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1.
Arch Argent Pediatr ; 120(6): 391-397, 2022 Dec.
Artigo em Espanhol, Inglês | MEDLINE | ID: mdl-36374057

RESUMO

INTRODUCTION: Childhood neurodevelopmental disorders account for 10% of the causes of childhood disability. The search for medical care leads to therapeutic itineraries routes taken by individuals to seek health care where diagnostic and treatment opportunities arise. Our objective was to explore these itineraries in order to understand the opportunities and barriers to the implementation of therapies and child rearing patterns promoting neurodevelopment. POPULATION AND METHODS: Qualitative study using in-depth interviews with children's parents (between June 2018 and November 2019). The analysis was based on the social model of disability and Vygotsky's approach to child development. RESULTS: A total of 16 interviews were conducted. Considering the time of diagnosis and the age when the therapeutic itinerary started, 2 groups were identified: those who started from birth to 2 years old (early initiation) and those who started from 3 years old (late childhood initiation). In the first group, the search for treatment starts at an early stage, while in the other group, decisions on the initiation and/or type of treatments are prolonged over time. Late initiation was accompanied by difficulties in school, periods of uncertainty, distress and/or family conflicts due to the complexities of parenting. CONCLUSIONS: Therapeutic itineraries started early in some cases and at a later stage in others. The initiation of treatments made it possible to use tools to bridge the gap of discrepancies between the biological and cultural lines of development.


Introducción. Los trastornos en el neurodesarrollo infantil constituyen un 10 % de las causas de discapacidad en la niñez. La búsqueda de atención médica configura itinerarios terapéuticos, entendidos como los procesos de búsqueda y atención para el cuidado de la salud, donde surgen oportunidades de diagnóstico y tratamiento. El objetivo fue explorar dichos itinerarios para comprender las oportunidades y barreras que se presentan para instaurar terapias y pautas de crianza que promuevan el neurodesarrollo. Población y métodos. Estudio cualitativo mediante entrevistas en profundidad a madres y padres de niños (de junio de 2018 a noviembre de 2019). El análisis se realizó sobre la base del modelo social de la discapacidad y del de desarrollo infantil propuesto por Vygotsky. Resultados. Se realizaron 16 entrevistas. Considerando la edad de inicio de los itinerarios terapéuticos y el diagnóstico, se identificaron dos grupos: aquellos que los comenzaron desde el nacimiento hasta los 2 años (inicio precoz) y quienes lo hicieron a partir de los 3 años (inicio en la primera infancia e infancia tardía). En el primero se habilita tempranamente la búsqueda de tratamiento, mientras que en el segundo se prolongaron en el tiempo las decisiones sobre el inicio y/o el tipo de terapias. El inicio tardío se acompañó de dificultades en la escuela, períodos de incertidumbre, angustia y/o conflictos familiares por las complejidades de la crianza. Conclusiones. Los itinerarios terapéuticos se iniciaron en forma precoz en algunos casos y tardía en otros. El inicio de tratamientos permitió incorporar herramientas para acortar la brecha de incongruencia entre las líneas biológica y cultural de desarrollo.


Assuntos
Crianças com Deficiência , Transtornos do Neurodesenvolvimento , Criança , Humanos , Pré-Escolar , Pais , Poder Familiar , Educação Infantil , Transtornos do Neurodesenvolvimento/etiologia , Transtornos do Neurodesenvolvimento/terapia
2.
N Engl J Med ; 387(18): 1661-1672, 2022 11 03.
Artigo em Inglês | MEDLINE | ID: mdl-36322845

RESUMO

BACKGROUND: Whether higher parenteral amino acid intake improves outcomes in infants with extremely low birth weight is unclear. METHODS: In this multicenter, parallel-group, double-blind, randomized, placebo-controlled trial, we assigned infants with birth weights of less than 1000 g at 8 neonatal intensive care units to receive amino acids at a dose of 1 g per day (intervention group) or placebo in addition to usual nutrition for the first 5 days after birth. The primary outcome was survival free from neurodisability as assessed with the Bayley Scales of Infant and Toddler Development and neurologic examination at 2 years, corrected for gestational age at birth. Secondary outcomes were the components of the primary outcome as well as the presence or absence of neonatal disorders, the rate of growth, and nutritional intake. RESULTS: We enrolled 434 infants (217 per group) in this trial. Survival free from neurodisability was observed in 97 of 203 children (47.8%) in the intervention group and in 102 of 205 (49.8%) in the placebo group (adjusted relative risk, 0.95; 95% confidence interval [CI], 0.79 to 1.14; P = 0.56). Death before the age of 2 years occurred in 39 of 217 children (18.0%) in the intervention group and 42 of 217 (19.4%) in the placebo group (adjusted relative risk, 0.93; 95% CI, 0.63 to 1.36); neurodisability occurred in 67 of 164 children (40.9%) in the intervention group and 61 of 163 (37.4%) in the placebo group (adjusted relative risk, 1.16; 95% CI, 0.90 to 1.50). Neurodisability was moderate to severe in 27 children (16.5%) in the intervention group and 14 (8.6%) in the placebo group (adjusted relative risk, 1.95; 95% CI, 1.09 to 3.48). More children in the intervention group than in the placebo group had patent ductus arteriosus (adjusted relative risk, 1.65; 95% CI, 1.11 to 2.46). In a post hoc analysis, refeeding syndrome occurred in 42 of 172 children in the intervention group and 26 of 166 in the placebo group (adjusted relative risk, 1.64; 95% CI, 1.09 to 2.47). Eight serious adverse events occurred. CONCLUSIONS: In infants with extremely low birth weight, extra parenteral amino acids at a dose of 1 g per day for 5 days after birth did not increase the number who survived free from neurodisability at 2 years. (Funded by the New Zealand Health Research Council and others; ProVIDe Australian New Zealand Clinical Trials Registry number, ACTRN12612001084875.).


Assuntos
Aminoácidos , Recém-Nascido de Peso Extremamente Baixo ao Nascer , Lactente Extremamente Prematuro , Doenças do Sistema Nervoso , Transtornos do Neurodesenvolvimento , Pré-Escolar , Humanos , Lactente , Recém-Nascido , Aminoácidos/administração & dosagem , Aminoácidos/efeitos adversos , Aminoácidos/uso terapêutico , Austrália , Permeabilidade do Canal Arterial/etiologia , Método Duplo-Cego , Nutrição Parenteral/métodos , Terapia Intensiva Neonatal , Transtornos do Neurodesenvolvimento/diagnóstico , Transtornos do Neurodesenvolvimento/etiologia , Transtornos do Neurodesenvolvimento/prevenção & controle , Doenças do Sistema Nervoso/diagnóstico , Doenças do Sistema Nervoso/etiologia , Doenças do Sistema Nervoso/prevenção & controle
3.
Rev. neurol. (Ed. impr.) ; 75(7): 189-197, Oct 1, 2022. ilus, tab
Artigo em Espanhol | IBECS | ID: ibc-209614

RESUMO

Introducción: Los trastornos del neurodesarrollo tienen una etiología multifactorial que resulta de la interacción entre factores biológicos y ambientales. La base biológica de muchos de estos trastornos se comprende sólo parcialmente, lo que hace que las intervenciones terapéuticas, especialmente las farmacológicas, sean particularmente difíciles. El impacto del cannabis medicinal en los trastornos neurológicos y psiquiátricos se ha estudiado durante mucho tiempo. Este estudio tuvo como objetivo revisar los estudios clínicos y preclínicos actualmente disponibles con respecto al uso de cannabinoides en trastornos del neurodesarrollo pediátrico y llamar la atención sobre el posible papel terapéutico del cannabidiol en este campo. Desarrollo: El cannabidiol es un modulador del sistema endocannabinoide y ejerce sus efectos tanto en cerebros en desarrollo como en cerebros maduros a través de numerosos mecanismos. El cannabidiol tiene un límite de toxicidad relativamente alto, y la bibliografía actual sugiere que puede tener propiedades ansiolíticas, antipsicóticas y neuroprotectoras. La evidencia clínica sugiere que el tratamiento temprano con cannabidiol podría ser una terapia prometedora para los trastornos del desarrollo neurológico, incluida la discapacidad intelectual, los trastornos del espectro autista, los tics y el trastorno por déficit de atención/hiperactividad. Conclusiones: Es de esperar que esta revisión llame la atención sobre un cuerpo emergente de evidencia sobre el potencial significativo del cannabidiol para mejorar de manera segura muchos de los síntomas comunes que afectan a niños y adolescentes con trastornos del neurodesarrollo, especialmente el trastorno del espectro autista.(AU)


INTRODUCTION: Neurodevelopmental disorders have a multifactorial etiology that results from the interaction between biological and environmental factors. The biological basis of many of these disorders is only partially understood, which makes therapeutic interventions, especially pharmacological ones, particularly difficult. The impact of medical cannabis on neurological and psychiatric disorders has been studied for a long time. This study aimed to review the currently available clinical and pre-clinical studies regarding the use of cannabinoids in pediatric neurodevelopmental disorders and to draw attention to the potential therapeutic role of cannabidiol in this field. DEVELOPMENT: Cannabidiol is an endocannabinoid system modulator and exerts its effects on both developing and mature brains through numerous mechanisms. Cannabidiol holds a relatively high toxicity limit and current literature suggests that it may have anxiolytic, antipsychotic, and neuroprotective properties. Clinical evidence suggests that early treatment with cannabidiol might be a promising therapy for neurodevelopmental disorders, including intellectual disability, autism spectrum disorders, tics, and attention/deficit hyperactivity disorder. CONCLUSIONS: This review hopefully draws attention to an emerging body of evidence concerning cannabidiol’s significant potential to safely improve many of the common symptoms affecting children and adolescents with neurodevelopmental disorders, especially autism spectrum disorder.(AU)


Assuntos
Humanos , Criança , Adolescente , Canabinoides , Transtornos do Neurodesenvolvimento/etiologia , Transtornos do Neurodesenvolvimento/diagnóstico , Transtorno do Espectro Autista , Endocanabinoides , Transtorno do Deficit de Atenção com Hiperatividade/tratamento farmacológico , Neurologia , Pediatria , Psicologia da Criança , Maconha Medicinal
4.
Nutrients ; 14(18)2022 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-36145129

RESUMO

The intake of foods containing polyphenols can have a protective role to avoid comorbidities during pregnancy and, at the same time, promote transgenerational health. This review aims to describe the effect of polyphenol intake through supplements or polyphenol-rich foods during pregnancy on the incidence and evolution of gestational diabetes mellitus (GDM), as well as the link with the neurodevelopment of the fetus. Using PRISMA procedures, a systematic review was conducted by searching in biomedical databases (PubMed, Cinahl and Scopus) from January to June 2022. Full articles were screened (n = 419) and critically appraised. Fourteen studies were selected and were divided into two different thematic blocks considering (i) the effect of polyphenols in GDM and (ii) the effect of GDM to mental disorders in the offspring. A positive relationship was observed between the intake of polyphenols and the prevention and control of cardiometabolic complications during pregnancy, such as GDM, which could be related to thwarted inflammatory and oxidative processes, as well as neuronal factors. GDM is related to a greater risk of suffering from diseases related to neurodevelopment, such as attention deficit hyperactivity disorder, autism spectrum disorder and learning disorder. Further clinical research on the molecule protective mechanism of polyphenols on pregnant women is required to understand the transgenerational impact on fetal neurodevelopment.


Assuntos
Transtorno do Espectro Autista , Diabetes Gestacional , Transtornos do Neurodesenvolvimento , Diabetes Gestacional/epidemiologia , Diabetes Gestacional/prevenção & controle , Suplementos Nutricionais , Feminino , Humanos , Transtornos do Neurodesenvolvimento/epidemiologia , Transtornos do Neurodesenvolvimento/etiologia , Transtornos do Neurodesenvolvimento/prevenção & controle , Polifenóis/farmacologia , Gravidez , Gestantes
5.
Nutrients ; 14(15)2022 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-35956326

RESUMO

Obesity is a main risk factor for the onset and the precipitation of many non-communicable diseases. This condition, which is associated with low-grade chronic systemic inflammation, is of main concern during pregnancy leading to very serious consequences for the new generations. In addition to the prominent role played by the adipose tissue, dysbiosis of the maternal gut may also sustain the obesity-related inflammatory milieu contributing to create an overall suboptimal intrauterine environment. Such a condition here generically defined as "inflamed womb" may hold long-term detrimental effects on fetal brain development, increasing the vulnerability to mental disorders. In this review, we will examine the hypothesis that maternal obesity-related gut dysbiosis and the associated inflammation might specifically target fetal brain microglia, the resident brain immune macrophages, altering neurodevelopmental trajectories in a sex-dependent fashion. We will also review some of the most promising nutritional strategies capable to prevent or counteract the effects of maternal obesity through the modulation of inflammation and oxidative stress or by targeting the maternal microbiota.


Assuntos
Microbiota , Transtornos do Neurodesenvolvimento , Obesidade Materna , Disbiose/complicações , Feminino , Humanos , Inflamação/complicações , Transtornos do Neurodesenvolvimento/etiologia , Obesidade/complicações , Obesidade Materna/complicações , Gravidez , Fatores de Risco
6.
Brain Dev ; 44(10): 706-714, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-35999144

RESUMO

BACKGROUND: This hypothesis-testing study evaluated the relationship between fetal alcohol syndrome (FAS) and neurodevelopmental disorder (ND) diagnoses within the Independent Healthcare Research Database (IHRD). METHODS: De-identified eligibility and claim healthcare records prospectively generated from the 1990-2012 Florida Medicaid system were analyzed using SAS software. There were 89,766 children continuously eligible with ≥10 outpatient office visits during the 120 month period following birth in the cohort examined. A total of 321 children were diagnosed with FAS. Autism spectrum disorder (ASD) (n = 922), tics (n = 551), attention deficit disorder/attention deficit-hyperactivity disorder (ADD/ADHD) (n = 20,260), mental retardation (MR) (n = 915), and specific delays in development (SDD) (n = 24,630) incidence rates were examined using frequency risk ratio (RR) and logistic regression models. RESULTS: The incidence rate of tics (RR = 5.68), ADD/ADHD (RR = 2.30), MR (RR = 7.83), SDD (RR = 2.88), and ASD (RR = 6.74) were significantly increased among FAS diagnosed children as compared to undiagnosed children. Adjusted (for gender, race, residency, and date of birth) odds ratios (ORs) were significantly increased for tics (OR = 4.87), ADD/ADHD (OR = 3.40), MR (OR = 7.91), SDD (OR = 9.56), and ASD (OR = 6.87) when comparing the FAS diagnosed children to undiagnosed children. CONCLUSION: Tens of thousands of American children with lifetime costs in the billions of US dollars were estimated to be impacted by FAS-associated NDs. These impacts are particularly tragic because FAS is dependent upon lifestyle.


Assuntos
Transtorno do Deficit de Atenção com Hiperatividade , Transtorno do Espectro Autista , Transtornos do Espectro Alcoólico Fetal , Deficiência Intelectual , Transtornos do Neurodesenvolvimento , Tiques , Criança , Gravidez , Feminino , Humanos , Estudos Longitudinais , Transtornos do Espectro Alcoólico Fetal/epidemiologia , Transtorno do Espectro Autista/epidemiologia , Transtorno do Espectro Autista/etiologia , Transtorno do Espectro Autista/diagnóstico , Estudos de Coortes , Transtornos do Neurodesenvolvimento/epidemiologia , Transtornos do Neurodesenvolvimento/etiologia , Transtorno do Deficit de Atenção com Hiperatividade/epidemiologia
7.
J Perinatol ; 42(10): 1380-1384, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-35831577

RESUMO

OBJECTIVE: To study the impact of an evidence-based neuroprotection care (NPC) bundle on long-term neurodevelopmental impairment (NDI) in infants born extremely premature. STUDY DESIGN: An NPC bundle targeting predefined risk factors for acute brain injury in extremely preterm infants was implemented. We compared the incidence of composite outcome of death or severe neurodevelopmental impairment (sNDI) at 21 months adjusted age pre and post bundle implementation. RESULTS: Adjusting for confounding factors, NPC bundle implementation associated with a significant reduction in death or sNDI (aOR, 0.34; 95% CI 0.17-0.68; P = 0.002), mortality (aOR, 0.31; 95% CI (0.12-0.79); P = 0.015), sNDI (aOR, 0.37; 95% CI: 0.12-0.94; P = 0.039), any motor, language, or cognitive composite score <70 (aOR, 0.48; 95% CI: 0.26-0.90; P = 0.021). CONCLUSION: Implementation of NPC bundle targeting predefined risk factors is associated with a reduction in mortality or sNDI in extremely preterm infants.


Assuntos
Transtornos do Neurodesenvolvimento , Pacotes de Assistência ao Paciente , Nascimento Prematuro , Feminino , Humanos , Incidência , Lactente , Lactente Extremamente Prematuro , Recém-Nascido , Transtornos do Neurodesenvolvimento/epidemiologia , Transtornos do Neurodesenvolvimento/etiologia , Transtornos do Neurodesenvolvimento/prevenção & controle , Neuroproteção
9.
Pediatr Res ; 92(5): 1350-1356, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-35725918

RESUMO

BACKGROUND: Sodium fluctuations in very preterm neonates and their neurodevelopmental consequences are not well described. METHODS: We assessed the changes in plasma sodium and glucose in the first days of life in very preterm neonates and studied the association of glucose-corrected plasma sodium fluctuations on neurodevelopmental outcomes. We included 147 consecutive neonates born before 29 weeks of gestation in our center and retrospectively obtained plasma sodium, glucose, and glucose-corrected sodium levels. Neurodevelopmental assessment was obtained from the Canadian Neonatal Follow-Up Network. RESULTS: Mean ± standard deviation of plasma sodium changes within the first 10 days of life were 16.2 ± 6.0, 14.8 ± 5.3, and 11.1 ± 5.2 mmol/l in neonates born ≤25, 25-26, and 26-27 weeks of gestation, respectively (p < 0.001). Non-steroidal anti-inflammatory drug administration was associated with larger plasma sodium fluctuation. Eighty-six percent had a known neurological status at 18 months. Higher fluctuations in glucose-corrected plasma sodium were associated with death or neurodevelopmental impairment at 18 months corrected age (B = 3.19, 95% CI [1.24, 5.14]), and this association remained after adjustment for gestational age (B = 2.1, 95% CI [0.16, 4.04]). CONCLUSIONS: Neonates born very preterm show fluctuations in glucose-corrected plasma sodium during the first days of life, which may increase the risk of death or developmental impairment. IMPACT: Risk factors and neurodevelopmental consequences of plasma sodium changes in early neonatal life of preterm infants are not well characterized. This study shows for the first time that glucose-corrected plasma sodium fluctuations within the first days of life are more severe in preterm infants receiving non-steroidal anti-inflammatory drugs (NSAIDs) and are associated with death or neurodevelopmental impairment at 18 months corrected age. Large plasma sodium and glucose fluctuations should be expected more often in preterm infants receiving NSAIDs and should be avoided.


Assuntos
Doenças do Prematuro , Transtornos do Neurodesenvolvimento , Lactente , Feminino , Recém-Nascido , Humanos , Recém-Nascido Prematuro , Estudos Retrospectivos , Canadá , Idade Gestacional , Retardo do Crescimento Fetal , Anti-Inflamatórios , Sódio , Glucose , Anti-Inflamatórios não Esteroides , Transtornos do Neurodesenvolvimento/etiologia
10.
J Neural Transm (Vienna) ; 129(5-6): 627-642, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35624406

RESUMO

Following introduction of the monoamine oxidase type B inhibitor selegiline for the treatment of Parkinson's disease (PD), discovery of the action mechanism of Alzheimer's disease-modifying agent memantine, the role of iron in PD, and the loss of electron transport chain complex I in PD, and development of the concept of clinical neuroprotection, Peter Riederer launched one of the most challenging research project neurodevelopmental aspects of neuropsychiatric disorders. The neurodevelopmental theory holds that a disruption of normal brain development in utero or during early life underlies the subsequent emergence of neuropsychiatric symptoms during later life. Indeed, the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition and the International Classification of Diseases, 11th Revision categorize autism spectrum disorder and attention deficit hyperactivity disorder in neurodevelopmental disorders (NDDs). More and more evidence, especially from preclinical studies, is revealing that neurodevelopmental pathology is not limited to the diagnostic class above, but also contributes to the development of other psychiatric disorders such as schizophrenia, bipolar disorder, and obsessive-compulsive disorder as well as neurodegenerative diseases such as PD and Huntington's disease. Preclinical animal research is taking a lead in understanding the pathomechanisms of NDDs, searching for novel targets, and developing new neuroprotective agents against NDDs. This narrative review discusses emerging evidence of the neurodevelopmental etiology of neuropsychiatric disorders, recent advances in modelling neurodevelopmental pathogenesis, potential strategies of clinical neuroprotection using novel kynurenine metabolites and analogues, and future research direction for NDDs.


Assuntos
Transtorno do Espectro Autista , Transtornos do Neurodesenvolvimento , Fármacos Neuroprotetores , Animais , Transtorno do Espectro Autista/tratamento farmacológico , Humanos , Cinurenina , Transtornos do Neurodesenvolvimento/etiologia , Transtornos do Neurodesenvolvimento/prevenção & controle , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/uso terapêutico , Selegilina
11.
Early Hum Dev ; 169: 105574, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35561519

RESUMO

BACKGROUND: Advances in surgical techniques to tackle critical congenital heart diseases (CHD) have enhanced the survival rates and life expectancy of children born with heart disease. Studies to better acknowledge their neurodevelopmental trajectory have paramount implications. OBJECTIVE: The aim of this study is to examine the nature of brain MRI findings in infants born with critical congenital heart diseases needing intervention in the first 6 months of life, with the help of an MRI scoring system and correlation with long term neurodevelopmental outcomes. METHODS: Brain MRI scans of eligible infants were extracted from database, reexamined to categorize, and score them into three main functional areas: cognitive/grey matter, motor/white matter, and visual. The scoring system also included stage of myelination and presence of punctate hemorrhages. The correlation of individual and total MRI scores with neurodevelopmental assessment using Bayley Scales for Infant and Toddler Development- version 3 (BSID III) were examined via logistic regression models while controlling for confounding variables. RESULT: Median (IQR) MRI score was 6 (4-7) with grey matter score of 2 (1-4). Initial BSID III scores were 80 ± 15, 80 ± 18, and 81 ± 19 for cognitive, motor and language components, respectively. The MRI cognitive score had direct correlation with respiratory index prior to surgery (cc = 0.47, p = 0.03) and cross-clamping time (cc = 0.65, p = 0.001). It displayed a significant inverse correlation with language scores for BSID III at 9 months (R = -0.42, p = 0.04) which lost significance in subsequent visits. CONCLUSION: This pilot study proved the feasibility of correlating structural brain abnormalities in MRI with later brain developmental deficits in infants with CHD. We envision establishing a standardized MRI scoring system to be performed on a large multi-center cohort that would help better predict and measure brain injury in infants with CHDs.


Assuntos
Cardiopatias Congênitas , Transtornos do Neurodesenvolvimento , Substância Branca , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Cardiopatias Congênitas/diagnóstico por imagem , Cardiopatias Congênitas/patologia , Cardiopatias Congênitas/cirurgia , Humanos , Lactente , Imageamento por Ressonância Magnética/métodos , Transtornos do Neurodesenvolvimento/diagnóstico por imagem , Transtornos do Neurodesenvolvimento/epidemiologia , Transtornos do Neurodesenvolvimento/etiologia , Projetos Piloto
12.
Life Sci ; 298: 120526, 2022 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-35367466

RESUMO

Lactation is a crucial postnatal programming window which can interfere with child development and predispose to metabolic disorders later in life, as insulin resistance and obesity. Although breastfeeding is known to prevent many diseases in the newborn, changes in milk composition have been correlated with alterations in central nervous system maturation and differentiation. Changes in milk quality and quantity may predispose to metabolic disorders later in life but have also been linked to the development of neuronal diseases. Maternal metabolic condition, diet and behaviours have been considered determinant for metabolic programming in the child, although the mechanisms involved remain to be elucidated. Some of such mechanisms may also be related with the increasing prevalence of neurodevelopmental and behavioural diseases in the younger generations. This review focuses on the interconnected risks between changes of maternal metabolic status/unbalanced diets during lactation and offspring's development of metabolic and neurodevelopmental disorders. Furthermore, the present review reunites the current knowledge about the mechanisms underlying the association between these disorders and highlights the need of further exploring the impact of lactation period on neurodevelopmental and metabolic outcomes.


Assuntos
Doenças Metabólicas , Transtornos do Neurodesenvolvimento , Aleitamento Materno , Criança , Feminino , Humanos , Recém-Nascido , Lactação/fisiologia , Fenômenos Fisiológicos da Nutrição Materna , Transtornos do Neurodesenvolvimento/etiologia , Responsabilidade Social
13.
Front Endocrinol (Lausanne) ; 13: 860110, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35370942

RESUMO

The internal and external environment of the mother during the developmental stages of the fetus affects the offspring's health. According to the developmental origins of health and disease (DOHaD) theory, environmental factors influence the offspring and also affect health in adulthood. Recently, studies based on this theory have gained attracted attention because of their clinical utility in identifying the risk groups for various diseases. Neurodevelopmental disorders (NDDs) such as autism spectrum disorder (ASD) and attention-deficit hyperactivity disorder (ADHD) can be caused by exposure to certain prenatal environments during pregnancy. This review describes the latest findings on the effect of prenatal environment on the onset mechanism of NDDs based on the DOHaD theory. Unravelling the molecular mechanisms underlying the pathogenesis of NDDs is important, because there are no therapeutic drugs for these disorders. Furthermore, elucidating the relationship between the DOHaD theory and NDDs will contribute to the popularization of preventive medicine.


Assuntos
Transtorno do Deficit de Atenção com Hiperatividade , Transtorno do Espectro Autista , Transtornos do Neurodesenvolvimento , Adulto , Transtorno do Deficit de Atenção com Hiperatividade/etiologia , Transtorno do Espectro Autista/complicações , Feminino , Humanos , Mães , Transtornos do Neurodesenvolvimento/etiologia , Gravidez , Fatores de Risco
14.
Annu Rev Neurosci ; 45: 425-445, 2022 07 08.
Artigo em Inglês | MEDLINE | ID: mdl-35436413

RESUMO

Mounting evidence indicates that microglia, which are the resident immune cells of the brain, play critical roles in a diverse array of neurodevelopmental processes required for proper brain maturation and function. This evidence has ultimately led to growing speculation that microglial dysfunction may play a role in neurodevelopmental disorder (NDD) pathoetiology. In this review, we first provide an overview of how microglia mechanistically contribute to the sculpting of the developing brain and neuronal circuits. To provide an example of how disruption of microglial biology impacts NDD development, we also highlight emerging evidence that has linked microglial dysregulation to autism spectrum disorder pathogenesis. In recent years, there has been increasing interest in how the gut microbiome shapes microglial biology. In the last section of this review, we put a spotlight on this burgeoning area of microglial research and discuss how microbiota-dependent modulation of microglial biology is currently thought to influence NDD progression.


Assuntos
Transtorno do Espectro Autista , Microbioma Gastrointestinal , Transtornos do Neurodesenvolvimento , Transtorno do Espectro Autista/patologia , Encéfalo/fisiologia , Humanos , Microglia/fisiologia , Transtornos do Neurodesenvolvimento/etiologia , Transtornos do Neurodesenvolvimento/patologia
15.
Dev Med Child Neurol ; 64(10): 1246-1253, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-35383902

RESUMO

AIM: To determine whether early-life respiratory trajectories are associated with neurodevelopmental impairment (NDI) in infants born very and extremely preterm. METHOD: The daily type of respiratory supports in the first 8 weeks after birth were analysed in 546 infants (285 males, 261 females; median gestational age = 28.0 weeks, interquartile range = 3 weeks), comprising 301 infants born very preterm (gestation = 28-30 weeks) and 245 infants born extremely preterm (gestation <28 weeks), who survived to discharge from 2004 to 2018 and received follow-up assessment by Bayley Scales of Infant and Toddler Development at a corrected age of 24 months. NDI included cognition or motor impairment, moderate and severe cerebral palsy, or visual and hearing impairment. RESULTS: Clustering analysis identified three respiratory patterns with increasing severity: improving; slowly improving; and delayed improvement. These were significantly associated with increasing rates of NDI in infants born very and extremely preterm and smaller head circumference in infants born extremely preterm (both p < 0.001). By day 28, the proportion of infants who were under different categories of ventilation support significantly differed according to the three trajectory groups in infants born very and extremely preterm (both p < 0.05). Models that included adverse respiratory trajectories demonstrated more negative impacts on neurodevelopment than those without. INTERPRETATION: An adverse early-life respiratory trajectory was associated with NDI at follow-up, especially in infants born extremely preterm, suggesting a lung-brain axis of preterm birth. WHAT THIS PAPER ADDS: Clustering analysis identified three respiratory trajectories with increasing severity in infants born preterm. Increasing severity of respiratory trajectories was associated with increasing rates of neurodevelopmental impairment. Adverse respiratory trajectories had a significantly negative impact on neurodevelopmental outcomes.


OBJETIVO: Determinar se as trajetórias respiratórias no início da vida estão associadas ao comprometimento do neurodesenvolvimento (CND) em bebês nascidos muito e extremamente prematuros. MÉTODOS: O tipo diário de suporte respiratório nas primeiras 8 semanas após o nascimento foi analisado em 546 bebês (285 meninos, 261 meninas; idade gestacional mediana = 28,0 semanas, intervalo interquartil = 3 semanas), compreendendo 301 bebês nascidos muito prematuros (gestação = 28-30 semanas) e 245 bebês nascidos extremamente prematuros (gestação < 28 semanas), que sobreviveram à alta entre 2004 e 2018 e receberam avaliação de seguimento por meio da Bayley Scales of Infant and Toddler Development na idade corrigida de 24 meses. O CND incluiu deficiência cognitiva ou motora, paralisia cerebral moderada e grave ou deficiência visual e auditiva. RESULTADOS: A análise de agrupamento identificou três padrões respiratórios com gravidade crescente: melhorando; melhorando lentamente; e melhora tardia. Estes foram significativamente associados com taxas crescentes de CND em bebês nascidos muito e extremamente prematuros e menor perímetro cefálico em bebês nascidos extremamente prematuros (ambos p < 0,001). No dia 28, a proporção de bebês que estavam sob diferentes categorias de suporte ventilatório diferiu significativamente de acordo com os três grupos de trajetória em bebês nascidos muito prematuros e extremamente prematuros (ambos p < 0,05). Os modelos que incluíram trajetórias respiratórias adversas demonstraram mais impactos negativos no neurodesenvolvimento do que aqueles sem. INTERPRETAÇÃO: Uma trajetória respiratória adversa no início da vida foi associada ao CND no seguimento, especialmente em bebês nascidos extremamente prematuros, sugerindo um eixo pulmão-cérebro de nascimento prematuro.


Assuntos
Doenças do Prematuro , Transtornos do Neurodesenvolvimento , Nascimento Prematuro , Pré-Escolar , Feminino , Idade Gestacional , Humanos , Lactente , Lactente Extremamente Prematuro , Recém-Nascido , Doenças do Prematuro/epidemiologia , Masculino , Transtornos do Neurodesenvolvimento/epidemiologia , Transtornos do Neurodesenvolvimento/etiologia , Estudos Retrospectivos
17.
Arch Dis Child Fetal Neonatal Ed ; 107(5): 467-474, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35236745

RESUMO

OBJECTIVE: In 2010, the Dutch practice regarding initiation of active treatment in extremely preterm infants was lowered from 25 completed weeks' to 24 completed weeks' gestation. The nationwide Extremely Preterm Infants - Dutch Analysis on Follow-up Study was set up to provide up-to-date data on neurodevelopmental outcome at 2 years' corrected age (CA) after this guideline change. Design: National cohort study. PATIENTS: All live born infants between 240/7 weeks' and 266/7 weeks' gestational age who were 2 years' CA in 2018-2020. MAIN OUTCOME MEASURE: Impairment at 2 years' CA, based on cognitive score (Bayley-III-NL), neurological examination and neurosensory function. RESULTS: 651 of 991 live born infants (66%) survived to 2 years' CA, with data available for 554 (85%). Overall, 62% had no impairment, 29% mild impairment and 9% moderate-to-severe impairment (further defined as neurodevelopmental impairment, NDI). The percentage of survivors with NDI was comparable for infants born at 24 weeks', 25 weeks' and 26 weeks' gestation. After multivariable analysis, severe brain injury and low maternal education were associated with higher odds on NDI. NDI-free survival was 48%, 67% and 75% in neonatal intensive care unit (NICU)-admitted infants at 24, 25 and 26 weeks' gestation, respectively. CONCLUSIONS: Lowering the threshold has not been accompanied by a large increase in moderate-to-severely impaired infants. Among live-born and NICU-admitted infants, an increase in NDI-free survival was observed from 24 weeks' to 26 weeks' gestation. This description of a national cohort with high follow-up rates gives an accurate description of the range of outcomes that may occur after extremely preterm birth.


Assuntos
Doenças do Prematuro , Transtornos do Neurodesenvolvimento , Nascimento Prematuro , Criança , Pré-Escolar , Estudos de Coortes , Deficiências do Desenvolvimento/diagnóstico , Deficiências do Desenvolvimento/epidemiologia , Deficiências do Desenvolvimento/etiologia , Feminino , Seguimentos , Idade Gestacional , Humanos , Lactente , Lactente Extremamente Prematuro , Recém-Nascido , Doenças do Prematuro/diagnóstico , Transtornos do Neurodesenvolvimento/epidemiologia , Transtornos do Neurodesenvolvimento/etiologia , Gravidez
18.
Am J Obstet Gynecol ; 227(2): 287.e1-287.e17, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35305960

RESUMO

BACKGROUND: Evidence indicates that in utero exposure to chorioamnionitis might increase the risk of neurodevelopmental disorders in the offspring. However, findings on this topic have been inconsistent. OBJECTIVE: To examine the association between chorioamnionitis and neurodevelopmental disorders in offspring. STUDY DESIGN: This was a retrospective population-based cohort study in Sweden. A total of 2,228,280 singleton live births and stillbirths between 1998 and 2019 were included in our study population. Data on maternal characteristics and neurodevelopmental disorders in offspring were obtained by individual record-linkages of nationwide Swedish registries. Chorioamnionitis was identified using the National Medical Birth Register. Inpatient and outpatient diagnoses were obtained for cerebral palsy, autism, attention deficit hyperactivity disorder, epilepsy, and intellectual disability. Multivariable Cox proportional hazards regression was used to estimate the association between chorioamnionitis and each neurodevelopmental disorder with adjusted hazard ratios and 95% confidence intervals. A causal mediation analysis of the relationship between chorioamnionitis and neurodevelopmental disorders with preterm delivery (<37 weeks) was performed. RESULTS: A total of 5770 (0.26%) offspring were exposed to chorioamnionitis during pregnancy. During the study's follow-up time there were 4752 (0.21%) cases of cerebral palsy, 17,897 (0.80 %) cases of epilepsy, 50,570 (2.27 %) cases of autism, 114,087 (5.12%) cases of attention deficit hyperactivity disorder, and 14,574 (0.65%) cases of intellectual disability. After adjusting for potential confounders, exposure to chorioamnionitis increased the hazard ratios of cerebral palsy (adjusted hazard ratio, 7.43; 95% confidence interval, 5.90-9.37), autism (adjusted hazard ratio, 1.43; 95% confidence interval, 1.21-1.68), attention deficit hyperactivity disorder (adjusted hazard ratio, 1.17; 95% confidence interval, 1.03-1.33), and intellectual disability (adjusted hazard ratio, 1.99; 95% confidence interval, 1.53-2.58), whereas chorioamnionitis was not significantly associated with higher rates of epilepsy in offspring. Mediation analysis revealed that these associations were mainly explained through preterm delivery; however, increased risk was also observed among term infants. CONCLUSION: Chorioamnionitis increases the risk of neurodevelopmental disorders, particularly cerebral palsy, autism, attention deficit hyperactivity disorder, and intellectual disability. These associations were mainly mediated through preterm delivery. Efforts for timely identification and appropriate interventions to treat infections during pregnancy will have sustained benefits in reducing the burden of neurologic complications in children at the population level.


Assuntos
Transtorno do Espectro Autista , Paralisia Cerebral , Corioamnionite , Epilepsia , Deficiência Intelectual , Transtornos do Neurodesenvolvimento , Nascimento Prematuro , Efeitos Tardios da Exposição Pré-Natal , Transtorno do Espectro Autista/epidemiologia , Paralisia Cerebral/epidemiologia , Criança , Corioamnionite/epidemiologia , Estudos de Coortes , Epilepsia/epidemiologia , Feminino , Humanos , Lactente , Recém-Nascido , Deficiência Intelectual/complicações , Deficiência Intelectual/epidemiologia , Transtornos do Neurodesenvolvimento/epidemiologia , Transtornos do Neurodesenvolvimento/etiologia , Gravidez , Nascimento Prematuro/epidemiologia , Efeitos Tardios da Exposição Pré-Natal/epidemiologia , Estudos Retrospectivos
19.
Artigo em Inglês | MEDLINE | ID: mdl-35276404

RESUMO

Pregnant women represent a uniquely vulnerable population during an infectious disease outbreak, such as the COVID-19 pandemic. Although we are at the early stages of understanding the specific impact of SARS-CoV-2 exposure during pregnancy, mounting epidemiological evidence strongly supports a link between exposure to a variety of maternal infections and an increased risk for offspring neurodevelopmental disorders. Inflammatory biomarkers identified from archived or prospectively collected maternal biospecimens suggest that the maternal immune response is the critical link between infection during pregnancy and altered offspring neurodevelopment. This maternal immune activation (MIA) hypothesis has been tested in animal models by artificially activating the immune system during pregnancy and evaluating the neurodevelopmental consequences in MIA-exposed offspring. Although the vast majority of MIA model research is carried out in rodents, the nonhuman primate model has emerged in recent years as an important translational tool. In this review, we briefly summarize human epidemiological studies that have prompted the development of translationally relevant MIA models. We then highlight notable similarities between humans and nonhuman primates, including placental structure, pregnancy physiology, gestational timelines, and offspring neurodevelopmental stages, that provide an opportunity to explore the MIA hypothesis in species more closely related to humans. Finally, we provide a comprehensive review of neurodevelopmental alterations reported in current nonhuman primate models of maternal infection and discuss future directions for this promising area of research.


Assuntos
COVID-19 , Transtornos do Neurodesenvolvimento , Efeitos Tardios da Exposição Pré-Natal , Animais , Modelos Animais de Doenças , Feminino , Humanos , Macaca mulatta , Transtornos do Neurodesenvolvimento/etiologia , Pandemias , Placenta , Gravidez , SARS-CoV-2
20.
Int J Mol Sci ; 23(3)2022 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-35163133

RESUMO

The maternal diet during pregnancy is a key determinant of offspring health. Early studies have linked poor maternal nutrition during gestation with a propensity for the development of chronic conditions in offspring. These conditions include cardiovascular disease, type 2 diabetes and even compromised mental health. While multiple factors may contribute to these outcomes, disturbed epigenetic programming during early development is one potential biological mechanism. The epigenome is programmed primarily in utero, and during this time, the developing fetus is highly susceptible to environmental factors such as nutritional insults. During neurodevelopment, epigenetic programming coordinates the formation of primitive central nervous system structures, neurogenesis, and neuroplasticity. Dysregulated epigenetic programming has been implicated in the aetiology of several neurodevelopmental disorders such as Tatton-Brown-Rahman syndrome. Accordingly, there is great interest in determining how maternal nutrient availability in pregnancy might affect the epigenetic status of offspring, and how such influences may present phenotypically. In recent years, a number of epigenetic enzymes that are active during embryonic development have been found to require vitamin C as a cofactor. These enzymes include the ten-eleven translocation methylcytosine dioxygenases (TETs) and the Jumonji C domain-containing histone lysine demethylases that catalyse the oxidative removal of methyl groups on cytosines and histone lysine residues, respectively. These enzymes are integral to epigenetic regulation and have fundamental roles in cellular differentiation, the maintenance of pluripotency and development. The dependence of these enzymes on vitamin C for optimal catalytic activity illustrates a potentially critical contribution of the nutrient during mammalian development. These insights also highlight a potential risk associated with vitamin C insufficiency during pregnancy. The link between vitamin C insufficiency and development is particularly apparent in the context of neurodevelopment and high vitamin C concentrations in the brain are indicative of important functional requirements in this organ. Accordingly, this review considers the evidence for the potential impact of maternal vitamin C status on neurodevelopmental epigenetics.


Assuntos
Deficiência de Ácido Ascórbico/complicações , Ácido Ascórbico/farmacologia , Epigênese Genética , Regulação da Expressão Gênica no Desenvolvimento , Fenômenos Fisiológicos da Nutrição Materna , Transtornos do Neurodesenvolvimento/prevenção & controle , Neurogênese , Animais , Antioxidantes/farmacologia , Deficiência de Ácido Ascórbico/genética , Deficiência de Ácido Ascórbico/patologia , Feminino , Humanos , Transtornos do Neurodesenvolvimento/etiologia , Transtornos do Neurodesenvolvimento/patologia , Gravidez
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