Background: Ultrafast cerebral Doppler ultrasound enables simultaneous quantification and visualization of cerebral blood flow velocity. The aim of this study is to compare the use of conventional... Show moreBackground: Ultrafast cerebral Doppler ultrasound enables simultaneous quantification and visualization of cerebral blood flow velocity. The aim of this study is to compare the use of conventional and ultrafast spectral Doppler during anesthesia and their potential to show the effect of anesthesiologic procedures on cerebral blood flow velocities, in relation to blood pressure and cerebral oxygenation in infants undergoing inguinal hernia repair.Methods: A single-center prospective observational cohort study in infants up to six months of age. We evaluated conventional and ultrafast spectral Doppler cerebral ultrasound measurements in terms of number of successful measurements during the induction of anesthesia, after sevoflurane induction, administration of caudal analgesia, a fluid bolus and emergence of anesthesia. Cerebral blood flow velocity was quantified in pial arteries using conventional spectral Doppler and in the cerebral cortex using ultrafast Doppler by peak systolic velocity, end diastolic velocity and resistivity index.Results: Twenty infants were included with useable conventional spectral Doppler images in 72/100 measurements and ultrafast Doppler images in 51/100 measurements. Intraoperatively, the success rates were 53/60 (88.3%) and 41/60 (68.3%), respectively. Cerebral blood flow velocity increased after emergence for both conventional (end diastolic velocity, from 2.01 to 2.75 cm/s, p < 0.001) and ultrafast spectral Doppler (end diastolic velocity, from 0.59 to 0.94 cm/s), whereas cerebral oxygenation showed a reverse pattern with a decrease after the emergence of the infant (85% to 68%, p < 0.001).Conclusion: It is possible to quantify cortical blood flow velocity during general anesthesia using conventional and ultrafast spectral Doppler cerebral ultrasound. Cerebral blood flow velocity and blood pressure decreased, while regional cerebral oxygenation increased during general anesthesia. Ultrafast spectral Doppler ultrasound offers novel insights into perfusion within the cerebral cortex, unattainable through conventional spectral ultrasound. Yet, ultrafast Doppler is curtailed by a lower success rate and a more rigorous learning curve compared to conventional method. 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
Visser, S.S.M.; Diemen, W.J.M. van; Kervezee, L.; Hoogen, A. van den; Verschuren, O.; Pillen, S.; ... ; Dudink, J. 2021
Premature birth (before 37 weeks of gestation) has been linked to a variety of adverse neurological outcomes. Sleep problems are associated with decreased neurocognitive functioning, which is... Show morePremature birth (before 37 weeks of gestation) has been linked to a variety of adverse neurological outcomes. Sleep problems are associated with decreased neurocognitive functioning, which is especially common in children born preterm. The exact relationship between prematurity and sleep at school age is unknown. A systematic review is performed with the aim to assess the relationship between prematurity and sleep at school age (5th to 18th year of life), in comparison to sleep of their peers born full-term. Of 347 possibly eligible studies, nine were included. The overall conclusion is that prematurity is associated with earlier bedtimes and a lower sleep quality, in particular more nocturnal awakenings and more non-rapid eye movement stage 2 sleep. Interpretations and limitations of the review are discussed. Moreover, suggestions for future research are brought forward, including the need for a systematic approach with consistent outcome measures in this field of research. A better understanding of the mechanisms that influence sleep in the vulnerable group of children born preterm could help optimize these children's behavioral and intellectual development. (C) 2021 The Author(s). Published by Elsevier Ltd. Show less
Hazelhoff, E.M.; Dudink, J.; Meijer, J.H.; Kervezee, L. 2021
The circadian timing system optimizes health by temporally coordinating behavior and physiology. During mammalian gestation, fetal circadian rhythms are synchronized by the daily fluctuations in... Show moreThe circadian timing system optimizes health by temporally coordinating behavior and physiology. During mammalian gestation, fetal circadian rhythms are synchronized by the daily fluctuations in maternal body temperature, hormones and nutrients. Circadian disruption during pregnancy is associated with negative effects on developmental outcomes in the offspring, highlighting the importance of regular and robust 24-h rhythms over gestation. In the case of preterm birth (before 37 weeks of gestation), maternal cues no longer synchronize the neonate's circadian system, which may adversely affect the neonate. There is increasing evidence that introducing robust light-dark cycles in the Neonatal Intensive Care Unit has beneficial effects on clinical outcomes in preterm infants, such as weight gain and hospitalization time, compared to infants exposed to constant light or constant near-darkness. However, the biological basis for these effects and the relationship with the functional and anatomical development of the circadian system is not fully understood. In this review, we provide a concise overview of the effects of light-dark cycles on clinical outcomes of preterm neonates in the NICU and its alignment with the development of the circadian system. Show less
In the past three decades, cerebral ultrasound (CUS) has become a trusted technique to study the neonatal brain. It is a relatively cheap, non-invasive, bedside neuroimaging method available in... Show moreIn the past three decades, cerebral ultrasound (CUS) has become a trusted technique to study the neonatal brain. It is a relatively cheap, non-invasive, bedside neuroimaging method available in nearly every hospital. Traditionally, CUS was used to detect major abnormalities, such as intraventricular hemorrhage (IVH), periventricular hemorrhagic infarction, post-hemorrhagic ventricular dilatation, and (cystic) periventricular leukomalacia (cPVL). The use of different acoustic windows, such as the mastoid and posterior fontanel, and ongoing technological developments, allows for recognizing other lesion patterns (e.g., cerebellar hemorrhage, perforator stroke, developmental venous anomaly). The CUS technique is still being improved with the use of higher transducer frequencies (7.5-18 MHz), 3D applications, advances in vascular imaging (e.g. ultrafast plane wave imaging), and improved B-mode image processing. Nevertheless, the helpfulness of CUS still highly depends on observer skills, knowledge, and experience. In this special article, we discuss how to perform a dedicated state-of-the-art neonatal CUS, and we provide suggestions for structured reporting and quality assessment. Show less
Cerebellar hemorrhage (CBH) is a frequent complication of preterm birth and may play an important and under-recognized role in neurodevelopment outcome. Association between CBH size, location, and... Show moreCerebellar hemorrhage (CBH) is a frequent complication of preterm birth and may play an important and under-recognized role in neurodevelopment outcome. Association between CBH size, location, and neurodevelopment is still unknown. The main objective of this study was to investigate neurodevelopmental outcome at 2 years of age in a large number of infants with different patterns of CBH. Of preterm infants (<= 34 weeks) with known CBH, perinatal factors, neuro-imaging findings, and follow-up at 2 years of age were retrospectively collected. MRI scans were reassessed to determine the exact size, number, and location of CBH. CBH was divided into three groups: punctate (<= 4 mm), limited (> 4 mm but < 1/3 of the cerebellar hemisphere), or massive (>= 1/3 of the cerebellar hemisphere). Associations between pattern of CBH, perinatal factors, and (composite) neurodevelopmental outcome were assessed. Data of 218 preterm infants with CBH were analyzed. Of 177 infants, the composite outcome score could be obtained. Forty-eight out of 119 infants (40%) with punctate CBH, 18 out of 35 infants (51%) with limited CBH, and 18 out of 23 infants (78%) with massive CBH had an abnormal composite outcome score. No significant differences were found for the composite outcome between punctate and limited CBH (P = 0.42). The risk of an abnormal outcome increased with increasing size of CBH. Infants with limited CBH have a more favorable outcome than infants with massive CBH. It is therefore important to distinguish between limited and massive CBH. Show less
