Cerebral Palsy and Motor Impairment After Extreme Prematurity: Prediction of Diagnoses at Ages 2 and 10 Years.

OBJECTIVE: To identify perinatal factors in children born extremely preterm (EP) that were associated with motor impairment (MI) at 2 and 10 years of age and develop a predictive algorithm to estimate the risk of MI during childhood. STUDY DESIGN: Participants of the Extremely Low Gestational Age Newborns Study (ELGANS) were classified as: no MI, MI only at 2 years, MI only at 10 years, and MI at both 2 and 10 years, based on a standardized neurological examination at 2 and the Gross Motor Function Classification System (GMFCS) at 10 years of age. Least Absolute Shrinkage and Selection Operator (LASSO) regression was used to develop the final predictive model. RESULTS: Of the 849 study participants, 64 (7.5%) had a diagnosis of MI at both 2 and 10 years and 63 (7.4%) had a diagnosis of MI at 1 visit but not the other. Of 22 total risk factors queried, 4 variables most reliably and accurately predicted MI: gestational age, weight z-score growth trajectory during neonatal intensive care unit (NICU) stay, ventriculomegaly, and cerebral echolucency on head ultrasound. By selecting probability thresholds of 3.5% and 7.0% at ages 2 and 10, respectively, likelihood of developing MI can be predicted with a sensitivity and specificity of 71.2%/72.1% at age 2 and 70.7%/70.7% at age 10. CONCLUSION: In our cohort, the diagnosis of MI at 2 years did not always predict a diagnosis of MI at 10 years. Specific risk factors are predictive of MI and can estimate an individual infant's risk at NICU discharge of MI at age 10 years.

Cohort study: Neurological and cognitive-behavioral sequelae of acquired Zika virus infection among Nicaraguan children.

BACKGROUND: ZIKV has neuroinvasive properties, and in utero exposure can cause birth defects, but little is known about the neurological and neurocognitive impacts of acquired ZIKV infection, particularly in children. METHODS: We assessed neurological symptoms frequency among ZIKV-infected children within one year after ZIKV infection. Three to 5 years post-infection, these children and a matched group of uninfected children were assessed via questionnaires, neurological exams, and neuropsychological testing to evaluate the association between prior ZIKV infection and subsequent neurological symptoms, and cognitive-behavioral function. RESULTS: Among 194 ZIKV-infected children, 3 reported asthenia, 4 reported neck pain, and 10 reported back pain within one year post-infection. At follow-up, clinician-observed cranial nerve abnormalities were significantly more common among ZIKV-infected vs. uninfected children (16 vs. 3; p < 0.01), with vestibulocochlear nerve abnormalities observed most frequently. While ZIKV-infected children scored better than uninfected on cognitive measures, this difference was not clinically meaningful. CONCLUSIONS: Neurological signs, including paresthesia and cranial nerve abnormalities, were observed among ZIKV-infected participants in our study. However, we did not observe a meaningful link between acquired ZIKV infection and subsequent neurological, cognitive, or behavioral outcomes in a representative sample. An exception may be hearing impairment and loss, which should be explored further in future studies. IMPACT: Neurological symptoms, though rare, were observed and reported more frequently among ZIKV-infected vs. uninfected children. These included: asthenia, neck pain, back pain, paresthesia, and cranial nerve abnormalities. Neurocognitive and behavioral test scores were similar among ZIKV-infected and uninfected children. Our study suggests that ZIKV-infected children should be monitored for neurological symptoms and cranial neuropathy to better understand the full burden of acquired ZIKV infection among children.

Retinopathy of prematurity and neurodevelopmental outcome and quality of life at 10 years of age.

Objective: In a cohort of 10-year-old children born extremely preterm, we evaluated the hypothesis that increasing severity of retinopathy of prematurity (ROP) is associated with increasing frequency of unfavorable neurodevelopmental and quality of life outcomes. Study Design: Study participants were classified according to the severity of ROP. At 10 years of age, their neurocognitive abilities, academic achievement, and gross motor function were assessed, and they were evaluated for autism spectrum disorder, anxiety, depression, and quality of life. Results: After adjustment for sample attrition and confounders, only the association with lower quality of life persisted. Increasing severity of visual impairment was associated with worse neurodevelopmental outcomes and lower quality of life. Conclusion: Among extremely preterm children, severity of visual impairment, but not severity of ROP, was associated with adverse neurodevelopmental outcomes at 10 years of age. Both severe ROP and more severe visual impairment were associated with lower quality of life.

A Multi-Omics Approach to Defining Target Organ Injury in Youth with Primary Hypertension.

BACKGROUND: Primary hypertension in childhood tracks into adulthood and may be associated with increased cardiovascular risk. Studies conducted in children and adolescents provide an opportunity to explore the early cardiovascular target organ injury (CV-TOI) in a population free from many of the comorbid cardiovascular disease risk factors that confound studies in adults. METHODS: Youths (n=132, mean age 15.8 years) were stratified by blood pressure (BP) as low, elevated, and high-BP and by left ventricular mass index (LVMI) as low- and high-LVMI. Systemic circulating RNA, miRNA, and methylation profiles in peripheral blood mononuclear cells and deep proteome profiles in serum were determined using high-throughput sequencing techniques. RESULTS: VASH1 gene expression was elevated in youths with high-BP with and without high-LVMI. VASH1 expression levels positively correlated with systolic BP (r=0.3143, p=0.0034). The expression of hsa-miR-335-5p, one of the VASH1-predicted miRNAs, was downregulated in high-BP with high-LVMI youths and was inversely correlated with systolic BP (r=-0.1891, p=0.0489). GSE1 hypermethylation, circulating PROZ upregulation (log2FC=0.61, p=0.0049 and log2FC=0.62, p=0.0064), and SOD3 downregulation (log2FC=-0.70, p=0.0042 and log2FC=-0.64, p=0.010) were observed in youths with elevated BP and high-BP with high-LVMI. Comparing the transcriptomic and proteomic profiles revealed elevated HYAL1 levels in youths displaying high-BP and high-LVMI. CONCLUSIONS: The findings are compatible with a novel blood pressure-associated mechanism that may occur through impaired angiogenesis and extracellular matrix degradation through dysregulation of Vasohibin-1 and Hyaluronidase1 was identified as a possible mediator of CV-TOI in youth with high-BP and suggests strategies for ameliorating TOI in adult-onset primary hypertension.

Neurological and neuropsychological sequelae of Zika virus infection in children in León, Nicaragua / Secuelas neurológicas y neuropsicológicas de la infección por el virus del Zika en niños y niñas en León, Nicaragua / Sequelas neurológicas e neuropsicológicas da infecção pelo vírus zika em crianças em León, Nicarágua

ABSTRACT Objectives. To describe the presence and persistence of neurological and neuropsychological sequelae among children with acquired Zika virus infection and assess whether those sequelae were more common in children infected with Zika virus compared to uninfected children. Methods. We conducted a prospective cohort study of children with and without Zika virus infection in León, Nicaragua, using a standard clinical assessment tool and questionnaire to collect data on symptoms at three visits, about 6 months apart, and a battery of standardized instruments to evaluate neurocognitive function, behavior, depression, and anxiety at the last two visits. Results. Sixty-two children were enrolled, with no significant differences in demographics by infection group. Children infected with Zika virus had a range of neurological symptoms, some of which persisted for 6 to 12 months; however, no consistent pattern of symptoms was observed. At baseline a small percentage of children infected with Zika virus had an abnormal finger-to-nose test (13%), cold touch response (13%), and vibration response (15%) versus 0% in the uninfected group. Neurocognitive deficits and behavioral problems were common in both groups, with no significant differences between the groups. Children infected with Zika virus had lower cognitive efficiency scores at the 6-month visit. Anxiety and depression were infrequent in both groups. Conclusions. Larger studies are needed to definitively investigate the relationship between Zika virus infection and neurological symptoms and neurocognitive problems, with adjustment for factors affecting cognition and behavior, including mood and sleep disorders, home learning environment, history of neuroinvasive infections, and detailed family history of neuropsychological problems.

RESUMEN Objetivos. Describir la presencia y persistencia de secuelas neurológicas y neuropsicológicas en pacientes pediátricos que contrajeron la infección por el virus del Zika y evaluar si dichas secuelas fueron más comunes en los infectados con el virus del Zika en comparación con los no infectados. Métodos. Se realizó un estudio de cohorte prospectivo en pacientes pediátricos con y sin infección por el virus del Zika en León (Nicaragua), con una herramienta de evaluación clínica estándar y un cuestionario para recopilar datos sobre los síntomas en tres visitas, con aproximadamente seis meses de diferencia, y un conjunto de instrumentos estandarizados para evaluar la función neurocognitiva, el comportamiento, la depresión y la ansiedad en las últimas dos visitas. Resultados. Participaron 62 niños y niñas sin diferencias significativas en la demografía por grupo de infección. Los participantes infectados con el virus del Zika mostraron una variedad de síntomas neurológicos, algunos de los cuales persistieron entre 6 y 12 meses; no obstante, no se observó un patrón sistemático en los síntomas. Al inicio del estudio, un pequeño porcentaje de participantes infectados con el virus del Zika mostró resultados anormales a las pruebas dedo-nariz (13%), respuesta al tacto (frío) (13%) y respuesta a la vibración (15%), frente a un 0% en el grupo no infectado. Los déficits neurocognitivos y los problemas de comportamiento fueron comunes en ambos grupos, sin diferencias significativas entre los grupos. Los participantes infectados con el virus del Zika mostraron puntuaciones de eficiencia cognitiva más bajas en la visita a los 6 meses. La ansiedad y la depresión fueron poco frecuentes en ambos grupos. Conclusiones. Son necesarios estudios más amplios para investigar definitivamente la relación entre la infección por el virus del Zika y los síntomas neurológicos y los problemas neurocognitivos, haciendo ajustes para los factores relacionados con la cognición y el comportamiento, incluidos los trastornos del estado de ánimo y el sueño, el entorno de aprendizaje en el hogar, los antecedentes de infecciones neuroinvasivas y los antecedentes familiares detallados de problemas neuropsicológicos.

RESUMO Objetivos. Descrever a presença e a persistência de sequelas neurológicas e neuropsicológicas em crianças com infecção pelo vírus zika e avaliar se essas sequelas foram mais comuns em crianças infectadas pelo vírus zika em comparação com crianças não infectadas. Métodos. Realizamos um estudo de coorte prospectivo em crianças com e sem infecção pelo vírus zika em León, Nicarágua, usando uma ferramenta de avaliação clínica padrão e um questionário para coletar dados de sintomas em três consultas, com cerca de 6 meses de intervalo, além de um conjunto de ferramentas padronizadas para avaliar função neurocognitiva, comportamento, depressão e ansiedade nas duas últimas consultas. Resultados. Foram incluídas 62 crianças, sem diferenças significativas nas características demográficas por grupo de infecção. As crianças infectadas pelo vírus zika tinham uma gama de sintomas neurológicos, alguns dos quais persistiram por 6 a 12 meses. Entretanto, não se observou nenhum padrão consistente de sintomas. No início do estudo, uma pequena porcentagem de crianças infectadas com o vírus zika apresentou resultado anormal na prova índex-nariz (13%), resposta ao toque frio (13%) e sensibilidade vibratória (15%), em comparação a 0% no grupo não infectado. Déficits neurocognitivos e problemas comportamentais foram frequentes em ambos os grupos, mas sem diferenças significativas entre eles. As crianças infectadas com o vírus zika tiveram resultados mais baixos de eficiência cognitiva na consulta de 6 meses. Ansiedade e depressão não foram observadas com frequência em ambos os grupos. Conclusões. São necessários estudos mais amplos para investigar a relação exata entre a infecção pelo vírus zika e sintomas neurológicos e problemas neurocognitivos, com ajuste para fatores que afetam a cognição e o comportamento, incluindo distúrbios do humor e do sono, ambiente de aprendizagem em casa, história de infecções neuroinvasivas e história familiar detalhada de problemas neuropsicológicos.