Neurodevelopmental outcome in children with congenital cytomegalovirus infection: A prospective multicenter cohort study.

BACKGROUND: Congenital cytomegalovirus infection (cCMV) is the most common congenital infection worldwide and is a major cause of neurodevelopmental impairment in children. At this point there are insufficient data on neurodevelopmental outcome of children with cCMV, both symptomatic and asymptomatic. AIM: This study aimed to describe the neurodevelopmental outcome in a large prospective cohort of children with cCMV. METHODS: All children with cCMV, included in the Flemish cCMV register, were eligible for this study. Data on neurodevelopmental outcome was available in 753 children. Data on neuromotor, cognitive, behavioral, audiological and ophthalmological outcome were analyzed. RESULTS: Neurodevelopmental outcome was normal in 530/753 (70,4 %) at any age of last follow-up. Mild, moderate and severe neurodevelopmental impairment was found in 128/753 (16,9 %), 56/753 (7,4 %) and 39/753 (5,2 %), respectively. Adverse outcome is found both in the symptomatic and asymptomatic children (53,5 % versus 17,8 %). Autism spectrum disorder (ASD) was diagnosed more often than in the general population in Flanders (2,5 % versus 0,7 %). Speech and language impairment was found in 2 %, even in absence of hearing loss. CONCLUSION: Both symptomatic and asymptomatic cCMV children are at risk of sequelae, with higher risk in case of first trimester infection. During follow-up of this population, special attention should be given to the audiological follow-up, the presence of hypotonia at young age, the possible higher risk of ASD and the risk of speech and language impairment even in absence of hearing loss. Our results emphasize the need for multidisciplinary neurodevelopmental follow-up of all cCMV infected children.

Shedding a light on ultraviolet-C technologies in the hospital environment.

Ultraviolet (UV)-C light for disinfection has experienced a surge in popularity since the outbreak of COVID-19. Currently, many different UV-C systems, with varied properties that impact disinfection performance, are available on the market. Therefore this review aims to bundle the available information on UV-C disinfection to obtain an overview of its advantages, disadvantages, and performance-influencing parameters. A literature search was performed using the snowball search method in Google Scholar and PubMed with the following keywords: UV-C disinfection, UV-C dose, UV-C light source, UV-C repair mechanism, UV-C photoreactivation, and UV-C disinfection standards. The main parameters of UV-C disinfection are wavelength, dose, relative humidity, and temperature. There is no consensus about their optimal values, but, in general, light at a high dose and a spectrum of wavelengths containing 260 nm is preferred in an environment at room temperature with low relative humidity. This light can be generated by mercury-vapour, light-emitting diode (LED), pulsed-xenon, or excimer lamps. Multiple factors are detrimental to disinfection performance such as shadowing, a rough surface topography, a high level of contamination, repair mechanisms, and the lack of standardization. Also, there are health and safety risks associated with the UV-C technology when used in the proximity of people. UV-C disinfection systems have promising features and the potential to improve in the future. However, clarifications surrounding the different parameters influencing the technologies' effectiveness in hospital environment are needed. Therefore UV-C disinfection should currently be considered for low-level rather than high-level disinfection.

Compliance with international prevention guidelines for central-line-associated bloodstream infections in neonatal intensive care units in Belgium: a national survey.

BACKGROUND: Central-line-associated bloodstream infections (CLABSIs) are a preventable cause of morbidity among patients in neonatal intensive care units (NICUs). AIMS: To assess compliance with international guidelines for prevention of CLABSIs in Belgian NICUs, and to study unit characteristics contributing to CLABSIs. METHODS: A survey was undertaken to measure the adherence of various NICUs to the CLABSI prevention guidelines related to catheter insertion, catheter maintenance and quality control measurements. A Poisson regression model was used to estimate the CLABSI adjusted relative risk for each prevention guideline item implemented. Multi-variable linear regression was used to estimate associations between guideline compliance rate and facility characteristics and the incidence of CLABSIs for 2015-2016. FINDINGS: In Belgium, the overall CLABSI incidence density was 8.48/1000 central-line-days, and was higher in larger NICUs: 10.87‰ vs 6.69‰ (P<0.05). Adherence was highest for prevention items at catheter insertion (64%), and low for catheter maintenance and quality control items (47% and 50%, respectively). Superior adherence to insertion items (P=0.051) and quality performance items (P=0.004) was associated with decreased risk of CLABSIs, but this was not found for maintenance prevention items (P=0.279). After adjustment for guideline adherence, the size of the NICU was found to be an independent determinant for CLABSIs (P=0.002). CONCLUSIONS: In Belgium, the adherence of NICUs to international CLABSI prevention guidelines is moderate to poor. Compliance of NICUs with the guidelines is significantly associated with decreased CLABSI rates. The reasons for the gap between current practice in Belgian NICUs and international prevention guidelines need further investigation.

Management of the neonate at risk for early-onset Group B streptococcal disease (GBS EOD): new paediatric guidelines in Belgium.

Despite group B streptococcal (GBS) screening in late pregnancy and intrapartum antimicrobial prophylaxis, early-onset sepsis in neonates remains a common source of neonatal morbidity and mortality especially in preterm neonates. The identification of neonates with early-onset sepsis is usually based on perinatal risk factors. Clinical signs are aspecific and laboratory tests are not sensitive. Therefore, many clinicians will overtreat at-risk infants. Inappropriate treatment with antibiotics increases the risk for late-onset sepsis, necrotizing enterocolitis, mortality, and prolongs hospitalisation and costs. In 2003, the Belgian Health Council published guidelines for the prevention of perinatal GBS infections. This report presents the Belgian paediatric management guidelines, which have been endorsed by the Belgian and Flemish societies of neonatology and paediatrics. The most imported changes in the 2014 guidelines are the following: recommendations for a lumbar puncture; clarification of normal spinal fluid parameters and blood neutrophil indices corrected for gestation age; specific timing for diagnostic testing after birth; no indication for diagnostic testing in asymptomatic newborns unless additional risk factors; a revised algorithm for management of neonates according to maternal and neonatal risk factors; and premature infants described as those below 35 weeks instead of 37 weeks. The guidelines were made on the basis of the best evidence and on expert opinion when inadequate evidence exists.

Clinical predictive value of real-time PCR quantification of human cytomegalovirus DNA in amniotic fluid samples.

The aim of this study was to evaluate the diagnostic reliability and prognostic significance of the quantification of cytomegalovirus (CMV) DNA in amniotic fluid (AF). We retrospectively reviewed the results for 282 amniotic fluid samples that had been tested for CMV by a quantitative real-time PCR. We observed three cases in which no CMV genomes were detected in the AF but in which the children were nevertheless congenitally infected. Hence, we conclude that a negative result by PCR for CMV in AF cannot rule out the possibility of congenital infection. No false-positive PCR results were observed. A correlation between the CMV viral load in AF and the fetal and neonatal outcomes could not be demonstrated in our study. Instead, a correlation was found between the CMV viral load and the gestational age at the time of amniocentesis.

Urinary propofol metabolites in early life after single intravenous bolus.

BACKGROUND: /st> Propofol clearance is lower in neonates than in adults and displays extensive interindividual variability, in part explained by postmenstrual age (PMA) and postnatal age (PNA). Since propofol is almost exclusively cleared metabolically, urinary propofol metabolites were determined in early life and compared with similar observations reported in adults. METHODS: /st> Twenty-four hours urine collections were sampled after a single i.v. bolus of propofol (3 mg kg(-1)) in neonates undergoing procedural sedation. Clinical characteristics (PMA, PNA, weight, and cardiopathy) were recorded. Urine metabolites [propofol glucuronide (PG), 1- and 4-quinol glucuronide (QG)] were quantified using high-pressure liquid chromatography. Urine recovery (% administered dose) and the contribution of PG and QG to urinary elimination were calculated. Data were reported by median and range, analysed by Mann-Whitney U or Spearman's rank. RESULTS: /st> Eleven neonates (median PNA 11 days, PMA 38 weeks) were included. Median propofol metabolite recovery was 64% (range 34-98%). PG contributed 34% (range 8-67%) and QG 65% (range 33-92%). There was no significant correlation between either PMA, PNA, or cardiopathy and propofol metabolites. Compared with adults, the contribution of PG (34% vs 77%) was lower and the contribution of QG (65% vs 22%) was higher in neonates. CONCLUSIONS: /st> Propofol metabolism in neonates differs from adults, reflecting the age-dependent limited glucuronidation capacity. Hydroxylation to quinol metabolites already contributes to propofol metabolism. These differences likely explain the PMA- and PNA-dependent reduced propofol clearance in neonates.

Cerebrospinal fluid compartmental pharmacokinetics of amikacin in neonates.

To describe and investigate the covariate effects of cerebrospinal fluid (CSF) amikacin pharmacokinetics in neonates, CSF samples were prospectively collected from neonates in whom amikacin had been initiated before a diagnostic lumbar puncture was performed. CSF analysis (amikacin concentration, white blood count [WBC], glucose content, and protein concentration) and amikacin therapeutic drug monitoring results (peak and trough concentrations) in serum were recorded. Correlations (Spearman rank) between the CSF amikacin concentration and the CSF WBC and glucose and protein concentration were investigated. There were 44 CSF amikacin concentrations and 83 serum samples available from 43 neonates (mean postmenstrual age, 36 weeks [range, 26 to 41 weeks]; mean weight, 2.43 kg [range, 0.87 to 3.86 kg]). The median time interval between initiation of amikacin administration and CSF sampling was 25 h (range, 2.5 to 93.7 h). The median amikacin concentration in the CSF was 1.08 mg/liter (range, 0.34 to 2.65 mg/liter), and the mean trough and peak amikacin concentrations in serum were 3.8 +/- 2.5 mg/liter and 35.7 +/- 5.9 mg/liter, respectively. A correlation between CSF amikacin and CSF protein contents (P < 0.01, r = 0.41, 95% confidence interval = 0.13 to 0.63) but not between CSF WBC and CSF glucose was documented. A two-compartment (central and CSF) linear disposition model was used to estimate population pharmacokinetics. The half time for equilibration (T(eq)) between serum and CSF compartments was used as a measure of blood-brain barrier permeability. The T(eq) was 7.58 h (coefficient of variation [CV] = 49.1%) with a partition coefficient of 0.103 (CV = 26.4%). There was no relationship between the T(eq) and CSF WBC, CSF glucose content, or CSF protein content.

Maturational changes in the in vivo activity of CYP3A4 in the first months of life.

OBJECTIVE: To document maturational changes of the in vivo activity of CYP3A4 in the first months of life. METHODS: The contribution of tramadol (M), O-demethyl tramadol (M1, CYP2D6-mediated) and N-demethyl tramadol (M2, CYP3A4-mediated) to the overall elimination of tramadol and the log M/M2 was assessed in 24-hour urine collections during continuous intravenous tramadol administration. Correlations with perinatal characteristics (postnatal age (PNA) and postmenstrual age (PMA)) were studied. RESULTS: Of the total amount of tramadol administered in a 24-hour interval to 25 neonates and young infants (PMA 25 - 53 weeks), 34.5% (SD 6.1) were retrieved in the urine as parent compound or metabolite in a 24-hour interval. This retrieved material consisted primarily of tramadol 79% (SD 18), M1 10% (SD 17) and M2 3% (SD 3.4). The contribution of M (r2 = -0.53), M1 (r2 = 0.46) and M2 (r2 = 0.16) to overall M elimination correlated with increasing PMA. The mean log M/M2 was 1.44 (SD 0.46) and there was an inverse correlation between the log M/M2 ratio and PMA (r2 = -0.43, 95% CI for r = -0.84 to -0.34, p = 0.0006) and PNA (r2 = -0.25, 95% CI for r = -0.78 to -0.16, p = 0.008). The maturational half-life of the log M/M2 ratio was 16 - 20 weeks. In a multiple regression model, PMA was the only significant variable accounting for the interindividual variability in log M/M2. CONCLUSIONS: PMA was found to be the most important maturational change determing the in vivo activity of CYP3A4. The activity of CYP3A4 is relatively delayed in the first months of life compared to the developmental changes in CYP2D6 activity described earlier, however, the overall weak correlations reflect that PMA explains only in part the interindividual variability observed.

Ibuprofen and cerebral oxygenation and circulation.

The effect of prophylactic administration of ibuprofen on the cerebral circulation in preterm babies was measured with near infrared spectroscopy. No significant difference in the change in cerebral blood volume, change in cerebral blood flow, or tissue oxygenation index was found between administration of ibuprofen or placebo.

Continuous measurement of cerebral blood volume and oxygenation during rewarming of neonates.

AIM: To investigate the effect of rewarming in preterm infants presenting with hypothermia at admission. METHODS: The tissue oxygenation index (TOI), changes in cerebral blood volume (DeltaCBV) and changes in intravascular oxygenation (DeltaHbD) were measured in eight preterm infants, presenting with a temperature less than 35 degrees C at admission. RESULTS: A significant increase in HbD and TOI was seen in four patients (group A), while a significant increase in CBV and a decrease in HbD was seen in four other patients (group B). Retrospective analysis showed that group A had important signs of peripartal asphyxia. CONCLUSION: While infants with peripartal asphyxia showed an important increase in oxygenation during rewarming, no significant changes were seen in the non-asphyxiated infants.

Effects of co-administration of ibuprofen-lysine on the pharmacokinetics of amikacin in preterm infants during the first days of life.

The aim of this study was to assess the effects of intravenous co-administration of ibuprofen-lysine on the pharmacokinetics of amikacin during the first days of life in preterm infants. The pharmacokinetics of amikacin were retrospectively calculated in a cohort of 73 neonates (gestational age <31 weeks) who received either ibuprofen-lysine or placebo following inclusion in the multicentre ibuprofen prophylaxis study. Assuming a one-compartment model with instantaneous input and first-order output, there was no significant difference in the median distribution volume (0.63 vs. 0.59 liters/kg), but the median serum half-life (16.4 vs. 12.4 h) of amikacin was significantly longer (p <0.02), and the clearance (0.36 vs. 0.6 ml/kg/min; p <0.005) of amikacin was significantly lower in infants who received ibuprofen-lysine. We conclude that the time interval between consecutive amikacin administrations should be prolonged, if ibuprofen-lysine is co-administered.