M. A. Verboon-Maciolek

White matter damage in neonatal enterovirus meningoencephalitis

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.

Prognosis for neonates with enterovirus myocarditis

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.

Incidence of infections of ventricular reservoirs in the treatment of post-haemorrhagic ventricular dilatation: a retrospective study (1992-2003).

Background: Since 1992, infants with progressive posthaemorrhagic ventricular dilatation (PHVD) have been treated in the Neonatal Intensive Care Unit, Wilhelmina Children’s Hospital, Utrecht, The Netherlands, with a ventricular reservoir. Objective: To retrospectively study the incidence of infection using this invasive procedure. Methods: Between January 1992 and December 2003, 76 preterm infants were treated with a ventricular reservoir. Infants admitted during two subsequent periods were analysed: group 1 included infants admitted during 1992–7 (n = 26) and group 2 those admitted during 1998–2003 (n = 50). Clinical characteristics and number of reservoir punctures were evaluated. The incidence of complications over time was assessed, with a focus on the occurrence of infection of the reservoir. Results: The number of punctures did not change during both periods. Infection was significantly less common during the second period (4% (2/50) v 19.2% (5/26), p = 0.029). Conclusion: The use of a ventricular reservoir is a safe treatment to ensure adequate removal of cerebrospinal fluid in preterm infants with PHVD. In experienced hands, the incidence of infection of the ventricular reservoir or major complications remains within acceptable limits.

Neuro-Imaging Findings in Infants with Congenital Cytomegalovirus Infection: Relation to Trimester of Infection

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.

Application of UL144 Molecular Typing To Determine Epidemiology of Cytomegalovirus Infections in Preterm Infants

ABSTRACT Sequence analysis of the UL144 gene of human cytomegalovirus (CMV) was used to investigate the epidemiology of CMV infections in preterm infants. Nosocomial transmission of CMV from congenitally infected infant to preterm twins was excluded based on distinct molecular profiles of CMV strains. Indistinguishable molecular profiles between strains from the mother and the infant indicated postnatal acquisition of CMV through breastfeeding.

1394 Clinical Outcome of Neonatal Conssepsis with a Vancomycin-Sparing Regimen: Favourable Results with Cefazolin as First Choice Agent

Background and aims: The typical empiric antimicrobial treatment protocol for neonatal coagulase-negative staphylococci (CONS) sepsis includes vancomycin. However, the protocol in our NICU prescribes cefazolin to cover CONS. The susceptibility of CONS blood isolates to cefazolin and clinical outcome of infants with CONS sepsis was studied during 2000-2006. 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: 163/185 infants with proven CONS sepsis were treated with cefazolin. Median MIC value of cefazolin was 0.75-2 (range 0.01-256) µg/ml and 77-96% of all isolates was susceptible to cefazolin (MIC ≤8 µg/ml) during 2000-2006. In 121/140 (86%) infants with cefazolin-susceptible and 21/23 cases (91%) with cefazolin-resistant CONS isolate cefazolin was clinically efficacious. 12/17 second blood cultures in 19 non-responders yielded CONS with unchanged MIC. In 78% of good responders and 22% of non-responders a central venous catheter was removed at onset of sepsis. Nonresponders were switched to vancomycin. Conclusions: Majority of CONS isolates remained susceptible to cefazolin over a period of 7 years. Cefazolin is clinically efficacious in >85% of cases and can be recommended as first choice agent for therapy of CONS sepsis. Removal of a central venous catheter may be the most important therapeutic measure.

NO CEREBRAL WHITE MATTER DAMAGE DUE TO CONS SEPSIS IN PRETERM INFANTS DETERMINED BY APPARANT DIFUSSION COEFFICIENT (ADC) ON MRI

Background and aims: Neonatal sepsis may cause cerebral white matter (WM) damage in preterm infants, compromising outcome. Coagulase-negative staphylococcal (CONS) sepsis is a frequent cause of morbidity in preterm infants, however generally not developing into a fulminant disease. To determine the impact of CONS sepsis on cerebral WM, the ADC of 3 WM regions was measured using diffusion-weighted MRI (DW-MRI) performed at term-equivalent age. Methods: Cerebral DW-MRI was performed routinely in 81 preterm infants (GA< 31 weeks). Four infants with cerebral white matter damage due to venous infarction or hydrocephalus, before CONS sepsis occurred in 1, were excluded. The ADC of frontal, parietal and occipital WM was calculated in 31 infants with CONS sepsis and 50 infants without sepsis. Results: ADC values in parietal WM were significantly lower as compared to frontal or occipital WM in both groups (p< 0.001), indicating developmental differences (table 1). No differences were found in ADC values of infants with or without CONS sepsis in all 3 regions of cerebral WM. Conclusions: CONS sepsis in preterm infants is not associated with cerebral white matter damage as determined by ADCs in cerebral MRI at termequivalent age.