolescent characteristics and future human papillomavirus infection. Analysis was restricted to 3181 female subjects who were >12 years of age when risk factors were assessed in wave I (1994–1995) and who underwent human papillomavirus testing as young adults in wave III (2001–2002). The main outcome of interest was a positive test result for ≥1 of 4 human papillomavirus types (human papillomavirus-6, -11, -16, or -18) targeted by the human papillomavirus vaccine currently available in the United States. Separate analyses were performed for sexually active and virginal adolescents. Poststratification sampling weights were used to generate nationally representative estimates.

RESULTS. Although nearly one half (43%) of the female adolescents were sexually active in wave I, adolescent sexual activity status was not associated with future detection of vaccine-specific human papillomavirus infection. Furthermore, for both virginal and sexually active adolescents, none of the assessed risk factors was associated with increased odds of future vaccine-specific human papillomavirus infection in multivariate models. Similar results were obtained when all high-risk human papillomavirus types were assessed as the outcome measure.

CONCLUSIONS. Behavioral risk factors assessed during adolescence are inadequate predictors of future infection with vaccine-type human papillomavirus. A risk factor-based approach to human papillomavirus catch-up vaccination is unlikely to be an effective implementation strategy.

PATIENTS AND METHODS. This study was a cross-sectional analysis of 62 887 children and adolescents aged 5 to 17 years from the 2003–2004 National Survey of Children's Health, a nationally representative sample of children and adolescents in the United States. Attention-deficit disorder/attention-deficit/hyperactivity disorder was determined by response to the question "Has a doctor or health professional ever told you that your child has attention-deficit disorder or attention-deficit/hyperactive disorder, that is, ADD or ADHD?" Children and adolescents were classified as underweight, normal weight, at risk of overweight, or overweight according to BMI for age and gender.

RESULTS. After adjustment for age, gender, race/ethnicity, socioeconomic status, and depression/anxiety, children and adolescents with attention-deficit disorder/attention-deficit/hyperactivity disorder not currently using medication had ~1.5 times the odds of being overweight, and children and adolescents currently medicated for attention-deficit disorder/attention-deficit/hyperactivity disorder had ~1.6 times the odds of being underweight compared with children and adolescents without either diagnosis.

CONCLUSIONS. This study provides heightened awareness for pediatric providers about the relationship between attention-deficit disorder/attention-deficit/hyperactivity disorder, medication use, and weight status. Future work is needed to better understand the longitudinal and pharmacologic factors that influence the relationship between attention-deficit disorder/attention-deficit/hyperactivity disorder and weight status in children and adolescents.

METHODS. Internationally adopted children who were seen at our International Adoption Center and had a tuberculin skin test within 2 months of arrival to the United States were eligible for the study. Children not diagnosed with tuberculosis with initial testing were retested at least 3 months later. The prevalence of tuberculosis on arrival and after repeat testing was determined, and potential risk factors for infection were examined.

RESULTS. Of the 527 internationally adopted children with an initial tuberculin skin test completed, 111 (21%) had evidence of latent tuberculosis infection. Repeat tuberculosis testing was complete for 191 internationally adopted children (46.9% of those who had an initially negative tuberculin skin test). Latent tuberculosis infection was found in 20% of those who were retested. No children were found to have active tuberculosis disease. Children with an initially positive tuberculin skin test result had slightly higher weight-for-age z scores at their initial clinic visit, whereas those whose tuberculin skin test result was positive after repeat testing had slightly lower weight-for-age z scores. A strong correlation between BCG immunization and tuberculin skin test result was observed.

CONCLUSIONS. Latent tuberculosis infection is common in internationally adopted children. A high proportion of internationally adopted children had an initially false-negative tuberculin skin test. Repeat tuberculosis testing of all internationally adopted children with an initially negative tuberculin skin test should be the standard of care for identifying tuberculosis infection and preventing tuberculosis disease in this high-risk population.

METHODS. Between November 2000 and March 2003, pregnant mothers carrying infants at high risk for allergy were randomly assigned to receive a mixture of 4 probiotic species (Lactobacillus rhamnosus GG and LC705, Bifidobacterium breve Bb99, and Propionibacterium freudenreichii ssp shermanii) or a placebo for 4 weeks before delivery. Their infants received the same probiotics with 0.8 g of galactooligosaccharides, or a placebo, daily for 6 months after birth. Safety data were obtained from clinical examinations and interviews at follow-up visits at ages 3, 6, and 24 months and from questionnaires at ages 3, 6, 12, and 24 months. Growth data were collected at each time point.

RESULTS. Of the 1018 eligible infants, 925 completed the 2-year follow-up assessment. Infants in both groups grew normally. We observed no difference in neonatal morbidity, feeding-related behaviors (such as infantile colic), or serious adverse events between the study groups. During the 6-month intervention, antibiotics were prescribed less often in the synbiotic group than in the placebo group (23% vs 28%). Throughout the follow-up period, respiratory infections occurred less frequently in the synbiotic group (geometric mean: 3.7 vs 4.2 infections).

CONCLUSION. Feeding synbiotics to newborn infants was safe and seemed to increase resistance to respiratory infections during the first 2 years of life.

METHODS. Data were from a 2001 national survey of households with children (<18 years of age) with special health care needs, with a representative sample from each state. The outcomes examined included whether a family had any out-of-pocket expenditures during the previous 12 months related to the child's special health care needs, the amount of expenditure (absolute burden), and the amount of expenditure per $1000 of family income (relative burden). We used multilevel regression to examine state-level variability in financial burden, controlling for individual-level factors. We also examined the association between state median family income and state mean financial burden.

RESULTS. Overall, 82.5% of families reported expenditures of more than $0. Among these families, the mean unadjusted absolute burden was $752 and the relative burden was $19.6 per $1000. Adjusted state means ranged from $562 to $972 for absolute burden and from $14.5 to $32.3 per $1000 for relative burden. Families living in states with higher median family incomes had lower financial burdens across all 3 measures.

CONCLUSIONS. Families that are similar with respect to household demographic characteristics and the nature of their children's special health care needs have different out-of-pocket health expenditures depending on the state in which they live. Documenting and understanding this variability moves the field closer to the goal of establishing evidence-based, state policy recommendations aimed at reducing the financial burden of these vulnerable families.

METHODS. In this cluster-randomized, controlled trial (2002–2006), 137 Pediatric Research in Office Settings practices were randomly assigned and initiated patient recruitment for either an office-based violence-prevention intervention or a control group (educational handout on literacy promotion provided). Primary caregivers of children who were aged 2 to 11 years and presented for a well-child visit were surveyed at baseline and 1 and 6 months. Practitioners were trained to (1) review a parent previsit summary regarding patient-family behavior and parental concern about media use, discipline strategies, and children's exposure to firearms, (2) counsel using brief principles of motivational interviewing, (3) identify and provide local agency resources for anger and behavior management when indicated, and (4) instruct patient-families on use of tangible tools (minute timers to monitor media time/timeouts and firearm cable locks to store firearms more safely where children live or play). Main outcomes were change over time in self-reported media use <120 minutes per day, use of timeouts, and use of firearm cable locks.

RESULTS. Generalized estimating equation analysis revealed a significant effect at 6 months for decreased media use and safer firearm storage. The intervention group compared with the control group showed an increase in limiting media use to <120 minutes per day. There was no significant effect for timeout use. There was a substantial increase in storing firearms with cable locks for the intervention group versus a decrease for the control group.

CONCLUSIONS. This randomized, controlled trial demonstrated decreased media exposure and increased safe firearm storage as a result of a brief office-based violence-prevention approach.

METHODS. Nineteen practices (with 84 primary care providers) from a large urban community were trained by using quality-improvement methods with some academic detailing. Pretraining and posttraining adherence to evidence-based practices was assessed through review of patient charts.

RESULTS. Preintervention rates of guideline usage were uniformly low. After the intervention, primary care providers showed substantial improvement in their use of the guidelines for the assessment and treatment of elementary school-aged patients with newly diagnosed attention-deficit/hyperactivity disorder. Use of parent and teacher assessment rating scales increased from levels of 52% to 55% to levels of nearly 100%. Systematic monitoring of responses to medication improved from a baseline level of 9% to 40%.

CONCLUSIONS. Quality-improvement interventions such as the one used in this study seem quite effective in improving primary care providers’ practices at offices that express interest in improving the quality of care for attention-deficit/hyperactivity disorder. The design of the intervention, problems associated with improving and sustaining treatment monitoring, and issues related to generalizability of the intervention model are discussed.

PATIENTS AND METHODS. Cases of invasive pneumococcal disease among children (aged 0–17 years) were identified from 1977 through 2005 by using a national surveillance program in Denmark. Rate ratios were assessed in a case-control study by using 10 age- and gender-matched controls per case. Chronic diseases were defined a priori.

RESULTS. Among 1655 children with invasive pneumococcal disease, 19% had a history of chronic disease, according to our definition, versus 5% of controls. An increased risk of invasive pneumococcal disease was observed for children followed >30 days after initial hospital contact for a chronic disease, but it was also increased in children with ≥5 hospital contacts for any other reason. Children with a history of cancer, chronic renal disease, splenectomy, and transplantation were particularly susceptible to invasive pneumococcal disease. Adjusted for number of hospital contacts, the risk for children with other types of chronic disease was 1.4-fold more than for those with hospital contacts for any reason.

CONCLUSIONS. Cancer, chronic renal diseases, splenectomy, and transplantation were strongly associated with an increased risk of invasive pneumococcal disease in children. For children with other chronic diseases, their excess risk seemed to be attributable mostly to frail children having repeated hospital contact rather than their underlying condition.

METHODS. We conducted a cross-sectional survey of the 201 accredited pediatric residency programs in the United States, Puerto Rico, and the Caribbean from October 2006 to January 2007. Survey topics included resident interest and participation in electives, training opportunities, program support, and educational curricular content related to global health.

RESULTS. Of the 201 surveyed pediatric residency programs, 106 (53%) responded. Fifteen percent of responding programs reported that a majority of their residents were interested in global health. Fifty-two percent offered a global health elective within the previous year, and 47% had formally incorporated global health into their training curricula. Six percent of the programs reported a formalized track or certificate in global health. The median number of residents per program participating in global health electives within the previous year was 0 during postgraduate year 1, 1 during postgraduate year 2, and 2 during postgraduate year 3. The median number of all residents per program participating in a global health elective in the previous year was 3 (7.4% of program size). Among programs that offered a global health elective, support to participating residents included prerequisite clinical training (36%), cultural orientation (36%), language training (15%), faculty mentorship (82%), and postelective debriefing (77%). Fourteen percent of the programs provided full funding for resident electives. Characteristics of pediatric residency programs that were significantly associated with higher resident participation in a global health elective were larger program size, university affiliation, greater reported resident interest, and faculty involvement in global health.

CONCLUSIONS. More than half of the pediatric residency programs surveyed offered a global health elective in the previous year. An American Academy of Pediatrics survey 10 years earlier had shown 1 of 4 programs with global health electives. Observance of American Academy of Pediatrics consensus guidelines for global health electives varied widely among programs, and additional efforts should focus on resident preparation, mentorship, and funding.

PATIENTS AND METHODS. Data from a computerized children's immunization registry in Philadelphia were analyzed. Demographics and age at immunization with first 3 diphtheria-tetanus-acellular pertussis doses were examined from 2001 to 2005. Similar characteristics were evaluated for children who received pentavalent rotavirus vaccine doses during the first 6 months of its availability (August 2006 through January 2007).

RESULTS. During the 5-year period, 24 403 of 103 967 recipients of first diphtheria-tetanus-acellular pertussis vaccine were >12 weeks of age; only 56 411 of 79 564 first diphtheria-tetanus-acellular pertussis recipients ≤12 weeks of age received the first 3 doses at ages that they could have completed the pentavalent rotavirus vaccine series if vaccines were given at the same visit. Children using public providers were more likely to have delayed immunization. During the first 6 months of pentavalent rotavirus vaccine implementation, 5566 pentavalent rotavirus vaccine doses were recorded in the Kids Immunization Database/Tracking System: 3912 first doses, 1419 second doses, and 235 third doses. Of 3912 first-dose pentavalent rotavirus vaccine recipients, 770 were >12 weeks of age. Hospital-based providers were less likely to administer pentavalent rotavirus vaccine off-label.

CONCLUSIONS. With the current level of vaccine implementation and current pentavalent rotavirus vaccine recommendations for series initiation, a substantial proportion of children are expected to be excluded from receiving any pentavalent rotavirus vaccine or completing the series. In the first 6 months of availability, pentavalent rotavirus vaccine frequently was used off-label for age, underscoring the importance of education of immunization providers. Current outreach programs for finding 10-month-old toddlers delinquent for immunizations will not improve the possibility of protection against rotavirus.

METHODS. The medical charts (including the number of pneumococcal conjugate vaccine doses) for children with pneumococcal mastoiditis treated at Texas Children's Hospital between January 1995 and June 2007 were reviewed retrospectively. Isolates were serotyped with the capsular swelling method. Pulsed-field gel electrophoresis was performed on the 19A isolates and multilocus sequence typing on selected 19A clones.

RESULTS. Forty-one pneumococcal mastoiditis cases were identified, and 19A (n = 19) was the most common serotype. Before the introduction of pneumococcal conjugate vaccine (from 1995 to December 1999), 0 of 12 cases were 19A. Between April 2000 and October 2006, 15 cases of pneumococcal mastoiditis occurred, and 5 were 19A. Fourteen cases of pneumococcal mastoiditis occurred between November 2006 and June 2007, all of which were 19A. Mastoiditis caused by 19A isolates was more likely to present with subperiosteal abscess and was more likely to need intraoperative mastoidectomy than was mastoiditis caused by non-19A isolates. Multidrug resistance was also common among the 19A isolates; 13 (68%) of the 19A isolates were resistant to all antibiotics tested routinely. Pulsed-field gel electrophoresis analysis placed 14 (74%) of the 19 serotype 19A isolates into a highly related group; 12 isolates were classified as closely related, and 2 were possibly related. Multilocus sequence typing analysis placed the pulsed-field gel electrophoresis cluster isolates into clonal complex 271 (sequence types 320 and 1451).

CONCLUSIONS. At Texas Children's Hospital, 19A has become the predominant serotype causing pneumococcal mastoiditis, partly related to the emergence of multidrug-resistant clonal complex 271 strains. Subperiosteal abscesses and the need for mastoidectomy were more common in children with mastoiditis caused by serotype 19A isolates, compared with isolates of other serotypes.

METHODS. We conducted a large-scale newborn screening pilot program between October 2005 and March 2007. The screening involved measuring acid -glucosidase activity in dried blood spots of ~45% of newborns in Taiwan. The unscreened population was monitored as a control.

RESULTS. Of the 132 538 newborns screened, 1093 (0.82%) repeat dried blood-spot samples were requested and retested, and 121 (0.091%) newborns were recalled for additional evaluation. Pompe disease was confirmed in 4 newborns. This number was similar to the number of infants who received a diagnosis of Pompe disease in the control group (n = 3); however, newborn screening resulted in an earlier diagnosis of Pompe disease: patients were <1 month old compared with 3 to 6 months old in the control group.

CONCLUSIONS. To our knowledge, this is the first large-scale study to show that newborn screening for Pompe disease is feasible. Newborn screening allows for earlier diagnosis of Pompe disease and, thus, for assessment of the value of an earlier start of treatment.

METHODS. In an event-related functional MRI study, 28 first-time mothers were shown novel face images of their own 5- to 10-month-old infant and a matched unknown infant. Sixty unique stimuli from 6 categories (own-happy, own-neutral, own-sad, unknown-happy, unknown-neutral, and unknown-sad) were presented randomly for 2 seconds each, with a variable 2- to 6-second interstimulus interval.

RESULTS. Key dopamine-associated reward-processing regions of the brain were activated when mothers viewed their own infant's face compared with an unknown infant's face. These included the ventral tegmental area/substantia nigra regions, the striatum, and frontal lobe regions involved in (1) emotion processing (medial prefrontal, anterior cingulate, and insula cortex), (2) cognition (dorsolateral prefrontal cortex), and (3) motor/behavioral outputs (primary motor area). Happy, but not neutral or sad own-infant faces, activated nigrostriatal brain regions interconnected by dopaminergic neurons, including the substantia nigra and dorsal putamen. A region-of-interest analysis revealed that activation in these regions was related to positive infant affect (happy > neutral > sad) for each own–unknown infant-face contrast.

CONCLUSIONS. When first-time mothers see their own infant's face, an extensive brain network seems to be activated, wherein affective and cognitive information may be integrated and directed toward motor/behavioral outputs. Dopaminergic reward-related brain regions are activated specifically in response to happy, but not sad, infant faces. Understanding how a mother responds uniquely to her own infant, when smiling or crying, may be the first step in understanding the neural basis of mother–infant attachment.

METHODS. This was a retrospective cohort study of all preterm infants who were <37 weeks' gestation, had periventricular hemorrhagic infarction, and were admitted between 1995 and 2006. Ultrasound scans were reviewed for grading of germinal matrix hemorrhage, localization and extension of the infarction, and other abnormalities. Several clinical factors were scored. Outcome measures were mortality, cerebral palsy, and Gross Motor Function Classification System level. Odds ratios were calculated by univariate and multivariate logistic regression analyses.

RESULTS. Of 54 infants, 16 (30%) died. Twenty-five (66%) of 38 survivors developed cerebral palsy: 21 mild (Gross Motor Function Classification System levels 1 and 2) and 4 moderate to severe (levels 3 and 4). Several perinatal and neonatal risk factors were associated with mortality. After multivariate logistic regression, only use of inotropic drugs and maternal intrauterine infection were predictors of mortality. In survivors, only the most extended form of periventricular hemorrhagic infarction was associated with the development of cerebral palsy but not with severity of cerebral palsy. Cystic periventricular leukomalacia and concurrent grade 3 germinal matrix hemorrhage were associated with more severe cerebral palsy.

CONCLUSIONS. In preterm infants with periventricular hemorrhagic infarction, mortality occurred despite optimal treatment and was associated with circulatory failure and maternal intrauterine infection. In survivors, motor development was abnormal in 66%, but functional abilities were good in the majority. Extension and localization of the periventricular hemorrhagic infarction were not related to functional outcome.

METHODS. We reviewed all articles published in the New England Journal of Medicine, Journal of the American Medical Association, Annals of Internal Medicine, Pediatrics, Archives of Internal Medicine, and Archives of Adolescent and Pediatric Medicine during the first 3 months of 2005 and assessed each study's design and purpose. We compared articles focused on adults with those focused on children.

RESULTS. We included 370 original research reports in our analysis (New England Journal of Medicine, n = 46; Journal of the American Medical Association, n = 60; Annals of Internal Medicine, n = 27; Pediatrics, n = 130; Archives of Internal Medicine, n = 73; Archives of Adolescent and Pediatric Medicine, n = 34), of which 189 included only adults as subjects and 181 only children. Among adult studies, compared with child studies, there were more randomized, controlled trials (23.8% vs 8.8%) and systematic reviews (10.6% vs 1.7%) and fewer cross sectional studies (16.9% vs 40.9%). Study purposes also varied, with studies of therapies constituting 38.1% of adult studies, compared with 17.7% of child studies. In contrast, epidemiological studies, defined as studies describing the prevalence or incidence of diseases or risk factors or showing associations between risk factors and diseases, constituted 6.4% of adult studies, compared with 26.5% of child studies.

CONCLUSIONS. In 6 leading generalist and specialist journals, studies involving adults were significantly more likely than child studies to be randomized, controlled trials, systematic reviews, or studies of therapies. If such studies are to be viewed as the highest possible quality of evidence, then this difference has implications for quality of care for children and for funding and future directions in clinical research involving children.

METHODS. This was a cohort follow-up study for a median of 7 years of children who had mild-to-moderate asthma and initially were randomly assigned into the Childhood Asthma Management Program trial. Serial dual-energy radiograph absorptiometry scans of the lumbar spine for bone mineral density were performed for all patients. Annual bone mineral accretion was calculated for 531 boys and 346 girls who had asthma and were aged 5 to 12 years at baseline (84% of the initial cohort).

RESULTS. Oral corticosteroid bursts produced a dosage-dependent reduction in bone mineral accretion (0.052, 0.049, and 0.046 g/cm² per year) and an increase in risk for osteopenia (10%, 14%, and 21%) for 0, 1 to 4, and ≥5 courses, respectively, in boys but not girls. Cumulative inhaled corticosteroid use was associated with a small decrease in bone mineral accretion in boys but not girls but no increased risk for osteopenia.

CONCLUSIONS. Multiple oral corticosteroid bursts over a period of years can produce a dosage-dependent reduction in bone mineral accretion and increased risk for osteopenia in children with asthma. Inhaled corticosteroid use has the potential for reducing bone mineral accretion in male children progressing through puberty, but this risk is likely to be outweighed by the ability to reduce the amount of oral corticosteroids used in these children.

METHODS. We conducted a population-based, retrospective cohort study of 103 670 term, non–low birth weight infants enrolled in Tennessee Medicaid in 1995–2003. We monitored infants through the first year of life. Risk factors for bronchiolitis during infancy and rates of inpatient, emergency department, and outpatient visits during the study period were calculated by using claims data.

RESULTS. Over the 9 study years, rates of bronchiolitis visits were 238 outpatient visits per 1000 infant-years, 77 emergency department visits per 1000 infant-years, and 71 hospitalizations per 1000 infant-years. Average annual rates of bronchiolitis visits increased 41%, from 188 visits per 1000 infant-years to 265 visits per 1000 infant-years, from 1996–1997 to 2002–2003. Analysis of the linear trend in 500-g increments demonstrated a negative association between increasing birth weight and bronchiolitis diagnosis. There was a significant negative trend between maternal age and infant bronchiolitis diagnosis. Compared with infants of mothers 20 to 29 years of age, infants of mothers 15 to 19 years of age had a small increase in risk of having a bronchiolitis visit, whereas infants of older mothers (30–39 or 40–44 years of age) were less likely to have a visit.

CONCLUSIONS. The disease burden of bronchiolitis is substantial, with increasing rates of all types of visits among term, otherwise-healthy infants enrolled in Tennessee Medicaid between 1995 and 2003. Protective factors in this cohort of term infants included higher birth weight and older maternal age.

METHODS. In conjunction with the Helsinki Study of Very Low Birth Weight Adults, 162 very low birth weight individuals and 188 individuals who were born at term (mean age: 22.3 years [range: 18.5–27.1]) and did not have any major disability filled out a questionnaire. For analysis of their ages at events which had not occurred in all subjects, we used survival analysis (Cox regression), adjusted for gender, current height, parents' ages at the birth, maternal smoking during pregnancy, parental educational attainment, number of siblings, and parental divorce/death.

RESULTS. During their late teens and early adulthood, these very low birth weight adults were less likely to leave the parental home and to start cohabiting with an intimate partner. In gender-stratified analyses, these hazard ratios were similar between genders, but the latter was statistically significant for women only. These very low birth weight adults were also less likely to experience sexual intercourse. This relationship was statistically significant for women but not for men; however, very low birth weight women and men both reported a smaller lifetime number of sex partners than did control subjects.

CONCLUSIONS. Healthy young adults with very low birth weight show a delay in leaving the parental home and starting sexual activity and partnerships.

METHODS. We studied 35 term infants with early brain MRI scans after symptomatic neonatal hypoglycemia (median glucose level: 1 mmol/L) without evidence of hypoxic-ischemic encephalopathy. Perinatal data were compared with equivalent data from 229 term, neurologically normal infants (control subjects), to identify risk factors for hypoglycemia. Neurodevelopmental outcomes were assessed at a minimum of 18 months.

RESULTS. White matter abnormalities occurred in 94% of infants with hypoglycemia, being severe in 43%, with a predominantly posterior pattern in 29% of cases. Cortical abnormalities occurred in 51% of infants; 30% had white matter hemorrhage, 40% basal ganglia/thalamic lesions, and 11% an abnormal posterior limb of the internal capsule. Three infants had middle cerebral artery territory infarctions. Twenty-three infants (65%) demonstrated impairments at 18 months, which were related to the severity of white matter injury and involvement of the posterior limb of the internal capsule. Fourteen infants demonstrated growth restriction, 1 had macrosomia, and 2 had mothers with diabetes mellitus. Pregnancy-induced hypertension, a family history of seizures, emergency cesarean section, and the need for resuscitation were more common among case subjects than control subjects.

CONCLUSIONS. Patterns of injury associated with symptomatic neonatal hypoglycemia were more varied than described previously. White matter injury was not confined to the posterior regions; hemorrhage, middle cerebral artery infarction, and basal ganglia/thalamic abnormalities were seen, and cortical involvement was common. Early MRI findings were more instructive than the severity or duration of hypoglycemia for predicting neurodevelopmental outcomes.

PATIENTS AND METHODS. We collected information on infant botulism cases by active and passive surveillance, by provision of therapeutic Human Botulism Immune Globulin to suspected cases, and by searching the medical literature. We defined a case as laboratory-confirmed botulism that occurred in an infant ≤12 months of age that was not caused by the ingestion of botulinum toxin in food.

RESULTS. Twenty-six countries representing 5 continents reported the occurrence of at least 1 case of infant botulism among their residents. The United States, Argentina, Australia, Canada, Italy, and Japan, in this order, reported the largest number of cases. A history of honey exposure was significantly more common among case subjects hospitalized outside of the United States than among those who were recently hospitalized in California.

CONCLUSIONS. Most countries have not yet reported cases of infant botulism. This limited reporting of the disease to date contrasts with the known global occurrence of Clostridium botulinum spores in soils and dust and suggests that infant botulism may be underrecognized, underreported, or both. When bulbar palsies, hypotonia, and weakness are present, physicians should consider the possibility of infant botulism even if the patient has not been fed honey. Publication of additional case reports and surveillance summaries will enhance understanding of the occurrence and extent of this underrecognized disease.

METHODS. For 19 children (mean age: 6 years) with mild sleep-disordered breathing, and 14 healthy, ethnically similar and age-similar, control subjects, parents repeated the Pediatric Sleep Questionnaire an average of 12 months after adenotonsillectomy. Children with sleep-disordered breathing underwent repeated overnight measurement of mean oxyhemoglobin saturation. Neurobehavioral tests that yielded significant group differences preoperatively were readministered. Middle cerebral artery velocity measurements were repeated with blinding to sleep study and neuropsychological results, and mixed-design analyses of variance were performed.

RESULTS. The median Pediatric Sleep Questionnaire score significantly improved postoperatively, and there was a significant increase in mean overnight oxyhemoglobin saturation. The middle cerebral artery velocity decreased in the sleep-disordered breathing group postoperatively, whereas control subjects showed a slight increase. A preoperative group difference was reduced by the postoperative assessment, which suggests normalization of middle cerebral artery velocity in those with sleep-disordered breathing. The increase in mean overnight oxyhemoglobin saturation postoperatively was associated with a reduction in middle cerebral artery velocity in a subgroup of children. A preoperative group difference in processing speed was reduced postoperatively. Similarly, a trend for a preoperative group difference in visual attention was reduced postoperatively. Executive function remained significantly worse for the children with sleep-disordered breathing, compared with control subjects, although mean postoperative scores were lower than preoperative scores.

CONCLUSIONS. Otherwise-healthy young children with apparently mild sleep-disordered breathing have potentially reversible cerebral hemodynamic and neurobehavioral changes.

METHODS. In a single-center, randomized, placebo-controlled trial, we studied 107 six-week-old infants. The infants were randomly assigned to receive either an intramuscular injection of 400 µg of cobalamin or no intervention. Concentrations of cobalamin and folate in serum and total homocysteine, methylmalonic acid, and cystathionine in plasma were determined at enrollment and at the age of 4 months.

RESULTS. There were no significant differences between the intervention group (n = 54) and the control group (n = 53) in the concentrations of any vitamin marker at baseline (6 weeks). At 4 months, the supplement-treated infants had a 75% higher median serum cobalamin level and remarkable reductions in median plasma total homocysteine (from 7.46 to 4.57 µmol/L) and methylmalonic acid (from 0.58 to 0.20 µmol/L) levels, whereas levels of both metabolites were essentially unchanged during the follow-up period in the control group.

CONCLUSIONS. Cobalamin supplementation changed all markers of impaired cobalamin status (low cobalamin, high total homocysteine, and high methylmalonic acid levels) toward a profile observed in cobalamin-replete older children and adults. Therefore, the high total homocysteine and methylmalonic acid levels reported for a large fraction of infants reflect not immature metabolism but rather insufficient cobalamin levels to fully sustain cobalamin-dependent reactions fully.

METHODS. As part of the prospective, longitudinal, multisite study of children with prenatal cocaine exposure (Maternal Lifestyle Study), school records were reviewed for 943 children at 7 years to determine involvement in special education outcomes: (1) individualized education plan; (2) special education conditions; (3) support services; (4) special education classes; and (5) speech and language services. Logistic regression was used to examine the effect of prenatal cocaine exposure on these outcomes with environmental, maternal, and infant medical variables as covariates, as well as with and without low child IQ.

RESULTS. Complete data for each analysis model were available for 737 to 916 children. When controlling for covariates including low child IQ, prenatal cocaine exposure had a significant effect on individualized education plan. When low child IQ was not included in the model, prenatal cocaine exposure had a significant effect on support services. Male gender, low birth weight, white race, and low child IQ also predicted individualized education plan. Low birth weight and low child IQ were significant in all models. White race was also significant in speech and language services. Other covariate effects were model specific. When included in the models, low child IQ accounted for more of the variance and changed the significance of other covariates.

CONCLUSIONS. Prenatal cocaine exposure increased the likelihood of receiving an individualized education plan and support services, with adjustment for covariates. Low birth weight and low child IQ increased the likelihood of all outcomes. The finding that white children were more likely to get an individualized education plan and speech and language services could indicate a greater advantage in getting educational resources for this population.

METHODS. Randomized, controlled trials comparing higher- versus lower-dosage dexamethasone regimens in ventilated preterm infants were identified by searching the main electronic databases, references from relevant studies, and abstracts from the Societies for Pediatric Research (from 1990 onward). Eligibility and quality of trials were assessed, and data on study design, patient characteristics, and relevant outcomes were extracted.

RESULTS. Six studies that enrolled a total of 209 participants were included; 2 studies contrasted cumulative dexamethasone doses in the higher ranges (>2.7 mg/kg in the higher-dosage regimen) and 4 in the lower ranges (≤2.7 mg/kg in the higher-dosage regimen). Meta-analysis revealed no effect of dexamethasone dose on rates of death and neurodevelopmental sequelae in these 2 subgroups. Subgroup analysis of the studies contrasting dexamethasone doses in the higher ranges showed that the higher dose of dexamethasone was more effective in reducing the occurrence of chronic lung disease than was the lower dose. Interpretation of these data was hampered by the small samples of randomly assigned children, heterogeneity of study populations and designs, use of late rescue glucocorticoids, and lack of long-term neurodevelopmental data in some studies.

CONCLUSIONS. Recommendations for optimal dexamethasone doses for preterm infants at risk for chronic lung disease cannot be based on current evidence. A well-designed, large, randomized, controlled trial is urgently needed to establish the optimal dexamethasone dosage regimen.

METHODS. Children who were 5 to 12 years of age and presented to Mulago Hospital, Kampala, Uganda, with cerebral malaria (n = 44) or uncomplicated malaria (n = 54), along with healthy, asymptomatic community children (n = 89), were enrolled in a prospective cohort study of cognition. Cognitive testing was performed at enrollment and 2 years later. The primary outcome was presence of a deficit in ≥1 of 3 cognitive areas tested.

RESULTS. At 2-year follow-up testing, 26.3% of children with cerebral malaria and 12.5% with uncomplicated malaria had cognitive deficits in ≥1 area, as compared with 7.6% of community children. Deficits in children with cerebral malaria were primarily in the area of attention (cerebral malaria, 18.4%, vs community children, 2.5%). After adjustment for age, gender, nutrition, home environment, and school level, children with cerebral malaria had a 3.67-fold increased risk for a cognitive deficit compared with community children. Cognitive impairment at 2-year follow-up was associated with hyporeflexia on admission and neurologic deficits 3 months after discharge.

CONCLUSIONS. Cerebral malaria is associated with long-term cognitive impairments in 1 of 4 child survivors. Future studies should investigate the mechanisms involved so as to develop interventions aimed at prevention and rehabilitation.

METHODS. Data represent all health care encounters for infants who were born in South Carolina between 2000 and 2002 and were healthy at birth and continuously enrolled in fee-for-service Medicaid (n = 41696). We separately examined in the first and second years of life use of preventive care doctor visits, sick-infant doctor visits, emergency department visits, hospital admissions, and both emergency department visits and hospitalizations for ambulatory care–sensitive conditions. We compared these outcomes for infants of adolescent mothers (aged 11–17 years) and older mothers (aged 18–47 years), adjusting for individual characteristics of mothers and infants.

RESULTS. In unadjusted results, infants of adolescent mothers used more health care in 9 of 12 use categories. For example, in year 1, they had an average of 1.71 emergency department visits and 1.39 hospitalizations, compared with 1.26 and 1.18, respectively, for infants of older mothers. In results that were adjusted only for infant and delivery characteristics, they similarly used more services in most categories. After adjustment for either mothers' characteristics alone or those of both the infant/delivery and mothers, there was evidence that they had modestly more sick-infant doctor visits and hospital admissions in year 1 and notably more hospital admissions for ambulatory care–sensitive conditions.

CONCLUSIONS. Infants of adolescent mothers are more likely than infants of older mothers to use a variety of health care services that suggest poorer health. A considerable proportion of this greater use seems to be attributable to specific characteristics of mothers, such as socioeconomic characteristics, rather than to an inability that is common among adolescents to promote infant health or to use health care appropriately.

METHODS. We prospectively recruited preterm infants who needed mechanical ventilation and exogenous surfactant for treatment of moderate/severe respiratory distress syndrome and could not be extubated before day 3 of life. ¹³C-labeled dipalmitoyl-phosphatidylcholine was administered endotracheally as tracer before extubation, for estimation of surfactant disaturated phosphatidylcholine pool size and half-life. Patients were retrospectively divided into 3 groups, that is, extubation failure if, after extubation, they needed reintubation or continuous positive airway pressure treatment of ≥6 cmH₂O and fraction of inspired oxygen of >0.4, extubation success if they did not meet the failure criteria, and not extubated if they needed ongoing ventilation. Clinical and respiratory parameters were recorded hourly.

RESULTS. Reliable kinetic data could be obtained for 63 of the 88 enrolled neonates. Sixteen, 23, and 24 neonates were categorized in the extubation failure, extubation success, and not extubated groups, respectively. Clinical and demographic characteristics did not differ between the extubation failure and extubation success groups. Disaturated phosphatidylcholine pool size was smaller in the extubation failure group than in the extubation success group (25 ± 12 vs 43 ± 24 mg/kg) and was 37 ± 32 mg/kg in the not extubated group. Disaturated phosphatidylcholine half-life was 19 ± 7, 24 ± 12, and 28 ± 18 hours in the extubation failure, extubation success, and not extubated groups, respectively.

CONCLUSIONS. In a selected population of preterm infants with moderate/severe respiratory distress syndrome who could not be extubated in the first 3 days of life, infants who were reintubated or needed high continuous positive airway pressure settings after extubation had a smaller disaturated phosphatidylcholine pool size than did those who were successfully extubated or needed low continuous positive airway pressure settings.

METHODS. We fitted logistic regression models to estimate odds ratios and 95% confidence intervals for the independent and joint effects of these single-nucleotide polymorphisms and in utero and secondhand tobacco smoke exposure on asthma and wheeze outcomes.

RESULTS. Exposures to in utero maternal smoking and secondhand tobacco smoke were associated with wheezing. Children who were homozygous for the Arg16 allele and were exposed to maternal smoking in utero were at a threefold increased risk for lifetime wheeze compared with children who were unexposed and had at least 1 Gly16 allele. We found similar joint effects of secondhand tobacco smoke and Arg16Gly with wheezing. The risk for lifetime, current, and nocturnal wheeze increased with the number of smokers at home among Arg16 homozygous children. The results were consistent in 2 cohorts of children recruited in 1993 and 1996. Diplotype-based analyses were consistent with the single-nucleotide polymorphism–specific results. No associations were found for Glu27Gln.

CONCLUSIONS. Both in utero and childhood exposure to tobacco smoke were associated with an increased risk for wheeze in children, and the risks were greater for children with the Arg16Arg genotype or 2 copies of the Arg16–Gln27 diplotype. Exposures to smoking need to be taken into account when evaluating the effects of β2-adrenergic receptor gene variants on respiratory health outcomes.

METHODS. This confidential survey study was administered to adult volunteers via the Internet. The surveys depicted a hypothetical vignette of a threatened delivery at gestational age of 23 weeks, with prognostic outcome information framed as either survival with lack of disability (positive frame) or chance of dying and likelihood of disability among survivors (negative frame). Participants were randomly assigned to receive either the positively or negatively framed vignette. They were then asked to choose whether they would prefer resuscitation or comfort care. After completing the survey vignette, participants were directed to a questionnaire designed to test the secondary hypothesis and to explore possible factors associated with treatment decisions.

RESULTS. A total of 146 subjects received prognostic information framed as survival data and 146 subjects received prognostic information framed as mortality data. Overall, 24% of the sample population chose comfort care and 76% chose resuscitation. A strong trend was detected toward a framing effect on treatment preference; respondents for whom prognosis was framed as survival data were more likely to elect resuscitation. This framing effect was significant in a multivariate analysis controlling for religiousness, parental status, and beliefs regarding the sanctity of life. Of these covariates, only religiousness modified susceptibility to framing; participants who were not highly religious were significantly more likely to be influenced to opt for resuscitation by the positive frame than were participants who were highly religious.

CONCLUSIONS. Framing bias may compromise efforts to approach prenatal counseling in a nondirective manner. This is especially true for subsets of participants who are not highly religious.

METHODS. Data from 2558 infants in an ongoing prospective birth cohort study in the Netherlands were analyzed. Data on the main determinants (introduction of cow milk products and other food products), outcomes (eczema; atopic dermatitis [United Kingdom Working Party criteria]; recurrent wheeze; any sensitization; sensitization against cow milk, hen egg, peanut, and at least 1 inhalant allergen), and confounders were collected by repeated questionnaires at 34 weeks of gestation and 3, 7, 12, and 24 months postpartum. Information on sensitization was gathered by venous blood collections performed during home visits at age 2. Analyses were performed by multiple logistic regression analyses.

RESULTS. More delay in introduction of cow milk products was associated with a higher risk for eczema. In addition, a delayed introduction of other food products was associated with an increased risk for atopy development at the age of 2 years. Exclusion of infants with early symptoms of eczema and recurrent wheeze (to avoid reverse causation) did not essentially change our results.

DISCUSSION. Delaying the introduction of cow milk or other food products may not be favorable in preventing the development of atopy.

METHODS. Prospectively gathered, standardized, maternal and neonatal data for infants at ≥35 weeks of gestation who were born between January 1, 1994, and December 31, 2000, were extracted from the Nova Scotia Atlee Perinatal Database. Infants with Rh factor isoimmunization, significant congenital or chromosomal abnormalities, or severe peripartum asphyxia were excluded. Comparisons were made on the basis of peak total serum bilirubin levels. Diagnoses were obtained through data linkage with the Medical Services Insurance Database for office visits and the Canadian Institute for Health Information Database for hospital admissions. The registration file provided information allowing calculation of follow-up times, which were determined for each separate outcome. Follow-up periods ranged from 2 to 9 years, with the end point being the first time the diagnostic code was encountered in either database. Cox proportional-hazards regression analyses were used to examine the relationships between outcomes and total serum bilirubin levels.

RESULTS. Of 61238 infants included in the study cohort, 4010 (6.7%) did not have linkage data, which left 56019 infants for analysis. There were no cases of kernicterus and no significant differences in rates of cerebral palsy, deafness, developmental delay, or visual abnormalities between the groups. There were suggestions of associations with attention-deficit disorder in the severe hyperbilirubinemia group and with autism in the combined moderate and severe hyperbilirubinemia group.

CONCLUSIONS. There was no increase in adverse effects reported previously to be associated with bilirubin toxicity. Associations with developmental delay, attention-deficit disorder, and autism were observed.

METHODS. Thirty-five HIV-infected, 35 HIV-affected, and 90 control children aged 18 to 72 months were assessed by using the Bayley Scales of Infant Development II, Peabody Developmental Motor Scales, Snijders-Oomen Nonverbal Intelligence Test, and Rossetti Infant-Toddler Language Scale, as appropriate for age.

RESULTS. Overall, 60% of HIV-infected children had severe delay in cognitive function, 29% had severe delay in motor skills, 85% had delays in language expression, and 77% had delays in language comprehension, all significantly higher rates as compared with control children. Young HIV-infected children (aged 18–29 months) performed worse, with 91% and 82% demonstrating severe mental and motor delay, respectively, compared with 46% and 4% in older HIV-infected children (aged 30–72 months). HIV-affected children had significantly more motor and language expression delay than control children.

CONCLUSIONS. The impact of the HIV pandemic on children's neurodevelopment extends beyond the direct effect of the HIV virus on the central nervous system. AIDS orphans and HIV-negative children whose mothers had AIDS demonstrated significant delays in their neurodevelopment, although to a lesser degree and in fewer developmental domains than HIV-infected children. Young HIV-infected children were the most severely afflicted group, indicating the need for early interventions. Older children performed better as a result of a "survival effect," with only those children with less aggressive disease surviving.

METHODS. We collected data from infants ages birth to 12 months of age who were hospitalized after an apparent life-threatening event during a 5-year time period. Patients were evaluated for subsequent death, child abuse, or adverse neurological outcome (chronic epilepsy or developmental delay).

RESULTS. A total of 471 patients met inclusion criteria and were followed an average of 5.1 years. Two patients died after developing chronic epilepsy and severe developmental delay. Fifty-four (11%) patients were diagnosed as being a victim of child abuse, but only 2 were identified at initial presentation. There were 23 (4.9%) patients with adverse neurological outcomes, including 17 (3.6%) with chronic epilepsy and 14 (3.0%) with developmental delay. Of those who developed chronic epilepsy, 71% returned within 1 month of the initial apparent life-threatening event with a second event. Neurological evaluation at the time of the apparent life-threatening event had low yield for predicting those who would develop chronic epilepsy.

CONCLUSIONS. Infants who suffer an apparent life-threatening event are at risk for subsequent child abuse and adverse neurological outcomes. Deaths were uncommon and only occurred in the setting of severe developmental delay and seizure disorders. Neurological evaluation during hospitalization for a first apparent life-threatening event is of low yield, but close follow-up is essential.