Early-life stress affects Mongolian gerbil interactions with conspecific vocalizations in a sex-specific manner.

During development, early-life stress (ELS) impairs cognition, learning, and emotional regulation, in part by disrupting neural circuitry in regions underlying these higher-order functions. In addition, our recent work indicates that ELS also alters simple sensory perception: ELS impaired auditory perception and neural encoding of short gaps in sounds, which are essential for vocal communication. The combination of higher-order and basic sensory disruption suggests that ELS is likely to affect both the perception and interpretation of communication signals. We tested this hypothesis by measuring behavioral responses to conspecific vocalizations (those emitted by other gerbils) in ELS and untreated Mongolian gerbils. Because stress effects often differ by sex, we separately examined females and males. To induce ELS, pups were intermittently maternally separated and restrained from post-natal days (P) 9-24, a time window when the auditory cortex is most sensitive to external disruption. We measured the approach responses of juvenile (P31-32) gerbils to two types of conspecific vocalizations: an alarm call, which is emitted to alert other gerbils of a potential threat, and the prosocial contact call, which is emitted near familiar gerbils, especially after separation. Control males, Control females, and ELS females approached a speaker emitting pre-recorded alarm calls, while ELS males avoided this source, suggesting that ELS affects the response to alarm calls in male gerbils. During playback of the pre-recorded contact call, Control females and ELS males avoided the sound source, while Control males neither approached nor avoided, and ELS females approached the sound. These differences cannot be accounted for by changes in locomotion or baseline arousal. However, ELS gerbils slept more during playback, suggesting that ELS may reduce arousal during vocalization playback. Further, male gerbils made more errors than females on a measure of working memory, but the sex difference of cognition in this context may stem from novelty aversion rather than impaired memory. These data indicate that ELS influences behavioral responses to ethologically relevant communication sounds in a sex-specific manner, and are among the first to demonstrate an altered response to auditory stimuli following ELS. Such changes may arise from differences in auditory perception, cognition, or a combination of factors, and suggest that ELS may affect auditory communication in human adolescents.

Predictive validity of a qualitative and quantitative Prechtl's General Movements Assessment at term age: Comparison between preterm infants and term infants with HIE.

AIM: To determine (1) if the General Movement Optimality Score (GMOS) at term age enhances prediction of motor impairment at 12 and 24 months of age in high-risk infants, when compared to a global General Movement Assessment (GMA), and (2) compare predictive validity for two high-risk populations: infants born preterm and infants born at term with hypoxic ischaemic encephalopathy who have received therapeutic hypothermia. METHODS: Fifty-nine extremely preterm or term age infants with hypoxic ischaemic encephalopathy underwent term age GMA. A GMA score of normal or abnormal, and a comparative numerical General Movement Optimality Score (GMOS, total values 5-42) were assigned. Neurology and motor assessment were carried out at age 12 and 24 months using standardised assessments; Alberta Infant Motor Scale, Bayley Scales of Infant and Toddler Development or Ages and Stages Questionnaire. Outcomes were recorded as normal, motor delayed or cerebral palsy. Motor outcome prediction at 12 and 24 months of age was calculated using the GMA and, using ROC analysis, GMOS cut-off scores were determined. RESULTS: At 12 and 24 months global GMA sensitivity for preterms was 80% and 100%, and for Term HIE was 100% at both ages. Specificity values for preterm infants at 12 and 24 months were 68.8% and 60% versus 28.8% and 21.4% for term HIE. Median GMOS scores were lower in the term HIE group than the preterm group in the normal and poor repertoire categories. Optimality cut off scores enhanced specificity, but values remained low. INTERPRETATION: At term age, specificity for identification of infants with later normal motor outcome is low. The GMOS may assist identification of infants with the highest probability of motor impairment, enabling targeted intervention during critical periods for neuroplasticity.

Minor neurological signs and behavioural function at age 2 years in neonatal hypoxic ischaemic encephalopathy (HIE).

BACKGROUND: Neurodevelopmental follow-up in Neonatal Hypoxic Ischaemic Encephalopathy (HIE) typically focusses on major neuromotor (cerebral palsy, CP) and severe cognitive impairment. Outcomes in those without major neuromotor impairment are less well explored. OBJECTIVES: To examine behavioural, cognitive and neurological outcomes after neonatal HIE, in a clinical cohort of children without CP, at age 2 years. METHODS: Clinical routine outcome data from children admitted to a tertiary centre with neonatal HIE for hypothermia treatment between 05/08/09-30/05/2016. Children were assessed for neuromotor status - particularly minor neurological signs (MNS), with Bayley Scales of Infant and Toddler Development III (Bayley III) or Ages and Stages Questionnaire-3 (ASQ), Child Behavior Checklist 1.5-5 (CBCL), Quantitative Checklist for Autism in Toddlers (Q-CHAT). RESULTS: Of 107 children, 75.5% had normal neurology, 12.1% CP, 12.1% MNS. Children with CP were excluded from analyses. For those without CP, Bayley-III scores were in the average range for the majority; mild cognitive delay observed in 5%, 4.2% language, 1.3% motor development; severe delay in 1.3% for cognitive, 4.2% for language. More than in the normative population scored in clinical ranges for CBCL externalising, sleep, and other problems. No significant difference was seen for Q-CHAT. Children with MNS were significantly more likely to have impaired Bayley-III scores, parent-reported internalising, sleep, and other problems. CONCLUSIONS: In this clinical cohort, the majority of children had favourable outcome at 2 years. However, children with MNS were at risk for cognitive and behavioural difficulties and will benefit from enhanced clinical follow-up and support.

Parental perceptions of hypothermia treatment for neonatal hypoxic-ischaemic encephalopathy.

AIMS: Hypothermia Treatment (HT) is now the standard care for neonatal hypoxic-ischaemic encephalopathy (HIE). We conducted a survey to explore parental perceptions of HT as there is little information about this in the current literature. METHODS: Postal questionnaire survey included families (n = 51) whose babies received HT at Princess Anne Hospital, Southampton, UK, with 23 questions covering communication, clinical management, follow-up, and care in general. Statistical analysis of descriptive and analytical tests were done using Minitab 16. RESULTS: The response rate was 60.8%. All parents had concerns amongst which perceptions of pain and distress were described by 41%. Temporary concerns about bonding were common (83.8%), more so in babies transferred from other hospitals (p = .04). Only 61.3% felt they had a good understanding of HT. The need for improvements in the quality (71%) and frequency of communication (48.3%) were also highlighted. CONCLUSIONS: Parents were worried about pain and distress, bonding and about outcomes after HT. Consistency in communication, regular updates, involvement of parents in decision making, strong support mechanisms and balanced discussions about long term outcomes at an early stage are of high importance to families whose babies undergo HT.

Mortality over four decades after traumatic brain injury rehabilitation: a retrospective cohort study.

OBJECTIVE: To investigate mortality, life expectancy, risk factors for death, and causes of death in persons with traumatic brain injury (TBI). DESIGN: Retrospective cohort study. SETTING: Used data from an inpatient rehabilitation facility, the Social Security Death Index, death certificates, and the U.S. population age-race-sex-specific and cause-specific mortality rates. PARTICIPANTS: Persons with TBI (N=1678) surviving to their first anniversary of injury admitted to rehabilitation from an acute care hospital within 1 year of injury between 1961 and 2002. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Vital status, standardized mortality ratio, life expectancy, cause of death. RESULTS: Persons with TBI were 1.5 times more likely to die than persons in the general population of similar age, sex, and race, resulting in an estimated average life expectancy reduction of 4 years. Within the TBI population, the strongest independent risk factors for death after 1 year postinjury were being older, being male, having less education, having a longer hospitalization, having an earlier year of injury, and being in a vegetative state at rehabilitation discharge. After 1 year postinjury, persons with TBI were 49 times more likely to die of aspiration pneumonia, 22 times more likely to die of seizures, 4 times more likely to die of pneumonia, 3 times more likely to commit suicide, and 2.5 times more likely to die of digestive conditions than persons in the general population of similar age, sex, and race. CONCLUSIONS: This study demonstrated life expectancy after TBI rehabilitation is reduced and associated with specific risk factors and causes of death.