Follow-up after Pediatric Intensive Care Unit Admission:From mortality to morbidity

Although the survival rate of children admitted to the Pediatric Intensive Care Unit (PICU) has substantially increased during the past decades, long-term morbidity after PICU admission is a growing concern. Meta-analytic techniques were used to quantify intelligence outcome after PICU admission and to explore risk factors for poor intelligence outcome, based on a review of the existing literature. All studied PICU subgroups had lower intelligence compared to controls (range 0.38-0.88 SD). Later year of PICU admission, longer length of PICU stay, female sex and lower survival rates in the studied groups, were related to greater intelligence impairment. The studies in this thesis that focused on children with a history of invasive mechanical ventilation for bronchiolitis indicate that these children are at risk of adverse long-term neurocognitive functioning, academic performance and health-related quality of life regarding school functioning at 6-12 years of age. The observed adverse intelligence outcome was found to contribute to the observed academic underachievement regarding reading comprehension and arithmetic performance. Contrary to our hypothesis, we found no evidence for a relationship between exposure to sedatives, analgesics, anesthetics or a combination of these drugs and neurocognitive outcomes.The results of this thesis also show that one-quarter of children with a history of invasive mechanical ventilation for bronchiolitis had adverse long-term pulmonary outcomes at 6-12 years of age. The most frequent diagnosis in these children with morbidity was asthma. In the majority of the children, these adverse pulmonary outcomes had gone previously undetected. The presence of atopic disease in family and/or longer duration of invasive mechanical ventilation were associated with the presence of asthma at follow-up.At last, this thesis describes the process of successful development and implementation of a structured multidisciplinary follow-up program for patients and their parents after PICU admission in the Emma Children’s Hospital, Amsterdam UMC, the Netherlands

Acid sphingomyelinase (Asm) deficiency patients in The Netherlands and Belgium: Disease spectrum and natural course in attenuated patients

Item does not contain fulltextNiemann-Pick disease (NPD) is a neurovisceral lysosomal storage disorder caused by acid sphingomyelinase (ASM) deficiency, which can be categorized as either Niemann-Pick disease type A [NPD-A], with progressive neurological disease and death in early childhood, or as Niemann-Pick disease type B [NPD-B], with a more variable spectrum of manifestations. Enzyme replacement therapy (ERT) with recombinant sphingomyelinase is currently studied as potential treatment for NPD-B patients. The objective of this study is to characterize the clinical features of patients with ASM deficiency in the Netherlands and Belgium with focus on the natural disease course of NPD-B patients. Prospective and retrospective data on ASM deficient patients were collected in The Netherlands and part of Belgium. Patients with NPD-B that could be followed prospectively were evaluated every 6-12months for pulmonary function tests, 6minute walk test (6MWT), imaging (bone marrow infiltration measured by QCSI, organ volumes by MRI and CT scan of the lungs) and biochemical markers. Twenty-five patients with ASM deficiency were identified (13 males, 12 females, median age 13years, range 1-59years). Nine patients had died at the time of the study, including four NPD-A patients at the age of 1,1, 2, 3 and five NPDB patents at the age of 5, 6, 43, 56 and 60years. There was a high prevalence of homozygosity and compound heterozygosity for the common p.Arg608del mutation in 43% and 19% of NPD-B patients, respectively. In NPD-B patients, thrombocytopenia was present in most, while anemia and leucopenia were less common (33% and 6 % respectively). HDL cholesterol was reduced in most patients. Pulmonary disease was severe in several patients. Follow-up up to 11years revealed a gradual decrease in platelet count. Detailed investigations in 6 NPD-B patients with follow-up in 4 patients revealed remarkable stable disease parameters up to 6years, with some decline in pulmonary function and 6MWT. Bone marrow fat fractions were decreased, indicating the presence of storage macrophages. Lung involvement was not related to the extent of visceromegaly, cytopenia or bone marrow involvement. In conclusion, in NPD-B patients pulmonary disease is the most debilitating feature. Disease manifestations are mostly stable in attenuated patients. Bone marrow infiltration is a less prominent feature of the disease