A influência da data de nascimento no diagnóstico e tratamento de PHDA

2019/2020 Mariana Martins de Andrade A influência da data de nascimento no diagnóstico e tratamento de PHDA The influence of birth date in the diagnosis and treatment of ADHD Março, 2020 Mestrado Integrado em Medicina Área: Medicina Clínica - Pediatria Tipologia: Monografia Trabalho efetuado sob a Orientação de: Dr. Daniel José Dias Gonçalves Trabalho organizado de acordo com as normas da revista: Acta Médica Portuguesa Mariana Martins de Andrade A influência da data de nascimento no diagnóstico e tratamento de PHDA The influence of birth date in the diagnosis and treatment of ADHD Março, 2020 Dedico este trabalho, com gratidão, às pessoas que me ajudaram a chegar aqui: aos meus pais e irmã, que sempre me apoiaram de todas as formas, aos meus avós, tanto os que cá estão, como os que já partiram, ao meu namorado João, cujo apoio e exemplo me motivam a ir mais longe, aos amigos com quem partilhei o meu percurso académico. Agradeço, também, ao Dr. Daniel Gonçalves, por todo o apoio e disponibilidade. 1 The influence of birth date in the diagnosis and treatment of ADHD A influência da data de nascimento no diagnóstico e tratamento de PHDA Mariana Martins de Andrade, Faculty of Medicine, University of Porto, Portugal Daniel José Dias Gonçalves, MD, Department of Gynecology-Obstetrics and Pediatrics, Faculty of Medicine, University of Porto, Portugal Corresponding author: Mariana Martins de Andrade Faculdade de Medicina da Universidade do Porto Al. Prof. Hernâni Monteiro 4200 Porto Contact: [email protected] 2 The influence of birth date in the diagnosis and treatment of ADHD Abstract Background Multiple studies from different countries suggest that the youngest children within a classroom are more likely to be diagnosed and treated for attention-deficit/hyperactivity disorder (ADHD). This review aims to summarize the existing studies that focus on this topic and to provide some possible explanations for this positive relationship between a late birth date and the diagnosis and treatment of ADHD. Methods A literature search of PubMed was conducted, as well as some additional research for contextualization of the subject. In addition, some studies were included through snowball research. Results 24 studies exploring the relationship between birth date and the likelihood of being diagnosed and/or treated for ADHD were included in this review, including a total of 35.127.821 subjects, from 16 different countries. 19 studies (79%) showed a positive relationship between birth date and diagnosis and/or treatment of ADHD, whereas 5 studies (21%) failed to show such a relationship. Conclusions A child’s date of birth and relative age compared to other children in school class should be taken into account while investigating for the presence of ADHD, in order to avoid misdiagnosis and mistreatment based on a child’s relative immaturity. Keywords: ADHD; diagnosis; treatment; birth date; relative age 3 A influência da data de nascimento no diagnóstico e tratamento de PHDA Resumo Introdução Vários estudos realizados em diferentes países parecem sugerir que as crianças mais novas numa sala de aula têm maior probabilidade de vir a ser diagnosticadas com Perturbação de Hiperatividade e Défice de Atenção (PHDA) e a receber tratamento farmacológico. Com esta revisão, pretende-se reunir a evidência existente sobre este tópico e apresentar algumas possíveis explicações para esta relação entre uma data de nascimento tardia e o diagnóstico/tratamento de PHDA. Métodos Foi realizada uma pesquisa na plataforma PubMed, tendo alguns estudos sido incluídos através de snowball research. Foi, ainda, realizada pesquisa adicional para contextualização do tema. Resultados Foram incluídos nesta revisão 24 estudos, incluindo um total de 35.127.821 participantes de 16 países diferentes. Destes estudos, 19 (79%) apresentam resultados a favor da presença de uma relação positiva entre a data de nascimento e o diagnóstico/tratamento de PHDA, enquanto que 5 estudos (21%) não demonstram evidência de tal relação. Conclusão A data de nascimento de uma criança e a sua idade relativa em comparação com as outras crianças na mesma sala de aula devem ser tidas em consideração no diagnóstico de PHDA, por forma a evitar erros no diagnóstico e a instauração de tratamento desnecessário com base na imaturidade relativa da criança. Palavras-chave: PHDA; diagnóstico; tratamento; data de nascimento; idade relativa 4 Abbreviations ADHD – Attention-Deficit/Hyperactivity Disorder CAARS - Conners' Adult ADHD Rating Scale DSM-5 - Diagnostic and Statistical Manual of Mental Disorders, 5th edition SDQ – Strengths and Difficulties Questionnaire WURS - Wender Utah Rating Scale 11 Evans et al18 66 984 Children born within 120 days before the kindergarten eligibility cutoff date had a diagnosis rate of 9.67%, compared with 7.62% for those born within 120 days after the cutoff date. Similarly, there was a 0.5% difference in the use of stimulants between children born within 120 days before and after the cutoff date. The percentage of children who are using any stimulant varied between 6.5% for children born within 120 days before the cutoff date and 5.2% for those born afterwards. Librero et al20 20 237 Boys born in December were more likely to be prescribed methylphenidate or atomoxetine for ADHD than those born in January (OR 2.81, 95%CI 1.53-5.16). Zoega et al6 11 785 It found that children in the youngest third of class (born in September-December) were 50% more likely (95%CI 28%- 80%) to be prescribed stimulants for ADHD than those in the oldest third (born January-April). Elder21 11 784 Children born less than 181 days before their state’s eligibility cutoff date were roughly 50% more likely to receive a diagnosis of ADHD (0.075 vs 0.051) and to be prescribed behavioural medications by grade five (0.054 vs 0.035) than those born until 181 days after the cutoff dates. Dee et al22 8 092 Increasing the school starting age by 1 year reduces symptoms of inattention/hyperactivity at age 7 by 0.73 SD (i.e., - 0.147/0.201) and at age 11 by 0.69 SD (i.e., -0,131/0.190). Bonati et al23 4070 Comparing with boys born in January, the incidence ratio increased from 1.11 for boys born in February (95%CI 0.572.16) to 2.25 (95%CI 1.21-4.19) for those born in December. Gokçe et al24 3 696 This study found that the first grade group that began primary school before the age of 72 months had a higher prevalence of ADHD than the group that started school between the ages of 72-77 months (15.9% vs 9.4%; p<0.001) and the group that started school between the ages of 78-83 months (15.9% vs. 6.4%; p<0.001). Rivas-Juesas et al25 3 469 58% of boys and 80% of girls diagnosed with ADHD were born in the second semester of the year (the cutoff date in Spain is December 31), and the last semester of the year had the highest number of cases. Krabbe et al26 2218 The risk of being prescribed methylphenidate was more than double for children born in September and August (being September 1 the cutoff date), compared with children born in December and January (RR 2.43; 95%CI 1.09-5.42). Studies that show no relationship between date of birth and diagnosis/treatment of ADHD Pottegard et al27 932 032 Over the study period, the prevalence proportion ratio (PPR), comparing the youngest children in a grade (born OctoberDecember) and the oldest (born January-March) was 1.08 (95% CI, 1.04–1.12); however, between the years 2006-2012, the expected relative age effect was not observed (PPR 0.93; 95% CI, 0.89–0.97). 12 Dalsgaard et al28 418 396 No significative differences on the likelihood of having purchased ADHD medication (dexamphetamine, methylphenidate or atomoxetine) between children born in the end of December and children born in the beginning of January (OR 1.0014, 95%CI 0.9996-1.0031) Dalsgaard et al29 416 744 No significative differences on the likelihood of receiving an ADHD diagnosis between children born before and after the cutoff date were found. Kowalyk et al8 401 The relative age effect was not statistically significant for both the CAARS adult ADHD index and the WURS total score of retrospective childhood ADHD. Sciberras et al30 169 No relationship between being an early starter (born FebruaryApril) or a late starter (born May-July) and meeting criteria for ADHD diagnosis at either age 7 or age 10 was found. Discussion Most studies included in this review (79%) support a positive relationship between a late birth date and diagnosis/treatment of ADHD. Five of them (21%) were unable to show evidence of such a relationship; however, three of those were conducted in Denmark, a country with a very low prevalence of ADHD medication in children, where measures to avoid overdiagnosis have been adopted. The other two studies were very small and may not have a sufficiently large sample for this relationship to be evident. The relative age effect on clinical diagnosis of ADHD does not seem to be present before school-starting age, which may be explained by the fact that most symptoms of hyperactivity and inattention become evident in the classroom setting. In some studies, this relationship seemed to become less clear as students got older11,13,16,17,23 possibly due to the fact that most children with ADHD receive their diagnosis before age 12.11 This supports the maturational lag hypothesis, which postulates that ADHD is caused by a delay, rather than a deviation, on the development of brain functional networks, eventually catching up with the expected rate of development.31 On the other hand, two studies observed a stronger effect for higher grades.9,14 The accumulation of age-related misdiagnoses over time might provide an explanation for this, as well as the fact that, as children get older, they start going through standardized evaluations, making symptoms of ADHD more evident through inevitable comparisons in performance. By facing demands at school that are too high for their maturity level, younger children within a grade may react with behaviours that might be wrongly interpreted as ADHD symptoms.20 Also, due to increasingly higher expectations from parents and teachers for children’s education, some normal childhood behaviours may be interpreted as pathologic.12 There may also be underdiagnosis of older children in the classroom, whose relatively more mature behaviour, compared to their younger peers’ hyperactivity and inattentiveness, may disguise important ADHD symptoms. This may cause actual cases 13 of ADHD to be left undiagnosed, with possible long-term negative effects on academic success and social adjustment.21 Many studies found that the relative age effect was more evident among girls than boys.12-14,16,17,23,25 Others reported that it was statistically significant for boys, but not for girls15,20,23, a difference that can be explained by the smaller prevalence of ADHD in girls.20 Thus, no definitive conclusion has yet been reached about the relationship between gender and the relative age effect on the diagnosis and treatment of ADHD. Larger differences in ADHD prevalence in children born before and after school entry cutoff dates have been reported in countries with high prevalence of ADHD, suggesting that overdiagnosis of children born before cutoff dates may be an indicator for a broader tendency to overdiagnose ADHD.9 In this review, however, such a relationship was not clear regarding prescribing rates: a late birth date effect was evident for countries with both high (USA, Iceland) and low rates of ADHD treatment (Finland, Norway, Sweden and Italy). Jumps in ADHD prevalence around cutoff dates seem to be larger when the supply of doctors is shorter, when teaching conditions are worse (e.g. large class sizes) and when parents have a higher educational level (possibly making them more demanding regarding the behaviour and performance of their children).9 It might be wondered whether this variation in ADHD prevalence with birth date is caused by seasonal variations. However, the change in ADHD risk around school cutoff dates is sudden: Morrow et al12 found that children born three days before the cutoff had a higher risk of being diagnosed with ADHD than those born three days after, making this hypothesis unlikely. Besides, in this review, a late birth date effect was present for different cutoff dates. Teachers’ perceptions of child behaviour seem to be more influenced by relative age than parents’ perceptions. According to Elder21, there may be three explanations for this. First, when assessing a child’s behaviour and development, teachers compare the child to their classmates, whereas parents compare their child’s behaviour to others of roughly the same age, not necessarily the same grade. Secondly, teachers tend to be more objective in this assessment, since parents are prone to have a social desirability bias. Finally, teachers are more likely to use absolute, rather than relative, standards in the evaluation of a child’s behaviour. There seems to be a correlation between a teacher’s belief that a child has ADHD and the actual diagnosis. This comes from the fact that, although teachers are not responsible for diagnosing ADHD, the guidelines point out that symptoms must be present in more than one setting32; one of these settings is often the classroom, making teachers’ feedback very important in this process.21 Despite such strong associations, there is little awareness of the relationship between birth date and ADHD. In the study by Krabbe et al26, general practitioners and teachers were sent a questionnaire evaluating whether they were aware of this association: 70% of GPs and 67,5% of teachers were not. 14 Inappropriate diagnoses may lead to unnecessary treatment, implying direct financial costs and adverse health impacts. Not much is known about the long-term effects of ADHD medications; however, randomized clinical trials have found that these drugs affect the cardiovascular system, increasing heart rate and blood pressure; cases of cardiac sudden death have also been reported. Besides, ADHD medications have been associated with a significant reduction in children’s growth rates, increased suicidality and sleep disturbances.33 A solution that has been proposed for this issue is delaying school start for a year if the child is thought to be more immature than their peers, a practice known as academic redshirting. This allows them to become more mature and able to deal with the school environment. It is a common practice in Denmark, where only 60% of children born in the last quarter of the year before the cutoff date comply with school enrolment rules; this may contribute to the absence of a relative age effect on the diagnosis and treatment of ADHD in some studies performed in this country.29 The benefits of starting formal schooling at an older age may reflect two mechanisms, as postulated by Dee et al22: relative maturity, meaning that students may benefit from starting school at an older age simply because, by comparison with their younger peers, they have achieved more developmental milestones and perform better at school; and absolute maturity, reflecting the hypothesis that formal schooling is, objectively, more developmentally suitable for older children. Also in Denmark, only child psychiatrists and paediatricians are allowed to diagnose ADHD and prescribe stimulants, unlike most countries, where this can be done by general practitioners.28 This may also explain why, in some studies regarding this country, there was no significative effect of relative age on the diagnosis and treatment of ADHD, and it might be considered whether this measure could be adopted in other countries. Conclusion There seems to be sufficient evidence to affirm that a child’s late birth date compared to their classmates contributes to misdiagnosis and mistreatment of ADHD. Raising awareness about this relationship among parents, teachers and physicians is essential, as knowing how to distinguish between immature behaviours and ADHD symptoms can lead to a reduction in misdiagnosis. If being exposed to formal education at younger ages is causing this to happen, educational policies must be revised, regarding the distribution of children between classrooms and the choice of age-appropriate educational activities. School entry could become more flexible, with a case-by-case decision whether the child is mature enough to behave appropriately and be focused in class. As pharmacological treatment for ADHD may cause harm to children in many ways, avoiding misdiagnoses that lead to unnecessary treatment should be a priority. Thus, pharmacological treatment should be reserved for “real” diagnoses of ADHD. 15 References 1. Luo Y, Weibman D, Halperin JM, Li X. A Review of Heterogeneity in Attention Deficit/Hyperactivity Disorder (ADHD). Front Hum Neurosci. 2019;13:42. 2. National Institute of Mental Health. Attention-Deficit Hyperactivity Disorder. https://www.nimh.nih.gov/health/topics/attention-deficit-hyperactivity-disorderadhd/index.shtml. Accessed 27/09, 2019. 3. 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CONSENTIMENTO INFORMADO e APROVAÇÃO ÉTICA Todos os doentes (ou seus representantes legais) que possam ser identificados nas descrições escritas, fotografias e vídeos deverão assinar um formulário de consentimento informado para descrição de doentes, fotografia e vídeos. Estes formulários devem ser submetidos com o manuscrito (modelo disponível em http://www.actamedicaportuguesa.com/info/consentimento_informado_do_doente.doc). A Acta Médica Portuguesa considera aceitável a omissão de dados ou a apresentação de dados menos específicos para identificação dos doentes. Contudo, não aceitaremos a alteração de quaisquer dados. Os autores devem informar se o trabalho foi aprovado pela Comissão de Ética da instituição de acordo com a declaração de Helsínquia. 9. LÍNGUA Os artigos devem ser redigidos em português ou em inglês. Os títulos e os resumos têm de ser sempre em português e em inglês. NORMAS PUBLICAÇÃO