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Avaliação Epidemiológica e Neurobiológica da Exposição Intrauterina ao Paracetamol e suas Implicações na Etiopatogenia das Perturbações do Espetro do Autismo: Uma Revisão Narrativa
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Authors
Abstract(s)
Introdução: O paracetamol é diversamente utilizado como analgésico e antipirético
durante a gravidez, sendo considerado seguro em doses terapêuticas. No entanto,
estudos recentes sugerem uma possível associação entre a exposição pré-natal a este
fármaco e alterações no neurodesenvolvimento infantil, sobretudo perturbações do
espetro do autismo e perturbação de hiperatividade e défice de atenção. As perturbações
do espetro do autismo são caracterizadas por défices na comunicação e interação social,
comportamentos estereotipados e respostas sensoriais atípicas, com uma prevalência
crescente a nível global. Assim, é fundamental esclarecer a relação entre a exposição
intrauterina ao paracetamol e o risco de perturbações do espetro do autismo, visando
apoiar decisões clínicas e políticas de saúde mais seguras, diminuindo, possivelmente, a
prevalência destas perturbações.
Objetivos: Analisar de forma narrativa as evidências epidemiológicas e neurobiológicas
sobre a exposição intrauterina ao paracetamol e o seu impacto no
neurodesenvolvimento, com ênfase nas perturbações do espetro do autismo, para
contribuir para práticas de prescrição mais seguras.
Metodologia: Foi realizada uma revisão narrativa de artigos científicos publicados nos
últimos dez anos, incluindo revisões sistemáticas e estudos de coorte disponíveis em
bases de dados como PubMed e Scopus. Selecionaram-se publicações que abordassem a
exposição ao paracetamol durante a gestação e a sua possível implicação na
etiopatogenia das perturbações do espetro do autismo, considerando fatores de risco e
possíveis mecanismos neurobiológicos.
Resultados: A síntese dos estudos analisados sugere uma associação estatisticamente
significativa entre a exposição prolongada ou frequente ao paracetamol e um aumento
do risco de diagnóstico de perturbações do espetro do autismo na infância. Diversos
mecanismos biológicos foram propostos, nomeadamente a ação do paracetamol sobre o
stress oxidativo, a disfunção endócrina, a disfunção do sistema endocanabinóide e a
modulação de vias inflamatórias cerebrais, bem como a sua capacidade de atravessar a
barreira placentária.
Discussão/Conclusão: Embora ainda existam controvérsias relativamente à relação
causal, os resultados reforçam a necessidade de cautela na prescrição de paracetamol
durante a gravidez, sobretudo em regimes prolongados. A clarificação dos mecanismos
neurobiológicos envolvidos poderá contribuir para a adoção de medidas preventivas e para a elaboração de recomendações clínicas, equilibrando benefícios
analgésicos/antipiréticos e potenciais riscos no neurodesenvolvimento infantil.
Introduction: Paracetamol is widely used as an analgesic and antipyretic during pregnancy, generally considered safe at therapeutic doses. However, recent studies have raised concerns regarding a potential association between prenatal exposure to this drug and alterations in child neurodevelopment, particularly autism spectrum disorder and attention deficit hyperactivity disorder. Autism spectrum disorder is characterized by deficits in communication and social interaction, stereotyped behaviors, and atypical sensory responses, with a rising global prevalence. Therefore, it is essential to elucidate the relationship between intrauterine exposure to paracetamol and the risk of autism spectrum disorder, in order to inform safer clinical practices and public health policies, potentially contributing to a reduction in the prevalence of these conditions. Objectives: To conduct a narrative analysis of the epidemiological and neurobiological evidence regarding intrauterine exposure to paracetamol and its impact on neurodevelopment, with particular emphasis on autism spectrum disorder, aiming to support safer prescribing practices. Methodology: A narrative review was performed, focusing on scientific articles published over the past ten years, including systematic reviews and cohort studies available in databases such as PubMed and Scopus. Articles addressing paracetamol exposure during pregnancy and its potential role in the etiopathogenesis of autism spectrum disorder were selected, considering relevant risk factors and proposed neurobiological mechanisms. Results: The synthesis of the reviewed studies suggests a statistically significant association between prolonged or frequent exposure to paracetamol and an increased risk of autism spectrum disorder diagnosis in childhood. Several biological mechanisms have been proposed, notably the role of paracetamol in inducing oxidative stress, endocrine disruption, dysfunction of the endocannabinoid system, and modulation of neuroinflammatory pathways, as well as its ability to cross the placental barrier. Discussion/Conclusion: Although controversies persist regarding a definitive causal relationship, the findings underscore the need for caution in prescribing paracetamol during pregnancy, particularly in prolonged regimens. Clarification of the underlying neurobiological mechanisms may contribute to the adoption of preventive strategies and the development of clinical recommendations, balancing the analgesic and antipyretic benefits with potential risks to child neurodevelopment.
Introduction: Paracetamol is widely used as an analgesic and antipyretic during pregnancy, generally considered safe at therapeutic doses. However, recent studies have raised concerns regarding a potential association between prenatal exposure to this drug and alterations in child neurodevelopment, particularly autism spectrum disorder and attention deficit hyperactivity disorder. Autism spectrum disorder is characterized by deficits in communication and social interaction, stereotyped behaviors, and atypical sensory responses, with a rising global prevalence. Therefore, it is essential to elucidate the relationship between intrauterine exposure to paracetamol and the risk of autism spectrum disorder, in order to inform safer clinical practices and public health policies, potentially contributing to a reduction in the prevalence of these conditions. Objectives: To conduct a narrative analysis of the epidemiological and neurobiological evidence regarding intrauterine exposure to paracetamol and its impact on neurodevelopment, with particular emphasis on autism spectrum disorder, aiming to support safer prescribing practices. Methodology: A narrative review was performed, focusing on scientific articles published over the past ten years, including systematic reviews and cohort studies available in databases such as PubMed and Scopus. Articles addressing paracetamol exposure during pregnancy and its potential role in the etiopathogenesis of autism spectrum disorder were selected, considering relevant risk factors and proposed neurobiological mechanisms. Results: The synthesis of the reviewed studies suggests a statistically significant association between prolonged or frequent exposure to paracetamol and an increased risk of autism spectrum disorder diagnosis in childhood. Several biological mechanisms have been proposed, notably the role of paracetamol in inducing oxidative stress, endocrine disruption, dysfunction of the endocannabinoid system, and modulation of neuroinflammatory pathways, as well as its ability to cross the placental barrier. Discussion/Conclusion: Although controversies persist regarding a definitive causal relationship, the findings underscore the need for caution in prescribing paracetamol during pregnancy, particularly in prolonged regimens. Clarification of the underlying neurobiological mechanisms may contribute to the adoption of preventive strategies and the development of clinical recommendations, balancing the analgesic and antipyretic benefits with potential risks to child neurodevelopment.
Description
Keywords
Neurodesenvolvimento Exposição Intrauterina Paracetamol Perturbações do Espetro do Autismo Revisão Narrativa