Background/Objectives: The Hammersmith Infant Neurological Examination (HINE) is a standardized neurologic exam for infants between 2 and 24 months. Scores can be compared to optimality cutoffs as one component to support an early diagnosis of cerebral palsy (CP). Some prognosis is also possible for infants diagnosed with CP. We aimed to understand the longitudinal trajectories of HINE scores in infants who were ultimately diagnosed with CP. Methods: Clinical records were reviewed for children who were diagnosed with CP in two high-risk infant follow-up clinics with HINE scores from at least two visits between the corrected ages of 3 months and 2 years. Trajectories were calculated individually and by group for infants in four categories—term neonatal hypoxic ischemic encephalopathy (HIE), term perinatal arterial ischemic stroke (PAIS), premature infants with brain injury, and “Other” (term infants with congenital malformations and/or congenital hydrocephalus). The changes in HINE scores between clinic visits were compared using linear mixed-effect models with a random intercept, pulling data by diagnostic group across visits and accounting for within-child correlations of scores over the follow-up time. Results: The changes in HINE scores for sixty children (twenty-five with prematurity, eighteen with HIE, seven with PAIS, and ten in the other category) were assessed. The linear mixed-effect models indicated that the infants with PAIS had an estimated 10.8-point increase in total HINE scores after 9 months of age compared to earlier assessments (95% CI [2.5, 19.2]. There was no statistically significant improvement in the scores among the infants in the other brain injury groups. The infants with PAIS had an estimated 2.9-point increase in HINE asymmetry scores after 9 months of age compared to prior visits (95% CI [0.7, 5.1]). None of the other diagnostic categories had statistically significant increases in asymmetry scores over time. Conclusions: The children with PAIS with resultant hemiplegia showed increasing HINE scores throughout the first two years of life. In contrast, the HINE scores remained stable for those children with term HIE, prematurity-associated brain injury, and congenital malformations and/or congenital hydrocephalus diagnosed with CP. Tracking individual changes (or stability) in HINE scores can aid diagnosis, inform prognosis, and guide the design of clinical trials targeting neurologic injury.

Understanding if neonatal seizures (Sz) worsen brain injury and outcomes would optimize treatment decisions. We hypothesized that serum central nervous system-specific biomarkers would discriminate neonates with Sz and relate to outcomes. This is a retrospective cohort study (April 2009 to November 2019), including neonates in three groups: (1) only Sz without HIE (Sz-no HIE), (2) HIE with Sz (Sz-HIE), and (3) HIE without Sz (no Sz-HIE). Levels of glial fibrillary acidic protein (GFAP, astrocytic reactivity), Tau (neuronal injury), and neurofilament light chain (NF-L, axonal degeneration) were studied at admission/<6 h, <72 h, and 72-144 h of life against time to achieve full oral feeds and NICHD-NRN MRI score. In 145 neonates included (61% male; 33% black), admission GFAP levels were higher in Sz-HIE than in no Sz-HIE. During the first 72 hours of life, GFAP, Tau, and NF-L levels were similar between Sz-no HIE and Sz-HIE but higher than in no Sz-HIE. After 72 hours, NF-L and Tau remained higher in both Sz groups (versus no Sz-HIE). In adjusted regression models, higher Tau and NF-L percentiles related to longer time to reach full oral feeding and higher odds of more than minimal brain injury in MRI in Sz-HIE. Tau and NF-L levels are higher in those neonates developing Sz. Although relationships with worse brain injury may be driven by the HIE severity itself, modeling shows Sz as the most important feature, providing support to the notion that Sz may worsen brain injury in neonates with HIE even after TH.

Introduction: Inhibitory control during visually guided reaching allows for the development of flexible problem-solving in healthy infants born at term. Inhibitory control is often impaired among older children born preterm, but the developmental trajectory of inhibitory control in infants born preterm is not well understood. The objective of this study was to evaluate the developmental trajectory of inhibitory control on the Object Retrieval Task in infants born preterm. Methods: This was a cross-sectional study including a convenience sample of infants born preterm (less than 37 weeks), who were evaluated at corrected ages 5–6, 7–8, 9–10, 11–12, 13–15, and 16–18 months. Children born preterm with additional diagnoses of congenital anomalies, known genetic disorders, focal stroke, neoplasm, or maternal HIV exposure or children in the care of the state were excluded. Children in each of the age-groups were asked to retrieve a toy from a Plexiglas box with an opening on one side. The orientation of the opening was rotated over three trials, and the visually guided reach patterns were scored based on methods used by Diamond. Visually guided reach patterns ranged from perseverative hitting of the box to immediately reaching through the box opening. Analysis consisted of Fischer’s exact tests to compare categorical measures, Jonckheere-Terpstra tests to compare ordinal measures, F test from general linear models to compare continuous measures and ordinal logistic regression to assess the association between brain injury and reach patterns. Results: The majority of infants born preterm in corrected age-groups of 5–6, 7–8, and 9–10 months perseveratively hit the box regardless of the orientation of the opening. This pattern of predominant immature visually guided reaching persisted at 12 months corrected age in this cohort of infants born preterm, with 75% participants demonstrating an immature reach with the box opening at the front and to the left and 88% demonstrating this with the box opening to the right. Conclusions: In this cohort of preterm infants, developmental progression of inhibitory control and progression of visually guided reaching did not follow the same developmental trajectory observed in full term typically developing infants previously documented by Diamond (1994). While 100% of typically developing infants born at term in Diamond’s cohort demonstrated inhibitory control and mature visually guided reach patterns by age 12 months, 75% of participants in our cohort of infants born preterm continued to demonstrate a predominance of immature visually guided reach patterns. This study demonstrates identification of early impairments in inhibitory control using a resource-conscious, low-cost, and brief neurobehavioral assessment tool. This provides a window for early interventions to limit problems in executive dysfunction at school age and beyond.