Domenico M. Romeo

Neurodevelopmental outcome at 12 and 18 months in late preterm infants

BACKGROUND Late-preterms represent the 70% of the whole preterm population and are reported to be at higher risk for mortality and morbidity than term infants. AIMS To assess neurodevelopmental outcome in low-risk late-preterm infants at 12 and 18 months corrected age, to compare results of corrected and uncorrected age to those of term-born infants, to analyse the possible influence of gender on outcome. METHODS Sixty-one healthy infants born between 33 and 36 weeks gestational age without major brain lesions were assessed at 12 and 18 months corrected age using the Bayley II scale. A control group of 60 low-risk term born infants underwent the same assessment. RESULTS At 12 and 18 months corrected age late preterms showed a mean mental developmental index (MDI) similar to term infants. Comparing the results of the uncorrected age with term infants, the scores were significantly lower at both 12 and 18 months. No gender differences were observed in term-born infants, while male late-preterm infants showed lower MDI than peer females at both ages. CONCLUSIONS When correcting age for prematurity late-preterms have similar MDI scores to those obtained in term-born infants at 12 and 18 months. In contrast, when using chronological age there is a number of infants with low MDI. As cognitive abnormalities are reported at school age in late preterm infants, our findings raise the question on whether the results obtained using scores uncorrected for age may early identify the infants who will show cognitive difficulties at school age.

Attention Deficit Hyperactivity Disorder and Cognitive Function in Duchenne Muscular Dystrophy: Phenotype-Genotype Correlation

OBJECTIVES To assess attention deficit hyperactivity disorder (ADHD) in boys affected by Duchenne muscular dystrophy (DMD) and to explore the relationship with cognitive abilities and genetic findings. STUDY DESIGN Boys with DMD (n = 103; 4-17 years of age, mean: 12.6) were assessed using a cognitive test (Wechsler scales). Assessment of ADHD was based on the Diagnostic Statistical Manual, Fourth Edition, Text Revision criteria and on the long version of the Conners Parents and Teachers Rating Scales. RESULTS ADHD was found in 33 of the 103 boys with DMD. Attention problems together with hyperactivity (17/33) or in isolation (15/33) were more frequent than hyperactivity alone, which was found in 1 patient. Intellectual disability (ID) was found in 27/103 (24.6%). Sixty-two of the 103 boys had no ID and no ADHD, 9 had ID but no ADHD, 14 had ADHD but no ID, and 18 had both. ADHD occurred more frequently in association with mutations predicted to affect Dp140 expression (exon 45-55) and in those with mutations predicted to affect all dystrophin product, including Dp71 (ie, those that have promoter region and specific first exon between exons 62 and 63 but were also relatively frequent). CONCLUSIONS Our results suggest that ADHD is a frequent feature in DMD. The risk of ADHD appears to be higher in patients carrying mutations predicted to affect dystrophin isoforms expressed in the brain and are known to be associated with higher risk of cognitive impairment.

Early, Accurate Diagnosis and Early Intervention in Cerebral Palsy: Advances in Diagnosis and Treatment

Importance Cerebral palsy describes the most common physical disability in childhood and occurs in 1 in 500 live births. Historically, the diagnosis has been made between age 12 and 24 months but now can be made before 6 months’ corrected age. Objectives To systematically review best available evidence for early, accurate diagnosis of cerebral palsy and to summarize best available evidence about cerebral palsy–specific early intervention that should follow early diagnosis to optimize neuroplasticity and function. Evidence Review This study systematically searched the literature about early diagnosis of cerebral palsy in MEDLINE (1956-2016), EMBASE (1980-2016), CINAHL (1983-2016), and the Cochrane Library (1988-2016) and by hand searching. Search terms included cerebral palsy, diagnosis, detection, prediction, identification, predictive validity, accuracy, sensitivity, and specificity. The study included systematic reviews with or without meta-analyses, criteria of diagnostic accuracy, and evidence-based clinical guidelines. Findings are reported according to the PRISMA statement, and recommendations are reported according to the Appraisal of Guidelines, Research and Evaluation (AGREE) II instrument. Findings Six systematic reviews and 2 evidence-based clinical guidelines met inclusion criteria. All included articles had high methodological Quality Assessment of Diagnostic Accuracy Studies (QUADAS) ratings. In infants, clinical signs and symptoms of cerebral palsy emerge and evolve before age 2 years; therefore, a combination of standardized tools should be used to predict risk in conjunction with clinical history. Before 5 months’ corrected age, the most predictive tools for detecting risk are term-age magnetic resonance imaging (86%-89% sensitivity), the Prechtl Qualitative Assessment of General Movements (98% sensitivity), and the Hammersmith Infant Neurological Examination (90% sensitivity). After 5 months’ corrected age, the most predictive tools for detecting risk are magnetic resonance imaging (86%-89% sensitivity) (where safe and feasible), the Hammersmith Infant Neurological Examination (90% sensitivity), and the Developmental Assessment of Young Children (83% C index). Topography and severity of cerebral palsy are more difficult to ascertain in infancy, and magnetic resonance imaging and the Hammersmith Infant Neurological Examination may be helpful in assisting clinical decisions. In high-income countries, 2 in 3 individuals with cerebral palsy will walk, 3 in 4 will talk, and 1 in 2 will have normal intelligence. Conclusions and Relevance Early diagnosis begins with a medical history and involves using neuroimaging, standardized neurological, and standardized motor assessments that indicate congruent abnormal findings indicative of cerebral palsy. Clinicians should understand the importance of prompt referral to diagnostic-specific early intervention to optimize infant motor and cognitive plasticity, prevent secondary complications, and enhance caregiver well-being.

Neurological examination of preterm infants at term equivalent age

BACKGROUND We previously reported the neurological findings of the Dubowitz neonatal examination in a cohort of 157 low-risk preterms born between 25 and 33 weeks gestational age (GA) and examined at term equivalent age (TEA). Median and range of scores were wider than those found in term-born infants and preterms showed a different neurological behaviour in specific items. However, the cohort number was too small to draw any definitive conclusion about the distribution of findings. AIMS We provide normative data from a low-risk cohort of 380 preterm infants; we also assess the findings and their relationship to motor outcome in preterms with major cranial ultrasound (US) abnormality. STUDY DESIGN We assessed, at TEA, 380 low-risk preterms born <35 weeks gestation (range 25-34.9, median 29) with normal 2 year motor outcome and 85 preterm infants with major US abnormality. RESULTS At TEA low-risk preterms had less flexor limb tone, poorer head control but better visual following than term-born infants. For 28/34 of the neurological items the range and median scores were similar across gestational ages. In infants with major US lesions the range and median scores differed from low-risk preterms in 20/34 items; 40% of infants developing a diplegia and 80% developing a tetraplegia had >7 items outside the 90th centile; all infants with >12 items outside the 90th centile developed a tetraplegia. CONCLUSIONS We provide reference values for the neurological examination of low-risk preterms at TEA. In infants with major US abnormality the number of items outside the 90th centile was an indicator of outcome severity.

Hand movements at 3 months predict later hemiplegia in term infants with neonatal cerebral infarction

Aim  The aim of this study was to explore the predictive value of quantitative assessment of hand movements in 3‐month‐old infants after neonatal stroke.

Early neurodevelopmental assessment in Duchenne muscular dystrophy

The aim of this study was to assess neurodevelopmental profile in young boys affected by Duchenne muscular dystrophy and to establish the correlation between neurodevelopmental findings, and the type and site of mutations. A structured neurodevelopmental assessment (Griffiths Scale of Mental Development) was performed in 81 DMD boys before the age of four years (range: 7-47 months). The mean total DQ was 87 (SD 15.3). Borderline DQ (between 70 and 84) was found in 32% and DQ below 70 in 12.3% of the patients. Children with mutations upstream or in exon 44 had higher DQ than those with mutations downstream exon 44 which are associated with involvement of dystrophin isoforms expressed at high levels in brain. The difference was significant for total and individual subscale DQ with the exception of the locomotor subscale. Items, such as ability to run fast, or getting up from the floor consistently failed in all children, irrespective of the age or of the site of mutation. Our results help to understand the possible different mechanisms underlying the various aspects of neurodevelopmental delay, suggesting that the involvement of brain dystrophin isoforms may cause a delay in the maturation of coordination and dexterity.

Sleep disorders in children with cerebral palsy: neurodevelopmental and behavioral correlates

OBJECTIVES We aimed to estimate the frequency of sleep disorders in children with cerebral palsy (CP) using the Sleep Disturbance Scale for Children (SDSC) and to evaluate the relations between sleep disorders and motor, cognitive, and behavioral problems. METHODS One hundred and sixty-five children with CP ages 6-16 years (mean age, 11years) were assessed using the SDSC, the Gross Motor Function Classification System (GMFCS), the Wechsler Intelligence Scale for Children and the Child Behavior Check List (CBCL) to assess sleep, motor, cognitive, and behavioral problems, respectively. RESULTS An abnormal total sleep score was found in 19% of children with CP; more than 40% of children had an abnormal score on at least one SDSC factor. The SDSC total score was significantly associated (P<.01) with mental retardation, epilepsy, CBCL scores, and level 5 on the GMFCS. CONCLUSIONS Our results confirm that sleep disorders are common in children with cerebral palsy. The relationship between motor and cognitive behavior and epilepsy should be further explored to better understand how these factors influence one another to identify effective treatments and to improve the well-being of the child.

Application of the Sleep Disturbance Scale for Children (SDSC) in preschool age

BACKGROUND The Sleep Disturbance Scale for Children (SDSC) was originally validated on a sample of healthy children aged 6-16 years, investigating the occurrence of sleep disorders during the previous 6 months. AIMS The aim of this new study was to assess the psychometric properties of the SDSC in an Italian population of preschool children. METHODS The SDSC was distributed to the primary caregivers of children recruited via nurseries. Letters describing the study design and requesting the co-operation of the caregivers (parents) and co-signed by the investigators and by the head teacher were distributed with the questionnaire and collected by the teachers. Reliability analysis for evaluating internal consistency and item-total correlation coefficients, and factor analysis were performed. RESULTS During a 12-months study period, 601 questionnaires from healthy preschool age children (range 3-6 years) were collected. SDSC in preschool children showed a good level of internal consistency (Cronbachs alpha: 0.83) and six factors were derived from the factor analysis by using the principal component method of extraction and rotated with the varimax method: Parasomnias, Difficulty in initiating and maintaining sleep, Sleep disordered breathing, Disorders of excessive somnolence, Sleep hyperhydrosis and Non-restorative Sleep. CONCLUSIONS The statistical analysis, the internal consistency and the factor analysis support the use of SDSC as an evaluation tool even at preschool age. A different factorial structure from the original SDSC was found due to a different prevalence of the sleep disturbances in younger children, but with similar cut-off total SDSC score.

Use of the Hammersmith Infant Neurological Examination in infants with cerebral palsy: a critical review of the literature

The Hammersmith Infant Neurological Examination (HINE) has been proposed as one of the early neurological examination tools for the diagnosis of cerebral palsy (CP). The aim of the present study was to critically review the existing literature and our experience with the use of the HINE in infants at risk of CP. The published papers confirm that the HINE can play an important role in the diagnosis and prognosis of infants at risk of developing CP, and provide information on aspects of neurological findings impaired in different forms of CP and brain lesions.

Longitudinal cognitive assessment in healthy late preterm infants.

BACKGROUND Longitudinal cognitive development in late preterm (LP) infants has not been previously evaluated, using structured assessments. AIM To assess longitudinally cognitive development in a population of healthy LP infants from 12 months to preschool age. METHODS Sixty-two low-risk LP infants (33-36 weeks gestation) with normal or only minor findings on their cranial ultrasound scans were included in the study. They were assessed at 12 and 18 months corrected age using the Bayley Scales of Infant Development II to obtain the mental development index (MDI) and then at preschool age (mean age 62 ± 7 months) using the Wechsler Preschool and Primary Scale of Intelligence (WPPSI-R). RESULTS The MDI scores obtained at both 12 and 18 months corrected age were within the reported normative range. Using uncorrected ages, their scores were lower at both ages than those obtained using CA (p < 0.01). Full-scale IQ scores within the reported normal range were obtained at 5 years using the WPPSI-R for all but 6 children. Females had significantly higher scores than males (p < 0.001) for the MDI at both 12 and 18 months corrected and uncorrected age. No gender differences were found at preschool age using the WPPSI-R. CONCLUSIONS Our results suggest that over 90% of the low-risk late preterms reach an MDI and IQ at preschool age within normal range.