What is already known about this subject• Effects of size, renal function, age (postnatal age, gestational age and postmenstrual age) as predictors of vancomycin clearance in premature neonates are established, but the relative contribution of each component remains poorly quantified, largely because these variables are closely correlated.• We have quantified the covariates contributing to vancomycin clearance population parameter variability in order to establish the major covariates required for dosing predictions. Size, standardized using allometric models, was the primary covariate used in our analysis. What this study adds• Size explained 49.8%, postmenstrual age 18.2% and renal function 14.1% of clearance variability.• Descriptors of the relationship between age and clearance in premature neonates vary.• The use of a variable slope sigmoidal model to describe the relationship between clearance and postmenstrual age predicted an adult clearance of 3.79 l h − 1 70 kg − 1 (95% confidence interval 2.76, 4.98) from premature neonatal data. AimTo identify and quantify factors describing the variability of vancomycin clearance in premature neonates. MethodsPopulation pharmacokinetics were estimated (NONMEM) in 214 neonates [postmenstrual age (PMA) 30.4 weeks, range 24-34 weeks; postnatal age 11.9 days, range 1-27 days; weight 1.30 kg, range 0.42-2.6 kg] using therapeutic drug monitoring data. Covariate analysis included weight, PMA, serum creatinine, use of inotropes or ibuprofen, positive blood culture and respiratory support. A one-compartment linear disposition model with zero order input and first-order elimination was used to describe the data (604 observations). ResultsThe population estimate for volume of distribution ( V ) was 39 l 70 kg − 1 (coefficient of variation 19.4%). Clearance (CL) increased from 0.897 l h − 1 70 kg − 1 at 24 weeks PMA to 2.02 l h − 1 70 kg − 1 by 34 weeks PMA. The between-subject variability for CL was 18.6% and the between-occasion variability was 12.2%. The use of ibuprofen reduced clearance, but this effect was attributable to reduced renal function. Overall, 82% of the variability of CL was predictable. Size explained 49.8%, P MA 18.2% and renal function 14.1%. The use of a variable slope sigmoidal model to describe the relationship between clearance and PMA predicted an adult clearance of 3.79 l h − 1 70 kg − 1 (95% confidence interval 2.76, 4.98). ConclusionsSize, renal function and PMA are the major contributors to clearance variability in premature neonates. The small (18%) unexplained variability in clearance suggests target concentration intervention is unnecessary if size, age and renal function are used to predict the dose. Extrapolation to an adult clearance from neonatal data is possible using allometric size models and a function describing clearance maturation.B. J. Anderson et al.

• In cCMV, isolated periventricular T2-weighted signal hyperintensity has a good postnatal prognosis. • In cCMV, SNHL and neurological impairment can be predicted at 27 or 33 weeks. • In cCMV, fetal MR has a high NPV in predicting SNHL. • In cCMV, fetal MR has a high NPV in predicting neurological impairment.

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.

AimIdentify and quantify factors describing variability of amikacin clearance in preterm neonates at birth. MethodsPopulation pharmacokinetics of amikacin were estimated in a cohor t of 205 extreme preterm neonates [post conception age (PCA) 27.8, SD 1.8, range 24-30 weeks; weight 1.07, SD 0.34, range 0.45-1.98 kg, postnatal age < 72 h]. Covariate analysis included weight, PCA, Apgar score, prophylactic administration of a nonsteroidal antiinflammatory drug (NSAID) to the neonate, maternal indomethacin and betamethasone administration, and chorioamnionitis. ConclusionsSize and post-conception age are the major contributors to clearance variability in extreme premature neonates ( < 31 weeks PCA). The large (35% of total) unexplained variability in clearance reinforces the need for target concentration intervention to reduce variability in exposure to a safe and effective range.

Cytomegalovirus (CMV) is the leading cause of known congenital viral infections. Approximately 90% of congenitally infected newborns exhibit no clinical abnormalities at birth. In 5% to 15%, a wide spectrum of clinical signs is present at birth. Ophthalmological signs are seen in a large percentage of symptomatic patients but rarely in otherwise asymptomatic infants. Chorioretinitis, optic atrophy, and cortical visual impairment are the most frequent causes of visual problems in congenitally infected infants. There is no clear consensus in the literature on screening or treatment modalities concerning the ophthalmological aspects of congenital CMV. Further prospective studies are needed to set up guidelines for ophthalmological screening and treatment of infants with congenital CMV.