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In this study our aim was to present a series of experiments to evaluate the impact of pre-annotation: (1) on the speed of manual annotation of clinical notes and clinical trial announcements; and (2) test for potential bias if pre-annotation is utilized. The gold standard was 900 clinical trial announcements from clinicaltrials.gov website and 1655 clinical notes annotated for diagnoses, signs, symptoms, UMLS CUI and SNOMED CT codes. Two dictionary-based methods were used to pre-annotate the text. Annotation time savings ranged from 2.89% to 29.1% per entity. The pre-annotation did not reduce the IAA or annotator performance but reduced the time to annotate in every experiment. Dictionary-based pre-annotation is a feasible and practical method to reduce cost of annotation without introducing bias in the process.

Objective: 1) Develop a novel low cost task trainer which appropriately simulates the basic steps involved in a tonsillectomy procedure for the novice trainee. 2) Assess this task trainer for feasi...

Objective: 1) Describe the likelihood of contralateral hearing loss (HL) in patients with unilateral enlarged vestibular aqueduct (UEVA). 2) Detemine the positve predictive value of genetic testing in patients with UEVA. 3) Determine the correlation of temporal bone measurements in patients with UEVA.Method: Patients were identified from a database of children with sensorineural hearing loss (HL) and enlarged vestibular aqueduct (EVA) between 1998 and 2010. A group of patients with unilateral HL without EVA was also identified. Outcomes measured were HL phenotype, laterality of EVA, midpoint and operculum measurements, and genetic tests.Results: Fifty-five percent of patients with UEVA had HL in the contralateral ear. There was no difference in the rate of HL progression in patients with bilateral and unilateral EVA (P = .1). However, both EVA groups had higher rates of progression compared to patients with unilateral HL alone. A correlation was shown for the presence of HL at 250 Hz and the risk of more ...

Objective: 1) Evaluate the neural response telemetry (NRT) of patients with inner ear anomalies, and determine correlations between NRT and postoperative speech recognition thresholds (SRT). 2) Determine if higher incidence of negative intraoperative NRT exists in pediatric patients with inner ear anomalies, namely enlarged vestibular aqueduct syndrome (EVAS).Method: Retrospective chart review of pediatric patients who underwent cochlear implantation at a tertiary care pediatric referral center from 2001 to present. Patients with inner ear anomalies were age matched to controls without anomalies. Associations between abnormal NRT and perilymphatic gusher and correlations between NRT and audiometry were assessed.Results: Twenty-seven subjects with radiographic evidence of EVAS were evaluated; 35 ears implanted. Median age of implantation was 77.5 months. NRT was normal in 69%, abnormal 11%, marginal 6%, missing 4%. Intraoperative data revealed a perilymphatic gusher in 8 patients (23%); of which 50% had ab...

Objective: Cholesteatomas have a high-rate of recurrence, regardless of the surgical approach used. Our hypothesis was that use of the handheld CO2 laser would reduce recurrence of cholesteatoma by removing microscopic disease, particularly in challenging or difficult to treat areas.Method: A total of 384 mastoidectomies performed by a single-surgeon between 2006 and 2011 were reviewed (22 in the non-laser and 23 in the laser group that met the inclusion criteria). Outcome measures included recurrence rate and complication rates. Independent variables included smoking status, bilaterality and the extent of disease as assessed by Marres staging (1984).Results: Average follow-up was 25 months; average separation between the first and second stage was 8 months. There were 1 Marres stage 1, 29 stage 2, 1 stage 3, and 13 stage 4 patients and the distribution between the 2 groups was similar. There were no facial nerve paralysis cases, and 1 sensorineural (SNHL) hearing loss after the first procedure in the non...

Background Nosocomial [hospital-associated or neonatal intensive care unit (NICU)-associated] infections occur in as many as 10 to 36% of very low-birth-weight infants cared for in NICUs. Objective To determine the potentially avoidable, incremental costs of care associated with NICU-associated bloodstream infections. Study Design This retrospective study included all NICU admissions of infants weighing 401 to 1500 g at birth in the greater Cincinnati region from January 1, 2005, through December 31, 2007. Nonphysician costs of care were compared between infants who developed at least one bacterial bloodstream infection prior to NICU discharge or death and infants who did not. Costs were adjusted for clinical and demographic characteristics that are present in the first 3 days of life and are known associates of infection. Results Among 900 study infants with no congenital anomaly and no major surgery, 82 (9.1%) developed at least one bacterial bloodstream infection. On average, the cost of NICU care was $16,800 greater per infant who experienced NICU-associated bloodstream infection. Conclusion Potentially avoidable costs of care associated with bloodstream infection can be used to justify investments in the reliable implementation of evidence-based interventions designed to prevent these infections.

Background Children with sensorineural hearing loss have a high rate of additional disabilities beyond those expected by the impact of hearing loss on language and are identified later than children without hearing loss. Identifying these developmental delays and allowing earlier implementation of interventions specific to these concerns would improve care. Aims To determine whether the Ages and Stages Questionnaire© (ASQ) can identify unmet needs or unidentified developmental delays among young children with bilateral sensorineural hearing loss. Subjects Fifty children with any degree of bilateral sensorineural hearing loss, 6 months to 36 months of age recruited from a tertiary referral center and regional early intervention programs for children who are deaf/hard of hearing. Outcome measures The ASQ and comprehensive developmental evaluations with the Revised Gesell Developmental Schedules. Study design Sensitivities and specificities of the ASQ were calculated. Results While 32% of our population had a developmental delay outside the domain of communication, the ASQ had poor sensitivity on the overall score without the communication domain as well as for fine motor, cognitive, personal–social domains. It had good sensitivity for the domains of communication and gross motor skills and good specificity (ranging 83–85%) on specific domains as well as for the overall score (70%). Conclusions The ASQ does not provide an effective mean for identifying additional developmental concerns in young children with bilateral sensorineural hearing loss. Further studies are needed to determine how to identify additional disabilities in a timely manner among young children with hearing loss.

To compare the operative times and complications between patients who underwent minimal access cochlear implantation and standard technique cochlear implantation.Patients who underwent unilateral cochlear implantation by a single surgeon from 2001 to 2010. The minimal access technique of an approximately 2.5-3 cm post-auricular incision with creation of subperiosteal pocket for the device was compared to the longer standard "S" incision into the scalp (~8-10 cm) with bone well creation and suture fixation. Outcomes include operative times and complications.There were 122 unilateral implants, 73 (59.8%) in the minimal access group and 49 (40.2%) in the standard group. Mean total time in the operating room was lower in the minimal access group compared to the standard group (200±31 vs. 255±49 min, p.0001) as well as mean operative time (149.5±28 vs. 200±45 min, p.0001 respectively). There were 17 complications in the entire cohort with 8 and 9 complications in the minimal and standard groups respectively. Of the 17 complications, 12 were surgical technique-specific. Although it appeared that there were higher rates of major, technique-specific, and overall complications in the standard access group, these differences did not reach statistical significance.Patients undergoing minimal access cochlear implantation require shorter operative times when compared to the standard access cochlear implantation. In addition, low complication rates are observed for major, technique-specific, and overall complications. Minimal access cochlear implantation may be considered an equivalent and potentially superior technique.

To evaluate neonatal abstinence syndrome (NAS) treatment outcomes achieved using an optimized methadone weaning protocol developed using pharmacokinetic (PK) modeling compared with standard methadone weaning.This pre-post cohort study evaluated 360 infants who completed pharmacologic treatment for NAS with methadone as inpatients at 1 of 6 nurseries in southwest Ohio between January 2012 and March 2015. Infants were initially treated with a standard methadone weaning protocol (n = 267). Beginning in July 2014, infants were treated with a revised methadone weaning protocol developed using PK modeling (n = 93). Linear mixed models were used to calculate adjusted mean primary outcomes, including total duration of methadone treatment, total administered methadone dosage, and length of inpatient hospital stay, which were compared between weaning protocols. The use of adjunctive therapy for NAS treatment was examined as a secondary outcome.Infants who received NAS treatment with the revised protocol experienced a shorter duration of methadone treatment (13.1 vs 16.4 days; P.001) and shorter duration of inpatient treatment (18.3 vs 21.7 days; P.001) compared with infants receiving standard methadone weaning. No difference was observed in total methadone dosage administered (0.52 vs 0.52 mg/kg; P = .97) or in the use of adjunctive therapy (22.6% vs 25.5%; P = .68) between groups.Refinement of a standard methadone weaning protocol using PK modeling was associated with reduced duration of opioid weaning and shortened length of stay for pharmacologic treatment of NAS.

Objective To compare a subjective patient/family-derived voice handicap survey with an expert observer–derived method of evaluating voice disturbance in pediatric patients with vocal fold lesions (VFLs). Design Retrospective review. Setting Tertiary care referral center. Patients Thirty-eight children with VFLs referred for voice evaluation. Main Outcome Measures Pediatric Voice Handicap Index (pVHI) scores and Consensus Auditory-Perceptual Evaluation of Voice (CAPE-V) scores. Percentages for CAPE-V (100-point scale) and pVHI (92-point scale) were calculated for direct comparisons. Relationships between pVHI scores and CAPE-V scores were investigated using the Spearman rank correlation. Results Thirty-eight patients with VFLs (median age, 8.3 years; age range, 4.2-17.2 years; 63% males) were included from a database of more than 600 children and evaluated between November 15, 2005, and June 15, 2010. The median CAPE-V overall score was 30.3 (range, 1-67), and the normalized total pVHI score was 29.3 (range, 0-73) (P = .90). The Spearman rank correlation showed significant fair correlations between CAPE-V overall and functional pVHI and between CAPE-V strain and breathiness, and the pVHI total, functional, but none higher than ρ = 0.44 (P ≤ .03). The correlation was higher in males for CAPE-V loudness to total pVHI (ρ = 0.40, P = .04) and in females for CAPE-V breathiness (ρ = 0.58, P = .03) and strain (ρ = 0.55, P = .04) to total pVHI. Conclusions The CAPE-V and the pVHI are useful tools in the measurement of voice outcomes in children with VFLs. There are fair correlations between the CAPE-V and the pVHI, and they likely evaluate important yet different aspects of voice disturbance. Significant gender differences in these correlations should be further evaluated in future studies.

BACKGROUND: This is an update of a Cochrane Review first published in The Cochrane Library in Issue 1, 2003. Tonsillectomy continues to be one of the most common surgical procedures performed worldwide. Despite advances in anesthetic and surgical techniques, post‐tonsillectomy morbidity remains a significant clinical problem. OBJECTIVES: To assess the clinical efficacy of a single intraoperative dose of dexamethasone in reducing post‐tonsillectomy morbidity. SEARCH METHODS: We searched the Cochrane Ear, Nose and Throat Disorders Group Trials Register; the Cochrane Central Register of Controlled Trials (CENTRAL); PubMed; EMBASE; CINAHL; Web of Science; BIOSIS Previews; Cambridge Scientific Abstracts; ISRCTN; and additional sources for published and unpublished trials. The date of the most recent search was 29 October 2010, following a previous search in September 2002. SELECTION CRITERIA: Randomized, double‐blind, placebo‐controlled trials of a single dose of intravenous, intraoperative corticosteroid for pediatric patients (age < 18 years) who underwent tonsillectomy or adenotonsillectomy. DATA COLLECTION AND ANALYSIS: The first author extracted data regarding the primary outcome measures and measurement tools from the published studies. The first author also recorded data regarding study design, patient ages, procedures performed, dose of corticosteroid and method of delivery, as well as methodological quality. When data were missing from the original publications, we contacted the authors for more information. We performed data analysis with a random‐effects model, using the RevMan 5.1 software developed by the Cochrane Collaboration. MAIN RESULTS: We included 19 studies (1756 participants). We selected only randomized, placebo‐controlled, double‐blinded studies to minimize inclusion of poor quality studies. However, the risk of bias in the included studies was not formally assessed. Children receiving a single intraoperative dose of dexamethasone (dose range = 0.15 to 1.0 mg/kg) were half as likely to vomit in the first 24 hours compared to children receiving placebo (risk ratio (RR) 0.49; 95% confidence interval (CI) 0.41 to 0.58; P < 0.00001). Routine use in five children would be expected to result in one less patient experiencing post‐tonsillectomy emesis (risk difference (RD) ‐0.24; 95% CI ‐0.32 to ‐0.15; P < 0.00001). Children receiving dexamethasone were also more likely to advance to a soft/solid diet on post‐tonsillectomy day one (RR 1.45; 95% CI 1.15 to 1.83; P = 0.001) than those receiving placebo. Finally, postoperative pain was improved in children receiving dexamethasone as measured by a visual analog scale (VAS, 0 to 10) (MD ‐1.07; 95% CI ‐1.73 to ‐0.41; P = 0.001), which correlates clinically to a reduction in pain (on a VAS of 0 to 10) from 4.72 to 3.65. No adverse events were noted in the included studies. AUTHORS' CONCLUSIONS: The evidence suggests that a single intravenous dose of dexamethasone is an effective, safe and inexpensive treatment for reducing morbidity from pediatric tonsillectomy.

Along with early detection, early intervention (EI) is critical for children identified with hearing loss. Evidence indicates that many children with sensorineural hearing loss experience improved language abilities if EI services were initiated at an "early" age. The present study's objectives were to determine the impact of a state EI program on language over time of children with permanent hearing loss and evaluate the association of EI enrollment by age 6 months with early language skill development. Young children in a state EI program were included in this longitudinal study. Results indicate that children enrolled prior to age 6 months were more likely to have age-appropriate language skills at baseline than children enrolled at or after 6 months, and maintained age-appropriate skills over time. Children enrolled at or after 6 months had lower baseline skills but made significant language progress, irrespective of hearing loss severity.

Cricotracheal resection (CTR) is an effective treatment for moderate-to-severe laryngotracheal stenosis (LTS) in adults. However, one of the potentially significant sequela of this procedure is postoperative dysphonia and permanent voice alteration. The objective of this study is to characterize voice changes in adult patients with subglottic stenosis who have undergone CTR.Retrospective case-series.Acoustic, aerodynamic, and consensus auditory-perceptual evaluation of voice (CAPE-V) data were reviewed for consecutive adult patients undergoing CTR and perioperative voice evaluation from 2000 to 2010.Sixteen patients (median age 44 years, 94% female) underwent CTR and voice evaluation during the study period. Thirteen patients underwent postoperative evaluation and had a mean overall CAPE-V score of 47.5/100, mean fundamental frequency (F0) of 156.7 Hz, average estimated subglottic pressure of 10.0 cm H(2) O, and an average airflow of 224 mL/sec. Seven patients underwent pre- and postoperative evaluations and had a significant reduction in mean F0 (206.5 vs. 151.1 Hz, P = .002) and mean F0 for connected speech (194.9 vs. 152.7 Hz, P = .047), but not in median intensity, range, estimated subglottic pressure, or airflow. Median overall CAPE-V scores worsened, but did not reach statistical significance (12 vs. 61.5, P = .28). Seventy-one percent of patients underwent an increase in acoustic signal typing postoperatively.Although CTR is an effective treatment for adult LTS, it results in significant alteration of the adult voice. In particular, CTR decreases the fundamental frequency of connected speech and vowel phonation and changes the acoustic signal type. Patients should be counseled about these likely voice alterations prior to undergoing surgery.

OBJECTIVES: To test the hypothesis that the promotion of national guidelines recommending the transfer of high-risk mothers to subspecialty perinatal centers reduces mortality and morbidity through the reduction of preterm infants delivered at nontertiary maternity hospitals. METHODS: After implementation of hospital-based educational and communication programs emphasizing the importance of maternal transfer to subspecialty perinatal centers, we conducted a population-based cohort study of all live births delivered at maternity hospitals in greater Cincinnati from 2003 through 2007 (n = 1825). Birth weights measured between 500 and 1499 g and gestational ages were less than 32 weeks. Risk-adjusted outcomes were measured by multivariate logistic regression in 2 stages. We compared these findings with those from a similar study conducted at our institution that included infants with birth weights less than 1500 g born between September 1, 1995, and December 31, 1997 (n = 848). The primary outcome was the percentage decrease in infants born with very low birth weights at nontertiary centers compared with our previous study. RESULTS: The number of infants born with birth weights less than 1500 g and at less than 32 weeks' gestation delivered at hospitals without tertiary perinatal and neonatal care decreased from 25% to 11.8% between the 2 study periods. The odds of death or major morbidity for infants born with very low birth weights at nontertiary perinatal centers is 3 times that of infants born at subspecialty perinatal centers after controlling for demographic variations (odds ratio: 3.05 [95% confidence interval: 2.1–4.4]). CONCLUSIONS: Local promotion of national guidelines by neonatologists coincided with a significant reduction in the percentage of infants born with birth weights less than 1500 g and at less than 32 weeks' gestation who were not delivered at subspecialty perinatal centers, and, at 88.2%, this nearly achieves the Healthy People 2010 objective to deliver 90% of infants born with very low birth weights in subspecialty perinatal centers.

The number of children receiving cochlear implants (CIs) with significant disabilities in addition to their deafness has increased substantially. Unfortunately, children with additional disabilities receiving CIs have largely been excluded from studies on cochlear implant outcomes. Thus limited data exists on outcomes in this population to guide pre-implant counseling for anticipated benefits. The study objectives were: (1) evaluate differences in post-cochlear implant language skills between children with cochlear implants and developmental disabilities and age/cognitively matched controls; (2) quantify possible discrepancies between language level and cognitive level. Fifteen children with a developmental disability who received a CI were matched 1:1 on nonverbal cognitive ability and age to hearing controls. Language was evaluated using Preschool Language Scale-IV and reported as language quotients. Multivariable mixed models for matched pairs analyzed differences in language levels between groups. No significant differences were seen between CI and control groups regarding insurance, maternal education, or family income level. Results of the multivariable models indicated that compared to matched controls, the CI group had significantly lower mean receptive (24.6 points, p=0.002) and mean expressive (21.9 points, p=0.001) language quotients after controlling for confounders such as number of therapies and weekly hours in therapy. Significant discrepancies between language level and cognitive level were seen among CI participants only. Compared to age- and cognitively matched controls, children with CIs had significantly lower language levels with delays disproportionate to their cognitive potential. Mechanisms behind this performance-functional gap need to be understood to deliver appropriate intervention strategies for this special population.

Objectives:Preterminfantsareoftenfedpasteurizeddonormilkormother’s milk that has been stored frozen for up to 4 weeks. Our objectives were to assess the impact of pasteurization or prolonged storage at � 208C on the immunologic components of human milk and the capability of the different forms of human milk to support bacterial proliferation. Materials and Methods: The concentrations and activities of major host defense proteins in the whey fractions of mother’s milk stored for 4 weeks at � 208C or pasteurized human donor milk were compared with freshly expressed human milk. Proliferation of bacteria incubated in the 3 forms of human milk was assessed. Results: Relative to freshly expressed human milk, the concentrations of lysozyme, lactoferrin, lactoperoxidase, and secretory immunoglobulin A were reduced 50% to 82% in pasteurized donor milk and the activities of lysozyme and lactoperoxidase were 74% to 88% lower (P

OBJECTIVE: We examined and characterized variation among NICUs in the use of vitamin A supplementation for the prevention of bronchopulmonary dysplasia in extremely low birth weight infants. METHODS: An historical cohort study of extremely low birth weight infants admitted within 7 days after birth to NICUs participating in the Pediatric Health Information System database, between January 1, 2005, and March 31, 2008, was performed. NICU medical directors were surveyed to determine attitudes and decision-making regarding adoption of vitamin A supplementation. The proportion of infants receiving vitamin A at each center was measured over time. Patient and hospital characteristics associated with vitamin A use were examined. RESULTS: Among 4184 eligible infants cared for in 30 NICUs, 1005 infants (24%) received vitamin A. Eighteen centers (60%) used vitamin A for some patients. Infants discharged in 2007 (odds ratio: 2.7 [95% confidence interval: 1.4–5.3]) and 2008 (odds ratio: 2.8 [95% confidence interval: 1.4–5.8]), compared with 2005, were more likely to receive vitamin A. NICU medical directors from centers using vitamin A, compared with centers that did not adopt vitamin A supplementation, reported stronger beliefs in the efficacy of vitamin A to reduce the incidence of bronchopulmonary dysplasia (83% vs 33%; P = .03) and in the ease with which vitamin A could be implemented (75% vs 22%; P = .02). CONCLUSIONS: Although the use of vitamin A is increasing, marked variation across NICUs remains. Provider attitudes and system characteristics seem to influence vitamin A adoption.

To identify maternal and neonatal factors that impact response to methadone therapy for neonatal abstinence syndrome. This is a retrospective review of 128 infants that received pharmacotherapy for opiate withdrawal to identify factors associated with favorable response to methadone therapy. Maternal and neonatal data were analyzed with univariate statistics and multivariate logistic regression. Maternal methadone maintenance dose during pregnancy correlated with length of stay (P=0.009). There was an inverse correlation between the amount of mother's breast milk ingested and length of stay (β=−0.03, P=0.02). Methadone was initiated later, tapered more rapidly and was more successful as monotherapy in preterm infants. Five percent of infants were admitted to hospital again for rebound withdrawal following reduction of breast milk intake. Severity of neonatal abstinence syndrome may be mitigated by titrating methadone to the lowest effective dose during pregnancy and by encouraging breast milk feeds, which should be weaned gradually.

To investigate secretor gene fucosyltransferase 2 (FUT2) polymorphism and secretor phenotype in relation to outcomes of prematurity.Study infants were ≤32 weeks gestational age. Secretor genotype was determined from salivary DNA. Secretor phenotype was measured with H antigen, the carbohydrate produced by secretor gene enzymes, in saliva samples collected on day 9 ± 5. The optimal predictive cutoff point in salivary H values was identified with Classification and Regression Tree analysis. Study outcomes were death, necrotizing enterocolitis (NEC, Bell's stage II/III), and confirmed sepsis.There were 410 study infants, 26 deaths, 30 cases of NEC, and 96 cases of sepsis. Analyzed by genotype, 13% of 95 infants who were non-secretors, 5% of 203 infants who were heterozygotes, and 2% of 96 infants who were secretor dominant died (P = .01). Analyzed by phenotype, 15% of 135 infants with low secretor phenotype died, compared with 2% of 248 infants with high secretor phenotype (predictive value = 76%, P.001). Low secretor phenotype was associated (P.05) with NEC, and non-secretor genotype was associated (P = .05) with gram negative sepsis. Secretor status remained significant after controlling for multiple clinical factors.Secretor genotype and phenotype may provide strong predictive biomarkers of adverse outcomes in premature infants.

Quantify post-cochlear implant (CI) language among children with disabilities and determine the role of nonverbal cognitive quotients (NVCQ) in predicting language.Small cohort study in pediatric tertiary care center.Children (n = 20) with CIs and developmental disabilities were enrolled. Receptive and expressive language was reported as language quotients (LQs). Pre- and post-CI LQs were compared using the signed-rank test. Multiple regression models analyzed language while controlling for possible confounders.Five subjects had symptomatic cytomegalovirus, and four subjects had CHARGE syndrome with hearing loss etiology. Seventy-five percent had cognitive deficits, and 55% had motor delays. Median age of CI was 24 months; median CI duration was 27.7 months. The range of NVCQs for the study cohort was 27 to 115. Fifteen subjects had NVCQs80. Age at implantation, income, and number of siblings were not correlated with language. Although children had significant increases in language age pre- to post-CI, median LQs did not significantly change after implantation. NVCQ, age at hearing loss diagnosis, implant duration, and number of different therapies attended were significant in models. NVCQ contributed the most unique variance (67%; P = .0003). Pre-CI language performance did not predict post-CI performance.This study is the first step in addressing the effects of CIs on language among children with disabilities. Progress in language skills occurred for all participants, although rates of progress were slow and highly variable. NVCQ was the strongest predictor of language, although cognition is not always sufficient for good language development. Adapting therapeutic strategies may be essential to impact greater language progress in these complex children.

Objectives We performed a retrospective review to compare a subjective parental proxy-derived voice handicap survey to an observer-derived method of measuring voice perturbation in children who have undergone airway reconstruction. The main outcome measures were the Pediatric Voice Handicap Index (pVHI) total score and the Overall Severity score on the Consensus Auditory-Perceptual Evaluation of Voice (CAPE-V). Methods The percent Overall Severity CAPE-V score (score divided by 100) and the percent pVHI score (score divided by 92) were calculated. A Wilcoxon signed rank test was used to compare CAPE-V scores with the pVHI total scores. The relationship between the pVHI scores and the CAPE-V scores was investigated with a Spearman correlation. Subgroup analysis was performed to determine the relationship of surgery type to CAPE-V and pVHI scores. Results Fifty subjects with a history of airway surgery who were evaluated between 2005 and 2008 were identified. Forty-two of the 50 subjects had complete data for review. Their median age was 7.1 years (range, 3.3 to 17.9 years). Their pVHI total scores had a median of 30 (range, 1 to 80). Their Overall Severity CAPE-V scores had a median of 50.5 (range, 0 to 98). Their median CAPE-V percent was higher than their median pVHI percent (50.5% versus 32.6%; p = 0.0003). A weak correlation was found between the Overall Severity CAPE-V score and the pVHI total score (rho = 0.41; p = 0.0003). There was a trend toward higher Overall Severity CAPE-V scores in patients who underwent cricotracheal resection. The total number of airway surgeries was significantly correlated with the Overall Severity CAPE-V score (rho = 0.6; p < 0.0001) but not with the pVHI score. Conclusions Children who undergo airway reconstruction often have a resulting voice disturbance that can affect their lives in multiple dimensions. The results of this study revealed a weak-to-fair correlation between the parent-reported pVHI total score and expert ratings of voice quality using the CAPE-V. In this patient population, both of these tools provided important information regarding the relationship of the severity of voice disturbance to its handicapping effects.

Objectives: We sought to determine the incidence of secondary airway lesions in infants with laryngomalacia and to compare the incidences of these concomitant airway lesions in infants with severe, moderate, and mild laryngomalacia; to determine whether infants with mild or moderate laryngomalacia have a higher incidence of surgical intervention when a secondary airway lesion is present; and to determine whether the incidence of gastroesophageal reflux disease (GERD) is affected by the presence of a secondary airway lesion. Methods: We performed a retrospective review of a database consisting of 201 infants with a diagnosis of laryngomalacia treated at a pediatric tertiary referral center between June 1998 and June 2003. Data pertaining to demographic information, severity of laryngomalacia, presence of secondary airway lesions, and diagnosis of GERD were collected and analyzed. Results: Of the 201 infants, 104 (51.7%) were found to have a secondary airway lesion. Subglottic stenosis was found in 38.8%, and tracheomalacia in 37.8%. Of the infants with severe laryngomalacia, 30 (79%) had a diagnosis of a secondary lesion, compared with 51 (61.5%) of those with moderate and 23 (28.8%) of those with mild disease. Among infants with mild or moderate disease, those with secondary airway lesions were more likely to require surgical intervention than were infants without secondary airway lesions (27% versus 5.6%; p = 0.0002). There was no difference in the rates of secondary airway lesions in infants managed with supraglottoplasty versus tracheotomy. The incidence of GERD in this patient population was 65.6%. Infants with a secondary airway lesion were more likely to have GERD than were those without a secondary airway lesion (84.6% versus 45.4%; p < 0.0001). Conclusions: The incidence of secondary airway lesions in our population of infants with laryngomalacia was higher than those previously reported. The severity of disease correlated with the diagnosis of a secondary airway lesion. Secondary airway lesions lead to an increased incidence of surgical intervention and GERD in infants with laryngomalacia.

To evaluate the utility of weight-for-length (defined as gm/cm(3), known as the "ponderal index") as a complementary measure of growth in infants in neonatal intensive care units (NICUs).This was a secondary analysis of infants (n=1214) of gestational age 26 to 29 weeks at birth, included in a registry database (1991-2003), who had growth data at birth and discharge. Weight-for-age and weight-for-length were categorized as small (10th percentile), appropriate, or large (90th percentile).Statistical agreement between the weight-for-age and weight-for-length measures was poor (kappa=0.02 at birth, 0.10 at discharge; Bowker test for symmetry, P.0001). From birth to discharge, the percentage of small-for-age infants increased from 12% to 21%, the percentage of small-for-length infants decreased from 10% to 4%, the percentage of large-for-age infants remained similar (1%), and the percentage of large-for-length infants increased from 5% to 17%. At discharge, 92% of the small-for-age infants were appropriate or large-for-length, and 19% of the appropriate-for-age infants were large-for-length.Weight-for-age and weight-for-length are complementary measures. Weight-for-length or other measures of body proportionality should be considered for inclusion in routine growth monitoring of infants in the NICU.

To determine the association between human milk (HM) intake and risk of necrotizing enterocolitis (NEC) or death among infants 401 to 1000 g birth weight. Analysis of 1272 infants in the National Institute of Child Health and Human Development Neonatal Network Glutamine Trial was performed to determine if increasing HM intake was associated with decreased risk of NEC or death. HM intake was defined as the proportion of HM to total intake, to enteral intake and total volume over the first 14 days. Known NEC risk factors were included as covariates in Cox proportional hazard analyses for duration of survival time free of NEC. Among study infants, 13.6% died or developed NEC after 14 days. The likelihood of NEC or death after 14 days was decreased by a factor of 0.83 (95% confidence interval, CI 0.72, 0.96) for each 10% increase in the proportion of total intake as HM. Each 100 ml kg−1 increase in HM intake during the first 14 days was associated with decreased risk of NEC or death (hazard ratio, HR 0.87 (95% CI 0.77, 0.97)). There appeared to be a trend towards a decreased risk of NEC or death among infants who received 100% HM as a proportion to total enteral intake (HM plus formula), although this finding was not statistically significant (HR 0.85 (95% CI 0.60, 1.19)). These data suggest a dose-related association of HM feeding with a reduction of risk of NEC or death after the first 2 weeks of life among extremely low birth weight infants.

We assessed the utility of the modified Kigali combined (MKC) staging system for predicting survival in HIV-infected Zambian adults in a prospective, longitudinal, open cohort. From 1995 to 2004, HIV-discordant couples (one HIV-infected partner and one HIV-negative partner) were recruited from couples' voluntary counseling and testing centers in Lusaka, Zambia and followed at 3-month intervals. MKC stage, which incorporates clinical stage with erythrocyte sedimentation rate (ESR), hematocrit, and body mass index (BMI), was determined at enrollment. Kaplan–Meier survival and Cox proportional hazard methods were used to calculate median survival and relative hazards. We enrolled 1479 HIV-discordant couples with a combined 7305 person-years of follow-up. Among HIV-infected participants over the 9-year study period, there were 333 confirmed deaths. The time to 50% mortality was 8.5 years with MKC stage 1 and 2 disease compared to 3.7 years with MKC stage 4 disease at enrollment. Survival rates at 3 years were 85% with MKC stage 1 and 2 disease, 74% with MKC stage 3 disease, and 51% with MKC stage 4 disease. A total of 275 HIV-negative partners seroconverted during follow-up. In comparison, survival rates at 3 years were 94% for HIV-negative participants and 92% for participants who seroconverted during follow-up. In multivariate analysis, MKC stage 4 disease (HR = 3.7, 95% CI = 2.7–5.0) remained a strong predictor of mortality. Incorporating ESR, hematocrit, and BMI with clinical staging is a powerful, low-cost tool to identify HIV-infected adults at high risk for mortality.

Premature infants are at unique risk for developing acute kidney injury (AKI) due to incomplete nephrogenesis, early exposure to nephrotoxic medications, and coexisting conditions such as patent ductus arteriosus (PDA) and respiratory distress syndrome (RDS). Unfortunately, laboratory testing for the diagnosis of AKI in this population is problematic because of the physiology of both the placenta and the extra-uterine premature kidney. Recent research has led to the development of promising biomarkers for the early detection of AKI in children but there are no published reports in neonates. Our goal was to determine whether urine neutrophil gelatinase-associated lipocalin (NGAL) was detectable in premature infants and to correlate levels with gestational age, birth weight (BW), or indomethacin exposure. We enrolled 20 infants in four BW groups: 500-750, 751-1000, 1001-1250, and 1251-1500 g. Urine was collected every day for the first 14 d of life. Neonates born at earlier gestational ages and lower BWs had higher urine NGAL levels (p < 0.01). We conclude that urine NGAL is easily obtained in premature infants and that it correlates significantly with both BW and gestational age. The use of urinary NGAL as a biomarker of AKI in premature infants warrants further investigation.

Summary Objectives Caregivers of children who are deaf/hard of hearing have been reported to have greater stress than caregivers of children with normal hearing. The time of diagnosis is a particularly stressful time and stress levels may change over time based on varying needs at different life events. Thus, we hypothesized that stress experienced by caregivers evolves over time and is impacted by the duration since the diagnosis of hearing loss. Methods The 68-item pediatric hearing impairment caregiver experience (PHICE) is a validated questionnaire used to measure stress. The PHICE was administered to 152 caregivers of children with permanent hearing loss. Domain scores were converted into z-scores for analysis of trends of stress over time. Results Parents of children whose hearing loss was identified more than 60 months ago reported higher stress levels regarding educational aspects of their child's needs as compared to parents of children with less than 24 months or 24–60 months duration since diagnosis. Parents of children diagnosed with hearing loss within the preceding 24 months reported higher stress levels in the area of healthcare than parents of children diagnosed greater than 24 months ago. Conclusions Parental stressors change over time with respect to the time of diagnosis of hearing impairment. This phenomenon was observed irrespective of the age of diagnosis of hearing loss. As professionals serving families of children with hearing loss, we should be aware of changing stressors over time and identify the appropriate support services for families to meet those changing needs. By addressing those evolving stressors, the families’ ability to support and improve the outcomes for their children who are deaf or hard of hearing may be enhanced.

This study examines the impact of an intervention to promote dual-method contraceptive use among HIV concordant and discordant couples already using condoms for HIV prevention.A three-armed randomized, controlled trial was conducted at a voluntary HIV testing and counseling clinic in Lusaka, Zambia; 251 couples were randomized. Control couples received family planning education and referral to an outside clinic for nonbarrier contraceptives, intervention 1 couples received education and offer of contraceptives at the research clinic, and intervention 2 couples received intervention 1 plus a presentation designed to reduce outside pressures to conceive.There was a 3-fold higher contraceptive initiation rate in both intervention arms compared with the control arm. The interventions had no impact on incident pregnancy, largely due to high levels of contraceptive discontinuation and user failure. HIV-positive women who initially selected injectable contraception were less likely to abandon the method and significantly less likely to conceive than other study participants.Improving access to nonbarrier contraceptives among couples already using condoms for HIV prevention increased dual-method use. Selection of longer-acting injectable contraception was associated with lower pregnancy rates among HIV-positive women. Further research is needed to identify ways to help couples in this population continue to correctly use nonbarrier contraceptives.

HYPOTHESIS The purpose of this study is to test the hypothesis that virally encoded immunomodulatory genes play a role in cytomegalovirus (CMV)-related hearing loss. OBJECTIVE Cytomegalovirus is the leading cause of infectious-related congenital sensorineural hearing loss worldwide. Unfortunately, little is known about the pathophysiology of CMV-related injury to the developing ear. METHODS Viral mutagenesis techniques were developed that allow the deletion of a specific viral immunomodulatory gene, macrophage inflammatory protein (MIP) 1alpha homolog. We assessed the extent to which this gene product contributed to auditory pathologic findings in the guinea pig (GP) model. Eighteen weanling GPs (250-350 g) were used under an Institutional Animal Control and Use Committee-approved protocol. We analyzed preinoculation hearing using auditory brainstem response recordings. Intracochlear inoculations were performed on one group of six GPs with sterile viral media, 6 GPs with wild-type (WT) CMV virus, and 6 GPs with mutant "knockout" (KO) virus (with deleted MIP-1alpha homolog). Auditory brainstem responses were then obtained on postinoculation Days 7, 14, 21, and 28. RESULTS There was a significant difference in hearing between the KO group and the WT group, with significantly better hearing in the KO group. A comparison of the KO group to the sham group revealed no significant hearing differences between the groups. The WT group had significant threshold shifts by dose at all frequencies meeting our criteria of hearing loss (>30 dB). There were no statistical differences in the sham or KO group. CONCLUSION Virally encoded immunomodulatory genes such as MIP-1alpha seem to play a significant role in CMV-related hearing loss. This study is the first demonstration of the role of specific viral immune modulation genes in the in vivo pathogenesis of CMV-induced hearing loss in a relevant animal model.

Objectives To compare the spectrum, concentration, and activity of host defense proteins (HDPs) on the skin surface of newborns and adults, to assess variation in HDP concentrations in different anatomic regions in newborns, and to examine alteration in HDP concentrations with care practices. Study design Proteins recovered from tape discs applied to stratum corneum of 25 term newborns (forehead and posterior trunk) and 20 adults (forehead) were analyzed by Western analysis for 5 HDPs and for muramidase activity. Protein concentrations were compared in samples obtained after delivery, after the first bath, and at 24 hours of age. Results Total protein was 2.8-fold higher in adults compared with newborns. Lysozyme and lactoferrin were detected in all samples. In contrast to total protein, lysozyme concentrations and muramidase activity were 5-fold higher in newborns relative to adults and were not altered after bathing. Lysozyme concentrations were significantly higher over the trunk compared with the forehead in newborns. Conclusions The newborn skin surface is replete with prototypical HDPs, lysozyme, and lactoferrin. Bathing does not significantly diminish concentrations. These factors are likely to contribute importantly to the newborn infants' defense against invasive bacterial infections.

To correlate genetic and audiometric findings with a detailed radiologic analysis of the temporal bone in patients with enlarged vestibular aqueduct (EVA) to ascertain the contribution of SLC26A4 gene mutations to this phenotype.A retrospective review of patients with EVA identified in a database of pediatric hearing-impaired patients.A tertiary care pediatric referral center.Seventy-one children with EVA and screening results for SLC26A4 mutations.Genetic screening results, audiometric thresholds, and radiographic temporal bone measurements.Seventy-one children with EVA were screened for SLC26A4 mutations. Mutations were found in 27% of children overall, while only 8% had biallelic mutations. The mean initial pure-tone average (PTA) was 59 dB; the mean final PTA was 67 dB. A bilateral EVA was found in 48 (67%) of the children; a unilateral EVA was found in 23 (33%). Progressive hearing loss (in at least 1 ear) was seen in 29 (41%) of the patients. The strongest genotype-phenotype interaction was seen in children with a bilateral EVA. Among children with SLC26A4 mutations, there was a significantly wider vestibular aqueduct at the midpoint and a wider vestibule width (P.05) than in children without the mutation. Among patients with a bilateral EVA, children with any SLC26A4 mutation were more likely to have a more severe final PTA (64 dB vs 32 dB), larger midpoint measurement (2.1 vs 1.1 mm), and larger operculum measurement (3.0 vs 2.0 mm) than those without the mutation in their better-hearing ear (P.05).In a population of pediatric patients with an EVA and hearing loss, SLC26A4 mutations are a contributor to the phenotype. Our data suggest that other genetic factors also have important contributions to this phenotype. The presence of an abnormal SLC26A4 allele, even in the heterozygous state, was associated with greater enlargement of the vestibular aqueduct, abnormal development of the vestibule, and possibly a stable hearing outcome.

Objective The study goal was to determine the prevalence and clinical significance of a large vestibular aqueduct (LVA) in children with sensorineural hearing loss (SNHL). Study Design and Setting We conducted a retrospective review of a pediatric SNHL database. One hundred seven children with SNHL were selected and their radiographic and audiometric studies were evaluated. Radiographic comparisons were made to a group of children without SNHL. Results A vestibular aqueduct (VA) larger than the 95th percentile of controls was present in 32% of children with SNHL. Progressive SNHL was more likely to occur in ears with an LVA and the rate of progressive hearing loss was greater than in ears without an LVA. The risk of progressive SNHL increased with increasing VA size as determined by logistic regression analysis. Conclusions An LVA is defined as one that is ≥2 mm at the operculum and/or ≥1 mm at the midpoint in children with nonsyndromic SNHL. An LVA appears to be more common than previously reported in children with SNHL. A linear relationship is observed between VA width and progressive SNHL. Significance The finding of an LVA in children with SNHL provides diagnostic as well as prognostic information.

OBJECTIVE. The American Academy of Pediatrics recommended routine use of varicella vaccine in pediatric practice in 1995. We examined the impact of varicella immunization on population-based rates of pediatric varicella-related hospitalizations and emergency department (ED) visits in the years before and after introduction of varicella vaccine.STUDY DESIGN. Discharge data for hospitalizations and ED encounters from 1990 through 2003 were queried for patients RESULTS. During the 14-year study period, there were 3983 incident varicella cases; 335 patients were hospitalized and 3833 were treated only in the ED. The rate of varicella-related hospitalizations decreased from 15.7 cases per 100000 population to 5.5 cases per 100000 population between the prevaccine period (1990–1995) and the postvaccine period (1996–2003); varicella-related ED use decreased from 178.2 cases per 100000 population to 61.2 cases per 100000 population. In the prevaccine period, hospitalization and ED visit rates were significantly higher for black children than for white children. In the postvaccine period, hospitalization rates did not differ according to race but ED visit rates remained significantly higher for black children, compared with white children.CONCLUSIONS. Varicella-related hospitalization and ED visit rates decreased significantly for both white and black children in Hamilton County, Ohio, after the introduction of varicella vaccine, and the racial disparity found before licensure decreased after licensure.

A multicenter study of 308 children with Autism Spectrum Disorder (ASD) was conducted through the Collaborative Programs of Excellence in Autism (CPEA), sponsored by the National Institute of Child Health and Human Development, to compare the family history of autoimmune disorders in children with ASD with and without a history of regression. A history of regression was determined from the results of the Autism Diagnostic Interview-Revised (ADI-R). Family history of autoimmune disorders was obtained by telephone interview. Regression was significantly associated with a family history of autoimmune disorders (adjusted OR=1.89; 95% CI: 1.17, 3.10). The only specific autoimmune disorder found to be associated with regression was autoimmune thyroid disease (adjusted OR=2.09; 95% CI: 1.28, 3.41).

This study compared production of IL-2, IFN-γ, IL-4, IL-13, IL-5 and IL-10 in peripheral blood mononuclear cells from 20 children with autism spectrum disorder to those from matched controls. Levels of all Th2 cytokines were significantly higher in cases after incubation in media alone, but the IFN-γ/IL-13 ratio was not significantly different between cases and controls. Cases had significantly higher IL-13/IL-10 and IFN-γ/IL-10 than controls. Conclusion: Children with ASD had increased activation of both Th2 and Th1 arms of the adaptive immune response, with a Th2 predominance, and without the compensatory increase in the regulatory cytokine IL-10.

Summary Background Children with severe to profound sensorineural hearing loss due to GJB2 mutations have often been deemed good cochlear implant candidates. Studies on children with GJB2 mutations and cochlear implants have typically excluded children with additional disabilities. Objective To investigate the presence of additional disabilities among children with and without GJB2 mutations in a cochlear implant population. Methods A retrospective chart review was performed of children with non-syndromic sensorineural hearing loss (SNHL) who received a cochlear implant between 1993 and 2004. Results Among 108 children within the cochlear implant database; 46 patients met the inclusion criteria of idiopathic non-syndromic hearing loss. Sixteen children had GJB2 mutations, 12 were GJB2 negative, and 17 did not receive GJB2 testing but had no other identifiable etiology or risk factor contributing to hearing loss. The proportion of children with additional disabilities that would affect either pre-operative assessments or post-operative results in the GJB2 positive group was 44% compared to 33% of children in the GJB2 negative. Additional disabilities were present in 41% of the children who did not receive GJB2 testing. The disabilities in the GJB2 positive group included specific learning disability, apraxia, epileptiform aphasia, attention deficit disorder, global developmental delay, and gross motor delay. The GJB2 negative and those children not receiving GJB2 testing had motor delays, language delay, autism, specific learning disability, and attention deficit disorder. The proportion of children with at least 6 months CI use who relied on oral communication was 62% in the GJB2 positive group, 66% in the GJB2 negative group, and 38% in the untested group. A majority of the genetic alleles were 35delG (81%) and 10 of 16 (63%) patients with GJB2 mutations were homozygous 35delG. The rate of developmental diagnoses was similar in patients with homozygous GJB2 compared to compound heterozygous genotypes. Conclusions The presence of biallelic GJB2 mutations does not rule out non-hearing related disorders that can have an effect on speech, language and learning. Forty-four percent of children with GJB2 mutations had other conditions that could directly affect pre-implant evaluation and post-implant performance. This rate is similar to the reported prevalence among the overall population of children with hearing loss. All children should have a comprehensive evaluation of development and behavior regardless of the etiology of hearing loss.

Summary Objective To determine the relationship between the type of transducer used to perform pure-tone audiometry and the appearance of low-frequency hearing loss at 250 Hz and 500 Hz for patients with ventilation tubes. Methods Air conduction thresholds at 250 Hz and 500 Hz were measured using Telephonics TDH-49 supra-aural headphones and EARTONE 3-A insert earphones for patients with normal ears (N = 16) and patients with ventilation tubes (N = 114). Tympanometry was performed on each patient prior to audiometric testing. Audiometric test results obtained in normal ears were compared to results for patients with ventilation tubes. For analysis, the ventilation tube patients were separated into two groups, representative of ventilation tube type. Results Audiometric results obtained using the two transducer types at 250 Hz and 500 Hz revealed significant differences in threshold for patients with ventilation tubes. Thresholds obtained using insert earphones were generally worse than thresholds obtained using supra-aural headphones for this group. On average, difference in threshold was 14.15 dB worse with insert earphones at 250 Hz and 9.75 dB worse with insert earphones at 500 Hz for patients with Sheehy tubes. Average difference in threshold for patients with Donaldson tubes was 13.93 dB worse with insert earphones at 250 Hz and 8.93 dB worse with insert earphones at 500 Hz. In addition, thresholds were more variable for patients with ventilation tubes than normal ears at 500 Hz. There were no significant differences in threshold for normal ears using both transducers. Conclusions When performing pure-tone audiometry, choice of transducer can influence the accurate identification of a low-frequency hearing loss in patients with ventilation tubes. Low-frequency thresholds were generally worse using insert-style earphones to test subjects with tubes, resulting in the apparent identification of a hearing loss. However, with supra-aural headphones, no low-frequency hearing loss existed. There were no significant differences in threshold values using either transducer in normal ears.

Objective To determine the association between maternal milk levels of 2-linked fucosylated oligosaccharide and prevention of diarrhea as a result of Campylobacter, caliciviruses, and diarrhea of all causes in breast-fed infants. Study design Data and banked samples were analyzed from 93 breast-feeding mother-infant pairs who were prospectively studied during 1988-1991 from birth to 2 years with infant feeding and diarrhea data collected weekly; diarrhea was diagnosed by a study physician. Milk samples obtained 1 to 5 weeks postpartum were analyzed for oligosaccharide content. Data were analyzed by Poisson regression. Results Total 2-linked fucosyloligosaccharide in maternal milk ranged from 0.8 to 20.8 mmol/L (50%-92% of milk oligosaccharide). Moderate-to-severe diarrhea of all causes (n = 77 cases) occurred less often ( P = .001) in infants whose milk contained high levels of total 2-linked fucosyloligosaccharide as a percent of milk oligosaccharide. Campylobacter diarrhea (n = 31 cases) occurred less often ( P = .004) in infants whose mother's milk contained high levels of 2′-FL, a specific 2-linked fucosyloligosaccharide, and calicivirus diarrhea (n = 16 cases) occurred less often ( P = .012) in infants whose mother's milk contained high levels of lacto- N -difucohexaose (LDFH-I), another 2-linked fucosyloligosaccharide. Conclusion This study provides novel evidence suggesting that human milk oligosaccharides are clinically relevant to protection against infant diarrhea.

Summary Objective: To determine families’ perceived benefits of cochlear implants in children with multiple-handicaps. Methods: Parents/guardians of a child with a cochlear implant for at least 3 months, under the age of 18 years and had least one additional disability were recruited for participation through rehabilitation therapists. Families who did not have a child enrolled in therapy at the study center were contacted by mail. Families were asked a number of open-ended and close-ended questions. Interviews were audiotaped and transcribed, with answers to open-ended questions coded by themes. Results: We interviewed 19 families of 20 children and included 15 families of 16 children who had had at least 6 months of cochlear implant experience for this study. The mean time between implantation and study was 3 years (S.D. ± 2.2) with a range of 0.5–8 years. Children were highly compliant in wearing their device. Sixty-eight percent (11/16) of the children were enrolled in additional therapies beyond speech and aural rehabilitation therapies. Fifty percent of families (8/16) indicated they had no obstacles to accessing therapies. Insurance was the most common barrier to accessing therapies (18% of respondents). All children made communication progress post-implant as described by their families. All families felt that the cochlear implant team provided enough information prior to receiving the implant to help families make the appropriate decision about implanting their child. All families said that if they were to make the decision again, they would choose to have their child implanted. Conclusion: More children with multiple-handicaps are receiving cochlear implants. Very young children may undergo cochlear implantation only to be subsequently diagnosed with an additional impairment or disability at later ages. As a result, it is important to understand the specific needs of this population and the parental perceptions of benefit in order to provide the best services and opportunities for success with a cochlear implant. Although not all of the children gained gold standard speech and language outcomes, all children broadened their communication skills. In motivated families of children with additional disabilities, it is appropriate to provide them with the same opportunity to access audition and expand their communication abilities as any other child with a hearing impairment.

Human milk contains a variety of bioactive agents, including oligosaccharides, which are part of the innate defense system (Hanson et al. 1991; Zopf & Roth 1996; Newburg et al. 1998; Erney et al. 2000; Hamosh 2001; Chaturvedi et al. 2001). Oligosaccharides are the third largest solid constituent of human milk after lactose and lipids (Stahl et al. 1994; Zopf & Roth 1996; Erney et al. 2000; Chaturvedi et al. 2001; Hamosh 2001). α 1,2-Linked fucosylated oligosaccharides in human milk have been shown to inhibit host ligand binding to Campylobacter, caliciviruses, and other enteric pathogens (Newburg et al. 1990; Crane et al. 1994; Marionneau et al. 2002; Ruiz-Palacios et al. 2003; Huang et al. 2003). Significant variation exists between mothers in the quantity of α 1,2-linked fucosylated oligosaccharides in their milk. We conducted this study in breastfed infants to determine the clinical relevance of the observed variation in human milk fucosylated oligosaccharides in relation to protection offered infants against diarrhea due to Campylobacter jejuni and caliciviruses.

Iron deficiency is the most common nutrient deficiency associated with anemia in childhood (CDC 1998), affecting more than half of infants in developing countries (WHO 2001). Bioavailability of iron in human milk is high, yielding about 50% absorption (Dallman 1988; Oski 1993; Saarinen et al. 1977; Krebs 2001). Iron available for absorption is at its highest in early transitional milk and steadily decreases over the course of lactation (Siimes et al. 1979). By six months, complementary foods are needed to provide the nutrients necessary for infant development (Picciano 2001; Dewey 2001). It is not known if a critical period of vulnerability towards iron deficiency exists in infants.

Breastfed infants have a lower risk of diarrhea than infants fed artificial formula. Human milk components, including oligosaccharides, inhibit pathogens in vitro and are postulated to protect infants from disease. Most human milk oligosaccharides are fucosylated. The fucose terminus may be connected by an a 1,2 linkage catalyzed by a fucosyltransferase produced by the secretor gene (FUT2), or by an α1,3 or α1,4 linkage catalyzed by fucosyltransferases produced by the Lewis gene (FUT3) or other α1,3 transferase genes (FUT4,5,6,7,9) of this family. The secretor and Lewis genes also control expression of the Lewis blood group type (Erney et al. 2000, Henry et al. 1995). Some women are nonsecretors, i.e., they do not secrete 2-linked fucosyloligosaccharides into their milk and other bodily fluids. Even among secretors, however, the expression of milk fucosyloligosaccharides varies significantly (Chaturvedi et al. 2001, Erney et al. 2000, Thurl et al. 1997, Viverge et al. 1990). Enterotoxigenic Escherichia coli that produce stable toxin (ST-E. coli) is a common cause of diarrhea; the ability of stable toxin to cause diarrhea is inhibited by human milk α1,2-linked fucosyloligosaccharides in vitro and in vivo.

Background and objectives: Sexual behavior following voluntary HIV counseling and testing (VCT) is described in 963 cohabiting heterosexual couples with one HIV positive and one HIV negative partner (‘discordant couples’). Biological markers were used to assess the validity of self-report. Methods: Couples were recruited from a same-day VCT center in Lusaka Zambia. Sexual exposures with and without condoms were recorded at 3-monthly intervals. Sperm detected on vaginal smears pregnancy and sexually transmitted diseases (STD) including HIV gonorrhea syphilis and Trichomonas vaginalis were assessed. Results: Less than 3% of couples reported current condom use prior to VCT. In the year after VCT > 80% of reported acts of intercourse in discordant couples included condom use. Reporting 100% condom use was associated with 39–70% reductions in biological markers; however most intervals with reported unprotected sex were negative for all biological markers. Under-reporting was common: 50% of sperm and 32% of pregnancies and HIV transmissions were detected when couples had reported always using condoms. Positive laboratory tests for STD and reported extramarital sex were relatively infrequent. DNA sequencing confirmed that 87% of new HIV infections were acquired from the spouse. Conclusions: Joint VCT prompted sustained but imperfect condom use in HIV discordant couples. Biological markers were insensitive but provided evidence for a significant under-reporting of unprotected sex. Strategies that encourage truthful reporting of sexual behavior and sensitive biological markers of exposure are urgently needed. The impact of prevention programs should be assessed with both behavioral and biological measures. (authors)

Magnetic resonance imaging of the brain was performed in 26 preterm infants with necrotizing enterocolitis (NEC) or spontaneous intestinal perforation at term equivalent age. Infants with surgical NEC or spontaneous intestinal perforation had significantly more brain injury on magnetic resonance imaging compared with infants with medical NEC, even after adjustment for confounders.