Motor and cognitive outcomes of neonates with low birth weight in Brazil: a systematic review and meta-analysis.

BACKGROUND: Data on the outcomes of preterm newborns in South American countries are scarce. Given the great effect of low birth weight (LBW) and/or prematurity on children's neurodevelopment, it is extremely necessary to conduct studies on these phenomena in greater depth in more heterogeneous populations such as those ones from countries with limited resources. METHODS: We conducted a comprehensive literature search on databases including PubMed, the Cochrane Library, and Web of Science for articles published in Portuguese and English up to March 2021 involving children born and evaluated in Brazil. The analysis of the risk of bias was adapted from the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement and used to evaluate the methodology of the included studies. RESULTS: From the eligible trials, 25 articles were selected for qualitative synthesis, and 5 of those, for quantitative synthesis (meta-analysis). The meta-analyses showed that children born with LBW presented lower scores on motor development when compared with controls (standardized mean difference: -1.15; 95% confidence interval [95%CI]: -1.56--0.73]; I2: 80%) and also scored lower in terms of cognitive development (standardized mean difference: -0.71; 95% CI: -0.99--0.44; I2: 67%). CONCLUSION: The results of the present study reinforce that impaired motor and cognitive functions can be a significant long-term outcome of LBW. The lower the gestational age at delivery, the higher the risk of impairment in those domains. The study protocol was registered in the International Prospective Register of Systematic Reviews (PROSPERO) database under number CRD42019112403.

ANTECEDENTES: Dados sobre desfechos de recém-nascidos prematuros em países da América do Sul são escassos. Dado o grande efeito do baixo peso ao nascer (BPN) e/ou da prematuridade no neurodesenvolvimento das crianças, é extremamente necessária a realização de estudos que investiguem esses fenômenos com maior profundidade em populações mais heterogêneas. MéTODOS: Realizou-se uma busca da literatura em bases de dados, incluindo PubMed, Cochrane Library e Web of Science, por artigos publicados em português e inglês até março de 2021 envolvendo crianças nascidas e avaliadas no Brasil. A análise de risco de viés foi adaptada da declaração de Fortalecimento do Relato de Estudos Observacionais em Epidemiologia (Strengthening the Reporting of Observational Studies in Epidemiology, STROBE), que foi utilizada para avaliar a metodologia dos estudos. RESULTADOS: Dos estudos elegíveis, 25 artigos foram selecionados para síntese qualitativa, e 5 desses 25, para síntese quantitativa (metanálise). As metanálises mostraram que crianças nascidas com BPN apresentaram pontuação menor em desenvolvimento motor quando comparadas aos controles (diferença média padronizada, −1,15; intervalo de confiança de 95% [IC95%]: −1,56­−0,73]; I2: 80%) e pontuação também menor em termos de desenvolvimento cognitivo (diferença média padronizada, −0,71; IC95%: −0,992−0,44; I2: 67%). CONCLUSãO: Os resultados deste estudo reforçam que o comprometimento das funções motoras e cognitivas pode ser um desfecho significativo de longo prazo do BPN. Quanto menor a idade gestacional no momento do parto, maior o risco de prejuízo nesses domínios. O protocolo do estudo foi registrado no banco de dados International Prospective Register of Systematic Reviews (PROSPERO) sob o número CRD42019112403.

Motor and cognitive outcomes of neonates with low birth weight in Brazil: a systematic review and meta-analysis / Desfechos motores e cognitivos de recém-nascidos com baixo peso ao nascer no Brasil: uma revisão sistemática e metanálise

Abstract Background Data on the outcomes of preterm newborns in South American countries are scarce. Given the great effect of low birth weight (LBW) and/or prematurity on children's neurodevelopment, it is extremely necessary to conduct studies on these phenomena in greater depth in more heterogeneous populations such as those ones from countries with limited resources. Methods We conducted a comprehensive literature search on databases including PubMed, the Cochrane Library, and Web of Science for articles published in Portuguese and English up to March 2021 involving children born and evaluated in Brazil. The analysis of the risk of bias was adapted from the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement and used to evaluate the methodology of the included studies. Results From the eligible trials, 25 articles were selected for qualitative synthesis, and 5 of those, for quantitative synthesis (meta-analysis). The meta-analyses showed that children born with LBW presented lower scores on motor development when compared with controls (standardized mean difference: -1.15; 95% confidence interval [95%CI]: -1.56--0.73]; I2: 80%) and also scored lower in terms of cognitive development (standardized mean difference: -0.71; 95% CI: -0.99--0.44; I2: 67%). Conclusion The results of the present study reinforce that impaired motor and cognitive functions can be a significant long-term outcome of LBW. The lower the gestational age at delivery, the higher the risk of impairment in those domains. The study protocol was registered in the International Prospective Register of Systematic Reviews (PROSPERO) database under number CRD42019112403.

Resumo Antecedentes Dados sobre desfechos de recém-nascidos prematuros em países da América do Sul são escassos. Dado o grande efeito do baixo peso ao nascer (BPN) e/ou da prematuridade no neurodesenvolvimento das crianças, é extremamente necessária a realização de estudos que investiguem esses fenômenos com maior profundidade em populações mais heterogêneas. Métodos Realizou-se uma busca da literatura em bases de dados, incluindo PubMed, Cochrane Library e Web of Science, por artigos publicados em português e inglês até março de 2021 envolvendo crianças nascidas e avaliadas no Brasil. A análise de risco de viés foi adaptada da declaração de Fortalecimento do Relato de Estudos Observacionais em Epidemiologia (Strengthening the Reporting of Observational Studies in Epidemiology, STROBE), que foi utilizada para avaliar a metodologia dos estudos. Resultados Dos estudos elegíveis, 25 artigos foram selecionados para síntese qualitativa, e 5 desses 25, para síntese quantitativa (metanálise). As metanálises mostraram que crianças nascidas com BPN apresentaram pontuação menor em desenvolvimento motor quando comparadas aos controles (diferença média padronizada, -1,15; intervalo de confiança de 95% [IC95%]: -1,56--0,73]; I2: 80%) e pontuação também menor em termos de desenvolvimento cognitivo (diferença média padronizada, -0,71; IC95%: -0,992-0,44; I2: 67%). Conclusão Os resultados deste estudo reforçam que o comprometimento das funções motoras e cognitivas pode ser um desfecho significativo de longo prazo do BPN. Quanto menor a idade gestacional no momento do parto, maior o risco de prejuízo nesses domínios. O protocolo do estudo foi registrado no banco de dados International Prospective Register of Systematic Reviews (PROSPERO) sob o número CRD42019112403.

Translation and language validation of the Epworth sleepiness scale for children and adolescents (ESS-CHAD) into Brazilian Portuguese.

Objective: This study aimed to translate the Epworth sleepiness scale for children and adolescents (ESS-CHAD) into Brazilian Portuguese. Material and Methods: The translation and language validation processes were carried out through translation, back translation, technical review, assessment of verbal comprehension/clarity of the scale by experts (four pediatric neurologists). After they have reached a final version of the ESS-HAD a sample of asymptomatic children and adolescents that were participants in another sleep project were invited to read and complete the questionnaire to evaluate comprehension by the aimed population. Results: Two independent researchers made the forward translation and it has around 90% of concordance. Minor disagreements were related to the position of adjectives in the sentence. No major difficulties were reported by the 3rd researcher that performed the back translation. After a consensus meeting with the four participants, we have reached a final version of the questionnaire. In the cognitive interviews, the scale was reportedly easy to understand to the 23 respondents. One adolescent suggested clarifying whether question 2 (likelihood of falling asleep watching TV or a video), referred to daytime or nighttime. The total ESS-CHAD score in this asymptomatic sample varied from 0-17, a mean score of 7.08±5.65. Discussion: The final version of the ESS-CHAD in Brazilian Portuguese was approved by the copyright owners and was well understandable by caregivers and adolescents. More studies are now necessary to use this questionnaire in a larger target population to verify its validity and internal consistency.

Effects of non-invasive respiratory support on sleep in preterm infants evaluated by actigraphy.

OBJECTIVE: Few studies have evaluated sleep in preterm infants under non-invasive ventilatory support in neonatal intensive care units (NICU). The main objective of this study was to evaluate the influence of continuous positive airway pressure (CPAP) in the sleep of premature babies. MATERIAL AND METHODS: Crossover study in a NICU. We selected preterm infants with gestational age between 28 and 37 weeks using nasal CPAP. Eighteen preterm were included. Patients were monitored with actigraphy and with the Neonatal Behavioral Assessment Scale (NBAS). RESULTS: Results showed a reduction in sleep effciency, total sleep time and total sleep period during the CPAP period when compared to the non-CPAP. NBAS demonstrated significantly greater time of deep sleep and light sleep in the period without CPAP. CONCLUSION: Our data suggests that the use of CPAP, during the first week of life, in preterm neonates, is associated with transitory alterations of sleep organization.

Epilepsy after congenital zika virus infection: EEG and neuroimaging features.

PURPOSE: To describe epilepsy after congenital Zika virus infection (ZIKV) and its relationship with structural neuroimaging findings. METHODS: This was a cross-sectional study in children (aged 13-42 months) who were born with microcephaly due to ZIKV infection between 2015-2017. Patients underwent a brain imaging scan (magnetic resonance) and a video-EEG study. RESULTS: Among the patients (n = 43), 55.8 % were male, 88.4 % were born at term, mean head circumference at the birth was 29.7 ± 1.8 cm, and 44.8 % were infected in the first trimester of pregnancy. Neuroimaging was moderately abnormal in 30.2 % and severely abnormal in 46.5 % of patients. Early seizures (<6 months of age) were observed in 41.9 %. EEG background was abnormal when asleep or awake in 72.1 % and during sleep in 62.8 %. The interictal epileptogenic activity was recorded on 41/43 of the EEGs and was predominantly multifocal (62.8 %). An ictal EEG was obtained in 22 patients and 31.8 % had more than one seizure type. Sleep EEG (background) patterns, interictal epileptogenic activity (p = 0.046), interictal discharge localization (p = 0.015), type of ictal epileptogenic activity (p = 0.002), and localization of ictal discharge (p = 0.024) were significantly different between neuroimaging groups. The mild neuroimaging group had a higher chance of having more frequently normal sleep EEG patterns, no interictal epileptogenic activity and a further increase in the probability of walking without limitations, and less neurodevelopment delay. CONCLUSION: In patients with congenital Zika virus syndrome, epilepsy tended to be early and refractory. EEG features correlated with degree of neuroimaging abnormalities.

Review of neuroimaging findings in congenital Zika virus syndrome and its relation to the time of infection.

BACKGROUND: Many original articles and case series have been published emphasizing the neuroimaging findings of congenital Zika virus (ZIKV) infection. The majority of these studies do not follow a neuroradiological methodology to describe malformations and brain abnormalities resulting from ZIKV infection. The cause-and-effect correlation between the gestational period of maternal infection and the severity of encephalic changes at birth has rarely been reported. A systematic literature review was conducted on the neuroimaging findings in children affected with microcephaly due to ZIKV. METHODS: PubMed, Cochrane Library and Web of Science were searched for full-text articles published up to July 2019. Duplicate entries were removed. Two independent reviewers performed a quality assessment of all the studies included. RESULTS: A total of 2214 publications were identified. Of these 2170 were excluded by analysis of titles and abstracts, resulting in the inclusion of only eight articles. Chi-square and Fisher's exact tests were performed with a 95% confidence interval to verify the statistically significant differences in the neuroradiological findings between the cases of ZIKV infection in the first or second trimester of gestation. The studies published so far have described image abnormalities at random, without utilizing any pre-established neuroradiological criteria, and imaging modalities with different sensitivity and accuracy have been used, which jeopardizes a reliable and adequate statistical analysis. CONCLUSIONS: Neuroimaging abnormalities are much more prevalent and severe when the infection by ZIKV is contracted in the first or second trimester of pregnancy.

Evaluation of sleep organization in patients with attention deficit hyperactivity disorder (ADHD) and ADHD as a comorbidity of epilepsy.

OBJECTIVE/BACKGROUND: Epilepsy or attention deficit hyperactivity disorder (ADHD) can influence sleep organization in different ways. The aim of this study was to evaluate sleep organization in children and adolescents with ADHD and epilepsy, and to analyze the influence of methylphenidate. METHODS: This was an observational, cross-sectional study of children and adolescents with epilepsy, who were seizure free for at least three months, and were also diagnosed with ADHD. They were selected from the epilepsy and child neurology outpatient clinic of a university hospital in Brazil. After sample size calculation, patients were consecutively included into four different groups, with 21 patients each: epilepsy + ADHD using methylphenidate, epilepsy + ADHD not using methylphenidate, only ADHD, and a healthy control group. All participants were evaluated with the Sleep Disturbance Scale for Children (SDSC) and monitored with actigraphy for five nights/days. RESULTS: Actigraphic analysis showed a higher number of night awakenings in the epilepsy + ADHD groups; they were most prominent in the group without methylphenidate (p = 0.001). Parental reports demonstrated a higher risk for sleep disturbances in the epilepsy + ADHD without methylphenidate and the ADHD groups (p < 0.001). CONCLUSION: Primary ADHD as a comorbidity of epilepsy impairs sleep organization in children, and the use of short-acting methylphenidate seems to improve it. Both objective (actigraphic) and subjective (SDSC) measures showed significant sleep alterations between primary ADHD and ADHD as a comorbidity of epilepsy; this was most prominent in the group without methylphenidate.

Microcephaly and Zika virus: a clinical and epidemiological analysis of the current outbreak in Brazil / Microcefalia e vírus Zika: um olhar clínico e epidemiológico do surto em vigênciano Brasil

Abstract Objective: This study aimed to critically review the literature available regarding the Zika virus outbreak in Brazil and its possible association with microcephaly cases. Sources: Experts from Instituto do Cérebro do Rio Grande do Sul performed a critical (nonsystematic) literature review regarding different aspects of the Zika virus outbreak in Brazil, such as transmission, epidemiology, diagnostic criteria, and its possible association with the increase of microcephaly reports. The PubMed search using the key word “Zika virus” in February 2016 yielded 151 articles. The manuscripts were reviewed, as well as all publications/guidelines from the Brazilian Ministry of Health, World Health Organization and Centers for Disease Control and Prevention (CDC – United States). Summary of findings: Epidemiological data suggest a temporal association between the increased number of microcephaly notifications in Brazil and outbreak of Zika virus, primarily in the Brazil's Northeast. It has been previously documented that many different viruses might cause congenital acquired microcephaly. Still there is no consensus on the best curve to measure cephalic circumference, specifically in preterm neonates. Conflicting opinions regarding the diagnosis of microcephaly (below 2 or 3 standard deviations) that should be used for the notifications were also found in the literature. Conclusion: The development of diagnostic techniques that confirm a cause–effect association and studies regarding the physiopathology of the central nervous system impairment should be prioritized. It is also necessary to strictly define the criteria for the diagnosis of microcephaly to identify cases that should undergo an etiological investigation.

Resumo Objetivos: O objetivo deste estudo foi realizar uma revisão crítica da literatura sobre o surto de vírus Zika no Brasil e sua possível associação com casos de microcefalia. Fonte de dados: Especialistas em áreas afins do Instituto do Cérebro do Rio Grande do Sul realizaram uma revisão crítica (não sistemática) da literatura sobre o vírus Zika, suas formas de transmissão, a epidemia no Brasil, critérios diagnósticos e a possível associação com os casos crescentes de microcefalia. O uso da palavra chave “Zika virus” na base de dados do PubMed em fevereiro de 2016, retorna 151 publicações. Estes textos foram revisados assim como todas as publicações e recomendações do Ministério da Saúde, Organização Mundial da Saúde e Centro de Controle de Doenças (CDC – USA). Síntese dos dados: Os dados epidemiológicos sugerem uma relação temporal entre aumento da notificação de casos de microcefalia e o surto de vírus Zika, principalmente no Nordeste do Brasil. Agentes virais comprovadamente podem ser causadores de microcefalia congênita adquirida. Não existe um consenso sobre a melhor curva de perímetro cefálico a ser utilizada, principalmente nos prematuros. Assim como também existem divergências sobre a definição de microcefalia (abaixo de 2 ou 3 desvios padrões) a ser padronizada nas notificações. Conclusão: Deve-se priorizar o desenvolvimento de técnicas diagnósticas que confirmem uma relação causa–efeito e estudos sobre mecanismos da patogênese da infecção pelo Zika no sistema nervoso central. Também é necessário definir e universalizar os critérios diagnósticos para a identificação dos casos de microcefalia que devem ser submetidos à investigação etiológica.