Effect of Hypothermia and Severity of Hypoxic-Ischemic Encephalopathy in the Levels of C-Reactive Protein during the First 120 Hours of Life.

OBJECTIVE: This study aimed to describe normal C-reactive protein (CRP) levels of newborns diagnosed with hypoxic-ischemic encephalopathy (HIE) and assess the influence of therapeutic hypothermia (TH) and the severity of HIE. STUDY DESIGN: We prospectively recruited infants ≥35 weeks of gestational age diagnosed with HIE from 2000 to 2013 and compared CRP levels in the first 120 hours of life according to the severity of HIE and the use of TH, which was introduced in 2009. RESULTS: Moderate HIE was diagnosed in 115 newborns, severe HIE in 90 (hypothermia was performed in 151 cases), and mild HIE in 20. Cooled newborns showed lower levels of CRP in the first 34 hours, but reached higher median maximum CRP levels (15.4 vs. 8.5 mg/L), and at a significantly older age (53 vs. 17 hours). Levels of CRP in mild HIE were lower than those of moderate-severe forms. Moderate and severe HIE had similar CRP levels, but time to maximum CRP was significantly less in moderate cases. CONCLUSION: CRP levels of mild HIE are similar to healthy newborns, while CRP elevations can be expected in newborns with moderate-severe HIE. TH produced a slower rise, with a higher and late maximum CRP peak level.

Comparison of epidemiology and clinical characteristics of infections by human parechovirus vs. those by enterovirus during the first month of life.

UNLABELLED: Human parechoviruses (HPeV) have been recently recognized as important viral agents in paediatric infections. The aims of this study were to investigate the HPeV infection prevalence in infants <1 month in Spain and, secondly, to analyse the clinical and epidemiological characteristics of the infected patients compared with those infected by enterovirus (EV). Infants <1 month with neurological or systemic symptoms were included in a multicentre prospective study. EV and HPeV detection by RT-PCR and genotyping were performed in cerebrospinal fluids (CSF), sera or throat swabs. Out of the total of 84 infants studied during 2013, 32 were EV positive (38 %) and 9 HPeV positive (11 %). HPeV-3 was identified in eight cases and HPeV-5 in one. Mean age of HPeV-positive patients was 18 days. Diagnoses were fever without source (FWS) (67 %), clinical sepsis (22 %) and encephalitis (11 %). Leukocytes in blood and CSF were normal. Pleocytosis (p = 0.03) and meningitis (p = 0.001) were significantly more frequent in patients with EV infections than with HPeV. CONCLUSIONS: Although HPeV-3 infections were detected less frequently than EV, they still account for approximately 10 % of the cases analysed in infants younger than 1 month. HPeV-3 was mainly associated with FWS and without leukocytosis and pleocytosis in CSF. In these cases, HPeV screening is desirable to identify the aetiologic agent and prevent unnecessary treatment and prolonged hospitalization.

Biomarkers of Oxidative Stress in Healthy Infants within the First Three Days after Birth.

The clinical relevance of stress biomarkers in newborns is well established. Currently, oxidative stress (OS) parameters are seen to play an important role in neonatal resuscitation guidelines, and a link has been observed between the amount of oxygen delivered and the level of OS and the development of various pathologies. The aim of the current study was to investigate changes in neonatal plasma and urine OS status during the first hours after birth. A lower antioxidant capacity (TAC) and higher levels of malondialdehyde in blood were observed in newborns at the time of birth compared with results 48 h postnatally. The urine revealed a significant and progressive increase in TAC and creatinine during the first 36 h of life, with a progressive decline thereafter. Meanwhile, malondialdehyde in urine samples showed no significant differences over time. Overall, the correlation between blood and urine parameters was poor, except for the relationship between umbilical vein glutathione reduced/oxidized ratio and urine malondialdehyde (r = 0.7; p = 0.004) and between TAC in the umbilical artery and urine (r = -0.547; p = 0.013). The biomarkers evaluated in this study could be established as reference values for neonatal OS.

Neurodevelopmental Outcomes of Infants Younger Than 90 Days Old Following Enterovirus and Parechovirus Infections of the Central Nervous System.

Enteroviruses (EVs) and human parechoviruses (HPeVs) are a major cause of central nervous system (CNS) infection in young infants. They have been implicated in neurodevelopmental delay, however limited data are available. The aim of this study is to describe the clinical outcome of young infants and to assess and compare the medium-term neurodevelopment following CNS infections caused by EV and HPeV. A multicentre observational ambispective study was conducted between May 2013 and March 2018. Children under 3 months of age with EV or HPeV CNS infection excluding encephalitis were included. Infants were contacted 1 year after the acute infection and their neurological development was evaluated using the Ages and Stages Questionnaire-3 (ASQ-3). If any area assessed was abnormal during the first round of tests, a second round was completed 6 to 12 months later. Forty-eight young infants with EV and HPeV CNS infection were identified: 33 (68.8%) were positive for EV and 15 (31.3%) for HPeV. At first assessment 14 out of 29 EV (48.3%) and 3 out of 15 HPeV (20%) positive cases presented some developmental concern in the ASQ-3 test. EV-positive infants showed mild and moderate alteration in all domains analyzed and HPeV-positive infants showed mild alterations only in gross and fine motor domains. Significant alterations in communication were observed in EV-positive but not in HPeV-positive infants (31 vs. 0%, p = 0.016). At second assessment 4 out of 13 EV-positive patients (30.8%) showed mild to moderate concerns in communication and gross motor function domains and 3 out of 13 (23.1%) showed significant concern in fine motor function. Although CNS infections without associated encephalitis are generally assumed to be benign our study shows that at a median age of 18 months almost half of the EV-infected infants (48.3%) and 20% of HPeV-positive infants presented some developmental concern in the ASQ-3 test. We recommend monitor the neurological development of infants during the first years of life after HPeV CNS infection and especially after EV CNS infection, even in mild cases, for an early intervention and stimulation of psychomotor development if necessary.

Neurodevelopment medium-term outcome after parechovirus infection.

AIM: Human parechoviruses (HPeV) are responsible for fever without a source (FWS), sepsis-like illness and encephalitis in neonates and children under 3 months of age. Short-term outcome is generally good, but there is great concern about medium and long- term outcome of infants after HPeV infection. The aim of this study is to assess the medium-term outcome in infants following HPeV infection without encephalitis. METHODS: Patients who suffered HPeV infection involving cerebrospinal fluid were evaluated twice using Ages and Stages Questionnaire-3 (ASQ-3). The first evaluation was conducted at least one year after the infection and the second one year later. RESULTS: Sixteen patients were evaluated in the first assessment, and three of them presented mild alterations in motor function domains. Moreover, hypotonia was observed in the neurologic exam in one case, and hemiparesis in another case. In the second assessment fifteen patients were included, and only the patient with hemiparesis continued presenting gross motor disfunction, with complete recovery of the remaining patients. INTERPRETATION: We have observed a good medium-term prognosis in infants after HPeV infections, with improvement of mild motor alterations after at-home intervention. Infants who suffer HPeV infection without encephalitis seem to have a better prognosis than those with encephalitis.

[Epidemiological and clinical characteristics of infants admitted to hospital due to human parechovirus infections: A prospective study in Spain]. / Características epidemiológicas y clínicas de los lactantes hospitalizados por infecciones por parechovirus humanos. Estudio prospectivo en España.

INTRODUCTION: Human parechovirus (HPeV) is one of the recently described picornaviridae viruses that have been associated with fever of unknown origin (FUO), clinical sepsis, gastroenteritis, meningitis, or encephalitis in very young infants. The aim of this study is to describe the epidemiology and clinical features of these viruses. PATIENTS AND METHODS: A prospective multicentre 3-year study was conducted in 12 hospitals in Spain. Out of 850 specimens examined, 47 were positive (5.52%), with HPeV-3 being the most frequent (29 cases). Infections occurred throughout the year, but mainly in May and July, and a biennial distribution was observed. More than half (57%) were neonates, and only 2 children were older than 3 months. Fever was present in all children, with irritability in 45%, rash in 18.6%, and diarrhoea in 14%. The results of biochemical tests were all in normal range. The most common final diagnosis was FUO (61%), followed by clinical sepsis (29%). Up to 29% of infants were admitted to the intensive care unit, but only one patient had sequelae. RESULTS: Out of 850 specimens examined, 47 were positive (5.52%) for HPeV, with HPeV-3 being the most frequent (29 cases). Infections occurred throughout the year, but mainly in May and July, and a biennial distribution was observed. More than half (57%) were neonates, and only 2 children were older than 3 months. Fever was present in all children, with irritability in 45%, rash in 18.6%, and diarrhoea in 14%. The results of biochemical tests were all in normal range. The most common final diagnosis was FUO (61%), followed by clinical sepsis (29%). Up to 29% of infants were admitted to the intensive care unit, but only one patient had sequelae CONCLUSIONS: HPeV circulates in our country, mainly during spring and summer, and affects young infants with a FUO and clinical sepsis. Molecular diagnostic techniques in all hospitals could help in improving the management of patients with these infections.

Perinatal infection and hypoxic-ischemic encephalopathy: a pilot study.

Recent studies suggest a synergic effect of infection and hypoxia-ischemia in the causation of perinatal brain damage. We conducted a prospective pilot study on the presence of infection in hypoxic-ischemic encephalopathy (HIE), focusing on neurotropic viruses. Sixteen newborns with HIE were included in the study. There were no confirmed cases of viral infection. There was a case of bacterial early onset sepsis and four cases of suspected sepsis due to clinical and/or analytical signs, but with negative cultures. Our results do not support universal screening for viral infection in cases of HIE.

Human parechovius and enterovirus in neonates: Distinct infections with overlapping features.

INTRODUCTION: Human parechoviruses (HPeVs) have recently been added to the family Picornaviridae, where Enteroviruses (HEV) belong. The specific characteristics of HPeV infection in the neonate are not clear, and their involvement in neonatal infection is believed to be largely underestimated. HPeV type 3 has been recently linked to sepsis-like illness and neurological involvement in the newborn. OBJECTIVE: To assess the involvement of HPeV in central nervous system (CNS) infections throughout the neonatal period in term newborns, describe their clinical, analytical and cerebrospinal fluid (CSF) characteristics, and compare them to HEV infections. METHODS: Term newborns admitted for neurological symptoms or a suspected infection, aged 0-30 days were prospectively recruited (September 2012-August 2014). Bacterial cultures were performed in all patients. Viral tests were performed in CSF including: RT-PCR for cytomegalovirus, Herpes simplex type 1 and 2, Epstein-Barr virus, HEV and HPeV. HEV and HPeV positive samples were genotyped. RESULTS: Fifty-seven newborns were diagnosed of sepsis-like illness and/or CNS alteration. HEV (8.7%) and HPeV-3 (3.5%) were the two most common viral agents involved during the study period. The most frequent symptom at admission was fever. Irritability was present in 1/2 of HPeV and 1/5 of HEV cases. There were no other neurological symptoms. Blood and CSF analysis were unremarkable in HPeV infections. All cases resolved favorably. CONCLUSIONS: HPeV infection was clinically very similar to that of HEV, while it featured normal blood and CSF analysis. PRACTICE IMPLICATIONS: HPeV should be considered by clinicians in the differential diagnosis of neonatal infection, particularly when blood and CSF analysis are unremarkable.