Pediatric Primary Care of Children With Intrauterine Opioid Exposure: Survey of Academic Teaching Practices.

OBJECTIVE: Intrauterine opioid exposure (IOE) has increased over the last 2 decades and is associated with additional needs after birth. To date, no clinical guidelines address the primary care of children with IOE. We aimed to characterize clinician-reported screening and referral practices, barriers to effective primary care for children with IOE, and clinician- and practice-level characteristics associated with perceived barriers. METHODS: We conducted a cross-sectional survey of pediatric residents, pediatricians, and advanced practitioners at 28 primary care clinics affiliated with 7 pediatric residency programs (April-June 2022). We assessed screening and other clinical practices related to IOE and perceived barriers to addressing parental opioid use disorder (OUD). We used descriptive statistics to analyze survey responses, assessed the distribution of reported barriers, and applied a 2-stage cluster analysis to assess response patterns. RESULTS: Of 1004 invited clinicians, 329 (32.8%) responses were returned, and 325 pediatric residents and pediatricians were included in the final analytic sample. Almost all (99.3%) reported parental substance use screening as important, but only 11.6% screened routinely. Half of the respondents routinely refer children with IOE to early intervention services and social work. Lack of standard screening for substance use was the most frequently selected barrier to addressing parental OUD. Participants reporting fewer barriers to addressing parental OUD identified having greater access to OUD treatment programs and home visiting programs. CONCLUSIONS: Pediatricians report variations in primary care screenings and referrals for children with IOE. Access to parental OUD treatment programs may mitigate perceived barriers to addressing parental OUD in the pediatric office.

The role of an abbreviated ultrasound in the evaluation of necrotizing enterocolitis.

BACKGROUND: Bowel ultrasound is a useful diagnostic tool in the diagnosis and management of necrotizing enterocolitis (NEC) but can be time-consuming and requires technical expertise, particularly for assessing pneumatosis. Previous literature on sonographic evaluation of NEC has focused on a full bowel ultrasound protocol, but the utility of an abbreviated protocol primarily aimed at identifying high-risk sonographic findings without focused bowel assessment has not been well studied. OBJECTIVE: This study aims to describe the diagnostic accuracy of an abbreviated ultrasound protocol for identifying high-risk NEC findings. MATERIALS AND METHODS: This is a retrospective, institutional review board-approved study. We identified all abbreviated NEC ultrasounds performed between January 2014 and August 2022 at our institution. Exams were reviewed for the presence of high-risk findings including pneumoperitoneum, fluid collections, and complex free fluid. Clinical outcome was categorized as poor or good depending on if emergent surgical intervention or death related to NEC occurred. The frequency of follow-up NEC ultrasounds was reviewed to determine if new findings affected outcome. Sensitivity, specificity, and positive and negative predictive values were generated to assess the performance of the abbreviated ultrasounds to identify high-risk findings. RESULTS: A total of 84 abbreviated abdominal ultrasounds were performed on 73 children. Median age at the time of ultrasound was 41 days (interquartile range (IQR) 53 days) and median gestational age was 35 weeks and 3 days (IQR 80 days), and 44/73 (60%) were male. Thirteen ultrasounds had at least one high-risk finding with nine (69%) resulting in a poor outcome, including seven surgical interventions and four deaths. Two patients had surgical intervention and died as a result of necrotizing enterocolitis. Ultrasounds without high-risk findings were not associated with poor clinical outcomes. Sensitivity, specificity, positive predictive value, and negative predictive value of the abbreviated NEC ultrasound were 100% (95% CI 60-100%), 95% (95% CI 86-98%), 69% (95% CI 39-90%), and 100% (95% CI 94-100%), respectively. Twelve abbreviated ultrasounds were followed by a second NEC ultrasound within 5 days. Five follow-up ultrasounds demonstrated new high- or low-risk findings, but the new findings did not correlate with a change in outcome as predicted by the initial ultrasound. CONCLUSION: An abbreviated NEC ultrasound can be of clinical utility in predicting poor outcomes, particularly during non-business hours when resources are limited.

Factors Impacting Maltreatment Evaluation and Reports to Child Protective Services in Pediatric Substance Exposures.

OBJECTIVES: The objective of this study was to assess demographic, clinical, and psychosocial factors associated with pediatric substance exposures, describe the medical evaluation, and identify factors associated with social work (SW) and hospital-based child protection team (CPT) safety assessments and reports to child protective services (CPS). METHODS: We retrospectively reviewed charts of electronic medical records for children ages 0 to 72 months presenting for accidental ingestion evaluated May 1, 2015 to May 1, 2021 at a level 1 pediatric trauma center. Cases of environmental exposures, iatrogenic medication errors, dosing errors, and allergies/adverse reactions were excluded. Data were analyzed using descriptive statistics; χ 2 and multivariable logistic regression analysis assessed factors associated with two primary outcomes of interest, SW/CPT assessment and CPS report. RESULTS: Among 773 total cases of substance exposures during the studied time frame, 27% were referred to SW/CPT for further safety assessments and 15.4% were reported to CPS. Being admitted to the hospital, prescription medication or recreational/illegal/illicit substance exposures, and increasing psychosocial risk factors were found to be significantly associated with referrals. Age, race, and insurance status were not found to be associated. Toxicology screening was performed in only 24.7% of cases. Of those eligible for further imaging per hospital protocol, skeletal surveys were obtained in 5.5% of cases and head imaging was obtained in 9% of cases. CONCLUSIONS: There is significant variability in pediatric substance exposure assessment practices. Disparities based on demographic characteristics are uncommon. Perceived severity of condition, exposures involving recreational/illegal/illicit substances, and greater prevalence of family psychosocial adversities are associated with higher rates of SW/CPT assessment and CPS reports.

Dexmedetomidine Withdrawal Syndrome in Children in the PICU: Systematic Review and Meta-Analysis.

OBJECTIVES: To systematically review literature describing the clinical presentation, risk factors, and treatment for dexmedetomidine withdrawal in the PICU (PROSPERO: CRD42022307178). DATA SOURCES: MEDLINE/PubMed, Cochrane, Web of Science, and Scopus databases were searched. STUDY SELECTION: Eligible studies were published from January 2000 to January 2022 and reported clinical data for patients younger than 21 years old following discontinuation of dexmedetomidine after greater than or equal to 24 hours of infusion. DATA EXTRACTION: Abstracts identified during an initial search were screened and data were manually abstracted after full-text review of eligible articles. The Newcastle-Ottawa Scale was used to assess study quality. Summary statistics were provided and Spearman rank correlation coefficient was used to identify relationships between covariates and withdrawal signs. A weighted prevalence for each withdrawal sign was generated using a random-effects model. DATA SYNTHESIS: Twenty-three studies (22 of which were retrospective cohort studies) containing 28 distinct cohorts were included. Median cumulative dexmedetomidine exposure by dose was 105.95 µg/kg (range, 30-232.7 µg/kg), median dexmedetomidine infusion duration was 131.75 hours (range, 20.5-525.6 hr). Weighted estimates for proportion (95% CI) of subjects experiencing withdrawal signs across all cohorts were: hypertension 0.34 (range, 0.0-0.92), tachycardia 0.26 (range, 0.0-0.87), and agitation 0.26 (range, 0.09-0.77). Meta-analysis revealed no correlation between dexmedetomidine exposure variables and withdrawal signs. A moderate negative monotonic relationship existed between the proportion of patients who had undergone cardiac surgery and the proportion experiencing hypertension (correlation coefficient, -0.47; p = 0.048) and tachycardia (correlation coefficient, -0.57; p = 0.008), indicating that in cohorts with a higher proportion of patients who were postcardiac surgery, there were fewer occurrences of hypertension and or tachycardia. CONCLUSIONS: On review of the 2000-2022 literature, dexmedetomidine withdrawal may be characterized by tachycardia, hypertension, or agitation, particularly with higher cumulative doses or prolonged durations. Since most studies included in the review were retrospective, prospective studies are needed to further clarify risk factors, establish diagnostic criteria, and identify optimal management strategies.

Improved glycemic control either alone, or combined with antioxidant supplementation, fails to restore blood glutathione or markers of oxidative stress in adolescents with poorly controlled type 1 diabetes.

In earlier studies, we showed that adolescents with type 1 diabetes mellitus (T1DM) have significant glutathione (GSH) depletion and that GSH is reciprocally related to glycemic control. In both the general population and in those with diabetes, the use of over-the-counter antioxidant supplements is widespread. We hypothesized that improved glycemic control, alone or in combination with dietary antioxidants, would restore blood GSH pool. The study included 41 participants who were 15.8 ± 2.4 years of age (mean ± standard deviation) and with poorly controlled T1DM (hemoglobin A1c [HbA1c] 8.2 ± 0.6%). Erythrocyte GSH, and 3-nitrotyrosine, F2-isoprostane, and 8-hydroxy-2'-deoxy-guanosine (as markers of protein, lipid, and DNA oxidative stress, respectively) were determined in the postabsorptive state after blood glucose was maintained overnight near euglycemia. Participants were then randomized to a mix of antioxidants (vitamin C, selenium, zinc, vitamin E, ß-carotene) or placebo for 3 to 6 months, and diabetes management was intensified using CSII (n = 30) or multiple daily injections (n = 11) coupled with CDE phone calls and visits with a Nutritionist. A second, identical study was performed when/if a drop in HbA1c ≥0.5% was achieved. HbA1c levels dropped similarly in both groups (from 8.9 ± 1.0% to 7.9 ± 0.9% and 8.5 ± 0.6% to 7.7 ± 0.7% in placebo and antioxidant group, respectively). Neither total nor reduced GSH was altered by improved metabolic control. Markers of protein, lipid, and DNA oxidation remained unaltered. We conclude that, in youngsters with T1DM, neither a significant improvement in diabetes control over a 3-month period nor the regimen of dietary antioxidant supplied in the current study can mitigate oxidative stress. These findings suggest that, in adolescents with T1DM, (1) more sustained improvement of diabetes control may be needed to alleviate oxidative stress and (2) the putative benefit of antioxidant supplements remains to be proven.

Preliminary evidence of glycine as a biomarker of cardiovascular disease risk in children with obesity.

Glycine (GLY) is a substrate for a wide range of metabolic processes. Several preclinical and adult studies demonstrated inverse associations of GLY with obesity, cardiovascular disease (CVD) and diabetes. However, little evidence is available on relationships between GLY and CVD risk in children. We assessed links between circulating GLY and biomarkers of CVD in children with obesity. Participants included both male and females with normal weight (NW, n = 6) and obesity (OB, n = 15), with age 14-18 years and Tanner stage >IV. Concentrations of GLY, branched chain amino acids (BCAA), and 25-hydroxy vitamin-D [25(OH)D], glucose, insulin, adiponectin, high sensitivity C-reactive protein (hs-CRP), and interleukin-6 (IL-6) were measured using established techniques, and body composition by DXA. Homeostatic model assessment for insulin resistance (HOMA-IR) was calculated. Our study identified major relationships of GLY (p-value < 0.01 for all) of GLY with visceral fat (r2 = 0.40), BCAA (r2 = 0.44), HOMA-IR (r2 = 0.33), 25(OH)D (r2 = 0.48), IL-6 (r2 = 0.46) and adiponectin (r2 = 0.39). Given that CVD progression is a continuum and the disease itself is not present in children and biomarkers are typically used to monitor CVD in children, the links between GLY and biomarkers of CVD provide evidence for the first time of a potential role for GLY in CVD in children with obesity.

The Child Healthcare at MATER Pediatric Study (CHAMPS): a 2-arm cluster randomized control trial of group well child care for mothers in treatment for opioid use disorder and their children.

BACKGROUND: Studies suggest that group-based well child care-a shared medical appointment where families come together as a group to receive pediatric primary care-increases patient-reported satisfaction and adherence to recommended care. Evidence supporting the use of group well child care for mothers with opioid use disorder, however, is lacking. The overall objective of the Child Healthcare at MATER Pediatric Study (CHAMPS) trial is to evaluate a group model of well child care for mothers with opioid use disorder and their children. METHODS: CHAMPS is a single-site 2-arm cluster randomized controlled trial. A total of 108 mother-child dyads will be enrolled into the study. Twenty-six clusters of approximately 4 mother-infant dyads each will be randomized 1:1 to one of two study arms (intervention or control). Clustering will be based on child's month of birth. In the intervention arm, group well child care will be provided on-site at a maternal substance use disorder treatment program. Mother-child dyads in the control arm will receive individual well child care from one nearby pediatric primary care clinic. Dyads in both study arms will be followed prospectively for 18 months, and data will be compared between the two study arms. Primary outcomes include well child care quality and utilization, child health knowledge, and parenting quality. DISCUSSION: The CHAMPS trial will provide evidence to determine if a group well child care offered on-site at an opioid treatment program for pregnant and parenting women is beneficial over individual well child care for families impacted by maternal opioid use disorder. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT05488379. Registered on Aug. 04, 2022.

Variation of asthma characteristics with atopic march, gastroesophageal reflux, and ENT pathologies.

BACKGROUND: Asthma is a significant cause of morbidity and mortality in the pediatric population. Atopic dermatitis (AD) is often the first step in the atopic march leading to the development of asthma, allergic rhinitis, and food allergies in the future. OBJECTIVE: This study aimed to evaluate the severity differences between asthmatic children with and without atopic march in addition to characteristics of asthmatic patients with GER and ear-nose-and-throat (ENT) pathologies. METHODS: A total of 616 pediatric asthmatic patients were enrolled. The study subjects were divided into two groups. Group A included asthmatic children with a history of AD. Group B had asthmatic children without a history of AD. Multiple factors were studied, including sex, race/ethnicity, family history of atopy, asthma severity, allergic rhinitis, food allergies, smoke exposure, ear-nose-and-throat (ENT) pathologies, gastroesophageal reflux (GER), frequency of systemic steroid use, and hospital admission rates. RESULTS: Our results revealed that patients with atopic march are at risk of developing a higher severity of asthma, resulting in increased morbidity. In contrast, asthmatic patients without atopic march had a milder asthma severity, less need for steroids, and fewer hospital admissions. A higher prevalence of ENT pathologies and/or GER existed among asthmatic children without atopic march. CONCLUSION: Our findings suggest that patients with atopic march should be expected to exhibit a more severe phenotype of asthma with increased asthma morbidity. Asthmatic patients without atopic march had a milder asthma phenotype, less need for steroids, and fewer hospital admissions. A higher prevalence of ENT pathologies and/or GER existed among asthmatic children without atopic march.

Cardiopulmonary Exercise Testing Characterizes Silent Cardiovascular Abnormalities in Asymptomatic Pediatric Cancer Survivors.

Late-onset cardiovascular complications are serious concerns for pediatric cancer survivors (PCS) including those who are asymptomatic. We investigated whether cardiopulmonary exercise testing (CPET) can delineate the underlying pathophysiology of preclinical cardiovascular abnormalities in PCS. We examined CPET data via cycle ergometer in asymptomatic PCS with normal echocardiogram and age-matched controls. Peak and submaximal parameters were analyzed. Fifty-three PCS and 60 controls were studied. Peak oxygen consumption (VO2), peak work rate (WR), and ventilatory anaerobic threshold (VAT) were significantly lower in PCS than controls (1.86 ± 0.53 vs. 2.23 ± 0.61 L/min, 125 ± 45 vs. 154 ± 46 W, and 1.20 ± 0.35 vs. 1.42 ± 0.43 L/min, respectively; all p < 0.01), whereas peak heart rate (HR) and ventilatory efficiency (a slope of minute ventilation over CO2 production or ∆VE/∆VCO2) were comparable. Peak respiratory exchange ratio (RER) was significantly higher in PCS (p = 0.0006). Stroke volume (SV) reserve was decreased in PCS, indicated by simultaneous higher dependency on HR (higher ∆HR/∆WR) and lower peak oxygen pulse (OP). Twelve PCS with high peak RER (≥ 1.3) revealed lower pVO2 and VAT than the rest of PCS despite higher ventilatory efficiency (lower ∆VE/∆VCO2), suggesting fundamental deficiency in oxygen utilization in some PCS. Poor exercise performance in PCS may be mainly attributed to limited stroke volume reserve, but the underlying pathophysiology is multifactorial. Combined assessment of peak and submaximal CPET parameters provided critical information in delineating underlying exercise physiology of PCS.

Asthma control in normal weight and overweight/obese asthmatic children following adenotonsillectomy.

OBJECTIVES: Childhood adenotonsillar hypertrophy (ATH) with sleep-disordered breathing (SDB) frequently occurs concomitant with asthma. Adenotonsillectomy and reduction in asthma severity association has been reported. We describe changes in asthma control in nonobese or normal weight and obese/overweight children undergoing adenotonsillectomy for SDB. METHODS: This prospective, nonrandomized cohort trial with 6-month follow-up at a tertiary children's hospital enrolled 41 children with persistent asthma undergoing adenotonsillectomy for SDB. Children with significant chronic medical conditions, premature birth (< 28 weeks), or recent respiratory infection were excluded. Patients were stratified by baseline BMI into nonobese or normal weight (BMI < 85 percentile) and obese/overweight (BMI > 85%). The primary outcome was change in Childhood Asthma Control Test (cACT) scores 3 and 6 months following adenotonsillectomy. Secondary outcome examined improvement in Pediatric Asthma Caregiver's Quality of Life Questionnaire (PACQLQ) 3 and 6 months following adenotonsillectomy. RESULTS: Baseline characteristics were similar except for anthropometric measures and mean PACQLQ (P = .03). Children with nonobese or normal weight (n = 26) had statistically significant improvement in change in cACT at 3 (22.80 ± 2.33 vs. 17.86 ± 3.53, P < .001) and 6 (20.71±3.29 vs. 18.24 ± 4.16, P = .044) months compared with baseline. PACQLQ scores also improved at 3 (6.20 ± 0.87 vs. 4.56 ± 1.12, P < .001) and 6 (6.36 ± 0.72 vs. 4.93 ± 0.96, P < .001) months. Obese/overweight children (n = 10) had significant improvement in cACT scores at 6 months (20.00 ± 3.90 vs. 15.00 ± 6.90, P = .048). Change of cACT scores at 3 months (17.86 ± 3.53 vs. 14.86 ± 6.31, P = .272) was not significantly different. PACQLQ scores improved at 3 (5.47 ± 1.09 vs. 3.70 ± 0.85, P < .001) and 6 (5.75 ± 2.19 vs. 3.67 ± 1.04, P = .016) months. CONCLUSION: Nonobese or normal-weight children undergoing adenotonsillectomy demonstrated significant improvement in asthma control scores at 3 and 6 and obese/overweight children at 6 months. Using the PACQLQ, caregiver quality of life improved for all children at 3 and 6 months. Surgical management of ATH in children with comorbid SBD and asthma is a good treatment option.

Impact of dysglycemia and obesity on the brain in adolescents with and without type 2 diabetes: A pilot study.

OBJECTIVE: Both diabetes and obesity can affect the brain, yet their impact is not well characterized in children with type 2 (T2) diabetes and obesity. This pilot study aims to explore differences in brain function and cognition in adolescents with T2 diabetes and obesity and nondiabetic controls with obesity and lean controls. RESEARCH DESIGN AND METHODS: Participants were 12-17 years old (5 T2 diabetes with obesity [mean HgbA1C 10.9%], 6 nondiabetic controls with obesity and 10 lean controls). Functional MRI (FMRI) during hyperglycemic/euglycemic clamps was performed in the T2 diabetes group. RESULTS: When children with obesity, with and without diabetes, were grouped (mean BMI 98.8%), cognitive scores were lower than lean controls (BMI 58.4%) on verbal, full scale, and performance IQ, visual-spatial and executive function tests. Lower scores correlated with adiposity and insulin resistance but not HgbA1C. No significant brain activation differences during task based and resting state FMRI were noted between children with obesity (with or without diabetes) and lean controls, but a notable effect size for the visual-spatial working memory task and resting state was observed. CONCLUSIONS: In conclusion, our pilot study suggests that obesity, insulin resistance, and dysglycemia may contribute to relatively poorer cognitive function in adolescents with T2 diabetes and obesity. Further studies with larger sample size are needed to assess if cognitive decline in children with obesity, with and without T2 diabetes, can be prevented or reversed.

Utilising pneuRIP device in determining the adequacy of respiratory support when weaning high-flow nasal cannula in paediatric patients with acute respiratory distress: A pilot study.

AIM: Recognition of paediatric respiratory distress and timely intervention is critical, especially during the weaning phase of support in paediatric acute respiratory failure, as weaning too aggressively can lead to further setbacks in a patient's recovery. We aimed to determine if pulmonary function measurements obtained with the pneuRIP device, a noninvasive pulmonary function testing device that provides measurements of labored breathing index (LBI), phase angle and %rib cage (%RC) contribution to breathing, will provide predictive values to assess the adequacy of respiratory support while weaning from HFNC. METHODS: We reviewed patients ages 0-18 years admitted to the PICU for respiratory distress due to respiratory infections receiving HFNC. Patients with history of chronic lung disease and chronic neuromuscular disease with baseline habnormal breathing patterns were excluded. Phase angle, LBI and %RC were obtained every hour and with every wean of HFNC. Nine patients were enroled. RESULTS: Mean LBI range remained 1.27-1.68 when LBI was plotted as a function of the HFNC flow rate. Mean values of %RC contribution to breathing ranged 43.65-57.12 as a function of the HFNC flow rate. No significant deviations existed in either %RC (P = 0.16) or LBI (P = 0.16) during the weaning of HFNC. Mean phase angle for all subjects was 41.48°-74.12° for the duration of wean and showed significant deviation from baseline during the weaning process (p = 0.001). CONCLUSIONS: Measurements of LBI and %RC on the pneuRIP device effectively demonstrated tolerance of weaning HFNC during the recovery phase of acute respiratory failure from a respiratory infection.

Newly Diagnosed Children with Cancer Have Lower 25-Vitamin D Levels than Their Cancer-Free Peers: A Comparison across Age, Race, and Sex.

Children with cancer have a greater risk for vitamin D concerns because of compromised health before diagnosis, the disease itself, and treatments for the cancer. This IRB-approved retrospective, matched case−control study of children with and without cancer included three race categories: black, other, and Caucasian. This is the first study to directly compare serum 25-hydroxy vitamin D (25(OH)D) levels and status in newly diagnosed pediatric cancer patients with age-, sex-, and race-matched cancer-free children from the same geographic region of the US, all of whom are free from other conditions that negatively impact 25(OH)D levels. Univariable and multivariable ordinal logistic regressions were performed. In the 544 children (mean age of 8.5 years, 53% female), there were 136 newly diagnosed children with cancer and 408 matched non-cancer controls. Serum 25(OH)D levels at cancer diagnosis were lower (22.4 ng/mL) than in controls (30.1 ng/mL; p < 0.0001). Differences persisted across race (p < 0.001) and age (p < 0.001), but not sex. Older children exhibited lower 25(OH)D levels. Only 18.4% of the children with cancer had sufficient levels. Black children with cancer had the greatest rate of deficiency (39%). Race differences were evident: children of color (other and black) displayed higher levels of insufficiency; black children were most deficient.

A Combined Analysis of Peak and Submaximal Exercise Parameters in Delineating Underlying Mechanisms of Sex Differences in Healthy Adolescents.

Peak exercise parameters are considered the gold standard to quantify cardiac reserve in cardiopulmonary exercise testing (CPET). We studied whether submaximal parameters would add additional values in analyzing sex differences in CPET. We reviewed CPET of age-matched healthy male and female adolescents by cycle ergometer. Besides peak parameters, submaximal CPET parameters, including ventilatory anaerobic threshold (VAT), oxygen uptake efficiency slope (OUES), and submaximal slopes of Δoxygen consumption (ΔVO2)/Δwork rate (ΔWR), Δheart rate (ΔHR)/ΔWR, ΔVO2/ΔHR, and Δminute ventilation (ΔVE)/ΔCO2 production (ΔVCO2), were obtained. We studied 35 male and 40 female healthy adolescents. Peak VO2 (pVO2), peak oxygen pulse (pOP), and VAT were significantly lower in females than males (1.9 ± 0.4 vs. 2.5 ± 0.6 L/min; 10 ± 2.0 vs. 13.2 ± 3.5 ml/beat; 1.23 ± 0.3 vs. 1.52 ± 0.5 L/min, respectively, all p < 0.005). Females showed significantly lower pVO2, VAT, and OUES with the same body weight than males, implying higher skeletal muscle mass in males. When simultaneously examining ΔHR/ΔWR and pOP, females showed higher dependency on increases in HR than in stroke volume. Females demonstrated significantly lower pOP with the same levels of ΔVO2/ΔHR, suggesting more limited exercise persistence than males under an anaerobic condition at peak exercise. Oxygen uptake efficiency in relation to peak VE was significantly higher in males. There was no sex difference in either ΔVO2/ΔWR or ΔVE/ΔVCO2. Combinational assessment of peak and submaximal CPET parameters delineates the multiple mechanisms that contribute to the sex differences in exercise performance.

Impact of Plans of Safe Care on Prenatally Substance Exposed Infants.

OBJECTIVE: To assess the impact of recent federal statute changes mandating child welfare-based Plan of Safe Care (POSC) supportive programming and community-based linkages to treatment providers, resources, and services for families of infants affected by prenatal substance exposure (IPSE). STUDY DESIGN: Retrospective review of Delaware's statewide child welfare case registry data for IPSE birth notifications and subsequent hotline reports for serious physical injury/fatality concerns from November 1, 2018-October 31, 2020. Abstracted variables included IPSE sex, substance exposure type, family characteristics (maternal personal child welfare history or mental health diagnosis, treatment engagement), and POSC referrals. RESULTS: Of 1436 IPSE, 1347 (93.8%) had POSC support. Most IPSE (67.2%) had exposure to single substance types prenatally. Nearly 90% avoided out-of-home placement. Nearly one-fourth of mothers delivered a prior IPSE; 40% of mothers had personal histories of childhood protective services involvement. Also, 43.5% of mothers and 9.1% of fathers were referred to community-based resources, including substance use, mental health treatment, parenting classes, and home visiting nursing. Nearly 58% of IPSE were referred for pediatric/developmental assessment. Notably, 0.82% (11 out of 1347) of IPSE with POSC sustained serious physical or fatal injury. CONCLUSIONS: POSC promote supportive, potentially protective linkages to community-based programming for IPSE and their families.

Glycosaminoglycans as Biomarkers for Mucopolysaccharidoses and Other Disorders.

Glycosaminoglycans (GAGs) are present in proteoglycans, which play critical physiological roles in various tissues. They are known to be elevated in mucopolysaccharidoses (MPS), a group of rare inherited metabolic diseases in which the lysosomal enzyme required to break down one or more GAG is deficient. In a previous study, we found elevation of GAGs in a subset of patients without MPS. In the current study, we aim to investigate serum GAG levels in patients with conditions beyond MPS. In our investigated samples, the largest group of patients had a clinical diagnosis of viral or non-viral encephalopathy. Clinical diagnoses and conditions also included epilepsy, fatty acid metabolism disorders, respiratory and renal disorders, liver disorders, hypoglycemia, developmental disorders, hyperCKemia, myopathy, acidosis, and vomiting disorders. While there was no conclusive evidence across all ages for any disease, serum GAG levels were elevated in patients with encephalopathy and some patients with other conditions. These preliminary findings suggest that serum GAGs are potential biomarkers in MPS and other disorders. In conclusion, we propose that GAGs elevated in blood can be used as biomarkers in the diagnosis and prognosis of various diseases in childhood; however, further designed experiments with larger sample sizes are required.

Association of Positional Plagiocephaly and Developmental Delay Within a Primary Care Network.

OBJECTIVE: Previous research has suggested an association between plagiocephaly and developmental delay. However, study samples drawn from children seen in subspecialty clinics increase the potential for selection and referral bias. Our study evaluates the association between plagiocephaly and developmental delay and the timing of these diagnoses in a primary care setting, where plagiocephaly is commonly diagnosed and managed. METHODS: Our retrospective analysis used electronic medical record data from 45 primary care sites within a children's health system from 1999 to 2017, including children aged 0 to 5 years with diagnoses determined by physician diagnosis codes at primary care visits. Children were classified in the plagiocephaly group if diagnosis occurred by 12 months of age. Primary outcome was any developmental delay. Pearson χ2 test, Fisher exact test, and logistic regression analyses were conducted, with multivariable models adjusted for sex, race, ethnicity, insurance, prematurity status (22-36 weeks' gestation), primary care sites, birth year, and diagnoses of abnormal tone and torticollis. RESULTS: Of 77,108 patients seen by 12 months, 2315 (3.0%) were diagnosed with plagiocephaly, with an increase in diagnosis prevalence over the study time frame. Plagiocephaly was independently associated with an increased odds of any developmental delay diagnosis (adjusted odds ratio 1.50, 95% confidence interval 1.32-1.70). The diagnosis of plagiocephaly was recorded before the diagnosis of developmental delay in most cases when both diagnoses were present (374 of 404, 92.6%). CONCLUSION: Data from a large primary care cohort demonstrate an association between plagiocephaly and developmental delay, affirming findings in previous subspecialty literature.

Surveillance imaging in pediatric ependymoma.

BACKGROUND: Management of pediatric patients with ependymoma includes posttreatment surveillance imaging to identify asymptomatic recurrences. However, it is unclear whether early detection translates into improved survival. The objective was to determine whether detection of ependymoma relapses on surveillance imaging translates into a survival benefit. PROCEDURE: Patients with ependymoma aged <21 years at diagnosis treated in the Nemours' Children's Health System between January 2003 and October 2016 underwent chart review. Relapsed patients' charts were assessed for details of initial therapy, surveillance imaging regimen, details of relapse including detection and therapy, and outcome. Median follow up of the entire cohort was 6.5 years from diagnosis and 3.5 years from relapse. RESULTS: Ninety of 198 (45%) patients experienced relapse with 61 (68%) detected by surveillance imaging and 29 (32%) detected based on symptoms. Five-year OS in the surveillance group was 67% (confidence interval [CI] 55-82%, SE 0.1) versus 51% (CI 35-73%, SE 0.19) in the symptoms group (P = .073). From relapse, the 3-year OS in the surveillance group was 62% (CI 50-78%, SE 0.11) versus 55% (CI 39-76%, SE 0.17) in the symptoms group (P = .063) and the 3-year SPFS was 45% (CI 33-61%, SE 0.16) in the surveillance group versus 32% (CI 19-55%, SE 0.27) in the symptoms group (P = .028). CONCLUSION: Surveillance imaging may identify recurrences in patients when they are more amenable to salvage therapy, resulting in superior 3-year SPFS, but given limited salvage options for children with recurrent ependymoma, the survival advantage of frequent surveillance imaging in asymptomatic patients remains ambiguous.

Validation of the Healthcare Transition Outcomes Inventory for Young Adults With Type 1 Diabetes.

OBJECTIVE: We recently developed and content validated the Healthcare Transition Outcomes Inventory (HCTOI), a stakeholder vetted, multidimensional measure of the outcomes of the transition from pediatric to adult healthcare for young adults (YA) with type 1 diabetes (T1D). In this study, we aimed to evaluate the psychometric properties of the HCTOI. METHODS: We collected and analyzed cross-sectional data from 128 YA (18-25 years old) with T1D to evaluate the psychometric properties of the HCTOI. We conducted confirmatory factor analysis (CFA), item analysis, and examined reliability and validity in relation to measures of quality of life, diabetes distress, regimen adherence, and glycemic control. RESULTS: CFA supported a five-factor solution: integration of T1D into emerging adult roles, balance of parental support with T1D autonomy, establishing and maintaining continuity of care, forming a collaborative patient-provider relationship, and ownership of T1D. We reduced the HCTOI from 54 to 34 items. The HCTOI demonstrated adequate internal consistency (α's = 0.62-0.87) and significant correlations demonstrated construct (quality of life, diabetes distress) and criterion validity (adherence, glycemic control). CONCLUSIONS: The HCTOI demonstrated promising initial psychometric properties. As the first measure of the multiple dimensions of healthcare transition outcomes, the HCTOI provides a means to examine longitudinal relations between transition readiness and outcomes and to assess the efficacy or effectiveness of interventions and programs designed to improve the transition process for YA with T1D.