Ronny Geva

Neurodevelopmental outcome of children with intrauterine growth retardation: a longitudinal, 10-year prospective study.

One hundred twenty-three children with intrauterine growth retardation were prospectively followed from birth to 9 to 10 years of age in order to characterize their specific neurodevelopmental and cognitive difficulties and to identify clinical predictors of such difficulties. Perinatal biometric data and risk factors were collected. Outcome was evaluated at age 9 to 10 by neurodevelopmental, cognitive, and school achievement assessments. Sixty-three children served as controls who were appropriate for gestational age. Significant differences in growth (P < .001), neurodevelopmental scores (P < .001), intelligence quotient (IQ) (P < .0001), and school achievements measured by the Kaufmann Assessment Battery for Children (P < .001) were found between the children with intrauterine growth retardation and controls. Children with intrauterine growth retardation demonstrated a specific profile of neurocognitive difficulties at school age, accounting for lower school achievements. The best perinatal parameter predictive of neurodevelopment and IQ was the Cephalization Index (P < .001). Somatic catch-up growth at age 2 and at age 9 to 10 correlated with favorable outcome at 9 to 10 years of age.

Neuropsychological outcome of children with intrauterine growth restriction: a 9-year prospective study.

OBJECTIVE. The aim was to evaluate the effect of late-onset intrauterine growth restriction on the neuropsychological profile and on academic achievements at 9 years of age using a large-scale prospective paradigm. STUDY DESIGN. We followed up 123 infants diagnosed with late-onset intrauterine growth restriction yearly for 9 years. They were matched with 63 children for gestation age and multiple socioeconomic factors and evaluated by an extensive neuropsychological battery to assess intelligence quotient, academic achievements, learning and memory, visuomotor skills, visuospatial integration, attention, language, executive functions, and creativity. RESULTS. Children with intrauterine growth restriction had lower intelligence quotient and more frequent neuropsychological difficulties. Difficulties in executive functioning, inflexibility-creativity, and language, indicative of frontal lobe dysfunction, were typically affected by intrauterine growth restriction and were rarely identified in the control group. Learning difficulties accompanied by lower academic achievements were more prevalent in the intrauterine growth restriction group, particularly when anthropometric catch-up was incomplete. CONCLUSIONS. The longitudinal findings reaffirm that functional coherence depends on preestablished structural growth and reorganization of the central nervous system. The neuropsychological profile at 9 years of age indicates that late-onset intrauterine growth restriction compromises frontal network functioning.

Memory functions of children born with asymmetric intrauterine growth restriction

OBJECTIVE Learning difficulties are frequently diagnosed in children born with intrauterine growth restriction (IUGR). Models of various animal species with IUGR were studied and demonstrated specific susceptibility and alterations of the hippocampal formation and its related neural structures. The main purpose was to study memory functions of children born with asymmetric IUGR in a large-scale cohort using a long-term prospective paradigm. METHODS One hundred and ten infants diagnosed with IUGR were followed-up from birth to 9 years of age. Their performance was compared with a group of 63 children with comparable gestational age and multiple socioeconomic factors. Memory functions (short-term, super- and long-term spans) for different stimuli types (verbal and visual) were evaluated using Visual Auditory Digit Span tasks (VADS), Rey Auditory Verbal Learning Test (Rey-AVLT), and Rey Osterrieth Complex Figure Test (ROCF). RESULTS Children with IUGR had short-term memory difficulties that hindered both serial verbal processing system and simultaneous processing of high-load visuo-spatial stimuli. The difficulties were not related to prematurity, neonatal complications or growth catch-up, but were augmented by lower maternal education. Recognition skills and benefits from reiteration, typically affected by hippocampal dysfunction, were preserved in both groups. CONCLUSIONS Memory profile of children born with IUGR is characterized primarily by a short-term memory deficit that does not necessarily comply with a typical hippocampal deficit, but rather may reflect an executive short-term memory deficit characteristic of anterior hippocampal-prefrontal network. Implications for cognitive intervention are discussed.

A Neurobiological Model for the Effects of Early Brainstem Functioning on the Development of Behavior and Emotion Regulation in Infants: Implications for Prenatal and Perinatal Risk.

Neurobiological models propose an evolutionary, vertical-integrative perspective on emotion and behavior regulation, which postulates that regulatory functions are processed along three core brain systems: the brainstem, limbic, and cortical systems. To date, few developmental studies applied these models to research on prenatal and perinatal risk. We propose a conceptual model that incorporates three integrated levels of observations for the study of early risk: (a) brainstem-related physiological regulation of cyclic processes and sensory integration, e.g., vagal regulation, circadian rhythms; (b) emotion and attention regulation capacities that draw on the integration of brainstem and limbic systems; and (c) higher-level outcomes that draw on the intactness of brainstem and limbic networks, including socio-emotional self-regulation, inhibitory control, and cognitive processing. We discuss implications of the model for the development of regulatory capacities during the prenatal and early postnatal stages in infants born with specific perinatal risk. We underscore the importance of assessing sub-cortical and brainstem systems and the longitudinal effects of transitory brainstem dysfunction on physiological homeostasis, motivation, arousal-modulated attention, stress reactivity, and mother-infant co-regulation. The assessment of brainstem dysfunction can be conducted during hospitalization and may help detect infants at risk for the development of self-regulatory deficits at the first weeks of life.

Growth Patterns in Children With Intrauterine Growth Retardation and Their Correlation to Neurocognitive Development

The relationship between somatic growth and neurocognitive outcome was studied in a cohort of 136 children with intrauterine growth retardation. The children were followed up from birth to 9 to 10 years of age by annual measurements of growth parameters, neurodevelopmental evaluations, and IQ. The rate of catch-up for height between 1 and 2 years of age was significantly higher than the catch-up for weight (P < .001). The cognitive outcome at 9 to 10 years correlated with head circumference at all ages. The neurodevelopmental outcome at 9 to 10 years correlated with weight at all ages. Correlation with head circumference was more significant with IQ, while with weight it was stronger with the neurodevelopmental score. Height at 1 year was a significant predictor for IQ and neurodevelopmental outcome at 9 to 10 years. These findings are of distinct importance for prediction of subsequent neurodevelopmental outcome in children with intrauterine growth retardation.

Early Markers in Infants and Toddlers for Development of ADHD

Objective: Characterization of risk factors for ADHD in infancy may enable early intervention to diminish the symptoms that ensue. Method: In a retrospective study, the well-baby-care clinic records from birth to 18 months of age of 58 children diagnosed at school age for ADHD were compared with those of 58 control children, and the differences between the two groups were statistically analyzed. Results: Eight parameters during infancy were found to be significantly associated with later development of ADHD: at 0 to 1 month—advanced maternal age, lower maternal education, family history of ADHD, and social problems; at 3 and 18 months—decrease in head circumference percentile; at 9 and 18 months—delay in motor and language development, and difficult temperament. The predictive regression model accounted for 58% of the variance. Conclusion: This study highlights early risk markers in infants and toddlers that may predict the development of ADHD.

Alerting, orienting or executive attention networks: differential patters of pupil dilations

Attention capacities, alerting responses, orienting to sensory stimulation, and executive monitoring of performance are considered independent yet interrelated systems. These operations play integral roles in regulating the behavior of diverse species along the evolutionary ladder. Each of the primary attention constructs—alerting, orienting, and executive monitoring—involves salient autonomic correlates as evidenced by changes in reactive pupil dilation (PD), heart rate, and skin conductance. Recent technological advances that use remote high-resolution recording may allow the discernment of temporo-spatial attributes of autonomic responses that characterize the alerting, orienting, and executive monitoring networks during free viewing, irrespective of voluntary performance. This may deepen the understanding of the roles of autonomic regulation in these mental operations and may deepen our understanding of behavioral changes in verbal as well as in non-verbal species. The aim of this study was to explore differences between psychosensory PD responses in alerting, orienting, and executive conflict monitoring tasks to generate estimates of concurrent locus coeruleus (LC) noradrenergic input trajectories in healthy human adults using the attention networks test (ANT). The analysis revealed a construct-specific pattern of pupil responses: alerting is characterized by an early component (Pa), its acceleration enables covert orienting, and executive control is evidenced by a prominent late component (Pe). PD characteristics seem to be task-sensitive, allowing exploration of mental operations irrespective of conscious voluntary responses. These data may facilitate development of studies designed to assess mental operations in diverse species using autonomic responses.

The transition to oral feeding in low-risk premature infants: relation to infant neurobehavioral functioning and mother-infant feeding interaction.

BACKGROUND The achievement of oral feeding is a critical task for the premature infant-mother dyad, yet neurobehavioral and relational factors associated with feeding difficulties of low-risk premature infants during hospitalization are not well understood. AIM To examine the relations between infant neurobehavioral functioning, the transition to oral feeding, and the emerging mother-infant feeding relationship in premature infants. STUDY DESIGN AND SUBJECTS Ninety-seven low-risk premature infants (birth weight>1000 g; gestational age>30 weeks) and their mothers were followed at the NICU. Neurobehavioral functioning was assessed with the Rapid Neonatal Neurobehavioral Assessment Procedure. OUTCOME MEASURES The duration of the transition to oral feeding and specific feeding difficulties during the transition were assessed. Infant feeding robustness, suck and milk transfer rates, and maternal adaptability, affect, intrusiveness and distractibility were coded from videotaped mother-infant feeding interactions prior to discharge from the NICU. RESULTS Thirty percent of the infants presented feeding difficulties during the transition to oral feedings. Infants with abnormal neurobehavioral functioning (37% of the cohort) showed more feeding difficulties, slower suck rates, and lower feeding robustness, and their mothers displayed less adaptive and more intrusive behavior. Maternal intrusiveness was related to lower feeding robustness and to lower suck and milk transfer rates. Neurobehavioral functioning and maternal feeding behavior predicted feeding robustness. CONCLUSIONS Less intact neurobehavioral functioning in the neonatal period is related to difficulties during the transition to oral feeding and to less optimal early mother-infant feeding interactions. Low-risk premature infants with poor neurobehavioral functioning should receive special attention and care.

Feeding-based arousal effects on visual recognition memory in early infancy.

Arousal effects on a 1-trial visual recognition paired-comparison task were studied at newborn, 1-month, and 4-month test ages. Infants were tested before and after feeding, with arousal assumed to be lower after feeding. Newborns and 1-month-olds shifted from a familiarity preference before feeding to a novelty preference after feeding. A control group tested only after feeding confirmed that this shift was not due to increased stimulus exposure from the prefeeding test. By 4 months, infants showed novelty preferences independent of feeding. This age by arousal interaction for recognition memory extends previous knowledge by including endogenous arousal with age, stimulus, and length of exposure as contributors to familiarity-novelty preferences. It also extends and provides converging evidence for arousal effects on visual attention in early infancy found previously with preferential looking. A shift from subcortical to cortical dominance is supported.

Verbal short‐term memory span in children: long‐term modality dependent effects of intrauterine growth restriction

BACKGROUND Recent reports showed that children born with intrauterine growth restriction (IUGR) are at greater risk of experiencing verbal short-term memory span (STM) deficits that may impede their learning capacities at school. It is still unknown whether these deficits are modality dependent. METHODS This long-term, prospective design study examined modality-dependent verbal STM functions in children who were diagnosed at birth with IUGR (n = 138) and a control group (n = 64). Their STM skills were evaluated individually at 9 years of age with four conditions of the Visual-Aural Digit Span Test (VADS; Koppitz, 1981): auditory-oral, auditory-written, visuospatial-oral and visuospatial-written. Cognitive competence was evaluated with the short form of the Wechsler Intelligence Scales for Children--revised (WISC-R95; Wechsler, 1998). RESULTS We found IUGR-related specific auditory-oral STM deficits (p < .036) in conjunction with two double dissociations: an auditory-visuospatial (p < .014) and an input-output processing distinction (p < .014). Cognitive competence had a significant effect on all four conditions; however, the effect of IUGR on the auditory-oral condition was not overridden by the effect of intelligence quotient (IQ). CONCLUSIONS Intrauterine growth restriction affects global competence and inter-modality processing, as well as distinct auditory input processing related to verbal STM functions. The findings support a long-term relationship between prenatal aberrant head growth and auditory verbal STM deficits by the end of the first decade of life. Empirical, clinical and educational implications are presented.