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.

Context: Obese Hispanic adolescents (OHAs) with dysglycemia have increased cardiovascular disease risk burden. Objective: To investigate if nonalcoholic fatty liver disease (NAFLD) confers added risk for endothelial dysfunction in these youth. Design: Cross-sectional study. Setting: Academic institution. Participants: Thirty-six OHAs (15.3 ± 0.4 years), 20 with prediabetes and 16 with type 2 diabetes, with and without NAFLD. Intervention: Evaluation of reactive hyperemia index (RHI) and augmentation index (AIx) by peripheral arterial tonometry; muscle, hepatic, and adipose tissue insulin sensitivity (IS; hyperinsulinemic-euglycemic clamp 80 mu/m2/min, with [6,6 2H2]glucose and [2H5] glycerol); body composition; and abdominal and hepatic fat by magnetic resonance imaging/spectroscopy. Outcome Measures: RHI and AIx. Hypothesis: OHAs with dysglycemia and NAFLD have worse RHI and AIx vs those without NAFLD. Results: The NAFLD (n = 23) and non-NAFLD (n = 13) groups were of similar age, sex, glycemic status, body mass index, % body fat and abdominal fat. The NAFLD group had higher hepatic fat (P < 0.001) lower skeletal muscle IS (P = 0.01), hepatic IS (P = 0.01), and adipose tissue IS (P = 0.04). The NAFLD vs non-NAFLD group had lower RHI (1.4 ± 0.05 vs 1.7 ± 0.09, P = 0.002), greater AIx (–6.0 ± 1.6 vs –12.0 ± 2.1, P = 0.03). Hepatic fat was inversely related to RHI (r = –0.49, P = 0.002) and positively related to AIx (r = 0.45, P = 0.006). Hepatic IS (r = –0.42, P = 0.01) and adipose IS (r = –.54, P = 0.001) correlated with arterial stiffness (AIx). Conclusion: In OHAs with dysglycemia, NAFLD is associated with worse endothelial function. RHI and AIx were related to hepatic fat content. Vascular stiffness was related to hepatic and adipose tissue insulin resistance.

Objective: To evaluate the impact of a tuberculosis (TB) educational intervention (EI) on change in adolescent student knowledge and participation in a TB prevention program.Methods: From 2/2013-5/2015, students from 2 high schools in Houston, TX participated. The 25-min EI discussed TB bacteriology, epidemiology, symptoms, and indications for TB testing/treatment. Students completed pre-and post-quizzes. Immediately after the EI, students were invited to participate in voluntary TB risk-factor screening, testing and treatment. At 6 months, focus groups were conducted.Results: 895 students attended the EI. 827 students (92%) completed the EI quizzes. Knowledge improved by 12% (pre: 70%; post: 82%, p < 0.001); 78% shared their TB knowledge. Following the EI, 671/827 (81%) enrolled in a TB prevention program. Focus groups indicated that the EI stimulated student learning about TB and increased their willingness to participate.Conclusion: A brief, one-time, TB EI is an effective method to encourage adolescents to learn about TB and motivate their uptake of TB risk-factor screening, testing and treatment. Similar EIs should accompany TB prevention programs targeting adolescents.Practice implications: The study's procedures could be considered for incorporation into school-based TB prevention programs to improve the identification, testing and treatment of adolescents at risk for TB. (C) 2016 Elsevier Ireland Ltd. All rights reserved.

Background: Screening for and treating tuberculosis (TB) infection in children and adolescents is an effective way of decreasing future TB cases. However, current approaches leave many children at risk for TB unidentified. Methods: We recruited adolescent students from 2 public high schools (a magnet and a low-income) in the Houston Independent School District. Compared with the magnet school, the student population at the low-income school was larger, primarily Hispanic and economically disadvantaged. Students were educated about TB, and parents completed a risk factor questionnaire. Students with TB risk factors were tested using 2 interferon gamma release assays (IGRAs). Those with a positive IGRA received a 12-dose regimen of weekly isoniazid/rifapentine (3HP) administered via direct observation at school. Results: Nine hundred twenty-five students received TB education; 73% of their parents submitted the TB questionnaire. Eighty-six percent of students (n = 415) with a TB risk factor identified on the study questionnaire agreed to IGRA testing. Sixteen students had at least one positive IGRA (1% [magnet], 4.1% [low-income]; P = 0.005). Recent student travel to a high-risk country (7) or contact with TB disease (2) were associated with IGRA positivity (P < 0.05). All students with a positive IGRA accepted, tolerated and completed 3HP treatment at school. Conclusions: School-based TB education, screening, testing using IGRAs and administration of 3HP treatment is feasible to improve the identification and treatment of adolescent students at risk for TB.

AIMTo assess pediatric patients for choledocholithiasis. We applied current adult guidelines to identify predictive factors in children.METHODSA single-center retrospective analysis was performed at a tertiary children's hospital. We evaluated 44 consecutive pediatric patients who underwent endoscopic retrograde cholangiography (ERCP) for suspected choledocholithiasis. Patients were stratified into those with common bile duct stones (CBDS) at ERCP vs those that did not using the American Society of Gastrointestinal Endoscopy (ASGE) guidelines (Very Strong and Strong criteria) for suspected CBDS.RESULTSCBDS were identified in 84% at the time of ERCP. Abdominal ultrasound identified CBDS in 36% of patients. Conjugated bilirubin ≥ 0.5 mg/dL was an independent risk factor for CBDS (P = 0.003). The Very Strong (59.5%) and Strong (48.6%) ASGE criteria identified the majority of patients (P = 0.0001). A modified score using conjugated bilirubin had a higher sensitivity (81.2% vs 59.5%) and more likely to identify a stone than the standard criteria, odds ratio of 25.7 compared to 8.8. Alanine aminotransferase and gamma-glutamyl transferase values identified significant differences in a subset of patients with odds ratio of 4.1 and 3.25, respectively.CONCLUSIONCurrent adult guidelines identified the majority of pediatric patients with CBDS, but specific pediatric guidelines may improve detection, thus decreasing risks and unnecessary procedures.

BACKGROUND:Respiratory failure is a leading cause of neonatal mortality in the developing world. Bubble continuous positive airway pressure (bCPAP) is a safe, effective intervention for infants with respiratory distress and is widely used in developed countries. Because of its high cost, bCPAP is not widely utilized in low-resource settings. We evaluated the performance of a new bCPAP system to treat severe respiratory distress in a low resource setting, comparing it to nasal oxygen therapy, the current standard of care.METHODS:We conducted a non-randomized convenience sample study to test the efficacy of a low-cost bCPAP system treating newborns with severe respiratory distress in the neonatal ward of Queen Elizabeth Central Hospital, in Blantyre, Malawi. Neonates weighing >1,000 g and presenting with severe respiratory distress who fulfilled inclusion criteria received nasal bCPAP if a device was available; if not, they received standard care. Clinical assessments were made during treatment and outcomes compared for the two groups.FINDINGS:87 neonates (62 bCPAP, 25 controls) were recruited. Survival rate for neonates receiving bCPAP was 71.0% (44/62) compared with 44.0% (11/25) for controls. 65.5% (19/29) of very low birth weight neonates receiving bCPAP survived to discharge compared to 15.4% (1/13) of controls. 64.6% (31/48) of neonates with respiratory distress syndrome (RDS) receiving bCPAP survived to discharge, compared to 23.5% (4/17) of controls. 61.5% (16/26) of neonates with sepsis receiving bCPAP survived to discharge, while none of the seven neonates with sepsis in the control group survived.INTERPRETATION:Use of a low-cost bCPAP system to treat neonatal respiratory distress resulted in 27% absolute improvement in survival. The beneficial effect was greater for neonates with very low birth weight, RDS, or sepsis. Implementing appropriate bCPAP devices could reduce neonatal mortality in developing countries.

AimTo study whether DPD epitope-specific glutamate decarboxylase autoantibodies are found more frequently in children with milder forms of Type 1 diabetes.MethodsWe prospectively evaluated 75 children with new-onset autoimmune Type 1 diabetes, in whom we collected demographic, anthropometric and clinical data and measured islet autoantibodies. Glutamate decarboxylase 65 autoantibody-positive samples were analysed for epitope specificities using recombinant Fab against the DPD-defined epitope of glutamate decarboxylase 65.ResultsAfter adjustment for age, positive DPD epitope recognition was significantly associated with higher C-peptide levels at onset (P = 0.02, r(2)=0.21, n = 35), and high DPD recognition in the highest quartile tended to be associated with HbA(1c) 53 mmol/mol (7%) at the last follow-up [mean (sd) follow-up 1.3 (0.4) years; P = 0.07; for the model, P = 0.044, n = 30)]. Age- and sex-adjusted BMI percentile was significantly correlated with recognition of the DPD-defined epitope (P < 0.03, r(2)=0.14, n = 34), but this correlation was driven by the older age group (age 10 years; P = 0.016, r(2)=0.27, n = 21) and was not significant in younger children (P = 0.93, n = 13). There were no independent associations with sex, race/ethnicity, diabetic ketoacidosis, HbA(1c), HLA DR3-DQ2/DR4-DQ8 or autoantibody number.ConclusionsOur findings suggest that recognition of the DPD-defined glutamate decarboxylase 65 autoantibody epitope at Type 1 diabetes onset is directly associated with -cell function, BMI and age, which supports the hypothesis that immunological factors contribute to the clinical heterogeneity of Type 1 diabetes. Larger studies relating epitope-specific glutamate decarboxylase 65 autoantibody to clinical phenotype in children with Type 1 diabetes are warranted.

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.

PURPOSE:To measure serum levels of bevacizumab and to compare serum levels of free vascular endothelial growth factor (VEGF) and insulin-like growth factor-1 (IGF-1) in infants who were treated with either intravitreal injection of bevacizumab (IVB) or laser for type 1 retinopathy of prematurity (ROP).METHODS:Twenty-four infants with type 1 ROP were randomized into three treatment groups: IVB at 0.625 mg per eye per dose, IVB at 0.25 mg per eye per dose, and laser. Blood samples were collected prior to treatment and on posttreatment days 2, 14, 42, and 60. Weekly body weights were documented from birth until 60 days post treatment. Serum levels of bevacizumab, free VEGF, and IGF-1 were measured with enzyme-linked immunosorbent assay (ELISA).RESULTS:Serum bevacizumab was detected 2 days after the injection, peaked at 14 days, and persisted for up to 60 days with half-life of 21 days. Area under the curve (AUC) analysis showed that systemic exposure to bevacizumab was variable among the subjects and was dose dependent. Serum free VEGF levels decreased in all three subgroups 2 days post treatment, with more significant reductions found in both IVB-treated groups, P = 0.0001. Serum IGF-1 levels were lower in both IVB-treated groups.CONCLUSIONS:Clearance of bevacizumab from the bloodstream in premature infants takes at least 2 months. Although serum free VEGF levels decreased following either laser or bevacizumab treatment, the reductions were more significant in the IVB-treated groups. Potential long-term effects of systemic exposure to bevacizumab in infants need to be studied further.

Gonadal dysgenesis (GD) is associated with increased risk of gonadal malignancy. Determining a patient’s risk and appropriate timing of gonadectomy is challenging, but immunohistochemical markers (IHM) may help establish the diagnosis of malignant germ cell tumors (GCT). Our objective was to identify the prevalence of specific IHM expression in patients with GD and determine if the patterns of expression can help identify malignancy versus pre-malignancy state. We evaluated the published literature using the Grading of Recommendation, Assessment, Development, and Evaluation (GRADE) system to provide recommendations on the predictive role of IHM in the detection of germ cell malignancy.

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.

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.

Objectives/HypothesisAlterations in swallowing can occur after tracheotomy and can result in varying degrees of aspiration. In tracheotomized adult patients, use of a Passy Muir Speaking Valve (PMV) has been shown to decrease laryngeal penetration and aspiration of foods and liquids. The objective of this study was to determine if the PMV has a similar effect on laryngeal penetration and aspiration in tracheotomized children.Study DesignThis is a prospective case‐control study.MethodsPediatric patients with tracheotomies who were able to tolerate the PMV were identified. Modified barium swallow (MBS) was performed with and without the PMV. Two consistencies, thin liquids and purées, were used. Two speech language pathologists (SLPs), who were blinded to the PMV status, reviewed the recorded MBSs. Three swallows of each consistency were graded on an 8 point Penetration‐Aspiration Scale. Residue in the vallecula, piriform sinuses, and posterior pharyngeal wall was graded.ResultsTwelve patients were included for analysis. Laryngeal penetration and aspiration was decreased with purées over liquids (P = 0.5 and P = 0.005, respectively) with either the sham valve or the PMV. The presence of the PMV decreased piriform sinus residue (P = 0.01); however, it did not demonstrate a decrease in laryngeal aspiration or penetration.ConclusionUnlike in adults, the presence of PMV did not decrease laryngeal aspiration or penetration in children with tracheotomies. It did, however, improve piriform sinus residue.Level of Evidence3b. Laryngoscope, 124:1469–1474, 2014

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.

BACKGROUND:Food allergies affect 2.5% of the US population. Results of studies show that minorities have the highest prevalence of food allergies. The Houston Independent School District (HISD) has an urban, socioeconomically diverse population and the role of ethnicity and socioeconomic status (SES) with availability of epinephrine has not been explored in this population. OBJECTIVE:This study sought to understand the association of SES and the presence of epinephrine in urban schools. METHODS:A 6-item questionnaire about food allergy characteristics was sent by e-mail to one nurse per elementary school in the HISD to identify the number, characteristics and treatment of food allergic reactions, and the presence of epinephrine injectors. The reactions and presence of injectors were assessed for the previous school year. Schools were categorized by socioeconomic variables as "low" or "non-low" based on National School Lunch Program student participation. Poisson, logistic, and linear regression analyses were used for group comparisons. RESULTS:One or more children with food allergies were reported in 97% of responding schools, but only 43% of schools reported having epinephrine injectors. A larger number of injectors in schools were associated with students of higher SES (r(2) = 0.701; P < .001). There were 6 times more injectors in non-low SES schools than in low SES schools (P < .03). Low SES and limited English proficiency were associated with decreased epinephrine injectors in schools. CONCLUSION:In the HISD, epinephrine injectors were more likely to be found in non-low SES schools versus low SES schools. Because minority students are disproportionately highly represented in low SES schools, there appears to be a disparity in the availability of injectable epinephrine for minority students in HISD schools.

To catalogue patients with DSD and to assess the concordance of genotype and phenotype with sex assignment at birth compared to sex assignment before and following assessment by a Gender Medicine Team (GMT) at one institution, as an initial step in formulating standardized guidelines for management of these conditions.

BackgroundThis study evaluates the effectiveness and interpretation of hepatitis B (HBV) screening in an at-risk cohort of children with cancer or blood disorders.ProcedureWe 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.ResultsA 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.ConclusionsThe 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. Pediatr Blood Cancer 2014;61:865-868. (c) 2013 Wiley Periodicals, Inc.

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 (β+) 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+β- (52.1% of the children), A+β+ (32.8%), A-β+ (12.5%), and A-β- (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 β+ children, C-peptide >2 ng/mL was associated with lower HbA1c at onset (p = 0.0001) and, in the A+β+ 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-β+ 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.

OBJECTIVE:To examine the relationship between BMI and beta-cell function at diagnosis of autoimmune type 1 diabetes (T1D) in a large group of ethnically diverse children. METHODS:Cross-sectional analysis of 524 children (60.8% White, 19.5% Hispanic, 14.5% African-American, 5.2% other non-Hispanic; mean age = 9.8 yr [SD = 2.5]) with newly diagnosed autoimmune T1D. RESULTS:As much as 22.2% of children were overweight or obese. Median random serum C-peptide was 0.40 ng/mL (25th-75th percentiles = 0.3-0.8), with median glycemia of 366 mg/dL (25th-75th percentiles = 271-505). Median C-peptide was 0.3, 0.5, 0.7, and 0.85 ng/mL, respectively, in underweight, normal weight, overweight, and obese children (p < 0.0001, Kruskal-Wallis). In the final model (p < 0.0001), the odds of having preserved C-peptide (≥0.6 ng/mL) were increased by 2.4-fold (95% CI = 1.2-4.9, p < 0.015) and 4.1-fold (1.9-8.5, p < 0.0001), respectively, in overweight and obese compared to lean children; 1.3-fold per each year of age; 2.5-fold in girls compared to boys; 4-fold in children who presented without, compared to with, diabetes ketoacidosis (DKA); and decreased by 21% for each point increase in HbA1c. Tanner stage, race/ethnicity, glycemia, and number of anti-islet antibodies expressed were not independently associated with preserved C-peptide. The association between BMI and C-peptide levels was significant in children with and without preserved C-peptide. Excluding patients who presented with DKA and/or using BMI obtained 5 wk after diagnosis did not alter the results. CONCLUSION:Obese and overweight children compared to lean children have greater beta-cell function at the onset of autoimmune T1D. Prospective studies on the relationships among BMI, beta-cell function, and progression to clinical T1D are warranted.