Neurodevelopmental Comorbidities Research Articles

Management and outcomes of cochlear implantation in patients with congenital cytomegalovirus (cCMV)-related deafness

Objective: Congenital Cytomegalovirus (cCMV) is a well-defined cause for neonatal mortality and morbidity, particularly sensorineural hearing loss and other neurodevelopmental disruption. We present a retrospective study which provides an overview of the assessment and preoperative work-up for patients diagnosed with cCMV and their cochlear implant (CI) outcomes.Method: This was a retrospective case series study of all children with a confirmed diagnosis of cCMV who underwent cochlear implantation at St Thomas’ Hospital from 2003 to 2015. Data were collected on the preoperative audiology, imaging findings, and neurological assessment. CI outcomes were measured using the Speech Intelligibility Rating (SIR), Category of Auditory Performance (CAP), and Infant-Toddler Meaningful Auditory Integration Scale (IT-MAIS).Results: Eleven patients underwent cochlear implantation, 45% had severe-to-profound hearing loss, and 55% had bilateral profound hearing loss. The mean age at initial assessment was 2.1 years (median 1.7, range 0.6–7.5) and the mean age of implantation was 4.0 years (median 2.5, range 0.9–11.8). The mean length of follow-up was 4.8 years (median 2.3, range 1.5–14). Six patients had bilateral simultaneous implantation (55%), four bilateral sequential (36%), and one unilateral (9%). Nine patients had white matter changes on magnetic resonance imaging, largely in the periventricular and cortical regions. Of the 11 patients, 4 (36%) had associated neurological comorbidities and 3 (27%) had additional neurocognitive developmental delay of varying severity. The majority of patients showed improvement in auditory outcomes. No statistically significant correlation was found between age of implantation, neurocognitive, and neurological comorbidities or length of follow-up and hearing outcomes.Conclusion: While the overall outcomes were mixed, most children in our cohort were found to benefit from cochlear implantation. Our data also highlight the significant neurodevelopmental comorbidities associated with cCMV and their negative impact on CI outcomes. With the recent advances in medical treatment, this underlines the importance of multidisciplinary management of these patients.

Register-based study of the incidence, comorbidities and demographics of obsessive-compulsive disorder in specialist healthcare

BackgroundIncidence of obsessive-compulsive disorder (OCD) has been suspected to increase but nationwide epidemiological studies are limited. This study aims to examine sex-specific incidence time trends and characterize psychiatric and neurodevelopmental comorbidities and sociodemographic risk factors of OCD in specialist healthcare in Finland.MethodsA nationwide register-based study using data from four Finnish registers identified 3372 OCD cases and 13,372 matched controls (1:4). Cumulative incidence in subjects born between 1987 and 2001 was estimated at ages of 10, 15, 20 and 23 years. Conditional logistic regression was used to examine the sociodemographic factors.ResultsThe cumulative incidence of OCD was 0.4% by age 23. Incidence by age 15 among three cohorts increased from 12.4 to 23.7 /10000 live born males and 8.5 to 28.0 /10000 live born females. 73% of the sample had a comorbid condition. Males were significantly more comorbid with psychotic and developmental disorders; females were more comorbid with depressive and anxiety disorders (p <0.001). Higher maternal SES was associated with an increased risk of OCD (OR 1.4; 95% CI 1.1–1.6).ConclusionsThese findings suggest that incidence of treated OCD in specialist healthcare has increased. The reason may be increased awareness and rate of referrals but a true increase cannot be ruled out. Further research on risk factors of OCD is warranted.

Epileptic Encephalopathies as Neurodegenerative Disorders.

The epileptic encephalopathies are severe and often treatment-resistant conditions that are associated with a progressive disturbance of brain function, resulting in a broad range of neurological and non-neurological comorbidities. The concept of epileptic encephalopathies entails that the encephalopathy aspect of the overall condition is primarily driven by the epileptic activity of the disease, which often manifests as specific and pathological features on the electroencephalogram. Genetic factors in epileptic encephalopathies are increasingly recognized. As of 2016, more than 30 genes have been securely implicated as causative genes for genetic epileptic encephalopathies. Even though the traditional concept of epileptic encephalopathies entails that the progressive disturbance of brain dysfunction is primarily due to the abnormal hypersynchronous activity that underlies the seizure disorders, this strict concept rarely holds true for patients with identified genetic etiologies. More commonly, an underlying genetic etiology is thought to predispose both to the neurodevelopmental comorbidities and to the seizure phenotype with a complex interaction between both. In this chapter, we will elucidate to what extent neurodegeneration rather than epilepsy-related regression is a feature of the common epileptic encephalopathies, drawing parallels between two relatively separate fields of neurogenetic research.

Behavioral health in young adults with epilepsy: Implications for transition of care.

Neurodevelopmental and behavioral health disorders commonly occur with epilepsy, yet risk for young adults is unknown. The aim of this study was to determine the distribution and risk characteristics of neurodevelopmental and behavior health comorbidities among young adults with epilepsy compared with those among young adults with migraine and healthy controls. A case-control study examining hospital admission, outpatient, and emergency department (ED) visits for young adults with an ICD-9-CM diagnosis of epilepsy, migraine, or lower extremity fracture (LEF) was conducted. The association of epilepsy, migraine, or LEF with comorbidities was evaluated with univariate and multivariate polytomous logistic regression. From 2000 to 2013, 29,139 young adults ages 19 to 25years were seen in hospitals and EDs for epilepsy (5666), migraine (17,507), or LEF (5966). Young adults with epilepsy had higher proportions of behavioral health comorbidities (51.8%) compared with controls with migraine (37.6%) or LEF (21.6%). In young adults with epilepsy compared with migraine, the increased risk of having any behavioral health comorbidity was 76%, and neurodevelopmental comorbidity was 297%. After adjustment, young adults with epilepsy showed significantly higher odds of each behavioral health comorbidity compared with controls with migraine and LEF. Young adults with epilepsy are particularly susceptible to behavioral health and neurodevelopmental disorders. Results are discussed within the context of transition to adult care.

Screening for maternal postpartum depression during infant hospitalizations.

Postpartum depression is common and adversely affects children of afflicted mothers; postpartum depression recognition and treatment may improve outcomes. Hospitalization represents a potential health encounter for expanding screening and intervention. We aimed to assess for postpartum depression at infant hospitalization and examine postpartum depression risk factors in this population. We conducted a prospective observational study of 310 English- or Spanish-speaking women with an infant aged 2 weeks to 1 year admitted to a pediatric hospitalist service at a large urban freestanding children's hospital. Mothers completed demographic questionnaires, a maternal-infant bonding scale, and the Edinburgh Postpartum Depression Scale (EPDS). Mothers with an EPDS score of 10 or higher (positive screen) received counseling and mental health referrals. Postenrollment calls followed trends in EPDS score and resource utilization. Multivariate logistic regression assessed relationships among risk factors and positive screens. Eighty-seven mothers (28%) were EPDS+. Only 14.6% reported appropriate prior depression screening. Maternal factors associated with EPDS+ were poor social support (4.40, interquartile range [IQR] = 2.27-8.53) and history of psychiatric diagnoses (5.02, IQR = 2.49-10.15). Having an infant with neurodevelopmental comorbidities was associated with EPDS+ screens (2.78, IQR = 1.03-7.52). Of 21 initially EPDS+ mothers reached by phone, 8 (38%) utilized their doctor or referral resource, resulting in lower EPDS scores (F(1,19) = 5.743, P < 0.05) compared to those not seeking help. Postpartum depression screening during infant hospitalizations captures women previously unscreened. Low social support, past psychiatric diagnoses, or having infants with neurodevelopmental problems may increase postpartum depression risk. Journal of Hospital Medicine 2015;11:840-846. © 2015 Society of Hospital Medicine.

Cognitive and neurodevelopmental comorbidities in paediatric epilepsy.

Cognitive and behavioural comorbidities are often seen in children with epilepsy, and are more common and severe in refractory epilepsy. These comorbidities are associated with worse quality of life, increased behavioural and language problems and worse social skills, all of which adversely affect long-term psychosocial functioning. To enable early intervention and therapy, children and teens with epilepsy should be periodically screened for cognitive comorbidities. The location of the epileptic focus can, to a certain degree, predict the type(s) of comorbidity; however, the spectrum of disability is often broad, presumably because focal perturbations can cause network dysfunction. Comorbidities often result from underlying structural or functional pathology that has led to seizures. In selected cases, therapy targeting the underlying cause, such as the ketogenic diet for GLUT1 deficiency syndromes, may be remarkably effective in ameliorating both seizures and cognitive concerns. In many cases, however, cognitive impairment persists despite seizure control. In epileptic encephalopathies, frequent seizures and/or interictal epileptiform abnormalities exacerbate neurocognitive dysfunction, owing to synaptic reorganization or impaired neurogenesis, or to other effects on developing neural circuits, and prompt initiation of effective antiepileptic therapy is essential to limit cognitive comorbidities.

Neurodevelopmental comorbidity profile in specific learning disorders

Background: Specific learning disorders (SLD) are the common reasons for referral of an otherwise healthy child from a main stream school. Although children do have difficulties even in early learning years in pre-primary and primary school; a significant number of preadolescent children from mainstream school do present with such disabilities. Primary objective was to study the differential distribution of various comorbidities across SLD spectrum. Secondary objective was to check for prevalence of abnormal neurological examination findings including soft signs. Methods: After approval of institutional ethics committee, 100 consecutive case records of children presenting to the center were studied. Diagnosis was confirmed as per DSM V criteria. The clinical, psychological and neurological information was derived from notes of pediatrician, after SLD certification. Details about history, ADHD and comorbidities if any were recorded from parents where documented information was not sufficient. The prevalence of comorbidities was expressed as a percentage of total cases studied. Results: ADD of combined type was the commonest comorbidity seen in 53% cases. Other occasional comorbidities noted were epilepsy, autism, cerebral palsy, history of meningitis and febrile seizures. Speech and visuospatial skills were affected 10% and 41% in children with SLD and all of these had ADD. Soft neurological signs like astereognosis, graphesthesia, dysdiadochokinesia, dysmetria were seen in more than 20% cases. Abnormal antenatal and perinatal history was more common in ADHD with SLD. Conclusions: SLD children from mainstream schools usually have ADHD as commonest comorbidity. Often they should be looked for various neurological comorbidites like autism, epilepsy, cerebral palsy. Soft signs and motor delay need not be overlooked in view of comprehensive management. A large multicentric study is needed to look for soft neurological signs; neuroimaging may be needed in SLD to understand the disorders in cognitive spectrum.

Population‐based comparative analysis of risk of death in children and adolescents with epilepsy and migraine

Follow-up studies of children and adolescents with epilepsy (CAW-E) have revealed higher risk of mortality than children in the general population. The mortality experience of CAW-E relative to patients with other common neurologic disorders in the pediatric age group is yet undetermined. The objectives of this study are the following: (1) to compare the causes and the adjusted risk of death in CAW-E with that of children and adolescents with migraine (CAW-M) in reference to children and adolescents with lower extremity fracture (CAW-LEF), and children and adolescents in the general population; (2) to evaluate if disparate mortality risks exist by demographic characteristics. This retrospective cohort study included 56,781 children and adolescents 0-18 years of age hospitalized or treated in an emergency or outpatient department from 2000 to 2011 for epilepsy, migraine, or lower extremity fracture from all nonfederal health care facilities. Data on deaths were acquired from linked multiple causes of death data file using person-specific unique identifiers. Time of follow-up was from initial clinical encounter to time of death or censoring date of December 31, 2011. The association of risk characteristics with mortality was examined with Cox proportional hazard model after adjusting for potential confounders. Four hundred forty-seven CAW-E and 125 CAW-M died yielding mortality rates of 8.71 and 1.36 per 1,000 person-years, respectively. The 5-year risk of death was 4.38% for CAW-E, 0.68% for CAW-M, and 0.71% for CAW-LEF. Adjusted hazard ratios (HRs) were 3.81 (95% confidence interval [CI] 3.08-3.72) in CAW-E and 1.14 (95% CI 0.94-1.34) in CAW-M relative to CAW-LEF. Risk of death from neurodevelopmental comorbidities was 5.86 (95% CI 4.24-8.08) times greater than those without in the model that compared epilepsy with LEF. There is an elevated risk of death in CAW-E with neurodevelopmental comorbidities that remains to be proven.

Risk factors for reading disability in families with rolandic epilepsy.

The high prevalence and impact of neurodevelopmental comorbidities in childhood epilepsy are now well known, as are the increased risks and familial aggregation of reading disability (RD) and speech sound disorder (SSD) in rolandic epilepsy (RE). The risk factors for RD in the general population include male sex, SSD, and ADHD, but it is not known if these are the same in RE or whether there is a contributory role of seizure and treatment-related variables. An observational study of 108 probands with RE (age range: 3.6-22 years) and their 159 siblings (age range: 1-29 years; 83 with EEG data) were singly ascertained in the US or UK through a proband affected by RE. We used a nested case-control design, multiple logistic regression, and generalized estimating equations to test the hypothesis of an association between RD and seizure variables or antiepileptic drug treatment in RE; we also assessed an association between EEG focal sharp waves and RD in siblings. Reading disability was reported in 42% of probands and 22% of siblings. Among probands, RD was strongly associated with a history of SSD (OR: 9.64, 95% CI: 2.45-37.21), ADHD symptoms (OR: 10.31, 95% CI: 2.15-49.44), and male sex (OR: 3.62, 95% CI: 1.11-11.75) but not with seizure or treatment variables. Among siblings, RD was independently associated only with SSD (OR: 4.30, 95% CI: 1.42-13.0) and not with the presence of interictal EEG focal sharp waves. The principal risk factors for RD in RE are SSD, ADHD, and male sex, the same risk factors as for RD without epilepsy. Seizure or treatment variables do not appear to be important risk factors for RD in probands with RE, and there was no evidence to support interictal EEG focal sharp waves as a risk factor for RD in siblings. Future studies should focus on the precise neuropsychological characterization of RD in families with RE and on the effectiveness of standard oral-language and reading interventions.

PP10.1 – 3049: The incidence of autistic spectrum disorder in a cohort of 213 prematurely born children

Objective Preterm birth is emerging as a major health problem in the developed world. A significant modern risk factor is the widespread use of assisted reproductive technology (ART). We aim to prospectively study the additional risk of ART for developing autistic spectrum disorder (ASD) in comparison to naturally conceived preterm. Methods We prospectively followed 213 children of a cohort of 283 very low birth weight newborns born between 1998 and 2002. Their mean age was 12.8 years, 46% were males and 56% were the result of multiple pregnancies. 33% were conceived by ART while the mean gestational age was 30.8±2.4 and the mean birth weight was 1237±266 grams. The medical charts of all the participants were reviewed for neonatal complications, developmental milestones and current behavioral diagnoses. ASD was assessed using the A.S.S.Q. (Autism Spectrum Screening Questionnaire). Results The incidence of ASD was 24/213 (11.3%) and other neurodevelopmental comorbidities were: attention deficit hyperactivity disorder (ADHD, 26%), learning disabilities (25%), cerebral palsy (CP, 11%), epilepsy (6%) and intellectual disability (3%). No significant differences were found in the incidence of ASD and other neurodevelopmental comorbidities between the ART and naturally conceived groups. The ASD and non-ASD groups did not differ in birth weight, gestational age and Apgar score. However, significant differences were found for male gender (p=0.015), ADHD (p=0.085), epilepsy (p=0.033) and intellectual disability (ID, p=0.004). Conclusion We found the incidence of ASD in a cohort of preterms to be approximately ten times the incidence reported in the general Israeli population. ART was not found to be a risk factor for any neurodevelopmental disorder. ASD was not found to be associated with a lower Apgar score or CP. The association between ASD and male gender, ADHD, epilepsy and ID is well known and also evident in our cohort.

The incidence of unprovoked seizures and occurrence of neurodevelopmental comorbidities in children at the time of their first epileptic seizure and during the subsequent six months

To evaluate the incidence of unprovoked seizures in children and the prevalence of related neurodevelopmental comorbidities at the time of the presumed first seizure and six months thereafter. The medical records of all children (0-18 years of age) seeking medical attention as the result of a first unprovoked seizure between September 1, 2001 and December 31, 2006, and registered in the population-based Stockholm Incidence Registry of Epilepsy (SIRE) were reviewed. Neurodevelopmental comorbidities were evaluated on the basis of the medical records from this first visit and from other healthcare during the following six months. The incidence of unprovoked seizures was between 30 and 204/100,000 person years (n=766) in the different age groups. It was highest among the youngest children and lowest among the 18-year-olds with small gender differences. The most common neurodevelopment comorbidities were developmental delay (22%, CI: 19-25%), speech/language and learning difficulties (23%, CI: 20-26%) and intellectual disability (16%, CI: 13-18%). The types of neurodevelopmental comorbidity varied by age at the time of seizure onset, with cerebral palsy being more common among the 0-5-year-olds, attention deficits among the 6-16-year-olds, and autism and psychiatric diagnosis among the older children. An associated neurodevelopmental comorbidity was more common among those experiencing recurrent than single seizures during follow-up six months from the index seizure (42% versus 66%). In 68% (CI: 64-71%) of the children there was no known or suspected neurodevelopmental comorbidity. The incidence of unprovoked, non-febrile seizures among 0-18-year-olds included in the SIRE was 67/100,000 person-years. Neurodevelopmental comorbidities were common already at the time of onset of the seizure disorder, indicating that neither seizure treatment nor seizures were the underlying cause of other neurodevelopmental symptoms in these patients during the period studied.

Neurodevelopmental and neurobehavioral aspects of childhood epilepsy

Objective The aim of this study was to declare the frequency of neurodevelopmental, behavioral, and psychiatric comorbidities associated with epilepsy and the relation of these disorders with several variables, including age at onset of epilepsy, duration of epilepsy, type of epilepsy, antiepileptic medications (monotherapy or polytherapy), and seizure frequency. Patients and methods This cross-sectional study included 50 epileptic children selected from those regularly attending the Neurology Outpatient Clinic in Mansoura University Children Hospital and already diagnosed with primary epilepsy and maintained on antiepileptic medications. They were subjected to full general and neurological assessment, Wechsler Intelligence Scale (IQ), Child Behavior Checklist, and Developmental Profile-3. Data were analyzed using SPSS program, version 16. Results Children with prolonged duration and earlier onset of epilepsy performed worse on Developmental Profile-3 assessment as they showed significantly delayed cognition, in addition to more attention problems and low IQ. Increased frequency associated with delayed cognitive, social, and communication development, low IQ, and attention problems were observed. Moreover, those with polytherapy were more significantly affected as regards cognition, communication, IQ, attention, social problems, thought problems, and anxiety depression. No significant differences were found between effects of sodium valproate and carbamazepine, but a high dose of valproate was associated with higher incidence of low IQ and cognitive and attention problems. Cognition, communication, and attention were more affected in patients with generalized epilepsy in comparison with those with partial epilepsy. Conclusion Childhood epilepsy is associated with cognitive deficits, intellectual decline, and behavioral problems, which are multifactorial, such as age of onset, frequency, type of seizure, prolonged seizures, antiepileptic drugs, and duration of epilepsy.

Epilepsy beyond seizure: A population-based study of comorbidities

Comorbid conditions may affect the quality of life in persons with epilepsy (PWE) more than seizures. Using legally mandated healthcare encounter data, somatic, psychiatric, and neurodevelopmental comorbidities in a large population-based cohort of PWE, were compared to persons with migraine (PWM), a similar neurologic condition, and lower extremity fracture (PWLF), otherwise healthy controls. 64,188 PWE, 121,990 PWM, and 89,808 PWLF were identified from inpatient, outpatient, and emergency department from 2000 to 2011. Epilepsy was ascertained with ICD-9-CM code 345; migraine with 346; fracture of the tibia, fibula, and ankle with 823 and 824. Common comorbidities of epilepsy were identified from the literature. Differences in prevalence among PWE, PWM, and PWLF were assessed by comparison of 95% confidence intervals (CI) constructed under the assumption of independence and normal approximation. The association of the comorbid conditions with epilepsy and migraine, compared to lower extremity fracture, were evaluated with polytomous logistic regression controlling for demographic and mortality covariables. PWE had significantly elevated prevalence of comorbidities compared with PWM and PWLF. Compared with PWLF, the adjusted odds ratios (OR) of having both somatic and psychiatric/neurodevelopmental comorbidities were 5.44 (95% CI=5.25-5.63) and 2.49 (95% CI=2.42-2.55) in PWE and PWM, respectively. The association with epilepsy was the strongest for cognitive dysfunction (OR=28.1; 95% CI=23.3-33.8); autism spectrum disorders (OR=22.2; 95% CI=16.8-29.3); intellectual disability (OR=12.9; 95% CI=11.6-14.3); and stroke (OR=4.2; 95% CI=4.1-4.4). The absolute risk increase in PWE compared with PWM for any somatic or psychiatric/neurodevelopmental comorbidity was 58.8% and 94.3%, respectively. Identifying comorbidities that are strongly and consistently associated with seizures, particularly disorders with shared underlying pathophysiology, is critical in identifying specific research and practice goals that may ultimately improve the quality of life for PWE. This study contributes to that effort by providing population-based comorbidity data for PWE compared with PWM and PWLF.

Epilepsy and psychiatric comorbidity: A nationally representative population‐based study

In a nationally representative population-based study in England, we estimated the burden of psychiatric and neurodevelopmental comorbidities in people with epilepsy. We investigated whether any overrepresentation of comorbidities could be explained by epilepsy being a chronic medical or neurologic condition, or by the confounding effect of demographic and socioeconomic factors or other health conditions. The Adult Psychiatric Morbidity Survey 2007 comprised detailed interviews with 7,403 individuals living in private households in England. Doctor-diagnosed epilepsy (and asthma, diabetes, and migraine, chronic conditions for comparison) was ascertained by self-report, and extensive diagnostic and screening interviews were used to assess psychiatric and neurodevelopmental conditions. The estimated lifetime prevalence of epilepsy in the adult (≥ 16 years old) population of England was 1.2% (95% confidence interval [CI] 1.0-1.5). Almost one-third of the people with epilepsy had an International Classification of Diseases, Tenth Revision (ICD-10) anxiety or depressive disorder (compared with one in six people without epilepsy). Among these, social phobia and agoraphobia, generalized anxiety disorder, depression, and measures of suicidality had strong associations with epilepsy, which remained robust after accounting for potential confounders. These associations were consistently stronger than those in people with asthma or diabetes, and similar to those in people reporting migraine or chronic headaches. Epilepsy was also strongly associated with autism spectrum disorders (odds ratio [OR] 7.4, 95% CI 1.5-35.5) and possible eating disorders, and these associations were not evident in people with asthma, diabetes, or migraine. Psychiatric and neurodevelopmental conditions were overrepresented in people with epilepsy. These associations were stronger than with other nonneurologic chronic conditions, and not explained by confounding. Some overlap in the psychopathology observed in epilepsy and migraine cannot rule out the presence of common pathways of psychiatric comorbidity in neurologic conditions. However, associations of epilepsy with conditions such as autism spectrum disorders point to comorbidities specific to epilepsy that may not be shared by other neurologic conditions.

Pre-existing neurodevelopmental and neuropsychiatric difficulties in children with brain tumours: implications for future outcome studies

SIR–In recent months there has been renewed interest in promoting the early detection of brain tumours in children. Delay in the diagnosis of brain tumours causes distress to the patient, their family, and the clinician. Studies into the presenting features of children with newly diagnosed brain tumours have tended to concentrate on identifying discriminatory signs or symptoms in the child which would prompt earlier referral for further investigation. We would like to highlight our own observations about the importance of careful screening in these newly diagnosed patients for neurodevelopmental problems. Outcome studies in children with brain tumours have tended to concentrate on survival rates and on cognitive and developmental measures post treatment. There is currently a relative paucity of information regarding neurodevelopmental and neuropsychiatric disorders in children presenting with brain tumours prior to the commencement of treatment. Our paediatric Neuro-oncology Multidisciplinary Team thinks that there is a high prevalence of pre-existing neurodevelopmental and neuropsychiatric problems in children with brain tumours before treatment is started. We would suggest that the early identification of these problems has important implications both for the management of the individual child and for future outcome studies. We reviewed the clinical notes and neurodevelopmental histories of all children with newly diagnosed brain tumours presenting to our service between July 2006 and November 2009. During this period 131 children with newly diagnosed brain tumours were identified. In 13 out of 131 (9.9%) of these patients a pre-existing neurodevelopmental problem was documented (Table SI published online only). In all cases children had been under follow up by local Paediatric and Community Paediatric services. Diagnoses of speech and developmental delay had been made following assessment by these services, including use of the Griffiths Mental Development Scales. Particularly striking was the 6 out of 131 (4.6%) children with documented autistic spectrum disorders (ASDs), well above the 1% prevalence expected in the general population. These diagnoses were made following comprehensive patient multidisciplinary assessment, including either the 3Di computer assessment, the Autism Diagnostic Interview or the Diagnostic Interview for Social and Communication Disorders. In a number of children longstanding psychiatric comorbidity was also documented. As might be expected, a number of these children had confirmed diagnosis of tuberous sclerosis (n=4) or neurofibromatosis (n=2), conditions pre-disposing to both tumour development and neurodevelopmental problems. In a number of children no such predisposition could be found. It is uncertain to what extents direct tumour effects contributed to the neurodevelopmental problems for each individual child. There may be an as yet unrecognised genetic predisposition to both tumour and developmental problem. We believe that our case series demonstrates a high prevalence of neurodevelopmental problems, particularly ASDs, in children presenting with newly diagnosed brain tumours. We welcome ongoing work to promote the early identification of children with brain tumours and would like to take the opportunity to encourage clinicians involved in the management of these patients to consider routine screening for neurodevelopmental problems and psychiatric comorbidity in order to help determine the true prevalence of these problems in this important patient group.

Late Morbidity During Childhood and Adolescence in Previously Premature Neonates After Patent Ductus Arteriosus Closure

The health status of previously premature neonates after closure of a patent ductus arteriosus (PDA) was analyzed in childhood and adolescence. Physician questionnaires were used to study 180 hospital survivors among 210 consecutive premature neonates who underwent PDA closure between 1985 and 2005. Complete follow-up data were obtained for 129 patients (72%). During a median follow-up period of 7 years (range, 2-22 years), three late deaths (2.3%) had occurred. Only 45% of the patients were considered healthy. Morbidity included developmental delay (41.1%), pulmonary illness (12.4%), neurologic impairment (14.7%), hearing impairment (3.9%), gastrointestinal disease (3.1%), and thoracic deformity (1.2%). None of the adverse variables during the neonatal period (intraventricular hemorrhage, bradycardia apnea syndrome, bronchopulmonary dysplasia, pulmonary bleeding, hyaline membrane disease, artificial respiration time [continuous positive airway pressure + intubation], or necrotizing enterocolitis) statistically predicted respective system morbidity at the follow-up evaluation. Hyaline membrane disease (odds ratio, 2.5; p = 0.026) and longer hospitalization time (odds ratio, 1.2 days per 10 hospitalization days; p = 0.032) in the newborn period were significant predictors of an unhealthy outcome at the last follow-up evaluation. Survival until childhood after closure of a hemodynamically significant PDA in premature neonates is satisfactory. However, physical and neurodevelopmental co-morbidity persist for half of the patients, perhaps as a sequela of prematurity unrelated to ductus closure.