Neurodevelopmental outcome in one-year-old children born preterm: differences between low birth weight and very low birth weight.

BACKGROUND: In preterm infants, low birth weight represents one of the major risk factors for health and developmental issues. In Italy, most of the studies are focused on extremely preterm or Very and Extremely Low Birth Weight (VLBW, ELBW) children, whereas little data are available on the neurodevelopmental outcome of Low Birth Weight (LBW) children. We aimed to study the developmental profile of a group of preterm children at 12 months of corrected age, comparing cognitive, language and motor performances between LBW and VLBW. METHODS: We assessed 108 children born preterm (53 LBW and 55 VLBW) at 12 months of corrected age (M= 12.9 months; SD = .95) with Bayley-III. We compared the mean scores between and within groups and the rates of mild and severe delay using the Italian norms. RESULTS: LBW children performed better than VLBW peers, particularly in the cognitive and gross motor areas. No differences between groups were found in relation to language subscales. The rate of mild and severe delay is elevated in both groups, resulting significantly higher in the VLBW group only in the motor area. CONCLUSIONS: These results strongly suggest the need of a multidisciplinary follow-up to monitor the development of premature newborns, including those with birth weights above 1500 g. The early identification of cognitive, language and motor problems is essential to promote children's well-being and intervention prior to school entry.

The Floor Effect on the ABAS-II in Adolescents with Autism Spectrum Disorder.

The present study aimed at enhancing the assessment of adaptive behavior in adolescents with Autism Spectrum Disorder trough the Adaptive Behavior Assessment System-Second Edition. To overcome the limits underpinning floor effect, which are commonly observed with the traditional methods, the statistical Hessl method and its revision by Orsini, Pezzuti and Hulbert was adopted. The results showed a more variation using the former method compared to the latter: a greater impairment in Social versus Leisure skills emerged. Regarding the Conceptual domain, a greater deficit in Functional Academics was observed. In the Practical domain, we found a greater impairment in Self-Care skills. Conversely, Home Living skills appeared as a strength compared to other skills. The results are discussed in reference to literature.

Assessing the three attentional networks in children from three to six years: A child-friendly version of the Attentional Network Test for Interaction.

Attention involves three functionally and neuroanatomically distinct neural networks: alerting, orienting, and executive control. This study aimed to analyze the development of attentional networks in children aged between 3 and 6 years using a child-friendly version of the Attentional Network Test for Interaction (ANTI), the ANTI-Birds. The sample included 88 children divided into four age groups: 3-year-old, 4-year-old, 5-year-old, 6-year-old children. The results of this study would seem to indicate that between 4 and 6 years, there are no significant changes in attentional networks. Instead, between 3 and 4 years of age, children significantly improve all their attentional skills.

Prognostic factors and predictors of outcome in children with autism spectrum disorder: the role of the paediatrician.

BACKGROUND: Autism spectrum disorder is a complex condition with wide variation in type and severity that involves persistent challenges in social interaction, speech and nonverbal communication, restricted/repetitive behaviours and adaptive behaviours. In recent years, research has deepened the study of the predictive factors of optimal outcome, intended as indicators of positive trajectory in children with a previous diagnosis of autism who, after a therapeutic path, show a significant reduction in the "core" symptoms of autism and a positive evolution in social, adaptive, affective, and relational skills. METHODS: The study included 40 children aged 21 to 66 months, enrolled between 2015 and 2016 for an autism spectrum disorder clinical suspicious. Children were re-evaluated after at least 2 years of therapy and they were divided into two groups: the ASD-ASD group included children with a confirmed diagnosis of ASD, and the ASD-OO comparison group included children who no longer met the criteria for an autism classification. The aim of this retrospective study was to investigate the presence of cognitive, emotional and relational predictors capable of predicting the presence of optimal outcome in with a diagnosis of autism; the predictors taken into consideration were the intelligence quotient, the play, the emotional contagion and the understanding of other's intentions. In this way, it is possible to support clinicians in defining a more complete diagnostic framework of autism, using assessment tools that can be administered quickly and therefore suitable for short observation sessions in paediatric patients. RESULTS: The findings showed that 15 out of 40 children, after at least for 2 years, no longer fell into the diagnostic ASD category based on the ADOS-2, DSM-5 and clinical criteria. The children in the ASD-OO group initially had a higher IQ than those in the ASD-ASD group, lower severity of autistic symptoms, greater understanding of intentions, more emotional contagion, and better quality of play. The results suggest that the initial coexistence of skills in these areas at the time of the first diagnostic assessment may allow us to predict the possibility of achieving optimal outcome after 2 years of therapy. CONCLUSIONS: The data of this study highlight the importance of considering, during assessment, intelligence quotient, play, emotional contagion, and understanding of the intentions of others as potential prognostic predictors that can become useful tools for clinicians and paediatricians. This allows us to focus attention, in both the diagnostic and prognostic phases, on emotional-relational variables that can support the clinician in defining a more complete diagnostic framework and in planning a more personalized therapeutic path.

Parental perception of stress and emotional-behavioural difficulties of children with autism spectrum disorder and specific language impairment.

Background and aims: The daily challenges of caring for a child with autism spectrum disorder affect many areas of everyday life and parental well-being, as well as parents' ability to manage the needs of the family and the child concerned. A better understanding of parents' perception of their child's characteristics can allow better support for them and individualize intervention protocols in a more accurate way. The main objective of this study is the evaluation of the perception of stress by parents of children with autism compared to parents of children with specific language impairment. Methods: The parents of 87 children aged between 2 and 6 years were included in this study, 34 children with a specific language impairment diagnosis and 53 children with an autism spectrum disorder diagnosis (ASD) or at risk of developing it. They were asked to complete a self-report on perceived stress and rating scales on adaptive/problematic behaviours, executive functions and sensory profile of the child. Results: The results reveal that parents of ASD children, compared to the control group, showed significantly higher levels of stress, mainly due to the difficulty of managing unexpected events, the feeling of loss of control over one's life and the fear of not being able to cope with the adversities they were experiences. The most critical area, both for ASD and control group, concern the executive function related to emotional reactions. Conclusions: Thus, we argue that the difficulties in self-control, sensory modulation and emotional regulation, represent an element of stress for parents of children with developmental disorders.Implications: Regarding the difficulties of children with ASD, supporting the ways in which caregivers adapt to the signals of children is an important strategy, which has now become a key element of treatments for autism mediated by parents.

Parent-Reported Behavioural Changes in Children With Autism Spectrum Disorder During the COVID-19 Lockdown in Italy.

Autism Spectrum Disorders (ASD) are characterized by impairments in social interaction and reciprocal communication. During a pandemic, when social distancing becomes mandatory for all, both parents and children are not supported in-person by their therapists and cannot participate in usual therapies. This study reports the main clinical changes experienced by parents of children with during the first month of lockdown during the COVID-19 pandemic in Italy. Using standardized questionnaires, the families of 63 ASD children were interviewed in February and April 2020. Findings showed an increase in restricted and repetitive behaviours in about 30% of the sample; also, motor restlessness and sleep disturbances increased, with greater irritability and mood dysregulation. On the other hand, no changes emerged in personal self-care autonomies, in taste/smell sensitivity, and in auto or other-directed aggression. Despite the undeniable negative impact that lockdown can have on the psychosocial well-being of children, having maintained a continuity in supporting families, parental counselling (even if online and not in-person) helped families to redefine the meanings of behavioural changes of their children and to understand their adaptive functionality.

Neurodevelopmental outcome of Italian preterm children at 1year of corrected age by Bayley-III scales: An assessment using local norms.

BACKGROUND: Premature birth is often associated with neurodevelopmental difficulties throughout childhood. In the first three years of life, the Bayley Scales of Infant and Toddler Development-Third Edition (Bayley-III) constitute one of the most used tools for assessing child development. Since Bayley-III original norms are based on United States (US) population, it remains uncertain whether their use in other countries (e.g., European) is appropriate. AIMS: This research aimed to examine neurodevelopment of preterm infants and full-term infants, using Bayley-III US norms in comparison to Italian (IT) norms. Patterns of developmental outcomes for both infant groups were also explored. METHODS: 104 preterm and 58 full-term infants were included in the study. Bayley-III was used for neurodevelopmental assessment at 1year of corrected age, considering both IT and US norms for scores computation. RESULTS: Comparing scores obtained with IT vs US norms, differences in means were all significant across five subscales (p<0.05 at least) for preterm infants, whereas for full-term peers significant differences were found only for Receptive Language and Fine Motor subscales (p<0.001). Effect size (η2) ranged from 0.22 to 0.94. Within each group, significant discrepancies across subscales were found. Moreover, Italian preterm infants had significantly lower performances than full-term peers, excepting for Expressive Language and Gross Motor subscales. CONCLUSIONS: As regards to Italian 1-year children, our study seems to provide evidence for the tendency of Bayley-III US norms to overestimate development compared to IT norms. These findings emphasize the need to early detect children at risk for developmental delay and to plan early intervention.

ASSESSMENT OF A LONG-TERM DEVELOPMENTAL RELATIONSHIP-BASED APPROACH IN CHILDREN WITH AUTISM SPECTRUM DISORDER.

90 Italian children (72 boys, 18 girls) with a diagnosis of infantile autism (age range = 2.5-16.5 yr.) were assessed with a non-verbal intelligence test (Leiter-R). The test was repeated 3 times in four years. The measures used were IQ and Fluid Reasoning (FR), as evaluation of inductive and deductive reasoning, and the Autism Diagnostic Observation Schedule (ADOS), indicative of the severity of autistic symptoms at the beginning and at the end of therapy. The increase in the average IQ and FR scores at retests demonstrates the effectiveness of a treatment that emphasizes the centrality of the relationship-based approach. Moreover, the FR score at intake was predictive of a significant decrease of ADOS scores after four years of treatment, and of the increase in IQ observed in later evaluations. The data support the hypothesis that a relationship-based intervention allows cognitive improvement regardless of the autism severity expressed in the ADOS score.

Desmopressin and oxybutynin in monosymptomatic nocturnal enuresis: a randomized, double-blind, placebo-controlled trial and an assessment of predictive factors.

OBJECTIVES: To assess the efficacy of desmopressin plus oxybutynin and compare two starting dosages of desmopressin (120 and 240 µg) in a randomized, double-blinded, placebo-controlled trial for children with monosymptomatic nocturnal enuresis (MNE) resistant to desmopressin. The predictive factors of children with MNE responsive to desmopressin and combination therapy were also evaluated. PATIENTS AND METHODS: Our sample included 206 patients aged between 6 and 13 (mean age 10.6 ± 2.9 years), 117 males. All patients were required to have MNE. The patients were randomly divided into two groups: the first group was given oral melt 120 µg and the second group 240 µg, for 2 weeks. All patients who had experienced failure of treatment with sublingually administered desmopressin alone were given either desmopressin plus 5 mg oxybutynin or desmopressin plus placebo in a randomized, double-blinded trial for 4 weeks. As predictive factors, bladder volume and wall thickness index, nocturnal polyuria and voiding latency were considered. RESULTS: There was no significant difference between the 120 µg and 240 µg patients in terms of response. The oxybutynin group showed a higher rate of full and partial responses (45% success) compared with the placebo group (17% success), P < 0.01. The responders to combined oxybutynin and desmopressin had significantly lower bladder volume and wall thickness index than the other patients. CONCLUSIONS: Our findings highlight that anticholinergic agents may play an important role for a subset of children with enuresis who have a restricted bladder capacity and thickened bladder wall. Ultrasonography-measured bladder variables can provide useful predictive clues for MNE. Predictive factors can help to differentiate treatment subtypes and guide clinical management in primary nocturnal enuresis.

[ADHD and multimodal intervention]. / L'ADHD e l'intervento multimodale.

During the year 2003, the National Register of the Attention deficit hyperactivity disorder (ADHD) has been implemented in Italy. It was commissioned by the Ministry of Health to the Istituto Superiore di Sanità, which is its leading technical and scientific body, with the aim to set up a sound database gathering detailed information on the prescription of Ritalin at the national level. The latter represents the most diffused elective drug treatment for such an early-onset neuropsychiatric syndrome. To this aim, the more prevalent theories on the pathogenesis of ADHD and the debate on therapy are reviewed and discussed. This paper is aimed at emphasizing that this kind of systematic data gathering of such a Register has not to be meant an unconditional approval of a therapeutical approach based on drug therapy only. Pharmacological therapies may or may not be included within the frame of a multimodal complex treatment plan which should also rely on psychological intervention.

Methylphenidate administration to adolescent rats determines plastic changes on reward-related behavior and striatal gene expression.

Administration of methylphenidate (MPH, Ritalin) to children with attention deficit hyperactivity disorder (ADHD) is an elective therapy, but raises concerns for public health, due to possible persistent neurobehavioral alterations. Wistar adolescent rats (30 to 46 day old) were administered MPH or saline (SAL) for 16 days, and tested for reward-related and motivational-choice behaviors. When tested in adulthood in a drug-free state, MPH-pretreated animals showed increased choice flexibility and economical efficiency, as well as a dissociation between dampened place conditioning and more marked locomotor sensitization induced by cocaine, compared to SAL-pretreated controls. The striatal complex, a core component of the natural reward system, was collected both at the end of the MPH treatment and in adulthood. Genome-wide expression profiling, followed by RT-PCR validation on independent samples, showed that three members of the postsynaptic-density family and five neurotransmitter receptors were upregulated in the adolescent striatum after subchronic MPH administration. Interestingly, only genes for the kainate 2 subunit of ionotropic glutamate receptor (Grik2, also known as KA2) and the 5-hydroxytryptamine (serotonin) receptor 7 (Htr7) (but not GABA(A) subunits and adrenergic receptor alpha1b) were still upregulated in adulthood. cAMP responsive element-binding protein and Homer 1a transcripts were modulated only as a long-term effect. In summary, our data indicate short-term changes in neural plasticity, suggested by modulation of expression of key genes, and functional changes in striatal circuits. These modifications might in turn trigger enduring changes responsible for the adult neurobehavioral profile, that is, altered processing of incentive values and a modified flexibility/habit balance.

Beneficial effects of enriched environment on adolescent rats from stressed pregnancies.

The capacity of an early environmental intervention to normalize the behavioural and immunological dysfunctions produced by a stressed pregnancy was investigated. Pregnant Sprague-Dawley rats underwent three 45-min sessions per day of prenatal restraint stress (PS) on gestation days 11-21, and their offspring were assigned to either an enriched-environment or standard living cages throughout adolescence [postnatal days (pnd) 22-43]. Juvenile rats from stressed pregnancies had a prominent depression of affiliative/playful behaviour and of basal circulating CD4 T lymphocytes, CD8 T lymphocytes and T4/T8 ratio. They also showed increased emotionality and spleen and brain frontal cortex levels of pro-inflammatory interleoukin-1beta (IL-1beta) cytokine. A more marked response to cyclophosphamide (CPA: two 2 mg/kg IP injections) induced immunosuppression was also found in prenatal stressed rats. Enriched housing increased the amount of time adolescent PS rats spent in positive species-typical behaviours (i.e. play behaviour), reduced emotionality and reverted most of immunological alterations. In addition to its effects in PS rats, enriched housing increased anti-inflammatory IL-2 and reduced pro-inflammatory IL-1beta production by activated splenocytes, also producing a marked alleviation of CPA-induced immune depression. In the brain, enriched housing increased IL-1beta values in hypothalamus, while slightly normalizing these values in the frontal cortex from PS rats. This is a first indication that an environmental intervention, such as enriched housing, during adolescence can beneficially affect basal immune parameters and rats response to both early stress and drug-induced immunosuppression.

Acetyl-L-carnitine reduces impulsive behaviour in adolescent rats.

The attention deficit/hyperactivity disorder (ADHD) can affect human infants and adolescents. One important feature of this disorder is behavioural impulsivity. This study assessed the ability of chronic acetyl-L-carnitine (ALC, saline or 100 mg/kg SC, plus 50 mg/kg orally) to reduce impulsivity in a validated animal model for ADHD. Food-restricted rats were tested during adolescence (postnatal days, pnd, 30-45) in operant chambers with two nose-poking holes, one delivering one food pellet immediately, and the other five pellets after a delay. Delay length was increased over days (from 0 to 80 s). Individual differences in the preference-delay curve emerged, with the identification of two distinct subpopulations, i.e. one with a nearly horizontal curve and another with a very steep ("impulsive") slope. The impulsivity profile was slightly but consistently reduced by chronic ALC administration. Consistent results were also obtained with methylphenidate (MPH, saline or 3 mg/kg IP twice daily). Impulsive rats exhibited a lower metabolite/serotonin (5HIAA/5HT) ratio in the medial frontal cortex (MFC) and lower noradrenaline (NA) levels in the MFC and cingulate cortex (CC) when compared with the other subgroup. The ALC treatment increased NA levels in the CC and the 5HIAA/5HT ratio in both CC and MFC. Present data suggest that ALC, a drug devoid of psychostimulant properties, may have some beneficial effects in the treatment of ADHD children.

Environmental enrichment during adolescence reverses the effects of prenatal stress on play behaviour and HPA axis reactivity in rats.

Prenatal stress (PS) can produce profound and long-lasting perturbations of individual adaptive capacities, which in turn can result in an increased proneness to behavioural disorders. Indeed, in PS rats there is evidence of impaired social play behaviour, disturbances in a variety of circadian rhythms, enhanced anxiety and increased hypothalamic-pituitary-adrenal (HPA) axis reactivity. This study was designed to experimentally investigate the degree of reversibility of PS-induced disturbances of social play and HPA reactivity by assessing the effect of the enrichment of the physical environment on PS rats during periadolescence. PS subjects showed a reduced expression of social play behaviour and a prolonged corticosterone secretion in response to restraint stress, but both these effects were markedly reversed following environmental enrichment. Interestingly, the enrichment procedure increased social behaviour but had no effect on corticosterone secretion in nonstressed animals, indicating a differential impact of the postnatal environment as a function of prenatal background. As a whole, results clearly indicate that rats prenatally exposed to stress can benefit during periadolescence from the modulatory effects of an enriched environment. Moreover, they confirm that PS may well represent a suitable animal model for the design and testing of new therapeutic strategies for behavioural disorders produced by early insults.