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Strategies in Rapid Genetic Diagnostics of Critically Ill Children: Experiences From a Dutch University Hospital.

ABSTRACT: Background: Genetic disorders are a substantial cause of infant morbidity and mortality and are frequently suspected in neonatal intensive care units. Non-specific clinical presentation or limitations to physical examination can result in a plethora of genetic testing techniques, without clear strategies on test ordering. Here, we review our 2-years experiences of rapid genetic testing of NICU patients in order to provide such recommendations. Methods: We retrospectively included all patients admitted to the NICU who received clinical genetic consultation and genetic testing in our University hospital. We documented reasons for referral for genetic consultation, presenting phenotypes, differential diagnoses, genetic testing requested and their outcomes, as well as the consequences of each (rapid) genetic diagnostic approach. We calculated diagnostic yield and turnaround times (TATs). Results: Of 171 included infants that received genetic consultation 140 underwent genetic testing. As a result of testing as first tier, 13/14 patients received a genetic diagnosis from QF-PCR; 14/115 from SNP-array; 12/89 from NGS testing, of whom 4/46 were diagnosed with a small gene panel and 8/43 with a large OMIM-morbid based gene panel. Subsequent secondary or tertiary analysis and/or additional testing resulted in five more diagnoses. TATs ranged from 1 day (QF-PCR) to a median of 14 for NGS and SNP-array testing, with increasing TAT in particular when many consecutive tests were performed. Incidental findings were detected in 5/140 tested patients (3.6%). Conclusion: We recommend implementing a broad NGS gene panel in combination with CNV calling as the first tier of genetic testing for NICU patients given the often unspecific phenotypes of ill infants and the high yield of this large panel.

SUBMITTER: Imafidon ME

PROVIDER: S-EPMC8200558 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Adverse childhood experiences (ACEs) are linked to adverse health outcomes for adults and children in the United States. The prevalence of critically ill children who are exposed to ACEs is not known. Our objective was to compare the frequency of ACEs of critically ill children with that of the general pediatric population of Georgia and the United States using publicly available National Survey of Children's Health (NSCH) data. The impact of ACEs on patient-reported outcome measures of emotional, social, and physical health in critically ill children is not known. We sought to determine whether a higher total number of ACEs was associated with poorer patient-reported measures of emotional, social, and physical health. We conducted a prospective cross-sectional study of children < 18 years of age who were admitted to a 36-bed free-standing, quaternary academic pediatric intensive care unit in Atlanta, Georgia from June 2020-December 2021. Parents of patients who were admitted to the pediatric intensive care unit completed a survey regarding their child's ACEs, health care use patterns, and patient-reported outcome measures (PROMIS) of emotional, social, and physical health. Prevalence estimates of ACEs were compared with national and state data from the NSCH using Rao-Scott Chi-square tests. PROMIS measures reported within the PICU cohort were compared with population normed T-scores. The association of cumulative ACEs within the PICU cohort with patient-reported outcomes of emotional, social, and physical health were evaluated with a t-test. Among the 84 participants, 54% had ≥ 1 ACE, 29% had ≥ 2 ACEs, and 10% had ≥ 3 ACEs. Children with ≥ 2 ACEs had poorer anxiety and family relationship T-scores compared to those with ≤ 1 ACE. Given the high burden of ACEs in critically ill children, screening for ACEs may identify vulnerable children that would benefit from interventions and support to mitigate the negative effects of ACEs and toxic stress on emotional, social, and physical health.

Project description:BACKGROUND:In multicenter studies, tight glycemic control targeting a normal blood glucose level has not been shown to improve outcomes in critically ill adults or children after cardiac surgery. Studies involving critically ill children who have not undergone cardiac surgery are lacking. METHODS:In a 35-center trial, we randomly assigned critically ill children with confirmed hyperglycemia (excluding patients who had undergone cardiac surgery) to one of two ranges of glycemic control: 80 to 110 mg per deciliter (4.4 to 6.1 mmol per liter; lower-target group) or 150 to 180 mg per deciliter (8.3 to 10.0 mmol per liter; higher-target group). Clinicians were guided by continuous glucose monitoring and explicit methods for insulin adjustment. The primary outcome was the number of intensive care unit (ICU)-free days to day 28. RESULTS:The trial was stopped early, on the recommendation of the data and safety monitoring board, owing to a low likelihood of benefit and evidence of the possibility of harm. Of 713 patients, 360 were randomly assigned to the lower-target group and 353 to the higher-target group. In the intention-to-treat analysis, the median number of ICU-free days did not differ significantly between the lower-target group and the higher-target group (19.4 days [interquartile range {IQR}, 0 to 24.2] and 19.4 days [IQR, 6.7 to 23.9], respectively; P=0.58). In per-protocol analyses, the median time-weighted average glucose level was significantly lower in the lower-target group (109 mg per deciliter [IQR, 102 to 118]; 6.1 mmol per liter [IQR, 5.7 to 6.6]) than in the higher-target group (123 mg per deciliter [IQR, 108 to 142]; 6.8 mmol per liter [IQR, 6.0 to 7.9]; P<0.001). Patients in the lower-target group also had higher rates of health care-associated infections than those in the higher-target group (12 of 349 patients [3.4%] vs. 4 of 349 [1.1%], P=0.04), as well as higher rates of severe hypoglycemia, defined as a blood glucose level below 40 mg per deciliter (2.2 mmol per liter) (18 patients [5.2%] vs. 7 [2.0%], P=0.03). No significant differences were observed in mortality, severity of organ dysfunction, or the number of ventilator-free days. CONCLUSIONS:Critically ill children with hyperglycemia did not benefit from tight glycemic control targeted to a blood glucose level of 80 to 110 mg per deciliter, as compared with a level of 150 to 180 mg per deciliter. (Funded by the National Heart, Lung, and Blood Institute and others; HALF-PINT ClinicalTrials.gov number, NCT01565941 .).

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Strategies in Rapid Genetic Diagnostics of Critically Ill Children: Experiences From a Dutch University Hospital.

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