Neonatal Ampicillin/Gentamicin Exposure and the Risk of Childhood Obesity in South Bronx Pediatric Population.

OBJECTIVE: This study aimed to assess the association between neonatal antibiotic exposure and the risk of childhood obesity. STUDY DESIGN: This retrospective cohort study enrolled neonates born between 2011 and 2015 and followed up until 5 years. The incidence of obesity at 5 years old, and other characteristics were compared between the antibiotic-exposed and unexposed groups. Chi-square test was conducted on categorical variables and Student's t-test for normally distributed continuous variable. Significant variables (p < 0.05) in bivariate analysis were modelled in a stepwise multivariate logistic regression analysis to ascertain independent predictors of obesity at 5 years. RESULTS: Of the 1,447 subjects, 749 (51.8%) received ampicillin and gentamicin, and 333 (23%) were obese. Neonates exposed to antibiotics were more likely to be obese compared with those unexposed (26 vs. 20%, p = 0.01). In the adjusted model, this association persisted (adjusted odds ratio: 1.37, p = 0.02). CONCLUSION: Neonatal antibiotic exposure is associated with early childhood obesity and may play a significant role in the weight trajectories of these children. Hence, antibiotic stewardship in this period cannot be overemphasized. KEY POINTS: · Findings from our study showed that neonatal antibiotic exposure is associated with early childhood obesity.. · The prevalence of childhood obesity at 5 years is high (23%).. · Further exploration of the role of antibiotics on the gut microbiome and its effect on weight trajectories is needed..

Abnormal Peyer patch development and B-cell gut homing drive IgA deficiency in Kabuki syndrome.

BACKGROUND: Kabuki syndrome (KS) is commonly caused by mutations in the histone-modifying enzyme lysine methyltransferase 2D (KMT2D). Immune dysfunction is frequently observed in individuals with KS, but the role of KMT2D in immune system function has not been identified. OBJECTIVE: We sought to understand the mechanisms driving KS-associated immune deficiency (hypogammaglobulinemia [low IgA], splenomegaly, and diminished immunization responses). METHODS: We performed a comprehensive evaluation of humoral immunity and secondary lymphoid tissues in an established KS (Kmt2d+/ßGeo) mouse model and validated select findings in a patient with KS. RESULTS: Compared with wild-type littermates, Kmt2d+/ßGeo mice demonstrated deficiencies in multiple B-cell lineages and reduced serum IgA and elevated IgM levels across multiple ages. The bone marrow, spleen, and intestine of Kmt2d+/ßGeo mice contained diminished numbers of IgA-secreting cells, while elevated germinal center B cells were found in the mesenteric lymph node and Peyer patches. Kmt2d+/ßGeo mice have decreased size and numbers of Peyer patches, a finding confirmed in human samples. We identified deficiency of Itgb7 RNA and protein expression, a gene encoding an adhesion protein that mediates intestinal homing, and we demonstrated KMT2D-dependent control of ITGB7 expression in a human cell line. CONCLUSIONS: Kmt2d haploinsufficiency has broad deleterious effects on B-cell differentiation, specifically hampering gut lymphocyte homing and IgA+ plasma cell differentiation. Intestinal lymphoid defects caused by ITGB7 deficiency have not previously been recognized in KS, and these results provide new mechanistic insights into the pathogenesis of KS-associated immune deficiency.

The effect of age, sex, race/ethnicity, health insurance, and food specific serum immunoglobulin E on outcomes of oral food challenges.

Background: Although oral food challenge (OFC) is an important clinical procedure for diagnosing food allergy, there is a paucity of literature on the outcome of the procedure and specifically the patients on whom the procedure is performed from the aspects of their age, sex, race/ethnicity, health insurance status, and serum specific IgE to the food tested. Objective: We aimed to review results of OFC and determine the impact of patient age, sex, race/ethnicity, insurance status, private or public, and food specific serum IgE on the outcome of OFC. Methods: A retrospective chart review was performed of patients undergoing OFCs at a children's hospital outpatient allergy clinic over a two-year period. The outcome of OFC was allergic or non-allergic based on determination and documentation by the treating physician. A logistic regression model was built to determine the association between the OFC outcomes, age, and symptoms at the time of OFC. A Chi-square analysis was performed to check for any significant relationship between the OFC outcome and age when stratified by insurance status. Results: Five hundred and eight children underwent 641 OFCs. Twenty nine percent of OFCs had an allergic outcome with the most commonly challenged foods being peanuts, eggs, and milk. Patient age and gender, when stratified by insurance status, did not have a significant effect on OFC outcomes. Serum IgE to peanuts and egg was significantly different between allergic OFC and non-allergic outcome. Vomiting and urticaria/angioedema correlated with an allergic OFC outcome. Conclusion: OFCs confirm the food allergy diagnosis in about one-third of patients tested, and they should continue to be used when possible for an accurate diagnosis. Age, sex, and insurance status do not have a significant association with the outcome of OFC and cannot be added as predictive factors.