Introduction

OBJECTIVE: To evaluate developmental and social-emotional outcomes at 8 years of age for children with congenital diaphragmatic hernia (CDH), treated with or without neonatal extracorporeal membrane oxygenation (ECMO) between January 1999 and December 2003. DESIGN: Cohort study with structural prospective follow-up. SETTING: Level III University Hospital. PATIENTS: 35 children (ECMO: n=16; non-ECMO: n=19) were assessed at 8 years of age. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Intelligence and motor function. Concentration, behaviour, school performance, competence and health status were also analysed. RESULTS: Mean (SD) intelligence for the ECMO group was 91.7 (19.5) versus 111.6 (20.9) for the non-ECMO group (p=0.015). Motor problems were apparent in 16% of all participants and differed significantly from the norm (p=0.015) without differences between treatment groups. For all participants, problems with concentration (68%, p<0.001) and with behavioural attention (33%, p=0.021) occurred more frequently than in reference groups, with no difference between treatment groups. School performance and competence were not affected. CONCLUSIONS: Children with CDH-whether or not treated with neonatal ECMO-are at risk for long-term morbidity especially in the areas of motor function and concentration. Despite their impairment, children with CDH have a well-developed feeling of self-competence

Regulation of antigen-specific IgE, IgG1, and mast cell responses to ingested allergen by mucosal tolerance induction

Mucosal administration of soluble protein Ags results in profound immunologic nonresponsiveness, characterized by reduced production of Th1 and Th2 cytokines and concomitant suppressed Ig production. It has been suggested that Th2 cells are required for the induction and maintenance of this tolerogenic state. In this study, we show that oral tolerance induction abrogates subsequent Th2-driven Ag-specific IgE and IgG1 responses, while intranasal tolerance induction only blocks the production of IgE, but not IgG1. Consistent with suppressed IgE serum levels, elevated IFN-gamma production was observed in the spleens of tolerized mice. Moreover, both oral and intranasal tolerance induction were found to inhibit intestinal mast cell responses upon subsequent priming and intragastric provocation. Transfer of total splenocytes or purified CD4 , but not CD8 , T cells from intranasally tolerized mice clearly suppressed ongoing Ag-specific IgE, but not IgG1, responses in primed recipients. In addition, coadministration of IFN-gamma- neutralizing Abs completely blocked the transfer of suppression to primed recipients. These results show that Th2 cells can be subjected to tolerance induction, by inducing cross-regulatory, IFN-gamma- producing CD4 T cells. Moreover, our results point out differences in the regulation of T cell-dependent Ag-specific IgE and IgG1 responses

Regulation of antigen-specific IgE, IgG1, and mast cell responses to ingested allergen by mucosal tolerance induction

Mucosal administration of soluble protein Ags results in profound immunologic nonresponsiveness, characterized by reduced production of Th1 and Th2 cytokines and concomitant suppressed Ig production. It has been suggested that Th2 cells are required for the induction and maintenance of this tolerogenic state. In this study, we show that oral tolerance induction abrogates subsequent Th2-driven Ag-specific IgE and IgG1 responses, while intranasal tolerance induction only blocks the production of IgE, but not IgG1. Consistent with suppressed IgE serum levels, elevated IFN-gamma production was observed in the spleens of tolerized mice. Moreover, both oral and intranasal tolerance induction were found to inhibit intestinal mast cell responses upon subsequent priming and intragastric provocation. Transfer of total splenocytes or purified CD4 , but not CD8 , T cells from intranasally tolerized mice clearly suppressed ongoing Ag-specific IgE, but not IgG1, responses in primed recipients. In addition, coadministration of IFN-gamma- neutralizing Abs completely blocked the transfer of suppression to primed recipients. These results show that Th2 cells can be subjected to tolerance induction, by inducing cross-regulatory, IFN-gamma- producing CD4 T cells. Moreover, our results point out differences in the regulation of T cell-dependent Ag-specific IgE and IgG1 responses