Predicting mental and psychomotor delay in very pre-term infants using machine learning.

BACKGROUND: Very preterm infants are at elevated risk for neurodevelopmental delays. Earlier prediction of delays allows timelier intervention and improved outcomes. Machine learning (ML) was used to predict mental and psychomotor delay at 25 months. METHODS: We applied RandomForest classifier to data from 1109 very preterm infants recruited over 20 years. ML selected key predictors from 52 perinatal and 16 longitudinal variables (1-22 mo assessments). SHapley Additive exPlanations provided model interpretability. RESULTS: Balanced accuracy with perinatal variables was 62%/61% (mental/psychomotor). Top predictors of mental and psychomotor delay overlapped and included: birth year, days in hospital, antenatal MgSO4, days intubated, birth weight, abnormal cranial ultrasound, gestational age, mom's age and education, and intrauterine growth restriction. Highest balanced accuracy was achieved with 19-month follow-up scores and perinatal variables (72%/73%). CONCLUSIONS: Combining perinatal and longitudinal data, ML modeling predicted 24 month mental/psychomotor delay in very preterm infants ½ year early, allowing intervention to start that much sooner. Modeling using only perinatal features fell short of clinical application. Birth year's importance reflected a linear decline in predicting delay as birth year became more recent. IMPACT: Combining perinatal and longitudinal data, ML modeling was able to predict 24 month mental/psychomotor delay in very preterm infants ½ year early (25% of their lives) potentially advancing implementation of intervention services. Although cognitive/verbal and fine/gross motor delays require separate interventions, in very preterm infants there is substantial overlap in the risk factors that can be used to predict these delays. Birth year has an important effect on ML prediction of delay in very preterm infants, with those born more recently (1989-2009) being increasing less likely to be delayed, perhaps reflecting advances in medical practice.

Sensing echoes: temporal misalignment in auditory brainstem responses as the earliest marker of neurodevelopmental derailment.

Neurodevelopmental disorders are on the rise worldwide, with diagnoses that detect derailment from typical milestones by 3 to 4.5 years of age. By then, the circuitry in the brain has already reached some level of maturation that inevitably takes neurodevelopment through a different course. There is a critical need then to develop analytical methods that detect problems much earlier and identify targets for treatment. We integrate data from multiple sources, including neonatal auditory brainstem responses (ABR), clinical criteria detecting autism years later in those neonates, and similar ABR information for young infants and children who also received a diagnosis of autism spectrum disorders, to produce the earliest known digital screening biomarker to flag neurodevelopmental derailment in neonates. This work also defines concrete targets for treatment and offers a new statistical approach to aid in guiding a personalized course of maturation in line with the highly nonlinear, accelerated neurodevelopmental rates of change in early infancy.

Infants on the move: bibliometric analyses of observational vs. digital means of screening infant development.

Neurodevelopmental disorders are on the rise, yet their average diagnosis is after 4.5 years old. This delay is partly due to reliance on social-communication criteria, which require longer maturation than scaffolding elements of neuromotor control. Much earlier criteria could include reflexes, monitoring of the quality of spontaneous movements from central pattern generators and maturation of intentional movements and their overall sensation. General Movement Assessment (GMA) studies these features using observational means, but the last two decades have seen a surge in digital tools that enable non-invasive, continuous tracking of infants' spontaneous movements. Despite their importance, these tools are not yet broadly used. In this work, using CiteSpace, VOSViewer and SciMAT software, we investigate the evolution of the literature on GMA and the methods in use today, to estimate how digital techniques are being adopted. To that end, we created maps of key word co-occurrence networks, co-author networks, document co-citation analysis and strategic diagrams of 295 publications based on a search in the Web of Science, Dimensions and SCOPUS databases for: 'general movement assessment' OR 'general movements assessment'. The nodes on the maps were categorized by size, cluster groups and year of publication. We found that the state-of-the-art methodology to diagnose neurodevelopmental disorders still relies heavily on observation. Several groups in classical GMA research have branched out to incorporate new techniques, but few groups have adopted digital means. We report on additional analyses of methods and biosensors usage and propose that combining traditional clinical observation criteria with digital means may allow earlier diagnoses and interventional therapies for infants.

Neonatal brainstem function and 4-month arousal-modulated attention are jointly associated with autism.

The authors evaluated the contribution of initially abnormal neonatal auditory brainstem responses (ABRs) and 4-month arousal-modulated attention visual preference to later autism spectrum disorder (ASD) behaviors in neonatal intensive care unit (NICU) graduates. A longitudinal study design was used to compare NICU graduates with normal ABRs (n = 28) to those with initially abnormal ABRs (n = 46) that later resolved. At 4 months postterm age, visual preference (measured after feeding) for a random check pattern flashing at 1, 3, or 8 Hz and gestational age (GA) served as additional predictors. Outcome measures were PDD Behavior Inventory (PDDBI) scores at 3.4 years (standard deviation = 1.2), and developmental quotients (DQ) obtained around the same age with the Griffiths Mental Development Scales (GMDS). Preferences for higher rates of stimulation at 4 months were highly correlated with PDDBI scores (all P-values < 0.01) and the GMDS Hearing and Speech DQ, but only in those with initially abnormal ABRs. Effects were strongest for a PDDBI social competence measure most associated with a diagnosis of autism. For those with abnormal ABRs, increases in preference for higher rates of stimulation as infants were linked to nonlinear increases in severity of ASD at 3 years and to an ASD diagnosis. Abnormal ABRs were associated with later reports of repetitive and ritualistic behaviors irrespective of 4-month preference for stimulation. The joint occurrence of initially abnormal neonatal ABRs and preference for more stimulation at 4 months, both indices of early brainstem dysfunction, may be a marker for the development of autism in this cohort.

Neonatal Intensive-Care Unit Graduates Show Persistent Difficulties in an Intra-Dimensional Shift Card Sort.

Neonatal intensive-care unit (NICU) graduates, a group at risk for attention problems and ADHD, performed an intra-dimensional shift card sort at 34, 42, 51, and 60 months to assess executive function and to examine effects of individual risk factors. In the 'silly' game, children sorted cards (airplanes and dogs) so they were not the same as targets. In the 'same' game they did the opposite. Performance on the 'silly' game was poor, especially when it was presented first. Success in following 'silly' game rules improved with age, and was significantly linked to maternal education and birth weight for gestational age, a measure of intrauterine stress. Degree of CNS injury differentiated children who completed the task from children who did not, and also affected the need to repeat instructions in the 'same' game. These results confirm an increased likelihood of impairments in executive function during preschool years in NICU graduates.

The development of selective attention and inhibition in NICU graduates during the preschool years.

Neonatal intensive care unit (NICU) graduates have a higher incidence of attention problems including attention deficit hyperactivity disorder (ADHD). Thus, we examined the effect of risk factors (birth weight (BW), central nervous system (CNS) injury, gender, maternal education) on attention/inhibition during reaction time, continuous performance and Go/No-Go tasks at 42, 51, and 60 months (n = 271). Very low BW NICU graduates (<1,500 g) performed worse than typical BW ones (>2,500 g), displaying poorer target/non-target discrimination. Males responded faster than females, but made more false alarms and random responses. Despite short duration tasks, attention waned. Performance improved with age, but even at 60 months children had difficulty inhibiting random responding.

Auditory brainstem evoked responses in newborns with Down syndrome.

Auditory brainstem evoked responses (ABRs) were compared in 15 newborns with Down syndrome and 15 sex-, age-, and weight-matched control newborns. Participants had normal ABRs based upon values specific to 32- to 42-weeks postconceptional age. Although Wave III and Wave V component latencies and the Wave I-III interpeak latency (IPL) were shorter in ABRs of infants with Down syndrome, the Wave III-V IPL was not, pointing to anomalies in the lower rather than upper brainstem auditory pathways. Shorter Down syndrome ABR latencies have been reported at many ages. Extending these findings to newborns suggests that the underlying basis for this develops prenatally. ABR patterns in infants with Down syndrome were similar to reports for intrauterine growth restricted newborns.

Selective attention deficits associated with mild cognitive impairment and early stage Alzheimer's disease in adults with Down syndrome.

Adults with Down syndrome and early stage Alzheimer's disease showed decline in their ability to selectively attend to stimuli in a multitrial cancellation task. They also showed variability in their performance over the test trials, whereas healthy participants showed stability. These changes in performance were observed approximately 2 years prior to a physician's diagnosis of possible Alzheimer's disease, which was made when they were exhibiting declines in episodic memory suggestive of mild cognitive impairment. Performance on this task varied with the evolution of dementia, showed modestly good sensitivity and specificity, and was relatively easy to administer. Given these qualities this task could be a valuable addition to a neuropsychological battery intended for the assessment of mild cognitive impairment and Alzheimer's disease in adults with Down syndrome.

Successful aging in a 70-year-old man with down syndrome: a case study.

The authors present a case study of a 70-year-old man with Down syndrome ("Mr. C.") who they followed for 16 years and who does not exhibit declines in cognitive or functional capacities indicative of dementia, despite having well-documented, complete trisomy 21. The authors describe the age-associated changes that occurred over 16 years as well as provide detailed information regarding Mr. C.'s health and genetic status. To further emphasize Mr. C.'s successful aging, the authors compared his longitudinal performance profile with that of 2 peers of comparable level of intellectual functioning: 1 similar-aged man with clinical Alzheimer's disease and a younger man who was healthy. The authors present potential explanations for the phenotypic variability observed in individuals with Down syndrome.

Dual-task processing as a measure of executive function: a comparison between adults with Williams and Down syndromes.

Behavioral phenotypes of individuals with Williams syndrome and individuals with Down syndrome have been contrasted in relation to short-term memory. People with Down syndrome are stronger visuospatially and those with Williams syndrome are stronger verbally. We examined short-term memory, then explored whether dual-task processing further characterized behavioral phenotypes in 53 older adults with Down syndrome, 10 with Williams syndrome, and 39 controls. Short-term memory profiles generally conformed to those of younger individuals. Pegs placement and number repetition were performed singly and simultaneously. There were no etiology group performance differences on single tasks. During concurrent processing, all groups maintained single-task performance on pegs, but declined on number repetition. However, participants with Down syndrome declined more, suggesting relatively greater weakness in the dual-task processing component of executive function for this group.

Repetition priming in adults with Williams syndrome: age-related dissociation between implicit and explicit memory.

We examined implicit and explicit memory in adults with Williams syndrome. An age-related dissociation was found; repetition priming (reflecting implicit memory) did not show change with age, but free recall (reflecting explicit memory) was markedly reduced. We also compared the performance of adults with Williams syndrome to adults with Down syndrome and those with unspecified mental retardation. A similar dissociation was observed in adults with Down syndrome but not in adults with unspecified mental retardation. An IQ-related dissociation was also found. Implicit and explicit memory, therefore, show different degrees of association with age and IQ, supporting theories of these memory processes. Results also suggest that Williams syndrome, similar to Down syndrome, may be associated with precocious aging, resulting in the loss of some cognitive abilities.

Age-associated memory changes in adults with williams syndrome.

Age-associated changes on measures of episodic and working memory were examined in 15 adults with Williams Syndrome (WS; M age = 48.3 years, SD = 14.7; M IQ = 62.9, SD = 8.5) and their performance was compared to that of 33 adults with mental retardation (MR) with unspecified etiologies (M age = 54.2 years, SD = 8.9; M IQ = 61.7, SD = 6.5). Among the group with WS, older adults were significantly poorer than younger adults on the free recall task, a measure of episodic memory. Although this finding is consistent with normal aging, it occurred at a chronologically early age in adults with WS and was not found in their peers with unspecified MR. Although both groups showed small declines with age on a backward digit span task, a measure of working memory, for the group with WS the rate of decline on backward digit span was slower as compared to their performance on the free recall task. The findings from this study indicate a chronologically early and precipitous age-associated decrease in long-term, episodic memory in adults with WS.

Semantic and phonological loop effects on verbal working memory in middle-age adults with mental retardation.

Semantic and phonological loop effects on verbal working memory were examined among middle-age adults with Down syndrome and those with unspecified mental retardation in the context of Baddeley's working memory model. Recall was poorer for phonologically similar, semantically similar, and long words compared to recall of dissimilar short words. Compared to their peers, participants with Down syndrome had poorer recall in all categories except phonologically similar words. Most interestingly, semantic similarity lowered recall scores only in participants with Down syndrome. This selective effect of semantics reflects an influence of long-term memory on working memory and points to the need for additional explanations outside phonological loop processes to completely account for the relative impairment of verbal working memory among individuals with Down syndrome.

Implicit memory in aging adults with mental retardation with and without Down syndrome.

Effects of age and IQ on implicit memory in adults with mild or moderate mental retardation with and without Down syndrome were examined. When the etiologically defined groups were equated on age (and IQ), an age-associated difference in implicit memory performance was not evident. When data were reanalyzed, including only participants with unspecified mental retardation from a broader age range, we found a significant but small age-related difference and a significant but small IQ-related effect on implicit memory. In summary, although implicit memory showed an age-associated difference and IQ-associated variation in adults with mental retardation, these effects were relatively small. Data support existing theories proposing the relative invariance of implicit processes across a range of individual differences in age and intelligence.