Prescription patterns of home rescue benzodiazepines for febrile seizures.

OBJECTIVE: To describe the prescription patterns of home, non-intravenous rescue benzodiazepines (non-IV-rBZDs) for febrile seizures and the factors associated with their prescription. METHODS: Retrospective descriptive study using the MarketScan Commercial Database, a large database of employer-sponsored privately insured patients in the United States. We used data from January 1st 2006 to December 31st 2022. We studied patients with febrile seizures as the main code for the healthcare encounter (identified with International Classification of Diseases codes) with age from 6 months to 5 years of age and with at least 1 month of follow-up. RESULTS: There were a total of 82,835 patients [median (p25-p75) age 1.0 (1.0-2.0) years, 56.7 % males] with at least one febrile seizure, of whom 9,737 (11.8 %) filled at least one non-IV-rBZD prescription. Among the 9,737 patients who filled at least one prescription, the median (p25-p75) time from first febrile seizure to non-IV-rBZD prescription was 27 (2-186) days. Among the factors known at the time of the first febrile seizure, complex febrile seizure (OR: 3.51, 95 % CI: 3.24-3.79), and an initial inpatient hospitalization for febrile seizure (OR: 3.53, 95 % CI: 3.29-3.79) were the factors most strongly associated with filling a non-IV-rBZD prescription. In contrast, sex, rural patient's residence, and salary employment (versus other employment class) were not independently associated with filling a non-IV-rBZD prescription. Among the factors known at the end of follow-up, complex febrile seizures, type of initial encounter, and an eventual diagnosis of epilepsy were major independent factors associated with filling a non-IV-rBZD prescription. CONCLUSION: Only approximately 12 % of children with a febrile seizure filled a prescription for a home non-IV-rBZD. The major factors independently associated with prescription were complex febrile seizure, hospital admission, recurrent febrile seizures, and an eventual diagnosis of epilepsy.

Current Evidence: Seizures in Extremely Low Gestational Age Newborns (ELGANs).

Extremely low gestational age newborns (ELGANs) are born at or below 28 weeks of gestational age. Despite improved obstetric care, the incidence of preterm birth continues to rise in advanced countries. Preterm birth remains a major cause of infant mortality, and for infants who survive, neonatal seizures are a significant predictor of later neurologic morbidity. However, little is known about risk factors for neonatal seizures in ELGANs. Understanding the association between neonatal seizures and the development of other neurologic disorders is important given the increasing prevalence of ELGANs. Identifying risk factors that contribute to the development of neonatal seizures in ELGANs may offer insights into novel mechanisms of epileptogenesis in the developing brain and improvements in the prevention or treatment of seizures in preterm infants, including ELGANs. In this literature review, we outline the limitations of epidemiologic studies of neonatal seizures in ELGANs and discuss risk factors for neonatal seizures.

Evolution of antiseizure medication use and cost in the United States of America 2006-2021.

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.

Temporal trends in the cost and use of first-line treatments for infantile epileptic spasms syndrome.

OBJECTIVE: To describe the temporal trends in the cost and use of adrenocorticotropic hormone (ACTH), oral prednisolone, and vigabatrin, the first-line treatments for infantile epileptic spasms syndrome (IESS). METHODS: Retrospective observational study using the MarketScan Commercial database from 2006 to 2020. We identified patients with IESS diagnosed between birth and 18 months of age who received at least one of the first-line treatments within 60 days of diagnosis. Costs were adjusted for inflation using the Gross Domestic Product Implicit Price Deflator. RESULTS: A total of 1131 patients received at least one first-line treatment (median [p25 -p75 ] age: 6.3 [4.5-8.3] months, 55% male), of whom 592 patients received ACTH, 363 patients received oral prednisolone, and 355 patients received vigabatrin. After adjusting for inflation, the median average wholesale price of a 14-day course of treatment increased for ACTH from $3718 in 2006 to $100 457 in 2020, ~2700% (by a factor of 27), whereas it decreased for oral prednisolone from $169 in 2006 to $89 in 2020, ~50% (by a factor of 0.5), and increased for vigabatrin from $1206 in 2009 (first year with data on vigabatrin used for IESS) to $4102 in 2020, ~340% (by a factor of 3.4). During the first 60 days after diagnosis, inpatient admission days and costs where higher for ACTH than for oral prednisolone and vigabatrin-5.0 (3.0-8.3) days vs 2.0 (0.0-5.0) days vs 2.0 (0.0-6.0) days, p < .0001; and $32 828 ($14 711-$67 216) vs $16 227 ($0-$35 829) vs $17 844 ($0-$47 642), p < .0001. ACTH use decreased from representing 78% of first-line treatments in 2006 to 18% in 2020 (p < .0001). Sensitivity analyses confirmed the robustness of the results. SIGNIFICANCE: The gap between the cost of ACTH and the cost of oral prednisolone or vigabatrin has widened markedly from 2006 to 2020, whereas the relative proportion of ACTH use has decreased.

Health care resource utilization and costs before and after epilepsy surgery.

OBJECTIVE: To describe the demographics of epilepsy surgery utilization and its impact on health care resource use. METHODS: Retrospective descriptive study using the MarketScan commercial claims database. We studied children and adults who underwent epilepsy surgery in the USA in the period 2006-2019. Our main outcome was health care resource utilization. RESULTS: Among the 87,368 patients with refractory epilepsy, 2,011 (2.3%) patients underwent resective epilepsy surgery, 188 (0.2%) patients underwent partial or total hemispherectomy, and 183 (0.2%) patients underwent corpus callosotomy. The proportion of patients undergoing epilepsy surgery has barely increased in the period 2006 to 2019. The year of resective epilepsy surgery was associated with high healthcare costs per person-year [median (p25-p75): $140,322 ($88,749-$225,862)], but healthcare costs per person-year substantially decreased in the 5 years after compared to the 5 years before the year of resective epilepsy surgery [$7,691 ($2,738-$22,092) versus $18,750 ($7,361-$47,082), p-value < 0.0001]. This result held in all resective epilepsy surgery subgroups: children, adults, temporal, extratemporal, subdural EEG monitoring, stereoEEG monitoring, and no intracranial monitoring. Similarly, the year of hemispherectomy was associated with high healthcare costs per person-year [$260,983 ($154,791-$453,986)], but healthcare costs per person-year substantially decreased in the 5 years after compared to the 5 years before the year of hemispherectomy [$26,834 ($12,842-$52,627) versus $54,596 ($19,547-$136,412), p-value < 0.0001]. In contrast, the year of corpus callosotomy was associated with high healthcare costs per person-year [$162,399 ($108,150-$253,156)], but healthcare costs per person-year did not substantially decrease in the 5 years after than in the 5 years before the year of corpus callosotomy [$25,464 ($10,764-$69,338) versus $36,221 ($12,841-$85,747), p-value = 0.2142]. CONCLUSION: In privately insured patients in the USA, resective epilepsy surgery and hemispherectomy substantially decrease healthcare utilization in subsequent years. Epilepsy surgery may help contain costs in the field of epilepsy.

Quantitative MRI Characterization of the Extremely Preterm Brain at Adolescence: Atypical versus Neurotypical Developmental Pathways.

Background Extremely preterm (EP) birth is associated with higher risks of perinatal white matter (WM) injury, potentially causing abnormal neurologic and neurocognitive outcomes. MRI biomarkers distinguishing individuals with and without neurologic disorder guide research on EP birth antecedents, clinical correlates, and prognoses. Purpose To compare multiparametric quantitative MRI (qMRI) parameters of EP-born adolescents with autism spectrum disorder, cerebral palsy, epilepsy, or cognitive impairment (ie, atypically developing) with those without (ie, neurotypically developing), characterizing sex-stratified brain development. Materials and Methods This prospective multicenter study included individuals aged 14-16 years born EP (Extremely Low Gestational Age Newborns-Environmental Influences on Child Health Outcomes Study, or ELGAN-ECHO). Participants underwent 3.0-T MRI evaluation from 2017 to 2019. qMRI outcomes were compared for atypically versus neurotypically developing adolescents and for girls versus boys. Sex-stratified multiple regression models were used to examine associations between spatial entropy density (SEd) and T1, T2, and cerebrospinal fluid (CSF)-normalized proton density (nPD), and between CSF volume and T2. Interaction terms modeled differences in slopes between atypically versus neurotypically developing adolescents. Results A total of 368 adolescents were classified as 116 atypically (66 boys) and 252 neurotypically developing (125 boys) participants. Atypically versus neurotypically developing girls had lower nPD (mean, 557 10 × percent unit [pu] ± 46 [SD] vs 573 10 × pu ± 43; P = .04), while atypically versus neurotypically developing boys had longer T1 (814 msec ± 57 vs 789 msec ± 82; P = .01). Atypically developing girls versus boys had lower nPD and shorter T2 (eg, in WM, 557 10 × pu ± 46 vs 580 10 × pu ± 39 for nPD [P = .006] and 86 msec ± 3 vs 88 msec ± 4 for T2 [P = .003]). Atypically versus neurotypically developing boys had a more moderate negative association between T1 and SEd (slope, -32.0 msec per kB/cm3 [95% CI: -49.8, -14.2] vs -62.3 msec per kB/cm3 [95% CI: -79.7, -45.0]; P = .03). Conclusion Atypically developing participants showed sexual dimorphisms in the cerebrospinal fluid-normalized proton density (nPD) and T2 of both white matter (WM) and gray matter. Atypically versus neurotypically developing girls had lower WM nPD, while atypically versus neurotypically developing boys had longer WM T1 and more moderate T1 associations with microstructural organization in WM. © RSNA, 2022 Online supplemental material is available for this article.

Using an animated video to promote an informed discussion on SUDEP with adolescents.

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.

Neonatal Cranial Ultrasound Findings among Infants Born Extremely Preterm: Associations with Neurodevelopmental Outcomes at 10 Years of Age.

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.

Changes in Neurodevelopmental Outcomes From Age 2 to 10 Years for Children Born Extremely Preterm.

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.

Anxiety and Depression Correlates at Age 10 in Children Born Extremely Preterm.

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.

A Novel Parent Questionnaire for the Detection of Seizures in Children of Spanish-Speaking Families.

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.

Mentorship for Youth With Chronic Neurological Conditions in the Digital Era: An Innovative Approach to Supporting Transition.

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.

Mental Health Issues in Transition-Age Adolescents and Young Adults With Epilepsy.

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.

A Multimodal Telehealth Strategy to Improve Pediatric Epilepsy Care.

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.

Histologic chorioamnionitis and risk of neurodevelopmental impairment at age 10 years among extremely preterm infants born before 28 weeks of gestation.

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.

Clinical Implementation of a Parent Questionnaire to Identify Seizures in High-Risk Children.

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.

Hypotonia and Lethargy in a Two-Day-Old Male Infant.

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.

Association of Circulating Proinflammatory and Anti-inflammatory Protein Biomarkers in Extremely Preterm Born Children with Subsequent Brain Magnetic Resonance Imaging Volumes and Cognitive Function at Age 10 Years.

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.