OBJECTIVE: We aimed to describe the clinical features and outcome of human parechovirus (HPeV) encephalitis cases identified by the Australian Childhood Encephalitis (ACE) study. METHODS: Infants with suspected encephalitis were prospectively identified in 5 hospitals through the (ACE) study. Cases of confirmed HPeV infection had comprehensive demographic, clinical, laboratory, imaging, and outcome at discharge data reviewed by an expert panel and were categorized by using predetermined case definitions. Twelve months after discharge, neurodevelopment was assessed by using the Ages and Stages Questionnaire (ASQ). RESULTS: We identified thirteen cases of suspected encephalitis with HPeV infection between May 2013 and December 2014. Nine infants had confirmed encephalitis; median age was 13 days, including a twin pair. All had HPeV detected in cerebrospinal fluid with absent pleocytosis. Most were girls (7), admitted to ICU (8), and had seizures (8). Many were born preterm (5). Seven patients had white matter diffusion restriction on MRI; 3 with normal cranial ultrasounds. At discharge, 3 of 9 were assessed to have sequelae; however, at 12 months’ follow-up, by using the ASQ, 5 of 8 infants showed neurodevelopmental sequelae: 3 severe (2 cerebral palsy, 1 central visual impairment). A further 2 showed concern in gross motor development. CONCLUSIONS: Children with HPeV encephalitis were predominantly young, female infants with seizures and diffusion restriction on MRI. Cranial ultrasound is inadequately sensitive. HPeV encephalitis is associated with neurodevelopmental sequelae despite reassuring short-term outcomes. Given the absent cerebrospinal fluid pleocytosis and need for specific testing, HPeV could be missed as a cause of neonatal encephalopathy and subsequent cerebral palsy.

https://pediatrics.aappublications.org/content/pediatrics/early/2016/01/19/peds.2015-2848.full.pdf

Parechovirus Encephalitis and Neurodevelopmental Outcomes.

Bronchopulmonary dysplasia (BPD) is the most common cause of morbidity and mortality in preterm infants. A key histopathological feature of BPD is stunted late lung development, where the process o...

/pdf/recent-advances-in-our-understanding-of-the-mechanisms-of-3lk66wlk8b.pdf

Recent advances in our understanding of the mechanisms of lung alveolarization and bronchopulmonary dysplasia.

Enteroviruses generally cause mild and self-limited diseases, but they have been found to affect neonates much differently, and often more severely than older children. Clinical manifestations are difficult to differentiate from those of bacterial sepsis, such as fever, poor feeding, lethargy, respiratory distress and cardiovascular collapse. Severe life threatening complications, including hepatic necrosis with coagulopathy, meningoencephalitis and myocarditis, usually present during the first week of life. Factors affecting severity and outcome include virus serotype, mode of transmission, and presence or absence of passively acquired, serotype-specific maternal antibodies. Echoviruses and coxsackievirus B viruses are most common serotypes associated with the neonatal sepsis. An awareness of the clinical syndromes, recognition of the risk factors and monitoring parameters associated with severe cases and use of rapid reverse-transcriptase polymerase chain reaction test for viral load may help physicians in diagnosing severe cases in a timely manner. Prompt aggressive treatment including early intravenous immunoglobulin treatment may help in reducing morbidity and mortality. Enterovirus infections in neonates are common and should be routinely considered in the differential diagnosis of febrile neonates, particularly during enterovirus season. This article provides an overview of what is known about non-polio enteroviruses in neonates including epidemiology, transmission, clinical presentation, diagnosis, and treatment.

Enteroviral infection in neonates

Enterovirus (EV) is a common cause of infection in neonates. Neonates are at high risk of enterovirus infection with serious clinical manifestations and high lethality. This review systematically summarized the clinical characteristics of neonates with severe enteroviral infection to provide evidence for the identification and treatment of severe neonatal EV infection. PubMed, Embase, and Web of Science were searched for original studies on neonates with severe EV infections from January 1, 2000, to November 27, 2020. Two reviewers independently screened the literature, extracted the data, and performed a descriptive analysis. In total, 66 articles with 237 cases of severe neonatal enterovirus infection were included. All neonates developed severe complications. Among them, 46.0% neonates had hepatitis or coagulopathy, 37.1% had myocarditis, 11.0% had meningoencephalitis, and 5.9% had other complications such as hemophagocytic lymphohistiocytosis and pulmonary hemorrhage. The lethality rate of neonates with severe infection was 30.4%. The highest lethality rate was 38.6%, which was observed in neonates with myocarditis. In 70.5% neonates, the age at the onset of symptoms was less than 7 days. Coxsackievirus B infection was seen in 52.3% neonates. The most common symptoms included temperature abnormalities (127, 53.6%), rash (88, 37.1%), poor feeding (58, 24.5%), and respiratory symptoms (52, 21.9%). The main treatment included transfusion of empirical antibiotics (127, 53.6%), blood components (100, 42.2%), intravenous immunoglobulin (IVIG; 97, 40.9%), mechanical ventilation (51, 21.5%), and extracorporeal membrane oxygenation (ECMO; 43, 18.1%). Additionally, antiviral medications pleconaril (14, 5.9%) and pocapavir (3, 1.3%) were administered. Lethality was high in neonates with severe enterovirus infection, especially in those complicated with myocarditis. The most common symptoms included temperature abnormalities, rash, and poor feeding. The chief supportive treatment consisted of transfusion of blood components, mechanical ventilation, and ECMO. Empirical antibiotics and IVIG were widely used. Antiviral medications included pocapavir and pleconaril; however, more clinical evidence regarding their efficacy is needed.

/pdf/clinical-characteristics-of-severe-neonatal-enterovirus-2z0dp7ehdd.pdf

Clinical characteristics of severe neonatal enterovirus infection: a systematic review

Pyroptosis is a relatively newly discovered programmed cell death accompanied by an inflammatory response. In the classical view, pyroptosis is mediated by caspases-1,-4,-5,-11 and executed by GSDMD, however, recently it was demonstrated that caspase-3 and-8 also participate in the process of pyroptosis, by cleaving GSDMD/E and GSDMD respectively. Different from autophagy and apoptosis, many pores are formed on the cell membrane during pyroptosis, which makes the cell membrane lose its integrity, eventually leading to the release of cytokines interleukin(IL)-1β and IL-18. When the body is infected with pathogens or exposed to some stimulations, pyroptosis could play an immune defense role. It is found that pyroptosis exists widely in infectious and inflammatory respiratory diseases such as acute lung injury, bronchial dysplasia, chronic obstructive pulmonary disease, and asthma. Excessive pyroptosis may accompany airway inflammation, tissue injury, and airway damage, and induce an inflammatory reaction, leading to more serious damage and poor prognosis of respiratory diseases. This review summarizes the relationship between pyroptosis and related respiratory diseases.

/pdf/pyroptosis-and-respiratory-diseases-a-review-of-current-1kgtkx3g.pdf

Pyroptosis and respiratory diseases: A review of current knowledge

Intrauterine infection/inflammation plays an important role in the development of lung injury and bronchopulmonary dysplasia (BPD) in preterm infants, While a multifactorial genesis is likely, mechanisms involved in BPD after intrauterine infection/inflammation are largely unknown. Recent studies have suggested microRNAs (miRNAs) are likely to play a role. Therefore, this study aimed to study the effects and mechanisms of intrauterine infection/inflammation on lung development, and to identify miRNAs related to lung injury and BPD. An animal model of intrauterine infection/inflammation was established with pregnant SD rats endocervically inoculated with E.coli. The fetal and neonatal rats were observed at embryonic day (E) 17, 19, 21 and postnatal day (P) 1, 3, 7, 14, respectively. Body weight, lung weight, the expression levels of NLRP3, TNF-α, IL-lβ, IL-6, VEGF, Collagen I, SP-A, SP-B and SP-C in the lung tissues of fetal and neonatal rats were measured. Expression profiles of 1218 kinds of miRNAs in the lungs of neonatal rats were detected by miRNA microarray technique. Target genes of the identified miRNAs were predicted through online software. Intrauterine infection/inflammation compromised not only weight development but also lung development of the fetal and neonatal rats. The results showed significantly increased expression of NLRP3, TNF-α, IL-1β, IL-6, Collagen I, and significantly decreased expression of VEGF, SP-A, SP-B and SP-C in the fetal and neonatal rat lung tissues in intrauterine infection group compared to the control group at different observation time point (P < 0.05). Forty-three miRNAs with significant differential expression were identified. Possible target genes regulated by the identified miRNAs are very rich. Intrauterine infection/inflammation results in lung histological changes which are very similar to those observed in BPD. Possible mechanisms may include NLRP3 inflammasome activation followed by inflammatory cytokines expression up-regulated, inhibiting the expression of pulmonary surfactant proteins, interfering with lung interstitial development. There are many identified miRNAs which target a wide range of genes and may play an important role in the processes of lung injury and BPD.

/pdf/effects-and-molecular-mechanisms-of-intrauterine-infection-3wfrrtdgkl.pdf

Effects and molecular mechanisms of intrauterine infection/inflammation on lung development

OBJECTIVE To evaluate the efficacy and safety of intravenous immunoglobulin G (IVIG) in infants with ABO hemolytic disease of the newborn (HDN). METHODS Infants with moderate-to-severe ABO HDN during early neonatal period (<7 days) at our hospital in 2017 were included in this retrospective study. Patients treated with IVIG and phototherapy were classified as the IVIG group, and those who only received phototherapy were classified as the phototherapy only group. RESULTS Forty-six patients were classified into the IVIG group and 68 other patients were classified into the phototherapy only group. There was no significant difference in duration of phototherapy, hospitalization periods, needs for exchange transfusion, transfusions, and incidence of bilirubin-induced neurological sequelae between these two groups (P = 0.20, 0.27, 0.65, 0.47, 0.78, respectively). CONCLUSION It seems unnecessary to expose neonates to IVIG in moderate-to-severe ABO HDN when the available data show no appreciable benefits.

/pdf/intravenous-immunoglobulin-g-in-the-treatment-of-abo-4gab4o95w5.pdf

Intravenous immunoglobulin G in the treatment of ABO hemolytic disease of the newborn during the early neonatal period at a tertiary academic hospital: a retrospective study.

Aim
To explore the imaging findings of neonatal infants infected with enteroviruses.

Methods
A retrospective study was conducted on 12 patients who were diagnosed with encephalitis caused by enterovirus. Clinical presentation, cranial ultrasonography (cUS), magnetic resonance imaging (MRI) findings and neurodevelopment outcome of 12 cases were analysed.

Results
Twelve infants, with a gestational age of 35 to 39 weeks, presented at 36 to 41 weeks postmenstrual age with clinical symptoms of enterovirus infections. Ten of 12 neonatal infants had a fever and 4 of 12 presented with a sepsis-like illness. cUS in one preterm infant showed periventricular echogenicity. Neonatal MRI confirmed white matter changes in 12 infants. Follow-up of infants were 18 months. Outcome was variable with cerebral palsy in 2 infants and normal neurodevelopment outcome in 10 infants.

Conclusions
Enterovirus may cause severe central nervous system infection in the neonatal period. The neuroimaging studies are informative and should be a part of care for infants with enteroviruses.

Enterovirus infections are associated with white matter damage in neonates.

Aim

This study aims to investigate clinical characteristics and microbiological results and to assess the predictors for enterovirus infection in febrile neonates.



Methods

A prospective cohort study was conducted on 334 febrile patients (age: 0.33–28 days) in 2011–2012 years. Enterovirus RNA was detected by reverse transcription polymerase chain reaction on faeces or cerebrospinal fluid (CSF). Clinical characteristics were compared, and non-conditional logistic regression analysis was performed to determine independent predictors for enterovirus infection.



Results

There were 131 episodes of neonatal enterovirus infection (39.22%). Forty-eight (36.64%) developed respiratory symptoms, 69 (52.67%) had diarrhoea, 22 (16.79%) had poor feeding and 34 (25.95%) had rash. Eighteen (13.74%) had lower platelet counts, and CSF specimens were positive for enterovirus RNA in 44.27% (58/131) whose CSF revealed a mean white blood cell counts of 100.38 ± 147.97 cells/mm3 (range: 2–668 cells/mm3). The positivity of stool 38.92% (130/334) was significantly higher than that of CSF specimens 26.24% (58/221) for enterovirus RNA (P  3.25 (d) (OR: 2.293, 95% CI: 1.279–4.113), highest temperature >38.35 (°C) (OR: 2.094, 95% CI: 1.342–4.123) and negative bacterial culture (OR: 5.073, 95% CI: 1.504–17.114).



Conclusions

Our data indicated that enteroviruses should be routinely considered in the differential diagnosis of febrile neonates. The factors, which may predict the risk of neonatal enterovirus infection, were abnormal CSF test, thrombocytopenia, duration of fever >3.25 (d), highest temperature >38.35 (°C) and negative bacterial culture.

Enterovirus infection in febrile neonates: A hospital-based prospective cohort study

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Papers

Effects and molecular mechanisms of intrauterine infection/inflammation on lung development

Intravenous immunoglobulin G in the treatment of ABO hemolytic disease of the newborn during the early neonatal period at a tertiary academic hospital: a retrospective study.

Enterovirus infections are associated with white matter damage in neonates.

Enterovirus infection in febrile neonates: A hospital-based prospective cohort study