Association Between Third-Trimester Tdap Immunization and Neonatal Pertussis Antibody Concentration.

Importance: Immunization with tetanus, diphtheria, and acellular pertussis (Tdap) vaccine is recommended in the United States during weeks 27 through 36 of pregnancy to prevent life-threatening infant pertussis. The optimal gestation for immunization to maximize concentrations of neonatal pertussis toxin antibodies is unknown. Objective: To determine pertussis toxin antibody concentrations in cord blood from neonates born to women immunized and unimmunized with Tdap vaccine in pregnancy and optimal gestational age for immunization to maximize concentrations of neonatal antibodies. Design, Setting, and Participants: Prospective, observational, cohort study of term neonates in Houston, Texas (December 2013-March 2014). Exposures: Tdap immunization during weeks 27 through 36 of pregnancy or no Tdap immunization. Main Outcomes and Measures: Primary outcome was geometric mean concentrations (GMCs) of pertussis toxin antibodies in cord blood of Tdap-exposed and Tdap-unexposed neonates and proportions of Tdap-exposed and Tdap-unexposed neonates with pertussis toxin antibody concentrations of 15 IU/mL or higher, 30 IU/mL or higher, and 40 IU/mL or higher, cutoffs representing quantifiable antibodies or levels that may be protective until the infant immunization series begins. Secondary outcome was the optimal gestation for immunization to achieve maximum pertussis toxin antibodies. Results: Six hundred twenty-six pregnancies (mean maternal age, 29.7 years; 41% white, 27% Hispanic, 26% black, 5% Asian, 1% other; mean gestation, 39.4 weeks) were included. Three hundred twelve women received Tdap vaccine at a mean gestation of 31.2 weeks (range, 27.3-36.4); 314 were unimmunized. GMC of neonatal cord pertussis toxin antibodies from the Tdap-exposed group was 47.3 IU/mL (95% CI, 42.1-53.2) compared with 12.9 IU/mL (95% CI, 11.7-14.3) in the Tdap-unexposed group, for a GMC ratio of 3.6 (95% CI, 3.1-4.2; P < .001). More Tdap-exposed than Tdap-unexposed neonates had pertussis toxin antibody concentrations of 15 IU/mL or higher (86% vs 37%; difference, 49% [95% CI, 42%-55%]), 30 IU/mL or higher (72% vs 17%; difference, 55% [95% CI, 49%-61%]), and 40 IU/mL or higher (59% vs 12%; difference, 47% [95% CI, 41%-54%]); P < .001 for each analysis. GMCs of pertussis toxin antibodies were highest when Tdap vaccine was administered during weeks 27 through 30 and declined thereafter, reaching a peak at week 30 (57.3 IU/mL [95% CI, 44.0-74.6]). Conclusions and Relevance: Immunization with Tdap vaccine during the third trimester of pregnancy, compared with no immunization, was associated with higher neonatal concentrations of pertussis toxin antibodies. Immunization early in the third trimester was associated with the highest concentrations.

Pediatric Irritable Bowel Syndrome Patient and Parental Characteristics Differ by Care Management Type.

OBJECTIVES: This study evaluates whether certain patient or parental characteristics are associated with gastroenterology (GI) referral versus primary pediatrics care for pediatric irritable bowel syndrome (IBS). METHODS: A retrospective clinical trial sample of patients meeting pediatric Rome III IBS criteria was assembled from a single metropolitan health care system. Baseline socioeconomic status (SES) and clinical symptom measures were gathered. Various instruments measured participant and parental psychosocial traits. Study outcomes were stratified by GI referral versus primary pediatrics care. Two separate analyses of SES measures and GI clinical symptoms and psychosocial measures identified key factors by univariate and multiple logistic regression analyses. For each analysis, identified factors were placed in unadjusted and adjusted multivariate logistic regression models to assess their impact in predicting GI referral. RESULTS: Of the 239 participants, 152 were referred to pediatric GI, and 87 were managed in primary pediatrics care. Of the SES and clinical symptom factors, child self-assessment of abdominal pain duration and lower percentage of people living in poverty were the strongest predictors of GI referral. Among the psychosocial measures, parental assessment of their child's functional disability was the sole predictor of GI referral. In multivariate logistic regression models, all selected factors continued to predict GI referral in each model. CONCLUSIONS: Socioeconomic environment, clinical symptoms, and functional disability are associated with GI referral. Future interventions designed to ameliorate the effect of these identified factors could reduce unnecessary specialty consultations and health care overutilization for IBS.

Evidence-Based Management of Patients with 45,X/46,XY Gonadal Dysgenesis and Male Sex Assignment: from Infancy to Adulthood.

45,X/46,XY gonadal dysgenesis is a disorder of sexual differentiation with a wide clinical presentation, ranging from Turner-like females to individuals with genital ambiguity to azoospermic but otherwise normal-appearing males. Hence, patients can be assigned female or male sex. Female patients are managed according to the Turner Syndrome Guidelines, whereas males are managed on a case-by-case basis. Male patients present with multiple medical challenges: undervirilization, hypogonadism, gonadoblastoma risk, and short stature. Many require surgeries and hormonal treatments that are time-sensitive and irreversible. Nonetheless, these therapeutic decisions are made without evidence-based guidelines. This review describes the medical concerns and possible interventions in male patients with 45,X/46,XY dysgenesis for each stage of development. Interventions should be addressed within a patient-centered framework by a multidisciplinary team and after thorough discussion with the family. We use the GRADE system to appraise the existing evidence and provide recommendations based on the available evidence.

Unrecognized hepatitis B in pre-screened children with hematologic and oncologic conditions.

BACKGROUND: This study evaluates the effectiveness and interpretation of hepatitis B (HBV) screening in an at-risk cohort of children with cancer or blood disorders. PROCEDURE: We conducted a retrospective epidemiologic analysis of children who screened positive for HBV (HBsAg, HbcAb) from 1999 to 2009 at a quaternary children's hospital, focusing on patients with hematologic and oncologic conditions. Descriptive statistics were generated for demographics and serologies. Follow-up of positive serologies and clinical outcomes were analyzed. RESULTS: A total of 12,754 children were screened for HBV. Of 391 that screened positive, 118 had a hematologic or oncologic diagnosis. Leukemia, anemia, and thrombocytopenia comprised 84% of diagnoses. The majority (98%) tested HBcAb positive but only 20% received confirmatory HBV DNA testing. Three patients (13% of those HBV DNA tested) were identified to have chronic disease. HBV was not a known pre-existing condition, and chemotherapy preceded HBV diagnosis in all cases. CONCLUSIONS: The majority of children with cancer or blood disorders who screened HBV positive did not receive follow-up DNA testing, exposing them to reactivation risk and delaying definitive therapy. HBcAb may be the only indicator of chronic HBV infection and DNA confirmation should be routine. Our findings suggest a significant number of additional patients eligible for HBV treatment may have been identified with reflexive DNA testing.

Abdominal near-infrared spectroscopy measurements are lower in preterm infants at risk for necrotizing enterocolitis.

OBJECTIVE: Near-infrared spectroscopy is a noninvasive method of measuring local tissue oxygenation (StO2). Abdominal StO2 measurements in preterm piglets are directly correlated with changes in intestinal blood flow and markedly reduced by necrotizing enterocolitis. The objectives of this study were to use near-infrared spectroscopy to establish normal values for abdominal StO2 in preterm infants and test whether these values are reduced in infants who develop necrotizing enterocolitis. DESIGN: We conducted a 2-year prospective cohort study where we prospectively measured abdominal StO2 in preterm infants, to establish reference values for preterm infants, and compared the near-infrared spectroscopy values with preterm infants in the cohort that developed necrotizing enterocolitis. SETTING: Two neonatal ICUs: one at Texas Children's Hospital and the other at Ben Taub General Hospital in Houston, TX. PATIENTS: We enrolled 100 preterm infants (< 32 weeks' gestation and < 1,500 g birth weight) between January 2007 and November 2008. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Eight neonates with incomplete data were excluded. Mean abdominal StO2 in normal preterm infants (n = 78) during the first week of life was significantly higher than in those who later developed necrotizing enterocolitis (n = 14) (77.3% ± 14.4% vs 70.7% ± 19.1%, respectively, p = 0.002). An StO2 less than or equal to 56% identified preterm infants progressing to necrotizing enterocolitis with 86% sensitivity, 64% specificity, 96% negative predictive value, and 30% positive predictive value. Using logistic regression, StO2 less than or equal to 56% was independently associated with a significantly increased risk of necrotizing enterocolitis (odds ratio, 14.1; p = 0.01). Furthermore, infants with necrotizing enterocolitis demonstrated significantly more variation in StO2 both during and after feeding in the first 2 weeks of life. CONCLUSIONS: This study establishes normal values for abdominal StO2 in preterm infants and demonstrates decreased values and increased variability in those with necrotizing enterocolitis. Abdominal near-infrared spectroscopy monitoring of preterm infants may be a useful tool for early diagnosis and guiding treatment of necrotizing enterocolitis.

Body weight has no impact on self-esteem of minority children living in inner city, low-income neighborhoods: a cross-sectional study.

BACKGROUND: The relationship between body weight and self-esteem among underserved minority children is not well documented. METHODS: We measured the self-esteem profile using the Self-Perception Profile for Children among 910 minority children at 17 Houston community centers. RESULTS: Weight status had no effect on any of the self-esteem scores among the minority children (P ≥ 0.21). Black children had higher scholastic competence than Hispanic children (P = 0.05). Social acceptance was not affected by age, gender, and race/ethnicity (P ≥ 0.13). Significant age x gender (P = 0.006) and race x gender (P = 0.005) interactions were detected on athletic competence. The younger boys had higher athletic competence than the younger and older girls (P ≤ 0.01). The older boys had higher athletic competence than the older girls (P = 0.008) but their scores were not different from those of the younger girls (P = 0.07). Within each race/ethnicity group, boys had higher athletic competence than girls (P ≤ 0.03). Black boys had higher athletic competence than Hispanic girls (P = 0.007) but their scores were not different from those of the Hispanic boys (P = 0.08). Age and gender had no effect on physical appearance but black children had higher scores than Hispanic children (P = 0.05). Behavioral conduct was not affected by age, gender, or race/ethnicity (P ≥ 0.11). There was an age x gender interaction on global self-worth (P = 0.02) with boys having similar scores regardless of ages (P = 0.40) or ethnicity (P = 0.98). However, boys from both age groups had higher global self-worth than the older girls (P ≤ 0.04) but their scores were not different from those of the younger girls (P ≥ 0.07). CONCLUSIONS: For the first time, we documented that being normal weight did not necessarily guarantee positive self-esteem among minority children. Their self-esteem scores were similar to those found among children who were diagnosed with obesity and obesity-related co-morbidities and lower than those reported among normal-weight white children. Therefore, activities to promote self-esteem are important when working with underserved minority children in order to promote a healthy lifestyle.

Types of pediatric diabetes mellitus defined by anti-islet autoimmunity and random C-peptide at diagnosis.

OBJECTIVE: To test the hypothesis that anti-islet autoantibody expression and random serum C-peptide obtained at diagnosis define phenotypes of pediatric diabetes with distinct clinical features. SUBJECTS: We analyzed 607 children aged <19 yr consecutively diagnosed with diabetes after exclusion of 13% of cases with secondary diabetes (e.g., cystic fibrosis related, steroid induced) and 7.3% of cases lacking measurement of C-peptide and/or autoantibodies. METHODS: Autoantibody positivity (A+) was defined as ≥ 1 positive out of GAD65, insulin, and ICA512 antibodies. Preserved beta-cell function (ß+) was defined as random serum C-peptide at diagnosis ≥ 0.6 ng/mL. Body mass index (BMI) was measured at median 1.2 months after diagnosis. Characteristics at diagnosis and 2 yr (range 18-30 months) after diagnosis were compared among groups. RESULTS: Autoantibody expression and C-peptide at diagnosis defined the following groups: A+ß- (52.1% of the children), A+ß+ (32.8%), A-ß+ (12.5%), and A-ß- (2.6%). These four groups differed in gender, race/ethnicity, and clinical characteristics at diagnosis [i.e., age, pubertal development, obesity/overweight, diabetic ketoacidosis, glycemia, and hemoglobin A1c (HbA1c)] and at 2 yr (i.e., clinical diagnosis, treatment, and HbA1c) (all p < 0.0001). Among all ß+ children, C-peptide >2 ng/mL was associated with lower HbA1c at onset (p = 0.0001) and, in the A+ß+ subgroup, with higher frequency of achieving HbA1c < 7% at 2 yr (p = 0.03). All three patients (0.7% of total) with monogenic diabetes (maturity onset diabetes of the young, MODY) were A-ß+ with C-peptide between 0.6 and 2 ng/mL. CONCLUSIONS: Anti-islet autoantibodies status and serum random C-peptide at diagnosis define four distinct phenotypes of pediatric diabetes with prognostic value.

Sleep duration of underserved minority children in a cross-sectional study.

BACKGROUND: Short sleep duration has been shown to associate with increased risk of obesity. Childhood obesity is more prevalent among underserved minority children. The study measured the sleep duration of underserved minority children living in a large US urban environment using accelerometry and its relationship with BMI, socioeconomic status (SES), gender, ethnicity and physical activity. METHODS: Time spent on sleep and physical activity among 333 Hispanic and 150 black children (9-12 y) was measured objectively by accelerometry over 5-7 consecutive days. The children were recruited at 14 underserved community centers in Houston, Texas, between January 2009 and February 2011. Body weight and height were measured in duplicate. RESULTS: The majority of children (88.8%) wore the monitor for 6 consecutive days. The children slept 8.8 ± 0.6 (mean ± SD) h/d and spent 45 ± 24 min/d on moderate-vigorous physical activity (MVPA). Hispanic children slept 0.2 h/d longer (P<0.001) than black children. Obese children slept 0.2 h/d less (P<0.02) than normal-weight children. SES had no effect on sleep duration. There was a significant interaction between gender and age (P<0.03); girls aged 11-12 y slept 0.3 h/d less than boys and the younger girls. Children slept 0.6 h/d longer (P<0.001) during the weekend than weekdays. No relation was detected between sleep duration and MVPA time. CONCLUSIONS: Minority children living in a large metropolitan area in the US are not meeting the National Sleep Foundation recommendation for sleep duration of 10-11 h/d. Longitudinal studies based on objective measures are needed to establish causality between sleep duration and obesity risk among minority children.

Multicomponent school-initiated obesity intervention in a high-risk, Hispanic elementary school.

The aim of the study was to determine the effectiveness of a school-initiated cognitive and behavioral program to reduce childhood obesity. Height, weight, body mass index (BMI), and BMI z scores were obtained at the beginning and end of the school year at an intervention school (n = 1022) and at a control school (n = 692). The prevalence of overweight and obesity was 18.9% and 30.4% versus 19% and 30.2%, respectively, in the intervention and control schools. The incidence of overweight increased in the control school, but the incidence of obesity, weight, and BMI z scores increased significantly in the intervention school, suggesting that implementation of any school-based obesity intervention programs requires careful planning to achieve goals.

Association between left ventricular mass index and cardiac function in pediatric dialysis patients.

BACKGROUND: Left ventricular mass index (LVMI) is a surrogate of left ventricular hypertrophy and a predictor of cardiac morbidity and mortality in adults with hypertension. LVMI has not been linked to cardiovascular endpoints in children. The aim of this study was to identify an association between elevated LVMI and echocardiographic markers of systolic and diastolic function. METHODS: The study was a retrospective review of chronic dialysis patients from June 1995 to December 2009 at a single tertiary care children's hospital. The upper limit cutoffs for LVMI were set at >38.6 g/m(2.7), >51 g/m(2.7), and by age and sex-based normative values. Sixty-three patients (mean age 14.1 years, 56% males) were enrolled in the study, with a total of 287 echocardiograms. RESULTS: Post-dialysis hypertension was associated with elevated LVMI in both the >51 g/m(2.7) [odds ratio (OR) 2.9, 95% confidence interval (CI) 1.5-5.5] and normative (OR 3.4, 95% CI 1.5-7.7) models. Elevated LVMI, when defined by the >51 g/m(2.7) and normative models, was significantly associated with decreased shortening fraction (OR 4.1, 95% CI 1.7-9.8 and OR 5.4, 95% CI 1.3-22.9, respectively) and increased mitral E wave to lateral mitral tissue Doppler e' wave velocity ratio (E/e'; OR 3.5, 95% CI 1.1-11.2 and OR 4.5, 95% CI 1.0-21.6, respectively). CONCLUSIONS: Elevated LVMI is associated with decreased systolic and diastolic cardiac function, justifying its use as a surrogate of hypertensive cardiomyopathy in children undergoing chronic dialysis.

Restrictive physiology is associated with poor outcomes in children with hypertrophic cardiomyopathy.

Pediatric patients with hypertrophic cardiomyopathy (HCM) and restrictive physiology (RP) with poor outcomes have been identified, but data on their course are limited. Our goal was to delineate the clinical features and course of children with HCM and RP. An institutional review of 119 patients identified between 1985 and 2010 with the diagnosis of HCM was performed. The diagnosis of RP was based on >1 echocardiogram along with at least one of the following: left atrial enlargement without evidence of left ventricle dilation, E/E' ratio ≥ 10, and E/A ratio ≥ 3. Outcomes analysis was performed using Cox or Poisson regression when appropriate. RP was present in 50 (42%) patients. In patients without RP, 10-year freedom-from-death or aborted sudden cardiac death (aSCD), and death or heart transplant (HT), were 93.6 and 98.5%, respectively. In patients with RP, 10-year freedom-from-death or aSCD, and death or HT, were 59.0 and 71.2%, respectively. RP conferred a 3.5-fold increase in incidence rate of hospitalization (P = 0.01), a 3.8-fold increase in hazard of death or aSCD (P = 0.02), and a 5.7-fold increase in hazard of death or HT (P = 0.04). Assessment for RP is of paramount importance in children with HCM because those without RP have a good prognosis, and those with RP account for the majority of poor outcomes.

Assessment of DNA methylation at the interferon regulatory factor 5 (IRF5) promoter region in inflammatory bowel diseases.

BACKGROUND AND AIMS: A 5-bp insertion-deletion (indel) polymorphism in the promoter of interferon regulatory factor 5 (IRF5) has been associated with inflammatory bowel diseases (IBD). This polymorphism generates an additional binding site for the transcription factor SP1 and has been shown to augment the expression of IRF5. Additionally, it affects a CpG dinucleotide-dense genomic region. These features of the indel suggested that it may influence the epigenetic regulation of IRF5. The aim of this study was to investigate the potential effect of the 5-bp indel on the methylation pattern of four CpG sites upstream of the polymorphism. Possible CpG site methylation differences in this region between healthy persons and individuals suffering from IBD were also tested. METHODS: Genotype was determined by 4% polyacrylamide gel electrophoresis in 33 peripheral blood leukocyte (PBL) DNA samples. DNA methylation correlates of the genotypes were measured by bisulfite pyrosequencing. IRF5 promoter methylation in association to disease state was assessed in 87 proband (49 healthy, 18 Crohn's disease, 20 ulcerative colitis) PBL samples. RESULTS: The polymorphism did not affect the methylation pattern of the IRF5 promoter nor could we detect significant differences in the average, low methylation of the locus between healthy persons and individuals with IBD. CONCLUSIONS: These results implicate that epigenetic dysregulation of the IRF5 promoter is unlikely to be associated with IBD.

Recurrent seizure-related injuries in people with epilepsy at a tertiary epilepsy center: a 2-year longitudinal study.

Though seizure-related injuries (SRIs) among people with epilepsy (PWE) have recently gained much attention in the literature, most studies are retrospective and data are gathered indirectly through questionnaires or medical record documentation. We investigated SRIs and their associated risks in PWE attending a tertiary care center with direct and systematic inquiries during routine clinic follow-up visits over a 2-year period (N = 306). Past SRIs occurred in 54% of all patients, and 24% experienced recurrent SRIs during the study period. On multiple regression analyses, past SRI was associated with tonic-clonic seizures (TCSs) (3.2, 95% CI = 1.7-5.8) and cognitive handicap (4.3, 95% CI 1.5-16.1), and recurrent SRI was associated with TCSs (3.5, 95% CI = 1.6-7.9). Most recurrent SRIs (72%) involved head injury. SRIs are common when assessed systematically in a tertiary care setting, and TCSs represent a risk factor for recurrent SRIs. The potential clinical impact of recurrent SRIs on PWE requires further study.

Serum KL-6 level and the development of bronchiolitis obliterans syndrome in lung transplant recipients.

KL-6 is a glycoprotein expressed by pulmonary epithelial cells, and its serum level has been used as a marker of disease activity in a variety of respiratory illnesses. Previously, we showed that KL-6 was elevated in lung transplant recipients diagnosed with BOS. In this study, we followed serum KL-6 levels and lung functions prospectively in lung transplant recipients who were within the first five-yr post-transplant and had no evidence of BOS at the time of study entry. Mean peak KL-6 levels were 596.16 ± 309.32 U/mL in the nine recipients who developed BOS compared to 352.41 ± 140.68 in 36 recipients who did not (p = 0.05). Six of the nine patients with BOS had an absolute rise in KL-6 above baseline level >200 U/mL compared to two of the 37 who had the same increase in KL-6 but did not develop BOS. Using the 200 U/mL elevation of KL-6 from baseline as a threshold for a positive test would produce a sensitivity of 67%, specificity of 95%, PPV of 75%, and a NPV of 92%. In addition, mean KL-6 levels of patients during acute rejection were not significantly elevated compared to the prerejection mean KL-6 levels (p = 0.71). We conclude that serum KL-6 is a relatively specific marker of BOS in lung transplant recipients.

Automated external defibrillators and simulated in-hospital cardiac arrests.

OBJECTIVE: To test the hypothesis that pediatric residents would have shorter time to attempted defibrillation using automated external defibrillators (AEDs) compared with manual defibrillators (MDs). STUDY DESIGN: A prospective, randomized, controlled trial of AEDs versus MDs was performed. Pediatric residents responded to a simulated in-hospital ventricular fibrillation cardiac arrest and were randomized to using either an AED or MD. The primary end point was time to attempted defibrillation. RESULTS: Sixty residents, 21 (35%) interns, were randomized to 2 groups (AED = 30, MD = 30). Residents randomized to the AED group had a significantly shorter time to attempted defibrillation [median, 60 seconds (interquartile range, 53 to 71 seconds)] compared with those randomized to the MD group [median, 103 seconds (interquartile range, 68 to 288 seconds)] (P < .001). All residents in the AED group attempted defibrillation at <5 minutes compared with 23 (77%) in the MD group (P = .01). CONCLUSIONS: AEDs improve the time to attempted defibrillation by pediatric residents in simulated cardiac arrests. Further studies are needed to help determine the role of AEDs in pediatric in-hospital cardiac arrests.

Facial Nerve Grading System 2.0.

OBJECTIVE: To present an updated version of the original Facial Nerve Grading Scale (FNGS), commonly referred to as the House-Brackmann scale. STUDY DESIGN: Controlled trial of grading systems using a series of 21 videos of individuals with varying degrees of facial paralysis. RESULTS: The intraobserver and interobserver agreement was high among the original and revised scales. Nominal improvement is seen in percentage of exact agreement of grade and reduction of instances of examiners differing by more then one grade when using FNGS 2.0. FNGS 2.0 also offers improved agreement in differentiating between grades 3 and 4. CONCLUSION: FNGS 2.0 incorporates regional scoring of facial movement, providing additional information while maintaining agreement comparable to the original scale. Ambiguities regarding use of the grading scale are addressed.

Neonatal dietary cholesterol and alleles of cholesterol 7-alpha hydroxylase affect piglet cerebrum weight, cholesterol concentration, and behavior.

This experiment was designed to test the effect of polymorphism in the cholesterol 7-alpha hydroxylase (CYP7) gene locus and dietary cholesterol (C) on cerebrum C in neonatal pigs fed sow's milk formulas. Thirty-six pigs (18 male and 18 female) genetically selected for high (HG) or low (LG) plasma total C were weaned at 24-36 h after birth and assigned in a 2 x 2 x 2 factorial arrangement of treatments with 2 diets (0 or 0.5% C), 2 sexes, and 2 genotypes (HG and LG). Individually housed pigs consumed diets ad libitum for 42 d. Open-field behavior was tested at wk 2 and 4. All pigs were killed at 42 d of age, the cerebrum was weighed, and C content and concentration measured. All data were analyzed by general linear model ANOVA. Cerebrum weight was greater in HG than LG pigs (P < 0.03) but was not affected by diet or sex. Pigs fed C tended to have a higher cerebrum C concentration than those deprived (P = 0.12). At 2 wk, LG pigs explored a novel open-field environment less often (P < 0.001) than did HG pigs. At 4 wk, some LG pigs explored the open field but fewer (P < 0.001) vs. HG pigs retreated back to the safe area. There were no genotype x diet, genotype x sex, or diet x sex interactions affecting cerebrum weight, or C content or concentration. Polymorphism in the CYP7 gene locus affected cerebrum weight and behavior and dietary C tended to increase cerebrum C concentration in neonatal pigs. These findings in neonatal pigs have considerable potential importance in human infant nutrition and behavioral development.

Ventricular function and long-term pacing in children with congenital complete atrioventricular block.

OBJECTIVE: To determine the sequela of right ventricular pacing in children with congenital complete atrioventricular block. BACKGROUND: Pacing is a well-accepted therapy for patients with congenital complete atrioventricular block. The long-term sequela of right ventricular pacing in this population has not been well described. METHODS: We performed a cohort study on all patients with congenital complete atrioventricular block who underwent pacemaker implantation at our institution from 1972 to 2004. Patients with associated congenital heart disease or ventricular dysfunction prior to pacemaker implantation were excluded. RESULTS: A total of 63 patients were included in the study. The median age at pacemaker implantation was 6.5 years, with an average follow-up of 9.9 years. The cumulative dysfunction free survival at 20 years was 92%. In total, four patients (6%) were noted to develop LV dysfunction an average of 15.1 years after pacemaker implantation. Of 30 patients who were paced for >10 years, only three (10%) developed echocardiographic evidence of LV dysfunction. Right ventricular apex pacing and prolonged QRS duration were found to be predictive of decreased long-term LV systolic function (P < 0.05). CONCLUSIONS: Left ventricular dysfunction in patients with congenital complete atrioventricular block is a rare finding, even in those who have been paced for more than 10 years. Right ventricular apex pacing and prolonged QRS duration may be associated with decreased ventricular function over time. At this time, with such a low incidence of cardiac dysfunction, right ventricular pacing should be considered an acceptable first-line therapy in this population.

Safety and efficacy of nesiritide in pediatric heart failure.

BACKGROUND: We hypothesized that recombinant B-type natriuretic peptide (BNP) (nesiritide) could improve urine output and neurohormonal markers of heart failure without worsening renal function in pediatric patients. METHODS AND RESULTS: We analyzed our experience involving 140 nesiritide infusions in 63 consecutive children. Serum levels of BNP and electrolytes were measured before and after therapy. Dosing was begun at 0.01 mcg.kg.min without a bolus and titrated to a maximum of 0.03 mcg.kg.min, in 0.005-mcg.kg.min increments. Blood pressure, heart rate, and heart rhythm were monitored. In a substudy, 20 patients with decompensated cardiomyopathy-related heart failure received 72 hours of nesiritide with prospective assessment of aldosterone, norepinephrine, plasma renin, and endothelin-1 levels before and after therapy. The heart rate decreased significantly (P = .001). Urine output increased significantly on Days 1 and 3 (P < or = .001 and .004, respectively). The mean serum creatinine level decreased from 1.135 to 1.007 mg/dL (P < or = .001). In the substudy, aldosterone levels decreased from 37.5 +/- 57.1 to 20.5 +/- 41.9 ng/dL (P = .005). Plasma renin, norepinephrine, and endothelin-1 levels decreased nonsignificantly. Two infusions were discontinued because of hypotension. CONCLUSIONS: Nesiritide safely treated decompensated heart failure in children. Increased urine output reflected improving renal function. Improved neurohormonal markers were seen after 72 hours of therapy, and complications were uncommon.