[Posted 18/Sep/2023]

AUDIENCE: Pediatric, Family Medicine

KEY FINDINGS: Most autistic individuals show improved communication and social functioning as they age, but not all do. Trajectory group membership is correlated with socioeconomic status. Future research should investigate what drives these correlations.

BACKGROUND: The goal of this study was to describe the typical, longitudinal, developmental trajectories of communication and social functioning in individuals with autism spectrum disorder from childhood through adulthood and to determine the correlates of these trajectories.

DETAILS: Children with autism spectrum disorder who were born in California from 1992 through 2016 and enrolled with the California Department of Developmental Services were identified. Subjects with <4 evaluations in the database were excluded, resulting in a sample of 71,285 individuals. Score sequences were constructed based on evaluative items for communication and social functioning. Typical trajectories were identified using group-based latent trajectory modeling, and logistic regression was used to determine the odds of classification into a social adolescent decline trajectory by individual-, family-, and zip code-level factors. Six typical patterns of communication functioning and 7 typical patterns of social functioning were identified. Whereas the majority of autistic individuals exhibit improved communication functioning as they age, the majority of individuals exhibit steady social functioning. A small group of individuals (5.0%) exhibits high social functioning in childhood that declines in adolescence. Membership in this adolescent decline group is associated with maternal non-Hispanic white race and ethnicity, female sex, moderate levels of maternal education, lower zip code-level median home values and population density, and higher zip code-level inequality.

Copyright © American Academy of Pediatrics. All rights reserved.

Source: Fountain, C., Winter, A. S., Cheslack-Postava, K., et al. (2023). Developmental Trajectories of Autism . XXXXXXXX. 2023; 152(3): e2022058674. Published: September, 2023. DOI: 10.1542/peds.2022-058674.

A Non-A Priori Analysis.

[Posted 19/Sep/2023]

AUDIENCE: Nursing

KEY FINDINGS: Routine diaper changes in preterm infants may increase the risk for acute reductions in RrSO₂ as measured by NIRS; however, the impact on kidney health remains unknown. Larger prospective cohort studies assessing kidney function and outcomes related to this phenomenon are needed.

BACKGROUND: Reduction in oxygen delivery to developing kidneys of premature infants may be an important source for acute kidney injury in premature infants. Objective of this study is to describe changes in continuous kidney oxygenation (RrSO₂) measures before, during, and after routine diaper changes.

DETAILS: Method used: Non–a priori analysis of a prospective cohort that received continuous measurement of RrSO₂ with near-infrared spectroscopy (NIRS) over the first 14 days of life demonstrating acute RrSO₂ drops surrounding diaper changes. In total, 26 of 38 (68%) infants (<=1800 g) from our cohort exhibited acute drops in RrSO₂ that temporally correlated with diaper changes. Mean (SD) RrSO₂ baseline prior to each diaper change event was 71.1 (13.2), dropped to 59.3 (11.6) during diaper change, and recovered to 73.3 (13.2). There was a significant difference between means when comparing baseline to diaper change (P < .001; 95% CI, 9.9 to 13.8) and diaper change to recovery (P < .001; 95% CI, -16.9 to -11.2). The mean decrease in RrSO₂ during diaper change averaged 12 points (17%) below 15-minute RrSO₂ mean prior to diaper change, with quick recovery to prediaper change levels. No decreases in SpO₂, blood pressure, or heart rate were documented during the intermittent kidney hypoxic events.

Copyright © The National Association of Neonatal Nurses. All rights reserved.

Source: Marin, T., Ghosh, S., Cockfield, C., et al. (2023). Routine Diaper Change Alters Kidney Oxygenation in Premature Infants: A Non-A Priori Analysis. Advances in Neonatal Care. 2023; 23(5): 450-456. Published: October, 2023. DOI: 10.1097/ANC.0000000000001082.

[Posted 19/Sep/2023]

AUDIENCE: Endocrinology, Pediatric, Family Medicine

KEY FINDINGS: The research analyses suggest parent DD is a strong predictor of child HbA1c and is another modifiable treatment target for lowering child HbA1c.

BACKGROUND: Diabetes distress (DD) describes the unrelenting emotional and behavioral challenges of living with, and caring for someone living with, type 1 diabetes (T1D). We investigated associations between parent-reported and child-reported DD, T1D device use, and child glycated hemoglobin (HbA1c) in 157 families of school-age children.

DETAILS: Parents completed the Parent Problem Areas in Diabetes-Child (PPAID-C) and children completed the Problem Areas in Diabetes-Child (PAID-C) to assess for DD levels. Parents also completed a demographic form where they reported current insulin pump or continuous glucose monitor (CGM) use (ie, user/non-user). Authors measured child HbA1c using a valid home kit and central laboratory. We used correlations and linear regression for our analyses. Children were 49% boys and 77.1% non-Hispanic white (child age (mean±SD)=10.2±1.5 years, T1D duration=3.8±2.4 years, HbA1c=7.96±1.62%). Most parents self-identified as mothers (89%) and as married (78%). Parents' mean PPAID-C score was 51.83±16.79 (range: 16-96) and children's mean PAID-C score was 31.59±12.39 (range: 11-66). Higher child HbA1c correlated with non-pump users (r=-0.16, p<0.05), higher PPAID-C scores (r=0.36, p<0.001) and higher PAID-C scores (r=0.24, p<0.001), but there was no association between child HbA1c and CGM use. A regression model predicting child HbA1c based on demographic variables, pump use, and parent-reported and child-reported DD suggested parents' PPAID-C score was the strongest predictor of child HbA1c.

Copyright © BMJ Publishing Group Ltd. All rights reserved.

Source: Patton, S. R., Kahhan, N., Pierce, J. S., et al. (2023). Parental Diabetes Distress Is A Stronger Predictor Of Child HbA1c Than Diabetes Device Use In School-Age Children With Type 1 Diabetes. BMJ Open Diabetes Research and Care. 2023; 11(5): e003607. Published: September, 2023. DOI: 10.1136/bmjdrc-2023-003607.

A Study From Victims to Families

[Posted 6/Sep/2023]

AUDIENCE: Cardiology, Pediatric, Emergency Medicine

KEY FINDINGS: Genetic yield is higher in SUDC than in SIDS although, in both, it is contributed only by definitive-evidence genes. SIDS/SUDC cascade family screening facilitates establishment or dismissal of a diagnosis through definitive variant adjudication indicating that anonymity is no longer justifiable. Channelopathies may underlie a relevant fraction of SUDC. Binary classifications of genetic causality (pathogenic versus benign) could not always be adequate.

BACKGROUND: Sudden infant death syndrome (SIDS) is the leading cause of death up to age 1. Sudden unexplained death in childhood (SUDC) is similar but affects mostly toddlers aged 1 to 4. SUDC is rarer than SIDS, and although cardiogenetic testing (molecular autopsy) identifies an underlying cause in a fraction of SIDS, less is known about SUDC.

DETAILS: Seventy-seven SIDS and 16 SUDC cases underwent molecular autopsy with 25 definitive-evidence arrhythmia-associated genes. In 18 cases, another 76 genes with varying degrees of evidence were analyzed. Parents were offered cascade screening. Double-blind review of clinical-genetic data established genotype-phenotype correlations. The yield of likely pathogenic variants in the 25 genes was higher in SUDC than in SIDS (18.8% [3/16] versus 2.6% [2/77], respectively; P=0.03), whereas novel/ultra-rare variants of uncertain significance were comparably represented. Rare variants of uncertain significance and likely benign variants were found only in SIDS. In cases with expanded analyses, likely pathogenic/likely benign variants stemmed only from definitive-evidence genes, whereas all other genes contributed only variants of uncertain significance. Among 24 parents screened, variant status and phenotype largely agreed, and 3 cases positively correlated for cardiac channelopathies. Genotype-phenotype correlations significantly aided variant adjudication.

Copyright © The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell

Source: Kotta, M., Torchio, M., Bayliss, P., et al. (2023). Cardiac Genetic Investigation of Sudden Infant and Early Childhood Death: A Study From Victims to Families. J Am Heart Ass. 2023; 12(7): e029100. Published: September, 2023. DOI: 10.1161/JAHA.122.029100.

Post Hoc Analysis Results from a Phase III Trial

[Posted 30/Aug/2023]

AUDIENCE: Dermatology, Family Medicine

KEY FINDINGS: Treatment with dupilumab provides significant and sustained improvements within 2 weeks in AD signs, symptoms, and QoL in almost all children with severe AD, including those who did not achieve clear or almost clear skin by week 16.

BACKGROUND: Children with severe atopic dermatitis (AD) have a multidimensional disease burden. Objective of the trial was to assess the clinically meaningful improvements in AD signs, symptoms, and quality of life (QoL) in children aged 6-11 years with severe AD treated with dupilumab compared with placebo.

DETAILS: R668-AD-1652 LIBERTY AD PEDS was a randomized, double-blinded, placebo-controlled, parallel-group, phase III clinical trial of dupilumab with concomitant topical corticosteroids (TCS) in children aged 6-11 years with severe AD. This post hoc analysis focuses on 304 patients receiving either dupilumab or placebo with TCS and assessed the percentage of patients considered responsive to dupilumab treatment at week 16. At week 16, almost all patients receiving dupilumab + TCS (95%) demonstrated clinically meaningful improvements in AD signs, symptoms, or QoL compared with placebo + TCS (61%, p 0.0001). Significant improvements were seen as early as week 2 and sustained through the end of the study in the full analysis set (FAS) and the subgroup of patients with an Investigator’s Global Assessment score greater than 1 at week 16.

Copyright © Springer Nature. All rights reserved.

Source: Siegfried, E. C., Cork, M. J., Katoh, N., et al. (2023). Dupilumab Provides Clinically Meaningful Responses in Children Aged 6-11 Years with Severe Atopic Dermatitis: Post Hoc Analysis Results from a Phase III Trial. Am J Clin Dermatol. 2023; 4: 787-798. Published: September, 2023. DOI: 10.1007/s40257-023-00791-7.

A French Nationwide Cohort Study

[Posted 28/Aug/2023]

AUDIENCE: Pediatric, Oncology

KEY FINDINGS: In the first Tumeur Et Developpement analysis, 3 major themes have been identified: (1) germline mutations with or without known cancer predisposition, (2) postzygotic events responsible for genomic mosaicism, (3) coincidental associations. New pathways involved in cancer development need to be investigated to improve our understanding of childhood cancers.

BACKGROUND: Purpose of the study is to assess the associations between congenital abnormalities and pediatric malignancies and evaluate the potential underlying molecular basis by collecting information on pediatric patients with cancer and congenital abnormalities.

DETAILS: Tumeur Et Developpement is a national, prospective, and retrospective multicenter study recording data of children with cancer and congenital abnormalities. When feasible, blood and tumoral samples are collected for virtual biobanking. From June 2013 to December 2019, 679 associations between pediatric cancers and congenital abnormalities were recorded. The most represented cancers were central nervous system tumors (n = 139; 20%), leukemia and myelodysplastic syndromes (n = 123; 18.1%), and renal tumors (n = 101; 15%). Congenital abnormalities were not related to any known genetic disorder in 66.5% of cases. In this group, the most common anomaly was intellectual disability (22.3%), followed by musculoskeletal (14.2%) and genitourinary anomalies (12.4%). Intellectual disability was mostly associated with hematologic malignancies. Embryonic tumors (neuroblastoma, Wilms tumor, and rhabdomyosarcoma) were associated with consistent abnormalities, sometimes with a close anatomical neighborhood between the abnormality and the neoplasm.

Copyright © Elsevier Inc. All rights reserved.

Source: Semeraro, M., Fouquet, C., Vial, Y.t al. (2023). Pediatric Tumors and Developmental Anomalies: A French Nationwide Cohort Study. The Journal of Pediatrics. 2023; 259: 13451. Published: August, 2023. DOI: 10.1016/j.jpeds.2023.113451.