L S de Vries

University Medical Center Utrecht, Utrecht, Utrecht, Netherlands

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Publications (446)1191.9 Total impact

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    ABSTRACT: Germinal matrix-intraventricular haemorrhage (GMH-IVH) remains a serious problem in the very and extremely preterm infant. This article reviews current methods of diagnosis, treatment and neurodevelopmental outcome in preterm infants with low-grade and severe GMH-IVH. We conclude that there is still no consensus on timing of intervention and treatment of infants with GMH-IVH, whether or not complicated by post-haemorrhagic ventricular dilatation. The discrepancies between the studies underline the need for international collaboration to define the optimal strategy for these infants. © 2014 S. Karger AG, Basel.
    Neonatology 08/2014; 106(4):296-303. · 2.57 Impact Factor
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    ABSTRACT: Hyperperfusion may be related to outcome in neonates with hypoxic-ischemic encephalopathy (HIE). The purpose of this study was to evaluate whether arterial spin labelling (ASL) perfusion is associated with outcome in neonates with HIE and to compare the predictive value of ASL MRI to known MRI predictive markers.
    European radiology. 08/2014;
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    ABSTRACT: The human connectome is the result of an elaborate developmental trajectory. Acquiring diffusion-weighted imaging and resting-state fMRI, we studied connectome formation during the preterm phase of macroscopic connectome genesis. In total, 27 neonates were scanned at week 30 and/or week 40 gestational age (GA). Examining the architecture of the neonatal anatomical brain network revealed a clear presence of a small-world modular organization before term birth. Analysis of neonatal functional connectivity (FC) showed the early formation of resting-state networks, suggesting that functional networks are present in the preterm brain, albeit being in an immature state. Moreover, structural and FC patterns of the neonatal brain network showed strong overlap with connectome architecture of the adult brain (85 and 81%, respectively). Analysis of brain development between week 30 and week 40 GA revealed clear developmental effects in neonatal connectome architecture, including a significant increase in white matter microstructure (P < 0.01), small-world topology (P < 0.01) and interhemispheric FC (P < 0.01). Computational analysis further showed that developmental changes involved an increase in integration capacity of the connectivity network as a whole. Taken together, we conclude that hallmark organizational structures of the human connectome are present before term birth and subject to early development.
    Cerebral Cortex 05/2014; · 8.31 Impact Factor
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    ABSTRACT: Cerebral developmental venous anomaly (DVA) is considered a benign anatomical variant of parenchymal venous drainage; it is the most common vascular malformation seen in the adult brain. Despite its assumed congenital origin, little is known about DVA in the neonatal brain. We report here the first cohort study of 14 neonates with DVA. Fourteen infants (seven preterm) with DVA diagnosed neonatally using cranial ultrasound (cUS) and magnetic resonance imaging (MRI) from three tertiary neonatal units over 14 years are reviewed. DVA was first detected on cUS in 6 and on MRI in 8 of the 14 infants. The cUS appearances of DVA showed a focal fairly uniform area of increased echogenicity, often (86 %) adjacent to the lateral ventricle and located in the frontal lobe (58 %). Blood flow in the dilated collector vein detected by Doppler ultrasound (US) varied between cases (venous flow pattern in ten and arterialized in four). The appearance on conventional MRI was similar to findings in adults. Serial imaging showed a fairly constant appearance to the DVAs in some cases while others varied considerably regarding anatomical extent and flow velocity. This case series underlines that a neonatal diagnosis of DVA is possible with carefully performed cUS and MRI and that DVA tends to be an incidental finding with a diverse spectrum of imaging appearances. Serial imaging suggests that some DVAs undergo dynamic changes during the neonatal period and early infancy; this may contribute to why diagnosis is rare at this age.
    Neuroradiology 04/2014; · 2.70 Impact Factor
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    ABSTRACT: Brain oxygen consumption reflects neuronal activity and can therefore be used to investigate brain development or neuronal injury in neonates. In this paper we present the first results of a non-invasive MRI method to evaluate whole brain oxygen consumption in neonates. For this study 51 neonates were included. The T1 and T2 of blood in the sagittal sinus were fitted using the 'T2 prepared tissue relaxation inversion recovery' pulse sequence (T2-TRIR). From the T1 and the T2 of blood, the venous oxygenation and the oxygen extraction fraction (OEF) were calculated. The cerebral metabolic rate of oxygen (CMRO2) was the resultant of the venous oxygenation and arterial spin labeling whole brain cerebral blood flow (CBF) measurements. Venous oxygenation was 59±14% (mean±sd), OEF was 40±14%, CBF was 14±5ml/100g/min and CMRO2 was 30±12μmol/100g/min. The OEF in preterms at term-equivalent age was higher than in the preterms and in the infants with hypoxic-ischemic encephalopathy (p <0.01). The OEF, CBF and CMRO2 increased (p<0.01, <0.05 and <0.01) with postnatal age. We presented an MRI technique to evaluate whole-brain oxygen consumption in neonates non-invasively. The measured values are in line with reference values found by invasive measurements techniques. Preterms and infants with HIE demonstrated significant lower oxygen extraction fraction than the preterms at term-equivalent age. This could be due to decreased neuronal activity as a reflection of brain development or as a result of tissue damage, increased cerebral blood flow due to immature or impaired autoregulation, or could be caused by differences in postnatal age.
    NeuroImage 03/2014; · 6.25 Impact Factor
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    ABSTRACT: White matter injury and hemorrhage are common findings in extremely preterm infants. Large hemorrhages and extensive cystic lesions are identified with cranial ultrasound. MRI, which is more sensitive, is especially useful in the identification of small intraventricular hemorrhage; cerebellar hemorrhage; punctate lesion in the white matter and cerebellum; and diffuse, noncystic white matter injury. Imaging sequences such as diffusion-weighted, diffusion tensor, and susceptibility weighted imaging may improve recognition and prediction of outcome. These techniques improve understanding of the underlying pathophysiology of white matter injury and its effects on brain development and neurodevelopmental outcome.
    Clinics in perinatology 03/2014; 41(1):69-82. · 1.54 Impact Factor
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    ABSTRACT: The aim of the study was to compare clinical and neuroimaging characteristics and neurodevelopmental outcome in preterm infants with a periventricular haemorrhagic infarction (PVHI) located in the temporal or frontal periventricular white matter. The study was a retrospective hospital-based study of preterm infants with a frontal PVHI (n=21; 11 males, 10 females; mean birthweight 1527g; mean gestational age 30.3wks) or temporal PVHI (n=13; five males, eight females; mean birthweight 1205g; mean gestational age 30.2wks) admitted to the neonatal intensive care unit between 1990 and 2012. The clinical course, results of neuroimaging studies, and neurodevelopmental outcomes of preterm infants with a gestational age less than 34 weeks with a confirmed PVHI on early cranial ultrasonography and/or magnetic resonance imaging were reviewed. For assessment of neurodevelopmental outcome we used the Griffiths Mental Development Scales, the Movement Assessment Battery for Children, the Gross Motor Function Classification System, the Wechsler Preschool and Primary Scale of Intelligence, the Child Behavior Checklist, and ophthalmological assessment. An unfavourable neurodevelopmental outcome was defined as moderately or severely atypical neurological examination during the last visit: presence of cerebral palsy, epilepsy, a hearing or visual impairment, and/or atypical cognitive development (Griffiths Mental Development Scales developmental quotient or Wechsler Preschool and Primary Scale of Intelligence <85). Unfavourable outcome was observed in 12 out of 13 children with a temporal PVHI compared with six out of 21 children with a frontal PVHI (p=0.002). Only one of the included infants with a PVHI in the temporal white matter developed cerebral palsy, which was due to a parietal PVHI in the contralateral hemisphere. Cognitive impairment was noted in seven infants with a frontal PVHI and five with a temporal PVHI. There were more infants with a temporal PVHI who developed visual impairment (n=5) or behavioural problems (n=7) compared with those with a frontal PVHI (visual impairment (n=2), behavioural problems (n=3). PVHI located in the temporal or frontal lobe is almost invariably related to a typical motor outcome, but carries a risk of cognitive, behavioural, and visual problems, especially in infants with a PVHI located in the temporal lobe.
    Developmental Medicine & Child Neurology 02/2014; · 2.68 Impact Factor
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    ABSTRACT: We report on 6 infants who underwent elective surgery and developed postoperative encephalopathy, which had features most consistent with intraoperative cerebral hypoperfusion. All infants were <48 weeks' postmenstrual age and underwent procedures lasting 120 to 185 minutes. Intraoperative records revealed that most of the measured systolic blood pressure (SBP) values were <60 mm Hg (the threshold for hypotension in awake infants according to the Pediatric Advanced Life Support guidelines) but that only 11% of the measured SBP values were <1 SD of the mean definition of hypotension (<45 mm Hg) as reported in a survey of members of the Society for Pediatric Anesthesia in 2009. Four infants also exhibited prolonged periods of mild hypocapnia (<35 mm Hg). One infant did not receive intraoperative dextrose. All infants developed new-onset seizures within 25 hours of administration of the anesthetic, with a predominant cerebral pathology of supratentorial watershed infarction in the border zone between the anterior, middle, and posterior cerebral arteries. Follow-up of these infants found that 1 died, 1 had profound developmental delays, 1 had minor motor delays, 2 were normal, and 1 was lost to follow-up. Although the precise cause of encephalopathy cannot be determined, it is important to consider the role that SBP hypotension (as well as hypoglycemia, hyperthermia, hyperoxia, and hypocapnia) plays during general anesthesia in young infants in the development of infantile postoperative encephalopathy. Our observations highlight the lack of evidence-based recommendations for the lower limits of adequate SBP and end-tidal carbon dioxide in anesthetized infants.
    PEDIATRICS 02/2014; · 4.47 Impact Factor
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    ABSTRACT: To compare neurodevelopmental outcome, mean arterial blood pressure (MABP), and regional cerebral oxygenation (rSco2) between preterm neonates treated for hypotension and controls. Preterm neonates (N = 66) with a gestational age (GA) ≤32 weeks, without a patent ductus arteriosus, treated for hypotension (dopamine ≥5 μg/kg/min) were included. Neonates were matched to controls for GA, birth weight, sex, and year of birth. The rSco2 was determined by using near-infrared spectroscopy. Monitoring of MABP, rSco2, and arterial saturation was started at admission and continued for at least 72 hours. Neurodevelopmental outcome was assessed at 18 and 24 months' corrected age by using the Griffiths Mental Development Scales or the Bayley Scales of Infant and Toddler Development, Third Edition. Infants treated for hypotension spent more time with an MABP less than GA (median 9% vs 0%, P < .001) and time with an MABP/rSco2 correlation >0.5 (27% vs 17%, P < .001). Time spent with an rSco2 <50% and neurodevelopmental outcome at 18 and 24 months' corrected age were not significantly different between infants treated for hypotension and controls. The 26 neonates with an rSco2 <50% for >10% of time had a lower neurodevelopmental outcome at 18 months (median 99 vs 104, P = .02). An MABP less than GA (in weeks) was not associated with lower rSco2 or with lower neurodevelopmental outcome scores. However, regardless of MABP, low rSco2 was associated with lower neurodevelopmental outcome scores. Perfusion/oxygenation variables could be of additional value in neonatal intensive care.
    The Journal of pediatrics 01/2014; · 4.02 Impact Factor
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    ABSTRACT: Neonatal stroke, including perinatal arterial ischaemic stroke and cerebral sinovenous thrombosis, remains a serious problem in the neonate. This paper reviews the current evidence on epidemiology, pathogenesis, diagnostics and therapeutic options. Although our understanding of the underlying mechanisms and possible risk factors has improved, little progress has been made towards therapeutic options. Considering the high incidence of neurological sequelae, the need for therapeutic options is high and should be the focus of future research. This article is protected by copyright. All rights reserved.
    Acta Paediatrica 01/2014; · 1.97 Impact Factor
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    ABSTRACT: 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.
    Journal of Clinical Virology. 01/2014;
  • Gerda van Wezel-Meijler, Linda S de Vries
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    ABSTRACT: Cranial ultrasonography (cUS) is a reliable tool to detect the most frequently occurring congenital and acquired brain abnormalities in full-term and preterm neonates. Appropriate equipment, including a dedicated ultrasound machine and appropriately sized transducers with special settings for cUS of the newborn brain, and ample experience of the ultrasonographist are required to obtain optimal image quality. When, in addition, supplemental acoustic windows are used whenever indicated and cUS imaging is performed from admission throughout the neonatal period, the majority of the lesions will be diagnosed with information on timing and evolution of brain injury and on ongoing brain maturation. For exact determination of site and extent of lesions, for detection of lesions that (largely or partially) remain beyond the scope of cUS and for depiction of myelination, a single, well timed MRI examination is invaluable in many high risk neonates. However, as cUS enables bedside, serial imaging it should be used as the primary brain imaging modality in high risk neonates.
    Current Pediatric Reviews 01/2014; 10(1).
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    ABSTRACT: The longitudinal relaxation time of blood (T 1b) is influenced by haematocrit (Hct) which is known to vary in neonates. The purpose of this study was threefold: to obtain T 1b values in neonates, to investigate how the T 1b influences quantitative arterial spin labelling (ASL), and to evaluate if known relationships between T 1b and haematocrit (Hct) hold true when Hct is measured by means of a point-of-care device. One hundred and four neonates with 120 MR scan sessions (3 T) were included. The T 1b was obtained from a T 1 inversion recovery sequence. T 1b-induced changes in ASL cerebral blood flow estimates were evaluated. The Hct was obtained by means of a point-of-care device. Linear regression analysis was used to investigate the relation between Hct and MRI-derived R1 of blood (the inverse of the T 1b). Mean T 1b was 1.85 s (sd 0.2 s). The mean T 1b in preterm neonates was 1.77 s, 1.89 s in preterm neonates scanned at term-equivalent age (TEA) and 1.81 s in diseased neonates. The T 1b in the TEA was significantly different from the T 1b in the preterm (p < 0.05). The change in perfusion induced by the T 1b was -11% (sd 9.1%, p < 0.001). The relation between arterial-drawn Hct and R1b was R1b = 0.80 × Hct + 0.22, which falls within the confidence interval of the previously established relationships, whereas capillary-drawn Hct did not correlate with R1b. We demonstrated a wide variability of the T 1b in neonates and the implications it could have in methods relying on the actual T 1b as for instance ASL. It was concluded that arterial-drawn Hct values obtained from a point-of-care device can be used to infer the T 1b whereas our data did not support the use of capillary-drawn Hct for T 1b correction.
    NeuroImage. Clinical. 01/2014; 4:517-25.
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    ABSTRACT: Increased levels of end-tidal carbon monoxide (ETCOc) in preterm infants during the first day of life are associated with oxidative stress, inflammatory processes and adverse neurodevelopmental outcome at 2 years of age. Therefore, we hypothesized that early ETCOc levels may also be associated with impaired growth of unmyelinated cerebral white matter. From a cohort of 156 extremely and very preterm infants in which ETCOc was determined within 24 h after birth, in 36 infants 3D-MRI was performed at term-equivalent age to assess cerebral tissue volumes of important brain regions. Linear regression analysis between cerebral ventricular volume, unmyelinated white matter/total brain volume-, and cortical grey matter/total brain volume-ratio and ETCOc showed a positive, negative and positive correlation, respectively. Multivariable analyses showed that solely ETCOc was positively related to cerebral ventricular volume and cortical grey matter/total brain volume ratio, and that solely ETCOc was inversely related to the unmyelinated white matter/total brain volume ratio, suggesting that increased levels of ETCOc, associated with oxidative stress and inflammation, were related with impaired growth of unmyelinated white matter. Increased values of ETCOc, measured within the first 24 hours of life may be indicative of oxidative stress and inflammation in the immediate perinatal period, resulting in impaired growth of the vulnerable unmyelinated white matter of the preterm brain.
    PLoS ONE 01/2014; 9(3):e89061. · 3.53 Impact Factor
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    ABSTRACT: To perform a feasibility and safety study with recombinant human erythropoietin (rhEPO) in neonates with perinatal arterial ischemic stroke. Neonates with a magnetic resonance imaging-confirmed perinatal arterial ischemic stroke (n = 21) were treated with 1000 IU/kg rhEPO immediately after diagnosis and at 24 and 48 hours after the first dose. Repeat magnetic resonance imaging was performed when the patients were 3 months of age. Coagulation and hematologic variables (red blood cells, white blood cells, platelet counts) were performed in the first week after initiation of treatment. We also compared 10 patients who were treated with rhEPO with 10 historic infants with perinatal arterial ischemic stroke matched for the involved arterial branch to investigate whether rhEPO reduces the residual size of the infarction and subsequent brain growth between first and second scan. Seizures were a first symptom in 20 of 21 neonates. Heart rate, blood pressure, and coagulation function were in the normal range, as were red blood cells, white blood cells, and platelet counts. In a subgroup of 10 rhEPO-treated neonates, no differences were detected in residual infarction volumes or neurodevelopmental outcome compared with their historical nontreated counterparts. rhEPO in neonates with perinatal arterial ischemic stroke had no adverse effects on red blood cells, white blood cells, platelets counts, or coagulation. rhEPO, 3000 IU/kg in total, given during a 3-day period, appears to be a safe therapy. The beneficial effects remains to be demonstrated in a larger, randomized, double-blind, placebo-controlled trial.
    The Journal of pediatrics 12/2013; · 4.02 Impact Factor
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    ABSTRACT: Complex neonatal cardiac surgery is associated with cerebral injury. Especially aortic arch repair, requiring either deep hypothermic circulatory arrest(DHCA) or antegrade cerebral perfusion(ACP), entail a high risk of peri-operative injury. It is unknown, whether ACP results in less cerebral injury than DHCA. Thirty-seven neonates with an aortic arch obstruction presenting for uni- or biventricular repair, were randomized to either DHCA or ACP. Pre-operatively and one week after surgery, magnetic resonance imaging(MRI) was performed in 36 patients(one patient died during hospital stay). The presence of new postoperative cerebral injury was scored, and results were entered into a sequential analysis, which allows for immediate data analysis. After the 36th patient, it was clear that there was no difference between DHCA and ACP in terms of new cerebral injury. Pre-operatively, 50% of patients had evidence of cerebral injury. Postoperatively, 14/18(78%) of DHCA patients had new injury, versus 13/18(72%) of ACP(p=0.66). White matter injury(WMI) was the most common type of injury in both groups, but central infarctions occurred exclusively after ACP(0 vs. 6/18[33%];p=0.02). Early motor and cognitive outcome at 24 months was assessed and was similar between groups(p=0.28 and p=0.25,respectively). Additional analysis revealed lower postoperative arterial pCO2 as risk factor for new WMI(p=0.04). In this group of neonates undergoing complex cardiac surgery, we were unable to demonstrate a difference in the incidence of peri-operative cerebral injury after ACP compared to DHCA. Both techniques resulted in a high incidence of new WMI, with central infarctions occurring exclusively following ACP.
    Circulation 10/2013; · 15.20 Impact Factor
  • Paediatric Drugs 10/2013; · 1.72 Impact Factor
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    ABSTRACT: Abstract Objective: To describe our experience with a cohort of 295 infants with progressive ventricular dilatation occurring in the antenatal or neonatal period. Methods: A search was performed in our cranial ultrasound database. All records and images of infants in whom an imaging diagnosis of progressive ventricular dilatation had been made were retrieved. In addition, modes of treatment were analysed. Results: Between February 1991 and March 2012, 295 neonates were admitted to our level 3 neonatal intensive care unit (NICU), and developed progressive ventricular dilatation for which they required intervention. In the majority of these infants, progressive ventricular dilatation developed following IVH grade III or IV (240/295; 81%) of whom 214/240 (89%) were preterms. Temporary treatment with lumbar punctures and punctures from ventricular reservoirs was sufficient for the majority of the preterms. A ventricular reservoir was inserted in 216/295 infants (73%). The overall infection rate was low (6%). A ventriculoperitoneal shunt (VP shunt) was inserted in 32% of the whole cohort, revision within 3 months was necessary in 20%, and shunt-related infection occurred in 12%. Conclusions: This large, single-centre cohort study reports the management of progressive ventricular dilatation in newborn infants. We have shown that with our approach, complications stay within acceptable limits.
    The journal of maternal-fetal & neonatal medicine: the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians 08/2013; · 1.36 Impact Factor

Publication Stats

6k Citations
1,191.90 Total Impact Points


  • 1992–2014
    • University Medical Center Utrecht
      • • Department of Neonatology
      • • Department of Obstetrics
      • • Department of Surgery
      Utrecht, Utrecht, Netherlands
  • 2013
    • University of Helsinki
      • Department of Clinical Neurophysiology
      Helsinki, Province of Southern Finland, Finland
  • 1992–2013
    • Canisius-Wilhelmina Ziekenhuis
      Nymegen, Gelderland, Netherlands
  • 1999–2012
    • Utrecht University
      • • Department of Neonatology
      • • Langeveld Institute for the Study of Education and Development in Childhood and Adolescence
      Utrecht, Utrecht, Netherlands
  • 2010
    • University of Bristol
      Bristol, England, United Kingdom
    • Erasmus MC
      • Department of Bioinformatics
      Rotterdam, South Holland, Netherlands
  • 2008
    • VieCuri Medical Center Noord-Limburg
      Venloo, Limburg, Netherlands
  • 2005–2007
    • Imperial College London
      • Section of Paediatrics
      Londinium, England, United Kingdom
  • 1995–2001
    • Diakonessen Hospital Utrecht
      Utrecht, Utrecht, Netherlands
  • 1998–1999
    • University of Amsterdam
      • Faculty of Medicine AMC
      Amsterdam, North Holland, Netherlands
  • 1997
    • Georgetown University
      Washington, Washington, D.C., United States
  • 1996
    • University of London
      • Institute of Education
      London, ENG, United Kingdom
  • 1991
    • Ealing, Hammersmith & West London College
      Londinium, England, United Kingdom
  • 1990
    • University of Leuven
      Louvain, Flanders, Belgium