Predicting long-term neurocognitive outcome after pediatric intensive care unit admission for bronchiolitis-preliminary exploration of the potential of machine learning.

PURPOSE: For successful prevention and intervention, it is important to unravel the complex constellation of factors that affect neurocognitive functioning after pediatric intensive care unit (PICU) admission. This study aims (1) to elucidate the potential relevance of patient and PICU-related characteristics for long-term adverse neurocognitive outcome after PICU admission for bronchiolitis, and (2) to perform a preliminary exploration of the potential of machine learning as compared to linear regression to improve neurocognitive outcome prediction in a relatively small sample of children after PICU admission. METHODS: This cross-sectional observational study investigated 65 children aged 6-12 years with previous PICU admission for bronchiolitis (age ≤ 1 year). They were compared to demographically comparable healthy peers (n = 76) on neurocognitive functioning. Patient and PICU-related characteristics used for the prediction models were as follows: demographic characteristics, perinatal and disease parameters, laboratory results, and intervention characteristics, including hourly validated mechanical ventilation parameters. Neurocognitive outcome was measured by intelligence and computerized neurocognitive testing. Prediction models were developed for each of the neurocognitive outcomes using Regression Trees, k-Nearest Neighbors, and conventional linear regression analysis. RESULTS: The patient group had lower intelligence than the control group (p < .001, d = -0.59) and poorer performance in neurocognitive functions, i.e., speed and attention (p = .03, d = -0.41) and verbal memory (p < .001, d = -0.60). Lower intelligence was predicted by lower birth weight and lower socioeconomic status (R2 = 25.9%). Poorer performance on the speed and attention domain was predicted by younger age at follow-up (R2 = 53.5%). Poorer verbal memory was predicted by lower birth weight, younger age at follow-up, and greater exposure to acidotic events (R2 = 50.6%). The machine learning models did not reveal added value in terms of model performance as compared to linear regression. CONCLUSION: The findings of this study suggest that in children with previous PICU admission for bronchiolitis, (1) lower birth weight, younger age at follow-up, and lower socioeconomic status are associated with poorer neurocognitive outcome; and (2) greater exposure to acidotic events during PICU admission is associated with poorer verbal memory outcome. The findings of this study provide no evidence for the added value of machine learning models as compared to linear regression analysis in the prediction of long-term neurocognitive outcome in a relatively small sample of children. WHAT IS KNOWN: • Adverse neurocognitive outcomes are described in PICU survivors, which are known to interfere with development in other major domains of functioning, such as mental health, academic achievement, and socioeconomic success, highlighting neurocognition as an important outcome after PICU admission. • Machine learning is a rapidly growing field of artificial intelligence that is increasingly applied in health care settings, with great potential to capture the complexity of outcome prediction. WHAT IS NEW: • This study shows that lower birth weight, lower socioeconomic status, and greater exposure to acidotic events during PICU admission for bronchiolitis are associated with poorer long-term neurocognitive outcome after PICU admission. Results provide no evidence for the added value of machine learning models in a relatively small sample of children. • As bronchiolitis seldom manifests neurologically, the relation between acidotic events and neurocognitive outcome may reflect either potentially harmful effects of acidosis itself or related processes such as hypercapnia or hypoxic and/or ischemic events during PICU admission. This study further highlights the importance of structured follow-up to monitor long-term outcome of children after PICU admission.

Long-Term Follow-Up of Daily Life Functioning After Pediatric Intensive Care Unit Admission.

OBJECTIVE: To investigate the long-term impact of pediatric intensive care unit (PICU) admission on daily life functioning while exploring the potential mediating role of neurocognitive outcome. STUDY DESIGN: This cross-sectional observational study compared children aged 6-12 years with previous PICU admission (age ≤1 year) for bronchiolitis requiring mechanical ventilation ("patient group," n = 65) to demographically comparable healthy peers ("control group," n = 76). The patient group was selected because bronchiolitis is not expected to affect neurocognitive functioning in itself. Assessed daily life outcome domains were behavioral and emotional functioning, academic performance, and health-related quality of life (QoL). The role of neurocognitive outcomes in the relationship between PICU admission and daily life functioning was assessed by mediation analysis. RESULTS: The patient group did not differ from the control group regarding behavioral and emotional functioning but performed poorer on academic performance and school-related QoL (Ps ≤ .04, d = -0.48 to -0.26). Within the patient group, lower full-scale IQ (FSIQ) was associated with poorer academic performance and school-related QoL (Ps ≤ .02). Poorer verbal memory was associated with poorer spelling performance (P = .002). FSIQ mediated the observed effects of PICU admission on reading comprehension and arithmetic performance. CONCLUSIONS: Children admitted to the PICU are at risk for long-term adverse daily life outcomes in terms of academic performance and school-related QoL. Findings suggest that lower intelligence may contribute to academic difficulties after PICU admission. Findings underline the importance of monitoring daily life and neurocognitive functioning after PICU admission.

Factors Associated With Delirium in Children: A Systematic Review and Meta-Analysis.

OBJECTIVES: Pediatric delirium (PD) is a neuropsychiatric syndrome caused by a complex interplay between predisposing factors (e.g., age, cognitive impairment), acute illness, and environmental triggers. PD is associated with substantial morbidity and mortality. The objective of this study is to systematically review and evaluate factors associated with PD in hospitalized pediatric patients. DATA SOURCES: A systematic search of PubMed, Embase, Ovid Medline, Web- of-Science, Cochrane, CIHNAL, and Google Scholar databases was conducted for relevant studies (1990-2022). STUDY SELECTION: We included studies that compared pediatric patients with and without delirium. Reviews, editorials, congress abstracts, or studies that did not report factors for PD were excluded. No restrictions were imposed on language. DATA EXTRACTION: Title and abstract were independently screened by two reviewers. Individual characteristics, study design, and outcomes were independently extracted. DATA SYNTHESIS: Categorical dichotomous data were summarized across groups using Mantel-Haenszel odds ratios (ORs) with 95% 95% CIs. Either fixed-effect or random effects models were used as indicated by the results of a heterogeneity test. Of 1,846 abstracts, 24 studies were included. We identified 54 factors studied in univariate analyses, and 27 of these were associated with PD in multivariable analyses. In pooled analyses, greater odds of PD were associated with developmental delay (OR 3.98; 95% CI 1.54-10.26), need for mechanical ventilation (OR 6.02; 95% CI 4.43-8.19), use of physical restraints (OR 4.67; 95% CI 1.82-11.96), and receipt of either benzodiazepines (OR 4.10; 95% CI 2.48-6.80), opiates (OR 2.88; 95% CI 1.89-4.37), steroids (OR 2.02; 95% CI 1.47-2.77), or vasoactive medication (OR 3.68; 95% CI 1.17-11.60). CONCLUSIONS: In this meta-analysis, we identified seven factors associated with greater odds of developing delirium during pediatric critical illness.

Structured Multidisciplinary Follow-Up After Pediatric Intensive Care: A Model for Continuous Data-Driven Health Care Innovation.

OBJECTIVES: Morbidity after PICU admission for critical illness is a growing concern. Sequelae may occur in various domains of functioning and can only appropriately be determined through structured follow-up. Here, we describe the process of designing and implementing a structured multidisciplinary follow-up program for patients and their parents after PICU admission and show the first results illustrating the significance of our program. DESIGN: Prospective observational cohort study. SETTING: Outpatient PICU follow-up clinic. PATIENTS: Patients 0-18 years old admitted to our PICU. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: In our structured multidisciplinary follow-up program, follow-up care is provided by a pediatric intensivist and psychologist and in addition, depending on patient's critical illness and received PICU treatment(s), by a pediatric pulmonologist, cardiologist, neurologist, and/or neuropsychologist. All consultations are scheduled consecutively. Collected data are stored in a hospital-wide data warehouse and used for yearly health care evaluation sessions as well as scientific research. Challenges in organizing this follow-up program include technological challenges, providing time-efficient care, participation rate, and completeness of questionnaires. In our experience, a dedicated team is essential to tackle these challenges. Our first results, obtained in 307 of 388 referred patients (79.1%), showed the diversity of problems arising after PICU discharge, including physical, neurocognitive, and psychosocial sequelae. In addition, our data also reflected the risk of psychosocial problems among parents. Within the limited operation time of our follow-up program, the program has evolved based on our experiences and the data collected. CONCLUSIONS: We successfully developed and implemented a structured multidisciplinary follow-up program for patients and their parents after PICU admission. This program may help to timely initiate appropriate interventions, improve the standard of care during and after PICU admission, and facilitate scientific research on outcome and prognosis after PICU admission.

Neurocognitive, Psychosocial, and Quality of Life Outcomes After Multisystem Inflammatory Syndrome in Children Admitted to the PICU.

OBJECTIVES: To investigate neurocognitive, psychosocial, and quality of life (QoL) outcomes in children with Multisystem Inflammatory Syndrome in Children (MIS-C) seen 3-6 months after PICU admission. DESIGN: National prospective cohort study March 2020 to November 2021. SETTING: Seven PICUs in the Netherlands. PATIENTS: Children with MIS-C (0-17 yr) admitted to a PICU. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Children and/or parents were seen median (interquartile range [IQR] 4 mo [3-5 mo]) after PICU admission. Testing included assessment of neurocognitive, psychosocial, and QoL outcomes with reference to Dutch pre-COVID-19 general population norms. Effect sizes (Hedges' g ) were used to indicate the strengths and clinical relevance of differences: 0.2 small, 0.5 medium, and 0.8 and above large. Of 69 children with MIS-C, 49 (median age 11.6 yr [IQR 9.3-15.6 yr]) attended follow-up. General intelligence and verbal memory scores were normal compared with population norms. Twenty-nine of the 49 followed-up (59%) underwent extensive testing with worse function in domains such as visual memory, g = 1.0 (95% CI, 0.6-1.4), sustained attention, g = 2.0 (95% CI 1.4-2.4), and planning, g = 0.5 (95% CI, 0.1-0.9). The children also had more emotional and behavioral problems, g = 0.4 (95% CI 0.1-0.7), and had lower QoL scores in domains such as physical functioning g = 1.3 (95% CI 0.9-1.6), school functioning g = 1.1 (95% CI 0.7-1.4), and increased fatigue g = 0.5 (95% CI 0.1-0.9) compared with population norms. Elevated risk for posttraumatic stress disorder (PTSD) was seen in 10 of 30 children (33%) with MIS-C. Last, in the 32 parents, no elevated risk for PTSD was found. CONCLUSIONS: Children with MIS-C requiring PICU admission had normal overall intelligence 4 months after PICU discharge. Nevertheless, these children reported more emotional and behavioral problems, more PTSD, and worse QoL compared with general population norms. In a subset undergoing more extensive testing, we also identified irregularities in neurocognitive functions. Whether these impairments are caused by the viral or inflammatory response, the PICU admission, or COVID-19 restrictions remains to be investigated.

Long-term neurocognitive outcomes after pediatric intensive care: exploring the role of drug exposure.

BACKGROUND: Concerns exist regarding the impact of widely used clinical drugs on brain development. This study investigates long-term neurocognitive functioning in relation to frequently used drug exposure at the Pediatric Intensive Care Unit (PICU). METHODS: This study compared children aged 6-12 years with previous PICU admission (age ≤1 year) for bronchiolitis requiring mechanical ventilation (patient group, n = 65) to a demographically comparable control group (n = 76) on a broad range of neurocognitive outcomes. The patient group was selected because bronchiolitis seldom manifests neurologically and is therefore not expected to affect neurocognitive functioning in itself. The relation between exposure to sedatives, analgesics and anesthetics and neurocognitive outcomes was assessed by regression analyses. RESULTS: The patient group had lower intelligence than the control group (p < 0.001, d = -0.59) and poorer performance in neurocognitive functions; i.e., speed and attention (p = 0.03, d = -0.41) and verbal memory (p < 0.001, d = -0.60). Exposure to sedatives, analgesics and anesthetics was not related to neurocognitive outcomes. CONCLUSIONS: Children with PICU admission for bronchiolitis requiring mechanical ventilation are at risk of adverse neurocognitive outcomes. This study found no evidence for a role of exposure to sedatives, analgesics or anesthetics. Findings underline the importance of long-term follow-up after PICU admission, even in the absence of disease with neurological manifestation. IMPACT: Animal studies have indicated that exposing the maturing brain to clinical drugs may cause neurodegeneration. Clinical studies show mixed evidence regarding the association between clinical drugs and neurocognitive outcomes. This study provides evidence for considerably lower neurocognitive functioning among children with a history of PICU admission for bronchiolitis compared to healthy peers. Bronchiolitis seldom manifests neurologically and is therefore not expected to affect neurocognitive functioning in itself. We found no evidence supporting a relation between drug exposure (i.e., sedatives, analgesics and anesthetics) and long-term neurocognitive outcomes. Findings underline the importance of structured follow-up after PICU admission.

A Core Outcome Measurement Set for Pediatric Critical Care.

OBJECTIVES: To identify a PICU Core Outcome Measurement Set (PICU COMS), a set of measures that can be used to evaluate the PICU Core Outcome Set (PICU COS) domains in PICU patients and their families. DESIGN: A modified Delphi consensus process. SETTING: Four webinars attended by PICU physicians and nurses, pediatric surgeons, rehabilitation physicians, and scientists with expertise in PICU clinical care or research ( n = 35). Attendees were from eight countries and convened from the Pediatric Acute Lung Injury and Sepsis Investigators Pediatric Outcomes STudies after PICU Investigators and the Eunice Kennedy Shriver National Institute of Child Health and Human Development Collaborative Pediatric Critical Care Research Network PICU COS Investigators. SUBJECTS: Measures to assess outcome domains of the PICU COS are as follows: cognitive, emotional, overall (including health-related quality of life), physical, and family health. Measures evaluating social health were also considered. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Measures were classified as general or additional based on generalizability across PICU populations, feasibility, and relevance to specific COS domains. Measures with high consensus, defined as 80% agreement for inclusion, were selected for the PICU COMS. Among 140 candidate measures, 24 were delineated as general (broadly applicable) and, of these, 10 achieved consensus for inclusion in the COMS (7 patient-oriented and 3 family-oriented). Six of the seven patient measures were applicable to the broadest range of patients, diagnoses, and developmental abilities. All were validated in pediatric populations and have normative pediatric data. Twenty additional measures focusing on specific populations or in-depth evaluation of a COS subdomain also met consensus for inclusion as COMS additional measures. CONCLUSIONS: The PICU COMS delineates measures to evaluate domains in the PICU COS and facilitates comparability across future research studies to characterize PICU survivorship and enable interventional studies to target long-term outcomes after critical illness.

Long-Term Pulmonary Outcomes in Children Mechanically Ventilated for Severe Bronchiolitis.

OBJECTIVES: Bronchiolitis is a common indication for mechanical ventilation in the PICU. Both bronchiolitis and invasive mechanical ventilation may cause adverse long-term pulmonary outcomes. This study investigates children with a history of invasive mechanical ventilation for bronchiolitis, addressing: 1) the extent, 2) potential explanatory factors, and 3) possible impact on daily life activities of adverse long-term pulmonary outcomes. DESIGN: Single-center cohort study. SETTING: Outpatient PICU follow-up clinic. PATIENTS: Children 6-12 years old with a history of invasive mechanical ventilation for bronchiolitis (age < 2 yr). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Long-term pulmonary outcomes were assessed by a standardized questionnaire and by spirometry. Nineteen out of 74 included children (26%) had adverse long-term pulmonary outcomes, of whom the majority had asthma (14/74, 19%). By logistic regression analysis, we assessed whether background characteristics and PICU-related variables were associated with long-term pulmonary outcomes. In general, we failed to identify any explanatory factors associated with adverse long-term pulmonary outcomes. Nonetheless, atopic disease in family and longer duration of invasive mechanical ventilation (days) were associated with greater odds of having asthma at follow-up (odds ratio, 6.4 [95% CI, 1.2-36.0] and 1.3 [95% CI, 1.0-1.7], respectively). Adverse pulmonary outcome at follow-up was associated with more frequent use of pulmonary medication after PICU discharge. In comparison with those without adverse pulmonary outcomes, we did not identify any difference in frequency of sports performance or school absenteeism. CONCLUSIONS: In this single-center cohort, one-quarter of the children attending follow-up with a history of invasive mechanical ventilation for bronchiolitis had adverse, mostly previously undetected, long-term pulmonary outcomes at 6-12 years. Atopic disease in family and longer duration of invasive mechanical ventilation were associated with presence of asthma. The presence of adverse pulmonary outcomes was associated with more frequent use of pulmonary medication after PICU discharge.

Intelligence outcome of pediatric intensive care unit survivors: a systematic meta-analysis and meta-regression.

BACKGROUND: Long-term morbidity after pediatric intensive care unit (PICU) admission is a growing concern. Both critical illness and accompanying PICU treatments may impact neurocognitive development as assessed by its gold standard measure; intelligence. This meta-analysis and meta-regression quantifies intelligence outcome after PICU admission and explores risk factors for poor intelligence outcome. METHODS: PubMed, Embase, CINAHL and PsycINFO were searched for relevant studies, published from database inception until September 7, 2021. Using random-effects meta-analysis, we calculated the standardized mean difference in full-scale intelligence quotient (FSIQ) between PICU survivors and controls across all included studies and additionally distinguishing between PICU subgroups based on indications for admission. Relation between demographic and clinical risk factors and study's FSIQ effect sizes was investigated using random-effects meta-regression analysis. RESULTS: A total of 123 articles was included, published between 1973 and 2021, including 8,119 PICU survivors and 1,757 controls. We found 0.47 SD (7.1 IQ-points) lower FSIQ scores in PICU survivors compared to controls (95%CI -0.55 to -0.40, p < .001). All studied PICU subgroups had lower FSIQ compared to controls (range 0.38-0.88 SD). Later year of PICU admission (range 1972-2016) and longer PICU stay were related to greater FSIQ impairment (R2 = 21%, 95%CI -0.021 to -0.007, p < .001 and R2 = 2%, 95%CI -0.027 to -0.002, p = .03, respectively), whereas male sex and higher rate of survivors were related to smaller FSIQ impairment (R2 = 5%, 95%CI 0.001 to 0.014, p = .03 and R2 = 11%, 95%CI 0.006 to 0.022, p < .001, respectively). Meta-regression in PICU subgroups showed that later year of PICU admission was related to greater FSIQ impairment in children admitted after cardiac surgery and heart- or heart-lung transplantation. Male sex was related to smaller FSIQ impairment in children admitted after cardiac surgery. Older age at PICU admission and older age at follow-up were related to smaller FSIQ impairment in children admitted after heart- or heart-lung transplantation. CONCLUSIONS: PICU survivors, distinguished in a wide range of subgroups, are at risk of intelligence impairment. Length of PICU stay, female sex and lower rate of survivors were related to greater intelligence impairment. Intelligence outcome has worsened over the years, potentially reflecting the increasing percentage of children surviving PICU admission.

A Core Outcome Set for Pediatric Critical Care.

OBJECTIVES: More children are surviving critical illness but are at risk of residual or new health conditions. An evidence-informed and stakeholder-recommended core outcome set is lacking for pediatric critical care outcomes. Our objective was to create a multinational, multistakeholder-recommended pediatric critical care core outcome set for inclusion in clinical and research programs. DESIGN: A two-round modified Delphi electronic survey was conducted with 333 invited research, clinical, and family/advocate stakeholders. Stakeholders completing the first round were invited to participate in the second. Outcomes scoring greater than 69% "critical" and less than 15% "not important" advanced to round 2 with write-in outcomes considered. The Steering Committee held a virtual consensus conference to determine the final components. SETTING: Multinational survey. PATIENTS: Stakeholder participants from six continents representing clinicians, researchers, and family/advocates. MEASUREMENTS AND MAIN RESULTS: Overall response rates were 75% and 82% for each round. Participants voted on seven Global Domains and 45 Specific Outcomes in round 1, and six Global Domains and 30 Specific Outcomes in round 2. Using overall (three stakeholder groups combined) results, consensus was defined as outcomes scoring greater than 90% "critical" and less than 15% "not important" and were included in the final PICU core outcome set: four Global Domains (Cognitive, Emotional, Physical, and Overall Health) and four Specific Outcomes (Child Health-Related Quality of Life, Pain, Survival, and Communication). Families (n = 21) suggested additional critically important outcomes that did not meet consensus, which were included in the PICU core outcome set-extended. CONCLUSIONS: The PICU core outcome set and PICU core outcome set-extended are multistakeholder-recommended resources for clinical and research programs that seek to improve outcomes for children with critical illness and their families.

Complete and partial XYLT1 deletion in a patient with neonatal short limb skeletal dysplasia.

We report on a boy with a neonatal short limb skeletal dysplasia with serious medical complications, associated with one intragenic and one complete deletion of XYLT1. XYLT1 mutations have recently been reported as causative in recessive Desbuquois skeletal dysplasia (DBSD), but the skeletal features in our patient do not fit this diagnosis. It is possible that the phenotype of XYLT1 mutations extends to more aspecific types of short limb skeletal dysplasias and not to DBSD alone.

Chronic Complications After Femoral Central Venous Catheter-related Thrombosis in Critically Ill Children.

Prescription of thromboprophylaxis is not a common practice in pediatric intensive care units. Most thrombi are catheter-related and asymptomatic, without causing acute complications. However, chronic complications of these (a)symptomatic catheter-related thrombi, that is, postthrombotic syndrome (PTS) and residual thrombosis have not been studied. To investigate these complications, critically ill children of 1 tertiary center with percutaneous inserted femoral central venous catheters (FCVCs) were prospectively followed. Symptomatic FCVC-thrombosis occurred in 10 of the 134 children (7.5%; 95% confidence interval [CI], 2.4-9.5). Only FCVC-infection appeared to be independently associated (P=0.001) with FCVC-thrombosis. At follow-up 2 of the 5 survivors diagnosed with symptomatic thrombosis developed mild PTS; one of them had an occluded vein on ultrasonography. A survivor without PTS had a partial occluded vein at follow-up. Asymptomatic FCVC-thrombosis occurred in 3 of the 42 children (7.1%; 95% CI, 0.0-16.7) screened by ultrasonography within 72 hours after catheter removal. At follow-up, mild PTS was present in 6 of the 33 (18.2%; 95% CI, 6.1-30.3) screened children. Partial and total vein occlusion was present in 1 (3%) and 4 (12%) children, respectively. In conclusion, children on pediatric intensive care units are at risk for (a)symptomatic FCVC-thrombosis, especially children with FCVC-infection. Chronic complications of FCVC-thrombosis are common. Therefore, thromboprophylaxis guidelines are warranted in pediatric intensive care units to minimize morbidity as a result of FCVC-thrombosis.

Brown-Vialetto-Van Laere and Fazio Londe syndrome is associated with a riboflavin transporter defect mimicking mild MADD: a new inborn error of metabolism with potential treatment.

We report on three patients (two siblings and one unrelated) presenting in infancy with progressive muscle weakness and paralysis of the diaphragm. Metabolic studies revealed a profile of plasma acylcarnitines and urine organic acids suggestive of a mild form of the multiple acyl-CoA dehydrogenation defect (MADD, ethylmalonic/adipic acid syndrome). Subsequently, a profound flavin deficiency in spite of a normal dietary riboflavin intake was established in the plasma of all three children, suggesting a riboflavin transporter defect. Genetic analysis of these patients demonstrated mutations in the C20orf54 gene which encodes the human homolog of a rat riboflavin transporter. This gene was recently implicated in the Brown-Vialetto-Van Laere syndrome, a rare neurological disorder which may either present in infancy with neurological deterioration with hypotonia, respiratory insufficiency and early death, or later in life with deafness and progressive ponto-bulbar palsy. Supplementation of riboflavin rapidly improved the clinical symptoms as well as the biochemical abnormalities in our patients, demonstrating that high dose riboflavin is a potential treatment for the Brown-Vialetto-Van Laere syndrome as well as for the Fazio Londe syndrome which is considered to be the same disease entity without the deafness.

Course and predictors of posttraumatic stress disorder in parents after pediatric intensive care treatment of their child.

OBJECTIVE: To study posttraumatic stress disorder (PTSD) in parents after unexpected pediatric intensive care unit (PICU) treatment of their child and to identify risk factors for its development. METHOD: Parents completed PTSD questionnaires 3 and 9 months (N = 190) after PICU treatment. Risk factors included pretrauma data, medical data, social demographics and posttraumatic stress responses at 3 months. RESULTS: In total, 30.3% of parents met criteria for subclinical PTSD and 12.6% for clinical PTSD at 3 months. Clinical PTSD prevalence rates did not change over time. At 9 months, 10.5% of parents still met criteria for PTSD. Number of earlier stressful life events, earlier psychosocial care and posttraumatic stress responses at 3 months predicted persistent subclinical and clinical PTSD. CONCLUSIONS: PICU admission is a stressful event associated with persistent parental PTSD. Assessment of risk factors can facilitate detection of persistent PTSD for early intervention.

Single nucleotide polymorphisms in genes of circulatory homeostasis in surviving pediatric intensive care patients with meningococcal infection.

OBJECTIVE: In the course of a meningococcal infection, invasive and severe disease occurs in a restricted number of individuals. The predominant mechanism of death in case of meningococcal septic shock is circulatory failure. Inotropic requirements between patients vary widely. We investigated whether polymorphisms in genes regulating the hemodynamic response influence the amount of inotropics required or the susceptibility to severe meningococcal disease. DESIGN: Retrospective case control study. SETTING: Single-center pediatric intensive care unit (PICU). PATIENTS: Fifty-six cases (all consecutive patients admitted to the PICU between 1993 and 2001 with a proven meningococcal infection) and 136 controls. Patients were divided into two groups according to their inotropic requirements. INTERVENTION: DNA analysis was performed to determine the polymorphisms of the beta-adrenergic receptor gene-1, beta-adrenergic receptor gene-2, alpha-adducin, angiotensin converting enzyme, and angiotensin II type-1 receptor-1 genes. RESULTS: For the alpha-adducin gene a significant difference of the genotype distribution was found between the cases and controls. The odds ratio for admission to the PICU with meningococcal sepsis with or without meningitis, for carriers of the variant allele (Gly460Trp or Trp460Trp) was 2.1 (95% confidence interval 1.11-4.04; p < 0.02). Cases, homozygote for the wild-type allele of the beta-1 adrenergic receptor at locus 389, were more likely to have a low pediatric risk of mortality score on admission (odds ratio 3.6, 95% confidence interval 1.11-11.76). No difference was found in the distribution of the beta-adrenergic receptor gene-1, beta-adrenergic receptor gene-2, angiotensin converting enzyme, and angiotensin II type-1 receptor-1 polymorphisms between the two groups of patients or between cases and controls. CONCLUSIONS: Among patients admitted to the PICU with a meningococcal infection, the variant allele of the alpha-adducin gene was more prevalent compared with controls. Patients with the variant allele of the beta-adrenergic receptor gene-1 at locus 389 were more likely to have a high pediatric risk of mortality score on admission. The mechanism and clinical relevance of these findings is unclear.

Follow-up after paediatric intensive care treatment: parental posttraumatic stress.

AIM: To study the prevalence of posttraumatic stress in parents after an acute admission to a paediatric intensive care unit (PICU) and to determine risk factors for the development of posttraumatic stress. METHODS: Parents completed posttraumatic stress questionnaires three months after their child's discharge. This questionnaire measures both symptoms of posttraumatic stress disorder (PTSD) and enables determination of the full psychiatric diagnosis of PTSD. Medical and demographic data concerning their child were gathered from physical evaluations three months after discharge. Of 250 eligible families, 144 (57.6%) participated in this study. The questionnaires were completed by 140 mothers and 107 fathers. RESULTS: More than three-quarters of the parents experienced persistent symptoms of PTSD. In 21 mothers (15.0%) and 10 fathers (9.3%), the full psychiatric diagnosis of PTSD was determined. In six families, both parents had PTSD. Furthermore, a significant positive correlation was found between symptoms of PTSD of the mothers and the fathers. No obvious medical risk factors could be distinguished. CONCLUSION: The unexpected admission of a child to a PICU is a stressful event associated with parental posttraumatic stress. Treatment should not end after discharge. Follow-up care is warranted and research should be focused on prevention of these symptoms.