Implications of isolated white matter abnormalities on neonatal MRI in congenital CMV infection: a prospective single-centre study.

OBJECTIVE: Investigating the clinical implications of isolated white matter abnormalities on neonatal brain MRI in congenital cytomegalovirus (CMV). DESIGN: Prospective, observational. PATIENTS/INTERVENTIONS: Two paediatric radiologists, blinded to clinical data, independently scored the white matter in 286 newborns with congenital CMV. After assessing interobserver variability, mean score was used to categorise white matter (normal, doubtful or abnormal). Patients with other brain abnormalities were excluded. MAIN OUTCOME MEASURES: Hearing and neuromotor evaluation. RESULTS: Cohen's weighted kappa was 0.79 (95% CI 0.73 to 0.84). White matter was normal in 121 patients, doubtful in 62, abnormal in 28. Median clinical follow-up was 12.0 months (IQR 12.0-27.7 months). Neonatal hearing loss occurred in 4/27 patients (14.8%) with abnormal, 1/118 patients (0.8%) with normal and 1/62 patients (1.6%) with doubtful white matter (p<0.01). Impaired cognitive development was seen in 3/27 patients (11.1%) with abnormal, 3/114 patients (2.6%) with normal and 1/59 patients (1.7%) with doubtful white matter (p=0.104). Alberta Infant Motor Scale (AIMS) was below P75 in 21/26 patients (80.8%) with abnormal, 73/114 patients (64.0%) with normal and 36/57 patients (63.2%) with doubtful white matter (p=0.231). In a subgroup of patients with minimal clinical follow-up of 18 months, AIMS score was below P75 in 10/13 patients (76.9%) with abnormal, 13/34 patients (38.2%) with normal and 7/20 patients (35.0%) with doubtful white matter (p<0.05). CONCLUSIONS: Abnormal white matter was associated with neonatal hearing loss and mild, lower motor scores. A tendency towards impaired cognitive development was seen. Patients with doubtful white matter did not show worse clinical outcome.

The Impact of Intraventricular Hemorrhage and Periventricular Leukomalacia on Mortality and Neurodevelopmental Outcome in Very Preterm and Very Low Birthweight Infants: A Prospective Population-based Cohort Study.

OBJECTIVE: To survey the incidence of intraventricular hemorrhage (IVH) and periventricular leukomalacia (PVL) by gestational age and to report the impact on mortality and neurodevelopmental outcome in very preterm/very low birthweight infants. STUDY DESIGN: This was a population-based cohort study of 1927 very preterm/very low birthweight infants born in 2014-2016 and admitted to Flemish neonatal intensive care units. Infants underwent standard follow-up assessment until 2 years corrected age with the Bayley Scales of Infant and Toddler Development and neurological assessments. RESULTS: No brain lesion was present in 31% of infants born at <26 weeks of gestation and 75.8% in infants born at 29-32 weeks of gestation. The prevalence of low-grade IVH/PVL (grades I and II) was 16.8% and 12.7%, respectively. Low-grade IVH/PVL was not related significantly to an increased likelihood of mortality, motor delay, or cognitive delay, except for PVL grade II, which was associated with a 4-fold increase in developing cerebral palsy (OR, 4.1; 95% CI, 1.2-14.6). High-grade lesions (III-IV) were present in 22.0% of the infants born at <26 weeks of gestational and 3.1% at 29-32 weeks of gestation, and the odds of death were ≥14.0 (IVH: OR, 14.0; 95% CI, 9.0-21.9; PVL: OR, 14.1; 95% CI, 6.6-29.9). PVL grades III-IV showed an increased odds of 17.2 for motor delay and 12.3 for cerebral palsy, but were not found to be associated significantly with cognitive delay (OR, 2.9; 95% CI, 0.5-17.5; P = .24). CONCLUSIONS: Both the prevalence and severity of IVH/PVL decreased significantly with advancing gestational age. More than 75% of all infants with low grades of IVH/PVL showed normal motor and cognitive outcome at 2 years corrected age. High-grade PVL/IVH has become less common and is associated with adverse outcomes.

Expanding the molecular spectrum and the neurological phenotype related to CAMTA1 variants.

The CAMTA1-associated phenotype was initially defined in patients with intragenic deletions and duplications who showed nonprogressive congenital ataxia, with or without intellectual disability. Here, we describe 10 individuals with CAMTA1 variants: nine previously unreported (likely) pathogenic variants comprising one missense, four frameshift and four nonsense variants, and one missense variant of unknown significance. Six patients were diagnosed following whole exome sequencing and four individuals with exome-based targeted panel analysis. Most of them present with developmental delay, manifesting in speech and motor delay. Other frequent findings are hypotonia, cognitive impairment, cerebellar dysfunction, oculomotor abnormalities, and behavioral problems. Feeding problems occur more frequently than previously observed. In addition, we present a systematic review of 19 previously published individuals with causal variants, including copy number, truncating, and missense variants. We note a tendency of more severe cognitive impairment and recurrent dysmorphic features in individuals with a copy number variant. Pathogenic variants are predominantly observed in and near the N- and C- terminal functional domains. Clinical heterogeneity is observed, but 3'-terminal variants seem to associate with less pronounced cerebellar dysfunction.

Diagnosing Autism Spectrum Disorder in Toddlers Born Very Preterm: Estimated Prevalence and Usefulness of Screeners and the Autism Diagnostic Observation Schedule (ADOS).

This study estimated ASD prevalence in a cohort of 3-year-old very preterm children (N = 55) and investigated the usefulness of parent-reported ASD screeners and the ADOS-2. 12.7% received an ASD diagnosis by clinical judgment based on DSM-5 criteria. An additional 14.5% were classified as having a broader-autism-phenotype outcome. Sensitivity values for the screeners were poor, whereas specificity values ranged from poor to excellent. The ADOS-2 identified all children with ASD and had a fair specificity. These findings confirm the elevated ASD prevalence made by previous studies with preterm children but also highlight the challenges of successfully identifying ASD in this at-risk group. Caution is warranted when interpreting results of ASD instruments with the currently available cut-off scores and algorithms, especially when developmental challenges are present.

Motor outcome after perinatal stroke and early prediction of unilateral spastic cerebral palsy.

BACKGROUND: Unilateral spastic cerebral palsy (USCP) occurs in 30%-68% of infants with perinatal stroke. Early detection of USCP is essential for referring infants to early intervention. The aims of this study were to report motor outcomes after perinatal stroke, and to determine the predictive value of the General Movements Assessment (GMA) and Hand Assessment for Infants (HAI) for detection of USCP. MATERIALS AND METHODS: This was a prospective observational study involving infants with perinatal stroke. GMA was conducted between 10 and 15 weeks post term-age (PTA). The HAI was performed between 3 and 5 months PTA. Motor outcome was collected between 12 and 36 months PTA. RESULTS: The sample consisted of 46 infants. Fifteen children (32.6%) were diagnosed with CP, two children with bilateral CP and 13 with USCP. Abnormal GMA had a sensitivity of 85% (95% confidence interval [CI] 55-98%) and a specificity of 52% (95% CI 33-71%) to predict USCP. When asymmetrically presented FMs were also considered as abnormal, sensitivity increased to 100%, hence the specificity declined to 43%. A HAI asymmetry index cut-off of 23, had both a sensitivity and a specificity of 100% to detect USCP. CONCLUSION: Using GMA and HAI can enable prediction of USCP before the age of 5 months in infants with perinatal stroke. Nevertheless, GMA must be interpreted with caution in this particular population. The HAI was found to be a very accurate screening tool for early detection of asymmetry and prediction of USCP.

Neurodevelopmental outcomes of very preterm and very-low-birthweight infants in a population-based clinical cohort with a definite perinatal treatment policy.

BACKGROUND: With constant changes in neonatal care practices, recent information is valuable for healthcare providers and for parental counselling. The aim of the study was to describe the neurodevelopmental outcome in a cohort of very preterm (VPT)/very-low-birthweight (VLBW) infants at 2 years corrected age (CA). MATERIAL AND METHODS: This is a population-based cohort study of all infants born with a GA <31 weeks and/or BW < 1500 g between 2014 and 2016 admitted to the Flemish (Belgium) neonatal intensive care units. Infants had routine clinical follow-up around 2 years CA. The diagnosis of cerebral palsy (CP), visual and hearing impairments were recorded. Motor, cognitive and language outcomes were assessed using the Bayley-III. Neurodevelopmental impairment (NDI) was classified as mild (<1 standard deviation [SD]) or moderate-severe (<2SD) based on the defined categories of motor, cognitive, hearing, and vision impairments. RESULTS: Of the 1941 admissions, 92% survived to discharge and follow-up data were available for 1089 infants (61.1%). Overall, 19.3%, 18.9% and 41.8% of infants had a motor, cognitive and language delay, respectively. CP was diagnosed in 4.3% of the infants. Mild and moderate-to-severe NDI was observed in 25.2% and 10.9% of the infants, respectively. The number of infants with a normal outcome increased from nearly 40% in the category of GA<26 weeks to 70% for infants in the category of 30─31 weeks GA. CONCLUSION: At 2 years CA, 64% were free from NDI and 90% were free from moderate-to-severe NDI. However, a lower GA and BW are associated with higher rates of adverse neurodevelopmental outcomes at 2 years CA.

A Qualitative Photo Elicitation Research Study to elicit the perception of young children with Developmental Disabilities such as ADHD and/or DCD and/or ASD on their participation.

Participation, defined as 'involvement in life situations' according to the World Health Organisation, is a well-recognized concept and critical indicator of quality of life. In addition it has become an important outcome measure in child rehabilitation. However, little is known about the level of participation of young children with Developmental Disabilities. The aim of this study was to capture their subjective experiences of participation. An adapted informed consent based on a comic strip was used to get the children's assent. A Photo Elicitation study was used, in which photographs were taken by the children when they were involved in meaningful activities. The photographs were then used to facilitate communication with the children and to initiate in depth-interviews. Forty-seven interviews with 16 children between five and nine years were conducted based on their photographs. This method generated rich data, confirming that young children with Developmental Disabilities were able to inform us accurately on their experiences of participation. Data was analysed by means of an inductive thematic analysis. Results showed that children perceived their participation as satisfying when they can play, learn and join in family gatherings resulting in feelings of inclusion, recognition and belonging. When there are-on occasions-moments that their participation was obstructed, the children used two strategies to resolve it. Or they walked away from it and choose not to participate, or when autonomously motivated for the activity, they relied primarily on their context (i.e. mothers) as enabling their participation. Related to the data, children discussed themes related to their person, activities, connections and mediators between those themes. These themes fit well within earlier and current research on the subject of participation.

Parents' perspectives on participation of young children with attention deficit hyperactivity disorder, developmental coordination disorder, and/ or autism spectrum disorder: A systematic scoping review.

BACKGROUND: During the early years of a child's life, participation is essential for learning and development. Children with disabilities are at risk for decreased participation. The interplay between environment and participation is identified as one of the most important factors influencing successful participation. The objective of this scoping review was to synthesize peer-reviewed literature about barriers and facilitators of participation according to the perspective of parents of children younger than 6 years with Attention Deficit Hyperactivity Disorder (ADHD), Autism Spectrum Disorder (ASD), and/ or Developmental Coordination Disorder (DCD). METHODS: The scoping review followed Arksey and O'Malley's framework. Relevant studies were identified by a comprehensive search of scientific databases (PubMed and Web of Science). Studies describing perspectives of parents regarding their child's participation, written in English, and published between 2001 and September 2017 were included. RESULTS: A total of 854 articles were retrieved, with 13 meeting the criteria. Elements contributing to perceived barriers and facilitators were identified and organized according to the International Classification of Functioning, Child-Youth framework. Concepts contained in these studies were linked to "activities and participation" (general tasks and demands, such as bedtime and dinner routines, and social, civic life, such as play and leisure). Environment-focused factors identified were situated on "support and relationships, " "attitudes, " and "services, systems, and policies." CONCLUSION: The review revealed guidelines focusing on family-centred care, communication with, and providing information to parents with young children with developmental disabilities (ADHD, DCD, and/ or ASD).

Episodic Vestibular Symptoms in Children With a Congenital Cytomegalovirus Infection: A Case Series.

OBJECTIVE: Congenital cytomegalovirus (cCMV) infection is the most common non-genetic cause of sensorineural hearing loss in children. Although cCMV-induced vestibular loss is demonstrated in several studies, the occurrence of vertigo has been described in only two cases to date. The aim of this paper is to discuss the underlying pathophysiology of recurrent vestibular symptoms in children with cCMV, based on five cases investigated in our center and an extensive research of the literature. STUDY DESIGN: Retrospective case series. SETTING: Tertiary referral center. PATIENTS: This case series describes five pediatric cCMV-patients (three boys, two girls). Four of them were symptomatic at birth, one was asymptomatic. Three patients underwent cochlear implantation. The age of onset of the vestibular symptoms varied from 2;0 to 7;3 years of age. INTERVENTION: None. MAIN OUTCOME MEASURES: Details regarding the patient history and results of cranial imaging, audiological, vestibular, and neurological assessments were collected retrospectively. RESULTS: The selected cases suffered from recurrent vestibular symptoms. All patients had delayed onset, fluctuating, and/or progressive hearing loss. In all cases, the attacks were accompanied with nausea and vomiting and occurred without clear-cut trigger. Migraine and epilepsy often were proposed as first diagnosis, although they could not be confirmed eventually. Four out of five patients were diagnosed with a peripheral vestibular deficit. CONCLUSIONS: Diagnosis of vestibular symptoms in children with cCMV is complex, given the multiple morbidities than can occur. Peripheral vestibular causes should be considered in the diagnosis, as important vestibular deficits are demonstrated in this population.

Mutation update for the SATB2 gene.

SATB2-associated syndrome (SAS) is an autosomal dominant neurodevelopmental disorder caused by alterations in the SATB2 gene. Here we present a review of published pathogenic variants in the SATB2 gene to date and report 38 novel alterations found in 57 additional previously unreported individuals. Overall, we present a compilation of 120 unique variants identified in 155 unrelated families ranging from single nucleotide coding variants to genomic rearrangements distributed throughout the entire coding region of SATB2. Single nucleotide variants predicted to result in the occurrence of a premature stop codon were the most commonly seen (51/120 = 42.5%) followed by missense variants (31/120 = 25.8%). We review the rather limited functional characterization of pathogenic variants and discuss current understanding of the consequences of the different molecular alterations. We present an expansive phenotypic review along with novel genotype-phenotype correlations. Lastly, we discuss current knowledge of animal models and present future prospects. This review should help provide better guidance for the care of individuals diagnosed with SAS.

Neurodevelopmental outcome in very preterm and very-low-birthweight infants born over the past decade: a meta-analytic review.

AIM: The purpose of this systematic review was to provide an up-to-date global overview of the separate prevalences of motor and cognitive delays and cerebral palsy (CP) in very preterm (VPT) and very-low-birthweight (VLBW) infants. METHOD: A comprehensive search was conducted across four databases. Cohort studies reporting the prevalence of CP and motor or cognitive outcome from 18 months corrected age until 6 years of VPT or VLBW infants born after 2006 were included. Pooled prevalences were calculated with random-effects models. RESULTS: Thirty studies were retained, which included a total of 10 293 infants. The pooled prevalence of cognitive and motor delays, evaluated with developmental tests, was estimated at 16.9% (95% confidence interval [CI] 10.4-26.3) and 20.6% (95% CI 13.9-29.4%) respectively. Mild delays were more frequent than moderate-to-severe delays. Pooled prevalence of CP was estimated to be 6.8% (95% CI 5.5-8.4). Decreasing gestational age and birthweight resulted in higher prevalences. Lower pooled prevalences were found with the Third Edition of the Bayley Scales of Infant Development than with the Second Edition. INTERPRETATION: Even though neonatal intensive care has improved over recent decades, there is still a wide range of neurodevelopmental disabilities resulting from VPT and VLBW births. However, pooled prevalences of CP have diminished over the years. WHAT THIS PAPER ADDS: The Bayley Scales of Infant and Toddler Development, Third Edition reported lower pooled prevalences of motor and cognitive delays than the Second Edition. The pooled prevalence of cerebral palsy in infants born extremely preterm was reduced compared with previous meta-analyses.

FOXP1-related intellectual disability syndrome: a recognisable entity.

BACKGROUND: Mutations in forkhead box protein P1 (FOXP1) cause intellectual disability (ID) and specific language impairment (SLI), with or without autistic features (MIM: 613670). Despite multiple case reports no specific phenotype emerged so far. METHODS: We correlate clinical and molecular data of 25 novel and 23 previously reported patients with FOXP1 defects. We evaluated FOXP1 activity by an in vitro luciferase model and assessed protein stability in vitro by western blotting. RESULTS: Patients show ID, SLI, neuromotor delay (NMD) and recurrent facial features including a high broad forehead, bent downslanting palpebral fissures, ptosis and/or blepharophimosis and a bulbous nasal tip. Behavioural problems and autistic features are common. Brain, cardiac and urogenital malformations can be associated. More severe ID and NMD, sensorineural hearing loss and feeding difficulties are more common in patients with interstitial 3p deletions (14 patients) versus patients with monogenic FOXP1 defects (34 patients). Mutations result in impaired transcriptional repression and/or reduced protein stability. CONCLUSIONS: FOXP1-related ID syndrome is a recognisable entity with a wide clinical spectrum and frequent systemic involvement. Our data will be helpful to evaluate genotype-phenotype correlations when interpreting next-generation sequencing data obtained in patients with ID and/or SLI and will guide clinical management.

Language development of children born following intracytoplasmic sperm injection (ICSI) combined with assisted oocyte activation (AOA).

BACKGROUND: The effect of assisted reproduction technology (ART) on language development is still unclear. Moreover, different techniques are introduced at rapid pace and are not always accompanied by extensive follow-up programmes. AIMS: To investigate the language development of 3-10-year-old children born following ART using intracytoplasmic sperm injection (ICSI) combined with assisted oocyte activation (AOA), which is a highly specialized technique applied in cases with a history of fertilization failure following conventional ICSI. Secondly, a comparison is made between the language development of singletons and twins. METHODS & PROCEDURES: Twenty children, six boys and 14 girls, born following ICSI combined with AOA and older than 3 years were included in the study. The mean age of the children was 5;4 years (range = 3;1-10;4 years; SD = 1;8 years). Expressive and receptive language development were assessed using the Clinical Evaluation of Language Fundamentals (CELF-IV-NL) for children older than 5 years and the Reynell Developmental Language Scales (RTOS) for children younger than or equal to 5 years. OUTCOMES & RESULTS: The mean total score for language ability (in percentiles) was 56.8 (SD = 33.6), which corresponds to normal language skills. Significantly higher scores were found for AOA singletons compared with twins. For the general language, none of the children scored within the clinical zone for language disability corresponding with a percentile lower than 5. CONCLUSION & IMPLICATIONS: This study presents the first data concerning language outcome in 3-10-year-old children born following AOA. General language scores of the AOA children in this study are located within the normal ranges. The language development of singletons was significantly better compared with twins. Although the results are reassuring for language development, in future long-term follow-up studies in this population are necessary.

Exploring the role of neural mirroring in children with autism spectrum disorder.

Investigating the underlying neural mechanisms of autism spectrum disorder (ASD) has recently been influenced by the discovery of mirror neurons. These neurons, active during both observation and execution of actions, are thought to play a crucial role in imitation and other social-communicative skills that are often impaired in ASD. In the current electroencephalographic study, we investigated mu suppression, indicating neural mirroring in children with ASD between the ages of 24 and 48 months and age-matched typically developing children, during observation of goal-directed actions and non-goal-directed mimicked hand movements, as well as during action execution. Results revealed no significant group differences with significant central mu suppression in the ASD children and control children during both execution and observation of goal-directed actions and during observation of hand movements. Furthermore, no significant correlations between mu suppression on one hand and quality of imitation, age, and social communication questionnaire scores on the other hand were found. These findings challenge the "broken mirror" hypothesis of ASD, suggesting that impaired neural mirroring is not a distinctive feature of ASD.

Predictability of cerebral palsy and its characteristics through neonatal cranial ultrasound in a high-risk NICU population.

The aim of the study is to evaluate the predictive value of various types of brain injury detected by ultrasound in the neonatal period for the occurrence of cerebral palsy and its characteristics in a large cohort of high-risk infants. Thousand twenty-one consecutively NICU-admitted high-risk infants were assessed up to the corrected age of at least 2 years. Cerebral palsy (CP) was categorised into spastic or non-spastic, bilateral or unilateral and mild, moderate or severe CP. Different types of brain injury were identified by serial cranial ultrasound (US) during the NICU stay: white matter disease (WMD), haemorrhage, cerebral infarction, deep grey matter and parasagittal cerebral injury. There is a significant overall association between different types of brain injury and gestational age. Only 4% of the children with normal US develop CP. In the presence of any abnormal US image, the likeliness to develop CP is at least seven times higher. Within the group of infants with WMD and haemorrhage, the degree of brain involvement has a clear impact on the occurrence of CP. Concerning the characteristics of CP, deep grey matter lesion predict non-spastic CP versus spastic CP (OR = 31, P < 0.001). Cerebral infarction and haemorrhage grade IV are strong predictors of unilateral spastic CP versus bilateral spastic CP (OR = 49 and 24, respectively, P < 0.001). Deep grey matter lesion is a significant predictor for severe versus mild and moderate CP (OR = 6). In conclusion, neonatal cranial US is a useful tool in predicting CP and its characteristics.

Stability of motor problems in young children with or at risk of autism spectrum disorders, ADHD, and or developmental coordination disorder.

AIM: The aim of this study was to investigate the stability of motor problems in a clinically referred sample of children with, or at risk of, autism spectrum disorders (ASDs), attention-deficit-hyperactivity disorder (ADHD), and/or developmental coordination disorder (DCD). METHOD: Participants were 49 children (39 males, 10 females; mean age 5y 6 mo, SD 10 mo) with various developmental problems, a Movement Assessment Battery for Children (M-ABC) score on or below the 15th centile, and an IQ of 70 or more. Sixteen children were at risk of developing ADHD, 15 children had a diagnosis of, or were at risk of developing ASD, and 18 children had neither diagnosis. Children were reassessed 2 to 3 years later. RESULTS: At follow-up (mean age 7y 11 mo; SD 1y), the mean M-ABC score was significantly increased, and in 22 children was no longer below the 15th centile. A general linear model to compare the difference in M-ABC scores in the three groups of children demonstrated a significant difference between groups (p=0.013), with the age at the initial assessment as a significant covariate (p=0.052). The group of children with or at risk of ASD showed less improvement in motor performance. INTERPRETATION: Motor problems among preschool age children are not always stable, but appear to be so in most children with ASDs.

Influence of gestational age on nosologic CP characteristics in a high-risk population.

The aim of this study is to investigate the interrelationship between gestational age (GA) and nosologic characteristics (type, distribution and severity) of cerebral palsy (CP) in a cohort of high-risk infants. One thousand ninety-nine consecutively neonatal intensive care unit-admitted high-risk infants (i.e., all infants with a GA less than 30 weeks and specified infants with GA >or= 30 weeks with a complicated neonatal course and/or brain lesion) were prospectively assessed up to the corrected age of 2 years or more. In 177 (16%) of these infants, CP was diagnosed. Of these infants, 26 were extremely preterm infants (GA 23-27 weeks), 62 very preterm (28-31 weeks), 36 moderately preterm (32-36) and 53 term infants (GA >or= 37 weeks). Spastic CP was significantly more present in the three preterm groups (77%, 90% and 72%, respectively) compared with the term ones (42%). At variance, dyskinetic CP was present in nearly half of the term group (47%) and remarkably less in all three preterm age groups (12%, 7% and 22%, respectively). Ataxic CP (7%) was of rare occurrence in all age groups. Distributive classification showed that bilateral spastic CP gradually dropped from 100% in the extremely preterm group down to 50% in the term infants. Inversely, unilateral spastic CP rises steeply with advancing GA. Severity of CP was significantly associated with birth year period in favour of mild CP. In high-risk neonates, dyskinetic CP increases steeply with increasing GA, whereas spastic CP decreases. Bilateral and unilateral involvements are gradually and oppositely changing with gestational age. It is tempting to explain the maturity-related association by gestational age-specific brain injuries.

Delineation of a critical region on chromosome 18 for the del(18)(q12.2q21.1) syndrome.

Deletions involving the long arm of chromosome 18 have been reported in many patients. Most of these deletions are localized in the distal half of the long arm (18q21.1 --> qter) and are detectable by standard cytogenetic analysis. However, smaller interstitial deletions leading to a recognizable phenotype and residing in the region around chromosome band 18q12.3 (bands q12-q21) are less common. Here we report on an interstitial deletion of less than 1.8 Mb within chromosomal band 18q12.3. The phenotypic features of the propositus correspond well with those observed in patients with larger cytogenetically detectable deletions encompassing chromosome band 18q12.3. The deletion enabled us to define a critical region for the following features of the del(18)(q12.2q21.1) syndrome: hypotonia, expressive language delay, short stature, and behavioral problems.

Influence of gestational age on the type of brain injury and neuromotor outcome in high-risk neonates.

This study was an investigation of a possible correlation between either the gestational age (GA) and type of brain injury or between the gestational age and type, distribution and severity of cerebral palsy (CP). Four hundred sixty-one children with a birthweight > or = 1250 g and GA > or = 30 weeks with a complicated neonatal period and/or brain injury on serial cerebral ultrasound were selectively followed at the regional Center for Developmental Disorders. The children were divided into a preterm and term group. There were 40 children with cerebral palsy in the preterm group and 38 children with cerebral palsy in the term group. Various types of brain injury diagnosed by echography were nosologically classified. The type, distribution and severity of cerebral palsy were also registered. The type of brain injury most frequently occurring in the term group was hypoxic-ischemic injury to the basal ganglia (39%), focal ischemia (18%), subcortical hemorrhage (13%) and parasagittal cerebral injury (10%). In the preterm group 39% of the children with cerebral palsy had periventricular leukomalacia, 24% intraventricular hemorrhage and 18% persistent flares. There was a significant correlation between the GA and type of brain injury (P < 0.001; Cramer's V = 0.76) and between the GA and type (P = 0.004; Cramer's V = 0.47) and distribution (P < 0.001; Cramer's V = 0.55) of CP. There was no significant correlation between the GA and severity of CP. The type of brain injury detected by serial ultrasound during the neonatal period, as well as the type and location of CP detected during later childhood, are all GA-dependent in at-risk newborn infants with a birthweight of > or = 1,250 g and GA > or = 30 weeks.

Outcome at 3 years of age in a population-based cohort of extremely preterm infants.

OBJECTIVE: To assess health and neurodevelopmental outcome at 3 years of age in neonatal intensive care unit (NICU)-surviving children who were born at 26 or fewer weeks of gestation in a geographically defined region of Belgium from 1999 through 2000. METHODS: The study included a clinical examination and a standardized neurologic and developmental assessment. Disabilities were defined by international criteria. In 97% (92 of 95) of the children, accurate information on the presence of overall disability could be collected. RESULTS: Thirty-six percent (95% confidence interval [CI] 25-47%) of the formally assessed children (28 of 77) had deficient neuromotor development, with 5% of them showing severe sensory-communicative impairment. Mean (+/-standard deviation) scores on the Mental Developmental Index and Psychomotor Developmental Index were 81.2 (18.8) and 73.2 (17.8), respectively. Seventy percent (95% CI 60-80%) had a mental (Mental Developmental Index) or psychomotor (Psychomotor Developmental Index) impairment or both, assessed to be more than 1 standard deviation below the population mean. Mental and psychomotor outcome did not differ significantly when compared according to either gestational age, gender, or multiple birth (all P>.05). When either minor central dysfunction or cerebral palsy was not taken into account, normal mental development was recorded in 62% of the subjects. The cumulative of poor outcome (ie, disability- or prematurity-related death) among the 95 infants discharged alive was estimated to be 58% (95% CI 48-68%), representing 25 (26%) mildly-to-moderately disabled and 28 (29%) severely disabled toddlers, including two infants whose postdischarge deaths were directly related to prematurity. CONCLUSION: The average developmental outcome is poor in children born as extremely preterm infants. Finding early predictors of adverse outcome is a major challenge.