Search

Aim: This study evaluated the recognition and management practices with regard to congenital cytomegalovirus (cCMV) infections by a select group of experts and through a national surveillance study., Method: A questionnaire was sent to international experts involved in mother and infant care in 2014-2015. Monthly surveillance was conducted among Dutch paediatricians for cases of cCMV infections from 2013 until 2015., Results: The questionnaire was completed by 63/103 (62%) respondents, who indicated that recognition and management practices varied. Maternal screening was performed by 17/63 (27%) and infant screening by 3/61 (5%) of the respondents. Infant CMV diagnostics were most frequently initiated due to hepatosplenomegaly and/or an increase in liver transaminases. Management practices included cranial ultrasound (57/63, 91%) and audiological follow-up in symptomatic (61/63, 97%) and asymptomatic (52/63, 83%) infants. In terms of antiviral treatment, 46/63 (73%) treated symptomatic infants only and 6/63 (9%) treated all infected infants. In total, 48 cases were registered through the Dutch surveillance study and 43/48 (90%) infants were symptomatic., Conclusion: This study indicates that infants with cCMV infection were insufficiently recognised and highlights the need for consensus on management practices. Screening of infants and the development of an international management guideline are recommended., (©2017 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.)

Background: Congenital cytomegalovirus (cCMV) infection early in pregnancy may result in major disabilities. Cerebral abnormalities detected using cranial ultrasound (cUS) and magnetic resonance imaging (MRI) have been related to neurological sequelae., Objective: To evaluate the additional value of MRI and assess the relationship between time of infection during pregnancy and outcome in infants with cCMV infection., Methods and Study Design: Demographic and clinical data were collected in infants with cCMV infection (1992-2013). Trimester of infection, neuro-imaging results and outcome were reviewed. Cerebral abnormalities were categorized into none, mild (lenticulostriate vasculopathy, germinolytic cysts, high signal intensity on T2-weighted images) and severe (migrational disorder, ventriculomegaly, cerebellar hypoplasia). Results were statistically analysed., Results: Thirty-six infants were eligible for analysis. cUS was performed in all and cranial MRI in 20 infants. Migrational disorders were only diagnosed using MRI (p < 0.01). In 17 infants trimester of infection was ascertained. Seven out of 10 infants infected during the first trimester had severe abnormalities on cUS (5 confirmed on MRI) and adverse sequelae; 3 had no/mild abnormalities on cUS/MRI and normal outcome. Two out of 3 infants infected during the second trimester with no/mild abnormalities on cUS/MRI had normal outcome; 1 with mild cUS and MRI abnormalities developed sensorineural hearing loss. Four infants infected during the third trimester with no/mild abnormalities on cUS/MRI had normal outcome., Conclusion: Infants with a first trimester cCMV infection are most at risk of severe cerebral abnormalities and neurological sequelae. MRI, and not cUS, enables an early diagnosis of migrational disorders, which can improve prediction of outcome., (© 2015 S. Karger AG, Basel.)

Background: Congenital cytomegalovirus infection is a leading cause of long-term sequelae. Cytomegalovirus is also frequently transmitted to preterm infants postnatally, but these infections are mostly asymptomatic. A correlation between cytomegalovirus genotypes and clinical manifestations has been reported previously in infants with congenital infection, but not in preterm infants with postnatal infection., Objectives: The main objective of this study was to investigate cytomegalovirus genotype distribution in postnatal and congenital cytomegalovirus infection and its association with disease severity., Methods: Infants admitted to the neonatal intensive care unit of the University Medical Center Utrecht, The Netherlands between 2003-2010 and diagnosed with postnatal or congenital cytomegalovirus infection were included. Classification of cytomegalovirus isolates in genotypes was performed upon amplification and sequencing of the cytomegalovirus UL55 (gB) and UL144 genes. Clinical data, cerebral abnormalities, neurodevelopmental outcome and viral load were studied in relation to genotype distribution., Results: Genotyping results were obtained from 58 preterm infants with postnatal cytomegalovirus infection and 13 infants with congenital cytomegalovirus infection. Postnatal disease was mild in all preterm infants and all had favourable outcome. Infants with congenital infection were significantly more severely affected than infants with postnatal infection. Seventy-seven percent of these infants were symptomatic at birth, 2/13 died and 3/13 developed long-term sequelae (median follow-up 6 (range 2-8) years). The distribution of cytomegalovirus genotypes was comparable for postnatal and congenital infection. UL55 genotype 1 and UL144 genotype 3 were predominant genotypes in both groups., Conclusions: Distribution of UL55 and UL144 genotypes was similar in asymptomatic postnatal and severe congenital CMV infection suggesting that other factors rather than cytomegalovirus UL55 and UL144 genotype are responsible for the development of severe disease.

Background: Cytomegalovirus (CMV) is the most frequently contracted virus in preterm infants. Postnatal infection is mostly asymptomatic but is sometimes associated with severe disease. To diagnose an infection, urine or saliva samples can be tested for CMV-DNA by real-time polymerase chain reaction (rtPCR). Although the diagnostic accuracy of testing saliva samples has not been determined in preterm infants, saliva is widely used because it is easier to obtain than urine., Objectives: To determine whether screening of saliva is equivalent to urine to detect a postnatal CMV infection in preterm infants., Study Design: Between 2010 and 2013 saliva and urine samples were collected from infants admitted to the Neonatal Intensive Care Unit of the University Medical Center Utrecht and born with a gestational age (GA) below 32 weeks. Urine samples were obtained within three weeks after birth and urine and saliva samples at term equivalent age (40 weeks GA) and tested for CMV-DNA by rtPCR. Infants with a congenital CMV infection were excluded., Results: Of 261 preterm infants included in the study, CMV-DNA was detected in urine of 47 and in saliva of 43 children. Of 47 infants with postnatal CMV infection, CMV was detected in 42 saliva samples (sensitivity 89.4%; CI 76.9-96.5). Of 214 children without postnatal CMV infection, one saliva sample tested positive for CMV (specificity 99.5%; CI 97.4-99.9)., Conclusions: Screening saliva for CMV-DNA by rtPCR is inferior to urine to diagnose postnatal CMV infections in preterm infants., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Immunological mechanisms influencing the risk of mother-to-child cytomegalovirus (CMV) transmission in preterm infants have not been studied sufficiently. In this study, the correlation between maternal and neonatal serum anti-CMV IgG levels and risk of postnatal CMV transmission in preterm infants was assessed. Anti-CMV IgG levels of 79 CMV seropositive mothers and their 94 infants were determined in peripheral blood samples collected within 3 days after delivery. Postnatal CMV infection was detected in 39/94 (41%) infants by PCR on urine at term-equivalent age (gestational age 40 weeks) after congenital infection was excluded. Maternal or infant anti-CMV IgG levels were not significantly different between infants with and without postnatal CMV infection. The anti-CMV IgG infant-mother ratio showed a significant positive correlation with gestational age (range 25-32 weeks, R(2)  = 0.218, P < 0.001), reaching 1.0 at 32 weeks of gestation. Anti-CMV IgG infant-mother ratio was significantly lower in infants with postnatal CMV infection (P = 0.015). In conclusion, the risk of postnatal CMV transmission is related to low gestational age and low anti-CMV IgG infant-mother ratio., (Copyright © 2013 Wiley Periodicals, Inc.)

Background: Detection of white matter (WM) abnormalities on MRI is important regarding the neurodevelopmental outcome in preterm infants. The long-term neurodevelopmental outcome of preterm infants with postnatal cytomegalovirus (CMV) infection has not been studied extensively., Objectives: We aimed to assess WM microstructure in preterm infants with postnatal CMV infection using diffusion tensor imaging., Methods: Infants <32 weeks' gestational age (GA) admitted to our hospital between 2007 and 2010, who had cerebral diffusion tensor imaging at term-equivalent age (40 weeks' GA) were included. CMV PCR in urine collected at term-equivalent age was performed to diagnose postnatal CMV infection. Congenital infection was excluded. In the frontal, parietal and occipital WM mean diffusivity, fractional anisotropy (FA), radial and axial diffusivity were calculated. Neurodevelopmental outcome was assessed at 16 months' corrected age using Griffiths' Mental Developmental Scales., Results: Twenty-one postnatally infected and 61 noninfected infants were eligible. Both groups were comparable regarding GA, birth weight and age at MRI. There was a significant difference in median FA of the occipital WM between infected and noninfected infants (0.13 [IQR 0.11-0.16] versus 0.16 [IQR 0.14-0.18], p = 0.002). There were no differences in short-term neurodevelopmental outcome between infected and noninfected infants., Conclusions: A significantly reduced FA suggests microstructural changes in the occipital WM of postnatally infected infants. These microstructural changes do not appear to result in impaired neurodevelopmental outcome at 16 months' corrected age., (Copyright © 2013 S. Karger AG, Basel.)

Cytomegalovirus is an important cause of sensorineural hearing loss in children. In contrast to congenitally infected infants, little is known about hearing in preterm infants with postnatal cytomegalovirus infection. We studied the hearing in 64 preterm infants during the first year of life and in 18 during the second year of life. None of the infants developed sensorineural hearing loss.

Objective: To study risk factors and cranial ultrasound (cUS) findings in a large cohort of preterm infants, admitted to a neonatal intensive care unit and diagnosed with postnatally acquired cytomegalovirus (CMV) infection., Study Design: This prospective, observational study was performed from April 2007 until June 2009 among 315 infants born <32 weeks of gestation. Postnatal CMV infection was diagnosed by CMV PCR on urine collected at term-equivalent age. In CMV-positive infants, congenital infection was excluded. The authors compared the clinical and demographic data, feeding pattern and cUS results of infected and non-infected patients. Logistic regression analysis was performed., Results: In 39 of 315 infants, the diagnosis of postnatal CMV infection has been made. The majority of CMV-infected infants (33/39.85%) did not develop any symptoms of CMV infection. The most important, independent risk factors of postnatal CMV infection were non-native Dutch maternal origin (OR 9.6 (95% CI 4.3 to 21.5)) and breast milk (OR 13.2 (95% CI 1.7 to 104.5)). The risk of infection significantly increased in infants with lower gestational age (GA) (OR 0.7 (95% CI 0.5 to 0.9)). Lenticulostriate vasculopathy (LSV) was significantly more often present in infants with CMV infection (OR 4.1 (95% CI 1.9 to 8.8))., Conclusions: Postnatal CMV infection is an asymptomatic infection among preterm infants. Infants with lower GA are at greatest risk of postnatal CMV infection, especially when fed with fresh breast milk from their non-native Dutch mother. LSV not present at birth but confirmed at term-equivalent age can suggest a postnatal CMV infection.

Background: A correlation between cytomegalovirus (CMV) load in urine and severity of disease in congenitally infected infants has previously been reported. CMV load in postnatally infected infants has not been studied before., Objective: To investigate CMV load in urine of infants with postnatal or congenital infection and correlate this with clinical symptoms of CMV disease and cerebral abnormalities., Study Design: Infants admitted to our NICU between July 2000 and February 2010, and diagnosed with congenital or postnatal CMV infection were included. Clinical symptoms of CMV infection, cranial ultrasonography (cUS) and magnetic resonance imaging (MRI) findings were evaluated. CMV urine loads of postnatally infected infants were analyzed and compared with CMV urine loads of congenitally infected infants., Results: Seventeen infants with congenital CMV infection and 45 infants with postnatal CMV infection were included. Thirteen/17 (76%) congenitally infected infants had clinical symptoms of CMV infection at birth and 11/17 (65%) had cerebral abnormalities diagnosed by neuro-imaging. None of the four asymptomatic infants had cerebral abnormalities. Of the postnatally infected infants 43/45 (96%) did not develop any clinical symptoms of CMV infection, but in 23/45 (51%) cerebral abnormalities such as lenticulostriate vasculopathy and germinolytic cysts were identified. The median CMV load in postnatally infected infants was significantly lower than in congenitally infected infants (1.0×10(5)copies/ml versus 8.5×10(6)copies/ml, p<0.001, respectively)., Conclusions: CMV load in urine is significantly lower in infants with postnatal CMV infection than in infants with congenital CMV infection irrespective of clinical symptoms of CMV infection or cerebral abnormalities., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Background: The incidence of coagulase-negative staphylococcal (CoNS) sepsis is high in neonatal intensive care units (NICUs) and treatment significantly adds to the antibiotic pressure, increasing the threat of resistance. Because infants recover within 24-48 h, blood cultures are negative within 48 h and CRP normalizes within 72 h, we reduced anti-CoNS treatment from 7 to 3 days in infants with uncomplicated CoNS sepsis., Objectives: The aim of the study was to evaluate the effect of short (3 days) treatment duration for CoNS sepsis., Methods: All infants with CoNS sepsis from January 2006 to September 2010 were evaluated. Before 2008 the duration of anti-CoNS treatment was 7 days, but in 2008 it was reduced to 3 days, provided that infants recovered within 48 h, CRP value decreased, thrombocytes were normal and central venous catheters were either not present or removed. Clinical results of treatment for 3 days were compared with 7 days of treatment., Results: There were 142 infants with CoNS sepsis who were eligible for 3 days of antimicrobial treatment duration, 62 (44%) from the period 2006-2008 were treated over 7 days (Group 1) and 80 (56%) from the period 2008-2010 were treated over 3 days (Group 2). Clinical characteristics were not different between the groups. All infants recovered within 48 h and CoNS sepsis did not relapse., Conclusions: Antibiotic treatment for CoNS sepsis may be shortened to 3 days when clinical improvement is rapid and central lines are not present. Prospective randomized studies are needed to confirm the results of this single-center study. Future studies may reveal the effects on the development of antimicrobial resistance., (Copyright © 2011 S. Karger AG, Basel.)

We describe 5 preterm and 3 term infants who presented with seizures during rotavirus infection within 6 weeks after birth. Six of these infants developed late-onset cystic periventricular leukomalacia. Four of the preterm infants had neurodevelopmental delay, and 4 (near) term infants had normal early outcome., (Copyright © 2012 Mosby, Inc. All rights reserved.)

Objectives: Indwelling central venous catheters are the most important risk factors for the development of sepsis attributable to coagulase-negative staphylococci among preterm infants admitted to neonatal intensive care units. In addition, removal of a central venous catheter also may cause coagulase-negative staphylococci sepsis, which may be prevented by the short-term administration of an anti-staphylococcal agent during the procedure of removal. The administration of a specific anti-staphylococcal agent (cefazolin) was evaluated for the prevention of central venous catheter removal-associated coagulase-negative staphylococci sepsis., Design: A prospective, open, randomized, controlled intervention study., Setting: Twenty-eight-bed neonatal intensive care unit at a tertiary care children's hospital., Patients: Eighty-eight preterm infants (gestational age <37 wks) admitted to the neonatal intensive care unit with indwelling percutaneously inserted central venous catheters., Intervention: From April 2007 to January 2010, infants were randomized to receive two doses of cefazolin during removal of the percutaneously inserted central venous catheter (intervention group, n = 44) or no antimicrobial agent (control group, n = 44). Percutaneously inserted central venous catheter removal-associated sepsis was defined as sepsis occurring <48 hrs after removal of the percutaneously inserted central venous catheter., Measurements and Main Results: Clinical characteristics and central venous catheter duration did not show differences between both groups. Five infants (11%) of the control group developed coagulase-negative staphylococci sepsis <48 hrs after removal of the percutaneously inserted central venous catheter compared to none (0%) in the intervention group (p = .021)., Conclusions: Two doses of the anti-staphylococcal agent cefazolin during the procedure of removal of a percutaneously inserted central venous catheter were effective in the prevention of coagulase-negative staphylococci sepsis. It is recommended to include this regimen in the guidelines on management of central venous catheters in very-low-birth-weight infants.

Nosocomial infections are serious complications among preterm infants admitted to neonatal intensive care units (NICU). Hand hygiene is one of the most effective measures to prevent these infections. This study, performed in a tertiary level NICU, highlights the importance of a multimodal intervention program for adherence to hand hygiene. The compliance with hand hygiene among health care workers of the NICU increased significantly from 23% in the baseline assessment to 50% in the second assessment and the incidence of sepsis decreased from 13.4% to 11.3% after implementation of an intervention program.

Background: The typical empiric therapy for coagulase-negative staphylococcal (CONS) sepsis includes vancomycin. In our neonatal intensive care unit, we have consistently avoided the use of vancomycin to treat CONS sepsis, except for specific cases, and have used instead cefazolin as empiric agent., Objectives: The clinical outcome of infants with CONS sepsis was evaluated in relation to the susceptibility of CONS blood isolates to cefazolin over a period of 7 years., Methods: Clinical characteristics, symptoms of sepsis and antibiotic use were studied retrospectively. Susceptibility of CONS blood isolates to cefazolin was determined by E-test., Results: Of 163 infants with proven CONS sepsis, 121/140 (86%) infants with a cefazolin-susceptible (minimum inhibition concentration (MIC) ≤8 mg/l) and 21/23 (91%) with a cefazolin-resistant (MIC ≥32 mg/l) blood isolate were treated with cefazolin. 21 (13%) infants were switched to vancomycin, in only 3 of them CONS had become resistant to cefazolin. The majority (81%) of the infants with a good response to cefazolin had the indwelling central venous catheter removed, in contrast to only 22% of the infants with cefazolin treatment failure. Median cefazolin MIC values were 0.75-2 mg/l during the study period., Conclusions: The great majority of infants with CONS sepsis was successfully treated with cefazolin. The use of vancomycin could be restricted to specific cases. Despite the consistent use of cefazolin in neonatal CONS sepsis over an extended period of time, cefazolin MIC values remained low and in the susceptible range. Removal of the central venous catheter in infants with clinical symptoms of sepsis is an important therapeutic measure., (Copyright © 2011 S. Karger AG, Basel.)

Objective: To assess the severity of the disease and the long-term cardiac prognosis for neonates who developed enterovirus (EV) myocarditis within the first weeks of life., Design: Clinical presentation, echocardiographic and ECG findings and the outcome of seven infants with EV myocarditis admitted to the intensive care unit are reported. Additionally, 28 previously reported cases are described., Results: Seven neonates presented with cardiac failure within 17 days after birth requiring respiratory and circulatory support. Echocardiography showed dilatation and severe dysfunction of the left ventricle in all and mitral regurgitation in six. In six patients the echocardiographic pattern resembled myocardial infarction. ECG showed complete loss of the R-wave and a new Q-wave in the left precordial leads in all. Two infants died and five developed long-term cardiac sequelae requiring medication. In all survivors aneurysm formation in the left ventricular wall was found weeks to months later. One patient is awaiting heart transplantation. Coxsackie virus B was detected in blood, cerebrospinal fluid, nasopharyngeal swab or stool by PCR or culture. The mortality of previously described neonates combined with our seven cases was 31% (11/35). Among the survivors 66% (16/24) developed severe cardiac damage. Only 23% (8/35) of the infants fully recovered., Conclusions: EV myocarditis is a rare but severe disease in the neonatal period, which often leads to death or results in serious chronic cardiac sequelae like chronic heart failure, aneurysm formation within the left ventricle and mitral regurgitation. Chronic cardiac drug therapy is necessary in the majority of these patients.

Data of 11 infants (median gestational age and birth weight 30 weeks and 1520 g, respectively) with severe human rhinovirus infection (HRV) are described. Nine of 11 (82%) were preterm infants and 7 of these 9 (78%) became infected during their stay in the neonatal intensive care unit. All infants presented with respiratory distress and all needed respiratory support for a median of 6 days. Radiologic findings included perihilar streakiness, atelectasis, focal consolidation, and hyperinflation. The diagnosis of HRV infection was made by real-time polymerase chain reaction in nasopharyngeal aspirate. All infants recovered from their HRV infection. HRV can cause severe disease in preterm infants requiring respiratory support.

Background: In an era with increased maternal antibiotic use, patterns in early- and late-onset sepsis and antibiotic susceptibility may have changed., Objectives: To identify longitudinal trends in causative microorganisms for neonatal sepsis and analyze antibiotic susceptibility of all blood isolates of infants with sepsis., Methods: Early- and late-onset sepsis cases from 29 years (1978-2006) were studied retrospectively, in five clusters of 5 years (period I-V) and one cluster of 4 years (period VI), including antibiotic susceptibility profiles of blood isolates during the years 1999-2006., Results: The incidence of early-onset sepsis decreased (p < 0.01) from 4% during period I (1978-1982) to 1.2% during period VI (2003-2006). 78% of the infants with group B streptococcal (GBS) sepsis were premature during period I, compared to 47% during period VI (p < 0.05). The incidence of early-onset Gram-negative infections remained low during all periods. The incidence of late-onset sepsis, predominantly caused by coagulase-negative staphylococci (CONS) and Staphylococcus aureus, increased since period III from 7.1 to 13.9% in period VI (p < 0.01). Infections due to fungi or yeasts were rare (incidence <0.3%). The majority of CONS blood isolates were oxacillin-resistant, but vancomycin-susceptible. 95% of CONS blood isolates were susceptible for first-generation cephalosporins. Amoxicillin/clavulanic acid-resistant Escherichia coli were infrequent causes of infection., Conclusions: The incidence of early-onset sepsis mainly caused by GBS decreased. In contrast, the incidence of late-onset sepsis, predominantly caused by CONS, increased significantly. The incidence of fungal and yeast infections remained low. The majority of CONS blood isolates were susceptible for first-generation cephalosporins., (Copyright 2009 S. Karger AG, Basel.)

Objective: To assess the role of human parechoviruses (HPeVs) as a cause of neonatal cerebral infection and to report neuroimaging findings of newborn infants with encephalitis caused by HPeVs., Methods: Clinical presentation, cranial ultrasonography, magnetic resonance imaging (MRI) findings, and neurodevelopmental outcome of 10 infants admitted to a neonatal intensive care unit and diagnosed with encephalitis caused by HPeVs are reported., Results: Nine of 10 infants, with a gestational age of 29 to 41 weeks, presented at 36 to 41 weeks postmenstrual age with clinical seizures. Seven had a fever and six had a rash. Clinical presentation was similar to that of infants with enterovirus infection. Cranial ultrasonography showed increased echogenicity in the periventricular white matter in all infants. Neonatal MRI confirmed white matter changes in nine infants, which changed to gliosis on later MRI. Outcome was variable with cerebral palsy in one, a suspect outcome at 18 months in one, learning disabilities at 7 years of age in one, epilepsy in one, and normal neurodevelopmental outcome in five children. Follow-up of one infant was only 9 months., Interpretation: HPeVs should be added to the list of neurotropic viruses that may cause severe central nervous system infection in the neonatal period. White matter injury can be visualized with cranial ultrasonography, but more detailed information is obtained with MRI and especially diffusion-weighted imaging. Because clinical presentation of HPeV encephalitis is similar to that of enterovirus, real-time polymerase chain reaction for both viruses should be performed in atypical presentation of neonatal seizures.

Background: Enteroviruses (EV) are an important cause of neonatal disease including hepatitis, meningoencephalitis, and myocarditis that can lead to death or severe long-term sequelae. Less is known about severe neonatal infection caused by the parechoviruses (PeV) of which type 1 (PeV1) and type 2 (PeV2) were previously known as echovirus 22 and echovirus 23. They belong to the same family of Picornaviridae as the EV. Of the PeV, so far only PeV3 has been associated in 2 recent reports with severe neonatal infection including involvement of central nervous system., Methods: We compared the clinical signs, diagnosis, laboratory data, cerebral imaging, and neurodevelopmental outcome of 11 neonates with PeV infection with 21 infants with EV infection treated in our hospital between 1994 and 2006. The diagnosis of EV infection or PeV infection was confirmed by a positive EV and/or PeV real time-polymerase chain reaction on blood, cerebrospinal fluid, (CSF) or stool or a viral culture of stool, nasopharyngeal swab, and/or CSF., Results: The 32 infants presented with sepsis-like illness and the most frequent signs were: fever, seizures, irritability, rash, and feeding problems. All patients received antibiotic treatment. Eleven of 21 infants infected with EV and 7 of 11 infants infected with PeV were full-term. Differentiation between the infants infected with EV and PeV on the basis of fever, irritability, rash, and seizures was not possible. Myocarditis was exclusively seen in 4 patients infected by EV. Eight of 11 patients with a PeV infection had meningoencephalitis of whom only 1 infant developed pleocytosis in the CSF. Serum C-reactive protein and CSF protein values were significantly higher in infants with EV infection than in those with PeV infection. Cerebral imaging of all infants with EV or PeV cerebral infection showed mild to severe white matter abnormalities. In 1 infant with EV infection and 3 infants with PeV infection, neurodevelopmental delay occurred. Mortality and long-term sequelae were mainly associated with myocarditis in the infants who were infected with EV (4 of 21)., Conclusions: It is not possible to distinguish neonatal PeV from EV infection on the basis of clinical signs. Neonates with PeV or EV infection present with sepsis-like illness and the most frequent signs are fever, seizures, irritability, rash, and feeding problems.

Outbreaks with Enterobacter spp. have been described frequently in neonatal intensive care units (NICUs). This study investigated the factors that determine whether a neonate becomes colonised with Enterobacter spp., how long colonisation continues and whether the termination of isolation measures leads to spread of the organism. Neonates transferred from the NICUs of tertiary care hospitals were screened for the presence of Enterobacter spp. and any potential predictors for colonisation recorded. Those infected were monitored during their hospital stay and colonised neonates were screened every month for six months. Isolation infection control precautions were lifted and all neonates were screened for the presence of Enterobacter spp. six and 12 months later. Fifteen colonised neonates and 33 non-colonised controls were identified for study. Multivariate analysis showed that antibiotic therapy for more than three days and an Apgar score of <8 after 1 min were independently associated with Enterobacter spp. colonisation. Molecular typing using single-enzyme amplified-fragment length polymorphism (seAFLP) analysis revealed 22 different seAFLP genotypes. Three infants remained colonised with the same Enterobacter genotype after discharge; however, most neonates lost their strain or became colonised with another genotype. Lifting infection control measures for neonates colonised with Enterobacter spp. in a neonatal ward did not lead to increased incidence of colonisation and none of the infants became infected. Isolating neonates with susceptible Enterobacter spp. was not found to be necessary.

Imaging data concerning infection of the central nervous system (CNS) in neonates are usually confined to small groups of infants. We have reviewed the imaging findings in 96 preterm and full-term infants admitted to our neonatal intensive care unit over a 15 year period. Neuro-imaging, especially cranial ultrasound (CUS) and magnetic resonance imaging (MRI) provided useful information; CUS allows the early and later detection of calcification, germinolytic and parenchymal cysts, ventricular dilatation and strands and ependymal abnormality; diffusion weighted imaging (DWI) is especially useful in the acute stage of bacterial and viral infections, while conventional MRI helps in the detection of neocortical dysplasia in CMV infection and defining cerebellar abnormality.

The authors report six neonates with enteroviral meningoencephalitis. Five infants presented with prolonged seizures, and one presented with systemic enteroviral disease. Cranial ultrasonography showed increased echogenicity in the periventricular white matter, and MRI confirmed mild to severe white matter damage in all infants, which looked similar to periventricular leukomalacia. Two infants developed cerebral palsy: one was neurologically suspect at age 18 months, and three were developmentally normal.

Interleukin-6 (IL-6), interleukin-8 (IL-8), and procalcitonin (PCT) are important parameters in the diagnosis of sepsis and for differentiating between viral and bacterial infection in children. We compared the value of IL-6, IL-8, and PCT with C-reactive protein (CRP) in the diagnosis and treatment of late-onset sepsis among infants admitted to the neonatal intensive care unit (group I) and febrile infants admitted to general hospitals from home (group II). Group I was divided into subgroups Ia, positive blood culture (all Gram-positive cocci); Ib, negative blood culture; and Ic, controls. Group II was divided into subgroups IIa, systemic enterovirus infection, and IIb, no enterovirus infection. Enterovirus was identified by real-time (RT) polymerase chain reaction (PCR) and/or by culture in blood and cerebrospinal fluid (CSF). The positive predictive values of IL-6, IL-8, and PCT (78%, 72%, and 83%, respectively) were better than that of CRP (63%) in the diagnosis of neonatal sepsis. After 48 h of antibiotic treatment, IL-6 and IL-8 levels significantly decreased and PCT stabilized in clinically recovered patients, suggesting that these markers may be useful in distinguishing patients in which antibiotic treatment may be discontinued. Among infants of subgroup IIa, 80%-90% had normal values of IL-6, IL-8, and PCT, whereas CRP was increased in 40%. In conclusion, IL-6, IL-8, and PCT are better parameters than CRP in the diagnosis and follow-up of neonatal sepsis due to coagulase-negative staphylococci (CoNS) and in the exclusion of bacterial infection among those with enteroviral infection among febrile infants presenting from home.

Background: The incidence of viral infections in patients treated in the neonatal intensive care unit (NICU) is not well-known. We summarized the data of all patients with laboratory-confirmed viral infections admitted at the NICU of our hospital during the period of 1992-2003., Objectives: To determine the incidence of viral infections among infants hospitalized in a NICU, the associated clinical manifestations and their outcome., Methods: Retrospective analysis of epidemiologic, virologic and clinical data from infants with proven viral infection. The diagnosis viral infection was confirmed by positive viral culture and/or polymerase chain reaction from clinical samples., Results: Viral infection was confirmed in 51 of 5396 infants (1%) admitted to the NICU; 20 (39%) had an enterovirus and parechovirus (EV/PEV) infection, 15 (29%) a respiratory syncytial virus (RSV) infection, 5 (10%) a rotavirus infection, 3 (6%) a cytomegalovirus (CMV) infection, 2 (4%) an adenovirus infection, 2 (4%) a parainfluenza virus infection, 2 (4%) a herpes simplex virus infection, 1 (2%) a rhinovirus infection and 1 (2%) a rubella virus infection. Three of the infants presented at birth with symptomatic rubella virus, CMV or herpes simplex virus infection. RSV infection developed mostly in hospitalized infants (60%), and 93% of infections occurred during the winter (November-March). The clinical presentations of EV/PEV disease were sepsis-like illness, prolonged seizures in term infants and gastrointestinal disease in preterm infants. RSV, parainfluenza virus, rhinovirus and CMV caused respiratory disease, predominantly in preterm infants. Gastrointestinal disease was seen only in preterm infants with adenovirus, rotavirus or EV/PEV infection. Mortality and serious sequelae were high in patients infected with EV/PEV (10 and 15%, respectively)., Conclusions: The incidence of viral infection in the NICU was 1%. Enteroviral infections were the most frequently diagnosed infections, occurred often in term infants born at home and presented with sepsis-like illness or seizures. Preterm infants hospitalized from birth mainly developed gastrointestinal disease caused by rotavirus and adenovirus infection or respiratory disease caused by RSV, parainfluenza and CMV infection. Enteroviruses were responsible for the highest mortality and development of serious sequelae.

Congenital cytomegalovirus (CMV) infection can lead to severe neurological sequelae and (progressive) sensorineural deafness. Neonatal imaging data is mainly based on cranial ultrasound (US) and computed tomography (CT). The additional value of magnetic resonance imaging (MRI) was assessed in congenital CMV infection. The eleven infants studied had a gestational age between 34 and 41 weeks and a birth weight between 1000 and 2780 grams. All but 2 of the infants presented with microcephaly and jaundice at birth. The diagnosis was confirmed postnatally in all infants by isolation of the virus or a polymerase chain reaction (PCR) from the urine. Cranial US was performed in all, MRI in 6 during the neonatal period and later in infancy in 2. Auditory brainstem evoked responses (ABR) were performed in all survivors. US showed periventricular calcifications and/or lenticulostriate vasculopathy associated with mild to moderate ventricular dilatation in 10 of the 11 children. Periventricular (pseudo) cysts were seen in 6 children, being occipital in 4, temporal in 3 and fronto-parietal in 1. The cerebellum appeared to be small in 4 children. MRI provided additional information in 6 of the 8 children. Polymicrogyria in the perisylvian region was seen in 4 children, hippocampal dysplasia in 3 and cerebellar hypoplasia in 4 children. Abnormal signal intensity in the white matter was seen in 4 infants. ABRs were abnormal in 7 of the 9 children. Four children died in the neonatal period, 4 developed severe neurological sequelae, associated with epilepsy and sensorineural deafness in 3. Three children were still too young to be tested, but 2 of these showed sensorineural deafness. MRI provided important additional information, especially with regard to associated polymicrogyria, hippocampal dysplasia, and cerebellar hypoplasia. Calcifications were better seen using US. A combination of US and neonatal MRI should be recommended instead of a CT which is still recommended in the literature.

During summer and fall, enterovirus infections are responsible for a considerable proportion of hospitalizations of young infants. We prospectively studied the incidence of enterovirus infections via real-time polymerase chain reaction (PCR) in blood, feces, and cerebrospinal fluid samples from infants

The epidemiological, virological, and clinical data of 119 infants less than 30 days of age with enteroviral infection collected from January 1993 to November 1995 by the diagnostic virology laboratories were analyzed retrospectively. Ninety-eight isolates (83%) were obtained in the period of May 1 to December 1 with a peak in the summer months. Sixty-five percent (n = 78) of neonates became ill within the first 2 weeks of life. Echoviruses and Coxsackie virus type B were isolated most frequently, in 77 (65%) and 29 (24%) infants, respectively. Diagnosis was made by viral isolation from stool, nasopharyngeal swab, cerebrospinal fluid, and blood. One hundred four (87%) infants developed fever and 25 (21%) infants had diarrhea. A clinical diagnosis of sepsis was made in 42 (35%) infants and meningitis was diagnosed in 28 (24%) cases. The great majority of sepsis cases (36/86%) occurred in infants less than 15 days of age. In conclusion, non-polio enteroviruses (especially echoviruses) are a common and underreported cause of neonatal infection in the Netherlands in the summer months and are associated with a clinical diagnosis of sepsis or meningitis cases in the first 2 weeks of life in a high proportion of cases., (Copyright 2002 Wiley-Liss, Inc.)

In 2 infants, a girl and a boy, congenital viral infection was diagnosed in the neonatal period. The prenatal examination (serologic investigation for Toxoplasma gondii, rubella virus, cytomegalovirus, herpes simplex virus and syphilis (TORCHES)) was negative. In both cases prenatal ultrasonography was abnormal and suggested intrauterine infection. The infants were born with typical symptoms of multisystem disease, known as symptomatic congenital cytomegalovirus infection (jaundice, petechiae, hepatosplenomegaly, intrauterine growth retardation, microcephaly and cerebral calcifications) and congenital rubella syndrome (intrauterine growth retardation, congenital heart disease, cataract, hepatosplenomegaly and cerebral calcifications), respectively. Both had severe cerebral damage. To diagnose severe congenital infection in the first trimester of pregnancy in presence of congenital anomalies in utero there are other possible methods than TORCHES investigation, such as polymerase chain reaction and virus culture in amniotic fluid or in foetal blood obtained by cord puncture.

Unlabelled: Since the mid-1980s, an increase in incidence of invasive disease caused by group A streptococci has been noted amongst adults and children; however, neonatal disease is still rare. Between 1979 and 1998, seven neonates with severe group A streptococcal disease were admitted to our neonatal intensive care unit. The clinical presentation, treatment and outcome are described. In three cases of early-onset disease vertical transmission was documented., Conclusion: Because the incidence of group A streptococcal disease in the general population seems to have increased over the last two decades, we should be aware of the possibility and particularly the severity of group A streptococcal disease in the neonatal period.