Visual neglect: does it exist in children with unilateral brain lesion? A systematic review.

Visual Neglect (VN) is a common neuropsychological disorder in adults with unilateral brain lesion (UBL), characterized by the failure to attend and to report sensory events occurring in one side of space, contralateral to an area of brain damage. Less is known about VN expression in children following brain injury. The aim of this systematic review is to evaluate the presence of VN in UBL children and to identify the best neuropsychological assessment's tool for this population. A comprehensive search of 4 databases (Pubmed, Cochrane Database, SCOPUS, DARE) was undertaken from May 2020 to January 2021. Inclusion criteria were (i) subjects less than 18 years with cerebral lesions and with MRI, (ii) specific neuropsychological assessments for VN, (iii) studies published in English since 2000. A total of 309 articles were found in the initial search but only 10 observational studies met the full inclusion criteria. In these studies, 1051 subjects were evaluated for VN, of them 749 were controls and 302 had brain lesions. The two most common types of neuropsychological tools used in children with unilateral brain damage to assess the presence of VN were target cancellation tests and drawing tests.This review confirms the possibility that children with UBL can develop VN, even if it is not very clear which brain structure's characteristics can increase this risk. Children with right lesion showed visuo-spatial attention deficits focalized on the contralateral side, compatible with diagnosis of VN, while children with left lesion showed more generalized attention difficulties. The overall level of evidence correlating the presence of VN and different types of UBL in children was low and neuropsychological assessment of VN for children are sparse. Some important limitations of this review must be reported: the limited number of studies included, the administration of various types of tests to evaluate VN, the lack of information regarding the cognitive level of children in most of the studies. Further research is needed to understand patterns of VN based on brain structure and time since lesion.Systematic Review Registration: ID on PROSPERO: CRD42021281993.

PROMPT to improve speech motor abilities in children with cerebral palsy: a wait-list control group trial protocol.

BACKGROUND: Children with cerebral palsy (CP) often have communication impairments, including speech altered intelligibility. Multiple levels of disrupted speech have been reported in CP, which negatively impact on participation and quality of life, with increase of care needs. Augmentative Alternative Communication (AAC) is an option, with debated benefits and limitations, in particular for its functional use. This is supported by a substantial lack of defined evidences in favor of direct speech articulation intervention in CP. Motor learning-based interventions are effective in CP and are the basis of speech motor interventions such as PROMPT (Prompts for Restructuring Oral Muscular Phonetic Targets). The PROMPT speech motor treatment provides tactile-kinesthetic inputs to facilitate articulatory movements by dynamic modelling, resulting in more efficient motor patterns that can be integrated into speech and communication. In CP, exploratory evidences support the feasibility and preliminarily advantages on intelligibility of motor speech treatments, such as PROMPT, with increased speech motor control, also documented by kinematic analyses. METHODS: A randomized waitlist-control trial will be conducted in children aged between 3- and 10-years having CP and dysarthria (estimated sample size = 60 children). Children will be allocated in the immediate intervention or in the waitlist control group. The intervention consists of an intensive 3 weeks period of twice-a-day administration of PROMPT. Standard care will be administered in the control (waitlist) group. After repeated baseline assessments (T0), the PROMPT treated group will undergo the experimental 3-week intervention period, with T1 assessment at the end. A further T2 assessment will be provided at medium term (3 months after the end of the intervention) for evaluating the stability of intervention. Primary and secondary speech clinical and kinematics outcome measures will be collected at T0, T1 and T2. DISCUSSION: This paper describes the study protocol consisting of a RCT with two main objectives: (1) to evaluate the or short-term benefits of an intensive speech motor intervention on speech and intelligibility in children with CP and the stability of the intervention at medium term; (2) to describe the kinematic correlates of speech motor control modifications. TRIAL REGISTRATION: Trial registration date 06/12/2019; ClinicalTrials.gov Identifier: NCT04189159 .

LUNCH-Lung Ultrasound for early detection of silent and apparent aspiratioN in infants and young CHildren with cerebral palsy and other developmental disabilities: study protocol of a randomized controlled trial.

BACKGROUND: Children with neurological impairment may have dysphagia and/or gastro-esophageal reflux disease (GERD), which predispose to complications affecting the airways, increasing risk for aspiration-induced acute and chronic lung disease, or secondarily malnutrition, further neurodevelopmental disturbances, stressful interactions with their caregivers and chronic pain. Only multidisciplinary clinical feeding evaluation and empirical trials are applied to provide support to the management of feeding difficulties related to dysphagia or GERD, but no standardized feeding or behavioral measure exists at any age to assess aspiration risk and support the indication to perform a videofluoroscopic swallowing study (VFSS) or a fibre-optic endoscopic examination of swallowing (FEES), in particular in newborns and infants with neurological impairments. Lung ultrasound (LUS) has been proposed as a non-invasive, radiation-free tool for the diagnosis of pulmonary conditions in infants, with high sensitivity and specificity. METHODS: A RCT will be conducted in infants aged between 0 and 6 years having, or being at risk for, cerebral palsy, or other neurodevelopmental disease that determines abnormal muscular tone or motor developmental delay assessed by a quantitative scale for infants or if there is the suspicion of GERD or dysphagia based on clinical symptoms. Infants will be allocated in one of 2 groups: 1) LUS-monitored management (LUS-m); 2) Standard care management (SC-m) and after baseline assessment (T0), both groups will undergo an experimental 6-months follow-up. In the first 3 months, infants will be evaluated a minimum of 1 time per month, in-hospital, for a total of 3 LUS-monitored meal evaluations. Primary and secondary endpoint measures will be collected at 3 and 6 months. DISCUSSION: This paper describes the study protocol consisting of a RCT with two main objectives: (1) to evaluate the benefits of the use of LUS for monitoring silent and apparent aspiration in the management of dysphagia and its impact on pulmonary illness and growth and (2) to investigate the impact of the LUS management on blood sample and bone metabolism, pain and interaction with caregivers. TRIAL REGISTRATION: Trial registration date 02/05/2020; ClinicalTrials.gov Identifier: NCT04253951 .

Automating Quantitative Measures of an Established Conventional MRI Scoring System for Preterm-Born Infants Scanned between 29 and 47 Weeks' Postmenstrual Age.

BACKGROUND AND PURPOSE: Conventional MR imaging scoring is a valuable tool for risk stratification and prognostication of outcomes, but manual scoring is time-consuming, operator-dependent, and requires high-level expertise. This study aimed to automate the regional measurements of an established brain MR imaging scoring system for preterm neonates scanned between 29 and 47 weeks' postmenstrual age. MATERIALS AND METHODS: This study used T2WI from the longitudinal Prediction of PREterm Motor Outcomes cohort study and the developing Human Connectome Project. Measures of biparietal width, interhemispheric distance, callosal thickness, transcerebellar diameter, lateral ventricular diameter, and deep gray matter area were extracted manually (Prediction of PREterm Motor Outcomes study only) and automatically. Scans with poor quality, failure of automated analysis, or severe pathology were excluded. Agreement, reliability, and associations between manual and automated measures were assessed and compared against statistics for manual measures. Associations between measures with postmenstrual age, gestational age at birth, and birth weight were examined (Pearson correlation) in both cohorts. RESULTS: A total of 652 MRIs (86%) were suitable for analysis. Automated measures showed good-to-excellent agreement and good reliability with manual measures, except for interhemispheric distance at early MR imaging (scanned between 29 and 35 weeks, postmenstrual age; in line with poor manual reliability) and callosal thickness measures. All measures were positively associated with postmenstrual age (r = 0.11-0.94; R2 = 0.01-0.89). Negative and positive associations were found with gestational age at birth (r = -0.26-0.71; R2 = 0.05-0.52) and birth weight (r = -0.25-0.75; R2 = 0.06-0.56). Automated measures were successfully extracted for 80%-99% of suitable scans. CONCLUSIONS: Measures of brain injury and impaired brain growth can be automatically extracted from neonatal MR imaging, which could assist with clinical reporting.

A new protocol for assessing action observation and imitation abilities in children with Developmental Coordination Disorder: A feasibility and reliability study.

AIMS: To develop a new protocol for the assessment of action observation (AO) abilities and imitation of meaningful and non-meaningful gestures, to examine its psychometric properties in children with DCD and typically developing (TD) children. BACKGROUND: For learning manual skills, AO and imitation are considered fundamental abilities. Knowledge about these modalities in children with DCD is scarce and an assessment protocol is lacking. METHOD: The protocol consists of 2 tests. The AO test consists of two assembly tasks. The imitation test includes 12 meaningful and 20 non-meaningful gestures. Items of both tests are rated on a 4-point scale. Twelve children with DCD (mean age 8y3m, SD, 1.30) and 11 TD children (mean age 8y2m, SD 1.52) were enrolled. For inter-rater reliability, intraclass correlation coefficients (ICC) were calculated for the total score, weighted kappa and percentage agreement for single items. Known group validity was assessed by comparison of DCD and TD group (Wilcoxon rank sum test). For construct validity, the mABC-2 test was used. The protocol was adapted and confirmed by an intra and inter-rater reliability study (new sample of 11 DCD children, mean age 7y5m, SD 1.37). RESULTS: Excellent ICCs were reported for intra and inter-rater reliability for the final protocol. A significant difference between DCD and TD group was found for AO abilities (p < .01), for nonmeaningful gestures (p < .001). A significant correlation was reported between the AO test and the mABC-2 test (r = 56;p ≤0.0001). No significant correlations were revealed for the imitation tests. DISCUSSION AND CONCLUSION: The results support the psychometric properties of this protocol. When fully validated, it may contribute to map the deficits in AO abilities and imitation, to evaluate treatment effects of imitation and AO interventions.

Functional, neuroplastic and biomechanical changes induced by early Hand-Arm Bimanual Intensive Therapy Including Lower Extremities (e-HABIT-ILE) in pre-school children with unilateral cerebral palsy: study protocol of a randomized control trial.

BACKGROUND: Cerebral palsy (CP) causes motor, cognitive and sensory impairment at different extents. Many recent rehabilitation developments (therapies) have focused solely on the upper extremities (UE), although the lower extremities (LE) are commonly affected. Hand-arm Bimanual Intensive Therapy Including Lower Extremities (HABIT-ILE) applies the concepts of motor skill learning and intensive training to both the UE and LE. It involves constant stimulation of the UE and LE, for several hours each day over a 2-week period. The effects of HABIT-ILE have never been evaluated in a large sample of young children. Furthermore, understanding of functional, neuroplastic and biomechanical changes in infants with CP is lacking. The aim of this study is to carry out a multi-center randomized controlled trial (RCT) to evaluate the effects of HABIT-ILE in pre-school children with unilateral CP on functional, neuroplastic and biomechanical parameters. METHODS: This multi-center, 3-country study will include 50 pre-school children with CP aged 1-4 years. The RCT will compare the effect of 50 h (two weeks) of HABIT-ILE versus usual motor activity, including regular rehabilitation. HABIT-ILE will be delivered in a day-camp setting, with structured activities and functional tasks that will be continuously progressed in terms of difficulty. Assessments will be performed at 3 intervals: baseline (T0), two weeks later and 3 months later. Primary outcomes will be the Assisting Hand Assessment; secondary outcomes include the Melbourne Assessment-2, executive function assessments, questionnaires ACTIVLIM-CP, Pediatric Evaluation of Disability Inventory, Young Children's Participation and Environment Measure, Measure of the Process of Care, Canadian Occupational Performance Measure, as well as neuroimaging and kinematics measures. DISCUSSION: We expect that HABIT-ILE will induce functional, neuroplastic and biomechanical changes as a result of the intense, activity-based rehabilitation process and these changes will impact the whole developmental curve of each child, improving functional ability, activity and participation in the short-, mid- and long-term. Name of the registry: Changes Induced by Early HABIT-ILE in Pre-school Children With Uni- and Bilateral Cerebral Palsy (EarlyHABIT-ILE). TRIAL REGISTRATION: Trial registration number: NCT04020354-Registration date on the International Clinical Trials Registry Platform (ICTRP): November 20th, 2018; Registration date on NIH Clinical Trials Registry: July 16th, 2019.

Movement analysis in early infancy: Towards a motion biomarker of age.

BACKGROUND: Early motor development is characterized by progressive changes in general movements paralleled by a gradual organization of the four limbs' repertoire towards the midline, as shown by computerised movement analysis. AIMS: Our aim was to test the performance of quantitative computerised kinematic indexes as predictors of post-term age in an independent cohort of typically developing subjects at fidgety age, tested cross-sectionally. SUBJECTS: We selected twelve low risk term infants, who were video recorded between 9 and 20 weeks (fidgety age) during one spontaneous movements session. STUDY DESIGN: We correlated post-term age with I)indexes of coordination including interlimb correlation of velocity and position, II)indexes of distance, including interlimb and limb-to- ground, both expressed as linear distance and as probability of midline limbs position III)indexes of global movement quality by calculating Hjorth's activity, mobility and complexity parameters. All indexes were calculated for both upper and lower limbs. RESULTS: Significant positive correlations were found between post-term age and indexes of distance, and probability of occurrence of upper-limb antigravity patterns, and with both indexes of global movement quality. By combining linear and non-linear parameters related to the upper limb kinematics, we determined individual post-term age with a mean error of <1 week (5.2 days). No correlations were found between age and indexes of coordination. CONCLUSIONS: Quantitative computerised analysis of upper-limb movements is a promising predictor of post-term age in typically developing subjects at fidgety age.

Early motor signs of attention-deficit hyperactivity disorder: a systematic review.

ADHD is a common neurodevelopmental disorder with onset of symptoms typically in early childhood. First signs of the disorder, including language delay, motor delay and temperament characteristics, may be evident as early as infancy. The present review describes published evidence about early motor signs of either children with later symptoms of ADHD or a later diagnosis of the disorder. Nine published cohort studies were included after a systematic search of related terms in PubMed and PsycInfo databases. Study eligibility criteria included: (1) report on early motor function or any motor-related signs; (2) the presence of a participants' assessment by/at 12 months of age; (3) report of a later presence of ADHD symptoms. The limited number of reports included suggests an association between mild early neurological markers and later developmental coordination disorder and motor overflow movements. Unfortunately, due to their small sample sizes and focus on group reports rather than individuals, they have limited power to find strong associations. Early motor indicators of ADHD, if present, appear to be non-specific, and therefore not yet useful in clinical screening. Spontaneous motility seems to be a promising measure for early ADHD detection, although further studies with large cohorts are recommended to determine its clinical role in children at risk for ADHD.

Parent-Infant Interaction during the First Year of Life in Infants at High Risk for Cerebral Palsy: A Systematic Review of the Literature.

Introduction: Perinatal adverse events put neonates at high risk for short and long-term disabilities, including cerebral palsy (CP). The most recent guidelines about early intervention in infants with brain damage have emphasized the importance of family involvement from the very first phases of development. Early parent-infant interactions are pivotal in promoting infant cognitive and social developmental trajectories. However, little is known about the extent to which severe adverse perinatal events can affect the quality of early parent-infant interactions. Patients and Methods: We systematically searched five databases (PubMed, PsycINFO, EMBASE, CINAHL, and Cochrane Library) for the publications assessing parent-infant interactions in infants at high neurological risk within 1 year of age. Articles were selected if they involved direct comparison between high-risk populations and healthy controls or low-risk populations, and if quantitative or semiquantitative tools were used to assess the parent-infant interaction. Measures of parent-infant interaction included infant interactive behaviors, parental interactive behaviors, and dyadic interactive patterns. Results: The search yielded 18 publications that met the inclusion criteria. The articles represent a high level of heterogeneity in terms of infant neurological risk, infant age, and tools assessing interactive behaviors. Both infant and maternal behaviors within the investigated interactive exchanges were reported to be compromised, leading to subsequent overall impairment of the dyadic patterns. Conclusion: While the studies reviewed here provide general and important information, the review did not yield a clear picture of early dyadic interactions in high-risk infant populations. Further observational studies are warranted in order to provide a more accurate knowledge of the early dyadic exchanges between infants at high neurological risk and their parents, as they might provide a critical opportunity for early family centered habilitative interventions.

Neuroprocessing Mechanisms of Music during Fetal and Neonatal Development: A Role in Neuroplasticity and Neurodevelopment.

The primary aim of this viewpoint article is to examine recent literature on fetal and neonatal processing of music. In particular, we examine the behavioral, neurophysiological, and neuroimaging literature describing fetal and neonatal music perception and processing to the first days of term equivalent life. Secondly, in light of the recent systematic reviews published on this topic, we discuss the impact of music interventions on the potential neuroplasticity pathways through which the early exposure to music, live or recorded, may impact the fetal, preterm, and full-term infant brain. We conclude with recommendations for music stimuli selection and its role within the framework of early socioemotional development and environmental enrichment.

Validation of an MRI Brain Injury and Growth Scoring System in Very Preterm Infants Scanned at 29- to 35-Week Postmenstrual Age.

BACKGROUND AND PURPOSE: The diagnostic and prognostic potential of brain MR imaging before term-equivalent age is limited until valid MR imaging scoring systems are available. This study aimed to validate an MR imaging scoring system of brain injury and impaired growth for use at 29 to 35 weeks postmenstrual age in infants born at <31 weeks gestational age. MATERIALS AND METHODS: Eighty-three infants in a prospective cohort study underwent early 3T MR imaging between 29 and 35 weeks' postmenstrual age (mean, 32+2 ± 1+3 weeks; 49 males, born at median gestation of 28+4 weeks; range, 23+6-30+6 weeks; mean birthweight, 1068 ± 312 g). Seventy-seven infants had a second MR scan at term-equivalent age (mean, 40+6 ± 1+3 weeks). Structural images were scored using a modified scoring system which generated WM, cortical gray matter, deep gray matter, cerebellar, and global scores. Outcome at 12-months corrected age (mean, 12 months 4 days ± 1+2 weeks) consisted of the Bayley Scales of Infant and Toddler Development, 3rd ed. (Bayley III), and the Neuro-Sensory Motor Developmental Assessment. RESULTS: Early MR imaging global, WM, and deep gray matter scores were negatively associated with Bayley III motor (regression coefficient for global score ß = -1.31; 95% CI, -2.39 to -0.23; P = .02), cognitive (ß = -1.52; 95% CI, -2.39 to -0.65; P < .01) and the Neuro-Sensory Motor Developmental Assessment outcomes (ß = -1.73; 95% CI, -3.19 to -0.28; P = .02). Early MR imaging cerebellar scores were negatively associated with the Neuro-Sensory Motor Developmental Assessment (ß = -5.99; 95% CI, -11.82 to -0.16; P = .04). Results were reconfirmed at term-equivalent-age MR imaging. CONCLUSIONS: This clinically accessible MR imaging scoring system is valid for use at 29 to 35 weeks postmenstrual age in infants born very preterm. It enables identification of infants at risk of adverse outcomes before the current standard of term-equivalent age.

Network over-connectivity differentiates autism spectrum disorder from other developmental disorders in toddlers: A diffusion MRI study.

Advanced connectivity studies in toddlers with Autism Spectrum Disorder (ASD) are increasing and consistently reporting a disruption of brain connectivity. However, most of these studies compare ASD and typically developing subjects, thus providing little information on the specificity of the abnormalities detected in comparison with other developmental disorders (other-DD). We recruited subjects aged below 36 months who received a clinical diagnosis of Neurodevelopmental Disorder (32 ASD and 16 other-DD including intellectual disability and language disorder) according to DSM-IV TR. Structural and diffusion MRI were acquired to perform whole brain probabilistic and anatomically constrained tractography. Network connectivity matrices were built encoding the number of streamlines (DNUM ) and the tract-averaged fractional anisotropy (DFA ) values connecting each pair of cortical and subcortical regions. Network Based Statistics (NBS) was finally applied on the connectivity matrices to evaluate the network differences between the ASD and other-DD groups. The network differences resulted in an over-connectivity pattern (i.e., higher DNUM and DFA values) in the ASD group with a significance of P < 0.05. No contra-comparison results were found. The over-connectivity pattern in ASD occurred in networks primarily involving the fronto-temporal nodes, known to be crucial for social-skill development and basal ganglia, related to restricted and repetitive behaviours in ASD. To our knowledge, this is the first network-based diffusion study comparing toddlers with ASD and those with other-DD. Results indicate the detection of different connectivity patterns in ASD and other-DD at an age when clinical differential diagnosis is often challenging. Hum Brain Mapp 38:2333-2344, 2017. © 2017 Wiley Periodicals, Inc.

Diffusion Tractography Biomarkers of Pediatric Cerebellar Hypoplasia/Atrophy: Preliminary Results Using Constrained Spherical Deconvolution.

BACKGROUND AND PURPOSE: Advances in MR imaging modeling have improved the feasibility of reconstructing crossing fibers, with increasing benefits in delineating angulated tracts such as cerebellar tracts by using tractography. We hypothesized that constrained spherical deconvolution-based probabilistic tractography could successfully reconstruct cerebellar tracts in children with cerebellar hypoplasia/atrophy and that diffusion scalars of the reconstructed tracts could differentiate pontocerebellar hypoplasia, nonprogressive cerebellar hypoplasia, and progressive cerebellar atrophy. MATERIALS AND METHODS: Fifteen children with cerebellar ataxia and pontocerebellar hypoplasia, nonprogressive cerebellar hypoplasia or progressive cerebellar atrophy and 7 controls were included in this study. Cerebellar and corticospinal tracts were reconstructed by using constrained spherical deconvolution. Scalar measures (fractional anisotropy and mean, axial and radial diffusivity) were calculated. A general linear model was used to determine differences among groups for diffusion MR imaging scalar measures, and post hoc pair-wise comparisons were performed. RESULTS: Cerebellar and corticospinal tracts were successfully reconstructed in all subjects. Significant differences in diffusion MR imaging scalars were found among groups, with fractional anisotropy explaining the highest variability. All groups with cerebellar pathologies showed lower fractional anisotropy compared with controls, with the exception of cerebellar hypoplasia. CONCLUSIONS: This study shows the feasibility of constrained spherical deconvolution to reconstruct cerebellar and corticospinal tracts in children with morphologic cerebellar pathologies. In addition, the preliminary results show the potential utility of quantitative analysis of scalars of the cerebellar white matter tracts in children with cerebellar pathologies such as cerebellar hypoplasia and atrophy. Further studies with larger cohorts of patients are needed to validate the clinical significance of our preliminary results.

Sensorized pacifier to quantify the rhythmicity of non-nutritive sucking: A preliminary study on newborns.

Non-nutritive sucking (NNS) is one of the most significant spontaneous actions of infants. The suction/expression rhythmicity of NNS remains unknown. We developed a sensorized pacifier for an objective measurement of NNS. Two miniaturized digital pressure sensors are embedded into a commercial pacifier and they acquired suction and expression pressures simultaneously. Experimental tests with nine newborns confirmed that our device is suitable for the measurement of the natural NNS behavior and for the extrapolation of parameters related to the suction/expression rhythmicity. Preliminary results encourage future studies to evaluate the possibility to use these parameters as indicators of oral feeding readiness of premature infants.

Sensorized graspable devices for the study of motor imitation in infants.

Researches regarding neonatal imitation are of great clinical interest since they can provide evidences of an innate mechanism underlying action understanding; the study can be led through the analysis of infants' spontaneous movements, like grasping, that are recognized as markers of neural activity. To this aim, a portable and non-intrusive device has been designed and developed to measure infants' grasping during the presentation of specific visual stimuli. The device is composed of two soft handles with embedded pressure sensors. During trials action observation should produce an increase of the measured pressure exerted by the infant's hand, according to the imitation-based paradigm of the defined clinical protocol. The final prototype has been tested within a pilot study and it has been proved to be suitable for monitoring infants' imitation abilities, meeting all the clinical specifications in terms of size, weight, safety and sensitivity. Preliminary acquired results are a starting point to clarify mechanisms related to imitation and sensorimotor system growth. The present methodology could be employed to boosts investigation on the development of mirror neurons in infants.

Brain reorganization following intervention in children with congenital hemiplegia: a systematic review.

Noninvasive rehabilitation strategies for children with unilateral cerebral palsy are routinely used to improve hand motor function, activity, and participation. Nevertheless, the studies exploring their effects on brain structure and function are very scarce. Recently, structural neuroplasticity was demonstrated in adult poststroke patients, in response to neurorehabilitation. Our purpose is to review current evidence on the effects of noninvasive intervention strategies on brain structure or function, in children with unilateral cerebral palsy. The main literature databases were searched up to October 2013. We included studies where the effects of upper limb training were evaluated at neurofunctional and/or neurostructural levels. Only seven studies met our selection criteria; selected studies were case series, six using the intervention of the constraint-induced movement therapy (CIMT) and one used virtual reality therapy (VR). CIMT and VR seem to produce measurable neuroplastic changes in sensorimotor cortex associated with enhancement of motor skills in the affected limb. However, the level of evidence is limited, due to methodological weaknesses and small sample sizes of available studies. Well-designed and larger experimental studies, in particular RCTs, are needed to strengthen the generalizability of the findings and to better understand the mechanism of intervention-related brain plasticity in children with brain injury.

Are children born after assisted reproductive technology at increased risk of autism spectrum disorders? A systematic review.

STUDY QUESTION: Are children born after assisted reproductive technology (ART) at increased risk of autism spectrum disorders (ASD)? SUMMARY ANSWER: There is no evidence that ART significantly increases the risk of ASD in the offspring. WHAT IS KNOWN ALREADY: A few systematic reviews have explored the correlation between assisted conception and ASD with inconclusive results, partly due to the heterogeneity of diagnostic criteria and methodology in the different studies. STUDY DESIGN, SIZE, DURATION: Systematic review of 7 observational studies (2 cohort and 5 case-control) encompassing 9216 subjects diagnosed with ASD published since 2000. MATERIALS, SETTING, METHODS: Literature searches were conducted to retrieve observational studies on the risk of ASD in ART population. Databases searched included PubMed, EMBASE and PsycINFO. In order to obtain more consistent results, we only included the studies in which (i) subjects with either infantile autism or ASD could be identified according to international classification systems and (ii) the diagnosis was obtained from hospital records. Seven studies matched the inclusion criteria. MAIN RESULTS AND THE ROLE OF CHANCE: Four out of seven studies, including the two with the best quality scores, did not show an association between ART and ASD. The two papers supporting an increased risk of autism following ART had the lowest quality scores, due to major methodological limitations. Only one paper showed a protective role of ART. LIMITATIONS, REASONS FOR CAUTION: In spite of the strict inclusion criteria applied as to the diagnosis of ASD, the papers selected are heterogeneous in many aspects including study design, definitions of ART, data source and analysed confounders. WIDER IMPLICATIONS OF THE FINDINGS: At present, there is no evidence that ART is significantly associated with ASD and hence that current health policies should be modified. The divergent results of some of the studies suggest that further prospective, large and high-quality studies are still needed. STUDY FUNDING/COMPETING INTEREST(S): This work was supported, in part, by the Italian Ministry of Health and by Tuscany Region. The authors have no competing interests to declare. TRIAL REGISTRATION NUMBER: N/A.

Thyroid-stimulating hormone levels in the first days of life and perinatal factors associated with sub-optimal neuromotor outcome in pre-term infants.

AIM: To identify perinatal factors associated with sub-optimal neuromotor outcome in infants without evident central nervous system lesions (intraventricular hemorrhage/ periventricular leukomalacia), with gestational age ≤30 (group I) and of 31-32 weeks (group II). PATIENTS AND METHODS: A total of 102 premature infants admitted to the Neonatal Intensive Care Unit of Pisa, at 26-32 weeks of gestation, were studied. Data about perinatal factors and TSH values at 3-4 days of life were collected. The assessment of neuromotor development was performed at 18 months of corrected age, using the locomotor subscale of the Griffiths Scales of Mental Development. RESULTS: Risk factors supposed to be predictive of sub-optimal neuromotor outcome (odds ratio >1) were at ≤30 weeks: male sex, small for gestational age, patent duct arterious, respiratory distress syndrome, and at 31-32 weeks: Apgar at 5 min <7, respiratory distress syndrome, patent duct arterious and birth weight <1500 g. A strong correlation was also found between TSH screening values >4,3 mU/l and suboptimal neuromotor outcome in both groups. CONCLUSIONS: Several perinatal factors, acting on an immature and more vulnerable nervous system, such as the pre-term one, different for different gestational ages, are associated with a sub-optimal neuromotor outcome. Higher, but within the normal range, TSH values at screening seem to be a strong risk factor for neuromotor outcome in preterm infants without intraventricular hemorrhage or periventricular leukomalacia.