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1.
J Clin Virol ; 108: 141-146, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30316173

RESUMO

BACKGROUND: Human cytomegalovirus (HCMV) infection is the most common congenital infection in developed countries. Recent studies highlighted similar percentages of symptoms in HCMV congenitally-infected infants following either primary or non-primary maternal infections. OBJECTIVES: To highlight correlation between neonatal brain abnormalities, detected by ultrasounds and magnetic resonance image in HCMV congenitally-infected infants, and maternal virological parameters during pregnancy, especially in seroimmune mothers. STUDY DESIGN: We considered the 36 HCMV congenitally-infected infants (26 asymptomatic and 10 symptomatic) referred to our center over 4 consecutive years. Maternal serologic data during pregnancy were available for all cases. Neonatal cranial ultrasound and magnetic resonance images were related to maternal virological findings during pregnancy. RESULTS: Polymicrogyria was observed in 6/10 (60.0%) symptomatic and 0/26 (0%) asymptomatic newborns (p < 0.001). The 6 infants with polymicrogyria were all born to mothers who were HCMV IgG reactive with negative specific IgM, in the first trimester of pregnancy (range: 8-14 weeks). For these six women, pre-conceptional HCMV serologic information were absent and they all were considered immune for HCMV during pregnancy, therefore no further serologic investigation or specific educational and hygienic information were recommended during gestation. CONCLUSION: These data highlight the elevated frequency of polymicrogyria in HCMV congenitally-infected infants born to mothers defined as seroimmune in the early stage of pregnancy and having no pre-existing serologic information. The paper stresses the potential utility of pre-conceptional screening to define maternal infection reliably (primary vs non-primary), and allow evidence-based counseling in women with positive serology, suggesting also preventive hygienic measures during pregnancy.

3.
J Autism Dev Disord ; 47(5): 1490-1495, 2017 05.
Artigo em Inglês | MEDLINE | ID: mdl-28258350

RESUMO

The aim of this retrospective study, with prospective data collection, was to correlate congenital cytomegalovirus (CMV) infection with autism spectrum disorder (ASD) and to define its prevalence. Seventy proven congenitally-infected infants, born between 2007 and 2012, were referred to our centre for CMV diagnosis and follow-up, which consisted of a consolidated protocol allowing an early evaluation of autism. We considered four children 2-year old, two of whom, at the age of 3, were diagnosed with ASD demonstrating a 2-3 fold higher prevalence (2.86%), than that in general Italian population (0.66-1.36%).Our protocol enabled us to make the earliest diagnosis and highlight the role of the virus among other causes of autism, which may be a long term sequela of congenital CMV.


Assuntos
Transtorno do Espectro Autista/virologia , Infecções por Citomegalovirus/complicações , Transtorno do Espectro Autista/epidemiologia , Pré-Escolar , Infecções por Citomegalovirus/congênito , Infecções por Citomegalovirus/psicologia , Feminino , Humanos , Lactente , Recém-Nascido , Itália/epidemiologia , Masculino , Prevalência , Estudos Prospectivos , Estudos Retrospectivos
4.
J Med Virol ; 88(1): 120-6, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26118464

RESUMO

Given the difficulty in establishing the exact time of HCMV transmission from mother to fetus, HCMV intrauterine infection was investigated in 46 infected fetuses/newborns by correlating maternal and fetal parameters with clinical outcome according to the time interval between the onset of maternal infection and prenatal diagnosis. In detail, 17/28 (60.7%) asymptomatic and 18/18 (100%) symptomatic fetuses/newborns were infected as a consequence of a primary maternal HCMV infection acquired ≤8 weeks of gestational age, while 11/28 (39.3%) asymptomatic and 0/18 (0%) symptomatic fetuses/newborns were congenitally infected when maternal infection was acquired >8 weeks' gestation. Symptomatic fetal infections appeared to be associated with a maternal primary infection occurring at ≤ 8 weeks' gestation. Cordocentesis performed at 20 weeks' gestation should be restricted to high risk infected fetuses.


Assuntos
Infecções por Citomegalovirus/congênito , Infecções por Citomegalovirus/transmissão , Idade Gestacional , Transmissão Vertical de Doença Infecciosa , Complicações Infecciosas na Gravidez , Estudos de Coortes , Feminino , Humanos , Recém-Nascido , Gravidez , Diagnóstico Pré-Natal , Medição de Risco , Fatores de Tempo
5.
J Med Virol ; 86(12): 2163-70, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24777597

RESUMO

To investigate retrospectively the prognostic significance of maternal, fetal, and neonatal parameters and clinical outcome in 150 HCMV congenital infections during the period 1995-2009. HCMV fetal infection was investigated in amniotic fluid and fetal blood samples. HCMV congenital infection was confirmed in newborn urine and blood samples. Symptomatic infection was defined in HCMV-infected fetuses and in infected newborns on the basis of physical and instrumental findings. Follow-up at 3, 6, 12 months, and then annually up to school age, included clinical evaluation, funduscopic, audiologic, neurologic, and cognitive assessment. Overall, 122/150 (81.3%) newborns were asymptomatic and 28/150 (18.7%) were symptomatic at birth. The best prognostic maternal parameter of symptomatic infection at birth was gestational age at infection (P = 0.037). The best fetal virological markers were HCMV DNA levels in amniotic fluid (P < 0.001), antigenaemia levels (P = 0.007), HCMV DNA levels in blood (P = 0.004), and HCMV-specific IgM index values (P = 0.002). The only significant neonatal parameter was HCMV DNA level in blood [P = 0.006; OR, 3.62 (95% CI, 1.46-8.97)]. Symptoms at birth correlated significantly with long-term sequelae (P = 0.021). A trend towards a risk of sequelae in early (n = 15/58 examined) versus late (n = 6/57 examined) maternal infection was documented. The risk of symptomatic congenital infection at birth increased linearly with the number of significant maternal, fetal, and neonatal parameters.


Assuntos
Aconselhamento , Infecções por Citomegalovirus/congênito , Infecções por Citomegalovirus/patologia , Antígenos Virais/sangue , Sangue/virologia , Estudos de Coortes , Citomegalovirus/isolamento & purificação , DNA Viral/sangue , Feminino , Seguimentos , Idade Gestacional , Humanos , Recém-Nascido , Gravidez , Prognóstico , Estudos Retrospectivos , Urina/virologia , Carga Viral , Viremia
6.
Early Hum Dev ; 90 Suppl 1: S29-31, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24709452

RESUMO

Fetal HCMV infection is investigated by amniocentesis when a maternal primary infection is diagnosed or ultrasound (US/MRI) abnormalities are observed. In fetal blood, prognostic markers of symptomatic congenital infection may be evaluated for parental counseling. At birth, viral load measurement in body fluids may correlate with long-term sequelae, but the prognostic accuracy of symptomatic infection increases when maternal, fetal, and neonatal parameters are combined.


Assuntos
Infecções por Citomegalovirus/diagnóstico , Doenças Fetais/diagnóstico , Amniocentese , Biomarcadores/sangue , Biomarcadores/urina , Aconselhamento , Infecções por Citomegalovirus/congênito , Feminino , Humanos , Recém-Nascido , Transmissão Vertical de Doença Infecciosa , Gravidez
7.
Curr Drug Metab ; 14(2): 208-15, 2013 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-22935067

RESUMO

Congenital cytomegalovirus infection is the most common cause of nonhereditary sensorineural hearing loss and an important cause of psychomotor retardation. Newborns suffering from symptomatic congenital cytomegalovirus infection have been typically treated with i.v. ganciclovir (GCV). Nowadays valganciclovir (V-GCV), a mono-valyl ester pro-drug of GCV, is available as an oral syrup. The existing literature demonstrated that V-GCV is well absorbed from the gastrointestinal tract and is rapidly converted into GCV in the intestinal wall and liver. The mechanism of antiviral action is the same that has been described for GCV. All these characteristics make this formulation particularly suitable for the symptomatic congenitally infected newborns. In neonates, V-GCV oral formulation proved stable and constant GVC plasma concentrations, in the suggested therapeutic range. The syrup demonstrated to be clinically effective and well tolerated and to be appropriate for a prolonged post-discharge therapy avoiding the discomfort of hospitalization, reducing the risk for nosocomial infections and decreasing the cost for the National Health Service. This article reviews all the available literature about V-GCV syrup in the treatment of newborns and infants with congenital CMV infection with the regard to pharmacokinetics, pharmacodynamic properties and clinical use, focussing on new data and on our experience.


Assuntos
Antivirais/uso terapêutico , Infecções por Citomegalovirus/tratamento farmacológico , Ganciclovir/análogos & derivados , Animais , Antivirais/farmacologia , Infecções por Citomegalovirus/congênito , Interações de Medicamentos , Ganciclovir/farmacologia , Ganciclovir/uso terapêutico , Humanos , Recém-Nascido , Simportadores/metabolismo , Resultado do Tratamento , Valganciclovir
8.
J Matern Fetal Neonatal Med ; 25 Suppl 3: 57-62, 2012 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-23016620

RESUMO

Perinatal transmission of human cytomegalovirus (HCMV) infection in very low birth weight (VLBW) premature infants can lead to serious clinical symptoms and it has ben increasingly recognized that breast milk is the most frequent route of transmission. Breast milk is considered ideal food for newborns because of its nutritional value and anti-infectious components, but it can also be vehicle for viral and bacterial infection. The majority of HCMV seropositive mothers shed the virus into their breast milk and can transmit infection to their offspring. Perinatally acquired infections in full-term neonates are usually asymptomatic without sequelae due to protective maternal HCMV-specific antibodies received during pregnancy. In contrast, VLBW preterm infants are at risk of symptomatic infection with neutropaenia, thrombocytopaenia, sepsis-like syndrome and, less frequently, pneumonia and enteric infection. Postnatally acquired infection seems to spontaneously resolve without altering the clinical outcome. Ganciclovir treatment is restricted to severe symptomatic infections. Preterm infants with a gestational age <30 weeks, or with a birth weight <1000 g, are at greater risk of severe postnatal symptomatic HCMV infection, transmitted via maternal milk. The pasteurization of breast milk entirely eliminates infectivity and prevents virus transmission but alters nutritional and immunological milk properties, and freezing reduces, but does not eradicate, infectivity. Most authors encourage fresh maternal breastfeeding because its beneficial effects outweigh the risk of a transient infection, sequelae-free. Nevertheless, an individual decision based on the condition of health of the infant is important.


Assuntos
Infecções por Citomegalovirus/transmissão , Transmissão Vertical de Doença Infecciosa , Leite Humano/virologia , Aleitamento Materno , Citomegalovirus/isolamento & purificação , Infecções por Citomegalovirus/diagnóstico , Infecções por Citomegalovirus/prevenção & controle , Humanos , Recém-Nascido , Doenças do Recém-Nascido , Recém-Nascido de muito Baixo Peso
11.
J Matern Fetal Neonatal Med ; 23 Suppl 3: 45-8, 2010 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-20807160

RESUMO

Cytomegalovirus (CMV) is the most common cause of congenital infection affecting about 1% of all the live births worldwide. Its prevalence in the developed world seems to be slightly lower, ranging between 0.6 and 0.7%. Symptoms can be detected at birth in 10-15% of the congenitally infected of which 50-90% will develop sequelae, the most frequent being sensorineural hearing loss (SNHL), visual defect, psychomotor impairment, mental retardation, cerebral palsy and seizures. Eighty-five to 90% of the infected newborns are asymptomatic but 10-15% of them are equally at risk for sensorineural sequelae, like 20-30% of all the infected children. Therefore it is important a time prolonged and closer follow-up of infected children that we propose should be until 6 years of age. This should lead to an early intervention, better management and eventually even control the long-term sequelae. Infants born with symptomatic congenital infection have a worse prognosis than those with no evidence of clinical disease, and ganciclovir (GCV) intravenous 6 mg/kg every 12 h for 6 weeks is the most used therapy for symptomatic newborns. Valganciclovir (V-GCV) syrup is a pro-drug of GCV and presents high oral bioavailability. To date, it is possible to administer this drug at home, and the tolerability profile may allow for wider indications and longer treatments.


Assuntos
Infecções por Citomegalovirus/congênito , Infecções por Citomegalovirus/complicações , Infecções por Citomegalovirus/terapia , Doenças do Recém-Nascido/terapia , Antivirais/efeitos adversos , Antivirais/uso terapêutico , Criança , Infecções por Citomegalovirus/epidemiologia , Deficiências do Desenvolvimento/induzido quimicamente , Deficiências do Desenvolvimento/epidemiologia , Seguimentos , Ganciclovir/uso terapêutico , Perda Auditiva Neurossensorial/etiologia , Humanos , Recém-Nascido , Doenças do Recém-Nascido/diagnóstico , Doenças do Recém-Nascido/epidemiologia
12.
J Child Neurol ; 25(3): 368-70, 2010 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-19509410

RESUMO

Homocystinuria represents a group of hereditary metabolic disorders characterized by an accumulation of homocysteine in the serum and an increased excretion of homocysteine in the urine. The infantile form is severe: the main clinical findings are neurologic signs, associated with hematological signs and bone alterations. Immediate restoration of plasma amino acids is the primary goal and early diagnosis is crucial not to delay the onset of possible treatment. We report a case of homocystinuria with early onset: an initial symptomatology was undervalued by the pediatrician with a delay in diagnosis. Despite the therapy, the patient developed tetraventricular hydrocephalus requiring ventricular drainage. In conclusion, we want to remember the necessity to perform a complete metabolic workup in a patient with clinical manifestations suggestive for homocystinuria, and the importance of early recognition of the signs and symptoms of hypertensive hydrocephalus, a possible complication of this condition.


Assuntos
Apneia/diagnóstico , Homocistinúria/diagnóstico , Hidrocefalia/diagnóstico , Idade de Início , Apneia/patologia , Apneia/terapia , Encéfalo/patologia , Pré-Escolar , Diagnóstico Diferencial , Progressão da Doença , Feminino , Homocistinúria/patologia , Homocistinúria/terapia , Humanos , Hidrocefalia/patologia , Hidrocefalia/terapia , Imagem por Ressonância Magnética , Resultado do Tratamento
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