Linda S de Vries

Universitair Medisch Centrum Utrecht, Utrecht, Provincie Utrecht, Netherlands

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Publications (99)368.02 Total impact

  • Article: Neonatal neuroimaging predicts recruitment of contralesional corticospinal tracts following perinatal brain injury.
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    ABSTRACT: AIM: Unilateral perinatal brain injury may result in recruitment of ipsilateral projections originating in the unaffected hemisphere and development of unilateral spastic cerebral palsy (USCP). The aim of this study was to assess the predictive value of neonatal neuroimaging following perinatal brain injury for recruitment of ipsilateral corticospinal tracts. METHOD: Neonatal magnetic resonance imaging (MRI) and cranial ultrasound scans of 37 children (20 males, 17 females; median [range] gestational age 36 wks(+4) [26(+6) -42wks(+5) ] and birthweight 2312 g ([770-5230g]) with unilateral perinatal arterial ischaemic stroke (n=23) or periventricular haemorrhagic infarction (n=14) were reviewed and scored for involvement of the corticospinal trajectory. Hand function was assessed using the Assisting Hand Assessment (AHA) and transcranial magnetic stimulation (TMS) was performed (age range 7y 4mo-18y and 7mo) to determine the type of cortical motor organization (normal, mixed or ipsilateral). Neuroimaging scores were used to predict TMS patterns. RESULTS: Eighteen children developed USCP with ipsilateral corticospinal tract projections in 13 children (eight mixed, five ipsilateral). AHA scores decreased with increased ipsilateral projections. Asymmetry of the corticospinal tracts seen on neonatal MRI was predictive of development of USCP and recruitment of ipsilateral tracts (positive and negative predictive value of 73% and 91%). INTERPRETATION: Neonatal neuroimaging can predict recruitment of ipsilateral corticospinal tracts. Early knowledge of the expected pattern of cortical motor organization will allow early identification of children eligible for early therapy.
    Developmental Medicine & Child Neurology 05/2013; · 2.92 Impact Factor
  • Article: Diffusion-weighted imaging changes in cerebral watershed distribution following neonatal encephalopathy are not invariably associated with an adverse outcome.
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    ABSTRACT: AIM: Patterns of injury in term-born infants with neonatal encephalopathy following hypoxia-ischaemia are seen earlier and are more conspicuous on diffusion-weighted magnetic resonance imaging (DW-MRI) than on conventional imaging. Although the prognostic value of DW-MRI in infants with basal ganglia and thalamic damage has been established, data in infants in whom there is extensive injury in a watershed distribution are limited. The aim of this study was to assess cognitive and functional motor outcome in a cohort of infants with changes in a predominantly watershed distribution injury on neonatal cerebral MRI, including DWI. METHOD: DW-MRI findings in infants with neonatal encephalopathy following hypoxia-ischaemia were evaluated retrospectively. Twenty-two infants in whom DWI changes exhibited a predominantly watershed distribution were enrolled in the study (10 males, 12 females; mean birthweight 3337g, 2830-3900g; mean gestational age 40.5wks, 37.9-42.1wks). Follow-up MRI data at the age of 3 months (n=15) and over the age of 18 months (n=7) were analysed. In survivors, neurodevelopmental outcome was assessed with the Griffiths Mental Development Scales at the age of at least 18 months. Amplitude-integrated electroencephalography was used to score background patterns and the occurrence of epileptiform activity. RESULTS: DW-MRI revealed abnormalities that were bilateral in all infants and symmetrical in 10. The posterior regions were more severely affected in five infants and the anterior regions in three. Watershed injury occurred in isolation in 10 out of 22 infants and was associated with involvement of the basal ganglia and thalami in the other 12, of whom seven died. Cystic evolution, seen on MRI at age 3 months, occurred in three of the 15 surviving infants. Neurodevelopmental assessment of the surviving infants was performed at a median age of 35 months (range 18-48mo). Of the five survivors with basal ganglia and thalamic involvement, two developed cerebral palsy, one had a developmental quotient of less than 85, and two had a normal outcome. Of the 10 infants with isolated watershed injury, nine had an early normal motor and cognitive outcome. In all infants with a favourable outcome, background recovery was seen on amplitude integrated EEG within 48 hours after birth. CONCLUSION: Extensive DWI changes in a watershed distribution in term-born neonates are not invariably associated with adverse sequelae, even in the presence of cystic evolution. Associated lesions of the basal ganglia and thalami are a better predictor of adverse sequelae than the extent and severity of the watershed abnormalities seen on DW-MRI.
    Developmental Medicine & Child Neurology 04/2013; · 2.92 Impact Factor
  • Article: Neonatal thalamic hemorrhage is strongly associated with electrical status epilepticus in slow wave sleep.
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    ABSTRACT: PURPOSE: Thalamic hemorrhage has been associated with neonatal cerebral sinovenous thrombosis (CSVT), especially when the straight sinus is involved, and often presents with neonatal seizures. Early thalamic injury has previously been shown to predispose to epilepsy and electrical status epilepticus in slow wave sleep (ESES). The objective of this study was to assess the prevalence of sleep-induced epileptic electroencephalography (EEG) abnormalities and postneonatal epilepsy after neonatal thalamic hemorrhage associated with CSVT, in the absence of more widespread cerebral damage. METHODS: Between 2003 and 2008 15 neonates were diagnosed with a thalamic hemorrhage due to suspected or proven CSVT. Neurodevelopment and the history of seizures were assessed at follow-up in the outpatient clinic in all 14 survivors (age 2-9 years). Whole-night or sleep-deprived EEG recordings were obtained to assess the prevalence of interictal epileptiform activity (EA) and calculate a sleep-induced spike and wave index (SWI). KEY FINDINGS: Three children were diagnosed with classic ESES (SWI >85%). Two children had ESES spectrum disorder (SWI between 50% and 85%), and in two children significant sleep-induced epileptiform activity (SIEA) was noted (SWI between 25% and 50%). Two other children were diagnosed with focal epilepsy, in the absence of sleep-induced epileptiform EEG abnormalities. Five children (age 2-7 years) had normal EEG recordings at follow-up. Deficits in neurodevelopment were seen significantly more often in children with ESES, ESES spectrum, or SIEA. SIGNIFICANCE: Neonates with thalamic hemorrhage associated with straight sinus thrombosis, without evidence of more widespread cerebral damage, are at high risk of developing ESES (spectrum) disorder (35%), SIEA (14%), or focal epilepsy (14%). Electrographic abnormalities may already be present prior to recognition of cognitive deficits. Early diagnosis may guide parents and caregivers, and subsequent treatment may improve neurodevelopmental outcome. Routine annual sleep EEG recordings in children with neonatal thalamic injury following CSVT may improve recognition of ESES.
    Epilepsia 03/2013; · 3.96 Impact Factor
  • Article: Quantification of white matter injury following neonatal stroke with serial DTI.
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    ABSTRACT: Background:Diffusion tensor imaging (DTI) can be used to predict outcome following perinatal arterial ischemic stroke (PAIS), though little is known about white matter changes over time.Methods:Infants with PAIS were serially scanned in the neonatal period (n=15), at 3 months (n=16), and at 24 months (n=8). Fractional anisotropy (FA) values in five regions of interest (anterior and posterior limb of the internal capsule, corpus callosum, optic radiation and posterior thalamic radiation) were obtained and compared with FA values of healthy controls and neurodevelopmental outcome.Results:In the neonatal period, no differences in FA were found. At three months, the six infants who ultimately developed motor deficits showed lower FA-values in all affected regions. Four infants developed a visual field defect and showed lower FA values in the affected optic radiation at three months (0.22 vs 0.29, p=0.03). Finally, a correlation between FA-values of the corpus callosum at three months and the Griffiths developmental quotients was found (r =.66 p=0.03). At 24 months a similar pattern was observed.Conclusion:Neonatal FA measurements may underestimate the extent of injury following PAIS. FA measurements at three months could be considered a more reliable predictor of neurodevelopmental outcome and correlate with DTI findings at 24 months.Pediatric Research (2013); doi:10.1038/pr.2013.45.
    Pediatric Research 03/2013; · 2.70 Impact Factor
  • Article: Posthaemorrhagic ventricular dilatation: when should we intervene?
    Archives of Disease in Childhood - Fetal and Neonatal Edition 02/2013; · 3.05 Impact Factor
  • Article: Treatment of neonatal seizures.
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    ABSTRACT: Seizures occur more often during the neonatal period than at any other period of life. Precise incidence is difficult to delineate and depends on study population and criteria used for diagnosis of seizures. Controversy exists as to whether neonatal seizures themselves cause damage to the developing brain, or if the damage is primarily due to the underlying cause of the seizures. As a result of this controversy there is an ongoing discussion as to whether all seizures (both clinical and subclinical) should be treated. When (sub)clinical seizures are treated, there is no consensus about the most appropriate treatment for neonatal seizures and how to assess the efficacy of treatment. Current therapeutic options to treat neonatal seizures (i.e. primarily first generation antiepileptics) are relatively ineffective. There is an urgent need for prospective, randomized, controlled trials for efficacy and safety of these second-generation antiepileptic drugs in neonates. The aim of this review is to survey current knowledge regarding treatment of neonatal seizures in both term and preterm infants.
    Seminars in Fetal and Neonatal Medicine 02/2013; · 3.91 Impact Factor
  • Article: Neonatal posterior cerebral artery stroke: clinical presentation, MRI findings, and outcome.
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    ABSTRACT: AIM: To report the clinical presentation, magnetic resonance imaging (MRI) findings, and follow-up data of newborn infants with perinatal arterial ischemic stroke in the territory of the posterior cerebral artery (PCA). METHOD: Data on 18 newborn infants from three neonatal intensive care units (11 males, seven females) with an MRI-confirmed PCA stroke were analysed and reported. Infants were born at a mean gestational age of 38.7 weeks (SD 3.4) with a mean birthweight of 3244g (SD 850). RESULTS: Fourteen infants presented with clinical seizures. Five of these had associated hypoxic-ischemic encephalopathy, four had hypoglycaemia, and five had neither hypoxic-ischemic encephalopathy nor hypoglycaemia. Subclinical seizures were present in one infant with hypoxic-ischemic encephalopathy and one with meningitis. One preterm infant presented with apnoeas and one had hypoxic-ischemic encephalopathy without seizures. Neurodevelopmental follow-up of 17 children at a median age of 36 months (SD 28, range 12-120mo) showed five with a global delay. Two children with additional injury developed postneonatal epilepsy and one child with extensive injury developed hemiplegia. A visual field defect was observed in nine children (six hemianopia, three quadrantanopia). In the 11 children with a second MRI at 3 months, the asymmetry of the optic radiation correlated with the development of a visual field deficit. INTERPRETATION: Outcome after PCA stroke is fairly good, depending on additional brain injury. Follow-up is required, as subsequent visual field defects are frequently observed. Further research will be needed to clarify the role of hypoglycaemia in perinatal arterial ischemic stroke.
    Developmental Medicine & Child Neurology 01/2013; · 2.92 Impact Factor
  • Article: Clinical Management of Seizures in Newborns : Diagnosis and Treatment.
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    ABSTRACT: Neonatal seizures can be classified as tonic, clonic, myoclonic, and subtle. A clinical diagnosis is not easy as seizures are usually subtle in neonates. In the majority of newborn infants seizures are subclinical. On the other hand, not all abnormal movements identified by clinicians as clinical seizures are accompanied by electroencephalographic seizure discharges in the EEG. Precise incidence is difficult to delineate and depends on study population and criteria used for diagnosis of seizures. Controversy exists as to whether neonatal seizures themselves cause damage to the developing brain, or if the damage is primarily due to the underlying cause of the seizures. As a result of this controversy there is ongoing discussion whether all seizures (both clinical and subclinical) should be treated. In addition, when (sub)clinical seizures are treated, there is no consensus about the most appropriate treatment for neonatal seizures and how to assess the efficacy of treatment.Current therapeutic options to treat neonatal seizures (i.e. primarily first-generation antiepileptic drugs [AEDs]) are relatively ineffective. In practice, phenobarbital still remains the drug of first choice for EEG confirmed or suspected seizures. Benzodiazepines are also used in (phenobarbital) refractory cases. Several (small) studies indicate that lidocaine is an effective drug for refractory seizures as second- or third-line treatment. Although data are scarce, some AEDs with a wide acceptance in adult and pediatric neurology practice are being used to treat neonatal seizures (i.e. second-generation AEDs). These drugs are chemically different from all first-generation AEDs and they have an effect on other pathways so they provide new pharmacological targets for controlling seizures in newborns. Levetiracetam, topiramate, felbamate, bumetanide, lamotrigine and vigabatrin are examples of these second-generation AEDs.There is an urgent need for prospective, randomized, controlled trials to assess the efficacy and safety of these second-generation AEDs in neonates.The aim of this review is to provide an overview of the current knowledge of diagnosis, the effect on brain injury, and the treatment of neonatal seizures.
    Paediatric Drugs 01/2013; · 1.79 Impact Factor
  • Article: Anticonvulsant treatment of asphyxiated newborns under hypothermia with lidocaine: efficacy, safety and dosing.
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    ABSTRACT: BACKGROUND: Lidocaine is an antiarrythmicum used as an anticonvulsant for neonatal seizures, also during therpeutic hypothermia following (perinatal) asphyxia. Hypothermia may affect the efficacy, safety and dosing of lidocaine in these patients. OBJECTIVE: To study the efficacy and safety of lidocaine in newborns with perinatal asphyxia during moderate hypothermia, and to develop an effective and safe dosing regimen. METHODS: Hypothermic newborns with perinatal asphyxia and lidocaine for seizure control were included. Efficacy was studied using continuous amplitude-integrated electroencephalography. Safety was assessed using continuous cardiac monitoring. An optimal dosing regimen was developed with simulations using data from a pharmacokinetic model. Plasma samples were collected during hypothermia on consecutive mornings. RESULTS: A total of 22 hypothermic and 26 historical normothermic asphyxiated newborns with lidocaine were included. A response of 91% on epileptiform activity on the amplitude-integrated EEG was observed for lidocaine add-on therapy. No relationship between lidocaine or MEGX plasma concentrations and heart frequency could be identified. None of the newborns experienced cardiac arrythmias. Hypothermia reduced lidocaine clearance by 24% compared with normothermia. A novel dosing regimen was developed an initial bolus loading dose of 2 mg/kg, for patients with body weight 2.0-2.5 kg followed by consecutive continuous infusions of 6 mg/kg/h (for 3.5 h), 3 mg/kg/h (for 12 h), 1.5 mg/kg/h (for 12 h), or for patients with bodyweights 2.5-4.5 kg 7 mg/kg/h (for 3.5 h), 3.5 mg/kg/h (for 12 h), 1.75 mg/kg/h (for 12 h), before stopping. CONCLUSIONS: Lidocaine can be assumed to be an effective antiepileptic drug during hypothermia in asphyxiated neonates.
    Archives of Disease in Childhood - Fetal and Neonatal Edition 01/2013; · 3.05 Impact Factor
  • Article: The Course of Apparent Diffusion Coefficient Values following Perinatal Arterial Ischemic Stroke.
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    ABSTRACT: Diffusion weighted MR imaging (DWI) plays an important role in the diagnosis of perinatal arterial ischemic stroke (PAIS) during the acute phase. Its derived apparent diffusion coefficient (ADC) can be used to quantify the diffusion restriction. Aim of the current study was to identify the changes in ADC values in the acute phase following PAIS. A cohort of 36 infants with a confirmed PAIS who were examined once during the first ten days of life was studied. ADC values in the core of the ischemic tissue (iADC) were determined and correlated with postnatal age. ADC ratios (rADC) were calculated by dividing the iADC value by the ADC value of the corresponding area in the contralateral 'healthy' hemisphere. Infants were scanned between days two and ten. A non-linear increase in iADC and rADC values was observed over time and large middle cerebral artery strokes resulted in lower iADC and rADC values. Normalisation of rADC values was observed after day seven. rADC values were lower when compared to previously published rADC values of infants with hypoxic ischemic encephalopathy, suggesting more severe injury. Following PAIS, DWI showed decreased ADC values with a non-linear increase during the first week, and pseudonormalization after day 7, which limits the use of DWI to assess PAIS to the first week. Compared to previous studies, ADC values were lower when compared to infants with hypoxic ischemic encephalopathy, most likely due to more severe injury.
    PLoS ONE 01/2013; 8(2):e56784. · 4.09 Impact Factor
  • Article: Regional changes in brain perfusion during brain maturation measured non-invasively with Arterial Spin Labeling MRI in neonates.
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    ABSTRACT: PURPOSE: The purpose of this study was to evaluate if non-invasive Arterial Spin Labeling MR imaging can be used to assess changes in brain perfusion with age which reflect neonatal brain development. For this purpose regional perfusion values obtained with ASL MR imaging were evaluated as a function of postmenstrual age. MATERIALS AND METHODS: Pulsed ASL imaging was performed in 33 neonates with a postmenstrual age from 30 to 53 weeks. Whole brain cerebral blood flow (wbCBF), CBF in the basal ganglia and thalamus (BGT-CBF), in the occipital cortex (OC-CBF) and the frontal cortex (FC-CBF) were measured. Regional CBF values were expressed quantitatively (in ml/100gmin) and relative as a percentage of the wbCBF. RESULTS: Mean wbCBF increased significantly from 7±2ml/100gmin (mean±sd) at 31±2 weeks postmenstrual age to 12±3ml/100gmin at term-equivalent age (TEA) and 29±9ml/100gmin at 52±1 weeks postmenstrual age. Relative regional CBF was highest in the BGT at all time-points. Relative OC-and FC-CBF increased significantly from 31±2 weeks postmentrual age to TEA. A significant difference in relative BGT-CBF and OC-CBF was shown between infants at 31±2 weeks postmenstrual age and infants scanned at 52±1 weeks postmenstrual age. Relative perfusion in the BGT measured at TEA was significant different compared to 52±1 weeks postmenstrual age. CONCLUSION: In conclusion, regional differences in CBF and changes with postmenstrual age could be detected with ASL in neonates. This suggests that ASL can be used as a non-invasive tool to investigate brain maturation in neonates.
    European journal of radiology 11/2012; · 2.65 Impact Factor
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    Article: Antemortem cranial MRI compared with postmortem histopathologic examination of the brain in term infants with neonatal encephalopathy following perinatal asphyxia.
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    ABSTRACT: AIM: To compare antemortem cranial MRI with postmortem histopathological examination of the brain in full-term infants with neonatal encephalopathy following perinatal asphyxia. PATIENTS AND METHODS: In this retrospective observational cohort study, 23 infants with neonatal encephalopathy who subsequently died, were analysed. Infants underwent antemortem cranial MRI and postmortem histopathological examination of the brain. MRI included T1, T2 and diffusion-weighted sequences. Histopathology included staining with H&E, and monoclonal antibodies to CD68 and HLA-DR. Histological abnormalities were compared with MRI in 10 different brain regions. RESULTS: All neonates underwent cranial MRI within 7 days after birth (median day 3, IQR 2-4 days). Infants died on median day 4 (IQR 2-5 days). Histopathology demonstrated significantly (p=0.0016) more abnormal regions (median 10, IQR 7-10) per patient than did MRI (median 8, IQR 5-9). The number of cases with abnormalities in the thalamus, basal ganglia, posterior limb of the internal capsule (PLIC), cerebral cortex and cerebellum were not significantly different between MRI and histopathology. By contrast, the hippocampus (70% vs 96%, p=0.047), cerebral white matter (anterior 65% vs 96%, p=0.022, posterior 61% vs 91%, p=0.035) and brainstem (57% vs 96%, p=0.004) were confirmed to be affected more often on histopathological examination than with MRI. CONCLUSIONS: Whereas early postnatal MR imaging is excellent in detecting injury to the basal ganglia and thalamus, PLIC, cortex and cerebellum, it may underestimate injury to the hippocampus, cerebral white matter, and the brainstem in term infants with neonatal encephalopathy following perinatal asphyxia.
    Archives of Disease in Childhood - Fetal and Neonatal Edition 11/2012; · 3.05 Impact Factor
  • Article: Neurologic Assessment Tool for Screening Preterm Infants at Term Age.
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    ABSTRACT: The screening assessment tool of the Dubowitz neonatal neurologic assessment was adapted for preterm infants. The findings identified as "warning signs" in preterm infants were identical to those found in full-term infants, suggesting that this screening tool can also be used in preterm infants at term age.
    The Journal of pediatrics 08/2012; · 4.02 Impact Factor
  • Article: Cerebral white matter and neurodevelopment of preterm infants after -coagulase--negative staphylococcal sepsis.
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    ABSTRACT: OBJECTIVE:: Coagulase-negative staphylococci are the most common pathogens causing late-onset sepsis in the neonatal intensive care unit. Neonatal sepsis can be associated with cerebral white matter damage in preterm infants. Neurodevelopment has been shown to be correlated with apparent diffusion coefficients, fractional anisotropy, and axial and radial diffusivities of the white matter. DESIGN:: Prospective cohort study. SETTING:: Twenty-eight-bed neonatal intensive care unit at a tertiary care children's hospital. PATIENTS:: Seventy preterm infants (gestational age <32 wks), 28 with coagulase-negative staphylococcal sepsis (group 1) and 42 without sepsis (group 2). INTERVENTION:: The values of apparent diffusion coefficients, fractional anisotropy, and axial and radial diffusivity of three white matter regions (parietal, frontal, and occipital), estimated with diffusion-tensor magnetic resonance imaging with a 3.0-T magnetic resonance imaging system, were obtained at term-equivalent age. Neurodevelopmental outcome assessments were performed at 15 months (Griffiths Mental Developmental Scales) and 24 months (Bayley Scales of Infant and Toddler Development, Third Edition) corrected age. MEASUREMENTS AND MAIN RESULTS:: Values of apparent diffusion coefficients, fractional anisotropy, and axial and radial diffusivity of the left and right white matter regions were equal in all patients. There was no significant difference in apparent diffusion coefficient values (mean of total: 1.593 ± 0.090 × 10mm/sec and 1.601 ± 0.117 × 10mm/sec, respectively, p = .684), fractional anisotropy values (mean of total: 0.19 ± 0.04 and 0.19 ± 0.03, respectively, p = .350), radial diffusivity (mean of total: 1.420 ± 0.09 × 10mm/sec and 1.425 ± 0.12 × 10mm/sec, respectively, p = .719), and axial diffusivity (mean of total: 1.940 ± 0.12 × 10mm/sec and 1.954 ± 0.13 × 10mm/sec, respectively, p = .590) in the three combined regions between the two groups. No significant differences were found in neurodevelopmental outcome at 24 months. CONCLUSIONS:: No association was found between coagulase-negative staphylococcal sepsis in preterm infants and cerebral white matter damage as determined by values of apparent diffusion coefficients, fractional anisotropy, and radial and axial diffusivity at term-equivalent age, and no adverse effect was seen on early neurodevelopmental outcome.
    Pediatric Critical Care Medicine 07/2012; · 3.13 Impact Factor
  • Article: Amplitude-integrated electroencephalography in newborns with inborn errors of metabolism.
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    ABSTRACT: Background: The utility of amplitude-integrated electroencephalography (aEEG) monitoring has been established for patients with neonatal hypoxic-ischemic encephalopathy. Objective: To evaluate the role of aEEG in the diagnostic process and treatment of patients with encephalopathy due to inborn errors of metabolism. Methods: Cases collected through an international registry were divided into 5 groups of metabolic disorders. Common aEEG features were sought for each group. Results: In total, 21/30 (70%) cases had abnormal aEEG background patterns, 18/30 (60%) showed seizure activity. Patients with disorders of energy metabolism, hyperammonemia, and organic/amino acidopathies often showed marked aEEG depression with seizure activity. In contrast, aEEGs of patients with peroxisomal disorders did not show major background abnormalities but seizures were present in 5/6 subjects. We report two features of interest: firstly, two tracings displayed an unusual upward shift of the lower aEEG amplitude margin. Secondly, aEEGs of infants with non-ketotic hyperglycinemia showed a pattern we refer to as 'high-frequency burst-suppression pattern'. Conclusions: aEEG in patients with inborn errors of metabolism frequently reveals abnormalities and assists clinicians in the clinical assessment, management and monitoring of these patients.
    Neonatology 07/2012; 102(3):203-11. · 2.66 Impact Factor
  • Article: Hearing in preterm infants with postnatally acquired cytomegalovirus infection.
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    ABSTRACT: Cytomegalovirus is an important cause of sensorineural hearing loss in children. In contrast to congenitally infected infants, little is known about hearing in preterm infants with postnatal cytomegalovirus infection. We studied the hearing in 64 preterm infants during the first year of life and in 18 during the second year of life. None of the infants developed sensorineural hearing loss.
    The Pediatric Infectious Disease Journal 05/2012; 31(10):1082-4. · 3.58 Impact Factor
  • Article: Risk factors for perinatal arterial ischaemic stroke in full-term infants: a case-control study.
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    ABSTRACT: The incidence of perinatal arterial ischaemic stroke (PAIS) is about 1 in 2300 live births. Evidence about the aetiology is still lacking. The aim of this study was to identify maternal, perinatal and neonatal risk factors for symptomatic PAIS in full-term infants. Each full-term infant with PAIS was matched to three healthy controls for gestational age, date of birth and hospital of birth. Antenatal and perinatal risk factors were studied using univariate and multivariate conditional logistic regression analysis. Fifty-two infants were diagnosed with PAIS. Significant risk factors in the univariate analysis (p<0.05) were nulliparity (64% vs 47%), maternal fever (>38°C) during delivery (10% vs 1%), fetal heart rate decelerations (63% vs 16%), meconium-stained amniotic fluid (44% vs 17%), emergency caesarean section (35 vs 2%), Apgar score (1 min) ≤3 (29% vs 1%), Apgar score (5 min) <7 (25% vs 1%), umbilical artery pH <7.10 (56% vs 10%), hypoglycaemia <2.0 mmol/l (29% vs 3%) and early-onset sepsis/meningitis (14% vs 2%). In the multivariate analysis, maternal fever (OR 10.2; 95% CI 1.3 to 78.5), Apgar score (5 min) <7 (OR 18.1; 95% CI 3.4 to 96.8), hypoglycaemia <2.0 mmol/l (OR 13.0; 95% CI 3.2 to 52.6) and early-onset sepsis/meningitis (OR 5.8; 95% CI 1.1 to 31.9) were significantly associated with PAIS. Maternal fever during delivery and early-onset sepsis/meningitis were found to be involved with PAIS as was previously noted. Apgar score (5 min) <7 and hypoglycaemia were found to be important risk factors in term PAIS.
    Archives of Disease in Childhood - Fetal and Neonatal Edition 03/2012; 97(6):F411-6. · 3.05 Impact Factor
  • Article: Changes in carotid blood flow after unilateral perinatal arterial ischemic stroke.
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    ABSTRACT: Little is known about changes in carotid blood flow after perinatal arterial ischemic stroke (PAIS). The aim of this study was to assess the blood flow in the internal carotid arteries (ICAs) after unilateral PAIS. The carotid flow (ml/min) was measured noninvasively by means of two-dimensional phase-contrast magnetic resonance angiography (2D PC-MRA) in 25 full-term infants who had unilateral PAIS within 10 d after birth. In 17 infants a second 2D PC-MRA was carried out at the age of 3 mo. Asymmetry of carotid blood flow was calculated at both time points, and the circle of Willis (CoW) was assessed with a three-dimensional (3D) time-of-flight MRA. On the early magnetic resonance imaging (MRI), a significant increase in ipsilateral blood flow was observed (7.7%, 95% confidence interval (CI) 3.0-14.9%), which persisted after correcting for CoW configuration. At 3 mo, this asymmetry was no longer observed. No relationship was found between the asymmetry in blood flow and either stroke size or postnatal age at scan. A higher blood flow in the ipsilateral ICA was observed during the acute phase after unilateral PAIS, and this disappeared after 3 mo. Further research into the role of hyperperfusion after PAIS may suggest new approaches to neuroprotection.
    Pediatric Research 03/2012; 72(1):50-6. · 2.70 Impact Factor
  • Article: Active head lifting from supine in early infancy: an indicator for non-optimal cognitive outcome in late infancy.
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    ABSTRACT: To explore whether active head lifting from supine (AHLS) in early infancy is associated with cognitive outcome in the second year of life. The presence of AHLS was always recorded in the notes of infants admitted to our tertiary neonatal intensive care unit. Random sampling was used to pair infants with AHLS with two comparison infants without AHLS whose sex, gestational age, birth year (1993-2009), time of assessment, and developmental test (Griffiths Mental Development Scales, Mental Scale of the Bayley Scales of Infant Development-II, or cognitive subtest of the Bayley Scales of Infant and Toddler Development-III) were comparable. Brain injury identified from neonatal cranial ultrasound scans was classified as no - mild or moderate - severe. Z-scores of cognitive test outcomes were calculated for multivariable analysis. Eighty-seven preterm (34 males, 53 females) and 40 term (17 males, 23 females) infants with AHLS were identified. AHLS was documented at a mean (corrected) age of 7.0 (SD 1.7) and 8.1 (SD 2.2) months respectively. The cognitive assessments were performed at a mean corrected age of 15.7 (SD 1.7) and 23.9 (SD 1.6) months in preterm infants, and 19.1 (SD 2.3) months in term infants. The mean cognitive outcome of preterm and term infants with AHLS was lower than that of infants without AHLS (p=0.002 and p=0.004 respectively). This remained after excluding infants with cerebral palsy with matching comparison infants (p=0.001 in preterm and p=0.001 in term infants). The mean difference was highest (1.35SD) between term male infants and comparison infants (p=0.001). AHLS is associated with a less favourable cognitive outcome in the second year of life in preterm as well as in term-born infants than in comparison infants.
    Developmental Medicine & Child Neurology 03/2012; 54(6):538-43. · 2.92 Impact Factor
  • Article: Urine viral load and correlation with disease severity in infants with congenital or postnatal cytomegalovirus infection.
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    ABSTRACT: A correlation between cytomegalovirus (CMV) load in urine and severity of disease in congenitally infected infants has previously been reported. CMV load in postnatally infected infants has not been studied before. To investigate CMV load in urine of infants with postnatal or congenital infection and correlate this with clinical symptoms of CMV disease and cerebral abnormalities. Infants admitted to our NICU between July 2000 and February 2010, and diagnosed with congenital or postnatal CMV infection were included. Clinical symptoms of CMV infection, cranial ultrasonography (cUS) and magnetic resonance imaging (MRI) findings were evaluated. CMV urine loads of postnatally infected infants were analyzed and compared with CMV urine loads of congenitally infected infants. Seventeen infants with congenital CMV infection and 45 infants with postnatal CMV infection were included. Thirteen/17 (76%) congenitally infected infants had clinical symptoms of CMV infection at birth and 11/17 (65%) had cerebral abnormalities diagnosed by neuro-imaging. None of the four asymptomatic infants had cerebral abnormalities. Of the postnatally infected infants 43/45 (96%) did not develop any clinical symptoms of CMV infection, but in 23/45 (51%) cerebral abnormalities such as lenticulostriate vasculopathy and germinolytic cysts were identified. The median CMV load in postnatally infected infants was significantly lower than in congenitally infected infants (1.0×10(5)copies/ml versus 8.5×10(6)copies/ml, p<0.001, respectively). CMV load in urine is significantly lower in infants with postnatal CMV infection than in infants with congenital CMV infection irrespective of clinical symptoms of CMV infection or cerebral abnormalities.
    Journal of clinical virology: the official publication of the Pan American Society for Clinical Virology 03/2012; 54(2):121-4. · 3.12 Impact Factor

Institutions

  • 2002–2013
    • Universitair Medisch Centrum Utrecht
      • Department of Neonatology
      Utrecht, Provincie Utrecht, Netherlands
  • 2010
    • Universiteit Utrecht
      • Langeveld Institute for the Study of Education and Development in Childhood and Adolescence
      Utrecht, Provincie Utrecht, Netherlands
    • University of Bristol
      Bristol, ENG, United Kingdom
  • 2004–2009
    • Canisius-Wilhelmina Ziekenhuis
      Nijmegen, Provincie Gelderland, Netherlands
  • 2003–2007
    • Imperial College London
      • • Section of Paediatrics
      • • Faculty of Medicine
      London, ENG, United Kingdom