One-Year Neurodevelopmental Outcomes After Neonatal Opioid Withdrawal Syndrome: A Prospective Cohort Study.

Purpose: The aims of this study were, in a cohort of children with neonatal opioid withdrawal syndrome (NOWS), (a) to report 1-year neurodevelopmental outcomes and specifically characterize speech, language, and hearing outcomes and (b) to report the prevalence of cleft lip and/or cleft palate. Method: This prospective observational cohort study includes newborns with confirmed in utero opioid exposure who received pharmacological treatment for NOWS. During 1-year-old developmental visits, we administered standardized assessments (Bayley Scales of Infant and Toddler Development-Third Edition [Bayley-III] or Developmental Assessment of Young Children-Second Edition [DAYC-2]-due to COVID-19 restrictions). We compared Bayley-III scores to standardized population means using one-sample z tests. We report estimates, 95% confidence intervals, and two-sided p values. Results: We enrolled 202 infants (October 2018 to March 2020). Follow-up at 1-year was 80%. Infants with NOWS had lower Bayley-III scores at 1 year compared to published norms for cognitive, language, and motor domains. One infant with NOWS was diagnosed with isolated cleft palate and Pierre Robin sequence. All infants passed the newborn hearing screen, and 7.5% had a formal hearing evaluation after neonatal intensive care unit discharge, with 40% having abnormal or inconclusive results; middle ear effusion was the leading cause of abnormal hearing (66.7%). Ten percent of children received a speech-language pathology referral prior to 2 years of age. Infants born to mothers with mental health conditions were more likely to have Bayley-III or DAYC-2 scores below 95 in language or motor domains. Conclusions: Infants with pharmacologically treated NOWS have significantly lower cognitive, language, and motor scores on standardized developmental testing compared to population means at 1 year of age. Early speech-language pathology referral is frequently necessary to promote optimal development in this population. Supplemental Material: https://doi.org/10.23641/asha.20044403.

Predictive value of the test of infant motor performance and the Hammersmith infant neurological examination for cerebral palsy in infants.

BACKGROUND: Current recommendations for early detection tools for cerebral palsy (CP) include assessments that vary in feasibility and resource requirements. The predictive value of less resource-intensive tools has not been fully explored. AIMS: To determine the predictive value of the Test of Infant Motor Performance (TIMP) at 3-4 months corrected age (CA) for CP, and whether administration of both the TIMP and the Hammersmith Infant Neurological Exam (HINE) improves early CP detection. STUDY DESIGN: Five-year retrospective observational study of infants who received the TIMP and the HINE at 3-4 months CA in a high-risk follow-up clinic. TIMP and HINE cut-off scores (alone and in combination) were compared for CP discriminatory ability. SUBJECTS: Of patients with HINE scores (n = 1389; 676 [48.7 %] female; median gestational age at birth 31 weeks [interquartile range 29-34 weeks]), 1343 had concurrent TIMP scores available. OUTCOME MEASURES: Clinical diagnosis of CP. RESULTS: HINE total score <57 had optimal CP predictive value (AUC = 0.815; 77 % sensitivity; 91 % specificity) compared to optimal TIMP cut-off (1 SD below the mean, AUC = 0.71; 52 % sensitivity; 94 % specificity) and all tested TIMP and HINE combinations (all p < 0.001). CONCLUSIONS: HINE total score <57 at 3-4 months CA had the best CP predictive value, confirming its value absent first-line detection tools. Concurrent administration of TIMP did not improve predictive value.

Exceeding expectations after perinatal risks for poor development: associations in term- and preterm-born preschoolers.

OBJECTIVE: To define parenting/social characteristics associated with better-than-expected cognitive and motor outcomes in preschoolers at similar perinatal biological risk-level including various gestational ages at birth (GA) and perinatal complications. STUDY DESIGN: Prospective cohort study (n = 87) of children at four years, median GA 29 weeks (IQR 26, 38). Assessments included Differential Ability Scales, Movement Assessment Battery, parenting styles, and social risk scores. Perinatal risk factors were weighted based on regression models for each outcome; individual calculated risk scores became predictors to extract standardized residuals from the mean (>1 SD above mean = better-than-expected). Mixed-effect regressions examined associations between positive adaptation and parenting/social factors. RESULT: Perinatal risk scores explained 21-53% outcome variability. Children across all GA displayed positive adaptation. Children of parents with higher authoritarian scores had higher odds of better-than-expected outcomes (OR 1.17, p = 0.0002). CONCLUSION: Parental structure may promote positive adaptation at preschool age in children with perinatal risk factors for poor development, including extreme prematurity.

Hammersmith Infant Neurological Examination Clinical Use to Recommend Therapist Assessment of Functional Hand Asymmetries.

PURPOSE: To determine whether asymmetry scores derived from the Hammersmith Infant Neurological Examination (HINE) can provide cutoff scores for recommending in-depth assessment of upper extremity functional deficits by therapists using the Hand Assessment for Infants (HAI). METHODS: Observational study in a clinical laboratory with the HINE and the HAI administered concurrently to 101 infants 3 to 12 months corrected age developing typically or atypically. Predictive value of HINE asymmetry scores for atypical HAI was determined. RESULTS: Total HINE asymmetry scores of 4 or greater had 100% sensitivity and 88% or greater specificity for identifying infants with an asymmetric HAI score of 3 or greater point difference between hands. CONCLUSIONS: For infants receiving a total HINE asymmetry score of 4 or greater, referral to therapists for HAI assessment may be beneficial to precisely evaluate function and determine the need for targeted upper extremity interventions.

Standardized Neurodevelopmental Surveillance of High-risk Infants Using Telehealth: Implementation Study during COVID-19.

INTRODUCTION: Neurodevelopmental surveillance is critical for high-risk infants following neonatal intensive care discharge and is traditionally performed in-person. COVID-19 interruption of regular surveillance necessitated a rapid development of telehealth models for effective and standardized care. METHODS: We used implementation science and lean methodologies to develop an effective telehealth neurodevelopmental surveillance program for high-risk infants. Interventions included reorganization of visit flow processes and a telehealth toolkit for standardized neurological and developmental assessments. We tested and improved our intervention through plan-do-study-act cycles, value-added analysis, and parent- and provider-satisfaction questionnaires. Process metrics (standard elements, subspecialty referrals, diagnostic tests, and prescriptions ordered) were compared in group-level analyses between telehealth patients (N = 97) March 16, 2020-July 1, 2020 and a matched in-person cohort at the same period the previous year. Run charts examined shifts in balancing measures (provider efficiency and missed visits) over 8 weeks before and after implementation. RESULTS: Primary outcomes were visit completion (100%), patient parent satisfaction (>90% strongly agreed or agreed telehealth procedures were valuable and easy to use) and ability to accurately diagnose cerebral palsy (no statistical difference with comparison visits). Providers (N = 6) rated telehealth experiences favorably. Process metrics indicated no differences between telehealth and in-person visits (all P > 0.05). Following telehealth implementation, provider efficiency increased to near baseline (median 88.9% versus 91.7%) and median missed visits decreased to 0% from 20% (in-person). CONCLUSIONS: Implementation of telehealth for neurodevelopmental surveillance in a tertiary high-risk infant follow-up clinic successfully provided standardized and timely care during stay-at-home orders; broader telehealth applications may overcome access barriers in this field.

Assessments and Interventions for Spasticity in Infants With or at High Risk for Cerebral Palsy: A Systematic Review.

BACKGROUND: The majority of children with cerebral palsy develop spasticity, which interferes with motor development, function, and participation. This systematic review appraised current evidence regarding assessments and interventions for spasticity in children aged less than two years with or at high risk for cerebral palsy and integrated findings with parent preferences. METHODS: Five databases (CINAHL, EMBASE, OVID/Medline, SCOPUS, and PsycINFO) were searched. Included articles were screened using PRISMA guidelines. Quality of the evidence was reviewed by two independent reviewers using Quality Assessment of Diagnostic Accuracy Studies, second edition (QUADAS-2), the RTI Item Bank on Risk of Bias and Precision of Observational Studies (RTI), or The Cochrane Collaboration's tool for assessing risk of bias in randomized trials (RoB). An online survey was conducted regarding parent preferences through social media channels. RESULTS: Twelve articles met inclusion criteria. No high-quality assessment tool emerged for this population. Six interventions (botulinum toxin-A, orthotic use, radial extracorporeal shock wave therapy, erythropoietic stimulating agents, medical cannabis, and homeopathy) were identified. There was low-quality evidence for the use of botulinum toxin-A and radial extracorporeal shock wave therapy to improve short-term outcomes. Survey respondents indicated that spasticity assessments and interventions are highly valued, with nonpharmacologic interventions ranked most preferably. CONCLUSIONS: Further research is needed to validate assessments for spasticity in children younger than two years. Conditional recommendations can be made for botulinum toxin-A and radial extracorporeal shock wave therapy based on low level of evidence to reduce spasticity in children aged less than two years.

Protocol and Feasibility-Randomized Trial of Telehealth Delivery for a Multicomponent Upper Extremity Intervention in Infants With Asymmetric Cerebral Palsy.

BACKGROUND: Past work showed that an in-person, therapist-guided, parent-implemented multicomponent intervention increased the motor functioning of the more affected upper extremity (UE) in infants with asymmetric cerebral palsy. The authors document treatment fidelity and provide initial testing of telehealth intervention delivery in a new subject sample. METHODS: The authors adapted the intervention manual used in the previous trial for telehealth. Infants (6-24 months) were randomly assigned to intervention (n = 7) or waitlist (n = 6). The intervention prescribed soft-constraint wear on the less affected UE for 6 hours, 5 d/wk, and exercises. After an initial in-person training session, three 15- to 45-minute telehealth sessions were performed. RESULTS: Median weekly constraint wear was 21 hours (interquartile range = 10.3-29.7); average parent-treatment fidelity was 95.7% (SD 11.2). A significant large (Cohen d = 0.92) between-group differences occurred on fine motor functioning of more affected UEs. CONCLUSION: The telehealth intervention was feasible and potentially effective, but a larger trial is needed to evaluate efficacy.

The role of the NOP receptor in regulating food intake, meal pattern, and the excitability of proopiomelanocortin neurons.

We evaluated the role of the nociceptin/orphanin FQ (NOP) receptor in regulating food intake, meal pattern and the activity of hypothalamic arcuate (ARC) neurons. The microstructural analysis of food intake and meal pattern was performed under both food-deprived and ad libitum conditions. Whole-cell patch clamp recordings were obtained using the in vitro hypothalamic slice preparation and biocytin-filled electrodes. NOP receptor knockout mice exhibited significantly reduced body weight. Fasting-induced hyperphagia was diminished for the first 2h of a 6-h re-feeding period, and was associated with decreased meal duration and size, as well as a biphasic effect on meal frequency. The genotype effect observed under ad libitum conditions was comparatively unremarkable. Orphanin FQ/nociceptin (OFQ/N) was able to decrease evoked excitatory postsynaptic current amplitude, increase the S(2):S(1) ratio via the paired-pulse paradigm, and decrease miniature excitatory postsynaptic current frequency in ARC neurons from wild type animals but not NOP receptor knockouts. In addition OFQ/N activated a reversible outward current that was antagonized by the G-protein activated, inwardly-rectifying K(+) (GIRK) channel blocker tertiapin in wild type but not NOP knockout animals. Both the presynaptic and postsynaptic actions of OFQ/N were observed in ARC neurons subsequently determined to be immunopositive for characteristic phenotypic markers of anorexigenic proopiomelanocortin (POMC) neurons. Taken together, these results demonstrate the contribution of the NOP receptor in controlling food intake and meal pattern, as well as glutamate release and GIRK1 channel activity at POMC synapses.