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1.
Seizure ; 112: 128-138, 2023 Nov.
Article En | MEDLINE | ID: mdl-37832279

OBJECTIVE: To describe the evolution in use and cost of antiseizure medications (ASM) in the United States of America (USA). METHODS: Retrospective descriptive study using the IBM MarketScan Commercial Database (data of privately-insured patients) for the years 2006 to 2021. We identified patients with epilepsy who were on ASM. We adjusted cost for inflation with the Gross Domestic Product Implicit Price Deflator. RESULTS: We evaluated 347,158 patients (46.9 % males; median (p25-p75) age: 33 (17-49) years; 28 % with pediatric-onset epilepsy and 72 % with adult-onset epilepsy) with a total of 1,385,382 person-years and 588,285,065 ASM prescription days. The most commonly prescribed (as percentage of prescription days) ASMs in 2006 were valproate (18 %) and lamotrigine (17 %) in pediatric-onset epilepsy and phenytoin (21 %) and carbamazepine (17 %) in adult-onset epilepsy, but starting in the 2010s, levetiracetam and lamotrigine became the most commonly prescribed ASMs in both pediatric-onset (in 2021, levetiracetam 25 %, lamotrigine 16 %) and adult-onset (in 2021, levetiracetam 27 %, lamotrigine 20 %) epilepsy. The proportion of generic ASM use increased 3.6-fold: from 23 % of prescription days in 2006 to 83 % of prescription days in 2021. The median (p25-p75) average wholesale price (AWP) per person-year increased by 102 % from $2,684 ($990-$5,509) in 2006 to $5,417 ($2,858-$12,310) in 2021. The increases were greater in absolute terms for brand-name ASMs by 419 %: $3,109 ($1,564-$5,068 in 2006 and $16,149 ($12,950-$23,377) in 2021 than for generic ASMs by 462 %: $699 ($457-$1,678) in 2006 and $3,931 ($2,618-$6,081) in 2021. The costs directly borne by the patient (copay, coinsurance, deductibles, and pharmacy processing fees) increased by 69 % for brand-name ASMs from $393 ($246-$570) in 2006 to $665 ($335-$1,308) in 2021, but decreased by 37 % for generic ASMs from $147 ($98-$213) in 2006 to $92 ($51-$141) in 2021. CONCLUSIONS: The median cost of ASMs per person-year approximately doubled from 2006 to 2021. The increase in use of generic ASMs probably helped buffer the growing costs of ASMs. However, generic ASMs already represent 83 % of prescription days in 2021, with limited room to further contain costs by just increasing the proportion of generics.


Epilepsy , Phenytoin , Adult , Male , Child , Humans , Female , Lamotrigine , Levetiracetam , Retrospective Studies , Drugs, Generic/therapeutic use , Epilepsy/drug therapy , Epilepsy/epidemiology , Anticonvulsants/therapeutic use
2.
Epilepsy Behav ; 122: 108182, 2021 09.
Article En | MEDLINE | ID: mdl-34256339

PURPOSE: The purpose of this study was to create and test an animated video to teach adolescent patients about Sudden Unexpected Death in Epilepsy (SUDEP). METHOD: Thirty-nine patients and thirteen parents watched the SUDEP video and completed at least one survey. Patients with epilepsy aged 14+ and their parents were recruited to watch the video during neurology clinic visits. Parents of minors provided verbal permission for their child to view the video. Participants were asked to complete pre- and post-video surveys. Data analysis included Fischer's exact tests for comparative data and percentages for categorical variables. RESULTS: After watching the SUDEP video, 100% of parents and patients agreed that the video provided helpful knowledge, and 100% of parents and 96% of patients agreed that patients with epilepsy should know about SUDEP. Half of the parents surveyed, and 20% of patients, felt increased concerns after watching the video. Patients rated their understanding of SUDEP significantly higher after watching the video (p < 0.001). CONCLUSION: Participants in this study thought that it was important for patients with epilepsy to know about SUDEP, and all agreed that the animated SUDEP video provided helpful knowledge. While some parents endorsed increased concerns after watching the video, the majority of parents still agreed to allow their child to watch the video. Adolescent education on SUDEP using a family-centered approach may be an important method of encouraging harm-reducing behaviors that can be lifesaving for patients with epilepsy. The standard of practice for SUDEP disclosure should continue to be face-to-face discussion with providers, and we propose this video as a tool to elevate and inform those discussions.


Epilepsy , Sudden Unexpected Death in Epilepsy , Adolescent , Child , Death, Sudden , Epilepsy/complications , Humans , Parents , Risk Factors
3.
J Pediatr ; 237: 197-205.e4, 2021 10.
Article En | MEDLINE | ID: mdl-34090894

OBJECTIVE: To examine the association between neonatal cranial ultrasound (CUS) abnormalities among infants born extremely preterm and neurodevelopmental outcomes at 10 years of age. STUDY DESIGN: In a multicenter birth cohort of infants born at <28 weeks of gestation, 889 of 1198 survivors were evaluated for neurologic, cognitive, and behavioral outcomes at 10 years of age. Sonographic markers of white matter damage (WMD) included echolucencies in the brain parenchyma and moderate to severe ventricular enlargement. Neonatal CUS findings were classified as intraventricular hemorrhage (IVH) without WMD, IVH with WMD, WMD without IVH, and neither IVH nor WMD. RESULTS: WMD without IVH was associated with an increased risk of cognitive impairment (OR 3.5, 95% CI 1.7, 7.4), cerebral palsy (OR 14.3, 95% CI 6.5, 31.5), and epilepsy (OR 6.9; 95% CI 2.9, 16.8). Similar associations were found for WMD accompanied by IVH. Isolated IVH was not significantly associated these outcomes. CONCLUSIONS: Among children born extremely preterm, CUS abnormalities, particularly those indicative of WMD, are predictive of neurodevelopmental impairments at 10 years of age. The strongest associations were found with cerebral palsy.


Cerebral Intraventricular Hemorrhage/complications , Cerebral Intraventricular Hemorrhage/diagnostic imaging , Infant, Premature, Diseases/diagnostic imaging , Leukoencephalopathies/complications , Leukoencephalopathies/diagnostic imaging , Neurodevelopmental Disorders/epidemiology , Age Factors , Cerebral Intraventricular Hemorrhage/therapy , Child , Cohort Studies , Critical Care , Echoencephalography , Female , Hospitalization , Humans , Infant, Extremely Premature , Infant, Newborn , Infant, Premature, Diseases/therapy , Leukoencephalopathies/therapy , Male , Neurodevelopmental Disorders/diagnosis , United States
4.
Pediatrics ; 147(5)2021 05.
Article En | MEDLINE | ID: mdl-33824183

OBJECTIVES: Evidence-based care of extremely preterm infants (<28 weeks' gestation) depends heavily on research in which a primary outcome is infant neurodevelopmental impairment (NDI), yet it is unclear how well NDI in infancy predicts long-term NDI. In this study, we aim to assess the relationship between 2- and 10-year neurodevelopment using a well-known 2-year definition and a 10-year definition developed by an expert panel. METHODS: Using data from the Extremely Low Gestational Age Newborn Study cohort, we classified 2-year NDI using definitions developed by the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network. We classified 10-year NDI using definitions developed by an expert panel, which added epilepsy and ASD at 10 years. RESULTS: Of 1506 infants, 80% survived. Data sufficient to classify severity of NDI at both 2 and 10 years were available for 67% of survivors (n = 802). Among children classified as having moderate to severe NDI at 2 years, 63% had none to mild NDI at 10 years; among children classified as having profound NDI at 2 years, 36% had none to mild NDI at 10 years. Cohen's κ statistic indicated minimal to fair agreement between NDI at 2 and 10 years (0.34, P < .001). CONCLUSIONS: NDI in infancy, as defined in this study, only weakly predicts NDI in middle childhood. For the parents at risk for delivery of an extremely preterm infant, a hopeful message can be taken from our findings that one-third of surviving children classified as having profound NDI and nearly two-thirds of those classified as having moderate to severe NDI at 2 years had none to mild NDI at 10 years.


Neurodevelopmental Disorders/classification , Child , Child, Preschool , Cohort Studies , Female , Humans , Infant, Extremely Premature , Male , Severity of Illness Index
5.
J Pediatr Psychol ; 46(4): 422-432, 2021 04 16.
Article En | MEDLINE | ID: mdl-33398339

Objective Anxiety and depression rates are known to be elevated in prematurely-born children and adolescents. This prospective study examines demographic, academic, and physical health correlates of anxiety and depression symptoms in a sample of 10-year-old children who were born extremely preterm. Methods Participants were 889 (51.2% male; 62.3% White) children who were born <28 weeks gestation. Child and family demographic data were collected at birth. When the children were 10, parents (n = 871) and teachers (n = 640) rated the level of anxiety and depression in children through the Child Symptom Inventory-4. Child academic functioning was assessed via the Wechsler Individual Achievement Test-III. Parents completed questionnaires about child academic functioning and physical health issues. Data analyses were conducted with multivariate linear modeling. Results Level of prematurity was significantly related to both parent and teacher reports of anxiety. Public health insurance and individualized education program (IEP) status were associated with both parent and teacher reports of depression. Hispanic ethnicity, public insurance, IEP status, and asthma were significantly associated with both parent-reported anxiety and depression. Gross motor impairment was associated with parent-reported anxiety and teacher-reported depression. Child obesity was associated with teacher reports of anxiety, while male sex was significantly related to teacher reports of depression. Conclusion This pattern of findings may suggest hypotheses for future research on models of the development and persistence of anxiety and depression within this particularly vulnerable group of children.


Child Behavior Disorders , Depression , Adolescent , Anxiety/diagnosis , Anxiety/epidemiology , Child , Depression/diagnosis , Depression/epidemiology , Female , Humans , Infant, Extremely Premature , Infant, Newborn , Male , Parents , Prospective Studies
6.
J Child Neurol ; 36(6): 461-467, 2021 05.
Article En | MEDLINE | ID: mdl-33336600

BACKGROUND: We developed and validated a Spanish seizure screen for children based on a previously validated English seizure screen that could be administered by a trained research assistant in a 2-step process, approximating the clinical diagnostic process of a pediatric epilepsy specialist. This questionnaire was designed to study seizure prevalence in a research population of children at risk for epilepsy. METHODS: Spanish-speaking parents of children 6 months to 17 years old were recruited from the pediatric neurology clinics at Boston Medical Center and interviewed using a computerized questionnaire. A computerized algorithm of parent responses rendered a seizure classification of positive or negative. Blinded to questionnaire results, pediatric neurologists served as the diagnostic gold standard, ranking each patient event using a 4-level scale based on clinical history and examination: (1) not likely, (2) indeterminate, (3) probable, and (4) almost certain where rankings of 3 or 4 lead to a diagnosis of seizure. RESULTS: The questionnaire was completed by 163 enrolled parents. The seizure screen demonstrated a 94.2% sensitivity and 93.7% specificity for identifying seizures. The positive predictive value was 87.5%, and the negative predictive value was 97.2%. CONCLUSIONS: This pediatric seizure questionnaire was both sensitive and specific for detecting clinically confirmed seizures. This tool may be useful to clinicians and researchers in screening large populations of children, decreasing the time and cost of added neurologic assessments.


Parents , Seizures/diagnosis , Surveys and Questionnaires/standards , Adolescent , Adult , Child , Female , Hispanic or Latino , Humans , Language , Male , Reproducibility of Results , Sensitivity and Specificity , Translations
8.
Semin Pediatr Neurol ; 36: 100857, 2020 Dec.
Article En | MEDLINE | ID: mdl-33308521

This article aims to highlight the impact of mentorship on the lives of youth with chronic conditions (YCC). Here, we focus on the concepts of mentoring and technology as a means to support transitioning YCC. This is in response to the urgent need for effective healthcare transition strategies and the increasing importance and prevalence of technology in healthcare and health systems. This article also highlights an e-mentoring program for youth with epilepsy, an intervention that bridges the fields of mentoring, transition, and technology. While there is need for further research in these areas, consideration of these factors are highly relevant to the effort to improve health for this generation of YCC.


Mentoring , Nervous System Diseases/therapy , Social Support , Telemedicine , Transition to Adult Care , Adolescent , Adult , Chronic Disease , Humans , Young Adult
9.
Semin Pediatr Neurol ; 36: 100856, 2020 Dec.
Article En | MEDLINE | ID: mdl-33308524

Mental health disorders are prevalent in patients with epilepsy, and adolescents are at particularly high risk. The reason for higher rates of anxiety, depression and suicide in young patients with epilepsy is likely multifactorial, and therefore the approach to treatment has proven challenging. In this review, we discuss important mental health topics for adolescents and young adults with epilepsy, as well as evidence for management. In the past several years, advances have been made in the transition of epilepsy care from pediatric to adult providers, creating a promising method for epilepsy patient engagement and empowerment. Future research into the mental health outcomes from these transition programs may lead to better strategies to support young patients with epilepsy.


Epilepsy/therapy , Mental Disorders/therapy , Transition to Adult Care , Adolescent , Adult , Comorbidity , Epilepsy/epidemiology , Humans , Mental Disorders/epidemiology , Young Adult
10.
Pediatr Clin North Am ; 67(4): 629-634, 2020 08.
Article En | MEDLINE | ID: mdl-32650859

A team of providers, researchers, patients, and families created a novel telehealth tool to improve communication across a variety of systems involved in pediatric epilepsy care. This tool facilitates in-home telemedicine appointments and saves costs for patients and hospital systems alike within the context of a population highly affected by health care disparities.


Epilepsy/therapy , Telemedicine/methods , Adolescent , Child , Communication , Epilepsy/economics , Healthcare Disparities , Humans , Patient-Centered Care , Telemedicine/economics , Videoconferencing
11.
Am J Obstet Gynecol ; 223(5): 745.e1-745.e10, 2020 11.
Article En | MEDLINE | ID: mdl-32387324

BACKGROUND: Extremely preterm infants whose placenta had histologic evidence of chorioamnionitis have early brain dysfunction, but little is known about neurologic development at 10 years of age. OBJECTIVE: We investigated the association between histologic chorioamnionitis and neurodevelopmental impairment at 10 years among children born <28 weeks' gestation (extremely preterm). STUDY DESIGN: The multicenter Extremely Low Gestational Age Newborns study enrolled extremely preterm newborns from 2002 to 2004 at 14 hospitals in the United States. Chorioamnionitis was defined by histologic stage (early, moderate, and advanced) and grade (mild/moderate and severe) of chorionic plate and umbilical cord inflammation. The children were examined for cerebral palsy at 2 years and for autism spectrum disorder, cognitive impairment (intelligence quotient >2 standard deviations below the mean), and epilepsy at the age of 10 years by blinded evaluators using validated measures. Multivariable logistic regression with generalized estimating equations was used. RESULTS: Among 805 placentas, 43% (347/805) had histologic chorioamnionitis by moderate or advanced maternal stage, 36% (286/805) by severe maternal grade, 18% (132/737) by moderate or advanced fetal stage, and 1% (10/737) by severe fetal grade. The frequencies of impairments were 11% (88/767) for cerebral palsy, 7% (56/773) for autism spectrum disorder, 15% (120/788) for cognitive impairment, and 7% (52/763) for epilepsy. After adjustment for maternal age, body mass index, race, insurance status, maternal education, tobacco use, infant sex, and multiple gestations, the adjusted odds ratio for the association between histologic chorioamnionitis and cerebral palsy years was increased with advanced maternal stage (adjusted odds ratio, 2.5; 95% confidence interval, 1.6-3.9), severe maternal grade (adjusted odds ratio, 2.0; 95% confidence interval, 1.2-3.4), moderate fetal stage (adjusted odds ratio, 2.20; 95% confidence interval, 2.1-2.2), and mild or moderate fetal grade (adjusted odds ratio, 1.5; 95% confidence interval, 1.0-2.2). Similarly, the adjusted odds ratio for the association between histologic chorioamnionitis and epilepsy was increased with advanced maternal stage (adjusted odds ratio, 1.5; 95% confidence interval, 1.3-1.6) and severe fetal grade (adjusted odds ratio, 5.9; 95% confidence interval, 1.9-17.8). In addition, the adjusted odds ratio for the association between histologic chorioamnionitis and autism spectrum disorder was increased with mild or moderate fetal grade (adjusted odds ratio, 1.7; 95% confidence interval, 1.0-2.9). Histologic chorioamnionitis was not associated with cognitive impairment. These findings held after adjustment for gestational age at delivery. In contrast to histologic chorioamnionitis, a clinical diagnosis of chorioamnionitis was not associated with neurodevelopmental impairment. CONCLUSION: Histologic chorioamnionitis may be associated with some forms of neurodevelopmental impairment at 10 years of life among infants born <28 weeks' gestation.


Autism Spectrum Disorder/epidemiology , Cerebral Palsy/epidemiology , Chorioamnionitis/epidemiology , Cognitive Dysfunction/epidemiology , Epilepsy/epidemiology , Intellectual Disability/epidemiology , Adult , Child , Chorioamnionitis/pathology , Female , Humans , Infant, Extremely Premature , Infant, Newborn , Neurodevelopmental Disorders/epidemiology , Pregnancy , Prospective Studies , Severity of Illness Index , United States/epidemiology , Young Adult
12.
J Child Neurol ; 35(7): 485-491, 2020 06.
Article En | MEDLINE | ID: mdl-32207663

BACKGROUND: This study evaluated the effectiveness of a parent-completed questionnaire for detecting seizures in high-risk children. METHODS: A 2-part seizure screen for children up to 12 years of age with suspected autism spectrum disorder, developmental delay, or seizure, was implemented in 12 Massachusetts clinics serving populations with high health disparities. Primary care providers and developmental behavioral pediatricians administered part 1, a brief highly sensitive screen. If the result was positive, a research assistant administered part 2, a more detailed screen with higher specificity. Positive part 2 results prompted a specialized assessment by a pediatric neurologist. Screening data were evaluated for detection of seizures or other diagnoses, reason for conducting the screen, and appointment outcomes. Data analysis included chi-squared tests, percentages for categorical variables, and means for numerical data. RESULTS: Of 207 administered seizure questionnaires, 78% of children screened positive on part 1. Of those, 94% of families completed part 2 by telephone, and 64 individuals screened positive. The screen helped to detect 15 new seizure diagnoses and 35 other neurologic diagnoses. Average time to first scheduled appointment was 23.8 days. The no-show rate was 7%. CONCLUSIONS: The seizure questionnaire effectively identified seizures and other disorders in a diverse population of high-risk children. Broader use of this low-cost screening tool could improve access to care for children with suspected seizures, increase seizure recognition, and help allocate resources more effectively.


Autism Spectrum Disorder/complications , Developmental Disabilities/complications , Epilepsy/complications , Parents , Seizures/diagnosis , Seizures/etiology , Surveys and Questionnaires/statistics & numerical data , Child , Child, Preschool , Female , Humans , Infant , Male , Massachusetts
13.
Pediatrics ; 144(1)2019 07.
Article En | MEDLINE | ID: mdl-31227563

A 2-day old term male infant was found to be hypotonic and minimally reactive during routine nursing care in the newborn nursery. At 40 hours of life, he was hypoglycemic and had intermittent desaturations to 70%. His mother had an unremarkable pregnancy and spontaneous vaginal delivery. The mother's prenatal serology results were negative for infectious risk factors. Apgar scores were 9 at 1 and 5 minutes of life. On day 1 of life, he fed, stooled, and voided well. Our expert panel discusses the differential diagnosis of hypotonia in a neonate, offers diagnostic and management recommendations, and discusses the final diagnosis.


Acyl-CoA Dehydrogenase, Long-Chain/deficiency , Congenital Bone Marrow Failure Syndromes/diagnosis , Lethargy/etiology , Lipid Metabolism, Inborn Errors/diagnosis , Mitochondrial Diseases/diagnosis , Muscle Hypotonia/etiology , Muscular Diseases/diagnosis , Congenital Bone Marrow Failure Syndromes/therapy , Diagnosis, Differential , Humans , Hypothermia/etiology , Infant, Newborn , Lipid Metabolism, Inborn Errors/therapy , Male , Mitochondrial Diseases/therapy , Muscular Diseases/therapy
14.
J Pediatr ; 210: 81-90.e3, 2019 07.
Article En | MEDLINE | ID: mdl-31076229

OBJECTIVES: To examine elevated neonatal inflammatory and neurotrophic proteins from children born extremely preterm in relation to later childhood brain Magnetic Resonance Imaging volumes and cognition. STUDY DESIGN: We measured circulating inflammation-related proteins and neurotrophic proteins on postnatal days 1, 7, and 14 in 166 children at 10 years of age (73 males; 93 females). Top quartile levels on ≥2 days for ≥3 inflammation-related proteins and for ≥4 neurotrophic proteins defined exposure. We examined associations among protein levels, brain Magnetic Resonance Imaging volumes, and cognition with multiple linear and logistic regressions. RESULTS: Analyses were adjusted for gestational age at birth and sex. Children with ≥3 elevated inflammation-related proteins had smaller grey matter, brain stem/cerebellar, and total brain volumes than those without elevated inflammation-related proteins, adjusted for neurotrophic proteins. When adjusted for inflammation-related proteins, children with ≥4 neurotrophic proteins, compared with children with no neurotrophic proteins, had larger grey matter and total brain volumes. Higher grey matter, white matter, and cerebellum and brainstem volumes were significantly correlated with higher IQ. Grey and white matter volumes were correlated with each other (r = -0.18; P = .021), and cerebellum and brainstem was highly correlated with grey matter (r = 0.55; P < .001) and white matter (r = 0.29; P < .001). Adjusting for other brain compartments, cerebellum and brainstem was associated with IQ (P = .016), but the association with white matter was marginally significant (P = .051). Grey matter was not associated with IQ. After adjusting for brain volumes, elevated inflammation-related proteins remained significantly associated with a lower IQ, and elevated neurotrophic proteins remained associated with a higher IQ. CONCLUSIONS: Newborn inflammatory and neurotrophin protein levels are associated with later brain volumes and cognition, but their effects on cognition are not entirely explained by altered brain volumes.


Brain/anatomy & histology , Brain/diagnostic imaging , Cognition , Infant, Extremely Premature/blood , Magnetic Resonance Imaging , Biomarkers/blood , Blood Proteins/analysis , Child , Female , Humans , Infant, Newborn , Inflammation/blood , Male , Nerve Growth Factors/blood , Organ Size , Prospective Studies
15.
J Perinatol ; 39(6): 774-783, 2019 06.
Article En | MEDLINE | ID: mdl-30918341

OBJECTIVE: To identify specific risk factors for epilepsy for individuals born extremely preterm. STUDY DESIGN: In a prospective cohort study, at 10-year follow-up, children were classified as having epilepsy or seizures not associated with epilepsy. We evaluated for association of perinatal factors using time-oriented, multinomial logistic regression models. RESULTS: Of the 888 children included in the study, 66 had epilepsy and 39 had seizures not associated with epilepsy. Epilepsy was associated with an indicator of low socioeconomic status, maternal gestational fever, early physiologic instability, postnatal exposure to hydrocortisone, cerebral white matter disease and severe bronchopulmonary dysplasia. Seizure without epilepsy was associated with indicators of placental infection and inflammation, and hypoxemia during the first 24 postnatal hours. CONCLUSIONS: In children born extremely preterm, epilepsy and seizures not associated with epilepsy have different risk profiles. Though both profiles included indicators of infection and inflammation, the profile of risk factors for epilepsy included multiple indicators of endogenous vulnerability.


Chronic Disease Indicators , Epilepsy/etiology , Infant, Extremely Premature , Child , Epilepsy/epidemiology , Female , Follow-Up Studies , Humans , Infant, Newborn , Infant, Newborn, Diseases/epidemiology , Mothers/statistics & numerical data , Placenta/microbiology , Pregnancy , Prevalence , Prospective Studies , Risk Factors , Severity of Illness Index , Socioeconomic Factors , Surveys and Questionnaires
16.
J Perinatol ; 38(7): 908-916, 2018 07.
Article En | MEDLINE | ID: mdl-29808002

OBJECTIVE: To describe the accuracy of the Bayley Scales of Infant Development-Second Edition (BSID-II) Mental Development Index (MDI) at 2 years of age for prediction of cognitive function at school age of children born extremely preterm. DESIGN: Study participants were enrolled in the Extremely Low Gestational Age Newborn Study between 2002 and 2004. Two-thirds of surviving children (n = 795) were assessed at 2 years with the BSID-II and at 10 years with an intelligence quotient (IQ) test. We computed test characteristics for a low MDI (<70), including predictive value positive. RESULTS: Almost two-thirds of children with a low MDI had a normal IQ (≥ 70) at 10 years. Concordance between MDI and IQ was highest among children with major motor and/or sensory impairment, and when MDI was adjusted for gestational age. CONCLUSION: Most children born extremely preterm with low BSID-II MDI at 2 years have normal intelligence at school age.


Cognitive Dysfunction/epidemiology , Developmental Disabilities/diagnosis , Infant Mortality/trends , Infant, Extremely Premature , Neuropsychological Tests , Age Factors , Child Development/physiology , Child, Preschool , Cognition , Cohort Studies , Developmental Disabilities/epidemiology , Developmental Disabilities/etiology , Female , Gestational Age , Humans , Infant , Infant, Newborn , Intensive Care Units, Neonatal , Male , Prognosis , Retrospective Studies , Risk Assessment , Sex Factors , Survivors , United States
17.
Pediatr Neurol ; 79: 45-52, 2018 02.
Article En | MEDLINE | ID: mdl-29310907

BACKGROUND: This study aims to determine the prevalence of neurodevelopmental impairments at age ten years among children born extremely preterm (less than 28 weeks gestational age) and to offer a framework for categorizing neurological limitations. METHODS: A multicenter, prospective cohort follow-up study recruited 889 ten-year-old children born from 2002 to 2004. We assessed prevalence of cognitive impairment, measured by intelligent quotient and tests of executive function, cerebral palsy (CP), autism spectrum disorder (ASD), and epilepsy singly and in combination. The three levels of impairment severity were: category I-no major neurodevelopmental impairment; category II-normal cognitive ability with CP, ASD, and/or epilepsy; and category III-children with cognitive impairment. RESULTS: A total 214 of 873 children (25%) had cognitive impairment, 93 of 849 children (11%) had CP, 61 of 857 children (7%) had ASD, and 66 of 888 children (7%) had epilepsy. Further, 19% of all children had one diagnosis, 10% had two diagnoses, and 3% had three diagnoses. Decreasing gestational age was associated with increasing number of impairments (P < 0.001). Half the children with cognitive impairment and one third of children with CP, ASD, or epilepsy had a single impairment. Six hundred one (68% [95% CI, 64.5%-70.7%]) children were in category I, 74 (8% [95% CI, 6.6%-10.3%]) were in category II, and 214 (24% [95% CI 21.7%-27.4%]) were in category III. CONCLUSIONS: Three quarters of children had normal intellect at age ten years; nearly 70% were free of neurodevelopmental impairment. Forty percent of children with impairments had multiple diagnoses.


Autism Spectrum Disorder/epidemiology , Cerebral Palsy/epidemiology , Cognitive Dysfunction/epidemiology , Epilepsy/epidemiology , Infant, Extremely Premature , Child , Comorbidity , Developmental Disabilities/epidemiology , Follow-Up Studies , Humans , Prospective Studies , Severity of Illness Index
18.
Pediatr Neurol ; 73: 13-19, 2017 Aug.
Article En | MEDLINE | ID: mdl-28619377

OBJECTIVE: We evaluated the incidence of seizures and epilepsy in the first decade of life among children born extremely premature (less than 28 weeks' gestation). METHOD: In a prospective, multicenter, observational study, 889 of 966 eligible children born in 2002 to 2004 were evaluated at two and ten years for neurological morbidity. Complementing questionnaire data to determine a history of seizures, all caregivers were interviewed retrospectively for postneonatal seizures using a validated seizure screen followed by a structured clinical interview by a pediatric epileptologist. A second pediatric epileptologist established an independent diagnosis based on recorded responses of the interview. A third epileptologist determined the final diagnosis when evaluators disagreed (3%). Life table survival methods were used to estimate seizure incidence through ten years. RESULTS: By age ten years, 12.2% (95% confidence interval: 9.8, 14.5) of children had experienced one or more seizures, 7.6% (95% confidence interval: 5.7, 9.5) had epilepsy, 3.2% had seizure with fever, and 1.3% had a single, unprovoked seizure. The seizure incidence increased with decreasing gestational age. In more than 75% of children with seizures, onset was after one year of age. Seizure incidence was comparable in both sexes. Two-thirds of those with epilepsy had other neurological disorders. One third of children with epilepsy were not recorded on the medical history questionnaire. SIGNIFICANCE: The incidence of epilepsy through age ten years among children born extremely premature is approximately 7- to 14-fold higher than the 0.5% to 1% lifetime incidence reported in the general pediatric population. Seizures in this population are under-recognized, and possibly underdiagnosed, by parents and providers.


Epilepsy/epidemiology , Infant, Extremely Premature , Seizures/epidemiology , Age Factors , Cerebral Palsy/epidemiology , Child , Cognition Disorders/epidemiology , Cognition Disorders/etiology , Epilepsy/diagnostic imaging , Female , Gestational Age , Head/pathology , Humans , Incidence , Male , Neuropsychological Tests , Prospective Studies , Retrospective Studies , Seizures/diagnostic imaging , Ultrasonography
19.
J Child Neurol ; 31(8): 1057-61, 2016 07.
Article En | MEDLINE | ID: mdl-26961263

Benign paroxysmal torticollis of infancy is an unusual movement disorder, often accompanied by a family history of migraine. Some benign paroxysmal torticollis cases are associated with CACNA1A mutations. The authors sought to determine the frequency of CACNA1A mutations in benign paroxysmal torticollis by testing 8 children and their parents and by searching the literature for benign paroxysmal torticollis cases with accompanying CACNA1A mutations or other disorders linked to the same gene. In our 8 benign paroxysmal torticollis cases, the authors found 3 different polymorphisms, but no pathogenic mutations. By contrast, in the literature, the authors found 4 benign paroxysmal torticollis cases with CACNA1A mutations, 3 with accompanying family histories of 1 or more of familial hemiplegic migraine, episodic ataxia, and paroxysmal tonic upgaze. Thus, CACNA1A mutations are more likely to be found in children with benign paroxysmal torticollis if accompanied by family histories of familial hemiplegic migraine, episodic ataxia, or paroxysmal tonic upgaze.


Calcium Channels/genetics , Genetic Predisposition to Disease , Mutation , Torticollis/genetics , Cohort Studies , Genetic Association Studies , Humans , Infant , Infant, Newborn
20.
Pediatr Neurol ; 54: 64-69.e1, 2016 Jan.
Article En | MEDLINE | ID: mdl-26552646

BACKGROUND: We developed a seizure questionnaire that could be administered by a trained research assistant in a two-step process, approximating the clinical diagnostic process of a pediatric epileptologist. This questionnaire was designed to study seizure prevalence in a research population of 10-year-old children at risk for epilepsy. METHODS: English-speaking parents of children 6 months to 12 years old were recruited from the pediatric neurology clinics at Boston Medical Center and interviewed using a computerized questionnaire. An algorithm of parent responses rendered a 4-level ranking scale of seizure probability for events: (1) not likely, (2) indeterminate, (3) probable, (4) almost certain. Blinded to questionnaire results, pediatric neurologists served as the diagnostic gold standard, ranking each patient event using the same four-level scale based on clinical history and examination. RESULTS: The questionnaire was completed by 150 of 177 (84.7%) enrolled parents. Seizure prevalence among participants was 38.6%. The seizure questionnaire yielded a fitted receiver operating characteristic area of 0.93 (95% confidence interval [CI], 0.89-0.97). Based on optimal sensitivity and false-positive fraction, we dichotomized the questionnaire results as consistent with seizure (levels 3 and 4) or without seizure (levels 1 and 2). Overall, findings included a 91.4% sensitivity (95% CI, 84.2%-98.6%) and an 82.6% specificity (95% CI, 74.9%-90.4%). The positive predictive value was 76.8% (95% CI, 66.9%-86.8%) and the negative predictive value was 93.8% (95% CI, 88.6%-99.1%). CONCLUSIONS: This pediatric seizure questionnaire was both sensitive and specific for detecting clinically confirmed seizures. This tool may be useful to researchers and clinicians in screening large populations of children, decreasing the time and cost of added neurological assessments.


Diagnosis, Computer-Assisted/methods , Parents , Seizures/diagnosis , Algorithms , Child , Child, Preschool , Computers , Decision Support Systems, Clinical , Electroencephalography , False Positive Reactions , Female , Humans , Infant , Male , Prevalence , ROC Curve , Risk , Seizures/epidemiology , Seizures/physiopathology , Sensitivity and Specificity , Single-Blind Method
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