Prematurity affects brain development and increases risk for neurodevelopmental impairments. Yet reliable biomarkers for at-risk infants remain limited. We developed brain-age prediction models using diffusion magnetic resonance imaging-derived white matter features from two datasets: (1) the developing Human Connectome Project (dHCP; 368 healthy infants) and (2) a clinical sample collected at the Lucile Packard Children's Hospital (LPCH; 162 high-risk preterm infants). The goals of this study were (1a) to construct a white matter neonatal brain-age model including full-term and preterm neonates from a large research data set, (1b) to evaluate the accuracy of a separate brain-age model using the same architecture but trained and evaluated via cross-validation on a restricted subset of very preterm infants (<32 weeks gestational age) from the same data set to improve comparability with our clinical cohort; (2) to determine if a similar model can predict brain-age based on clinical MRI scans from high-risk neonates born preterm; and (3) to evaluate whether this preterm white matter-based brain-age model provides information about the infant's health beyond conventional clinical and demographic measures. White matter features demonstrated strong predictive performance in the dHCP dataset (within 3.9 days) and the LPCH clinical dataset (within 6.6 days). However, brain-age metrics (i.e., brain-age gap) showed no significant associations with health complications measured by a composite score of common prematurity complications. While tractometry-derived brain-age models accurately characterize brain maturation in the neonatal brain, their sensitivity to clinical complications in preterm infants appears limited. Global white matter maturation measures derived from clinical grade data may be insufficiently sensitive to capture the cumulative burden of prematurity-related morbidities, suggesting need for multimodal or longitudinal biomarkers.

AimThis study determined the prevalence of positive autism screening results at 18-30 months of age and the presence of an autism diagnosis among children with congenital heart disease (CHD).MethodsSecondary analysis of data from Stanford site of California Perinatal Quality Care Collaborative and Lucile Packard Children's Hospital electronic health records. Participants (N = 94) were children born between 2016-2020 with CHD who required surgery before discharge from the intensive care unit and had a High-Risk Infant Follow-Up (HRIF) visit at age 18-30 months. Heart disease was classified as cyanotic or acyanotic. Outcomes were results of the Modified Checklist for Autism-Revised/Follow-up (M-CHAT-R/F) at the HRIF visit and evidence of a subsequent autism diagnostic code. We compared sociodemographic, clinical, and medical factors across screen results and autism diagnosis.ResultsPrevalence of positive autism screens was 14.6% and autism diagnosis was 11.7%. The factor associated with screen results was age; children with positive screens were younger than children with negative screens. Use of public insurance and Risk Stratification for Congenital Heart Surgery-2 scores were higher in children with autism. Performance of M-CHAT-R/F in relation to autism diagnosis showed sensitivity of 66%, positive predictive value of 57%, and higher specificity and negative predictive values.ConclusionIn this sample, children with CHD were >3 times more likely to have positive autism screens and the diagnosis of autism than children in the general population. Early screening for autism is critical in children with CHD to promote early diagnosis and intervention.

Objective:To examine group differences and continuity in caregiving environments of infants born preterm from Spanish- and English-speaking families. Study Design:We conducted a prospective cohort study of Spanish- (n = 17) and English-speaking (n = 23) families of infants born preterm (< 32 weeks gestation). Caregiver-infant engagement was assessed neonatally via hospital visitation and skin-to-skin (STS) care, and at home via child-directed adult word counts/hour (CD-AWC/hour) from all-day audio recordings. Result:No significant group differences were observed in family visitation, neonatal STS care, or in-home verbal engagement, although STS care rates varied considerably, especially within Spanish-speaking families. Across both groups, greater STS care was associated with higher CD-AWC/hour at home. Conclusion:Spanish- and English-speaking families showed comparable patterns of caregiver-infant engagement, as a group, however, many Spanish-speaking families engaged in less STS than English-speaking families. STS care predicted caregiver-infant verbal engagement at home, highlighting continuity from hospital to home.

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Autism is more common among children born preterm than children born at term. This study determined the prevalence of positive autism screening among children born preterm and evaluated sociodemographic, clinical, and neurodevelopmental factors associated with positive screens. Secondary analyses of data from Lucile Packard Children’s Hospital High Risk Infant Follow-up clinic. Infants born < 32 weeks gestation between 2016 and 2020, who attended the clinic at 18–30 months, were classified into two groups based on results of Modified Checklist for Autism in Toddlers-Revised with Follow-Up (M-CHAT-R/F): positive-screen (score > 2) and negative-screen (≤ 2). We compared sociodemographics, clinical factors, and language development across groups. The prevalence of positive screens was 12.2

BACKGROUND AND OBJECTIVES:Preterm birth is associated with altered white matter development and long-term neurodevelopmental impairments. Skin-to-skin care has known benefits for physiologic regulation and bonding in preterm infants, but impacts on early brain structure remain unclear. The aim of this study was to describe the association between in-hospital skin-to-skin care and white matter microstructure in very preterm infants, focusing on frontolimbic tracts involved in stress regulation and socioemotional development. METHODS:The design was a single-center retrospective observational analysis of clinical data from the electronic medical records and diffusion MRI scans. Participants were infants born at <32 weeks gestational age (GA) who received a routine predischarge MRI. Skin-to-skin care was quantified as duration per instance and daily exposure rate (in minutes) before the MRI was obtained. Diffusion MRI assessed mean diffusivity (MD) and fractional anisotropy (FA) in the cingulum, anterior thalamic radiations (ATRs), and uncinate fasciculus. Hierarchical regression models evaluated associations between skin-to-skin care and white matter metrics, adjusting for GA, medical acuity, postmenstrual age at scan, and MRI coil type. RESULTS:A total of 88 preterm infants (mean GA 29 weeks; 49% female) were included. Skin-to-skin care duration per instance was positively associated with MD in the cingulum (B = 0.002, 95% CI 0.0004-0.003, ΔR2 = 0.080) and ATRs (B = 0.002, 95% CI 0.0003-0.003, ΔR2 = 0.057). Skin-to-skin care daily exposure rate was also positively associated with ATR MD (B = 0.038, 95% CI 0.001-0.076, ΔR2 = 0.046). Both skin-to-skin metrics were negatively associated with ATR FA (duration: B = -0.0005, 95% CI -0.001 to -0.0001, ΔR2 = 0.046; rate: B = -0.016, 95% CI -0.028 to -0.004, ΔR2 = 0.075). No significant associations were found for the uncinate fasciculus. Findings remained significant after adjusting for socioeconomic status and visitation frequency and after excluding infants with white matter injury. DISCUSSION:Skin-to-skin care was associated with neonatal white matter microstructure in specific frontolimbic tracts. Limitations include the retrospective design and single-center setting. Future studies should consider how early caregiving experiences, such as skin-to-skin care, may influence brain development in preterm infants.

Background and Objectives:Preterm birth is associated with altered white matter development and long-term neurodevelopmental impairments. Skin-to-skin care (kangaroo care) has well-documented benefits for physiological stability and bonding, but its association with neonatal brain structure remains unclear. This study explored the association between in-hospital skin-to-skin care and neonatal white matter microstructure in frontal and limbic pathways that are linked to stress regulation and socio-emotional development, processes potentially influenced by affective touch during skin-to-skin care. Methods:This retrospective study analyzed electronic medical records and diffusion MRI data collected from 86 preterm infants (<32 weeks gestational age) in a single NICU. Skin-to-skin care exposure was quantified as total duration (minutes/instance) and rate (minutes/day) of sessions. Diffusion MRI scans obtained before hospital discharge assessed mean diffusivity (MD) and fractional anisotropy (FA) in the cingulate, anterior thalamic radiations (ATR), and uncinate fasciculus. Hierarchical regression models examined associations between skin-to-skin care and white matter microstructure, adjusting for gestational age, health acuity, postmenstrual age at scan, and MRI coil type. Sensitivity analyses controlled for socioeconomic status and NICU visitation frequency. Results:Skin-to-skin care duration was positively associated with MD in the cingulate (B = 0.002, p = 0.016) and ATR (B = 0.002, p = 0.020). Skin-to-skin care rate was also positively linked to MD in the ATR (B = 0.040, p = 0.041). Skin-to-skin care duration and rate were not associated with FA in the cingulate but skin-to-skin duration and rate were negatively associated with FA in the ATR (duration: B = -0.001, p = 0.020; rate: B = -0.017, p = 0.008). No significant associations were found for the uncinate fasciculus. Findings remained robust after adjusting for socioeconomic status and visitation frequency. Discussion:This study provides novel evidence linking in-hospital experiences of skin-to-skin care to neonatal white matter development. These findings have important implications for understanding how family-centered neuroprotective practices, such as skin-to-skin care, may affect brain development to improve long-term developmental outcomes.

Importance:Early identification and treatment of Attention-Deficit/Hyperactivity Disorder (ADHD) symptoms in preschool-age children is important for mitigating social-emotional and academic problems. Clinical practice guidelines recommend first-line behavior intervention before considering medication treatment for children 4-5-years-old. Objective:To assess variation in rates of ADHD identification and rates and timing of medication treatment in children 3-5-years-old in primary care settings across eight US pediatric health systems and to identify patient factors associated with the time from diagnosis to prescription. Design:Retrospective cohort study of electronic health records. Setting:Primary care clinics affiliated with eight academic institutions participating in the PEDSnet Clinical Research Network. Participants:Children 3-5-years-old seen in primary care between 2016-2023. Exposure:ADHD diagnosis at age 4-5 years. Main Outcomes and Measures:Outcomes: (1) rate of ADHD diagnosis; (2) rate of stimulant and non-stimulant prescription after diagnosis before age 7, (3) time from first ADHD-related diagnosis (including symptom-level diagnoses) to medication prescription. Independent variables: institution, year of diagnosis, patient age, sex, race/ethnicity, medical insurance, and presence of comorbidities. Results:Of 712,478 children seen in primary care at ages 3-5 years, 9,708 (1.4%) received an ADHD diagnosis at age 4-5 years (range 0.5-3.1% across institutions). Of those with ADHD, 76.4% (n=7414) were male, 39.0% (n=3782) were White. Of 9,708 preschool-age children with ADHD, 68.2% (6624) were prescribed ADHD medications before age 7, 42.2% (n=4092) were prescribed medications within 30 days of the first documentation of an ADHD-related diagnosis (range 26.0-49.0% across institution). Asian (aHR 0.50, CI 0.38-0.65), Hispanic (aHR 0.75, CI 0.70-0.81), and Black (aHR 0.90, CI 0.85-0.96) children with ADHD were less likely to be prescribed medication early compared to White children. Older (aHR 1.64, CI 1.57-1.72), male (aHR 1.74, CI 1.11-1.24) and publicly insured (aHR 1.10, CI 1.04-1.17) patients were more likely to be prescribed medication early compared to younger, female and privately insured patients, respectively. Conclusion and Relevance:Many preschool-age children with ADHD seen in primary care in 8 large pediatric health systems were prescribed medications at or shortly after the first documented diagnosis. Future analysis of clinical documentation is needed to understand the reasoning behind early prescription patterns.

Purpose To determine if reading development between ages 6 and 8 years related to changes in fractional anisotropy (FA) in the optic radiations (OR), and if these associations were similar in children born full term (FT) and preterm (PT) and in language tracts. Methods FT (n=34) and PT (n=34) children completed the Word Identification subtest of the Woodcock Reading Mastery Test at 6, 7, and 8 years. Diffusion MRI (96-directions, b=2500sec/mm2) was acquired at 6 and 8 years. Probabilistic tractography identified bilateral OR and three left-hemisphere language tracts: inferior longitudinal fasciculus (ILF), superior longitudinal fasciculus (SLF), and arcuate fasciculus (AF). Linear mixed models determined if FA changes in these tracts were associated with reading growth. Results Rates of reading growth were similar in both groups. For the OR, FA change from 6 to 8 years was negatively associated with reading growth in both groups. A similar pattern was observed in the left ILF but not in the SLF or AF. Conclusion Individual differences in reading development were associated with FA change of the OR and left ILF in FT and PT children. Negative associations implicate increasing axonal diameter and/or complexity in fiber structure as drivers of faster reading development.

Objective:Early speech experiences are presumed to contribute to the development of brain structures involved in processing speech. Previous research has been limited to correlational studies. Here, we conducted a randomized trial with neonates born preterm to determine whether increased exposure to maternal speech during NICU hospitalization is causally linked to structural white matter maturation. Study design:We enrolled 46 neonates born preterm (24-31 weeks gestational age). Participants were randomly assigned to receive increased (T: n = 21) or routine (C: n = 25) exposure to mother's speech. The T-group heard 10-min audio recordings of their mothers reading a children's story two times/hour between 10pm and 6am, increasing speech exposure by 2.67 h/day. The C-group did not hear recorded speech. At near-term-equivalent age, we obtained two high-angular resolution diffusion MRI (scan 1: b = 700, scan 2: b = 1500) and T1 relaxometry scans. We assessed mean diffusivity (MD), pre-registered primary outcome (NCT02847689), of the left and right arcuate fasciculus, tracts implicated in language processing. Secondary outcomes included fractional anisotropy (FA) and R1 (1/T1). We hypothesized that neonates randomized to the T-group would show evidence for increased maturation within the arcuate, indexed as decreased MD and increased FA and R1, compared to neonates in the C-group. Results:Groups were equivalent on medical and demographic variables. Linear mixed models demonstrated that compared to the C-group, the T-group demonstrated significantly lower MD in the left (scan 1: β = -0.11, Marginal R2 = 0.27; scan 2: β = -0.12, Marginal R2 = 0.33) but not right arcuate (scan 1: β = -0.06, Marginal R2 = 0.09; scan 2: β = -0.03, Marginal R2 = 0.01). The T-group also demonstrated significantly higher FA (scan 1 β = 0.02, Marginal R2 = 0.20; scan 2: β = 0.03, Marginal R2 = 0.31) and R1 (β = 0.02, Marginal R2 = 0.39) in the left but not right arcuate. Conclusion:Preterm neonates with increased maternal speech exposure showed more mature left arcuate microstructure, supporting a causal role of exposure to speech in brain development. Enhancing speech exposure in the NICU may benefit preterm children's language outcomes.

Importance:Early identification and treatment of attention-deficit/hyperactivity disorder (ADHD) symptoms in preschool-age children is important for mitigating social, emotional, and academic problems. Clinical practice guidelines recommend first-line behavior intervention before considering medication treatment for children aged 4 to 5 years. Objective:To assess variation in rates of ADHD identification and rates and timing of medication initiation in children aged 3 to 5 years in primary care settings across 8 US pediatric health systems and to identify patient factors associated with the time from diagnosis to prescription. Design, Setting, and Participants:This retrospective cohort study used electronic health records from primary care clinics affiliated with 8 academic institutions participating in the PEDSnet Clinical Research Network. Participants were children aged 3 to 5 years seen between 2016 to 2023. Data were extracted from the PEDSnet database on April 18, 2025. Exposure:ADHD diagnosis at age 4 to 5 years. Main Outcomes and Measures:The primary outcomes were (1) rate of ADHD diagnosis, (2) rate of stimulant and nonstimulant prescription after diagnosis before age 7 years, and (3) time from first ADHD-related diagnosis (including symptom-level diagnoses) to medication prescription. Independent variables included institution, year of diagnosis, patient age, sex, race and ethnicity, medical insurance, and presence of comorbidities. Multivariable Cox proportional hazards models were used to estimate associations between clinical and demographic variables and time from diagnosis to prescription. Results:Of 712 478 children seen in primary care at age 3 to 5 years, 9708 (1.4%) received an ADHD diagnosis at age 4 to 5 years (range across institutions, 0.5%-3.1%; median [IQR] age at first ADHD-related diagnosis, 5.31 [4.86-5.66] years). Of those with ADHD, 7414 (76.4%) were male, 1762 (18.1%) were Hispanic, 122 (1.3%) were non-Hispanic Asian, 3014 (31.0%) were non-Hispanic Black, 479 (4.9%) were non-Hispanic multiracial, 3782 (39.0%) were non-Hispanic White, 148 (1.5%) were non-Hispanic other, and 401 (4.1%) were of unknown race and ethnicity. Of 9708 preschool-age children with ADHD, 6624 (68.2%) were prescribed ADHD medications before age 7 years, and 4092 (42.2%) were prescribed medications within 30 days of the first documentation of an ADHD-related diagnosis (range across institutions, 26.0%-49.0%). Asian (adjusted hazard ratio [aHR], 0.51; 95% CI, 0.38-0.68), Hispanic (aHR, 0.75; 95% CI, 0.70-0.81), and Black (aHR, 0.88; 95% CI, 0.83-0.94) children with ADHD were less likely to be prescribed medication early compared with White children. Older vs younger patients (aHR, 1.62; 95% CI, 1.55-1.69), male vs female patients (aHR, 1.17; 95% CI, 1.11-1.25), and publicly insured vs privately insured patients (aHR, 1.09; 95% CI, 1.03-1.15) were more likely to be prescribed medication early. Conclusion and Relevance:In this retrospective cohort study of preschool-age children with ADHD seen in primary care in 8 large pediatric health systems, many children were prescribed medications at or shortly after the first documented diagnosis. Analysis of clinical documentation is needed to understand early prescription patterns.

Infants from lower-socioeconomic (SES) backgrounds are at increased risk for compromised developmental outcomes compared to infants from higher-SES backgrounds. Features of caregiver-child interactions have been proposed as mechanisms through which SES-related factors are associated with child outcomes. This study assessed whether rates of tactile interactions between neonates and family members (skin-to-skin caregiving) served as a mechanism, that is, statistically mediated, SES-related developmental disparities in infants born preterm (n = 95). Infants from lower-SES backgrounds experienced less skin-to-skin care and scored lower on developmental assessments than infants from higher-SES backgrounds. Infants who experienced more skin-to-skin care had better outcomes than infants who experienced less skin-to-skin care. Critically, the direct association between SES and outcomes was significantly reduced after controlling for skin-to-skin care rates. Thus, SES-related disparities were linked to caregiving experiences as early as the neonatal period. Parallel analyses on non-skin-to-skin tactile care (swaddled holding, touch, and massage) revealed no associations, highlighting the specificity of skin-to-skin caregiving. These findings make substantial contributions to developmental theory and offer concrete and scalable recommendations for intervention.

Family navigation (FN) has emerged as a promising intervention for reducing barriers and addressing social and economic inequities in autism service delivery. Little is known regarding the implementation and effectiveness of FN for children with autism. The aims of this scoping review are to: (1) summarize the breadth, quantity, and characteristics of the existing literature on FN for children diagnosed with autism; (2) describe the models and outcomes of FN for this population; and (3) identify knowledge gaps and provide directions for future research. Authors used Arksey and O’Malley’s methodological framework for scoping reviews. Searches were conducted in PubMed, CINAHL, Embase, Social Services Abstracts, and Web of Science, resulting in identification of 308 papers. Two independent raters completed title/abstract and full-text screenings. Data was extracted using a researcher-developed tool. Results synthesis involved content and construct analysis and descriptive numerical summaries. 17 publications met inclusion criteria. Among these, seven studies evaluated FN models delivered by professional or peer navigators. Three studies investigated FN tools. The remaining seven papers included five qualitative and two mixed methods studies that provided valuable insights on improving FN programs. Overall, studies on FN models reported positive impacts on family activation and well-being, knowledge, and service access and utilization. None addressed improvements in child developmental status or behavioral profiles. FN is a promising intervention for improving family outcomes and increasing service access and utilization. Further research is needed to establish best practices, identify child- and family-centered outcome metrics, and promote scalability and sustainability.

Family navigation (FN) is a promising intervention for reducing barriers and addressing inequities in healthcare, but engaging families in FN can be challenging. This study assessed FN engagement for historically underserved families of children newly diagnosed with autism. Objectives were to (1) describe FN engagement rates across four stages: recruitment, enrollment, retention, and involvement; (2) examine family characteristics influencing recruitment, enrollment, and retention; and (3) evaluate the receipt of autism-specific services based on family characteristics and number of interactions with navigators. This descriptive cohort study included families who were Medicaid recipients or self-identified as Hispanic/Latino or Black/African-American. Spanish-English bilingual, bicultural navigators provided FN through semi-structured sessions and brief contacts with participants. Descriptive statistics analyzed family demographics and engagement rates. Regression analyses examined family characteristics predictive of successful engagement and service receipt. Of 292 eligible families, 210 (71.9

This descriptive cohort study documented continuity between family-delivered skin-to-skin care rates for preterm infants in the NICU and amount of child-directed speech at child age 9 months. Involvement in skin-to-skin care may be an early marker of caregiver engagement and a target for early interventions that support positive caregiver-infant interactions.

CASE: Leo is a 28-month-old boy from a monolingual Spanish-speaking family who was referred to a developmental-behavioral pediatrics (DBP) clinic for concerns regarding autism. His parents migrated to the United States 8 years ago and currently live and work on a farm. He was born in a US hospital after an uncomplicated pregnancy and has been generally healthy. His parents first became concerned about his development when he was 16 months old. He stopped saying mama/dada in Spanish and started lining up random objects. He had frequent temper tantrums and was difficult to console during unexpected changes in his routine. He screened positive on the Modified Checklist for Autism in Toddlers, Revised with Follow-Up (M-CHAT-R/F) at his 18-month well-child visit, and his pediatrician referred him to the local early intervention program. Calls from the early intervention program to his parents were unanswered. At his 24-month well-child visit, he again screened positive on the M-CHAT-R/F, and his pediatrician placed a referral for a DBP consultation. During the DBP visit at 28 months of age, developmental testing indicated his receptive and expressive language skills to be in the extremely low range, with significant scatter in his cognitive and adaptive skills. Behavioral observations were consistent with parental history and showed differences in social communication and interaction, the presence of repetitive behaviors, and extreme distress with transitions. He was diagnosed with autism spectrum disorder. Recommendations, including referral to early intervention, applied behavior analysis therapy, speech and language therapy, audiology evaluation, and genetic testing, were discussed with his parents through an interpreter. An autism packet, written in Spanish, with detailed information about autism and community resources was given to the family. By the time of a follow-up DBP visit 6 months later, Leo had not started on any early intervention or therapeutic services. Where do you go from here?

Background Severe neonatal inflammatory conditions in very preterm infants (VPT: <32 weeks gestational age, GA) are linked to adverse neurodevelopmental outcomes. Differences in white matter (WM) microstructure of the corpus callosum (CC) have been observed at age 6 in VPT children with a history of severe neonatal inflammation. The goal of this study was to determine whether these CC differences can be detected at term-equivalent age using diffusion MRI (dMRI), and whether neonatal inflammation is associated with altered WM in additional tracts implicated in the encephalopathy of prematurity. Methods We conducted a retrospective study of VPT infants (n = 152) born at 22–32 weeks GA, classified based on the presence (I+, n = 80) or absence (I-, n = 72) of severe neonatal inflammatory conditions (bronchopulmonary dysplasia, necrotizing enterocolitis, or culture-positive sepsis). Analysis of covariance (ANCOVA) assessed group differences in near-term dMRI mean fractional anisotropy (FA) and mean diffusivity (MD) across seven segments of the CC and the anterior thalamic radiation, arcuate fasciculus, cingulum, corticospinal tract, inferior longitudinal fasciculus, superior cerebellar peduncle, and uncinate fasciculus. Due to imbalance of GA in the full sample, secondary ANCOVA analyses were performed in a GA-matched subset (n = 42) to further isolate the effect of inflammation. Results FA was significantly lower in the I+ group compared to the I- group in the anterior frontal, posterior parietal, temporal, and occipital segments of the CC, and in the cingulum, inferior longitudinal fasciculus, and superior cerebellar peduncle. This general pattern persisted in the GA-matched subset, with significant differences in the anterior frontal and temporal CC segments. Conclusions VPT infants with severe neonatal inflammation had lower FA in multiple white matter tracts, suggesting that inflammation-related alterations in WM development begin in the neonatal period. The observed differences detected using dMRI at term-equivalent age corroborate prior findings and may provide a window of opportunity for early identification of VPT infants at increased risk of poor neurodevelopmental outcomes.