This thesis provides an overview of the current epidemiology of neonatal NI, including CLABSI. While highlighting the importance of this complication, it has laid the foundation for the development... Show moreThis thesis provides an overview of the current epidemiology of neonatal NI, including CLABSI. While highlighting the importance of this complication, it has laid the foundation for the development and evaluation of several prevention and reduction strategies. The incidence of sepsis among certain neonatal subpopulations such as neonates with hemolytic disease of the fetus and newborn remains high, illustrating the need to re-calibrate indications for central-line placement and CLABSI prevention measures. In contrast to what was hypothesized, a significant positive effect of several interventions and changes in clinical practice, including the implementation of single-room care and a multi-modal strategy, could not be supported. On the other hand, support was found for behavioral change tools such as ‘nudges’ which seem to be a more promising avenue in the reduction of NI, providing such tools can be tailored to the clinical micro-system and context-specific needs of NICU-healthcare workers. Furthermore, nationwide CLABSI surveillance provided a unique insight into the current burden of neonatal CLABSI in The Netherlands, although the optimization of digital infrastructures, data availability and accessibility are urgently needed to perform forthcoming benchmarking initiatives. Even though much progress has been made, we are far from done in the battle against neonatal NI. Show less
PurposeEarly recognition of seizures in neonates secondary to pathogenic variants in potassium or sodium channel coding genes is crucial, as these seizures are often resistant to commonly used anti... Show morePurposeEarly recognition of seizures in neonates secondary to pathogenic variants in potassium or sodium channel coding genes is crucial, as these seizures are often resistant to commonly used anti-seizure medications but respond well to sodium channel blockers. Recently, a characteristic ictal amplitude-integrated electroencephalogram (aEEG) pattern was described in neonates with KCNQ2-related epilepsy. We report a similar aEEG pattern in seizures caused by SCN2A- and KCNQ3-pathogenic variants, as well as conventional EEG (cEEG) descriptions.MethodsInternational multicentre descriptive study, reporting clinical characteristics, aEEG and cEEG findings of 13 neonates with seizures due to pathogenic SCN2A- and KCNQ3-variants. As a comparison group, aEEGs and cEEGs of neonates with seizures due to hypoxic-ischemic encephalopathy (n = 117) and other confirmed genetic causes affecting channel function (n = 55) were reviewed.ResultsIn 12 out of 13 patients, the aEEG showed a characteristic sequence of brief onset with a decrease, followed by a quick rise, and then postictal amplitude attenuation. This pattern correlated with bilateral EEG onset attenuation, followed by rhythmic discharges ending in several seconds of post-ictal amplitude suppression. Apart from patients with KCNQ2-related epilepsy, none of the patients in the comparison groups had a similar aEEG or cEEG pattern.DiscussionSeizures in SCN2A- and KCNQ3-related epilepsy in neonates can usually be recognized by a characteristic ictal aEEG pattern, previously reported only in KCNQ2-related epilepsy, extending this unique feature to other channelopathies. Awareness of this pattern facilitates the prompt initiation of precision treatment with sodium channel blockers even before genetic results are available. Show less
Aim: To evaluate the inter-and intraindividual variation of predicted nasogastric tube insertion lengths by nurses working in two neonatal intensive care units in the Netherlands, using a mannequin... Show moreAim: To evaluate the inter-and intraindividual variation of predicted nasogastric tube insertion lengths by nurses working in two neonatal intensive care units in the Netherlands, using a mannequin model. Methods: A total of 110 nurses (55 nurses from Center A and 55 from Center B) were asked to predict the nasogastric tube insertion length on a neonatal mannequin. We evaluated the length and prediction method used by the nurses. We also estimated the number of tubes that would have correctly been placed in the stomach of a neonate according to the seize of the mannequin.Results: The mean predicted insertion length of the nasogastric tube was 30.0 cm with an inter -individual variation of 12 cm (range 24-36 cm). The mean intraindividual variation was 0.75 cm. The two centers used two different prediction methods in their local guidelines, but overall at least 6 different methods were used by the nurses. We estimated that 77% (85/110) of the tubes would have ended in the body of the mannequins stomach, while 10% (11/110) would have ended in the esophagus and 13% (14/110) would have ended against the stomach lining or in the duodenum.Conclusion: Nurses in two neonatal intensive care units used many different methods which lead to a large interindividual variation in predicted insertion lengths of the nasogastric tubes. Regular evaluations using this mannequin model could lead to more uniformity and reduce the risk of tube misplacement in neonates. Show less
Jansen, S.J.; Hoeven, A. van der; Akker, T. van den; Veenhof, M.; Asmuth, E.G.J. von; Veldkamp, K.E.; ... ; Lopriore, E. 2022
Nosocomial bloodstream infections (NBSIs), commonly due to central-line associated bloodstream infections (CLABSI), contribute substantially to neonatal morbidity and mortality. We aimed to... Show moreNosocomial bloodstream infections (NBSIs), commonly due to central-line associated bloodstream infections (CLABSI), contribute substantially to neonatal morbidity and mortality. We aimed to identify longitudinal changes in incidence of NBSI, microbiological-spectrum, and antibiotic exposure in a large cohort of preterm neonates admitted to the neonatal intensive care unit. We retrospectively assessed differences in annual rates of NBSI (per 1000 patient-days), CLABSI (per 1000 central-line days), and antibiotic consumption (per 1000 patient-days) among preterm neonates (< 32 weeks' gestation) hospitalized between January 2012 and December 2020. Multi-state Markov models were created to model states of progression of NBSI and infection risk given a central-line on days 0, 3, 7, and 10 of admission. Of 1547 preterm infants, 292 (19%) neonates acquired 310 NBSI episodes, 99 (32%) of which were attributed to a central-line. Over the years, a significant reduction in central-line use was observed (p < 0.001), although median dwell-time increased (p = 0.002). CLABSI incidence varied from 8.83 to 25.3 per 1000 central-line days, with no significant difference between years (p = 0.27). Coagulase-negative staphylococci accounted for 66% of infections. A significant decrease was found in antibiotic consumption (p < 0.001). Probability of NBSI decreased from 16% on day 3 to 6% on day 10. NBSI remains a common problem in preterm neonates. Overall antibiotic consumption decreased over time despite the absence of a significant reduction in infection rates. Further research aimed at reducing NBSI, in particular CLABSI, is warranted, particularly with regard to limiting central-line dwell-time and fine-tuning insertion and maintenance practices. Show less
Jansen, S.J.; Lopriore, E.; Berkhout, R.J.M.; Hoeven, A. van der; Saccoccia, B.; Boer, J.M. de; ... ; Bekker, V. 2020
Introduction Nosocomial infections (NIs) are a major source of iatrogenic harm in neonatal intensive care units (NICUs). The influence of the infrastructure of NICUs on NIs is not well documented.... Show moreIntroduction Nosocomial infections (NIs) are a major source of iatrogenic harm in neonatal intensive care units (NICUs). The influence of the infrastructure of NICUs on NIs is not well documented. This study aims to examine the effect of single-room units (SRU) versus open-bay units (OBU) on the incidence of NIs, including central-line-associated bloodstream infections (CLABSI), in preterm neonates. Methods All preterm neonates (< 32 weeks gestational age) admitted to our NICU were included. Two study periods were compared: one prior to (May 2015-May 2017) and one following (May 2017-May 2019) transition from OBU to SRU. Incidence density (number of infections per 1000 patient-days) and cumulative incidence (number of infections per 100 neonates) for NIs were calculated. CLABSIs were calculated per 1000 central-line days. U chart analysis was performed to determine special-cause variation in quarterly CLABSI and NI rates. Multivariate competing risk regression was performed to identify independent NI risk factors. Results Of the 712 included infants, 164 (23%) infants acquired >= 1 NIs. No differences were found in incidence density (13.68 vs. 12.62, p = 0.62) or cumulative incidence of NI (23.97 vs. 22.02, p = 0.59) between OBU and SRU. CLABSIs showed a similar non-significant reduction after the move (14.00 vs. 10.59, p = 0.51). U chart analysis did not identify unit transition as a potential source of special-cause variation for CLABSI and NI. Competing risks regression analysis revealed longer duration of invasive mechanical ventilation as a significant risk factor for NI (subhazards ratio: 1.03 per day on ventilation, p = 0.01). Conclusion Single-rooms are not associated with a significant reduction in NIs in the NICU. This study therefore does not add evidence that could support the transition to SRUs if based only on a large multimodal infection control strategy. Recommendations to build SRUs would require a wider justification, also taking into account other SRU benefits. Show less
Renal clearance is responsible for the elimination of a large number of water-soluble drugs and metabolites and is therefore of large importance when characterizing the pharmacokinetics of drugs.... Show moreRenal clearance is responsible for the elimination of a large number of water-soluble drugs and metabolites and is therefore of large importance when characterizing the pharmacokinetics of drugs. Renal clearance includes glomerular filtration, tubular secretion and reabsorption and each of these processes is subject to different developmental changes. To estimate the renal clearance of drugs in children, a thorough understanding of these developmental changes in the different subprocesses contributing to renal function is needed. Therefore the aim of the research described in this thesis was to characterize the developmental changes in renal function over the entire pediatric age range. To this end, a system-based pharmacology approach was applied implicating that within the models for the different subprocesses contributing to renal function a distinction was made between system-specific and drug-specific properties. The transition to a more system-based pharmacology approach and the combination of different strategies (extrapolation to other drugs, adult data or non-clinical data) will result in an approach focusing on the underlying system instead of focusing on the drugs and may facilitate development of pharmacokinetic models and evidence-based dosing regimens in the pediatric population. Show less
Bijleveld, Y.; Haan, T. de; Toersche, J.; Jorjani, S.; Lee, J. van der; Groenendaal, F.; ... ; Mathot, R. 2014
Accurate and precise bilirubin and albumin measurements are essential for proper management of jaundiced neonates. Data hereon are lacking for Dutch laboratories. We aimed to determine variability... Show moreAccurate and precise bilirubin and albumin measurements are essential for proper management of jaundiced neonates. Data hereon are lacking for Dutch laboratories. We aimed to determine variability of measurements of bilirubin and albumin concentrations typical for (preterm) neonates. Aqueous, human serum albumin-based samples with different concentrations of bilirubin (100, 200, 300, 400, and 500 and 30 g/L) were sent to laboratories of all Dutch neonatal intensive care units ( of the specimens were measured using locally available routine analytical methods. The mean, standard deviation, and coefficients of variations (CV) were calculated per sample. Bilirubin concentrations were underestimated in the absence of albumin (maximal CV 26.0%). When the albumin concentration was 10 or 20 g/L, the bilirubin concentrations of the samples were overestimated (maximal CV 14.1% and 9.2%, respectively). Variability increased with higher weighed-in bilirubin concentrations. Measured albumin levels were ~10% lower than albumin levels of manufactured samples. Bilirubin concentration did not influence albumin measurements. The maximal CV was 6.8%. In conclusion, interlaboratory variability of bilirubin and albumin measurements is high. Recalibration and introduction of a specific quality assessment scheme for neonatal samples is recommended to ensure exchangeability of bilirubin and albumin measurements among laboratories and to control the observed large variability.μmol/L) and albumin (0, 10, 15, 20, 25,n=10). Bilirubin and albumin recoveries Show less
Nowadays many advanced MR imaging techniques are available for detection of hypoxic-ischemic brain injury in young infants. In tertiary referral centres and large children__s hospitals, these... Show moreNowadays many advanced MR imaging techniques are available for detection of hypoxic-ischemic brain injury in young infants. In tertiary referral centres and large children__s hospitals, these techniques are used on a regular basis. However, a considerable proportion of young infants with hypoxic-ischemic brain injury are imaged in primary and secondary care centres where experience with these advanced techniques is limited. Consequently, cranial ultrasonography and the conventional MR imaging techniques, such as T1- and T2-weighted imaging remain the mainstay of neonatal neuroimaging today. The purpose of this thesis was to study diagnostic and predictive MR imaging features of hypoxic-ischemic brain injury in young infants. We focused on T1-, T2-, and diffusion-weighted imaging, since these are applied on a large scale in primary and secondary centres. It may be anticipated that in the future, the use of these techniques will increase as experience with these techniques increases and access to MR imaging machines becomes more widespread. To identify all cases of neonatal hypoxic-ischemic brain injury and for optimal outcome prediction, a combination of diagnostic modalities is mandatory. For the diagnosis and outcome prediction of hypoxic-ischemic brain injury in young infants, clinical assessment, neuroimaging (cranial ultrasonography and MR imaging), and EEG are complementary. Show less
