RESUMO
Congenital cytomegalovirus (cCMV) is among the most common congenital infections globally. Of 85%-90% cCMV-infected infants without symptoms at birth, 10%-15% develop sequelae, most commonly sensorineural hearing loss (SNHL); their childhood neurodevelopmental outcomes are less well understood. Embase and MEDLINE were searched for publications from 16th September 2016 to 9th February 2024 to identify studies reporting primary data on neurodevelopmental outcomes in children with asymptomatic cCMV (AcCMV), measured using assessment tools or as evaluated by the study investigators, clinicians, educators, or parents. The Newcastle-Ottawa scale was applied to studies to assess risk of bias. Of 28 studies from 18 mostly high-income countries, there were 5-109 children with AcCMV per study and 6/28 had a mean or median age at last follow-up of ≥5 years. Children with AcCMV had better neurodevelopmental outcomes than children with symptomatic cCMV in 16/19 studies. Of 9/28 studies comparing AcCMV with CMV-uninfected children, six reported similar outcomes whilst three reported differences limited to measures of full-scale intelligence and receptive vocabulary among children with AcCMV and SNHL, or more generally in motor impairment. Common limitations of studies for our question were a lack of cCMV-uninfected controls, heterogeneous definitions of AcCMV, lack of focus on neurodevelopment, selection bias and inadequate follow-up. There was little evidence of children with AcCMV having worse neurodevelopmental outcomes than CMV-uninfected children, but this conclusion is limited by study characteristics and quality; findings highlight the need for well-designed and standardised approaches to investigate long-term sequelae.
Assuntos
Infecções Assintomáticas , Infecções por Citomegalovirus , Humanos , Infecções por Citomegalovirus/congênito , Infecções por Citomegalovirus/virologia , Infecções por Citomegalovirus/complicações , Infecções por Citomegalovirus/diagnóstico , Infecções Assintomáticas/epidemiologia , Recém-Nascido , Transtornos do Neurodesenvolvimento/virologia , Criança , Lactente , Pré-Escolar , Perda Auditiva Neurossensorial/virologia , CitomegalovirusRESUMO
BACKGROUND: Data on long-term neurodevelopmental outcomes of normocephalic children (born with normal head circumference) exposed to Zika virus in utero are scarce. We aimed to compare neurodevelopmental outcomes in normocephalic children up to age 48 months with and without Zika virus exposure in utero. METHODS: In this prospective cohort study, we included infants from two cohorts of normocephalic children born in León and Managua, Nicaragua during the 2016 Zika epidemic. In León, all women pregnant during the two enrolment periods were eligible. In Managua, mother-child pairs were included from three districts in the municipality of Managua: all women who became pregnant before June 15, 2016, and had a due date of Sept 15, 2016 or later were eligible. Infants were serologically classified as Zika virus-exposed or Zika virus-unexposed in utero and were followed up prospectively until age 48 months. At 36 months and 48 months of age, the Mullen Scales of Early Learning (MSEL) assessment was administered. Primary outcomes were MSEL early learning composite (ELC) scores at 30-48 months in León and 36-48 months in Managua. We used an inverse probability weighting generalised estimating equations model to assess the effect of Zika virus exposure on individual MSEL cognitive domain scores and ELC scores, adjusted for maternal education and age, poverty status, and infant sex. FINDINGS: The initial enrolment period for the León cohort was between Jan 31 and April 5, 2017 and the second was between Aug 30, 2017, and Feb 22, 2018. The enrolment period for the Managua cohort was between Oct 24, 2019, and May 5, 2020. 478 mothers (482 infants) from the León cohort and 615 mothers (609 infants) from the Managua cohort were enrolled, of whom 622 children (303 from the León cohort; 319 from the Managua cohort) were included in the final analysis; four children had microcephaly at birth and thus were excluded from analyses, two from each cohort. 33 (11%) of 303 children enrolled in León and 219 (69%) of 319 children enrolled in Managua were exposed to Zika virus in utero. In both cohorts, no significant differences were identified in adjusted mean ELC scores between Zika virus-exposed and unexposed infants at 36 months (between-group difference 1·2 points [95% CI -4·2 to 6·5] in the León cohort; 2·8 [-2·4 to 8·1] in the Managua cohort) or at 48 months (-0·9 [-10·8 to 8·8] in the León cohort; 0·1 [-5·1 to 5·2] in the Managua cohort). No differences in ELC scores between Zika virus-exposed and unexposed infants exceeded 6 points at any time between 30 months and 48 months in León or between 36 months and 48 months in Managua, which was considered clinically significant in other settings. INTERPRETATION: We found no significant differences in neurodevelopmental scores between normocephalic children with in-utero Zika virus exposure and Zika virus-unexposed children at age 36 months or 48 months. These findings are promising, supporting typical neurodevelopment in Zika virus-exposed normocephalic children, although additional follow-up and research is warranted. FUNDING: National Institute of Child Health and Development, National Institute of Allergy and Infectious Diseases, and Fogarty International Center. TRANSLATION: For the Spanish translation of the abstract see Supplementary Materials section.
Assuntos
Desenvolvimento Infantil , Complicações Infecciosas na Gravidez , Efeitos Tardios da Exposição Pré-Natal , Infecção por Zika virus , Humanos , Nicarágua/epidemiologia , Infecção por Zika virus/epidemiologia , Feminino , Estudos Prospectivos , Pré-Escolar , Gravidez , Masculino , Efeitos Tardios da Exposição Pré-Natal/epidemiologia , Efeitos Tardios da Exposição Pré-Natal/virologia , Lactente , Complicações Infecciosas na Gravidez/epidemiologia , Complicações Infecciosas na Gravidez/virologia , Zika virus , Adulto , Transtornos do Neurodesenvolvimento/epidemiologia , Transtornos do Neurodesenvolvimento/virologiaRESUMO
Prenatal exposure to viral pathogens has been known to cause the development of neuropsychiatric disorders in adulthood. Furthermore, COVID-19 has been associated with a variety of neurological manifestations, raising the question of whether in utero SARS-CoV-2 exposure can affect neurodevelopment, resulting in long-lasting behavioral and cognitive deficits. Using a human ACE2-knock-in mouse model, we have previously shown that prenatal exposure to SARS-CoV-2 at later stages of development leads to fetal brain infection and gliosis in the hippocampus and cortex. In this study, we aimed to determine whether infection of the fetal brain results in long-term neuroanatomical alterations of the cortex and hippocampus or in any cognitive deficits in adulthood. Here, we show that infected mice developed slower and weighed less in adulthood. We also found altered hippocampal and amygdala volume and aberrant newborn neuron morphology in the hippocampus of adult mice infected in utero. Furthermore, we observed sex-dependent alterations in anxiety-like behavior and locomotion, as well as hippocampal-dependent spatial memory. Taken together, our study reveals long-lasting neurological and cognitive changes as a result of prenatal SARS-CoV-2 infection, identifying a window for early intervention and highlighting the importance of immunization and antiviral intervention in pregnant women.
Assuntos
COVID-19 , Modelos Animais de Doenças , Hipocampo , Complicações Infecciosas na Gravidez , Efeitos Tardios da Exposição Pré-Natal , SARS-CoV-2 , Animais , Feminino , Gravidez , Camundongos , Efeitos Tardios da Exposição Pré-Natal/virologia , Hipocampo/patologia , Complicações Infecciosas na Gravidez/virologia , Complicações Infecciosas na Gravidez/patologia , Masculino , Comportamento Animal , Humanos , Ansiedade , Enzima de Conversão de Angiotensina 2/metabolismo , Neurônios/patologia , Neurônios/virologia , Transtornos do Neurodesenvolvimento/virologiaRESUMO
It is unclear if SARS CoV-2 infection during pregnancy is associated with adverse neurodevelopmental repercussions to infants. We assessed pediatric neurodevelopmental outcomes in children born to mothers with laboratory-confirmed SARS CoV-2 infection during pregnancy. Neurodevelopmental outcomes of in-utero exposed children were compared to that of pre-pandemic control children in Los Angeles (LA), CA, USA and Rio de Janeiro, Brazil. Bayley Scales of Infant and Toddler Development, 3rd edition (Bayley-III), the gold standard tool for evaluating neurodevelopment until 36 months of age and Ages and Stages Questionnaires (ASQ-3), a frequently used screening instrument for evaluating neurodevelopment in this same age group were the assessment tools used. Developmental delay (DD) was defined as having a score < - 2 SD below the norm (< 70) in at least one of three Bayley-III domains, (cognitive, motor or language) or a score below the cut-off (dark zone) in at least one of five ASQ-3 domains (communication, gross motor, fine motor, problem solving, personal-social). Exposed children were born between April 2020 and December 2022 while control children were born between January 2016 to December 2019. Neurodevelopmental testing was performed in 300 children total: 172 COVID-19 exposed children between 5-30 months of age and 128 control children between 6-38 months of age. Bayley-III results demonstrated that 12 of 128 exposed children (9.4%) had DD versus 2 of 128 controls (1.6%), p = 0.0007. Eight of 44 additional exposed children had DD on ASQ-3 testing. Fully, 20 of 172 exposed children (11.6%) and 2 of 128 control children (1.6%), p = 0.0006 had DD. In Rio, 12% of exposed children versus 2.6% of controls, p = 0.02 had DD. In LA, 5.7% of exposed children versus 0 controls, p = 0.12 had DD. Severe/critical maternal COVID-19 predicted below average neurodevelopment in the exposed cohort (OR 2.6, 95% CI 1.1-6.4). Children exposed to antenatal COVID-19 have a tenfold higher frequency of DD as compared to controls and should be offered neurodevelopmental follow-up.
Assuntos
COVID-19 , Deficiências do Desenvolvimento , Complicações Infecciosas na Gravidez , Efeitos Tardios da Exposição Pré-Natal , SARS-CoV-2 , Humanos , Feminino , COVID-19/epidemiologia , Gravidez , Pré-Escolar , Lactente , Masculino , Deficiências do Desenvolvimento/etiologia , Deficiências do Desenvolvimento/virologia , Deficiências do Desenvolvimento/epidemiologia , SARS-CoV-2/isolamento & purificação , Brasil/epidemiologia , Complicações Infecciosas na Gravidez/virologia , Efeitos Tardios da Exposição Pré-Natal/virologia , Adulto , Transtornos do Neurodesenvolvimento/etiologia , Transtornos do Neurodesenvolvimento/virologia , Desenvolvimento Infantil , Los Angeles/epidemiologiaAssuntos
Implantes Cocleares , Infecções por Citomegalovirus , Humanos , Infecções por Citomegalovirus/congênito , Feminino , Masculino , Pré-Escolar , Criança , Implante Coclear/métodos , Citomegalovirus , Lactente , Transtornos do Neurodesenvolvimento/etiologia , Transtornos do Neurodesenvolvimento/virologia , Transtornos do Neurodesenvolvimento/epidemiologiaRESUMO
INTRODUCTION: During the early coronavirus disease (COVID-19) pandemic in 2020, researchers cautioned about the potential neuroinvasive capability of the virus and long-term neurological consequences. Although a few preliminary studies have found delayed communication, fine motor, and problem-solving skills in infants after COVID-19 infection, there continues to be a paucity of data on long-term development of neonates diagnosed with COVID-19. METHODS: We conducted a prospective study of 20 neonates who acquired severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection during the first wave of the pandemic (April-July 2020). At 18-24 months corrected age, we assessed neurodevelopment by Bayley Scales of Infant and Toddler Development, the third edition (BSID-III), along with growth, hearing, and vision evaluation. RESULTS: The mean corrected age at assessment was 21 months 11 days ± 1 month 28 days. We found developmental delay in nearly half of the children with scores below one standard deviation in either of the BSID-III domains. Mild delay in either motor, cognitive, or language domains was found in 9 (45%) children and moderate delay in 2 (10%). Expressive language, fine motor, and receptive language were predominantly affected. None of the children had hearing impairment, blindness, or significant growth faltering including clinically severe microcephaly. The mean composite cognitive, language, and motor scores were significantly lower in those with neurodevelopmental delay (p value - 0.02, 0.000, and 0.03, respectively) without any differences in their disease characteristics. CONCLUSION: Neonates infected with SARS-CoV-2 have an increased risk of developmental delays in expressive language, fine motor, and receptive language skills at 18-24 months of age. The severity of delays is predominantly mild.
Assuntos
COVID-19 , Desenvolvimento Infantil , Deficiências do Desenvolvimento , Humanos , COVID-19/epidemiologia , COVID-19/complicações , Estudos Prospectivos , Masculino , Feminino , Lactente , Recém-Nascido , Deficiências do Desenvolvimento/epidemiologia , Deficiências do Desenvolvimento/etiologia , Deficiências do Desenvolvimento/virologia , SARS-CoV-2 , Pré-Escolar , Transtornos do Neurodesenvolvimento/virologia , Transtornos do Neurodesenvolvimento/etiologia , Transtornos do Neurodesenvolvimento/epidemiologiaRESUMO
Pregnant individuals with viral illness may experience significant morbidity and have higher rates of pregnancy and neonatal complications. With the growing number of viral infections and new viral pandemics, it is important to examine the effects of infection during pregnancy on both the gestational parent and the offspring. Febrile illness and inflammation during pregnancy are correlated with risk for autism, attention deficit/hyperactivity disorder, and developmental delay in the offspring in human and animal models. Historical viral epidemics had limited follow-up of the offspring of affected pregnancies. Infants exposed to seasonal influenza and the 2009 H1N1 influenza virus experienced increased risks of congenital malformations and neuropsychiatric conditions. Zika virus exposure in utero can lead to a spectrum of abnormalities, ranging from severe microcephaly to neurodevelopmental delays which may appear later in childhood and in the absence of Zika-related birth defects. Vertical infection with severe acute respiratory syndrome coronavirus-2 has occurred rarely, but there appears to be a risk for developmental delays in the infants with antenatal exposure. Determining how illness from infection during pregnancy and specific viral pathogens can affect pregnancy and neurodevelopmental outcomes of offspring can better prepare the community to care for these children as they grow. IMPACT: Viral infections have impacted pregnant people and their offspring throughout history. Antenatal exposure to maternal fever and inflammation may increase risk of developmental and neurobehavioral disorders in infants and children. The recent SARS-CoV-2 pandemic stresses the importance of longitudinal studies to follow pregnancies and offspring neurodevelopment.
Assuntos
Complicações Infecciosas na Gravidez , Efeitos Tardios da Exposição Pré-Natal , Viroses , Humanos , Gravidez , Feminino , Complicações Infecciosas na Gravidez/virologia , Viroses/complicações , Infecção por Zika virus/complicações , Transtornos do Neurodesenvolvimento/etiologia , Transtornos do Neurodesenvolvimento/virologia , Transtornos do Neurodesenvolvimento/epidemiologia , COVID-19/epidemiologia , Animais , Desenvolvimento Infantil , Deficiências do Desenvolvimento/etiologia , Deficiências do Desenvolvimento/epidemiologia , Deficiências do Desenvolvimento/virologia , Influenza Humana/epidemiologia , Recém-Nascido , Lactente , SARS-CoV-2Assuntos
COVID-19 , SARS-CoV-2 , Humanos , SARS-CoV-2/isolamento & purificação , Feminino , Gravidez , Efeitos Tardios da Exposição Pré-Natal , Transtornos do Neurodesenvolvimento/virologia , Transtornos do Neurodesenvolvimento/etiologia , Transtornos do Neurodesenvolvimento/diagnóstico , Desenvolvimento Infantil , Complicações Infecciosas na Gravidez/virologia , Recém-Nascido , Criança , Dinâmica não Linear , LactenteRESUMO
It was late 2015 when Northeast Brazil noticed a worrying increase in neonates born with microcephaly and other congenital malformations. These abnormalities, characterized by an abnormally small head and often neurological impairment and later termed Congenital Zika Syndrome, describe the severity of neurodevelopmental and nephrological outcomes in early childhood, and the implication of microcephaly at birth. The purpose of the study was to describe the neurodevelopmental outcomes in children exposed to Zika virus during fetal life, with and without microcephaly at birth. The systematic review included research studies about the neurodevelopmental outcomes with and without microcephaly, as well as nephrological outcomes in early childhood. We searched PubMed, Crossref, PsycINFO, Scopus, and Google Scholar publications and selected 19 research articles published from 2018 to 2021. Most studies have linked the severity of microcephaly in childbirth to the neurodevelopmental and urinary outcomes in early childhood. However, most children without microcephaly at birth develop typically, while others may be at risk for language impairment.
Assuntos
Doenças do Recém-Nascido/virologia , Doenças do Sistema Nervoso/virologia , Transtornos do Neurodesenvolvimento/virologia , Doenças Urológicas/virologia , Infecção por Zika virus/virologia , Zika virus/fisiologia , Brasil , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Doenças do Recém-Nascido/psicologia , Masculino , Doenças do Sistema Nervoso/psicologia , Transtornos do Neurodesenvolvimento/psicologia , Doenças Urológicas/psicologia , Zika virus/genética , Infecção por Zika virus/congênito , Infecção por Zika virus/psicologiaRESUMO
INTRODUÇÃO: A comprovação da associação de microcefalia no Brasil com a infecção congênita pelo Zika vírus, leva a necessidade de estudos sobre a repercussão no desenvolvimento das crianças decorrentes do comprometimento do sistema nervoso central (SNC). OBJETIVO: Avaliar o desenvolvimento neuropsicomotor (DNPM) de crianças expostas à infecção congênita pelo Zika vírus e sua associação com características e diagnósticos pré natais, neonatais e pós natais da mãe/criança. MÉTODOS: Estudo transversal com crianças de zero a três anos, nascidas entre 2015 e 2018, classificadas com infecção congênita pelo Zika vírus. Na coleta das características clínicas e sócio demográficas, utilizou-se um questionário semiestruturado e na avaliação do DNPM o Teste de Triagem de Denver II. Na associação, utilizou-se o teste exato de Fisher (p<0,05). RESULTADOS: Avaliou-se 30 crianças, 46,67% apresentavam alterações do DNPM, os maiores foram na linguagem (46,67%) e motricidade fina (43,33%). 23,33% tinham mais que 24 meses, idade que se associou a alterações do DNPM (p<0,012). A infecção predominou entre 4 e 12 semanas de gestação e obteve associação com os atrasos do DNPM (p<0,002). 46,67% das crianças apresentaram microcefalia e 40% calcificações cerebrais, ambos com associação a atrasos no DNPM (p<0,001). Em exame físico 36,7% apresentaram alterações de postura e persistência de reflexos primitivos, 40% hiperirritabilidade, 33,33% disfagia e deformidades articulares, todas com associação importante com as alterações no DNPM (p<0,001). CONCLUSÕES: Crianças expostas à infecção congênita pelo Zika vírus apresentaram atrasos no DNPM e quanto mais precoce a infecção na gravidez, maior o envolvimento do sistema nervoso central.
INTRODUCTION: The proof of the association of microcephaly in Brazil with congenital Zika virus infection leads to the need for studies on the impact on children's development resulting from the involvement of the central nervous system (CNS). OBJECTIVE: To evaluate the neuropsychomotor development (NPMD) of children exposed to congenital Zika virus infection and its association with prenatal, neonatal, and postnatal characteristics and diagnoses of the mother/child. METHODS: Cross-sectional study with children aged zero to three years, born between 2015 and 2018, classified with congenital Zika virus infection. In the collection of clinical and socio-demographic characteristics, a semistructured questionnaire was used, and the Denver II Screening Test was used to assess the DNPM. In the association, Fisher's exact test was used (p<0.05). RESULTS: Thirty children were evaluated; 46.67% had DNPM alterations, the greatest ones were in the language (46.67%) and fine motor skills (43.33%). 23.33% were older than 24 months, an age-associated with changes in DNPM (p<0.012). Infection predominated between 4 and 12 weeks of gestation and was associated with DNPM delays (p<0.002). 46.67% of children had microcephaly and 40% cerebral calcifications, both associated with DNPM delays (p<0.001). On physical examination, 36.7% had changes in posture and persistence of primitive reflexes, 40% hyperirritability, 33.33% dysphagia, and joint deformities, all with an important association with changes in DNPM (p<0.001). CONCLUSIONS: Children exposed to congenital Zika infection had developmental delays. It is noteworthy that the earlier the infection in pregnancy, the greater the involvement of the central nervous system of children.
Assuntos
Humanos , Masculino , Feminino , Recém-Nascido , Lactente , Pré-Escolar , Transtornos do Neurodesenvolvimento/virologia , Infecção por Zika virus/congênito , Estudos Transversais , Fatores SociodemográficosRESUMO
Since Zika virus (ZIKV) first emerged as a public health concern in 2015, our ability to identify and track the long-term neurological sequelae of prenatal Zika virus (ZIKV) infection in humans has been limited. Our lab has developed a rat model of maternal ZIKV infection with associated vertical transmission to the fetus that results in significant brain malformations in the neonatal offspring. Here, we use this model in conjunction with longitudinal magnetic resonance imaging (MRI) to expand our understanding of the long-term neurological consequences of prenatal ZIKV infection in order to identify characteristic neurodevelopmental changes and track them across time. We exploited both manual and automated atlas-based segmentation of MR images in order to identify long-term structural changes within the developing rat brain following inoculation. The paradigm involved scanning three cohorts of male and female rats that were prenatally inoculated with 107 PFU ZIKV, 107 UV-inactivated ZIKV (iZIKV), or diluent medium (mock), at 4 different postnatal day (P) age points: P2, P16, P24, and P60. Analysis of tracked brain structures revealed significantly altered development in both the ZIKV and iZIKV rats. Moreover, we demonstrate that prenatal ZIKV infection alters the growth of brain regions throughout the neonatal and juvenile ages. Our findings also suggest that maternal immune activation caused by inactive viral proteins may play a role in altered brain growth throughout development. For the very first time, we introduce manual and automated atlas-based segmentation of neonatal and juvenile rat brains longitudinally. Experimental results demonstrate the effectiveness of our novel approach for detecting significant changes in neurodevelopment in models of early-life infections.
Assuntos
Transmissão Vertical de Doenças Infecciosas , Imageamento por Ressonância Magnética/métodos , Transtornos do Neurodesenvolvimento/virologia , Neuroimagem/métodos , Complicações Infecciosas na Gravidez/virologia , Infecção por Zika virus/complicações , Zika virus/fisiologia , Animais , Modelos Animais de Doenças , Feminino , Transtornos do Neurodesenvolvimento/diagnóstico por imagem , Gravidez , Complicações Infecciosas na Gravidez/diagnóstico por imagem , Ratos , Zika virus/patogenicidade , Infecção por Zika virus/diagnóstico por imagemRESUMO
BACKGROUND: Data on the neurodevelopment of children who experienced central nervous system (CNS) infections with enteroviruses (EV) or parechoviruses (hPeV) is scarce and mostly limited to follow up of short-term outcomes. METHODS: Parents of children who presented between 2014 and 2019, underwent a lumbar puncture and whose cerebrospinal fluid was polymerase chain reaction positive for EV or hPeV, were asked to complete a care-giver-administered neurodevelopmental assessment tool (The Ages and Stages Instrument [ASQ3]). Clinical data of the infective episode were collected from patient notes. RESULTS: Of 101 children, 43 (10 hPeV+, 33 EV+) submitted ASQ3 results. Median age at assessment was 38.9 months (interquartile range, 15.4-54.8), the follow-up interval 3 years (median 37 months; interquartile range, 13.9-53.1). Age, inflammatory markers, and cerebrospinal fluid pleocytosis during the infective event were not associated with ASQ3 scores. In 23 children (17 EV+, 6 hPeV+), no neurodevelopmental concerns were reported. Two more had preexisting developmental delay and were excluded. Of the remaining, 18/41 (43.9%) reported ASQ3 scores indicating need for monitoring or professional review in at least 1 category, not differing by pathogen (EV 14/31, 45.2%; hPeV 4/10, 40%; P = 0.71). Seven children will require formal review, scoring ≥2 SD below the mean in at least 1 category (6/31 EV+, 1/10 hPeV+, P = 0.7), 3 scored ≥2 SD below the mean in more than 1 area. CONCLUSIONS: Parent-administered developmental assessment of children with a history of early picornavirus infection of the CNS identified a subgroup that requires formal neurodevelopmental review. Wider application of community-based developmental screening will complement our understanding of the impact of CNS infections in early childhood.
Assuntos
Infecções do Sistema Nervoso Central/complicações , Infecções do Sistema Nervoso Central/virologia , Transtornos do Neurodesenvolvimento/diagnóstico , Transtornos do Neurodesenvolvimento/etiologia , Pais , Infecções por Picornaviridae/complicações , Picornaviridae/genética , Criança , Pré-Escolar , Enterovirus/genética , Seguimentos , Humanos , Lactente , Programas de Rastreamento/métodos , Transtornos do Neurodesenvolvimento/virologia , Parechovirus/genética , Picornaviridae/patogenicidade , Infecções por Picornaviridae/líquido cefalorraquidiano , Inquéritos e QuestionáriosRESUMO
OBJECTIVE: To perform a systematic literature review to analyze existing data on the neurological effects of coronavirus on newborns. DATA: sources: We followed the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P), and searched the PubMed and Embase platforms for the keywords [brain damage OR pregnancy OR developmental outcomes] and [coronavirus OR SARS-CoV-2 OR SARS-CoV OR MERS-CoV] between January 1, 2000 and June 1, 2020. DATA: synthesis: Twenty-three reports described the course of pregnant women exposed to SARS-CoV-2, SARS-CoV, or MERS-CoV during the gestational period, eight to SARS-CoV-2, eight to SARS-CoV, and seven to MERS-CoV. No data were found on abnormalities in brain development or on a direct link between the virus and neurological abnormalities in the human embryo, fetus, or children. Spontaneous miscarriage, stillbirth, and termination of pregnancy were some complications connected with SARS/MERS-CoV infection. SARS-CoV-2 is not currently associated with complications in the gestational period. CONCLUSIONS: The literature has no data associating exposure to coronavirus during pregnancy with brain malformations and neurodevelopmental disorders. However, despite the lack of reports, monitoring the development of children exposed to SARS-CoV-2 is essential given the risk of complications in pregnant women and the potential neuroinvasive and neurotropic properties found in previous strains.
Assuntos
Encefalopatias/etiologia , Deficiências do Desenvolvimento/etiologia , Efeitos Tardios da Exposição Pré-Natal/virologia , SARS-CoV-2 , Encefalopatias/virologia , Deficiências do Desenvolvimento/virologia , Feminino , Humanos , Transtornos do Neurodesenvolvimento/etiologia , Transtornos do Neurodesenvolvimento/virologia , Gravidez , Efeitos Tardios da Exposição Pré-Natal/etiologia , Fatores de RiscoRESUMO
OBJECTIVE: We examined relationships between plasma biomarkers and neurodevelopment in children from sub-Saharan Africa with perinatal HIV (PHIV) with controlled viremia on antiretroviral therapy (ART). DESIGN: Longitudinal retrospective cohort study of children with controlled blood HIV replication. METHODS: Children (Nâ=â213; 57% girls) started ART at less than 3âyears of age, had neurodevelopmental assessments (cognition, attention/impulsivity, motor proficiency, global executive functions) at 5-11âyears, and achieved controlled viremia (HIV-1 RNA <400âcopies/ml for ≥9âmonths before initial assessment). Twenty-three plasma biomarkers were measured at onset of controlled viremia, week 0 (first neurodevelopmental assessment), and week 48 (second neurodevelopmental assessment). Factor analysis was conducted at each time point. Multivariable linear regressions assessed associations between factors and neurodevelopmental scores. RESULTS: Median age at week 0 was 7.0âyears. Eighteen biomarkers loaded on six factors: a (L-10, IFNγ, IFNα2, IL-1ß, IL-6, IP-10, TNFα); B (sCD163, sICAM-1, sVCAM-1, CRP); C (sE-selectin, sP-selectin); D [MIP-1ß, vascular endothelial growth factor (VEGF)-A]; E (sCD14, CRP); and F (CX3CL1, MCP-1). Higher factor B scores were consistently associated with worse cognition and attention/impulsivity, and higher factor D scores with better attention/impulsivity. CONCLUSION: These results suggest a detrimental effect of increased endothelial cell activation (sICAM-1, sVCAM-1) and monocyte/macrophage scavenger function (sCD163) and a beneficial effect of increased CCR5 ligand and HIV entry blocker MIP-1ß and angiogenesis stimulant-VEGF concentrations on the neurodevelopment of children with PHIV. The model that emerges is of vascular inflammation leading to neurodevelopmental deficits. The role of persistent HIV replication in the central nervous system also needs to be further explored.
Assuntos
Biomarcadores/sangue , Infecções por HIV , Transtornos do Neurodesenvolvimento/virologia , Criança , Pré-Escolar , Feminino , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Humanos , Masculino , Gravidez , Estudos Retrospectivos , ViremiaRESUMO
BACKGROUND: Parechovirus A type 3 (PeV-A3) is associated with central nervous system infection in young infants. There are limited data regarding long-term outcomes, mostly reported from Australia and European populations. The objective of this study was to assess frequency of neurodevelopmental impairment (NDI) following PeV-A3 infection in our US cohort. METHODS: Infants hospitalized during the 2014 outbreak with laboratory-confirmed PeV-A3 infection were evaluated with medical history, neurologic examination, parental completion of Ages and Stages Questionnaire and developmental assessment using Bayley Scales of Infant and Toddler Development, Third Edition cognitive, motor and language quotients. Determination of NDI was based on published criteria. Relationship of severity of PeV disease to outcome measures was determined using Fisher exact, χ2 and Mann-Whitney U test as appropriate. RESULTS: Nineteen children, term gestation, were evaluated at ~3 years of age; PeV-A3 illness was uncomplicated for 6 (32%), complex, non-neurologic for 9 (47%) and encephalitis/seizures for 4 (21%). No differences were noted in mean Bayley Scales of Infant and Toddler Development, Third Edition quotients between infants by clinical presentation. Quotients for all were within 1 SD of population norms. Two (11%) children had mild NDI; 1 with mild cerebral palsy. Ages and Stages Questionnaire results included 11% at referral level and 37% suspect concern. Parents of 6 (32%) noted behavior concerns. These findings were unrelated to severity of the PeV-A3 illness. CONCLUSIONS: Parent concerns were identified frequently following infant PeV-A3 disease. Eleven percent had neurodevelopmental impairment at 3 years of age. Severity at presentation did not correlate with adverse childhood outcomes. Longitudinal developmental monitoring following infantile PeV-A3 disease is warranted.
Assuntos
Infecções do Sistema Nervoso Central/virologia , Transtornos do Neurodesenvolvimento/epidemiologia , Parechovirus/patogenicidade , Infecções por Picornaviridae/complicações , Infecções por Picornaviridae/epidemiologia , Infecções do Sistema Nervoso Central/epidemiologia , Pré-Escolar , Estudos de Coortes , Seguimentos , Hospitalização/estatística & dados numéricos , Humanos , Transtornos do Neurodesenvolvimento/virologia , Parechovirus/classificação , Parechovirus/genética , Infecções por Picornaviridae/líquido cefalorraquidiano , Infecções por Picornaviridae/diagnóstico , Índice de Gravidade de Doença , Estados Unidos/epidemiologiaRESUMO
BACKGROUND: The objective of this study was to describe the case literature of human coronavirus infections in the nervous system of children, including from SARS-CoV-2, and to provide guidance to pediatric providers for managing the potential long-term effects on neurodevelopment of human coronavirus infections in the nervous system. METHODS: Using a structured strategy, the PubMed and Ovid:Embase databases were queried for articles about the clinical presentation and pathophysiology of coronavirus infections in the nervous system of children and young adults, aged 0 to 24 years. RESULTS: Of 2302 articles reviewed, 31 described SARS-CoV-2 infections in the nervous system of children and 21 described other human coronaviruses: HCoV-229E, HCoV-NL63, HCoV-OC43, HCoV-HKU1, MERS-CoV, SARS-CoV-1. Excepting MERS-CoV, we found cases of neurological disease in children from each human coronavirus. Children with non-SARS-CoV-2 infections have suffered acute flaccid paralysis, acute disseminated encephalomyelitis, encephalitis, and seizures. In addition, cases of ischemic, hemorrhagic, and microvascular strokes have occurred in children with SARS-CoV-2. Patients with multisystem inflammatory syndrome in children have suffered encephalitis, stroke, pseudotumor cerebri syndrome, and cytotoxic lesions of deep brain structures. Despite these reports, few articles evaluated the impact of human coronavirus infections on long-term neurodevelopmental domains including cognitive, language, academic, motor, and psychosocial outcomes. CONCLUSIONS: Neurological manifestations of human coronavirus infections can cause severe disease in children. The case literature suggests a critical gap in knowledge of the long-term effects on child neurodevelopment of these infections. As the current SARS-CoV-2 pandemic continues, this gap must be filled to facilitate optimal outcomes in recovering children.
Assuntos
COVID-19/complicações , Doenças do Sistema Nervoso/diagnóstico , Doenças do Sistema Nervoso/virologia , Transtornos do Neurodesenvolvimento/diagnóstico , Transtornos do Neurodesenvolvimento/virologia , Vigilância da População , Adolescente , Fatores Etários , Criança , Pré-Escolar , Humanos , Lactente , Recém-Nascido , Fatores de TempoRESUMO
Hand, foot and mouth disease (HFMD) is a common infectious disease in western Asia area and the full range of the long-term sequelae of HFMD remains poorly described. We conducted a retrospective hospital-based cohort study of HFMD patients with central nervous system (CNS) complications caused by EV-A71 or CV-A16 between 2010 and 2016. Patients were classified into three groups, including CNS only, autonomic nervous system (ANS) dysregulation, and cardiorespiratory failure. Neurologic examination, neurodevelopmental assessments, Magnetic Resonance Imaging (MRI) and lung function, were performed at follow up. Of the 176 patients followed up, 24 suffered CNS only, 133 ANS dysregulation, and 19 cardiorespiratory failure. Median follow-up period was 4.3 years (range [1.4-8.3]). The rate of neurological abnormalities was 25% (43 of 171) at discharge and 10% (17 of 171) at follow-up. The rates of poor outcome were significantly different between the three groups of complications in motor (28%, 38%, 71%) domain (p=0.020), but not for cognitive (20%, 24%, 35%), language (25%, 36%, 41%) and adaptive (24%, 16%, 26%) domains (p = 0.537, p = 0.551, p = 0.403). For children with ventilated during hospitalization, 41% patients (14 of 34) had an obstructive ventilatory defect, and one patient with scoliosis had mixed ventilatory dysfunction. Persistent abnormalities on brain MRI were 0% (0 of 7), 9% (2 of 23) and 57% (4 of 7) in CNS, ANS and cardiorespiratory failure group separately. Patients with HFMD may have abnormalities in neurological, motor, language, cognition, adaptive behaviour and respiratory function. Long-term follow-up programmes for children's neurodevelopmental and respiratory function may be warranted.
Assuntos
Infecções por Enterovirus/epidemiologia , Enterovirus/isolamento & purificação , Doença de Mão, Pé e Boca/epidemiologia , Insuficiência Cardíaca/epidemiologia , Transtornos do Neurodesenvolvimento/epidemiologia , Insuficiência Respiratória/epidemiologia , Sistema Nervoso Autônomo/virologia , Aptidão Cardiorrespiratória , Sistema Nervoso Central/virologia , Criança , Pré-Escolar , China/epidemiologia , Enterovirus/genética , Infecções por Enterovirus/virologia , Feminino , Seguimentos , Doença de Mão, Pé e Boca/virologia , Insuficiência Cardíaca/virologia , Hospitalização , Humanos , Lactente , Recém-Nascido , Pacientes Internados , Imageamento por Ressonância Magnética , Masculino , Transtornos do Neurodesenvolvimento/virologia , Reação em Cadeia da Polimerase , Insuficiência Respiratória/virologia , Estudos RetrospectivosAssuntos
Encéfalo/crescimento & desenvolvimento , COVID-19/fisiopatologia , Desenvolvimento Fetal , Transtornos do Neurodesenvolvimento/virologia , Complicações Infecciosas na Gravidez/fisiopatologia , Efeitos Tardios da Exposição Pré-Natal/virologia , Encéfalo/embriologia , Encéfalo/virologia , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , GravidezRESUMO
Background: When acquired during pregnancy, Zika virus (ZIKV) infection can cause substantial fetal morbidity, however, little is known about the long-term neurodevelopmental abnormalities of infants with congenital ZIKV exposure without microcephaly at birth. Methods: We conducted a cross sectional study to characterize infants born with microcephaly, and a retrospective cohort study of infants who appeared well at birth, but had possible congenital ZIKV exposure. We analyzed data from the Dominican Ministry of Health's (MoH) National System of Epidemiological Surveillance. Neurodevelopmental abnormalities were assessed by pediatric neurologists over an 18-month period using Denver Developmental Screening Test II. Results: Of 800 known live births from 1,364 women with suspected or confirmed ZIKV infection during pregnancy, 87 (11%) infants had confirmed microcephaly. Mean head circumference (HC) at birth was 28.1 cm (SD ± 2.1 cm) and 41% had a HC on the zero percentile for gestational age. Of 42 infants with possible congenital ZIKV exposure followed longitudinally, 52% had neurodevelopmental abnormalities, including two cases of postnatal onset microcephaly, during follow-up. Most abnormalities resolved, though two infants (4%) had neurodevelopmental abnormalities that were likely associated with ZIKV infection and persisted through 15-18 months. Conclusions: In the DR epidemic, 11% of infants born to women reported to the MoH with suspected or confirmed ZIKV during pregnancy had microcephaly. Some 4% of ZKV-exposed infants developed postnatal neurocognitive abnormalities. Monitoring of the cohort through late childhood and adolescence is needed.
Assuntos
Anormalidades Congênitas/virologia , Microcefalia/virologia , Transtornos do Neurodesenvolvimento/virologia , Complicações Infecciosas na Gravidez/virologia , Infecção por Zika virus/epidemiologia , Zika virus , Adolescente , Criança , Anormalidades Congênitas/epidemiologia , Estudos Transversais , República Dominicana/epidemiologia , Epidemias , Feminino , Humanos , Lactente , Recém-Nascido , Microcefalia/epidemiologia , Gravidez , Complicações Infecciosas na Gravidez/epidemiologia , Estudos Retrospectivos , Infecção por Zika virus/diagnósticoRESUMO
The developing brain is especially vulnerable to infection and suboptimal nutrition during the pre- and early postnatal periods. Exposure to maternal human immunodeficiency virus (HIV) infection and antiretroviral therapies (ART) in utero and during breastfeeding can adversely influence infant (neuro) developmental trajectories. How early life nutrition may be optimised to improve neurodevelopmental outcomes for infants who are HIV-exposed has not been well characterised. We conducted an up-to-date evidence review and meta-analysis on the influence of HIV exposure in utero and during breastfeeding, and early life nutrition, on infant neurodevelopmental outcomes before age three. We report that exposure to maternal HIV infection may adversely influence expressive language development, in particular, and these effects may be detectable within the first three years of life. Further, while male infants may be especially vulnerable to HIV exposure, few studies overall reported sex-comparisons, and whether there are sex-dependent effects of HIV exposure on neurodevelopment remains a critical knowledge gap to fill. Lastly, early life nutrition interventions, including daily maternal multivitamin supplementation during the perinatal period, may improve neurodevelopmental outcomes for infants who are HIV-exposed. Our findings suggest that the early nutritional environment may be leveraged to improve early neurodevelopmental trajectories in infants who have been exposed to HIV in utero. A clear understanding of how this environment should be optimised is key for developing targeted nutrition interventions during critical developmental periods in order to mitigate adverse outcomes later in life and should be a priority of future research.