Transtorno de déficit de atenção/hiperatividade em crianças muito prematuras e/ou com muito baixo peso ao nascer : avaliação da prevalência e desenvolvimento de uma calculadora de risco

A incidência de nascimento prematuro e de baixo peso ao nascer permanece alta em todo o mundo. Além de uma alta taxa de mortalidade, os sobreviventes podem enfrentar muitas morbidades ao longo da vida, como transtornos motores, sensoriais, cognitivos e psiquiátricos, especialmente os recém-nascidos muito prematuros (MP) e os de muito baixo peso (MBPN). O transtorno de déficit de atenção/hiperatividade (TDAH), um transtorno psiquiátrico com alta prevalência, morbidade e custos em saúde, é um dos problemas do neurodesenvolvimento mais comuns descritos nessa população. Embora os recém-nascidos MP/MBPN pareçam ter maior risco futuro de TDAH, a magnitude desse risco não está bem definida. Além disso, vários fatores de risco pré-natais e neonatais podem desempenhar um papel significativo na associação ou etiologia do TDAH em indivíduos MP/MBPN. O objetivo desta tese de doutorado é de revisar sistematicamente e meta-analisar o risco de indivíduos MP/MBPN de desenvolver tanto TDAH como apresentarem uma sintomatologia dimensional do transtorno em comparação com controles com idade e/ou peso de nascimento normais. Buscou-se também desenvolver um modelo preditivo multivariável e criar uma calculadora de risco individualizada para ajudar os médicos a identificar, entre os recém-nascidos MP/MBPN, aqueles com maior probabilidade de ter TDAH no futuro usando preditores rotineiramente coletados nas unidades de terapia intensiva neonatal. No primeiro artigo, em uma revisão sistemática e meta-análise de doze estudos (n=1.787), mostrou-se que tanto os sujeitos MP/MBPN quanto os extremamente prematuros/extremamente baixo peso ao nascer (EP/EBPN) apresentam maior risco de TDAH [Razão de Chances (RC): 3,04; IC 95%, 2,19–4,21]. As análises de subgrupos demonstraram que, quanto mais extremos os casos, maiores as RC (MP/MBPN, RC: 2,25; IC 95%, 1,56–3,26; EP/EBPN, RC: 4,05; IC 95%, 2,38–6,87). Concluímos que os indivíduos MP/MBPN têm um risco aumentado de diagnóstico de TDAH em comparação com os controles, e esses achados são ainda mais fortes no grupo EP/EBPN. Por fim, no segundo artigo, construímos um escore de risco e uma calculadora de risco para o TDAH, com base em sete fatores de risco avaliados em uma coorte clínica de 104 crianças MP/MBPN (sepse tardia confirmada por hemocultura, enterocolite necrosante, convulsões neonatais, leucomalácia periventricular, síndrome do desconforto respiratório, tempo de internação e número total de sintomas de TDAH da mãe). A calculadora, disponível em https://jscalc.io/calc/unaQG5TuvzVzuzmV, apresentou bons parâmetros de desempenho e é uma ferramenta clínica prática potencial para a identificação precoce de crianças MP/MBPN com alto risco de diagnóstico futuro de TDAH. A presente tese de doutorado trouxe elementos para o dimensionamento da associação entre MP/MBPN e TDAH e constatou quais fatores de risco podem predizer um futuro diagnóstico de TDAH.The incidence of preterm birth and low birth weight remains high worldwide. Besides a high mortality rate, survivors can face many lifelong morbidities, such as motor, sensorial, cognitive, and psychiatric disorders, especially very preterm (VP) and very low birth weight (VLBW) newborns. Attention-deficit/hyperactivity disorder (ADHD), a psychiatric disorder with high prevalence, morbidity, and health costs, is one of the most common neurodevelopmental disorders described in this population. Although VP/VLBW newborns seem to have a higher risk of later ADHD, the magnitude of the risk is not well-defined. Also, several pre-/perinatal risk factors may play a significant role in the association or etiology of ADHD in VP/VLBW individuals. The purpose of this doctoral thesis was to systematically review and meta-analyze the risk of VP/VLBW individuals to develop ADHD categorical diagnosis/dimensional symptomatology compared to controls with normal birth age and/or weight. In addition, we sought to develop a multivariable predictive model and to build an individualized risk calculator to help clinicians to identify, among VP/VLBW newborns, those who are most likely to have ADHD in the future using predictors that are routinely collected in neonatal intensive care unit setting. In the first article, in a systematic review and meta-analysis of twelve studies (n=1,787), we showed that both VP/VLBW and extremely preterm/extremely low birth weight (EP/ELBW) subjects have a higher risk of developing ADHD [odds ratio (OR): 3.04; 95% CI, 2.19–4.21]. Subgroup analyses demonstrated that the more extreme the cases, the higher the ORs (VP/VLBW, OR: 2.25; 95% CI, 1.56–3.26; EP/ELBW, OR: 4.05; 95% CI, 2.38–6.87). We concluded that VP/VLBW subjects have an increased risk of ADHD diagnosis compared to controls and these findings are even stronger in the EP/ELBW group. Finally, in the second article, we built a risk score and a risk calculator for ADHD based on seven risk factors assessed in a clinical cohort of 104 VP/VLBW children (late-onset sepsis confirmed by blood culture, necrotizing enterocolitis, neonatal seizures, periventricular leukomalacia, respiratory distress syndrome, length of hospital stay and total number of maternal ADHD symptoms). The calculator, available at https://jscalc.io/calc/unaQG5TuvzVzuzmV, showed good performance parameters and is a potential practical clinical tool for early identification of VP/VLBW children at high risk of future ADHD diagnosis. The present doctoral thesis shed light on the magnitude of the association between VP/VLBW children and ADHD and found which risk factors can predict future ADHD diagnosis

Does ADHD worsen inhibitory control in preschool children born very premature and/or with very low birth weight?

Introduction: Deficits in executive functioning, especially in inhibitory control, are present in children born very premature and/or with very low birth weight (VP/VLBW) and in children with attention-deficit/ hyperactivity disorder (ADHD). Objective: To evaluate whether ADHD imposes additional inhibitory control (IC) deficits in preschoolers born VP/VLBW. Methods: 79 VP/VLBW (4 to 7 years) children were assessed for ADHD using the Schedule for Affective Disorders and Schizophrenia for School Aged Children – Present and Lifetime Version (K-SADS-PL). IC was measured with Conners’ Kiddie Continuous Performance Test (K-CPT 2) and the Behavior Rating Inventory of Executive Function – Preschool Version (BRIEF-P). Results: No significant differences were found between ADHD (n = 24) and non-ADHD children (n = 55) for any of the measures (p = 0.062 to p = 0.903). Both groups had deficits in most K-CPT 2 scores compared to normative samples, indicating poor IC and inconsistent reaction times. Conclusions: ADHD does not aggravate IC deficits in VP/VLBW children. Either neuropsychological tasks and parent reports of executive functions (EFs) may not be sensitive enough to differentiate VP/VLBW preschoolers with and without ADHD, or these children’s EFs are already so impaired that there is not much room for additional impairments imposed by ADHD

Training attention control of very preterm infants: protocol for a feasibility study of the Attention Control Training (ACT)

Background Children born preterm may display cognitive, learning, and behaviour difficulties as they grow up. In particular, very premature birth (gestation age between 28 and less than 32 weeks) may put infants at increased risk of intellectual deficits and attention deficit disorder. Evidence suggests that the basis of these problems may lie in difficulties in the development of executive functions. One of the earliest executive functions to emerge around 1 year of age is the ability to control attention. An eye-tracking-based cognitive training programme to support this emerging ability, the Attention Control Training (ACT), has been developed and tested with typically developing infants. The aim of this study is to investigate the feasibility of using the ACT with healthy very preterm (VP) infants when they are 12 months of age (corrected age). The ACT has the potential to address the need for supporting emerging cognitive abilities of VP infants with an early intervention, which may capitalise on infants’ neural plasticity. Methods/design The feasibility study is designed to investigate whether it is possible to recruit and retain VP infants and their families in a randomised trial that compares attention and social attention of trained infants against those that are exposed to a control procedure. Feasibility issues include the referral/recruitment pathway, attendance, and engagement with testing and training sessions, completion of tasks, retention in the study, acceptability of outcome measures, quality of data collected (particularly, eye-tracking data). The results of the study will inform the development of a larger randomised trial. Discussion Several lines of evidence emphasise the need to support emerging cognitive and learning abilities of preterm infants using early interventions. However, early interventions with preterm infants, and particularly very preterm ones, face difficulties in recruiting and retaining participants. These problems are also augmented by the health vulnerability of this population. This feasibility study will provide the basis for informing the implementation of an early cognitive intervention for very preterm infants. Trial registration Registered Registration ID: NCT03896490. Retrospectively registered at Clinical Trials Protocol Registration and Results System (clinicaltrials.gov)

Sintomas psiquiátricos gerais e depressivos não foram preditivos de mortalidade em uma coorte de idosos saudáveis no sul do Brasil

General psychiatric symptoms may interfere with the ability of individuals to take care of their health, to get involved with activities and develop social abilities, thereby increasing risk of death. Objective: To evaluate general psychiatric symptoms as predictive factors for mortality in a community elderly cohort in Southern Brazil. Methods: 345 healthy elderly, aged ≥60 years, from the catchment area of Hospital de Clinicas de Porto Alegre were followed from 1996. Data for the present study were drawn from the period 1996-2004. General psychiatric symptoms (Self-Reporting Questionnaire – SRQ), depressive symptoms (Montgomery-Asberg depressive rating scale), and Mini Mental State Examination scores at baseline were included in the study. Socio-demographic, medical conditions, and functional capacity were also analyzed. The outcome was vital status at follow-up obtained from family members, hospital records and checked against official death registers. Results: Of the 345 baseline individuals, 246 were followed-up. The global mortality rate over the study period was 36.9% (N=90). Those who deceased during the period were older (73.5±7.5), more dependent overall, and more cognitively impaired than the living elderly (univariate analyses). In the logistic regression, only age (OR=0.93; p=0.003) and functional capacity (OR=0.22; p=0.007) remained significant in the final equation. Conclusion: Psychiatric symptoms presented no association with mortality in the present sample. Older age and functional incapacity were risk factors for mortality.Sintomas psiquiátricos gerais podem interferir com a capacidade do indivíduo cuidar de sua saúde, de envolver-se com outras atividades e desenvolver habilidades sociais, aumentando o risco de morte. Objetivo: Avaliar se os sintomas psiquiátricos são preditores de mortalidade em uma coorte de idosos de uma comunidade do sul do Brasil. Métodos: 345 idosos saudáveis, com idade igual ou superior a 60 anos, da área de abrangência de um hospital universitário de uma cidade do sul do Brasil foram acompanhados desde 1996. Os dados desse estudo representam o período de avaliação de 1996 a 2004. Os sintomas psiquiátricos na avaliação inicial foram medidos através do Self-Reporting Questionnaire (SRQ) e da Escala Montgomery-Asberg para sintomas depressivos (MADRS) e as variáveis independentes foram desempenho cognitivo no Mini Exame do Estado Mental (MEEM). Dados sócio-demográficos, questionário sobre condições sociais e de saúde, e capacidade funcional também foram analizados. O desfecho principal foi mortalidade durante o seguimento, obtida através de familiares e registros de óbito. Resultados: Dos 345 idosos “baseline”, dados foram obtidos de 246 no seguimento. Taxa de mortalidade global no seguimento foi de 36.9% (N=90). Aqueles que faleceram durante o período de avaliação eram mais idosos (73,5±7,5), mais globalmente dependentes e comprometidos do ponto de vista cognitivo do que os idosos que permaneceram vivos (análises univariadas). Na regressão logística, apenas idade (RC=0,93; p=0,003) e capacidade funcional (RC=0,22; p=0,007) mantiveram significância na equação final. Conclusões: Sintomas psiquiátricos não mostraram efeito preditor para mortalidade na presente amostra. Maior idade e incapacitação foram fatores de risco para mortalidade

General psychiatric or depressive symptoms were not predictive for mortality in a healthy elderly cohort in Southern Brazil

Abstract General psychiatric symptoms may interfere with the ability of individuals to take care of their health, to get involved with activities and develop social abilities, thereby increasing risk of death. Objective: To evaluate general psychiatric symptoms as predictive factors for mortality in a community elderly cohort in Southern Brazil. Methods: 345 healthy elderly, aged ³60 years, from the catchment area of Hospital de Clinicas de Porto Alegre were followed from 1996. Data for the present study were drawn from the period 1996-2004. General psychiatric symptoms (Self-Reporting Questionnaire - SRQ), depressive symptoms (Montgomery-Asberg depressive rating scale), and Mini Mental State Examination scores at baseline were included in the study. Socio-demographic, medical conditions, and functional capacity were also analyzed. The outcome was vital status at follow-up obtained from family members, hospital records and checked against official death registers. Results: Of the 345 baseline individuals, 246 were followed-up. The global mortality rate over the study period was 36.9% (N=90). Those who deceased during the period were older (73.5±7.5), more dependent overall, and more cognitively impaired than the living elderly (univariate analyses). In the logistic regression, only age (OR=0.93; p=0.003) and functional capacity (OR=0.22; p=0.007) remained significant in the final equation. Conclusion: Psychiatric symptoms presented no association with mortality in the present sample. Older age and functional incapacity were risk factors for mortality