Cerebral Palsy and Motor Impairment After Extreme Prematurity: Prediction of Diagnoses at Ages 2 and 10 Years.

OBJECTIVE: To identify perinatal factors in children born extremely preterm (EP) that were associated with motor impairment (MI) at 2 and 10 years of age and develop a predictive algorithm to estimate the risk of MI during childhood. STUDY DESIGN: Participants of the Extremely Low Gestational Age Newborns Study (ELGANS) were classified as: no MI, MI only at 2 years, MI only at 10 years, and MI at both 2 and 10 years, based on a standardized neurological examination at 2 and the Gross Motor Function Classification System (GMFCS) at 10 years of age. Least Absolute Shrinkage and Selection Operator (LASSO) regression was used to develop the final predictive model. RESULTS: Of the 849 study participants, 64 (7.5%) had a diagnosis of MI at both 2 and 10 years and 63 (7.4%) had a diagnosis of MI at 1 visit but not the other. Of 22 total risk factors queried, 4 variables most reliably and accurately predicted MI: gestational age, weight z-score growth trajectory during neonatal intensive care unit (NICU) stay, ventriculomegaly, and cerebral echolucency on head ultrasound. By selecting probability thresholds of 3.5% and 7.0% at ages 2 and 10, respectively, likelihood of developing MI can be predicted with a sensitivity and specificity of 71.2%/72.1% at age 2 and 70.7%/70.7% at age 10. CONCLUSION: In our cohort, the diagnosis of MI at 2 years did not always predict a diagnosis of MI at 10 years. Specific risk factors are predictive of MI and can estimate an individual infant's risk at NICU discharge of MI at age 10 years.

Assessing Neonatal Intensive Care Unit (NICU) Graduates Across Varied Settings: A Study on the Feasibility of the Baby Moves App.

We assessed the feasibility of obtaining parent-collected General Movement Assessment videos using the Baby Moves app. Among 261 participants from 4 Chicago NICUs, 70% submitted videos. Families living in higher areas of childhood opportunity used the app more than those from areas of lower opportunity.

Understanding the multidimensional neurodevelopmental outcomes in children after congenital Zika virus exposure.

Since 2016, international research groups have focused on assessing outcomes of children with in utero Zika virus (ZIKV) exposure. While the more severe outcomes of congenital Zika syndrome (CZS) occur in up to 10% of children with antenatal exposure, early findings among ZIKV-exposed children without CZS ages 0-5 years suggest that they may also have differences in multiple domains of neurodevelopment. Thus, longitudinal follow-up of all children with antenatal ZIKV exposure has been recommended. This review presents a summary of neurodevelopmental phenotypes of infants and children following antenatal ZIKV exposure. We present a multidimensional framework to understand child neurodevelopment from an interdisciplinary and whole-child perspective (International Classification of Functioning, Disability and Health model) and multi-domain ZIKV Outcome Toolboxes. The toolboxes are for clinicians, researchers, child educators, and others to implement longitudinal multi-domain neurodevelopmental assessments between ages 0-12 years. Recent innovations in telehealth and neuroimaging can help evaluate outcomes in ZIKV exposed children. The objective is to describe the multiple facets of neurodevelopmental focused care that can support the health, function, and well-being of children with antenatal ZIKV exposure. The research and clinical follow-up strategies are applicable to ZIKV and other congenital infectious or environmental exposures that can impact child neurodevelopment. IMPACT: International longitudinal cohort studies have revealed a range of differences in neurodevelopment among children with antenatal Zika virus (ZIKV) exposure. A multidimensional and whole-child framework is necessary to understand the neurodevelopment of children with antenatal ZIKV exposure in relation to family life, community participation, and environment. Multi-domain toolboxes that utilize parent questionnaires and child evaluations are presented. These toolboxes can be used internationally alongside telehealth, brain imaging, and other innovations to improve understanding of child outcomes.

Preschool neurodevelopment in Zika virus-exposed children without congenital Zika syndrome.

BACKGROUND: Children with in utero Zika virus (ZIKV) exposure without congenital Zika syndrome (CZS) are at risk for abnormal neurodevelopment. Preschool-age outcomes for children with antenatal ZIKV exposure have not yet been established. METHODS: Children with in utero ZIKV exposure and non-exposed controls had neurodevelopmental evaluations at age 3-5 years in Sabanalarga, Colombia. Cases did not have CZS and were previously evaluated prenatally through age 18 months. Controls were born before ZIKV arrival to Colombia. Neurodevelopmental assessments included Pediatric Evaluation of Disability Inventory (PEDI-CAT), Behavior Rating Inventory of Executive Function (BRIEF-P), Bracken School Readiness Assessment (BSRA), and Movement Assessment Battery for Children (MABC). Family demographics and child medical history were recorded. RESULTS: Fifty-five ZIKV-exposed children were evaluated at mean age 3.6 years and 70 controls were evaluated at 5.2 years. Family demographics were similar between groups. BRIEF-P t-scores were higher for cases than controls in shift and flexibility domains. Cases had lower PEDI-CAT mobility t-scores compared to controls. There was no difference in MABC between groups. In 11% of cases and 1% of controls, parents reported child mood problems. CONCLUSIONS: Children with in utero ZIKV exposure without CZS may demonstrate emerging differences in executive function, mood, and adaptive mobility that require continued evaluation. IMPACT: Preschool neurodevelopmental outcome in children with in utero Zika virus exposure is not yet known, since the Zika virus epidemic occurred in 2015-2017 and these children are only now entering school age. This study finds that Colombian children with in utero Zika virus exposure without congenital Zika syndrome are overall developing well but may have emerging differences in executive function, behavior and mood, and adaptive mobility compared to children without in utero Zika virus exposure. Children with in utero Zika virus exposure require continued multi-domain longitudinal neurodevelopmental evaluation through school age.

Prospective Risk Stratification Identifies Healthcare Utilization Associated with Home Oxygen Therapy for Infants with Bronchopulmonary Dysplasia.

OBJECTIVE: To test whether prospective classification of infants with bronchopulmonary dysplasia identifies lower-risk infants for discharge with home oxygen who have fewer rehospitalizations by 1 year after neonatal intensive care unit discharge. STUDY DESIGN: This is a prospective single-center cohort that included infants from 2016 to 2019 with bronchopulmonary dysplasia, defined as receiving respiratory support at 36 weeks of postmenstrual age. "Lower-risk" infants were receiving ≤2 L/min nasal cannula flow, did not have pulmonary hypertension or airway comorbidities, and had blood gas partial pressure of carbon dioxide <70 mm Hg. We compared 3 groups by discharge status: lower-risk room air, lower-risk home oxygen, and higher-risk home oxygen. The primary outcome was rehospitalization at 1 year postdischarge, and the secondary outcomes were determined by the chart review and parent questionnaire. RESULTS: Among 145 infants, 32 (22%) were lower-risk discharged in room air, 49 (32%) were lower-risk using home oxygen, and 64 (44%) were higher-risk. Lower-risk infants using home oxygen had rehospitalization rates similar to those of lower-risk infants on room air (18% vs 16%, P = .75) and lower rates than higher-risk infants (39%, P = .018). Lower-risk infants using home oxygen had more specialty visits (median 10, IQR 7-14 vs median 6, IQR 3-11, P = .028) than those on room air. Classification tree analysis identified risk status as significantly associated with rehospitalization, along with distance from home to hospital, inborn, parent-reported race, and siblings in the home. CONCLUSIONS: Prospectively identified lower-risk infants discharged with home oxygen had fewer rehospitalizations than higher-risk infants and used more specialty care than lower-risk infants discharged in room air.

Adults with Cerebral Palsy Require Ongoing Neurologic Care: A Systematic Review.

Cerebral palsy (CP) neurologic care and research efforts typically focus on children. However, most people with CP are adults. Adults with CP are at increased risk of new neurologic conditions, such as stroke and myelopathy, that require ongoing neurologic surveillance to distinguish them from baseline motor impairments. Neurologic factors could also contribute to the motor function decline, chronic pain, and chronic fatigue that are commonly experienced by adults with CP. Based on a systematic literature review, we suggest (1) guidelines for neurologic surveillance and neurologist referral and (2) clinical research questions regarding the evolving neurologic risks for adults with CP. ANN NEUROL 2021;89:860-871.

Validity of The Warner Initial Developmental Evaluation of Adaptive and Functional Skills (WIDEA-FS): a daily activity criterion checklist for infants and toddlers.

BACKGROUND: The Warner Initial Developmental Evaluation of Adaptive and Functional Skills (WIDEA-FS) is a 50-item, criterion-specified questionnaire that assesses a child's adaptive skills in everyday context and can be used in high-risk follow-up settings to identify risk for adverse neurodevelopmental outcome. Our aim was to validate the WIDEA-FS by comparing a sample of typically developing children to children with special health needs and to compare results to the Capute Scales, which include domains of including both the Cognitive Adaptive Test (CAT) and the Clinical Linguistic and Auditory Milestone Scale (CLAMS). METHODS: Six hundred and sixty children (typically developing and having special healthcare needs) aged 0-36 months completed the WIDEA-FS, the CAT, and the CLAMS assessments. RESULTS: Children with special health needs scored significantly lower on the WIDEA than those with typical development. WIDEA-FS subscales were significantly associated with the CAT (WIDEA-FS self-care 0.87, social cognition 0.89) and the CLAMS (WIDEA-FS communication 0.96, social cognition 0.92) tests. CONCLUSIONS: The WIDEA-FS has concurrent validity with the CAT and CLAMS and construct validity in that children with special health needs have significantly poorer performance on the WIDEA-FS than children with typical development. IMPACT: The WIDEA-FS demonstrated both construct validity and concurrent validity with the Capute Scales, including the Cognitive Adaptive Test (CAT) and the Clinical Linguistic and Auditory Milestone Scale (CLAMS). This is the first study to validate the use of the WIDEA-FS in children with typical development and children with special healthcare needs. The WIDEA-FS is a quick and valid checklist that can be used to assess neurodevelopmental functioning during daily activities in typically developing children and those at risk for neurodevelopmental differences.

Concurrent validity of the Warner Initial Developmental Evaluation of Adaptive and Functional Skills and the Bayley Scales of Infant and Toddler Development, Third Edition.

AIM: To determine the concurrent validity of the Warner Initial Developmental Evaluation of Adaptive and Functional Skills (WIDEA-FS), a criterion-specified questionnaire that assesses a child's adaptive skills in everyday contexts, and the Bayley Infant and Toddler Scales of Development, Third Edition (Bayley-III). METHOD: In a prospective cohort study, 431 WIDEA-FS and Bayley-III assessments were completed among 341 children, aged 10 to 36 months corrected age (158 females, 183 males; median [interquartile range] gestational age at birth 32wks [29-38]), monitored in a high-risk neonatal intensive care unit follow-up clinic. RESULTS: WIDEA-FS scores were significantly associated with Bayley-III scores in all domains. Lower scores on the WIDEA-FS were significantly associated with an increased risk of adverse developmental performance on all Bayley-III scales. The association was strongest for motor and language Bayley-III scores when tested at <30 months of age, and for cognitive Bayley-III scores when tested at ≥30 months of age. INTERPRETATION: The WIDEA-FS has concurrent validity with the Bayley-III and may be a useful tool in high-risk follow-up settings. WHAT THIS PAPER ADDS: WIDEA-FS mobility, communication, and social cognition domains are concurrently valid in infants at high-risk for neurodevelopmental disability. Bayley-III motor, language, and cognitive composite scores are concurrently valid in the same group. The WIDEA-FS mobility and communication domains may be most clinically useful in children <30 months.

Protocol for implementation of an evidence based parentally administered intervention for preterm infants.

BACKGROUND: Multi-sensory behavioral interventions for preterm infants have the potential to accelerate feeding, growth, and optimize developmental trajectories and increase parents' interactive engagement with their infants. However, few neonatal intensive care units (NICUs) provide evidence-based standardized early behavioral interventions as routine care. Lack of implementation is a major gap between research and clinical practice. H-HOPE, is a standardized behavioral intervention with an infant- directed component (Massage+) and a parent-directed component (four participatory guidance sessions that focus on preterm infants' behaviors and appropriate responses). H-HOPE has well documented efficacy. The purpose of this implementation study is to establish H-HOPE as the standard of care in 5 NICUs. METHODS: The study employs a Type 3 Hybrid design to simultaneously examine the implementation process and effectiveness in five NICUs. To stagger implementation across the clinical sites, we use an incomplete stepped wedge design. The five participating NICUs were purposively selected to represent different acuity levels, number of beds, locations and populations served. Our implementation strategy integrates our experience conducting H-HOPE and a well-established implementation model, the Consolidated Framework for Implementation Research (CFIR). The CFIR identifies influences (facilitators and barriers) that affect successful implementation within five domains: intervention characteristics, outer setting (the hospital and external events and stakeholders), inner setting (NICU), implementers' individual characteristics, and the implementation process. NICUs will use the CFIR process, which includes three phases: Planning and Engaging, Executing, and Reflecting and Evaluating. Because sustaining is a critical goal of implementation, we modify the CFIR implementation process by adding a final phase of Sustaining. DISCUSSION: This study builds on the CFIR, adding Sustaining H-HOPE to observe what happens when sites begin to maintain implementation without outside support, and extends its use to the NICU acute care setting. Our mixed methods analysis systematically identifies key facilitators and barriers of implementation success and effectiveness across the five domains of the CFIR. Long term benefits have not yet been studied but may include substantial health and developmental outcomes for infants, more optimal parent-child relationships, reduced stress and costs for families, and substantial indirect societal benefits including reduced health care and special education costs. TRIAL REGISTRATION: ClinicalTrials.gov registration number NCT04555590 , Registered on 8/19/2020.

Successfully Negotiating Life Challenges: Learnings From Adults With Cerebral Palsy.

Despite facing multidimensional inequalities, some adults with cerebral palsy achieve positive social outcomes (e.g., independent living, employment, and romantic relationships). We interviewed 23 adults (aged 23-47 years) about how they successfully negotiated the challenges of adulthood. Common to all life situations was doing what others (people without cerebral palsy) do. Origins of success lay in their formative experiences (e.g., typical parental expectations with commensurate support and acceptance and supported involvement in school life). Their present functioning (e.g., positive self-concept, well-honed social skills, and physical fitness) combined with present contexts (e.g., expectations of involvement in adult activities and accessible and accommodating environments) enabled them to find ways of negotiating challenges. Finding a way included drawing on knowledge and skills, gravitating toward those who are comfortable with difference, maintaining function, and using natural and paid supports. The findings suggest multiple avenues for supporting people with cerebral palsy to achieve positive social outcomes.

Prematurity and cardiovascular risk at early adulthood.

BACKGROUND: Theories of early stress exposure and allostatic load offer a lifespan perspective to adult health after prematurity based on these early stressors affecting endocrine and metabolic systems. In this study, we examine cardiovascular and metabolic risk by comparing two groups of preterm infants who experienced a full spectrum of neonatal illness and a term-born group at age 23. METHODS: Of the 215 infants recruited at birth, 84% participated at age 23. The cohort included 45 full-term (FT), 24 healthy preterm (HPT), and 111 sick preterm (SPT) infants. Socio-economic status was equivalent across groups. Cardiovascular and metabolic outcomes were as follows: blood pressure (BP), fasting glucose and lipid profiles, weight, waist-hip ratio (WHR), and body mass index (BMI). Clinical and subclinical ranges were compared across neonatal groups and gender. RESULTS: At age 23, the HPT and SPT groups had higher systolic BP compared with the FT group. The SPT group had lower weight compared with the FT and HPT groups. No group differences were found on diastolic BP, glucose, total cholesterol, high-density lipids, low-density lipids, triglycerides, BMI, or WHR. Preterm males had more systolic hypertension and low high-density lipids than FT males. Former preterm males and females had high WHR ratios and BMI at 23 years. Subclinical prehypertensive rates were highest for the HPT female group, followed by the SPT females. Only one (4.2%) HPT adult male was clinically diabetic. CONCLUSIONS: As young adults, HPT and SPT infants had early indicators of cardiovascular risk but no indicators of metabolic risk. There is utility in using clinical and subclinical ranges to identify early cardiovascular risk in early adulthood.

Adverse Childhood Experiences Are Associated with Unmet Healthcare Needs among Children with Autism Spectrum Disorder.

OBJECTIVE: To explore associations between level of adverse childhood experiences (ACEs) and unmet healthcare needs among children with autism spectrum disorder (ASD) using a population-based sample. STUDY DESIGN: Cross-sectional data from the 2011-2012 National Survey of Child Health were analyzed to estimate prevalence of unmet healthcare needs among children with ASD, aged 2-17 years (ASD = 1624; estimated population = 1 174 871). Multivariate Poisson and logistic regression models were used to estimate the relationship between reported ACEs and unmet healthcare needs among children with ASD. RESULTS: After we adjusted for all other variables, children with ASD who experienced 1-2 ACEs and 3+ ACEs were associated with 1.78 (P < .05) and 2.53 (P < .01) times the incidence rate of unmet healthcare needs in comparison with children without ACEs. Compared with children who experienced 0 ACEs, the adjusted odds of any unmet healthcare need were 2.34 (P < .01) and 2.66 (P < .01) for children with 1-2 ACEs and 3 + ACEs, respectively. CONCLUSION: Although limited to cross-sectional data, our study provides compelling evidence on the link between ACEs and unmet healthcare needs among children with ASD. It advances understanding of risk factors in the child and community context that contribute to health disparities and negatively impact healthcare access and use in this population.

The Test of Infant Motor Performance at 3 months predicts language, cognitive, and motor outcomes in infants born preterm at 2 years of age.

AIM: To determine the relationship between the Test of Infant Motor Performance (TIMP) at 3 months and cognitive, language, and motor outcomes on the Bayley Scales of Infant and Toddler Development, Third Edition (Bayley-III) at 2 years of age in high-risk infants born preterm. METHOD: One hundred and six infants (47 females, 59 males) born at earlier than 31 weeks gestational age were prospectively tested with the TIMP at 10 to 15 weeks after term age and were assessed again with the Bayley-III at 2 years corrected age. Sensitivity and specificity were calculated for various cut points of the TIMP z-score and Bayley-III composite scores of no more than 85. RESULTS: The TIMP z-scores at 10 to 15 weeks of age were significantly associated with all three subscales on the Bayley-III at 2 years of age (p<0.001). Using a TIMP z-score cutoff of -0.5, specificity was relatively high for cognitive (87%), language (88%), and motor (89%) outcomes, but sensitivity was low (cognitive 41%, language 49%, motor 57%). INTERPRETATION: This study demonstrates that the TIMP is related to cognitive, language, and motor outcomes on the Bayley-III at 2 years of age in high-risk infants born preterm. WHAT THIS PAPER ADDS: The Test of Infant Motor Performance (TIMP) predicts Bayley Scales of Infant and Toddler Development, Third Edition outcomes at 2 years of age. The TIMP is relatively good at discriminating between children who will and will not have typical development.

Health Impact of Participation for Vulnerable Youth With Disabilities.

OBJECTIVE: We investigated the mental health impact of participation for youth with disabilities (YWD) in the child welfare system who had experienced victimization in the previous year. METHOD: Nationally representative data were obtained from the second National Survey of Child and Adolescent Well-Being. Our sample consisted of 247 YWD ages 11-17 yr. Multivariable probit regression analysis and a robust variance estimator were used to test the relationships among disability status, participation, and clinical depression. RESULTS: The probability of reporting clinical depression was 4 times higher for victimized YWD who reported lower breadth of participation than for victimized YWD who reported higher breadth of participation (6% vs. 26%; p = .03). CONCLUSION: Occupational therapy aimed at increasing opportunities for engagement in activities may enhance the mental health of the most vulnerable YWD. Participation in meaningful activities can improve both overall health and transition to independence for vulnerable YWD.

ADHD, learning difficulties and sleep disturbances associated with KCNJ11-related neonatal diabetes.

OBJECTIVES: Mutations in KCNJ11 are the most common cause of permanent neonatal diabetes mellitus (NDM). Approximately 25% of patients have obvious neurological dysfunction, but whether milder related problems might be more common has been unclear. We sought to assess the prevalence of parental concerns about learning, behavior, attention deficit hyperactivity disorder (ADHD), social competency, and sleep in subjects with KCNJ11-related NDM compared to unaffected sibling controls. STUDY DESIGN: Subjects or their guardians in the University of Chicago Monogenic Diabetes Registry completed a survey examining learning, behavior, ADHD and sleep. Thirty subjects with KCNJ11 -related NDM and 25 unaffected sibling controls were assessed. Data were analyzed using GraphPad Prism 6. Nonparametric analysis was performed using Fisher's exact test for group comparisons. RESULTS: Thirteen (43%) individuals with KCNJ11 -related NDM had treatment for or a diagnosis of ADHD compared to two (8%) of the sibling controls (P < 0.05). Compared to their sibling controls, individuals with KCNJ11 mutations had significant differences in behavior difficulties, social awareness, academic achievement and the need for an Individualized Education Plan (IEP). As seen in other neurodevelopmental disorders, individuals with KCNJ11 mutations also had significantly higher rates of sleep difficulties (P < 0.01). CONCLUSION: Patients with KCNJ11 -related NDM are at an increased risk for delays in learning, social-emotional and behavioral development, ADHD and sleep difficulties based on parent report. Early identification, along with integrated medical and developmental support, may promote better neurodevelopmental outcomes for this unique population. Further investigation utilizing detailed neuropsychological testing will better define the neurodevelopmental consequences of KATP mutations.

Disparities in adversity among children with autism spectrum disorder: a population-based study.

AIM: People with autism spectrum disorders (ASDs) experience disparities in health. An important but overlooked risk factor for health disparities in the ASD population is adverse childhood experiences (ACEs). The purpose of this study was to identify the prevalence of ACEs among families of children with and without ASD, using a population-based sample. METHOD: Data from the 2011 to 2012 National Survey of Child Health were analyzed to estimate prevalence of ACEs among families of children with and without ASD, age 3 to 17 years (ASD=1611; estimated population=1 165 34). The child's ASD status was obtained from parent report; ACEs were assessed with the modified Adverse Childhood Experiences Scale. Bivariate and multinomial logistic regression analyses were utilized to investigate the relationship between ACEs and childhood ASD status. RESULTS: ASD status among children was significantly and independently associated with higher probability of reporting one to three ACEs (adjusted relative risk ratio [aRRR] 1.53; 95% CI: 1.16-2.0; p<0.010) and four or more ACEs (aRRR 1.99; 95% CI: 1.35-2.91; p<0.010). INTERPRETATION: Children with ASD may experience a greater number of family and neighborhood adversities, potentially compromising their chances for optimal physical and behavioral health outcomes. Assessment and reduction of ACEs among families of young people with ASD could potentially contribute to the reduction of population health disparities.

Victimization and restricted participation among young people with disabilities in the US child welfare system.

AIM: The aim of this study was to assess the role of disability and victimization in young people's participation in developmentally salient activities by analyzing a nationally representative group of young people from the child welfare system (CWS). METHOD: Data were obtained from interviews with young people and their parents, recorded by the second National Survey of Child and Adolescent Well-Being (NSCAW II). The sample group consisted of 405 females and 270 males, ranging in age from 11 to 17 years (mean age 13y 6mo), and residing with families throughout the USA. The relationships among disability status, victimization, and participation were explored using weighted logistic regression analysis. RESULTS: Controlling for demographical and family-related factors, the probability of young people with disabilities (YWD), involved with the CWS, reporting two or more victimizations was 120% higher (p<0.01) than that of young people without disabilities. YWD in the CWS were almost twice as likely as young people without disabilities to report participation in only one or no developmentally salient activities. Controlling for all other variables, the odds of restricted participation were 6.8-fold higher (p<0.05) for victimized YWD in the CWS. INTERPRETATION: Young people with disabilities who report victimization are significantly less likely than their typically developing peers to participate in developmentally salient activities. Without coordinated efforts to prevent victimization of YWD in the CWS, there will be significant barriers to their participation, well-being, and independent living outcomes.