Neonatal inflammation and its association with asthma and obesity in late childhood among individuals born extremely preterm.

BACKGROUND: Asthma and obesity are frequent outcomes among individuals born extremely preterm and are associated with decreased lifespan. Neonatal inflammation is associated with chronic neurodevelopmental disorders; however, it is less studied in association with other later childhood chronic disorders in this population. METHODS: Fourteen hospitals in 5 U.S. states enrolled 1506 infants born before 28 weeks of gestation in the Extremely Low Gestational Age Newborn cohort in 2004-2014. Neonatal blood spots were collected on postnatal days 1, 7, 14, 21, and 28, and used to measure 14 inflammation-related proteins. Associations were evaluated between high (top quartile) levels of proteins and two chronic health disorders at ages 10 and 15 years: physician-diagnosed asthma and obesity (body mass index ≥95th percentile). RESULTS: Few associations were found between high levels of 14 inflammation-related proteins, either on a single day or on multiple days, and either asthma or obesity. Similarly, few associations were found in analyses stratified by sex or presence/absence of prenatal inflammation. CONCLUSIONS: In extremely preterm newborns, systemic elevations of inflammation-related proteins during the neonatal period were not associated with childhood asthma and obesity outcomes at 10 or 15 years of age. IMPACT: In the large multi-center Extremely Low Gestational Age Newborn (ELGAN) cohort, sustained elevation of neonatal levels of inflammation-related proteins was not consistently associated with asthma or obesity outcomes at 10 or 15 years of age. This finding contrasts with reported associations of perinatal inflammation with obesity at 2 years and neurodevelopmental disorders at 2-15 years in the ELGANs, suggesting that unlike neurodevelopment, peripubertal obesity and asthma may be driven by later childhood exposures. Future research on perinatal mechanisms of childhood asthma and obesity should account for both fetal and later exposures and pathways in addition to inflammation at birth.

User-Centered Framework for Implementation of Technology (UFIT): Development of an Integrated Framework for Designing Clinical Decision Support Tools Packaged With Tailored Implementation Strategies.

BACKGROUND: Electronic health record-based clinical decision support (CDS) tools can facilitate the adoption of evidence into practice. Yet, the impact of CDS beyond single-site implementation is often limited by dissemination and implementation barriers related to site- and user-specific variation in workflows and behaviors. The translation of evidence-based CDS from initial development to implementation in heterogeneous environments requires a framework that assures careful balancing of fidelity to core functional elements with adaptations to ensure compatibility with new contexts. OBJECTIVE: This study aims to develop and apply a framework to guide tailoring and implementing CDS across diverse clinical settings. METHODS: In preparation for a multisite trial implementing CDS for pediatric overweight or obesity in primary care, we developed the User-Centered Framework for Implementation of Technology (UFIT), a framework that integrates principles from user-centered design (UCD), human factors/ergonomics theories, and implementation science to guide both CDS adaptation and tailoring of related implementation strategies. Our transdisciplinary study team conducted semistructured interviews with pediatric primary care clinicians and a diverse group of stakeholders from 3 health systems in the northeastern, midwestern, and southeastern United States to inform and apply the framework for our formative evaluation. RESULTS: We conducted 41 qualitative interviews with primary care clinicians (n=21) and other stakeholders (n=20). Our workflow analysis found 3 primary ways in which clinicians interact with the electronic health record during primary care well-child visits identifying opportunities for decision support. Additionally, we identified differences in practice patterns across contexts necessitating a multiprong design approach to support a variety of workflows, user needs, preferences, and implementation strategies. CONCLUSIONS: UFIT integrates theories and guidance from UCD, human factors/ergonomics, and implementation science to promote fit with local contexts for optimal outcomes. The components of UFIT were used to guide the development of Improving Pediatric Obesity Practice Using Prompts, an integrated package comprising CDS for obesity or overweight treatment with tailored implementation strategies. TRIAL REGISTRATION: ClinicalTrials.gov NCT05627011; https://clinicaltrials.gov/study/NCT05627011.

Comparison of Telemedicine Usage at Two Distinct Medicaid-Focused Pediatric Clinics.

Objective: To compare telemedicine versus office visit use at two Medicaid-focused pediatric primary care clinics. Methods: Retrospective cohort study from March 15, 2020 - March 15, 2021 at two Medicaid-focused pediatric primary care clinics. Site A and Site B care for different populations (Site B care for mostly immigrant families with preferred language Spanish). Outcomes included the percent of visits conducted through telemedicine and reason for visit. Descriptive statistics, univariable and multivariable mixed multilevel logistic regression, were used to assess relationship between patient demographics and telemedicine use. Results: Out of 17,142 total visits, 13% of encounters at Site A (n = 987) and 25% of encounters at Site B (n = 2,421) were conducted using telemedicine. Around 13.8% of well-child care (n = 1,515/10,997), 36.2% of mental health care (n = 572/1,581), and 25.0% of acute care/follow-up (n = 1,893/7,562) were telemedicine visits. After adjustment for covariates, there was no difference in odds of a patient having any telemedicine use by preferred language, sex, or payor. Patients 1-4 years of age had the lowest odds of telemedicine use. At Site A, patients who identified as Non-Hispanic Black (odds ratio [OR] = 0.33, 95% confidence interval [CI] = 0.24-0.45), Hispanic/Latinx (OR = 0.40, 95% CI = 0.24-0.66), or other race/ethnicity (OR = 0.35, 95% CI = 0.23-0.55) had lower odds of telemedicine use in comparison to Non-Hispanic White. Conclusions: Telemedicine was successfully accessed by Medicaid enrollees for different types of pediatric primary care. There was no difference in telemedicine use by preferred language and payor. However, differences existed by age at both sites and by race/ethnicity at one site. Future research should explore operational factors that improve telemedicine access for marginalized groups.

Positive Outliers: A Mixed Methods Study of Resiliency to Childhood Obesity in High-Risk Neighborhoods.

OBJECTIVE: Despite the high prevalence of obesity and the clustering of risk by neighborhood, few studies have examined characteristics which promote healthy child weight in neighborhoods with high obesity risk. We aimed to identify protective factors for children living in neighborhoods with high obesity risk. METHODS: We identified neighborhoods with high obesity risk using geolocated electronic health record data with measured body mass index (BMI) from well-child visits (2012-2017). We then recruited caregivers with children aged 5 to 13 years who lived in census tracts with mean child BMI percentile ≥72 (February 2020-August 2021). We used sequential mixed methods (quantitative surveys, qualitative interviews) to compare individual, interpersonal, and perceived neighborhood factors among families with children at a healthy weight (positive outliers [PO]) versus families with ≥1 child with overweight or obesity (controls). Regression models and comparative qualitative analysis were used to identify protective characteristics. RESULTS: Seventy-three caregivers participated in the quantitative phase (41% PO; 34% preferred Spanish) and twenty in the qualitative phase (50% PO; 50% preferred Spanish). The frequency of healthy caregiver behaviors was associated with being a PO (Family Health Behavior Scale Parent Score adjusted ß 3.67; 95% CI 0.52-6.81 and qualitative data). Protective factors also included caregivers' ability to minimize the negative health influences of family members and adhere to family routines. CONCLUSIONS: There were few differences between PO and control families. Support for caregiver healthy habits and adherence to healthy family routines emerged as opportunities for childhood obesity prevention in neighborhoods with high obesity risk.

Developmental Milestone Attainment in US Children Before and During the COVID-19 Pandemic.

Importance: Restrictions related to the COVID-19 pandemic disrupted the lives of young children, but the association between the pandemic and any changes in early childhood developmental milestone achievement in the US remains unclear. Objectives: To determine the association between the COVID-19 pandemic and changes in developmental screening scores among US children aged 0 to 5 years and to investigate whether caregivers self-reported more worries about their children or concerns about children's behavior during the pandemic, regardless of milestone achievement. Design, Setting, and Participants: This was a cohort study using an interrupted time series analysis comparing prepandemic (March 1, 2018, to February 29, 2020), interruption (March 1 to May 31, 2020), and intrapandemic (June 1, 2020, to May 30, 2022) periods among 50 205 children (randomly sampled from a population of 502 052 children) aged 0 to 5 years whose parents or caregivers completed developmental screening at pediatric visits at US pediatric primary care practices participating in a web-based clinical process support system. Exposure: COVID-19 pandemic period. Main Outcomes and Measures: Age-standardized Ages and Stages Questionnaire, Third Edition (ASQ) domain scores (communication, personal-social, problem-solving, gross motor, fine motor), and rate of caregivers' concerns about the child's behavior or worries about the child as measured on the ASQ. Results: A total of 50 205 children (25 852 [51.5%] male; mean [SD] age, 18.6 [16.0] months) and 134 342 ASQ observations were included. In adjusted models, significant age-specific mean score decreases from prepandemic to intrapandemic were observed in communication (-0.029; 95% CI, -0.041 to -0.017), problem-solving (-0.018; 95% CI, -0.030 to -0.006), and personal-social (-0.016; 95% CI, -0.028 to -0.004) domains. There were no changes in fine or gross motor domains prepandemic to intrapandemic. For infants aged 0 to 12 months, similar effect sizes were observed but only for communication (-0.027; 95% CI, -0.044 to -0.011) and problem-solving (-0.018; 95% CI, -0.035 to -0.001). After accounting for age-standardized ASQ scores, caregiver worries about the child increased slightly in the intrapandemic period compared with the prepandemic period (rate ratio, 1.088; 95% CI, 1.036-1.143), but there were no changes in caregiver concerns about the child's behavior. While changes in developmental screening scores were modest (2%-3%), nationwide, this could translate to more than 1500 additional recommended developmental referrals over baseline each month. Conclusions and Relevance: Modest changes in developmental screening scores are reassuring in the short term but may tax an already overburdened developmental behavioral pediatrics infrastructure. Continued attention to developmental surveillance is critical since the long-term population- and individual-level implications of these changes are unclear.

Pediatric Medical Subspecialist Use in Outpatient Settings.

Importance: A first step toward understanding whether pediatric medical subspecialists are meeting the needs of the nation's children is describing rates of use and trends over time. Objectives: To quantify rates of outpatient pediatric medical subspecialty use. Design, Setting, and Participants: This repeated cross-sectional study of annual subspecialist use examined 3 complementary data sources: electronic health records from PEDSnet (8 large academic medical centers [January 1, 2010, to December 31, 2021]); administrative data from the Healthcare Integrated Research Database (HIRD) (14 commercial health plans [January 1, 2011, to December 31, 2021]); and administrative data from the Transformed Medicaid Statistical Information System (T-MSIS) (44 state Medicaid programs [January 1, 2016, to December 31, 2019]). Annual denominators included 493 628 to 858 551 patients younger than 21 years with a general pediatric visit in PEDSnet; 5 million beneficiaries younger than 21 years enrolled for at least 6 months in HIRD; and 35 million Medicaid or Children's Health Insurance Program beneficiaries younger than 19 years enrolled for any amount of time in T-MSIS. Exposure: Calendar year and type of medical subspecialty. Main Outcomes and Measures: Annual number of children with at least 1 completed visit to any pediatric medical subspecialist in an outpatient setting per population. Use rates excluded visits in emergency department or inpatient settings. Results: Among the study population, the proportion of girls was 51.0% for PEDSnet, 51.1% for HIRD, and 49.3% for T-MSIS; the proportion of boys was 49.0% for PEDSnet, 48.9% for HIRD, and 50.7% for T-MSIS. The proportion of visits among children younger than 5 years was 37.4% for PEDSnet, 20.9% for HIRD, and 26.2% for T-MSIS; most patients were non-Hispanic Black (29.7% for PEDSnet and 26.1% for T-MSIS) or non-Hispanic White (44.9% for PEDSnet and 43.2% for T-MSIS). Annual rates for PEDSnet ranged from 18.0% to 21.3%, which were higher than rates for HIRD (range, 7.9%-10.4%) and T-MSIS (range, 7.6%-8.6%). Subspecialist use increased in the HIRD commercial health plans (annual relative increase of 2.4% [95% CI, 1.6%-3.1%]), but rates were essentially flat in the other data sources (PEDSnet, -0.2% [95% CI, -1.1% to 0.7%]; T-MSIS, -0.7% [95% CI, -6.5% to 5.5%]). The flat PEDSnet growth reflects a balance between annual use increases among those with commercial insurance (1.2% [95% CI, 0.3%-2.1%]) and decreases in use among those with Medicaid (-0.9% [95% CI, -1.6% to -0.2%]). Conclusions and Relevance: The findings of this cross-sectional study suggest that among children, 8.6% of Medicaid beneficiaries, 10.4% of those with commercial insurance, and 21.3% of those whose primary care is received in academic health systems use pediatric medical subspecialty care each year. There was a small increase in rates of subspecialty use among children with commercial but not Medicaid insurance. These data may help launch innovations in the primary-specialty care interface.

The Effect of an Obesity Prevention Intervention Among Specific Subpopulations: A Heterogeneity of Treatment Effect Analysis of the Greenlight Trial.

Background: Understanding how different populations respond to a childhood obesity intervention could help optimize personalized treatment strategies, especially with the goal to reduce disparities in obesity. Methods: We conducted a secondary analysis of the Greenlight Cluster Randomized Controlled Trial, a health communication focused pediatric obesity prevention trial, to evaluate for heterogeneity of treatment effect (HTE) by child biological sex, caregiver BMI, caregiver reported race and ethnicity, primary language, and health literacy. To examine HTE on BMI z-score from 2 to 24 months of age, we fit linear mixed effects models. Results: We analyzed 802 caregiver-child pairs, of which 52% of children were female, 58% of households reported annual family income of <$20,000, and 83% did not have a college degree. We observed evidence to suggest HTE by primary language (p = 0.047 for Spanish vs. English) and the combination of primary language and health literacy (p = 0.01). There was insufficient evidence to suggest that the Greenlight intervention effect differed by biological sex, caregiver BMI, or by race/ethnicity. Conclusions: This HTE analysis found that the Greenlight obesity prevention intervention had a more beneficial effect on child BMI z-score over 2 years for children of caregivers with limited health literacy and for caregivers for whom Spanish was the primary language.

Application of Physiologically Based Pharmacokinetic Modeling to Characterize the Effects of Age and Obesity on the Disposition of Levetiracetam in the Pediatric Population.

BACKGROUND: Levetiracetam is an antiseizure medication used for several seizure types in adults and children aged 1 month and older; however, due to a lack of data, pharmacokinetic (PK) variability of levetiracetam is not adequately characterized in certain populations, particularly neonates, children younger than 2 years of age, and children older than 2 years of age with obesity. OBJECTIVE: This study aimed to address the gap by leveraging PK data from two prospective standard-of-care pediatric trials (n = 88) covering an age range from 1 month to 19 years, including those with obesity (64%), and applying a physiologically based PK (PBPK) modeling framework. METHODS: A published PBPK model of levetiracetam for children aged 2 years and older was extended to pediatric patients younger than 2 years of age and patients older than 2 years of age with obesity by accounting for the obesity and age-related changes in PK using PK-Sim® software. The prospective pediatric data, along with the literature data for neonates and children younger than 2 years of age, were used to evaluate the extended PBPK models. RESULTS: Overall, 82.4% of data fell within the 90% interval of model-predicted concentrations, with an average fold error within twofold of the accepted criteria. PBPK modeling revealed that children with obesity had lower weight-normalized clearances (0.053 L/h/kg) on average than children without obesity (0.063 L/h/kg). The effect of maturation was well-characterized, resulting in comparable PBPK-simulated, weight-normalized clearances for neonates and children younger than 2 years of age reported from the literature. CONCLUSIONS: PBPK modeling simulations revealed that the current US FDA-labeled pediatric dosing regimen listed in the prescribing information can produce the required exposure of levetiracetam in these target populations with dose adjustments for children with obesity aged 4 years to younger than 16 years.

The Injury Prevention Program to Reduce Early Childhood Injuries: A Cluster Randomized Trial.

BACKGROUND AND OBJECTIVES: The American Academy of Pediatrics designed The Injury Prevention Program (TIPP) in 1983 to help pediatricians prevent unintentional injuries, but TIPP's effectiveness has never been formally evaluated. We sought to evaluate the impact of TIPP on reported injuries in the first 2 years of life. METHODS: We conducted a stratified, cluster-randomized trial at 4 academic medical centers: 2 centers trained their pediatric residents and implemented TIPP screening and counseling materials at all well-child checks (WCCs) for ages 2 to 24 months, and 2 centers implemented obesity prevention. At each WCC, parents reported the number of child injuries since the previous WCC. Proportional odds logistic regression analyses with generalized estimating equation examined the extent to which the number of injuries reported were reduced at TIPP intervention sites compared with control sites, adjusting for baseline child, parent, and household factors. RESULTS: A total of 781 parent-infant dyads (349 TIPP; 432 control) were enrolled and had sufficient data to qualify for analyses: 51% Hispanic, 28% non-Hispanic Black, and 87% insured by Medicaid. Those at TIPP sites had significant reduction in the adjusted odds of reported injuries compared with non-TIPP sites throughout the follow-up (P = .005), with adjusted odds ratios (95% CI) of 0.77 (0.66-0.91), 0.60 (0.44-0.82), 0.32 (0.16-0.62), 0.26 (0.12-0.53), and 0.27 (0.14-0.52) at 4, 6, 12, 18, and 24 months, respectively. CONCLUSIONS: In this cluster-randomized trial with predominantly low-income, Hispanic, and non-Hispanic Black families, TIPP resulted in a significant reduction in parent-reported injuries. Our study provides evidence for implementing the American Academy of Pediatrics' TIPP in routine well-child care.

Language Disparities in Caregiver Satisfaction with Physician Communication at Well Visits from 0-2 Years.

OBJECTIVE: This study aimed to describe caregiver satisfaction with physician communication over the first two years of life and examine differences by preferred language and the relationship to physician continuity. METHODS: Longitudinal data were collected at well visits (2 months to 2 years) from participants in a randomized controlled trial to prevent childhood obesity. Satisfaction with communication was assessed using the validated Communication Assessment Tool (CAT) questionnaire. Changes in the odds of optimal scores were estimated in mixed-effects logistic regression models to evaluate the associations between satisfaction over time and language, interpreter use, and physician continuity. RESULTS: Of 865 caregivers, 35% were Spanish-speaking. Spanish-speaking caregivers without interpreters had lower odds of an optimal satisfaction score compared with English speakers during the first 2 years, beginning at 2 months [OR 0.64 (95% CI: 0.43, 0.95)]. There was no significant difference in satisfaction between English-speaking caregivers and Spanish-speaking caregivers with an interpreter. The odds of optimal satisfaction scores increased over time for both language groups. For both language groups, odds of an optimal satisfaction score decreased each time a new physician was seen for a visit [OR 0.82 (95% CI: 0.69, 0.97)]. CONCLUSION: Caregiver satisfaction with physician communication improves over the first two years of well-child visits for both English- and Spanish-speakers. A loss of physician continuity over time was also associated with lower satisfaction. Future interventions to ameliorate communication disparities should ensure adequate interpreter use for primarily Spanish-speaking patients and address continuity issues to improve communication satisfaction.

Infant Feeding Outcomes From a Culturally-Adapted Early Obesity Prevention Program for Immigrant Chinese American Parents.

OBJECTIVE: To examine whether a cultural adaptation of an early childhood obesity prevention program promotes healthy infant feeding practices. METHODS: Prospective quasi-experimental study of a community-engaged multiphasic cultural adaptation of an obesity prevention program set at a federally qualified health center serving immigrant Chinese American parent-child dyads (N = 298). In a group of historical controls, we assessed early infant feeding practices (breastfeeding, sugar-sweetened beverage intake) in 6-month-olds and then the same practices alongside early solid food feeding practices (bottle weaning, fruit, vegetable, sugary or salty snack consumption) in 12-month-olds. After implementation, we assessed these practices in an intervention cohort group at 6 and 12 months. We used cross-sectional groupwise comparisons and adjusted regression analyses to evaluate group differences. RESULTS: At 6 months, the intervention group had increased odds of no sugar-sweetened beverage intake (aOR: 5.69 [95% confidence interval (CI): 1.65, 19.63], P = .006). At 12 months, the intervention group also had increased odds of no sugar-sweetened beverage intake (aOR: 15.22 [95% CI: 6.33, 36.62], P < .001), increased odds of bottle weaning (aOR: 2.34 [95% CI: 1.05, 5.23], P = .03), and decreased odds of sugary snack consumption (aOR: 0.36 [0.18, 0.70], P = .003). We did not detect improvements in breastfeeding, fruit, vegetable, or salty snack consumption. CONCLUSIONS: A cultural adaptation of a primary care-based educational obesity prevention program for immigrant Chinese American families with low income is associated with certain healthy infant feeding practices. Future studies should evaluate cultural adaptations of more intensive interventions that better address complex feeding practices, such as breastfeeding, and evaluate long-term weight outcomes.