Introduction: There is no consensus regarding the efficacy of add-on therapy with levetiracetam (LEV) in the treatment of seizures in neonates. The aim of this study was to evaluate the efficacy... Show moreIntroduction: There is no consensus regarding the efficacy of add-on therapy with levetiracetam (LEV) in the treatment of seizures in neonates. The aim of this study was to evaluate the efficacy of add-on therapy with LEV for achieving >80% seizure reduction after phenobarbital (PB) treatment. Methods: Retrospective cohort study of near term neonates admitted to the neonatal intensive care unit with EEG-confirmed seizures despite treatment with PB as first-line therapy and using LEV as 2nd-, 3rd- or 4th-line treatment. Antiseizure medication was administered according to national guidelines. All neonates were monitored with 2-channel amplitude-integrated electroencephalography. The total seizure burden in minutes, 2 h before and 4 h after administration of LEV, was calculated using raw EEG. Primary outcome was the efficacy of LEV in achieving >80% seizure reduction. The efficacy of additional midazolam (MDZ) and lidocaine (LDC) was also calculated. Results: A total of 47 full-term neonates were included. The mean total loading dose of LEV was 40 mg/kg (36–44 mg/kg). Seizure etiology consisted of hypoxic-ischemic encephalopathy (n = 11), hemorrhagic or ischemic stroke (n = 16), central nervous system infection (n = 8), genetic (n = 8), metabolic disorders (n = 3), and unknown (n = 1). Following LEV administration, >80% seizure reduction was observed in 17% (8/47) of neonates, whereas it was 23% (6/26) after MDZ and 92% (23/25) after LDC administration. Discussion: Although the cumulative loading dose of LEV was low and the group of infants studied was heterogeneous, the efficacy of LEV as add-on therapy for the treatment of seizures in neonates was limited. The highest seizure reduction rate was seen after LDC administration. Show less
Objective To evaluate the association between neuroimaging and outcome in infants with congenital cytomegalovirus (cCMV), focusing on qualitative MRI and quantitative diffusion-weighted imaging of... Show moreObjective To evaluate the association between neuroimaging and outcome in infants with congenital cytomegalovirus (cCMV), focusing on qualitative MRI and quantitative diffusion-weighted imaging of white matter abnormalities (WMAs).Methods Multicentre retrospective cohort study of 160 infants with cCMV (103 symptomatic). A four-grade neuroimaging scoring system was applied to cranial ultrasonography and MRI acquired at <= 3 months. WMAs were categorised as multifocal or diffuse. Temporal-pole WMAs (TPWMAs) consisted of swollen or cystic appearance. Apparent diffusion coefficient (ADC) values were obtained from frontal, parieto-occipital and temporal white matter regions. Available follow-up MRI at >= 6 months (N=14) was additionally reviewed. Neurodevelopmental assessment included motor function, cognition, behaviour, hearing, vision and epilepsy. Adverse outcome was defined as death or moderate/severe disability.Results Neuroimaging scoring was associated with outcome (p<0.001, area under the curve 0.89 +/- 0.03). Isolated WMAs (IWMAs) were present in 61 infants, and WMAs associated with other lesions in 30. Although TPWMAs and diffuse pattern often coexisted in infants with IWMAs (p<0.001), only TPWMAs were associated with adverse outcomes (OR 7.8; 95% CI 1.4 to 42.8), including severe hearing loss in 20% and hearing loss combined with other moderate/severe disabilities in 15%. Increased ADC values were associated with higher neuroimaging scores, WMAs based on visual assessment and IWMAs with TPWMAs. ADC values were not associated with outcome in infants with IWMAs. Findings suggestive of progression of WMAs on follow-up MRI included gliosis and malacia.Conclusions Categorisation of neuroimaging severity correlates with outcome in cCMV. In infants with IWMAs, TPWMAs provide a guide to prognosis. Show less
Objective To study the potential role of ventricular volume (VV) estimation in the management of posthemorrhagic ventricular dilatation related to the need for ventriculoperitoneal (VP)-shunt... Show moreObjective To study the potential role of ventricular volume (VV) estimation in the management of posthemorrhagic ventricular dilatation related to the need for ventriculoperitoneal (VP)-shunt insertion and 2-year neurodevelopmental outcome in infants born preterm.Study design We included 59 patients from the Early vs Late Ventricular Intervention Study from 4 participating centers. VV was manually segmented in 209 3-dimensional ultrasound scans and estimated from 2-dimensional ultrasound linear measurements in a total of 1226 ultrasounds. We studied the association of both linear measurements and VV to the need for VP shunt and 2-year neurodevelopmental outcome in the overall cohort and in the 29 infants who needed insertion of a reservoir. We used general estimating equations to account for repeated measures per individual.Results Maximum pre-reservoir VV (beta coefficient = 0.185, P = .0001) and gestational age at birth (beta = -0.338; P = .0001) were related to the need for VP shunt. The estimated optimal single VV measurement cut point of 17 cm(3) correctly classified 79.31% with an area under the curve of 0.76 (CI 95% 0.74-0.79). Maximum VV (beta = 0.027; P = .012) together with VP shunt insertion (beta = 3.773; P = .007) and gestational age (beta = -0.273; P = .0001) were related to cognitive outcome at 2 years. Maximum ventricular index and anterior horn width before reservoir insertion were independently associated with the need of VP shunt and the proposed threshold groups in the Early vs Late Ventricular Intervention Study trial were associated with long-term outcome.Conclusions Pre-reservoir VV measurements were associated with the need for VP-shunt insertion and 2-year cognitive outcome among infants born preterm with posthemorrhagic ventricular dilatation. 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
Vos, T.W. de; Zagten, M. van; Haas, M. de; Oepkes, D.; Tan, R.N.G.B.; Schoot, C.E. van der; ... ; Klink, J.M.M. van 2023
ObjectiveTo evaluate the neurodevelopmental outcome at school age in children newly diagnosed with fetal and neonatal alloimmune thrombocytopenia (FNAIT).Study designThis observational cohort study... Show moreObjectiveTo evaluate the neurodevelopmental outcome at school age in children newly diagnosed with fetal and neonatal alloimmune thrombocytopenia (FNAIT).Study designThis observational cohort study included children diagnosed with FNAIT between 2002 and 2014. Children were invited for cognitive and neurological testing. Behavioral questionnaires and school performance results were obtained. A composite outcome of neurodevelopmental impairment (NDI) was used, defined, and subdivided into mild-to-moderate and severe NDI. Primary outcome was severe NDI, defined as IQ <70, cerebral palsy with Gross Motor Functioning Classification System level ≥ III, or severe visual/hearing impairment. Mild-to-moderate NDI was defined as IQ 70-85, minor neurological dysfunction or cerebral palsy with Gross Motor Functioning Classification System level ≤ II, or mild visual/hearing impairment.ResultsIn total, 44 children were included at a median age of 12 years (range: 6-17 years). Neuroimaging at diagnosis was available in 82% (36/44) of children. High-grade intracranial hemorrhage (ICH) was detected in 14% (5/36). Severe NDI was detected in 7% (3/44); two children had high-grade ICH, and one had low-grade ICH and perinatal asphyxia. Mild-to-moderate NDI was detected in 25% (11/44); one child had high-grade ICH, and eight children were without ICH, yet for two children, neuroimaging was not performed. Adverse outcome (perinatal death or NDI) was 39% (19/49). Four children (9%) attended special needs education, three of whom had severe NDI and one had mild-to-moderate NDI. Total behavioral problems within the clinical range were reported in 12%, which is comparable with 10% in the general Dutch population.ConclusionChildren who are newly diagnosed with FNAIT are at increased risk for long-term neurodevelopmental problems, even those without ICH. Show less
Objectives: Corticosteroids are used to prevent or treat lung disease of prematurity. While neurological side effects have been reported, detailed effects on cerebellar growth are unknown. This... Show moreObjectives: Corticosteroids are used to prevent or treat lung disease of prematurity. While neurological side effects have been reported, detailed effects on cerebellar growth are unknown. This study aimed to compare cerebellar growth in premature infants who received dexamethasone or hydrocortisone to premature infants who did not receive postnatal corticosteroids. Study Design: Retrospective case-control study in infants born at a gestational age of <29 weeks and admitted to two level 3 neonatal intensive care units. Exclusion criteria were severe congenital anomalies and cerebellar or severe supratentorial lesions. Infants were treated with dexamethasone (unit 1) or hydrocortisone (unit 2) for chronic lung disease. Controls (unit 1) did not receive postnatal corticosteroids. Sequential head circumference (HC) and ultrasound measurements of transcerebellar diameter (TCD), biparietal diameter (BPD), and corpus callosum-fastigium length (CCFL) were performed until 40 weeks' postmenstrual age (PMA). Growth was assessed using linear mixed models correcting for PMA at measurement, sex, HC z-score at birth, and a propensity score indicating illness severity. Group differences before treatment were assessed using linear regression. Results: 346 infants were included (68 dexamethasone, 37 hydrocortisone, 241 controls). Before starting corticosteroids, TCD, BPD, and HC measurements did not differ between patients and controls at a comparable PMA. After starting treatment, both types of corticosteroid had a negative association with TCD growth. BPD, CCFL, and HC growth were not negatively affected. Conclusion: Administration of dexamethasone and hydrocortisone are both associated with impaired cerebellar growth in premature infants without evident negative associations with cerebral growth. Show less
Background: Psychosocial development in monochorionic (MC) twins born after selective fetal growth restriction (sFGR) has been unreported to date, despite its importance for daily functioning and... Show moreBackground: Psychosocial development in monochorionic (MC) twins born after selective fetal growth restriction (sFGR) has been unreported to date, despite its importance for daily functioning and future relationships. Aims: To investigate psychosocial development, attachment and school functioning in MC twins with sFGR and compare outcomes with the general population and between smaller and larger twins. Study design: Observational cohort study. Subjects: MC twins with sFGR (defined as a birth weight discordance >= 20 %) born between 2002 and 2017 and aged 3-17 years. Outcome measures: Multiple parent report questionnaires: the Child Behavior Checklist (social-emotional devel-opment and behavior), the (Early) Childhood Behavior Questionnaire Very Short Form (temperament), the Attachment Insecurity Screening Inventory (attachment) and a school functioning questionnaire. Results: Median age for the 48 twin pairs was 11 (interquartile range (IQR) 8-13) years. Attachment insecurity for both twins was higher than in the general population for ambivalence/resistance (34 % (21/62) vs. 16 %, p = 0.024) and total attachment insecurity (35 % (22/62) vs. 16 %, p = 0.016). Smaller twins had more internalizing behavioral problems, i.e. negative emotions and behaviors turned inwards (22 % (10/46) vs. 11 % (5/46), p = 0.021) and a higher negative affect, i.e. more likely to experience negative emotions (3.2 (2.9-3.7) vs. 2.9 (2.2-3.2), p = 0.009) than larger twins, as well as a lower secondary school level (p = 0.031). Conclusion: MC twins with sFGR have more ambivalent/resistant attachment insecurity following the compli-cated pregnancy course. Smaller twins have a tendency towards negative emotions and internalizing behaviors compared to larger twins, indicating an increased sensitivity for depression and anxiety. Show less
Vos, T.W. de; Haas, M. de; Oepkes, D.; Tan, R.N.G.B.; Schoot, C.E. van der; Steggerda, S.J.; ... ; Klink, J.M.M. van 2022
BACKGROUND: Children with fetal and neonatal alloimmune throm-bocytopenia face increased risk of intracranial hemorrhage potentially leading to developmental impairment. To prevent intracranial... Show moreBACKGROUND: Children with fetal and neonatal alloimmune throm-bocytopenia face increased risk of intracranial hemorrhage potentially leading to developmental impairment. To prevent intracranial hemorrhage, pregnant women with alloantibodies against fetal platelets are often treated with intravenous immunoglobulin. Intravenous immunoglobulin seems effective in vastly reducing the risk of fetal or neonatal bleeding complications. However, information on long-term neurodevelopment of these children is lacking. OBJECTIVE: This study aimed to evaluate long-term neurodevelopmental outcome in children with fetal and neonatal alloimmune thrombocytopenia who were treated with intravenous immunoglobulin antenatally. STUDY DESIGN: An observational cohort study was performed, including children of mothers treated with intravenous immunoglobulin during pregnancy because a previous child was diagnosed with fetal and neonatal alloimmune thrombocytopenia. Children were invited for a follow-up assessment including standardized cognitive and neurologic tests. The parents were asked to complete a behavioral questionnaire and school performance reports. The primary outcome was severe neurodevelopmental impairment, defined as severe cognitive impairment (intelligence quotient <70), cerebral palsy with Gross Motor Function Classification System Level >= 3, bilateral blindness, and/or bilateral deafness (requiring amplification). The secondary outcome was mild to moderate neurodevelopmental impairment, defined as either mild to moderate cognitive impairment (intelligence quotient <85), cerebral palsy with Gross Motor Function Classification System Level <= 2, minor neurologic dysfunction, vision loss, and/or hearing loss.RESULTS: Between 2003 and 2017, 51 children were live-born after antenatal intravenous immunoglobulin treatment. One family moved abroad and was therefore not eligible for inclusion. In total, 82% (41/50) of the eligible cases were included for neurodevelopmental assessment at a median age of 9 years and 8 months. Severe neurodevelopmental impairment was not detected. The incidence of mild to moderate neurodevelopmental impairment was 14% (6/41; 95% confidence interval, 6% -29%). The children's mean cognitive score, behavioral scores, and academic achievement were not different from those observed in the Dutch norm groups. Neuroimaging was performed in 90% (37/41) of cases. Severe intracranial hemorrhage was diagnosed in 2 cases (5%), one antenatally before the start of intravenous immunoglobulin and the other case 1 day after birth. Both cases had a normal neurodevelopmental outcome. CONCLUSION: The risk of neurodevelopmental impairment in children whose mothers were treated for fetal and neonatal alloimmune thrombocytopenia with antenatal intravenous immunoglobulin is comparable to that reported in the general population. Show less
Background: Singletons born after fetal growth restriction (FGR) are at increased risk of poor neurodevelopmental outcomes. Studies of singletons with FGR usually compare outcomes with those... Show moreBackground: Singletons born after fetal growth restriction (FGR) are at increased risk of poor neurodevelopmental outcomes. Studies of singletons with FGR usually compare outcomes with those without FGR, a comparison that is inherently biased by obstetrical, parental, and genetic factors. We aim to compare neurodevelopmental outcomes between the smaller and larger twin in a population of discordant identical twins who shared a single placenta (monochorionic diamniotic), naturally eliminating these confounders. Methods: This study is part of the cohort study LEMON of monochorionic diamniotic twins with selective FGR. All monochorionic diamniotic twins with selective FGR who were born in Leiden University Medical Center (Leiden, Netherlands) between March 1, 2002, and Dec 31, 2017, were eligible for inclusion. Twin pregnancies that were complicated by twin-twin transfusion syndrome, twin anaemia polycythaemia sequence, or monoamnionicity were excluded. Cognitive performance was evaluated with two standardised psychometric age-appropriate tests, producing a full-scale intelligence quotient (FSIQ). Motor functioning was assessed with a standardised neurological examination. A composite outcome of neurodevelopmental impairment (NDI) was used, subdivided into mild NDI (defined as FSIQ <85, minor neurological dysfunction or cerebral palsy grade 1, or mild visual or hearing impairment) and severe NDI (defined as FSIQ <70, severe neurological dysfunction, or severe visual or hearing impairment). Findings: Between Jan 25, 2021, and March 15, 2022, 47 twin pairs were enrolled in the study and underwent neurodevelopmental assessment. The median gestational age at birth was 33middot9 weeks (IQR 31middot3-36middot0) for the 47 included twin pairs, with median birthweights of 1400 g (1111-1875) in the smaller twin and 2003 g (1600-2680) in the larger twin. The median age at neurodevelopmental assessment was 11 years (8-13). Median FSIQ was 94 (86-101) for the smaller twin and 100 (92-108) for the larger twin (p<0middot0001). More smaller twins had mild NDI (17 [36%] of 47) than did the larger twins (five [11%] of 47; odds ratio 4middot8 [95% CI 1middot6-14middot1]; p=0middot0049). There was no difference in the proportion of children with severe NDI (two [4%] of 47 in both groups, p=1middot0). Interpretation: As mild NDI can impede children in their daily functioning, we recommend standardised long-term follow-up, including neurodevelopmental testing, for monochorionic diamniotic twins with selective FGR to facilitate early identification of children at risk. Show less
Objectives: Fetal growth restriction (FGR) may alter brain development permanently, resulting in lifelong structural and functional changes. However, in studies addressing this research question,... Show moreObjectives: Fetal growth restriction (FGR) may alter brain development permanently, resulting in lifelong structural and functional changes. However, in studies addressing this research question, FGR singletons have been compared primarily to matched appropriately grown singletons, a design which is inherently biased by differences in genetic and maternal factors. To overcome these limitations, we conducted a within-pair comparison of neonatal structural cerebral ultrasound measurements in monochorionic twin pairs with selective FGR (sFGR). Methods: Structural cerebral measurements on neonatal cerebral ultrasound were compared between the smaller and larger twins of monochorionic twin pairs with sFGR, defined as a birth-weight discordance (BWD) >= 20%, born in our center between 2010 and 2020. Measurements from each twin pair were also compared with those of an appropriately grown singleton, matched according to sex and gestational age at birth. Results: Included were 58 twin pairs with sFGR, with a median gestational age at birth of 31.7 (interquartile range, 29.9-33.8) weeks and a median birth weight of 1155 g for the smaller twin and 1725 g for the larger twin (median BWD, 32%). Compared with both the larger twin and the singleton, the smaller twin had significantly smaller cerebral structures (corpus callosum, vermis, cerebellum), less white/deep gray matter and smaller intracranial surface area and volume. Intracranial-volume discordance and BWD correlated significantly (R-2 = 0.228, P < 0.0001). The median intracranial-volume discordance was smaller than the median BWD (19% vs 32%, P < 0.0001). After correction for intracranial volume, only one of the observed differences (biparietal diameter) remained significant for the smaller twin vs both the larger twin and the singleton. Conclusions: In monochorionic twins with sFGR, neonatal cerebral ultrasound reveals an overall, proportional restriction in brain growth, with smaller cerebral structures, less white/deep gray matter and smaller overall brain-size parameters in the smaller twin. There was a positive linear relationship between BWD and intracranial-volume discordance, with intracranial-volume discordance being smaller than BWD. (c) 2021 International Society of Ultrasound in Obstetrics and Gynecology. Show less
Background: Perinatal arterial ischaemic stroke (PAIS) is an important cause of neurodevelopmental disabilities. In this first-in-human study, we aimed to assess the feasibility and safety of... Show moreBackground: Perinatal arterial ischaemic stroke (PAIS) is an important cause of neurodevelopmental disabilities. In this first-in-human study, we aimed to assess the feasibility and safety of intranasally delivered bone marrow-derived allogeneic mesenchymal stromal cells (MSCs) to treat PAIS in neonates. Methods: In this open-label intervention study in collaboration with all neonatal intensive care units in the Netherlands, we included neonates born at full term (>= 36 weeks of gestation) with MRI-confirmed PAIS in the middle cerebral artery region. All eligible patients were transferred to the neonatal intensive care unit of the Wilhelmina Children's Hospital. Neonates received one dose of 45-50 x 10(6) bone-marrow derived MSCs intranasally within 7 days of presenting signs of PAIS. The primary endpoints were acute and subacute safety outcomes, including vital signs, blood markers, and the occurrence of toxicity, adverse events, and serious adverse events. The occurrence of unexpected cerebral abnormalities by a repeat MRI at 3 months of age was a secondary endpoint. As part of standard clinical follow-up at Wilhelmina Children's Hospital, we assessed corticospinal tract development on MRI and performed motor assessments at 4 months of age. This study is registered with ClinicalTrials.gov, NCT03356821. Findings: Between Feb 11, 2020, and April 29, 2021, ten neonates were enrolled in the study. Intranasal administration of MSCs was well tolerated in all ten neonates. No serious adverse events were observed. One adverse event was seen: a mild transient fever of 38 degrees C without the need for clinical intervention. Blood inflammation markers (C-reactive protein, procalcitonin, and leukocyte count) were not significantly different pre-administration versus postadministration and, although thrombocyte levels increased (p=0.011), all were within the physiological range. Followup MRI scans did not show unexpected structural cerebral abnormalities. All ten patients had initial pre-Wallerian changes in the corticospinal tracts, but only four (40%) patients showed asymmetrical corticospinal tracts at follow-up MRI. Abnormal early motor assessment was found in three (30%) infants. Interpretation: This first-in-human study demonstrates that intranasal bone marrow-derived MSC administration in neonates after PAIS is feasible and no serious adverse events were observed in patients followed up until 3 months of age. Future large-scale placebo-controlled studies are needed to determine the therapeutic effect of intranasal MSCs for PAIS. Copyright (C) 2022 Published by Elsevier Ltd. All rights reserved. Show less
In this retrospective cohort study of the outcomes of infants born <32 week's gestation, moving from a traditional open bay neonatal unit to a new single-room unit was not associated with... Show moreIn this retrospective cohort study of the outcomes of infants born <32 week's gestation, moving from a traditional open bay neonatal unit to a new single-room unit was not associated with significant improvements in morbidity or mortality. Objective: In response to the increasing focus on family-centred care, neonatal intensive care unit (NICU) environments have gradually shifted towards the single-room design. However, the assumed benefits of this emerging design remain a subject of debate. Our goal was to evaluate the impact of single-room versus open-bay care on the risk of neonatal morbidity and mortality in preterm neonates. Design: Retrospective cohort study. Setting: Level III NICU. Patients: Neonates born Main outcome measures: Mortality and morbidities of a cohort of neonates admitted to a new, single-room unit (SRU) were compared with a historical cohort of neonates admitted to an open-bay unit (OBU). Group differences were evaluated and multivariable logistic regression analyses were performed. Results: Three-hundred and fifty-six and 343 neonates were admitted to the SRU and OBU, respectively. No difference in neonatal morbidities and mortality were observed between cohorts (bronchopulmonary dysplasia: OR 1.08, 95% CI 0.73 to 1.58, p=0.44; retinopathy of the prematurity stage >= 2: OR 1.36, 95% CI 0.84 to 2.22, p=0.10; intraventricular haemorrhage: OR 0.89, 95% CI 0.59 to 1.34, p=0.86; mortality: OR 1.55, 95% CI 0.75 to 3.20, p=0.28). In adjusted regression models, single-room care was independently associated with a decreased risk of symptomatic patent ductus arteriosus (adjusted OR 0.54, 95% CI 0.31 to 0.95). No independent association between single-room care and any of the other investigated outcomes was observed. Conclusions: Implementation of single-rooms in our NICU did not lead to a significant reduction in neonatal morbidity and mortality outcomes. Show less
Background: In many infants, treatment is started for suspicion of early onset sepsis (EOS), of whom the majority do not have an infection. Early prediction of the absence of a culture-proven... Show moreBackground: In many infants, treatment is started for suspicion of early onset sepsis (EOS), of whom the majority do not have an infection. Early prediction of the absence of a culture-proven sepsis (CPS) would significantly reduce the time of antibiotic treatment and hospitalization. Our objective was to analyze 3 criteria in infants with CPS: positive blood culture (BC) at 24 hours after the onset of suspicion of EOS (OSEOS), C-reactive protein (CRP) >= 10 mg/L and clinical signs of infection, so we can consequently consider to stop antibiotic treatment in infants without these criteria.Methods: We included all infants with suspicion of EOS from 2007 until 2020. The proportion was calculated of (1) infants with CPS with, at 24 hours, a positive BC and/or CRP >= 10 mg/L and/or clinical signs of infection and (2) infants without CPS with CRP <10 mg/L between 12 and 24 hours after OSEOS.Results: The BC showed growth of a pathogenic microorganism in 50 of 4120 included infants (1.2%). Time to positivity was >= 24 hours in 8 (16%) infants, of whom 7 infants had a raised CRP and/or clinical symptoms of infection within 24 hours. In 1095 (74%) of infants without CPS in whom CRP was measured between 12 and 24 hours after OSEOS, CRP was <10 mg/L.Conclusion: A combination of BC, CRP, and clinical signs of infection can diagnose 98% (49/50) of infants with CPS 24 hours after OSEOS. Based on normal CRP and the absence of a positive BC, the decision to stop antibiotics could have been brought forward to 24 hours in 74% of infants. Show less
Parmentier, C.E.J.; Steggerda, S.J.; Weeke, L.C.; Rijken, M.; Vries, L.S. de; Groenendaal, F. 2021
Objective To describe the clinical characteristics, MRI findings and neurodevelopmental outcome of infants with documented perinatal asphyxia and seizure onset within 24 hours after birth who were... Show moreObjective To describe the clinical characteristics, MRI findings and neurodevelopmental outcome of infants with documented perinatal asphyxia and seizure onset within 24 hours after birth who were not selected for therapeutic hypothermia (TH). Design Retrospective cohort study. Setting and patients (Near-)term infants with documented perinatal asphyxia referred to two Dutch level III neonatal units with neonatal encephalopathy (NE) and seizures Main outcome measures Clinical characteristics, findings on cranial MRI performed within 8 days after birth and neurodevelopmental outcome assessed using the Griffiths Mental Development Scales at 18 months or Bayley Scales of Infant and Toddler Development-Third Edition at 2 years of age. Results 39 infants were included. All had abnormalities on MRI. Predominant white matter/watershed injury was the most common pattern of injury, 23 (59%). 7 (18%) infants had predominant basal ganglia/thalamus injury, 3 (8%) near total brain injury, 5 (13%) arterial ischaemic stroke, 1 (3%) an intraventricular haemorrhage. Adverse outcome was seen in 51%: 6 died, 11 developed cerebral palsy (spastic n=8, dyskinetic n=3), 2 had neurodevelopmental delay, 1 had severe hearing impairment. Conclusions All infants with documented perinatal asphyxia and seizure onset within 24 hours after birth who did not receive TH had abnormalities on MRI. 51% had an adverse outcome. Better methods for recognition of infants who might benefit from TH and careful neurodevelopmental follow-up are urgently needed.In a retrospective cohort study, all infants with perinatal asphyxia and early seizure onset who did not receive therapeutic hypothermia had MRI abnormalities and half died or had poor neurodevelopmental outcome. Show less
There are many neuro-imaging studies on the presence of brain lesions in the preterm infant, using cranial ultrasound (cUS) and/or term equivalent age MRI (TEA-MRI). These studies however tend to... Show moreThere are many neuro-imaging studies on the presence of brain lesions in the preterm infant, using cranial ultrasound (cUS) and/or term equivalent age MRI (TEA-MRI). These studies however tend to focus on germinal matrix-intraventricular hemorrhage (GMH-IVH) and white matter injury. Data about perinatal arterial ischemic stroke (PAIS) or cerebral sinovenous thrombosis (CSVT) in the preterm infant are very limited. In fact, several large cohort studies on neuro-imaging in preterm infants do not even mention neonatal stroke.(1-4) Most studies about PAIS exclude preterm infants.(5) The aim of this review was to provide an update on neonatal stroke in the preterm infant, with a focus on neuro-imaging findings. (c) 2021 The Authors. Published by Elsevier Inc. Show less
Boswinkel, V.; Sok, F.I.; Kruse-Ruijter, M.F.; Nijholt, I.M.; Jansen, F.A.R.; Haak, M.C.; ... ; Wezel-Meijler, G. van 2021
Background: Brain growth in moderate preterm (MP; gestational age (GA) 32(+0)-33(+6) weeks) and late preterm infants (LP; GA 34(+0)-36+6 weeks) may be impaired, even in the absence of brain injury... Show moreBackground: Brain growth in moderate preterm (MP; gestational age (GA) 32(+0)-33(+6) weeks) and late preterm infants (LP; GA 34(+0)-36+6 weeks) may be impaired, even in the absence of brain injury.Aims: The aims of this study were to assess brain measurements of MP and LP infants, and to compare these with full-term infants (GA > 37 weeks) using linear cranial ultrasound (cUS) at term equivalent age (TEA).Study design: cUS data from two prospective cohorts were combined. Two investigators performed offline measurements on standard cUS planes. Eleven brain structures were compared between MP, LP and full-term infants using uni-and multivariable linear regression.Results were adjusted for postmenstrual age at cUS and corrected for multiple testing. Results: Brain measurements of 44 MP, 54 LP and 52 full-term infants were determined on cUS scans at TEA. Biparietal diameter and basal ganglia-insula width were smaller in MP (-9.1 mm and -1.7 mm, p < 0.001) and LP infants (-7.0 mm and -1.7 mm, p < 0.001) compared to full-term infants. Corpus callosum - fastigium length was larger in MP (+2.2 mm, p < 0.001) than in full-term infants. No significant differences were found between MP and LP infants.Conclusions: These findings suggest that brain growth in MP and LP infants differs from full-term infants. Whether these differences have clinical implications remains to be investigated. Show less
Jansen, L.; Steenis, A. van; Berg-Huysmans, A.A. van den; Wiggers-de Bruine, S.T.; Rijken, M.; Vries, L.S. de; ... ; Steggerda, S.J. 2021
Objective To assess associations between neonatal brain injury assessed by magnetic resonance imaging and cognitive, motor, and behavioral outcomes at 2 and 10 years of age, in a longitudinal... Show moreObjective To assess associations between neonatal brain injury assessed by magnetic resonance imaging and cognitive, motor, and behavioral outcomes at 2 and 10 years of age, in a longitudinal cohort of children born very preterm.Study design There were 112 children born at <32 weeks of gestation who participated in a longitudinal prospective study on brain injury and neurodevelopmental outcome. Using the Kidokoro score, neonatal brain injury and altered brain growth in white matter, cortical and deep gray matter, and the cerebellum were assessed. Cognitive, motor, and behavioral outcomes were assessed during follow-up visits at both 2 (corrected) and 10 years of age.Results After adjusting for perinatal factors and level of maternal education, the global brain abnormality score was associated with cognition (B = -1.306; P = .005), motor skills (B = -3.176; P < .001), and behavior (B = 0.666; P = .005) at 2 years of age, but was not associated with cognition at 10 years of age. In the subgroup of children with a moderate-severe global brain abnormality score, magnetic resonance imaging was independently associated with cognitive impairment at 10 years of age. For children with milder forms of brain injury, only birth weight and level of maternal education were associated with cognitive outcomes.Conclusions Neonatal brain injury, assessed by a standardized scoring system, was associated with short-term neurodevelopmental outcomes, but only with motor skills and behavior in childhood. Environmental factors, such as level of maternal education, become more important for cognitive development as children grow older, especially for children with relatively mild neonatal brain injury. Show less
Objective: To investigate the rate and stability of impairments in children born preterm by assessing (1) early and school-age outcome in four developmental domains and (2) individual changes in... Show moreObjective: To investigate the rate and stability of impairments in children born preterm by assessing (1) early and school-age outcome in four developmental domains and (2) individual changes in outcome at both timepoints. Design: Prospective, longitudinal cohort study in children born in 2006-2007, <32 weeks' gestation. Follow-up at 2 and 10 years of age included standardized neurological, motor, cognitive and behavioral assessments. Children were categorized as having no, mild or moderate-severe impairment in these four domains. A composite impairment score was composed and the number of domains with impairments counted. For each child, individual outcomes at both timepoints were compared. Results: Follow-up at both time-points was available in 71/113(63%) children. At group level, there were no significant changes in the severity of impairments per domain. However, at individual level, there were less children with a mild abnormal composite score at 10 years of age (44 vs. 20%; p = 0.006), and more with a moderate-severe abnormal composite score (12 vs. 35%; p = 0.001). Especially children with normal/mild outcome at 2 years were likely to shift to other outcome categories over time. Conclusions: Children with early severe impairment are likely experiencing impairments later on, but early normal/mild abnormal outcomes should be interpreted with care, considering the large individual shifts over time. Long-term follow-up in all children born very preterm should therefore be continued to at least school-age. Show less
Background Preterm born children are at high risk for adverse motor neurodevelopment. The aim of this study was to establish the relationship between motor outcome and advanced magnetic resonance... Show moreBackground Preterm born children are at high risk for adverse motor neurodevelopment. The aim of this study was to establish the relationship between motor outcome and advanced magnetic resonance imaging (MRI) and electroencephalography (EEG) measures. Methods In a prospective cohort study of 64 very preterm born children, the motor outcome was assessed at 9.83 (SD 0.70) years. Volumetric MRI, diffusion tensor imaging (DTI), and EEG were acquired at 10.85 (SD 0.49) years. We investigated associations between motor outcome and brain volumes (white matter, deep gray matter, cerebellum, and ventricles), white matter integrity (fractional anisotropy and mean, axial and radial diffusivity), and brain activity (upper alpha (A2) functional connectivity and relative A2 power). The independence of associations with motor outcome was investigated with a final model. For each technique, the measure with the strongest association was selected to avoid multicollinearity. Results Ventricular volume, radial diffusivity, mean diffusivity, relative A2 power, and A2 functional connectivity were significantly correlated to motor outcome. The final model showed that ventricular volume and relative A2 power were independently associated with motor outcome (B = -9.42 x 10(-5), p = 0.027 and B = 28.9, p = 0.007, respectively). Conclusions This study suggests that a lasting interplay exists between brain structure and function that might underlie motor outcome at school age. ImpactThis is the first study that investigates the relationships between motor outcome and brain volumes, DTI, and brain function in preterm born children at school age. Ventricular volume and relative upper alpha power on EEG have an independent relation with motor outcome in preterm born children at school age. This suggests that there is a lasting interplay between structure and function that underlies adverse motor outcome. Show less
