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.

Potential epigenetic mechanisms in psychotherapy: a pilot study on DNA methylation and mentalization change in borderline personality disorder.

Genetic and early environmental factors are interwoven in the etiology of Borderline Personality Disorder (BPD). Epigenetic mechanisms offer the molecular machinery to adapt to environmental conditions. There are gaps in the knowledge about how epigenetic mechanisms are involved in the effects of early affective environment, development of BPD, and psychotherapy response. We reviewed the available evidence of the effects of psychotherapy on changes in DNA methylation and conducted a pilot study in a sample of 11 female adolescents diagnosed with BPD, exploring for changes in peripheral DNA methylation of FKBP5 gene, which encodes for a stress response protein, in relation to psychotherapy, on symptomatology and underlying psychological processes. For this purpose, measures of early trauma, borderline and depressive symptoms, psychotherapy outcome, mentalization, and emotional regulation were studied. A reduction in the average FKBP5 methylation levels was observed over time. Additionally, the decrease in FKBP5 methylation observed occurred only in those individuals who had early trauma and responded to psychotherapy. The results suggest an effect of psychotherapy on epigenetic mechanisms associated with the stress response. The finding that epigenetic changes were only observed in patients with early trauma suggests a specific molecular mechanism of recovery. The results should be taken with caution given the small sample size. Also, further research is needed to adjust for confounding factors and include endocrinological markers and therapeutic process variables.

Validation of the Family Health Behavior Scale for the Brazilian population

Abstract Objective: To validate the Family Health Behavior Scale (FHBS) for Brazilian families. Methods: The sample included 272 children aged 5 to 12 years old. Caregivers and their healthy answered the FHBS and questions about physical activity. In addition, anthropometric measurements of the children's weight and height were performed, as well as the bioimpedance exam. The scale was translated and the following validities were assessed: content (qualitative analysis and content validity index), construct (factor analysis) and concurrent validity (difference between domains and the total score with the categories of BMI, fat percentage and physical activity). Reliability (Cronbach's alpha, ceiling-floor effect, two-half test, intraclass correlation and Bland - Altman) was also assessed. Results: FHBS instrument performed well with regard to the psychometric properties in the Brazilian population. The content validity index was 0.987. Fit indices of the factor analysis were considered satisfactory, according to Bartlett's sphericity test (χ 2 = 1927, df = 351; p < 0.001) and the Kaiser-Meyer-Olkin index (KMO = 0.789). Concurrent validity, the differences between the mean of the domains and the total score between the categories of BMI (p = 0.011), percentage of fat (0.004) and physical activity (p < 0.001) were all significant. The reliability results were Cronbach's alpha internal consistency = 0.83, adequate ceiling-floor effect, 0.8105 (0.09 SD) two-half test, 0.626 intraclass correlation (95% CI: 0.406 to 0.777) and Bland - Altman -0.840 (-22.76 to 21.07). Conclusion: The FHBS adapted for the Brazilian population showed evidence of adequate psychometric performance.

Validation of the Family Health Behavior Scale for the Brazilian population.

OBJECTIVE: To validate the Family Health Behavior Scale (FHBS) for Brazilian families. METHODS: The sample included 272 children aged 5 to 12 years old. Caregivers and their healthy answered the FHBS and questions about physical activity. In addition, anthropometric measurements of the children's weight and height were performed, as well as the bioimpedance exam. The scale was translated and the following validities were assessed: content (qualitative analysis and content validity index), construct (factor analysis) and concurrent validity (difference between domains and the total score with the categories of BMI, fat percentage and physical activity). Reliability (Cronbach's alpha, ceiling-floor effect, two-half test, intraclass correlation and Bland - Altman) was also assessed. RESULTS: FHBS instrument performed well with regard to the psychometric properties in the Brazilian population. The content validity index was 0.987. Fit indices of the factor analysis were considered satisfactory, according to Bartlett's sphericity test (χ 2 = 1927, df = 351; p < 0.001) and the Kaiser-Meyer-Olkin index (KMO = 0.789). Concurrent validity, the differences between the mean of the domains and the total score between the categories of BMI (p = 0.011), percentage of fat (0.004) and physical activity (p < 0.001) were all significant. The reliability results were Cronbach's alpha internal consistency = 0.83, adequate ceiling-floor effect, 0.8105 (0.09 SD) two-half test, 0.626 intraclass correlation (95% CI: 0.406 to 0.777) and Bland - Altman -0.840 (-22.76 to 21.07). CONCLUSION: The FHBS adapted for the Brazilian population showed evidence of adequate psychometric performance.

Body composition parameters can better predict body size dissatisfaction than body mass index in children and adolescents.

PURPOSE: Recent studies suggest that body mass index is not a reliable enough measurement for body composition in individuals, particularly in older and younger people. However, most research on body image has used the body mass index (BMI) as a physiological predictor of body satisfaction, particularly in children. The aim of this study was to investigate whether body composition is a better predictor of body size dissatisfaction in children than BMI. METHODS: This is a cross-sectional study. Healthy children and adolescents aged 5-19 years, sex male and female, were recruited using a convenience sample in Brazil. BMI was measured according to the international standardization method and body composition was measured by bioelectrical impedance analysis (BIA) with a portable device model (BIA InBodyS10 multi-frequency, USA). Body size dissatisfaction was assessed using the Kakeshita's Figure Rating Scale for Brazilian Children. Data were analyzed with logistic regression analysis. RESULTS: A total of 547 participants were evaluated, including 54% females and 67% Caucasian, with a mean age of 11.4 ± 3.8 years. The mean BMI was 20.5 ± 4.6 kg/m2, and the mean percentages of fat and lean mass were 23.01 ± 10.59% and 72.84 ± 10.03%, respectively. In the multivariable model, only body composition was significantly associated with body size dissatisfaction (odds ratio: 1.849 (1.085-3.149, p = 0.024) and 1.828 (1.043-3.202, p = 0.035), respectively). CONCLUSIONS: Body composition measures can better predict body size dissatisfaction in children and adolescents than BMI. This result may be relevant for the design of future studies on physiological indicators and body satisfaction. LEVEL OF EVIDENCE: Level V, cross-sectional study.

Health-related quality of life in post-infectious bronchiolitis obliterans: agreement between children and their proxy / Qualidade de vida relacionada à saúde na bronquiolite obliterante pós-infecciosa: concordância entre as crianças e seus cuidadores

Abstract Objective: To assess the level of agreement in health-related quality of life between children with Post-infectious Bronchiolitis Obliterans and their parent (so-called proxy). Methods: Participants aged between 8and 17 years who had been previously diagnosed with Post-infectious Bronchiolitis Obliterans were regularly followed up at a pediatric pulmonology outpatient clinic. Parents or legal guardians (caregivers) of these patients were also recruited for the study. A validated and age-appropriate version of the Pediatric Quality of Life Inventory 4.0 was used for the assessment of health-related quality of life. Caregivers completed the corresponding proxy versions of the questionnaire. The correlation between self and proxy reports of health-related quality of life was determined by intra-class correlation coefficient and dependent t-tests. Results: The majority of participants were males (79.4%), and the average age was 11.8 years. Intra-class correlations between each of the Pediatric Quality of Life Inventory 4.0 domains and the total score were all lower than 0.6, with a range between 0.267 (poor) and 0.530 (fair). When the means of each domain and the total score of the questionnaires were compared, caregivers were observed to have a significantly lower health-related quality of life score than children, with the exception of the social domain in which the difference was not significant. However, the differences in score exceeded the critical threshold difference of four points in all other domains. Conclusion: Proxies of children and adolescents with Post-infectious Bronchiolitis Obliterans appear to consistently perceive their children as having lower health-related quality of life than how the patients perceive themselves.

Resumo: Objetivo: Avaliar o nível de concordância a respeito da qualidade de vida relacionada à saúde entre crianças com bronquiolite obliterante pós-infecciosa e seus pais (responsáveis). Métodos: Os participantes entre 8-17 anos, anteriormente diagnosticados com bronquiolite obliterante pós-infecciosa, foram acompanhados regularmente no ambulatório de pneumologia pediátrica. Os pais ou responsáveis legais (cuidadores) desses pacientes também foram convidados a participar do estudo. Uma versão validada e adequada para a idade do Inventário Pediátrico de Qualidade de Vida, versão 4.0, foi utilizada para a avaliação da qualidade de vida relacionada à saúde. Os cuidadores concluíram as versões do questionário correspondentes aos responsáveis. A correlação entre os autorrelatos e os relatos dos responsáveis da qualidade de vida relacionada à saúde foi determinada pelo coeficiente de correlação intraclasse e pelos testes t dependentes. Resultados: A maior parte dos participantes era do sexo masculino (79,4%) e a idade média foi 11,8 anos. As correlações intraclasse entre cada um dos domínios do Inventário Pediátrico de Qualidade de Vida e o escore total foram todas inferiores a 0,6, com intervalo entre 0,267 (baixo) e 0,530 (justo). Quando as médias de cada domínio e o escore total dos questionários foram comparados, observamos que os cuidadores apresentaram qualidade de vida relacionada à saúde significativamente menor em comparação com as crianças, com exceção do domínio social, no qual a diferença não foi significativa. Contudo, as diferenças no escore ultrapassaram o limite de diferença essencial de 4 pontos em todos os outros domínios. Conclusão: Os responsáveis pelas crianças e adolescentes com bronquiolite obliterante pós-infecciosa parecem perceber de forma consistente que suas crianças possuem qualidade de vida relacionada à saúde menor que os próprios pacientes.

Health-related quality of life in post-infectious bronchiolitis obliterans: agreement between children and their proxy.

OBJECTIVE: To assess the level of agreement in health-related quality of life between children with Post-infectious Bronchiolitis Obliterans and their parent (so-called proxy). METHODS: Participants aged between 8and 17 years who had been previously diagnosed with Post-infectious Bronchiolitis Obliterans were regularly followed up at a pediatric pulmonology outpatient clinic. Parents or legal guardians (caregivers) of these patients were also recruited for the study. A validated and age-appropriate version of the Pediatric Quality of Life Inventory 4.0 was used for the assessment of health-related quality of life. Caregivers completed the corresponding proxy versions of the questionnaire. The correlation between self and proxy reports of health-related quality of life was determined by intra-class correlation coefficient and dependent t-tests. RESULTS: The majority of participants were males (79.4%), and the average age was 11.8 years. Intra-class correlations between each of the Pediatric Quality of Life Inventory 4.0 domains and the total score were all lower than 0.6, with a range between 0.267 (poor) and 0.530 (fair). When the means of each domain and the total score of the questionnaires were compared, caregivers were observed to have a significantly lower health-related quality of life score than children, with the exception of the social domain in which the difference was not significant. However, the differences in score exceeded the critical threshold difference of four points in all other domains. CONCLUSION: Proxies of children and adolescents with Post-infectious Bronchiolitis Obliterans appear to consistently perceive their children as having lower health-related quality of life than how the patients perceive themselves.

Validation of the Inventaire du Milieu Familial Questionnaire (French version of the Infant/Toddler HOME) into the Brazilian Portuguese language / Validação do questionário Inventaire du Milieu Familial (versão francesa do Infant Toddler Home) para a língua portuguesa

Abstract Objective: To validate the Brazilian Portuguese version of the Family Environment Assessment questionnaire (Inventaire du Milieu Familial). Methods: The validation process was carried out in two stages. First, translation and back-translation were performed, and in the second phase, the questionnaire was applied in 72 families of children between 0 and 24 months for the validation process. The tool consists of the following domains: mother's communication ability; behavior; organization of the physical and temporal environment; collection/quantity of toys; maternal attitude of constant attention toward her baby; diversification of stimuli; baby's behavior. The following was performed for the scale validation: 1 - content analysis (judgment); 2 - construct analysis (factorial analysis - Kaiser-Meyer-Olkin, Bartlett, and Pearson's correlation tests); 3 - criterion analysis (calculation of Cronbach's alpha coefficient, intraclass correlations, and split-half correlations). Results: The mean age of the children was 9 ± 6.7 months, and of these, 35 (48.6%) were males. Most correlations between items and domains were significant. In the factorial analysis of the scale, Kaiser-Meyer-Olkin values were 0.76, Bartlett's test showed a p-value < 0.001, and correlation between items and domains showed a p-value < 0.01. Regarding the validity, Cronbach's alpha was 0.92 (95% CI: 0.89-0.94). The intraclass correlation among the evaluators was 0.97 (0.96-0.98) and split-half correlations, r: 0.60, with p < 0.01. Conclusions: The Portuguese version of the Inventaire du Milieu Familial showed good to excellent performance regarding the assessed psychometric properties.

Resumo Objetivo: Validar a versão em português do Questionário de Avaliação do Ambiente Familiar (Inventaire du Milieu Familial). Métodos: O processo de validação foi feito em duas etapas. Primeiramente, realizou-se a tradução e retrotradução e, na segunda fase, o questionário foi aplicado em 72 famílias de crianças entre zero e 24 meses para o processo de validação. O instrumento é formado pelos seguintes domínios: Capacidade de comunicação da mãe; Comportamento; Organização do ambiente físico e temporal; Acervo/quantidade de brinquedos; Implicação da mãe com seu bebê; Diversificação de estímulos; Comportamento do bebê. Para a validação da escala foi realizada: 1- análise de conteúdo (julgamento); 2- análise de construto (análise fatorial - testes Kaiser-Meyer-Olkin, Bartlett e correlação de Pearson); 3- análise de critério (cálculo do coeficiente alfa de cronbach, correlações intraclasse e correlações split-half). Resultados: A média de idade das crianças foi 9 ± 6,7 meses e, dessas, 35 (48,6%) eram do sexo masculino. A maioria das correlações entre os itens e os domínios foi significativa. Na análise fatorial da escala, os valores de Kaiser-Meyer-Olkin foram 0,76, teste de Bartlett com p < 0,001 e correlação entre os itens e domínios p < 0,01. Em relação à validade, o alfa de Cronbach foi de 0,92 (IC 95% 0,89-0,94). A correlação intraclasse entre os avaliadores foi de 0,97 (0,96-0,98) e correlações split-half r: 0,60 p < 0,01. Conclusões: A versão portuguesa do Inventaire du Milieu Familial apresentou um bom à excelente desempenho nas propriedades psicométricas avaliadas.

Validation of the Inventaire du Milieu Familial Questionnaire (French version of the Infant/Toddler HOME) into the Brazilian Portuguese language.

OBJECTIVE: To validate the Brazilian Portuguese version of the Family Environment Assessment questionnaire (Inventaire du Milieu Familial). METHODS: The validation process was carried out in two stages. First, translation and back-translation were performed, and in the second phase, the questionnaire was applied in 72 families of children between 0 and 24 months for the validation process. The tool consists of the following domains: mother's communication ability; behavior; organization of the physical and temporal environment; collection/quantity of toys; maternal attitude of constant attention toward her baby; diversification of stimuli; baby's behavior. The following was performed for the scale validation: 1 - content analysis (judgment); 2 - construct analysis (factorial analysis - Kaiser-Meyer-Olkin, Bartlett, and Pearson's correlation tests); 3 - criterion analysis (calculation of Cronbach's alpha coefficient, intraclass correlations, and split-half correlations). RESULTS: The mean age of the children was 9±6.7 months, and of these, 35 (48.6%) were males. Most correlations between items and domains were significant. In the factorial analysis of the scale, Kaiser-Meyer-Olkin values were 0.76, Bartlett's test showed a p-value<0.001, and correlation between items and domains showed a p-value<0.01. Regarding the validity, Cronbach's alpha was 0.92 (95% CI: 0.89-0.94). The intraclass correlation among the evaluators was 0.97 (0.96-0.98) and split-half correlations, r: 0.60, with p<0.01. CONCLUSIONS: The Portuguese version of the Inventaire du Milieu Familial showed good to excellent performance regarding the assessed psychometric properties.

The impact of methylphenidate on seizure frequency and severity in children with attention-deficit-hyperactivity disorder and difficult-to-treat epilepsies.

AIM: Difficult-to-treat epilepsies and attention-deficit-hyperactivity disorder (ADHD) often co-occur. Because of concerns about the use of stimulants in children with this comorbidity, the impact of ADHD treatment on seizure frequency and severity is not known. This pilot study evaluated the safety and efficacy of methylphenidate in this population. METHOD: After a 3 month period in which antiepileptic drugs were adjusted, 22 patients recruited from a specialist outpatient clinic for severe epilepsy (16 males, six females; mean age 11 y 2 mo, SD 3 y 2 mo) received methylphenidate for 3 months in an open label, non-controlled trial; four with generalized or multifocal (symptomatic/cryptogenic) epilepsy, one with generalized (idiopathic) epilepsy, 17 with partial (symptomatic/cryptogenic) epilepsy; five with partial seizures only, 17 with primarily or secondarily generalized seizures). Epilepsy, ADHD symptoms, and side effects were assessed using the Swanson, Nolan, and Pelham Questionnaire, the Child Behavior Checklist, the Hague Seizure Severity Scale, and the Side Effects Rating Scale. RESULTS: Methylphenidate significantly improved ADHD. After 3 months of treatment, 73% of patients no longer had clinically significant symptoms. Methylphenidate also reduced seizure severity (9-point median decrease on the Hague Seizure Severity Scale). Seizure frequency increased in four out of 22 patients, but only one patient withdrew from the study for this reason. Most patients experienced no major side effects. INTERPRETATION: These data are among the first showing that low doses of methylphenidate are safe and effective to treat ADHD symptoms in patients with difficult-to-treat epilepsies. Randomized controlled trials are needed to replicate the findings.