bluuebunny/crossref_metadata_2025 huggingface dataset:
Hepatitis A in Hispanic Children Who Live Along the United States–Mexico Border: The Role of International Travel and Food-Borne Exposures
Authors: Weinberg Michelle , Hopkins Jackie , Farrington Leigh , Gresham Louise , Ginsberg Michele , Bell Beth P.
Published: August 2004

Objectives. Hispanic children who live along the United States–Mexico border historically have had among the highest hepatitis A rates in the United States, but risk factors have not been well characterized. The objective of this study was to examine risk factors associated with acute hepatitis A virus (HAV) infection in Hispanic children who live along the United States–Mexico border in San Diego County, California.

Methods. In this case-control study, hepatitis A cases among Hispanic children who were younger than 18 years reported from June 1998 through August 2000 were matched by age group and exposure period to Hispanic children who were susceptible to HAV infection. Participants and their families were interviewed about demographic information and potential sources of HAV infection, including attending child care, food and waterborne exposures, cross-border and other international travel, and travel-related activities.

Results. Participants included 132 children with hepatitis A and 354 control subjects. The median age of study participants was 7 years (range: 1–17). Sixty-seven percent of case-patients traveled outside the United States during the incubation period, compared with 25% of the children without hepatitis A (odds ratio [OR]: 6.3; 95% confidence interval [CI]: 4.0–9.7); all children, except 1, had traveled to Mexico. In multivariate analysis, hepatitis A was associated with having eaten food from a taco stand or street food vendor (adjusted OR: 17.0; 95% CI: 4.1–71.1) and having eaten salad/lettuce (adjusted OR: 5.2; 95% CI: 1.3–20.1) during travel.

Conclusions. Hepatitis A among Hispanic children who live in an urban area of the United States–Mexico border is associated with cross-border travel to Mexico and food-borne exposures during travel. Travelers to areas where hepatitis A is endemic should receive hepatitis A vaccine before travel.
Conscious Sedation of Children With Propofol Is Anything but Conscious
Authors: Reeves Scott T. , Havidich Jeana E. , Tobin D. Patrick
Published: August 2004

Objective. To determine the depth of sedation required for bone marrow aspiration and intrathecal injection of chemotherapeutic agents in children using a bispectral (BIS) index monitor and clinical assessment by an independent observer.

Methods. Sixteen children who were undergoing 19 intrathecal chemotherapy and bone marrow aspirations were enrolled in the study. Their ages ranged from 23 months to 190 months with a mean of 79 months. The BIS index was recorded every 5 minutes by an independent observer. The patients received only intravenous propofol for sedation. There were no complications during the procedures.

Results. The mean BIS score was 62.8 ± 9.6. The mean low BIS score was 29.7 ± 13.7, indicating a level of deep sedation and/or general anesthesia was necessary to induce the desired stated of consciousness that would permit the practitioner to perform the procedure. The average dose of propofol was 166 ± 47 μg/kg/min. Mean Aldrete score for level of consciousness was 0.9 ± 0.4, indicating a depressed level of consciousness. The mean activity level was 1.0 ± 0.4, indicating impaired movement.

Conclusions. Children who undergo conscious sedation with propofol for intrathecal chemotherapy and bone marrow aspiration demonstrate BIS values and clinical assessments consistent with deep sedation. Because of an increased risk of adverse events when children undergo deep sedation, appropriate parental informed consent, age-appropriate resuscitative equipment, and skilled anesthesia personnel should be present for rescue in the event of cardiovascular and respiratory complications from deep sedation.
Neonatal Procedural Pain and Preterm Infant Cortisol Response to Novelty at 8 Months
Authors: Grunau Ruth E. , Weinberg Joanne , Whitfield Michael F.
Published: August 2004

Objectives. Stress systems may be altered in the long term in preterm infants for multiple reasons, including early exposure to procedural pain in neonatal intensive care. This question has received little attention beyond hospital discharge. Stress responses (cortisol) to visual novelty in preterm infants who were born at extremely low gestational age (ELGA; ≤28 weeks), very low gestational age (VLGA; 29–32 weeks), and term were compared at 8 months of age corrected for prematurity (corrected chronological age [CCA]). In addition, among the preterm infants, we evaluated whether cortisol levels at 8 months were related to neonatal exposure to procedural pain and morphine in the neonatal intensive care unit.

Methods. Seventy-six infants, 54 preterm (≤32 weeks’ GA at birth) and 22 term-born infants who were seen at 8 months CCA composed the study sample, after excluding those with major sensory, motor, or cognitive impairment. Salivary cortisol was measured before (basal) and 20 minutes after introduction of novel toys (post 1) and after developmental assessment (post 2).

Results. Salivary cortisol was significantly higher in ELGA infants at 8 months, compared with the VLGA and term groups before and after introduction of visual novelty. Term-born and VLGA infants showed a slight decrease in cortisol when playing with novel toys, whereas the ELGA group showed higher basal and sustained levels of cortisol. After controlling for early illness severity and duration of supplemental oxygen, higher basal cortisol levels in preterm infants at 8 months’ CCA were associated with higher number of neonatal skin-breaking procedures. In contrast, cortisol responses to novelty were predicted equally well by neonatal pain or GA at birth. No relationship between morphine dosing and cortisol response was demonstrated in these infants.

Conclusions. ELGA preterm infants show a different pattern of cortisol levels before and after positive stimulation of visual novelty than more maturely born, VLGA preterm and term-born infants. Exposure to high numbers of skin-breaking procedures may contribute to “resetting” basal arousal systems in preterm infants.
Epidemiology of Childhood Tuberculosis in the United States, 1993–2001: The Need for Continued Vigilance
Authors: Nelson Lisa J. , Schneider Eileen , Wells Charles D. , Moore Marisa
Published: August 2004

Objective. To describe trends and highlight epidemiologic and clinical characteristics of childhood tuberculosis (TB) in the United States.

Methods. All verified TB cases reported to the national TB surveillance system from 1993 to 2001 were included. A child was defined as a person younger than 15 years.

Results. A total of 11 480 childhood TB cases were reported. Case rates (TB cases/100 000 population) in all children declined from 2.9 (n = 1663) in 1993 to 1.5 (n = 931) in 2001. Among children, those who were younger than 5 years had the highest rate. California, Texas, and New York accounted for 48% of all childhood TB cases. In 2001, TB case rates were higher for foreign-born (12.2) than US-born children (1.1). Hispanic and non-Hispanic black children accounted for nearly three quarters of all cases. Twenty-four percent of children with TB were foreign-born children, with the largest number originating from Mexico (39.8%), the Philippines (8.6%), and Vietnam (5.7%). Most children had evidence of pulmonary TB disease (78.9%). Among culture-positive cases without previous TB, drug resistance to at least isoniazid was 7.3% and to isoniazid and rifampin was 1.6%. In 1999, 82.9% of children received directly observed therapy for at least part of their treatment and 94.8% completed treatment.

Conclusions. Although the overall TB case number among children is declining in the United States, certain groups of children (eg, younger children, racial and ethnic minorities, foreign-born) are at higher risk for TB. As the United States moves toward the elimination of TB, future efforts should endeavor to prevent all cases of childhood TB.
Developing Community-Specific Recommendations for First-Line Treatment of Acute Otitis Media: Is High-Dose Amoxicillin Necessary?
Authors: Garbutt Jane , St. Geme Joseph W. , May Ariane , Storch Gregory A. , Shackelford Penelope G.
Published: August 2004

Objectives. National recommendations are to use high-dose amoxicillin (80–90 mg/kg per day) to treat uncomplicated acute otitis media (AOM) in children who are at high risk for infection with nonsusceptible Streptococcus pneumoniae (NSSP). However, high-dose treatment may not be necessary if the local prevalence of NSSP is low. The objective of this study was to estimate the local prevalence of NSSP in children with acute upper respiratory illnesses and to develop community-specific recommendations for first-line empiric treatment of AOM.

Methods. We conducted a cross-sectional prevalence study in the offices of 7 community pediatricians in St Louis, Missouri. S pneumoniae was isolated from nasopharyngeal swabs collected from children who were younger than 7 years and had AOM, nonspecific upper respiratory infection, cough, acute sinusitis, or pharyngitis. Children were excluded from the study when they had received an antibiotic in the previous 4-week period. Parents and providers completed a brief questionnaire to assess risk factors for carriage of NSSP. On the basis of National Clinical Chemistry Laboratory Standards, isolates with a penicillin minimum inhibitory concentration ≥0.12 μg/mL were considered to be nonsusceptible to penicillin (NSSP), and isolates with a penicillin minimum inhibitory concentration >2 μg/mL were categorized as nonsusceptible to standard-dose amoxicillin (35–45 mg/kg per day; NSSP-A).

Results. S pneumoniae was isolated from the nasopharynx of 85 (40%) of 212 study patients (95% confidence interval [CI]: 33%–47%); 41 (48%) of 85 isolates were NSSP (95% CI: 37%–59%), and 6 (7%) were NSSP-A (95% CI: 1.5%–13%). Among the 212 study patients, the prevalence of NSSP was 19% (95% CI: 14%–25%), and the prevalence of NSSP-A was 3% (95% CI: 0.6%–5%). Carriage of NSSP was increased in child care attendees compared with nonattendees (29% vs 14%; odds ratio: 2.6; 95% CI: 1.3–5.2).

Conclusions. In our community, although the prevalence of NSSP among isolates of S pneumoniae identified from the nasopharynx of symptomatic children is high (48%), the probability of NSSP-A infection among symptomatic children is <5%. Our data support a recommendation to treat most children who have uncomplicated AOM with standard-dose amoxicillin. Children who attend child care or have recently received an antibiotic may require treatment with high-dose amoxicillin. Other communities may benefit from a similar assessment of the prevalence of NSSP and NSSP-A.
Marginal Increase in Cost and Excess Length of Stay Associated With Nosocomial Bloodstream Infections in Surviving Very Low Birth Weight Infants
Authors: Payne Nathaniel R. , Carpenter Joseph H. , Badger Gary J. , Horbar Jeffrey D. , Rogowski Jeannette
Published: August 2004

Objective. Nosocomial bloodstream infections (NBIs) are associated with serious morbidity and prolonged length of stay (LOS) in very low birth weight (VLBW) infants. However, the marginal costs and excess LOS associated with these infections have never been measured in different birth weight (BW) categories after adjustment for many of the potentially confounding demographic variables, comorbidities, and treatments. The objective of this study was to measure the marginal cost and excess LOS caused by NBIs in surviving VLBW infants in different BW categories.

Methods. This retrospective study examined data previously collected as part of the Neonatal Intensive Care Quality Improvement Collaborative 2000 and the Vermont Oxford Network clinical outcomes database. Univariate analyses and multiple regression were used to examine the effect of NBIs on hospital costs and LOS. Seventeen neonatal intensive care units that participated in the Neonatal Intensive Care Quality Improvement Collaborative 2000 submitted both clinical and financial data on their VLBW infants who were born from January 1, 1998, to December 31, 1999. This study included data from both university and community hospitals.

Results. NBIs occurred in 19.7% of 2809 patients included in this study. NBI was associated with significantly increased treatment costs for infants with BW 751 to 1500 g. The marginal costs of NBIs, as estimated by multiple regression, varied from $5875 for VLBW infants with a BW of 401 to 750 g to $12 480 for those with BW of 751 to 1000 g. LOS was significantly increased in all BW categories. The excess LOS estimated by multiple regression varied from 4 days in VLBW infants with a BW of 1001 to 1251 g to 7 days in those with a BW of 751 to 1000 g.

Conclusions. NBIs are associated with increased hospital treatment costs and LOS but by varying amounts depending on the BW. Preventing a single NBI could reduce the treatment costs of a VLBW infant by at least several thousand dollars. These savings are a greater percentage of the total treatment costs in VLBW infants with BW 1001 to 1500 g than in smaller infants.
Initial Hypoglycemia and Neonatal Brain Injury in Term Infants With Severe Fetal Acidemia
Authors: Salhab Walid A. , Wyckoff Myra H. , Laptook Abbot R. , Perlman Jeffrey M.
Published: August 2004

Objective. To determine the potential contribution of initial hypoglycemia to the development of neonatal brain injury in term infants with severe fetal acidemia.

Methods. A retrospective chart review was conducted of 185 term infants who were admitted to the neonatal intensive care unit between January 1993 and December 2002 with an umbilical arterial pH <7.00. Short-term neurologic outcome measures include death as a consequence of severe encephalopathy and evidence of moderate to severe encephalopathy with or without seizures. Hypoglycemia was defined as an initial blood glucose ≤40 mg/dL.

Results. Forty-one (22%) infants developed an abnormal neurologic outcome, including 14 (34%) with severe hypoxic ischemic encephalopathy who died, 24 (59%) with moderate to severe hypoxic ischemic encephalopathy, and 3 (7%) with seizures. Twenty-seven (14.5%) of the 185 infants had an initial blood sugar ≤40 mg/dL. Fifteen (56%) of 27 infants with a blood sugar ≤40 mg/dL versus 26 (16%) of 158 infants with a blood sugar >40 mg/dL had an abnormal neurologic outcome (odds ratio [OR]: 6.3; 95% confidence interval [CI]: 2.6–15.3). Infants with abnormal outcomes and a blood sugar ≤40 mg/dL versus >40 mg/dL had a higher pH (6.86 ± 0.07 vs 6.75 ± 0.09), a lesser base deficit (−19 ± 4 vs −23.8 ± 4 mEq/L), and lower mean arterial blood pressure (34 ± 10 vs 45 ± 14 mm Hg), respectively. There was no difference between groups in the proportion of infants who required cardiopulmonary resuscitation (7 [46%] vs 15 [57%]) and those with a 5-minute Apgar score <5 (11 [73%] vs 22 [85%]). By multivariate logistic analysis, 4 variables were significantly associated with abnormal outcome: initial blood glucose ≤40 mg/dL versus >40 mg/dL (OR: 18.5; 95% CI: 3.1–111.9), cord arterial pH ≤6.90 versus >6.90 (OR: 9.8; 95% CI: 2.1–44.7), a 5-minute Apgar score ≤5 versus >5 (OR: 6.4; 95% CI: 1.7–24.5), and the requirement for intubation with or without cardiopulmonary resuscitation versus neither (OR: 4.7; 95% CI: 1.2–17.9).

Conclusion. Initial hypoglycemia is an important risk factor for perinatal brain injury, particularly in depressed term infants who require resuscitation and have severe fetal acidemia. It remains unclear, however, whether earlier detection of hypoglycemia, such as in the delivery room, in this population could modify subsequent neurologic outcome.
Brain Volumes in Adult Survivors of Very Low Birth Weight: A Sibling-Controlled Study
Authors: Fearon Paul , O’Connell Paul , Frangou Sophia , Aquino Peter , Nosarti Chiara , Allin Matthew , Taylor Mark , Stewart Ann , Rifkin Larry , Murray Robin
Published: August 2004

Objectives. To establish whether adults who were born very low birth weight (VLBW) show altered volumes of certain brain structures.

Methods. Unmatched case-control study was conducted of 33 individuals from a cohort of VLBW (<1500g) infants who were born between 1966 and 1977 and 18 of their normal birth weight siblings. Whole brain, gray matter, ventricular, corpus callosum, and hippocampal volumes were measured on structural magnetic resonance imaging scans.

Results. VLBW individuals had a 46% increase in total ventricular volume and a 17% reduction in posterior corpus callosum volume. No differences in whole brain, gray matter, or hippocampal volumes were observed.

Conclusion. Specific differences exist in the volumes of certain brain structures in adults who were born VLBW compared with their normal birth weight siblings.
Clinical Outcomes of Near-Term Infants
Authors: Wang Marvin L. , Dorer David J. , Fleming Michael P. , Catlin Elizabeth A.
Published: August 2004

Objective. To test the hypothesis that near-term infants have more medical problems after birth than full-term infants and that hospital stays might be prolonged and costs increased.

Methods. Electronic medical record database sorting was conducted of 7474 neonatal records and subset analyses of near-term (n = 120) and full-term (n = 125) neonatal records. Cost information was accessed. Length of hospital stay, Apgar scores, clinical diagnoses (temperature instability, jaundice, hypoglycemia, suspicion of sepsis, apnea and bradycardia, respiratory distress), treatment with an intravenous infusion, delay in discharge to home, and hospital costs were assessed.

Results. Data from 90 near-term and 95 full-term infants were analyzed. Median length of stay was similar for near-term and full-term infants, but wide variations in hospital stay were documented for near-term infants after both vaginal and cesarean deliveries. Near-term and full-term infants had comparable 1- and 5-minute Apgar scores. Nearly all clinical outcomes analyzed differed significantly between near-term and full-term neonates: temperature instability, hypoglycemia, respiratory distress, and jaundice. Near-term infants were evaluated for possible sepsis more frequently than full-term infants (36.7% vs 12.6%; odds ratio: 3.97) and more often received intravenous infusions. Cost analysis revealed a relative increase in total costs for near-term infants of 2.93 (mean) and 1.39 (median), resulting in a cost difference of $2630 (mean) and $429 (median) per near-term infant.

Conclusions. Near-term infants had significantly more medical problems and increased hospital costs compared with contemporaneous full-term infants. Near-term infants may represent an unrecognized at-risk neonatal population.
A National Assessment of Children With Special Health Care Needs: Prevalence of Special Needs and Use of Health Care Services Among Children in the Military Health System
Authors: Williams Thomas V. , Schone Eric M. , Archibald Nancy D. , Thompson Joseph W.
Published: August 2004

Objective. Children are frequently perceived to be healthy, low-risk individuals with a majority of clinical services devoted to health maintenance and preventive clinical services. However, a subset of children have unique needs that require specialized care to achieve optimal health outcomes. The purpose of this research was to use survey tools that have been developed to identify children with special health care needs (CSHCN) to measure prevalence and resource needs of these children in the military health system (MHS).

Methods. The US Department of Defense manages the MHS, which is one of the largest integrated health care systems in the world and provides care to almost 2 000 000 children. We incorporated the CSHCN survey screener and assessment questions into the annual health care survey of beneficiaries who are eligible for benefits within the MHS. In addition, we used claims information available from inpatient and outpatient services. We used parent reports from the survey to estimate the prevalence of CSHCN. Incorporating claims data and restricting our analyses to those who were enrolled continuously in a military health maintenance organization (TRICARE Prime), we described utilization of different types of health care resources and compared CSHCN with their healthy counterparts. Finally, we examined alternative types of special needs and performed regression analyses to identify the major determinants of health needs and resource utilization to guide system management and policy development.

Results. CSHCN compose 23% of the TRICARE Prime enrollees who are younger than 18 years and whose parents responded to the survey. The needs of a majority of these children consist of prescription medications and services targeting medical, mental health, and educational needs. CSHCN experience 5 times as many admissions and 10 times as many days in hospitals compared with children without special needs. CSHCN are responsible for nearly half of outpatient visits for enrolled children and more than three quarters of inpatient days. Service utilization varies dramatically by type of special need and other demographic variables.

Conclusion. CSHCN represent a major challenge to organized systems of care and our society. Because they represent a group of children who are particularly at risk with potential for improved health outcomes, efforts to improve quality, coordinate care, and optimize efficiency should focus on this target population.
Insurance for Children With Special Health Care Needs: Patterns of Coverage and Burden on Families to Provide Adequate Insurance
Authors: Davidoff Amy J.
Published: August 2004

Objective. To update national estimates of insurance coverage for children with special health care needs (CSHCN) to reflect better the current economic and policy environment and to examine the burden on families and adequacy of coverage.

Methods. I analyzed data on children who were aged 0 to 17 and included in the sample child files of the 2000 and 2001 National Health Interview Survey (NHIS). CSHCN were identified using a noncategorical approach. Various measures of insurance coverage type, premium contributions, unmet need for care, and out-of-pocket spending were compared for CSHCN and children without special needs across all incomes and stratified by poverty status.

Results. Compared with other children, CSHCN had higher rates of public insurance (29.8% vs 18.5%), lower rates of private insurance (62.5% vs 69.1%), and a smaller percentage without insurance (8.1% vs 11.5%). More than 13% of low-income CSHCN were uninsured. Most (78.1%) families of CSHCN contributed to private insurance premiums. Family premium contributions for employer-sponsored insurance plans averaged $2058, or 4.4% of income; premiums for private nongroup insurance were higher ($3593) and consumed a larger percentage of income (6.6%). For children with insurance, rates of unmet need for specific services were relatively low, suggesting that insurance coverage was adequate. However, almost 20% of low-income CSHCN experienced some form of unmet need and of out-of-pocket spending was significantly higher for families with CSHCN compared with those without CSHCN.

Conclusions. CSHCN are more likely to have insurance coverage, but among low-income CSHCN, lack of insurance remains a problem. In addition, the burden on families of CSHCN to provide insurance is greater, yet coverage purchased is not always adequate to meet the needs of many children and places addition burdens on families to pay directly for care.
Bias in Reported Neurodevelopmental Outcomes Among Extremely Low Birth Weight Survivors
Authors: Castro Lisa , Yolton Kimberly , Haberman Beth , Roberto Nancy , Hansen Nellie I. , Ambalavanan Namasivayam , Vohr Betty R. , Donovan Edward F.
Published: August 2004

Objectives. The purpose of this study was to investigate possible bias in the evaluation of neurodevelopment and somatic growth at 18 to 22 months' postmenstrual age among extremely low birth weight (ELBW) survivors (401–1000 g at birth).

Methods. Data from a cohort of 1483 ELBW infant survivors who were born January 1993 through December 1994 and cared for at centers in the Neonatal Research Network of the National Institute of Child Health and Human Development were examined retrospectively. Children who were compliant with an 18- to 22-month follow-up visit, who visited but were not measured, or who made no visit were compared regarding 4 outcomes: 1) Bayley Scales of Infant Development, 2nd edition, Mental Developmental Index (MDI) <70 and 2) Psychomotor Developmental Index (PDI) <70, 3) presence or absence of cerebral palsy, and 4) weight <10th percentile for age. Logistic regression models were used to predict likelihood of these outcomes for children with no follow-up evaluation, and predicted probability distributions were compared across the groups.

Results. Compared with children who were lost to follow-up, those who were compliant with follow-up were more likely to have been 1 of a multiple birth, to have received postnatal glucocorticoids, and to have had chronic lung disease. These factors were significantly associated with MDI and PDI <70 in the compliant group. Chronic lung disease was associated with increased risk of cerebral palsy (CP). MDI and PDI scores <70 were found in 37% and 29% of children who were evaluated at follow-up, respectively. Prediction models revealed that 34% and 26% of infants in the no-visit group would have had MDI and PDI scores <70. Compliant children tended to have greater incidence of MDI <70 compared with those predicted in the no-visit group but not PDI <70. CP was identified in 17% of the compliant group and predicted for 18% of the no-visit group. Predicted probabilities of having CP were marginally higher among the no-visit infants compared with those who were compliant with follow-up. There were no statistically significant somatic growth differences among the compliant, visit but not measured, and no-visit groups.

Conclusion. ELBW infant survivors who weighed 401 to 1000 g at birth and who are compliant with follow-up evaluations may have worse Bayley Scales of Infant Development, 2nd edition, MDI scores than infants with no visit. Thus, follow-up studies based on infants who are compliant with follow-up care may lead to an overestimation of adverse outcomes in ELBW survivors.
What Follows Newborn Screening? An Evaluation of a Residential Education Program for Parents of Infants With Newly Diagnosed Cystic Fibrosis
Authors: Sawyer Susan M. , Glazner Judith A.
Published: August 2004

Objective. The diagnosis of a severe life-limiting condition, such as cystic fibrosis (CF), is generally followed by assessment and treatment of the child and education and counseling for parents. The introduction of newborn screening for CF provides an opportunity for standardized assessment and education. The aim of this study was to evaluate a 5-day residential assessment and education program for parents of infants who receive a diagnosis of CF after newborn screening.

Methods. Eligible parents had a 6- to 30-month-old infant with CF diagnosed by newborn screening. Parents were interviewed by telephone using a structured questionnaire that addressed 3 main themes: 1) initial communication of the diagnosis of CF, 2) the perceived value of the 5-day assessment and education program, and 3) the perceived advantages and disadvantages of the residential component (Care-By-Parent unit) of the program.

Results. Fifteen of 17 eligible families took part in the 5-day assessment and education program, 12 of whom used the residential Care-By-Parent unit. At the end of the program, parents believed that they had the knowledge and skills required to manage their child's CF at home. One hundred percent endorsed the timing of the assessment and education program immediately after the child's diagnosis and would recommend it to other families in the same situation. Perceived advantages of the residential program were not having to travel (89%), being able to concentrate on CF (50%), and the benefit of a “home base” at the hospital (39%). Twenty-two percent reported that financial costs related to participation (paternal time off work) were a disadvantage, 17% reported additional strain on family members caring for siblings, and 17% mentioned lack of comfort within the unit.

Conclusions. This time-intensive residential program was evaluated positively by parents of children with newly diagnosed CF. It provides a model for education programs after the diagnosis of CF by newborn screening, as well as for other pediatric conditions that require intensive parent education.
Cost-Effectiveness of Inhaled Nitric Oxide for the Management of Persistent Pulmonary Hypertension of the Newborn
Authors: Lorch Scott A. , Cnaan Avital , Barnhart Kurt
Published: August 2004

Objective. Inhaled nitric oxide (iNO) is a selective pulmonary vasodilator that has become part of the standard management for persistent pulmonary hypertension of the newborn (PPHN). This treatment modality, like many in neonatology, has not been well studied using quantitative economic techniques. The objective of this study was to evaluate the economic impact of adding iNO to the treatment protocol of PPHN for term infants from birth to the time of discharge from their initial hospitalization.

Methods. We used decision analysis modeling from a societal perspective to obtain an incremental cost-effectiveness ratio. Outcome probabilities were taken from the medical literature and a cohort of 123 infants who were treated with PPHN at The Children’s Hospital of Philadelphia between 1991 and 2002. Costs were estimated from daily resources used by these infants in 2001 dollars. Survival and quality-adjusted life years were used as effectiveness measures. One-way, threshold, and probabilistic sensitivity analyses were performed to assess the robustness of the base-case estimate.

Results. The addition of iNO to the treatment regimen of PPHN increased the cost of treating an infant by an average of $1141, primarily from an increased number of mechanical ventilation days. Use of iNO led to 3.4% more lives saved and a 6% increase in the average utility gained per infant. The incremental cost-effectiveness ratio was $33 234 per life saved and $19 022 per quality-adjusted life year gained. The model was robust to changes in outcome probabilities, cost, and utility variables. Only 3.6% of the trials using probabilistic sensitivity analysis found iNO to be more expensive with a worse outcome than conventional therapy alone, whereas 35.7% of the trials found iNO to be cheaper and more effective than conventional treatment alone.

Conclusions. iNO is cost-effective but not cost-saving in treating infants with PPHN from a societal perspective. There are critical time points during an infant’s hospitalization that could improve the efficiency and consequently the cost of care for this patient population.
Neonatal Loss of Motor Function in Human Spina Bifida Aperta
Authors: Sival Deborah A. , Weerden Tiemen W. van , Vles Johan S.H. , Timmer Albert , Dunnen Wilfred F.A. den , Staal-Schreinemachers A.L. , Hoving Eelco W. , Sollie Krystyne M. , Kranen-Mastenbroek Vivianne J.M. , Sauer Pieter J.J. , Brouwer Oebele F.
Published: August 2004

Objective. In neonates with spina bifida aperta (SBA), leg movements innervated by spinal segments located caudal to the meningomyelocele are transiently present. This study in neonates with SBA aimed to determine whether the presence of leg movements indicates functional integrity of neuronal innervation and whether these leg movements disappear as a result of dysfunction of upper motor neurons (axons originating cranial to the meningomyelocele) and/or of lower motor neurons (located caudal to the meningomyelocele).

Methods. Leg movements were investigated in neonates with SBA at postnatal day 1 (n = 18) and day 7 (n = 10). Upper and lower motor neuron dysfunction was assessed by neurologic examination (n = 18; disinhibition or inhibition of reflexes, respectively) and by electromyography (n = 12; absence or presence of denervation potentials, respectively).

Results. Movements, related to spinal segments caudal to the meningomyelocele, were present in all neonates at postnatal day 1. At day 1, leg movements were associated with signs of both upper (10 of 18) and lower (17 of 18) motor neuron dysfunction caudal to the meningomyelocele. In 7 of 10 neonates restudied after the first postnatal week, leg movements had disappeared. The absence of leg movements coincided with loss of relevant reflexes, which had been present at day 1, indicating progression of lower motor neuron dysfunction.

Conclusions. We conclude that the presence of neonatal leg movements does not indicate integrity of functional lower motor neuron innervation by spinal segments caudal to the meningomyelocele. Present observations could explain why fetal surgery at the level of the meningomyelocele does not prevent loss of leg movements.
Normal Annual Increase of Bone Mineral Density During Two Years in Patients With Cystic Fibrosis
Authors: Gronowitz Eva , Mellström Dan , Strandvik Birgitta
Published: August 2004

Objectives. To determine prospectively for 2 years the change in bone mineral density (BMD) in patients with cystic fibrosis (CF) and to correlate clinical data and routine biochemical parameters of bone metabolism and infection with BMD.

Methods. Fifty-four patients with CF, aged 6 to 33 years, were included. BMD was measured using dual-energy x-ray absorptiometry in lumbar spine (LS) and femoral neck (FN). Anthropometric data and biochemical markers of bone metabolism and infection were measured. The number of intravenous antibiotic courses per year (ivAC) and pulmonary function were assessed.

Results. The patients had normal anthropometric data and normal growth, but 36% and 33% of the patients had BMD z score <−1 standard deviation in LS and in FN, respectively. Nevertheless, BMD increased at a normal rate during the 2 years and was correlated to weight and lung function. Intact parathyroid hormone was positively correlated with the increase of BMD in both LS and FN during childhood. Blood sedimentation rate, serum concentration of immunoglobulin G, and ivAC were negatively correlated with BMD in FN. Patients with 2 more severe CF transmembrane conductance regulator mutations had significantly lower BMD in FN than other genetic combinations.

Conclusion. The study suggests that low BMD in CF is multifactorial and depends on infection and nutritional parameters. Differences in BMD of LS and FN suggested higher susceptibility to infection in FN at all ages. Longitudinal studies starting early before bacterial colonization would be valuable to determine the relative role of infection in the development of BMD in CF.
Molecular Epidemiology of Childhood Mitochondrial Encephalomyopathies in a Finnish Population: Sequence Analysis of Entire mtDNA of 17 Children Reveals Heteroplasmic Mutations in tRNAArg, tRNAGlu, and tRNALeu(UUR) Genes
Authors: Uusimaa Johanna , Finnilä Saara , Remes Anne M. , Rantala Heikki , Vainionpää Leena , Hassinen Ilmo E. , Majamaa Kari
Published: August 2004

Objectives. Many heteroplasmic point mutations in tRNA genes of mitochondrial DNA (mtDNA) have been associated with human diseases. We recently reported on a prospective 7-year study in which we enrolled 116 consecutive children with undefined encephalomyopathy. Seventeen of them were found to have both a defect in the mitochondrial respiratory chain and abnormal ultrastructure of muscle mitochondria, suggesting a clinically probable mitochondrial encephalopathy.

Methods. We determined the frequency of mtDNA mutations in these 17 children by analyzing the entire sequence of mtDNA by conformation-sensitive gel electrophoresis and sequencing.

Results. Three heteroplasmic tRNA mutations that were considered to be pathogenic were detected. Two of the mutations were novel transitions, 10438A>G in the tRNAArg gene and 14696A>G in the tRNAGlu gene, whereas the third one was 3243A>G, the common MELAS mutation. The mutant load was very high in the blood and skeletal muscle of the patients and markedly lower in the blood of asymptomatic maternal relatives. The 10438A>G mutation changes the nucleotide flanking the anticodon, whereas 14696A>G changes a nucleotide in the stem of the pseudouridine loop, creating a novel base pair and reducing the wobble.

Conclusions. Our results emphasize that the analysis of the entire sequence of mtDNA is worthwhile in the diagnostic evaluation of patients with clinically probable mitochondrial encephalomyopathy. The frequency of pathogenic mtDNA mutations was found to be 18% among children with biochemically and histologically defined mitochondrial disease, suggesting that the likelihood of nuclear DNA mutations in such a group is several times higher than that of mtDNA mutations.
Complications Associated With Image-Guided Gastrostomy and Gastrojejunostomy Tubes in Children
Authors: Friedman Jeremy N. , Ahmed Sabrina , Connolly Bairbre , Chait Peter , Mahant Sanjay
Published: August 2004

Objective. To evaluate the complications associated with the image-guided insertion of gastrostomy (G) and gastrojejunostomy (GJ) tubes in children, performed by the retrograde percutaneous route.

Methods. A convenience sample of 208 charts of 840 patients recorded as having G and/or GJ tubes placed by the interventional radiology service in a 4-year period (1995–1999) at the Hospital for Sick Children in Toronto, Canada, were selected for review. Complications were categorized as major (including subcutaneous abscess, peritonitis, septicemia, gastrointestinal bleeding, and death) or minor.

Results. In total, 253 tubes (208 G tubes, 41 GJ tubes, 4 G and GJ tubes) were placed in the 208 patients reviewed. The median age at the time of insertion was 15 months (range: 7 days–18 years). The most common diagnostic category was neurologic disease (47%). The main indications for tube insertion were recorded as failure to thrive (57%) and risk of aspiration (47%). Major complications were seen in 5% of patients. Peritonitis was noted in 3%, and there was 1 death related to tube insertion (0.4%). Minor complications were found in 73% of patients, including tube dislodgement (37%), tube leakage (25%), and G-tube site skin infection (25%). GJ tubes had a higher rate than G tubes of obstruction, migration, dislodgement, leakage, and intussusception. Site infection, gastroesophageal reflux, and bleeding from the site were seen less frequently in patients with GJ tubes compared with G tubes.

Conclusion. G and GJ tubes placed by the image-guided retrograde percutaneous method are associated with a wide range of complications. The majority of these are minor and are predominantly related to tube maintenance, but major complications, including death, do occur.
Gastrointestinal Involvement in Chronic Granulomatous Disease
Authors: Marciano Beatriz E. , Rosenzweig Sergio D. , Kleiner David E. , Anderson Victoria L. , Darnell Dirk N. , Anaya-O'Brien Sandra , Hilligoss Dianne M. , Malech Harry L. , Gallin John I. , Holland Steven M.
Published: August 2004

Objective. Chronic granulomatous disease (CGD) is a rare disorder of phagocyte oxidative metabolism. In addition to infectious complications, granulomatous lesions often involve hollow viscera, especially the gastrointestinal (GI) tract. The objective of this study was to evaluate the clinical presentation, prevalence, and consequences of GI involvement in patients with CGD.

Methods. The medical records of 140 patients with CGD (67% X-linked) followed at the National Institutes of Health were reviewed and abstracted for GI manifestations. All available GI pathology was reviewed.

Results. GI involvement was recorded in 46 (32.8%) of 140 patients with CGD, 89% of whom had X-linked inheritance. The median age at the time of initial GI manifestations was 5 years (range: 0.8–30 years); 70% of the affected patients presented with GI involvement in the first decade of life. Abdominal pain was the most frequent symptom (100%), and hypoalbuminemia was the most frequent sign (70%). Prednisone controlled symptoms and signs in the majority of affected patients, but relapse of symptoms occurred in 71%. GI involvement had no effect on mortality and was unassociated with interferon-γ use.

Conclusion. GI involvement is a common and recurring problem in CGD, especially in those with X-linked inheritance. Currently, there is no clear evidence for an infectious cause. The frequency of GI involvement is unaffected by the use of interferon-γ and does not affect mortality. GI involvement should be sought in patients who have CGD with abdominal pain, growth delay, or hypoalbuminemia.
Inhaled Corticosteroids and the Risk of Fractures in Children and Adolescents
Authors: Schlienger Raymond G. , Jick Susan S. , Meier Christoph R.
Published: August 2004

Objective. To determine whether children or adolescents who are exposed to inhaled corticosteroids (ie, beclomethasone, budesonide, fluticasone) are at a higher risk of having bone fractures compared with nonexposed individuals.

Methods. We performed a population-based nested case-control analysis using data from the United Kingdom–based General Practice Research Database. Within a base population of 273 456 individuals aged 5 to 79 years, we identified by International Classification of Diseases codes children or adolescents who were aged 5 to 17 years with a fracture diagnosis and up to 6 control subjects per case matched to cases on age, gender, general practice attended, calendar time, and years of history in the GPRD. We compared use of inhaled steroids before the index date between fracture cases and control patients.

Results. We identified 3744 cases and 21 757 matched control subjects aged 5 to 17 years. Current exposure to inhaled steroids did not reveal a substantially altered fracture risk compared with nonusers, even in individuals with current longer term exposure (ie, ≥20 prescriptions; adjusted odds ratio 1.15; 95% confidence interval: 0.89–1.48). In individuals with current or previous exposure to oral steroids, the adjusted odds ratio for current long-term inhaled steroid use compared with nonusers was 1.21 (95% confidence interval: 0.99–1.49).

Conclusions. Exposure to inhaled steroids does not materially increase the fracture risk in children or adolescents compared with nonexposed individuals.
Evaluation and Treatment of the Human Immunodeficiency Virus-1—Exposed Infant
Authors: King Susan M. ,   Committee on Pediatric AIDS,   Canadian Paediatric Society, Infectious Diseases and Immunization Committee
Published: August 2004

In developed countries, care and treatment are available for pregnant women and infants that can decrease the rate of perinatal human immunodeficiency virus type 1 (HIV-1) infection to 2% or less. The pediatrician has a key role in prevention of mother-to-child transmission of HIV-1 by identifying HIV-exposed infants whose mothers' HIV infection was not diagnosed before delivery, prescribing antiretroviral prophylaxis for these infants to decrease the risk of acquiring HIV-1 infection, and promoting avoidance of HIV-1 transmission through human milk. In addition, the pediatrician can provide care for HIV-exposed infants by monitoring them for early determination of HIV-1 infection status and for possible short- and long-term toxicities of antiretroviral exposure, providing chemoprophylaxis for Pneumocystis pneumonia, and supporting families living with HIV-1 infection by providing counseling to parents or caregivers.
Clinical Outcomes and Secondary Diagnoses for Infants Born With Hypoplastic Left Heart Syndrome
Authors: Connor Jean Anne , Arons Raymond R. , Figueroa Mayte , Gebbie Kristine M.
Published: August 2004

Objective. To explore clinical outcomes and secondary diagnoses present at discharge for infants born with hypoplastic left heart syndrome (HLHS), from a national perspective.

Methods. We examined hospitalizations for infants ≤30 days of age who were born with HLHS, using hospital discharge data from the 1997 Kids Inpatient Database. To explore treatment choices, clinical outcomes, and resource use, we used International Classification of Diseases, 9th Revision, Clinical Modification diagnostic and procedure codes to classify discharges according to type of surgical intervention versus no surgical intervention. To investigate outcomes in more detail, we identified secondary diagnoses noted at discharge, using International Classification of Diseases, 9th Revision, Clinical Modification codes, and stratified results according to type of surgical intervention.

Results. Of a total of 550 patients with HLHS, 234 underwent the Norwood procedure, 17 underwent orthotopic heart transplantation, and 106 died in the hospital with no reported surgical intervention. Although we found no demographic variables to be significantly associated with the type of treatment received, discharged patients who died without surgical intervention were significantly more likely to have received care in hospitals identified as small (odds ratio [OR]: 1.5; 95% confidence interval [CI]: 1.03–3.1) or not children’s hospitals (OR: 2.02; 95% CI: 1.13–3.6). Secondary diagnoses of cardiac arrest (OR: 2.0; 95% CI: 1.1–3.4) and seizures (OR: 2.6; 95% CI: 1.2–5.5) occurred more frequently in orthotopic heart transplantation cases than in Norwood procedure cases.

Conclusions. These data from a national perspective reflect outcomes of infants with HLHS during a time when rates of initial survival after surgical intervention were considered to be improved. These findings may be useful to clinicians when they are considering and recommending initial medical and surgical strategies currently being proposed for the treatment of HLHS.
Body Mass Index, Waist Circumference, and Clustering of Cardiovascular Disease Risk Factors in a Biracial Sample of Children and Adolescents
Authors: Katzmarzyk Peter T. , Srinivasan Sathanur R. , Chen Wei , Malina Robert M. , Bouchard Claude , Berenson Gerald S.
Published: August 2004

Objective. To derive optimal body mass index (BMI) and waist circumference thresholds for children and adolescents, to predict risk factor clustering.

Design. Cross-sectional receiver operating characteristic curve analysis.

Setting. The Bogalusa Heart Study, a community-based study of cardiovascular disease risk factors in early life.

Participants. A total of 2597 black and white children and adolescents, 5 to 18 years of age, who were examined between 1992 and 1994.

Main Outcome Measures. The presence or absence of ≥3 age-adjusted risk factors (low high-density lipoprotein cholesterol level, high low-density lipoprotein cholesterol level, high triglyceride level, high glucose level, high insulin level, and high blood pressure) was predicted from age-adjusted BMI and waist circumference values.

Results. The areas under the receiver operating characteristic curves were significantly different from 0.5 for both BMI and waist circumference for all gender/race groups, ranging from 0.73 to 0.82. The optimal BMI thresholds were at the 53rd and 50th percentiles for white and black male subjects, respectively, and at the 57th and 51st percentiles for white and black female subjects, respectively. Similarly, the optimal waist circumference thresholds were at the 56th and 50th percentiles for white and black male subjects, respectively, and at the 57th and 52nd percentiles for white and black female subjects, respectively. The sensitivity and specificity at the thresholds were similar for all gender/race groups, ranging from 67% to 75%.

Conclusions. The use of BMI and waist circumference for the prediction of risk factor clustering among children and adolescents has significant clinical utility. In this sample, race and gender differences in the optimal thresholds were minimal.