Pediatric Academic Societies

3160—Late Breakers: General Pediatrics; Medical Education and Dyslexia
Original Science Abstracts - Platform Session

LB1 8:00am
Evening Continuity Clinic: A Solution to Resident Work Hour Limitations?
Anda Kuo, Christine Ma and Robert Kamei. Department of Pediatrics, University of California San Francisco, San Francisco, California.

Background: The Accreditation Council for Graduate Medical Education (ACGME) has recently passed limitations on resident duty hours. Complying with these regulations poses a dilemma for residency programs where housestaff have post-call, afternoon continuity clinics. The post-call clinic violates the maximum number of work hours and also may cause sleep-deprivation and fatigue that affect resident performance with their continuity patients.
Objective: To evaluate housestaff experience with a pilot program that replaced post-call continuity clinics with evening continuity clinics.
Design/Methods: In August 2002, we began a pilot of evening continuity clinics at one continuity clinic site for University of California San Francisco (UCSF) pediatric residents. Instead of post-call clinics, 19 residents had evening continuity clinics added to a regular clinic day when they were neither post-call nor on-call. In January 2003, we surveyed housestaff satisfaction and experience with the evening clinics, particularly in comparison to post-call clinics.
Results: Nineteen of 23 pediatric residents at the pilot site participated in this pilot program. Four residents who opted to continue their post-call clinics had recently established an obesity clinic. Nineteen residents completed the survey (3 never had post-call clinic and 4 never had evening clinic).
The percentage of residents who rated overall satisfaction as good/outstanding was 80% for evening clinic and 12.5% for post-call clinic (p <0.01). All areas of patient care, medical education, and clinic infrastructure were better or equal in evening clinic in comparison to post-call clinic except for continuity of preceptors and access to medical services. Actual patient show rate for the evening clinic was not statistically different from regular afternoon housestaff continuity clinic (62% versus 69%, p=0.24).
Conclusion: Post-call afternoon continuity clinics violate the recent ACGME policy on resident work hours. Housestaff had greater satisfaction and a better clinic experience with evening clinic versus post-call clinic. Evening housestaff continuity clinic is a viable solution to meeting ACGME guidelines and may provide better patient care and resident education than post-call clinics.

LB2 8:15am
Maternal Depression and Infant Health Practices Among Low-Income Women
Esther K. Chung, Kelly F. McCollum, Irma T. Elo, Helen J. Lee, Tina M. Riley, Margarita Rubio, Jennifer F. Culhane. Dept. of Pediatrics, A.I. duPont Hospital for Children/Thomas Jefferson Medical College; Dept. of Obstetrics and Gynecology, Thomas Jefferson Medical College; and the Dept. of Sociology, Univ. of Pennsylvania, Philadelphia, PA.

BACKGROUND: Maternal depression affects 12 – 48% of mothers, with the highest rates reported among low-income mothers. Maternal depression is associated with inadequate prenatal care and negative parenting behaviors.
OBJECTIVES: To determine the relationships between maternal depression and maternal use of 1) infant health services, 2) parenting practices, and 3) injury prevention measures.
DESIGN/METHODS: Prospective, community-based survey. 774 mothers to date have been surveyed at 3 time-points pre- and post-partum. Maternal depressive symptoms were determined by the Center for Epidemiologic Studies Depression Scale (CES-D) at each time-point. Use of infant health services and preventative health practices were measured. ANOVA and Chi-square analyses were performed using STATA 6.0. Multiple logistic regression analyses were conducted, controlling for maternal race/ethnicity, nativity, education, income, age, employment status, parity, health, housing stability; and infant birth weight, age, and health status.
RESULTS: The sample consisted of single (74%), uninsured (63%), young (mean age: 23 + 6 yrs), low-income (mean income: $8,063/year), African American (68%) mothers. Forty-eight percent were depressed at one or two points (sometimes) and 12% at all points (always). When compared to mothers who were never depressed, always depressed mothers were 2.5 times (adjusted odds ratio [aOR] = 2.5; 95% confidence interval [CI] = 1.4, 4.4) as likely to have their child ever hospitalized, and 1.9 times (aOR = 1.9; 95% CI = 1.1, 3.3) as likely to use corporal punishment. Always depressed mothers were less likely to have smoke detectors in their home (aOR = 0.3, 95% CI = 0.1, 0.9) or use the back sleep position (aOR = 0.6; 95% CI = 0.3, 0.9) when compared to never depressed mothers.
CONCLUSIONS: Maternal depression persisting prepartum to postpartum is associated with an increased risk of infant hospitalization and use of corporal punishment; and a lower likelihood of having a smoke detector or using the back sleep position. Further efforts are needed to reduce maternal depression, which may impact the health and safety of young infants.

LB3 8:30am
Routine Use of Prevnar in a Pediatric Practice Profoundly Alters the Microbiology of Acute Otitis Media
Stan L. Block, James A. Hedrick, Christopher J. Harrison. Kentucky Pediatric Research, Bardstown, KY, and Pediatric Infectious Disease, Univ. of Louisville, Louisville, KY.

Background: Routine use of a new conjugated heptavalent pneumococcal vaccine (PCV-7) in children < 2 years could affect the microbiology and reduce overall episodes of acute otitis media (AOM) in vaccinees. In AOM, S. pneumoniae (SP) has been the most common (40-45%) pathogen recovered, and ~1/2 of strains were non-susceptible to penicillin (PNSP).
Setting: Since Summer 2000, > 95% of children in this 7-clinician, sole pediatric practice in rural central Kentucky had received at least 3 doses of PCV-7 by 7 m.o.
Objective: To determine changes in microbiology of AOM after routine implementation of PCV-7.
Methods: Middle ear isolates from a convenience sample of children with severe or refractory AOM were prospectively identified, as our routine for the last 10 years. Among children 7-24 months, we compared 296 AOM isolates from 1992-98 with 81 AOM isolates from Sept. 2000 to Feb. 2003.
Results: Children were from all socio-economic classes and 95% white. Comparing each time interval (92-98 vs. 00-03), proportion of sources of isolates differed slightly: tympanocentesis (85% vs. 75%), tympanostomy tube otorrhea (7% vs. 15%) and spontaneous otorrhea (8% vs. 10%) (p=0.054). Rates of SP were 49% vs. 32%; non-typeable H. influenzae 39% vs. 53% [beta-lactamase (+), 56% vs. 58%]; M. catarrhalis 9% vs. 12%; and S. pyogenes 3% vs. 2%. PCV-7 or PCV-7-related serotypes comprised 77% (n=140) and 55% (n=22) (p=0.033), of SP strains pre- and post- PCV-7, respectively. Gram (-) bacteria accounted for 2/3 of AOM isolates post-PCV-7 (p=0.26, O.R.=2.2)
Discussion: Overall SP and PCV-7 serotypes in AOM were significantly reduced by routine use of PCV-7 vaccine in our practice. PNSP comprised 30% of AOM isolates in 92-98, whereas all SP comprised only 32% of AOM in 00-03. Gram (-) bacteria may become 2-fold more likely than SP in de novo/refractory AOM in vaccinated young children provided that: 1) high uptake of PCV-7 occurs and 2) PCV-7 supply is adequate.

LB4 8:45am

Development of Left Occipito-Temporal Systems for Skilled Reading Following a Phonologically Based Intervention in Children

B. A. Shaywitz, S. E. Shaywitz, B. Blachman, K. R. Pugh, R. K. Fulbright, P. Skudlarski, W. E. Mencl, R. T. Constable, J. M. Holahan, K. E. Marchione, J. M. Fletcher, G. R. Lyon and J. C. Gore.

Reading disability (developmental dyslexia) is one of the most common neurobehavioral problems affecting children and adults. There is now a strong consensus that the central difficulty in dyslexia reflects a deficit within the language system, and more particularly, in a lower level component, phonology, which has to do with the ability to access the underlying sound structure of words. In young school-age children a deficit in phonology represents the most reliable and specific correlate of dyslexia. Such findings form the basis for the most successful and evidence-based interventions designed to improve reading. According to recent findings, provision of an evidence-based intervention at an early stage of reading instruction leads to the development of fluent reading (“the ability to read a text quickly, accurately and with proper expression”), the hallmark of skilled reading. Recent neurobiological findings implicate left hemisphere posterior brain systems in reading and, especially the left occipito-temporal “word form” area, as critical in skilled reading and that these posterior systems fail to function properly in dyslexic children and adults. This dysfunction in left hemisphere posterior reading circuits is already present in dyslexic children and cannot be ascribed simply to a lifetime of poor reading. Such evidence of a disruption in the normal reading pathways provides a neurobiological target for reading interventions. We used functional magnetic resonance imaging to study the effects of a phonologically based reading intervention on brain organization and reading fluency in 57 children ages 6.1-9.4 years; children comprised three experimental groups: Experimental intervention (n=37); community intervention (n=12) and community controls (n=28). Immediately after the year-long intervention, children taught with the experimental intervention had made significant gains in reading fluency and demonstrated increased activation in left hemisphere regions including the inferior frontal gyrus and the middle temporal gyrus and one year after the experimental intervention had ended these children were activating bilateral inferior frontal gyri and left superior temporal and occipito-temporal regions. These data indicate that teaching matters and that use of an evidence-based reading intervention can facilitate the development of those fast-paced neural systems that underlie skilled reading.

LB5 9:00am
The Use of Dexamethasone in Mild Croup: A Multi-center Randomized Controlled Trial
Candice Bjornson, Terry P. Klassen, Janielee Williamson, Rollin Brant, Amy Plint, Blake Bulloch, Lisa Evered, Craig Mitton, and David W. Johnson. Departments of Pediatrics, Faculties of Medicine, Universities of Calgary, Alberta (Edmonton), Ottawa, and Manitoba (Winnipeg), Canada.

BACKGROUND: The benefit of treating children with moderate to severe croup with dexamethasone (DEX) is well established. However, many children with croup have mild symptoms, and these children may not derive the same degree of benefit from treatment as those with more severe disease.
OBJECTIVES: To determine if the treatment of children who present to an emergency department (ED) with mild croup with a single dose of oral DEX: 1) reduces the rate of return to a health care provider for persistent croup symptoms within 7 days of treatment, and 2) reduces croup symptoms in the first 3 days following treatment as measured by the Telephone Out Patient (TOP) Score (a validated tool for assessing croup severity).
DESIGN/METHODS: Children (3 mos.-9 yrs.) with mild croup (Westley Croup Score < 2) evaluated at 4 pediatric EDs in 4 Canadian cities who met enrollment criteria and whose parents gave written informed consent were randomized to receive either a single oral dose of DEX (0.6mg/kg) or placebo (PLAC). All patients were initially discharged home and their primary caretaker was contacted by telephone 1,2,3, 7, and 21 days later. To enhance the accuracy of phone assessment, one trained study investigator utilizing a standardized questionnaire incorporating recordings of a barky cough and stridor conducted all 4 interviews with the same parent. Statistical methods included Fisher’s exact test for the difference in proportion of children per group returning for care by day 7, and proportional odds model for ordinal logistic regression for difference in the TOP scores on days 1,2, and 3.
RESULTS: Between Sept 2000 & Feb 2003, 720 patients were enrolled (359 DEX). 26/352 (7.4%) & 53/352 (15.1%) of those patients treated with DEX and PLAC, respectively, returned to a health care provider because of persistent symptoms (P=0.002, 95%CI for Difference 3.0 - 12.3%). Children treated with DEX had significantly lower TOP scores than those treated with PLAC (P=0.001).
CONCLUSIONS: Children with mild croup treated with a single oral dose of DEX, as compared with placebo, had substantially fewer croup symptoms and, as a result, markedly fewer return visits to a health care provider in the week following treatment.
Funded by Can. Institutes of Health Research

LB6 9:15am
Morbidity and Mortality Following RSV Associated Hospitalization Among Premature Canadian Infants
John Sampalis. McGill University and JSS Medical Research Inc. Montreal, Quebec, Canada

BACKGROUND/OBJECTIVES: Canadian guidelines reserve RSV prophylaxis for infants born <33 weeks GA with BPD. The impact of RSV associated hospitalization on subsequent use of hospital services and mortality in healthy preterm infants born 32-35 weeks GA is assessed. Pre-term infants are at increased risk for several conditions some of which may be presentable including RSV infections and hospitalizations. The purpose of the current study was to assess the impact of RSV infections on subsequent health care resource utilization in pre-term infants.
METHODS: Case control study using Canadian Institute of Health Information Discharge Abstract and Morbidity databases. Cases are healthy infants, born between 32-35 week gestation between 1998 and 2001 and hospitalized for proven, or probable RSV. Controls were matched to cases with respect to gestational age, gender and province. Infants with congenital abnormalities and BPD were excluded. Mean follow up was 1.66 years (Range: 1.4-3.0)
RESULTS: 2,415 cases of RSV associated hospitalizations were identified and matched to 20,254 controls. The mean (SD) age at the index admission was 0.65(0.44) years and 46% of the total study sample was male. Subsequent hospital services, excluding the index event, for cases and controls respectively were: Hospitalization: 2.96(2.81) vs. 1.28(1.42); Special Care Unit Visits: 0.67(1.70) vs. 0.40(0.33); Respiratory Therapy Visits: 0:31(0.70) vs. 0.13 (0.37); MD Consults: 3.61(4.54) vs. 0.89(1.12); In-hospital Procedures: 1.05(4.02) vs. 0.81(1.51); Out Patient Visits: 18.4(10.58) vs. 7.54(4.31); Total inpatient days: 14.71(18.69) vs. 5.04(7.09). All of these estimates were statistically significantly higher for the cases (p=0.001). Subsequent diagnoses for cases and controls respectively were: Respiratory conditions (64% vs. 13%); Fever (2.7% vs. 0.7%); Anorexia (2.2% vs. 0.6%); Lack of Normal Physiological Development (2.8% vs. 1.1%) (P<0.05); The rate of sudden death was 6.1% in the cases versus 0.3 % in the controls (p<0.05).
CONCLUSION: The results of this study show that RSV hospitalization in healthy premature infants is associated with a significant increase in subsequent health care resource utilization and mortality. These results support prophylaxis of premature infants against RSV hospitalization.
Funded by MedImmune, Inc.

LB7 9:30am
The Impact of Pulmonary Exacerbations on the Quality of Life of Patients with Cystic Fibrosis
Michael S. Yi, Joel Tsevat, Robert W. Wilmott, Uma R. Kotagal, and Maria T. Britto. Dept. of Internal Medicine, Univ. of Cincinnati Med. Ctr., Dept. of Pediatrics, Cincinnati Children’s Hospital Med. Ctr., Cincinnati, OH, Dept. of Pediatrics, Cardinal Glennon Children’s Hospital, St. Louis, MO.

BACKGROUND: Pulmonary exacerbations (PE) have been shown to negatively impact the health-related quality of life (HRQOL) of patients with cystic fibrosis (CF), but little is known about factors related to change in HRQOL after PE. Our objective therefore was to investigate the impact of PE on the HRQOL of patients with CF and to elucidate factors that are associated with changes post-PE.
METHODS: Patients with CF completed the questionnaires at 3 points in time: 1) at baseline, 2) at the beginning of the PE and 3) at follow-up after treatment. To measure HRQOL, we used the Child Health Questionnaire-Parent Form for patients < 18 years, and the SF-36 for patients ≥ 18 years. We examined the following predictor variables for association with change in Physical Summary (PHS) and Psychosocial Summary (PSS) HRQOL after PE: demographics, disease severity - % of predicted forced expiratory volume in 1 second (FEV₁), hospitalization, duration of antibiotic therapy, mode of antibiotic therapy, duration of nebulized therapy, presence or absence of pseudomonas colonization, weight change, and time between PE and follow-up. We used parametric and non-parametric univariate statistical analyses, and linear regression for multivariable analyses.
RESULTS: We collected data from 52 PE in 48 subjects. Their mean (SD) age at the time of PE was 15.8 (8.4) years; 27 (56.3%) were female; their mean (SD) baseline FEV₁ was 60.5% (27.9%); their mean (SD) standardized PHS score was 41.7 (12.9); their mean (SD) PSS score was 50.8 (9.3); and their mean (SD) time between the beginning of the PE (time 2) and followup (time 3) was 2.7 (2.0) months. In univariate analyses, PE were associated with a significant (p<0.05) decrease in FEV₁ (-10.5%) and PHS scores (-3.9 points). PSS scores did not significantly change with PE (-0.9 points). In multivariable analyses examining change in PHS and PSS from the beginning (time 2) of the PE to follow-up (time 3), no variables were significantly associated with change in PHS scores, but hospitalization was associated with relative improvement in PSS scores. When examining change from baseline (time 1) to follow-up (time 3), greater duration of antibiotic therapy and being hospitalized were associated with relative worsening in PHS scores, and hospitalization and being older were associated with relative improvement in PSS scores.
CONCLUSION: PE impact physical health more than psychosocial health in children and adults with CF. Being hospitalized was associated with relative improvement in PSS scores following PE but with relative worsening of PHS scores.

LB8 9:45am
Development of a Clinical Prediction Rule for Diagnosis of Streptococcal Pharyngitis in Children in Two Countries
Anne W. Rimoin, Hala Hamza, Adriana Vince, Shammim Qazi, Mark C. Steinhoff. Department of International Health, Pediatrics, Johns Hopkins Medical Institutions, Baltimore, MD; Cairo University, Cairo, Egypt, University Infectious Disease Hospital, Zagreb, Croatia WHO, Geneva, Switzerland. Background: Many regions do not have laboratory facilities to perform throat cultures for diagnosis of streptococcal pharyngitis. We therefore sought to develop a new clinical prediction rule (CPR) for diagnosis of group A beta hemolytic streptococcal (GABHS) pharyngitis without a laboratory.
Objectives: To develop a new CPR using patient history, signs and symptoms for pediatric GABHS pharyngitis in two countries.
Design/Method: In this prospective, descriptive study, we enrolled children of ages 2 – 12 years in 2 pediatric outpatient clinics in Zagreb, Croatia and Cairo, Egypt. (315 in Croatia, 997 in Egypt.) Using a standard format we recorded demographic data, history, signs and symptoms during physical examination and rapid antigen test for diagnosis of GABHS pharyngitis (Biostar Strep A OIA Max). Using regression techniques, a CPR was developed for each site to predict GABHS pharyngitis. Patient characteristics, signs, symptoms, and rapid test results were compared using appropriate statistical tests. Sensitivity, specificity, and diagnostic odds ratios (DOR) of the CPRs were compared.
Results: Using a rapid test, GABHS positivity differed between sites: 40% vs. 25% (p= .000). A CPR using signs of enlarged cervical lymph nodes or tonsillar enlargement in children presenting to clinics with complaint of cough, cold or sore/red throat had sensitivity /specificity DOR of 88%/33%/ 3.4 in Croatia, 84%/25%/1.8 in Egypt; 85%/26%/ 2.1 combining both populations.
Conclusion: In these populations, the recommended WHO CPR has a high specificity (90 – 93%) and DOR (2.9) but low sensitivity (9 – 17.2%), hence does not treat up to 91% of children who have GABHS pharyngitis. Our modified CPR has a higher sensitivity (identifying 85-88% of GABHS cases) and adequate specificity and has similar characteristics in two countries with different populations. This data indicates the need for prospective studies of proposed treatment guidelines in varied regions to characterize local performance in clinical settings.
Funded by USAID.

LB-9 4:15pm
Is Prenatal Magnesium Sulfate Immediately Prior to Very Preterm Birth Neuroprotective for Babies? The ACTOMgSO₄ Trial: A Randomized Placebo-Controlled Trial
Caroline A Crowther, Janet E Hiller, Lex W Doyle, Ross R Haslam, for the ACTOMgSO4 (Australasian Collaborative Trial of Magnesium Sulphate) Collaborative Group. University of Adelaide, Adelaide, Women’s and Children’s Hospital, Adelaide, The University of Melbourne and The Royal Women’s Hospital, Melbourne, Australia.

Background: Infants born very preterm have a high risk of dying in the newborn period or of surviving with cerebral palsy. Magnesium sulfate given to women immediately prior to preterm birth may reduce these risks.
Objective: To assess if prenatal magnesium sulfate was neuroprotective for the very preterm fetus.
Methods: Consenting women with a pregnancy <30 weeks’ gestational age where birth was planned or expected within 24 hours were randomized at 16 centers in Australia and New Zealand to either intravenous magnesium sulfate (loading dose 4 g over 20 minutes, then 1g per hour for up to 24 hours; n = 535) or an equal volume of normal saline placebo (n = 527). Primary outcomes in children at two years’ corrected age were total mortality and cerebral palsy.
Results: Side effects were reported in 89% of women given magnesium sulfate versus 38% of women given placebo; however, no women had serious side effects of therapy. Total mortality (13.8% vs 17.1%; adjusted relative risk [RR] 0.83, 95% CI 0.64-1.09), cerebral palsy in survivors (6.8% vs 8.2%; RR 0.83, 95% CI 0.54-1.27) and combined death or cerebral palsy (19.8% vs 24.0%; RR 0.83, 95% CI 0.66-1.03) were less frequent for babies exposed to magnesium sulfate, but none of the differences were statistically significant. Significantly fewer survivors exposed to magnesium sulfate had substantial motor dysfunction at 2 years of age (3.4% vs 6.6%; RR 0.51, 95% CI 0.29, 0.91).
Conclusions: The potential clinically important improvement in pediatric outcomes from magnesium sulfate given to women immediately prior to very preterm birth urgently needs confirmation in further trials. There do not appear to be serious harmful effects for the women or their children.
Funded, in part, by a grant from the National Health and Medical Research Council, Australia.

LB-10 4:30pm
Cesarean Rates and Neonatal Morbidity in a Low Risk Population
Jeffrey Gould, Beate Danielson, Lisa Korst, Roderic Phibbs, Kathy Chance, Elliot Main, David Wirtschafter, David Stevenson for the California Perinatal Quality Care Collaborative ( CPQCC)

BACKGROUND: The dramatic increase in cesarean section, and the demonstration that operative deliveries may not always be medically indicated, has led to a national effort to reduce cesarean births. It is generally assumed that lower cesarean rates are indicative of high quality obstetric care.
OBJECTIVE: To test this assumption in a statewide, low risk cohort
METHODS: Vital records and administrative discharge data for 748,604 California singleton live births without congenital abnormalities born 1998-2000 were used. 282 institutions were classified Average (160), Low (62) and High (60) cesarean (CS) hospitals on the basis of their cesarean rate in a low risk cohort of mothers without a previous cesarean, in labor at term, with no evidence of maternal, fetal, or placental complications. Neonatal outcomes and interventions determined by ICD-9-CM codes were compared across the three groups of hospitals.
RESULTS: Compared to Average CS hospitals, low risk infants born at Low CS hospitals had a higher incidence of morbidity and intervention suggesting that some infants might have benefited from cesarean delivery. Infants delivered at High CS rate hospitals also had increased morbidity and intervention suggesting that high cesarean rates in themselves are not protective.

CONCLUSION: Assessing the quality of obstetrical care will require strategies that go beyond the measurement of cesarean rates and include the evaluation of neonatal outcomes.

LB-11 4:45pm
Randomized Pilot Trial of Delivery Room CPAP in the ELBW Infant
N. Finer, W. Carlo, S. Duara, A. Fanaroff, E. Donovan, for the NICHD Neonatal Network.

Background: Prior studies suggest that early continuous airway positive pressure (CPAP) may be a beneficial form of ventilatory support for the ELBW infant by avoiding intubation, and subsequent chronic lung disease, and no prospective studies have evaluated the feasibility of this approach.
Objective: To prospectively evaluate the delivery room (DR) resuscitation and need for intubation of ELBW infants who were randomized to CPAP/PEEP or no CPAP/PEEP during resuscitation while avoiding delivery room intubation for surfactant administration.
Design/Methods: ELBW infants < 28 weeks gestation, born in 5 NICHD Network NICUs from July 2002 to January 2003 were randomized to receive either CPAP/PEEP or not using a t-piece resuscitator (Neopuff^®). No infant was to be intubated for the sole purpose of surfactant administration in the delivery room. Following NICU admission all non-intubated infants were placed on CPAP and were intubated for surfactant administration only after meeting specific criteria: an FiO2 > .3 with an SaO2 < 90% and/or a PaO2 < 45 torr, a PaCO2 > 55 torr, or apnea requiring bag and mask ventilation.
Results: Enrollment was 103 infants, 55 CPAP and 48 Control infants. Video recording of the resuscitation was performed for 71 infants. No infant was intubated in the DR only for surfactant. Intubation for resuscitation occurred in 27 of 55 CPAP infants and 19 of 48 control infants (p=.333). All infants of 23 weeks gestation required intubation for resuscitation in the delivery room, irrespective of treatment group, whereas only 4 of 22 (18%) infants of 27 weeks or greater required intubation. CPAP infants required a mean of 1.58 intubation attempts in the DR compared with 1.89 attempts for Control infants (p=.62) and the mean and median duration of the first intubation attempt was 35.8, and 30 seconds and 33 and 35 seconds for the CPAP and Control infants (p=.694). For infants not intubated in the DR, 36 infants were subsequently intubated in the NICU by day 7, 16 CPAP infants and 20 Control infants, (p=.207), with 80% of infants intubated by day 7.
Conclusions: Approximately 50% of infants less than 28 weeks gestation require intubation for resuscitation in the DR, unaffected by the use of DR CPAP/PEEP, and 80% are intubated by day 7. Early CPAP alone for ventilatory support is unlikely to be a successful intervention in such infants and these observations facilitate the appropriate planning of future studies.

LB-12 5:00pm
Early Surfactant Replacement in Spontaneously Breathing Premature Infants with RDS
Roger F. Soll, Jeanette M. Conner, Diantha Howard and the Investigators of the Early Surfactant Replacement Study. U of Vermont, Burlington, VT, Vermont Oxford Network, Burlington, VT.

Background: Spontaneously breathing premature infants with respiratory distress syndrome (RDS) may benefit from early surfactant treatment.
Objective: To evaluate the effect of intubation and early surfactant administration in spontaneously breathing premature infants with signs and symptoms of RDS.
Design: Multicenter RCT conducted at NICUs in the Vermont Oxford Network. Spontaneously breathing infants with birth weight 1501-2500 g were eligible for enrollment if they had respiratory distress requiring ³ 30% supplemental oxygen, a PCO2 < 65 mmHg, and a CXR compatible with RDS. Infants between 2 and 24 hours of age were randomly assigned to early intubation, surfactant treatment, and rapid extubation [ER Group] or standard respiratory management, including possible intubation and surfactant treatment based on clinical indications [SM Group]. The primary outcome measure was defined as the need for mechanical ventilation in the first week of life.
Results: 267 infants were randomized and enrolled at 33 participating centers. Infants in the ER Group (N=137) were comparable to those in the SM Group (N=130) regarding birth weight, gestational age, race, prenatal care, and need for initial respiratory support. Fewer infants randomized to the ER Group required mechanical ventilation during the first week of life [38% vs. 48%, p=0.07, Relative Risk (RR) 0.78, 95%CI 0.59, 1.03]. Infants in the ER Group received more surfactant doses than infants in the SM Group (1.3+/-0.7 vs. 0.8+/-1.1, p < 0.001). Pneumothorax occurred in 6% of the ER Group vs. 10% in the SM Group (RR 0.58, 95%CI 0.25, 1.35). There were no differences between the groups in pulmonary hemorrhage, patent ductus arteriosus, bacterial sepsis, intraventricular hemorrhage, and necrotizing enterocolitis.
Conclusion: Spontaneously breathing infants treated with early intubation, surfactant replacement, and rapid extubation appear to require less mechanical ventilation during the first week of life than infants who received standard respiratory care. Additionally, there was a trend towards a decreased rate of pneumothorax in infants in the early treatment group, a finding noted in previous studies of this treatment approach. (Partially funded by a grant from Ross Laboratories).

LB-13 5:15pm
Is Surfactant Therapy Beneficial in the Management of the Term Neonate with Congenital Diaphragmatic Hernia?
JoDee M. Anderson, and The Congenital Diaphragmatic Hernia Study Group. Department of Pediatrics, Stanford University, Stanford, California

BACKGROUND: Congenital diaphragmatic hernia (CDH) continues to be associated with significant morbidity and mortality. Numerous therapeutic modalities have been employed over the last decade to treat patients with CDH, however the efficacy of many of these interventions has not yet been determined. Previous studies have suggested that surfactant deficiency may play a role in the pulmonary pathology of CDH. The purpose of this analysis was to determine the benefit of surfactant on term infants with CDH.
OBJECTIVE: To evaluate the association of surfactant administration with survival, the need for ECMO and oxygen use at 30 days of life (CLD) in term infants with CDH.
METHODS: The present study utilized data from the 2,285 live born infants enrolled in the multi-center CDH Study Group Registry between 1995 and 2001. Infants > 37 weeks gestation with immediate distress at delivery were included in the analysis; those with major congenital anomalies were excluded. For univariate analysis, chi-square tests were used for categorical variables and unpaired t-tests were used for nominal variables. Factors identified as significant in univariate analysis were used in multiple regression analysis. Significance was defined as p<0.05.
RESULTS: 1075 patients were included in the analysis, 300 of which were treated with surfactant. Comparison of demographic and perinatal variables revealed that infants in the surfactant-treated group were of lower gestational age (38.8+1.1 vs. 39.1+1.3 weeks, p=0.012), more likely to be prenatally diagnosed (62% vs. 43%, p<0.0001), inborn (44% vs. 36%, p=0.016), and to have received CPR in the delivery room (21% vs. 16%, p=0.42). Infants in the surfactant-treated group were also more likely to have been treated with vasopressors (93% vs. 77%, p<0.0001) and inhaled nitric oxide (61% vs. 35%, p<0.0001). Regression analysis for surfactant use with demographic, perinatal and treatment variables showed that prenatal diagnosis, vasopressor use and iNO were significant independent risk factors. A separate analysis of prenatally diagnosed patients alone revealed that surfactant use was associated with significantly lower survival (57.3% vs, 70.3%, p=0.008). Among all infants, surfactant use was associated with significantly lower survival (61% vs. 73%, p=0.001), increased need for ECMO (62% vs. 45%, p<0.0001), and increased incidence of CLD (68% vs. 38%, p<0.0001).
CONCLUSION: In term neonates with CDH, surfactant use is associated with lower survival, increased ECMO use and increased incidence of CLD. Surfactant use does not appear to provide any benefit for the term infant with CDH.

LB-14 5:30pm
Combined Inhibition of Nitric Oxide (NO) and Prostaglandin (PG) Synthesis for Refractory Patent Ductus Arteriosus (PDA)
R. L. Keller, T. A. Tacy, R. I. Clyman. Dept of Pediatrics, University of California San Francisco, CA.

Background: Studies in premature animals suggest that 1) prolonged, complete closure of the ductus lumen is necessary to produce permanent anatomic closure; and 2) ductal NO production augments the effect of PGs on ductus patency. In premature newborns (<28 wks), a recurrent hemodynamically significant PDA frequently occurs after indomethacin (INDO) therapy if Doppler evidence of ductus patency is seen after the initial 3 INDO doses. We hypothesized that combination therapy with INDO and an NO synthase inhibitor (L-NMMA) would produce a tighter degree of ductus constriction than additional doses of INDO alone and would result in permanent closure if this degree of constriction could be maintained for >48 h.
Methods: From 1/99-2/03, 43 infants (<28 wks) who survived >1 wk had persistent Doppler ductal patency after receiving 3 doses of prophylactic INDO (0.2, 0.1, 0.1mg/kg). 11/43 newborns with persistent ductal flow after 3 INDO doses received a continuous L-NMMA infusion (in a Phase I/II trial designed to last 72 h) plus additional INDO therapy (0.1 mg/kg Q 24 hr x 3). 32/43 infants received additional INDO alone because L-NMMA was not available or the parents declined the study. These infants served as a comparison group.
Results: L-NMMA doses of 10-20 mg/kg/h raised serum creatinine and systemic blood pressure. Both conditions resolved with discontinued therapy or decreased dose. At 5 mg/kg/hr serum creatinine was stable but hypertension limited L-NMMA infusion rates. 91% (10/11) of the INDO+L-NMMA group had complete ductal constriction with no ductal flow seen on Doppler. Only 1/6 (17%) of the infants who received INDO+L-NMMA for >60 h (mean 70 + 4 h) developed a symptomatic PDA requiring surgical ligation. In contrast, all of the 5 infants who had <48 h (mean 35 + 9 h) of INDO+L-NMMA required PDA ligation. Only 47% (15/32) of the comparison group closed their ductus by Doppler; 68% (22/32) ultimately required surgical PDA ligation.
Conclusion: In this Phase I/II trial, INDO+L-NMMA produced tighter ductus constriction than INDO alone (P<.05). Combined therapy for >60 h had a higher permanent closure rate than a shortened course (P<.05) or INDO alone (P<.05). No significant differences in long-term adverse outcomes were seen.

LB-15 5:45pm
High-Dose Anti-D Immune Globulin Raises the Platelet Count in Newly Diagnosed Childhood ITP More Rapidly Than Standard-Dose Anti-D and Higher Than IVIg
Michael Tarantino, Guy Young, Salvatore Bertolone, Karen Kalinyak, Frank Shafer, Roshni Kulkarni, Lisa Weber, Diane Nugent for the Pediatric ITP Study Group. Comp. Bleeding Disorders Center, Peoria, IL, Children’s Hosp of Orange County, Orange, CA, U of Louisville, Louisville, KY, Children’s Hosp Medical Center, Cincinnati, OH; St. Christopher’s Hosp, Philadelphia, PA; Michigan State U, East Lansing, MI

Although the treatment of childhood ITP is controversial, a majority of pediatric hematologists treat newly diagnosed severe ITP with immune globulin. We conducted a multi-center, randomized prospective trial of immune globulin treatment as the initial therapy for 105 newly diagnosed ITP in Rh+ children, aged 1-18 years that presented with a platelet count < 20,000/µL. Subjects received either 1) single dose 50µg/kg anti-D, IV over 5-10 minutes, 2) single dose 75 µg/kg anti-D IV over 5-10 minutes, or 3) single dose 0.8g/kg, IVIg (brand not restricted), IV over 4-6 hours. Hematological parameters were monitored daily until the platelet count exceeded 50,000/µL, then weekly-to-monthly for six months. Adverse events were followed prospectively. Preliminary results are reported below.

* p=0.03, <0.005 for anti-D 75µg/kg v. IVIg 0.8g/kg and v. anti-D 50µg/kg, respectively.

Wet purpura (any of: mucosal hemorrhage, hemoptysis, melana, hematuria) was reported in 27% of subjects at study entry. By day 7 hemoglobin concentrations decreased by 1.5, 2 and 0.3 g/dL in arm 1, 2 and 3, respectively. No serious adverse events related to either drug were reported. One subject, presenting with dry purpura, was refractory to treatment and had an intracranial hemorrhage 3 months into the study. Adverse events were otherwise mild. In summary, Anti-D, 75µg/kg raised the platelet count in newly diagnosed childhood ITP more rapidly than standard-dose anti-D and significantly higher than single dose IVIg. Additional monitoring (ie chronicity, number of treatments) is ongoing. This study was funded, in part, by Nabi. Nabi did not participate in study execution or data analysis.

LB-16 6:00pm
International Formula-Based Nutritional Intervention for Infants Born to HIV-Infected Women
Ross E. McKinney, Maria Leticia S. Cruz, Christine Powell, Michael Hughes, James M. Oleske, Harland Winter, Carol Elgie, Lynette Purdue, David Wolf, Shiara Ortiz-Pujols, Nancy R. Calles, James McNamara, Jack Moye. Duke Univ. Med. Ctr., Durham, NC, Hospital dos Servidores do Estado, Rio de Janeiro, Brazil, Harvard Sch. Publ. Health, Boston, MA, Univ. Med. Dent. NJ, Newark, NJ, Mass. Gen. Hosp., Boston, MA, Frontier Sci. Tech. Res. Fndn., Amherst, NY, NIAID/NIH/DHHS, Bethesda, MD, Ross Products Div., Columbus, OH, Soc. Sci. Systems, Silver Spring, MD, Texas Children’s Hosp., Houston, TX, NICHD/NIH/DHHS, Bethesda, MD.

BACKGROUND/OBJECTIVE: HIV infection affects infant growth adversely. Breast-milk substitutes are recommended to prevent postnatal HIV transmission when safe and available. We evaluated the effect on growth of an increased caloric-density milk-based formula in infants born to HIV-infected women in the U.S. and Latin America.
METHOD: Pediatric AIDS Clinical Trials Group protocol 247 randomized 2,097 infants ≤17 d old and ≥1.8 kg in a double-blind trial of 26-kcal/oz compared with standard 20-kcal/oz infant formula. HIV DNA PCR was performed at study week (SW)4, CD4⁺ count at SW8, and anthropometry at each visit. Tolerability was assessed by caregiver report. Preliminary analysis was performed on data through SW8 from uninfected infants only. Growth measures were compared by t-test and linear regression, qualitative treatment differences by Fisher's exact test, and CD4⁺ count distributions by Wilcoxon's test.
RESULTS: Forty infants were HIV-infected. Of those remaining, 1,027 received 26-kcal/oz formula and 1,030 received standard formula. Treatment groups were comparable at baseline and in proportions lost to follow-up (11.4% vs. 10.5%) and completing treatment (77.6% vs. 78.3%). Weight (mean±SE) but not length or head circumference was greater with 26-kcal/oz (5.29±0.02 vs. 5.20±0.03 kg at SW8, p=0.01). No significant difference in tolerability or median CD4⁺ count was found. Differences with 26-kcal/oz formula were greater among infants at international sites (280 g in weight and 1.0 cm in length at SW8, both p=0.01).
CONCLUSION: Increased caloric-density formula feedings can increase growth over 8 or fewer weeks and are well tolerated in HIV-exposed newborns. Effects in HIV-infected infants specifically and beyond SW8 remain to be determined as this ongoing study completes follow-up and analysis. Similar interventions where feasible could provide a multifactorial effort to improve infant growth and prevent breast-milk HIV transmission.