Publications by authors named "Sidarto Bambang Oetomo"

26 Publications

  • Page 1 of 1

A Wearable Daily Respiration Monitoring System Using PDMS-graphene Compound Tensile Sensor for Adult.

Annu Int Conf IEEE Eng Med Biol Soc 2019 Jul;2019:1269-1273

A wearable respiration monitoring system based on Respiratory induction plethysmography (RIP) using a new Polydimethylsiloxane-graphene (PDMS-graphene) compound tensile sensor is proposed. The manufacture procedure of this novel resistance-based tensile sensor is presented together with a wireless acquisition system. The proposed sensor shows a high sensitivity during stretching and a promising cyclic stability for continuous 3,600 cycles. Statistical analysis confirms a high correlation of respiratory rate monitoring between the proposed system and a medical-level instrument. This proposed system based on RIP, using a new PDMS-graphene compound tensile sensor can acquire respiratory signal unobtrusively with high accuracy and satisfactory user experience, and thus has great potential in home monitoring scenarios.
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http://dx.doi.org/10.1109/EMBC.2019.8857144DOI Listing
July 2019

Anatomically Realistic Neonatal Heart Model for Use in Neonatal Patient Simulators.

J Vis Exp 2019 02 5(144). Epub 2019 Feb 5.

Department of Industrial Design, Eindhoven University of Technology.

Neonatal patient simulators (NPS) are artificial patient surrogates used in the context of medical simulation training. Neonatologists and nursing staff practice clinical interventions such as chest compressions to ensure patient survival in the case of bradycardia or cardiac arrest. The simulators used currently are of low physical fidelity and therefore cannot provide qualitative insight into the procedure of chest compressions. The embedding of an anatomically realistic heart model in future simulators enables the detection of cardiac output generated during chest compressions; this can provide clinicians with an output parameter, which can deepen the understanding of the effect of the compressions in relation to the amount of blood flow generated. Before this monitoring can be achieved, an anatomically realistic heart model must be created containing: two atria, two ventricles, four heart valves, pulmonary veins and arteries, and systemic veins and arteries. This protocol describes the procedure for creating such a functional artificial neonatal heart model by utilizing a combination of magnetic resonance imaging (MRI), 3D printing, and casting in the form of cold injection molding. Using this method with flexible 3D printed inner molds in the injection molding process, an anatomically realistic heart model can be obtained.
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http://dx.doi.org/10.3791/56710DOI Listing
February 2019

Changes in autonomic regulation due to Kangaroo care remain unaffected by using a swaddling device.

Acta Paediatr 2019 02 20;108(2):258-265. Epub 2018 Jul 20.

Department of Neonatology, Máxima Medical Centre, Veldhoven, The Netherlands.

Aim: To investigate the effects of a swaddling device known as the Hugsy (Hugsy, Eindhoven, the Netherlands) towards improving autonomic regulation. This device can be used both in the incubator and during Kangaroo care to absorb parental scent and warmth. After Kangaroo care, these stimuli can continue to be experienced by infants, while in the incubator. Additionally, a pre-recorded heartbeat sound can be played.

Method: Autonomic regulation was compared in preterm infants before, during and after Kangaroo care with and without the use of a swaddling device in a within-subject study carried out in a level III neonatal intensive care unit. Descriptive statistics and effect sizes were calculated corresponding to changes in heart rate, respiratory rate, oxygen saturation, temperature and heart rate variability on intervention versus control days.

Results: In this study of 20 infants with a median (interquartile range) gestational age of 28.4 (27-29.9) weeks, Kangaroo care was associated with a decrease in heart rate, respiratory rate and heart rate variability on both intervention and control days. There were no differences between intervention and control days.

Conclusion: The use of an alternative swaddling device aimed at facilitating Kangaroo care did not enhance autonomic regulation, as measured by vital signs and heart rate variability.
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http://dx.doi.org/10.1111/apa.14484DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6586026PMC
February 2019

Unlike Kangaroo care, mechanically simulated Kangaroo care does not change heart rate variability in preterm neonates.

Early Hum Dev 2018 06 5;121:27-32. Epub 2018 May 5.

Department of Neonatology, Máxima Medical Centre, Veldhoven, The Netherlands.

Background: While numerous positive effects of Kangaroo care (KC) have been reported, the duration that parents can spend kangarooing is often limited.

Aim: To investigate whether a mattress that aims to mimic breathing motion and the sounds of heartbeats (BabyBe GMBH, Stuttgart, Germany) can simulate aspects of KC in preterm infants as measured by features of heart rate variability (HRV).

Methods: A within-subject study design was employed in which every routine KC session was followed by a BabyBe (BB) session, with a washout period of at least 2 h in between. Nurses annotated the start and end times of KC and BB sessions. Data from the pre-KC, KC, post-KC, pre-BB, BB and post-BB were retrieved from the patient monitor via a data warehouse. Five time-domain features of HRV were used to compare both types of intervention. Two of these features, the percentage of decelerations (pDec) and the standard deviation of decelerations (SDDec), were developed in a previous study to capture the contribution of transient heart rate decelerations to HRV, a measure of regulatory instability.

Results: A total of 182 KC and 180 BabyBe sessions were analyzed in 20 preterm infants. Overall, HRV decreased during KC and after KC. Two of the five features showed a decrease during KC, and all features decreased in the post-KC period (p ≤ 0.01). The BB mattress as employed in this study did not affect HRV.

Conclusion: Unlike KC, a mattress that attempts to mimic breathing motion and heartbeat sounds does not affect HRV of preterm infants.
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http://dx.doi.org/10.1016/j.earlhumdev.2018.04.031DOI Listing
June 2018

Antenatal mother-infant bonding scores are related to maternal reports of infant crying behaviour.

J Reprod Infant Psychol 2017 11 31;35(5):480-492. Epub 2017 Jul 31.

e Department of Medical and Clinical Psychology , Tilburg University , Tilburg , The Netherlands.

Objective: To assess the relation between antenatal mother-infant bonding scores and maternal reports of infant crying behaviour.

Background: Crying is normal behaviour and it is important for parent-infant bonding. Even though bonding starts antenatally, the relation between antenatal bonding scores and infant crying behaviour has never been studied.

Method: A secondary analysis was performed on data that were gathered in a large prospective study within our region. Bonding was assessed using an antenatal bonding questionnaire at 32 weeks gestational age. The crying behaviour of infants was assessed with three questions at six weeks postpartum. Crying was termed excessive (EC+) when mothers perceived the crying to be 'every day', 'often' or 'very often', and with 'crying episodes lasting more than 30 minutes'; in other words, when mothers scored high on all three questions. The relation between bonding and crying was examined using a multiple logistic regression analysis, including adjustment for relevant variables, especially maternal depression as measured with the Edinburgh Depression Scale.

Results: In total, 894 women were included of whom 47 reported EC+ infants (5.3%). Antenatal bonding scores were significantly related to the reporting of crying behaviour, even after adjustment for relevant variables (p = 0.02). Each extra point on the bonding scale reduced the EC+ risk with 14% (OR = 0.86, 95% CI [0.76-0.97]).

Conclusion: Mothers with lower antenatal bonding scores were more likely to report an EC+ infant. Future research should further explore the concept of antenatal bonding, its relation with EC and risks associated with EC.
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http://dx.doi.org/10.1080/02646838.2017.1354360DOI Listing
November 2017

Viewpoints of Parents and Nurses on How to Design Products to Enhance Parent-Infant Bonding at Neonatal Intensive Care Units: A Qualitative Study Based on Existing Designs.

HERD 2018 04 10;11(2):20-31. Epub 2017 Oct 10.

2 Máxima Medical Center, Veldhoven, the Netherlands.

Aim: To investigate how product design can be used to improve parent-infant bonding in a neonatal intensive care unit.

Background: Impaired parent-infant bonding is an inevitable consequence of premature birth, which negatively influences development. Products, systems, or services that support the bonding process might counter these negative influences.

Method: The first step was to trace existing products by performing a literature search in PubMed, the university library, and Google. The identified existing designs were then used in semistructured interviews with nurses and parents to get insights into their desires and recommendations for product design to enhance bonding. Interviews contained open questions and a multiple-choice questionnaire based on the literature search.

Results: In total, 17 existing design types were used in interviews with 11 parents and 23 nurses. All nurses explicitly stated that practicality was the first criterion designs aimed at enhancing bonding definitely had to meet. All parents indicated that they would like to use a design to enhance bonding if that would contribute to their child's health and development. For both parents and nurses, the most valuable way to enhance bonding seemed to be products to improve Kangaroo care; however, their specific desires varied substantially. Therefore, seven recurring themes were defined, resulting in nine general recommendations and six opportunities intended to enhance parent-infant bonding.

Conclusion: This study provides design recommendations and opportunities based on parents' and nurses' expert opinions. Designing to enhance bonding is considered valuable; however, designs should match the stakeholders' desires and conditions.
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http://dx.doi.org/10.1177/1937586717728483DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5985569PMC
April 2018

An innovative design for cardiopulmonary resuscitation manikins based on a human-like thorax and embedded flow sensors.

Proc Inst Mech Eng H 2017 Mar 13;231(3):243-249. Epub 2017 Feb 13.

1 Department of Industrial Design, Eindhoven University of Technology, Eindhoven, The Netherlands.

Cardiopulmonary resuscitation manikins are used for training personnel in performing cardiopulmonary resuscitation. State-of-the-art cardiopulmonary resuscitation manikins are still anatomically and physiologically low-fidelity designs. The aim of this research was to design a manikin that offers high anatomical and physiological fidelity and has a cardiac and respiratory system along with integrated flow sensors to monitor cardiac output and air displacement in response to cardiopulmonary resuscitation. This manikin was designed in accordance with anatomical dimensions using a polyoxymethylene rib cage connected to a vertebral column from an anatomical female model. The respiratory system was composed of silicon-coated memory foam mimicking lungs, a polyvinylchloride bronchus and a latex trachea. The cardiovascular system was composed of two sets of latex tubing representing the pulmonary and aortic arteries which were connected to latex balloons mimicking the ventricles and lumped abdominal volumes, respectively. These balloons were filled with Life/form simulation blood and placed inside polyether foam. The respiratory and cardiovascular systems were equipped with flow sensors to gather data in response to chest compressions. Three non-medical professionals performed chest compressions on this manikin yielding data corresponding to force-displacement while the flow sensors provided feedback. The force-displacement tests on this manikin show a desirable nonlinear behaviour mimicking chest compressions during cardiopulmonary resuscitation in humans. In addition, the flow sensors provide valuable data on the internal effects of cardiopulmonary resuscitation. In conclusion, scientifically designed and anatomically high-fidelity designs of cardiopulmonary resuscitation manikins that embed flow sensors can improve physiological fidelity and provide useful feedback data.
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http://dx.doi.org/10.1177/0954411917691555DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5363502PMC
March 2017

Features of Heart Rate Variability Capture Regulatory Changes During Kangaroo Care in Preterm Infants.

J Pediatr 2017 Mar 15;182:92-98.e1. Epub 2016 Dec 15.

Department of Neonatology, Máxima Medical Center, Veldhoven, The Netherlands; Department of Pediatrics, Maastricht University Medical Center, Faculty of Health, Medicine and Life Sciences, School for Mental Health and Neuroscience, Maastricht University, Maastricht, The Netherlands.

Objective: To determine whether heart rate variability (HRV) can serve as a surrogate measure to track regulatory changes during kangaroo care, a period of parental coregulation distinct from regulation within the incubator.

Study Design: Nurses annotated the starting and ending times of kangaroo care for 3 months. The pre-kangaroo care, during-kangaroo care, and post-kangaroo care data were retrieved in infants with at least 10 accurately annotated kangaroo care sessions. Eight HRV features (5 in the time domain and 3 in the frequency domain) were used to visually and statistically compare the pre-kangaroo care and during-kangaroo care periods. Two of these features, capturing the percentage of heart rate decelerations and the extent of heart rate decelerations, were newly developed for preterm infants.

Results: A total of 191 kangaroo care sessions were investigated in 11 preterm infants. Despite clinically irrelevant changes in vital signs, 6 of the 8 HRV features (SD of normal-to-normal intervals, root mean square of the SD, percentage of consecutive normal-to-normal intervals that differ by >50 ms, SD of heart rate decelerations, high-frequency power, and low-frequency/high-frequency ratio) showed a visible and statistically significant difference (P <.01) between stable periods of kangaroo care and pre-kangaroo care. HRV was reduced during kangaroo care owing to a decrease in the extent of transient heart rate decelerations.

Conclusion: HRV-based features may be clinically useful for capturing the dynamic changes in autonomic regulation in response to kangaroo care and other changes in environment and state.
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http://dx.doi.org/10.1016/j.jpeds.2016.11.059DOI Listing
March 2017

A Review of Wearable Sensor Systems for Monitoring Body Movements of Neonates.

Sensors (Basel) 2016 Dec 14;16(12). Epub 2016 Dec 14.

Center for Intelligent Medical Electronics, Department of Electronic Engineering, School of Information Science and Technology, Fudan University, Shanghai 200433, China.

Characteristics of physical movements are indicative of infants' neuro-motor development and brain dysfunction. For instance, infant seizure, a clinical signal of brain dysfunction, could be identified and predicted by monitoring its physical movements. With the advance of wearable sensor technology, including the miniaturization of sensors, and the increasing broad application of micro- and nanotechnology, and smart fabrics in wearable sensor systems, it is now possible to collect, store, and process multimodal signal data of infant movements in a more efficient, more comfortable, and non-intrusive way. This review aims to depict the state-of-the-art of wearable sensor systems for infant movement monitoring. We also discuss its clinical significance and the aspect of system design.
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http://dx.doi.org/10.3390/s16122134DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5191114PMC
December 2016

Unobtrusive Monitoring of Neonatal Brain Temperature Using a Zero-Heat-Flux Sensor Matrix.

IEEE J Biomed Health Inform 2016 Jan 22;20(1):100-7. Epub 2014 Dec 22.

The temperature of preterm neonates must be maintained within a narrow window to ensure their survival. Continuously measuring their core temperature provides an optimal means of monitoring their thermoregulation and their response to environmental changes. However, existing methods of measuring core temperature can be very obtrusive, such as rectal probes, or inaccurate/lagging, such as skin temperature sensors and spot-checks using tympanic temperature sensors. This study investigates an unobtrusive method of measuring brain temperature continuously using an embedded zero-heat-flux (ZHF) sensor matrix placed under the head of the neonate. The measured temperature profile is used to segment areas of motion and incorrect positioning, where the neonate's head is not above the sensors. We compare our measurements during low motion/stable periods to esophageal temperatures for 12 preterm neonates, measured for an average of 5 h per neonate. The method we propose shows good correlation with the reference temperature for most of the neonates. The unobtrusive embedding of the matrix in the neonate's environment poses no harm or disturbance to the care work-flow, while measuring core temperature. To address the effect of motion on the ZHF measurements in the current embodiment, we recommend a more ergonomic embedding ensuring the sensors are continuously placed under the neonate's head.
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http://dx.doi.org/10.1109/JBHI.2014.2385103DOI Listing
January 2016

Maternal allopurinol administration during suspected fetal hypoxia: a novel neuroprotective intervention? A multicentre randomised placebo controlled trial.

Arch Dis Child Fetal Neonatal Ed 2015 May 15;100(3):F216-23. Epub 2014 Dec 15.

Department of Perinatology, University Medical Center, Utrecht, The Netherlands.

Objective: To determine whether maternal allopurinol treatment during suspected fetal hypoxia would reduce the release of biomarkers associated with neonatal brain damage.

Design: A randomised double-blind placebo controlled multicentre trial.

Patients: We studied women in labour at term with clinical indices of fetal hypoxia, prompting immediate delivery.

Setting: Delivery rooms of 11 Dutch hospitals.

Intervention: When immediate delivery was foreseen based on suspected fetal hypoxia, women were allocated to receive allopurinol 500 mg intravenous (ALLO) or placebo intravenous (CONT).

Main Outcome Measures: Primary endpoint was the difference in cord S100ß, a tissue-specific biomarker for brain damage.

Results: 222 women were randomised to receive allopurinol (ALLO, n=111) or placebo (CONT, n=111). Cord S100ß was not significantly different between the two groups: 44.5 pg/mL (IQR 20.2-71.4) in the ALLO group versus 54.9 pg/mL (IQR 26.8-94.7) in the CONT group (difference in median -7.69 (95% CI -24.9 to 9.52)). Post hoc subgroup analysis showed a potential treatment effect of allopurinol on the proportion of infants with a cord S100ß value above the 75th percentile in girls (ALLO n=5 (12%) vs CONT n=10 (31%); risk ratio (RR) 0.37 (95% CI 0.14 to 0.99)) but not in boys (ALLO n=18 (32%) vs CONT n=15 (25%); RR 1.4 (95% CI 0.84 to 2.3)). Also, cord neuroketal levels were significantly lower in girls treated with allopurinol as compared with placebo treated girls: 18.0 pg/mL (95% CI 12.1 to 26.9) in the ALLO group versus 32.2 pg/mL (95% CI 22.7 to 45.7) in the CONT group (geometric mean difference -16.4 (95% CI -24.6 to -1.64)).

Conclusions: Maternal treatment with allopurinol during fetal hypoxia did not significantly lower neuronal damage markers in cord blood. Post hoc analysis revealed a potential beneficial treatment effect in girls.

Trial Registration Number: NCT00189007, Dutch Trial Register NTR1383.
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http://dx.doi.org/10.1136/archdischild-2014-306769DOI Listing
May 2015

Mimo pillow--an intelligent cushion designed with maternal heart beat vibrations for comforting newborn infants.

IEEE J Biomed Health Inform 2015 May 18;19(3):979-85. Epub 2014 Aug 18.

Premature infants are subject to numerous interventions ranging from a simple diaper change to surgery while residing in neonatal intensive care units. These neonates often suffer from pain, distress, and discomfort during the first weeks of their lives. Although pharmacological pain treatment often is available, it cannot always be applied to relieve a neonate from pain or discomfort. This paper describes a nonpharmacological solution, called Mimo, which provides comfort through mediation of a parent's physiological features to the distressed neonate via an intelligent pillow system embedded with sensing and actuating functions. We present the design, the implementation, and the evaluation of the prototype. Clinical tests at Máxima Medical Center in the Netherlands show that among the nine of ten infants who showed discomfort following diaper change, a shorter recovery time to baseline skin conductance analgesimeter values could be measured when the maternal heartbeat vibration in the Mimo was switched ON and in seven of these ten a shorter crying time was measured.
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http://dx.doi.org/10.1109/JBHI.2014.2349153DOI Listing
May 2015

Non-contact heart rate monitoring utilizing camera photoplethysmography in the neonatal intensive care unit - a pilot study.

Early Hum Dev 2013 Dec 14;89(12):943-8. Epub 2013 Oct 14.

Department of Pediatrics, Máxima Medical Center, Veldhoven, The Netherlands. Electronic address:

Background: Presently the heart rate is monitored in the Neonatal Intensive Care Unit with contact sensors: electrocardiogram or pulse oximetry. These techniques can cause injuries and infections, particularly in very premature infants with fragile skin. Camera based plethysmography was recently demonstrated in adults as a contactless method to determine heart rate.

Aim: To investigate the feasibility of this technique for NICU patients and identify challenging conditions.

Study Design And Participants: Video recordings using only ambient light were made of 19 infants at two NICUs in California and The Netherlands. Heart rate can be derived from these recordings because each cardiovascular pulse wave induces minute pulsatile skin color changes, invisible to the eye but measurable with a camera.

Results: In all infants the heart beat induced photoplethysmographic signal was strong enough to be measured. Low ambient light level and infant motion prevented successful measurement from time to time.

Conclusions: Contactless heart rate monitoring by means of a camera using ambient light was demonstrated for the first time in the NICU population and appears feasible. Better hardware and improved algorithms are required to increase robustness.
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http://dx.doi.org/10.1016/j.earlhumdev.2013.09.016DOI Listing
December 2013

Efficacy of feed forward and feedback signaling for inflations and chest compression pressure during cardiopulmonary resuscitation in a newborn mannequin.

J Clin Med Res 2012 Aug 20;4(4):274-8. Epub 2012 Jul 20.

Maxima Medical Centre, Department of Pediatrics, division of neonatology, P.O. Box 7777, 5500 MB, Veldhoven, The Netherlands.

Background: The objective of the study was to evaluate a device that supports professionals during neonatal cardiopulmonary resuscitation (CPR). The device features a box that generates an audio-prompted rate guidance (feed forward) for inflations and compressions, and a transparent foil that is placed over the chest with marks for inter nipple line and sternum with LED's incorporated in the foil indicating the exerted force (feedback).

Methods: Ten pairs (nurse/doctor) performed CPR on a newborn resuscitation mannequin. All pairs initially performed two sessions. Thereafter two sessions were performed in similar way, after randomization in 5 pairs that used the device and 5 pairs that performed CPR without the device (controls). A rhythm score was calculated based on the number of CPR cycles that were performed correctly.

Results: The rhythm score with the device improved from 85 ± 14 to 99 ± 2% (P < 0.05). In the control group no differences were observed. The recorded pressures with the device increased from 3.1 ± 1.6 to 4.9 ± 0.8 arbitrary units (P < 0.05). The second performance of the teams showed significant better results for the group with the CPR device compared to the controls.

Conclusion: Feed forward and feedback signaling leads to a more constant rhythm and chest compression pressure during CPR.
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http://dx.doi.org/10.4021/jocmr865wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3409623PMC
August 2012

Multi-channel amplitude-integrated EEG characteristics in preterm infants with a normal neurodevelopment at two years of corrected age.

Early Hum Dev 2012 Apr 15;88(4):209-16. Epub 2011 Sep 15.

Máxima Medical Center, Veldhoven, The Netherlands.

Aim: To analyze quantitatively multi-channel amplitude-integrated EEG (aEEG) characteristics and assess regional differences.

Methods: We investigated 40 preterm infants (postmenstrual age, PMA: range 27-37 weeks) with normal follow-up at 24 months of age, at a median postnatal age of 8 days using 4-h EEG recordings according to the international 10-20 system reduced montage. Nine (3 transverse and 6 longitudinal) channels were selected and converted to aEEG registrations. For each aEEG registration, lower margin amplitude (LMA), upper margin amplitude (UMA) and bandwidth (UMA-LMA) were calculated.

Results: In all channels PMA and LMA showed strong positive correlations. Below 32 weeks of PMA, LMA was ≤5μV. Linear regression analysis showed a maximum LMA difference between channels of approximately 2 and 1μV at 27 and 37 weeks of PMA, respectively. The lowest are LMA values in the occipital channel and the highest values are in centro-occipital channels. In the frontal, centro-temporal and centro-occipital channels, UMA and bandwidth changed with PMA. No differences in LMA, UMA and bandwidth were found between hemispheres. Skewness of LMA values strongly correlated with PMA, positive skewness indicating an immature brain (PMA≤32 weeks) and negative skewness a maturing (PMA>32 weeks) brain.

Conclusions: We detected symmetric increase of aEEG characteristics, indicating symmetric brain maturation of the left and right hemispheres. Our findings demonstrate the clinical potential of computer-assisted analyses of aEEG recordings in detecting maturational features which are not readily identified visually. This may provide an objective and reproducible method for assessing brain maturation and long-term prognosis.
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http://dx.doi.org/10.1016/j.earlhumdev.2011.08.008DOI Listing
April 2012

Maturational changes in automated EEG spectral power analysis in preterm infants.

Pediatr Res 2011 Nov;70(5):529-34

Neonatal Intensive Care Unit, Máxima Medical Center, 5500 MB Veldhoven, The Netherlands.

Our study aimed at automated power spectral analysis of the EEG in preterm infants to identify changes of spectral measures with maturation. Weekly (10-20 montage) 4-h EEG recordings were performed in 18 preterm infants with GA <32 wk and normal neurological follow-up at 2 y, resulting in 79 recordings studied from 27(+4) to 36(+3) wk of postmenstrual age (PMA, GA + postnatal age). Automated spectral analysis was performed on 4-h EEG recordings. The frequency spectrum was divided in delta 1 (0.5-1 Hz), delta 2 (1-4 Hz), theta (4-8 Hz), alpha (8-13 Hz), and beta (13-30 Hz) band. Absolute and relative power of each frequency band and spectral edge frequency were calculated. Maturational changes in spectral measures were observed most clearly in the centrotemporal channels. With advancing PMA, absolute powers of delta 1 to 2 and theta decreased. With advancing PMA, relative power of delta 1 decreased and relative powers of alpha and beta increased, respectively. In conclusion, with maturation, spectral analysis of the EEG showed a significant shift from the lower to the higher frequencies. Computer analysis of EEG will allow an objective and reproducible analysis for long-term prognosis and/or stratification of clinical treatment.
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http://dx.doi.org/10.1203/PDR.0b013e31822d748bDOI Listing
November 2011

Rhythm of Life Aid (ROLA): an integrated sensor system for supporting medical staff during cardiopulmonary resuscitation (CPR) of newborn infants.

IEEE Trans Inf Technol Biomed 2010 Nov 18;14(6):1468-74. Epub 2010 May 18.

Department of Industrial Design, Eindhoven University of Technology, 5612 AZ, Eindhoven, The Netherland.

During the stress of cardiopulmonary resuscitation (CPR), it is difficult to maintain the right rhythm and correct ratio of insufflations to chest compressions and to exert the compressions at a constant pressure. In this paper, we propose and demonstrate an integrated sensor system-the "Rhythm of Life Aid" (ROLA) to support medical staff during CPR of newborn infants. The design concept is based on interactive audio and visual feedback with consideration of functionalities and user friendliness. A prototype ROLA device is built, consisting of a transparent foil integrated with pressure sensor and electroluminescent foil actuators for indication of the exerted chest compression pressure, as well as an audio box to generate distinctive sounds as audio guidance for insufflations and compressions. To evaluate the performance of the ROLA device, a sensory mannequin and a dedicated software interface are implemented to give immediate feedback and record data for further processing. Tests of the ROLA prototype on the sensory mannequin by ten pairs of a doctor and a nurse at Máxima Medical Centre in Veldhoven, The Netherlands show that the use of ROLA device achieves a more constant rhythm and pressure of chest compressions during CPR of newborn infants.
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http://dx.doi.org/10.1109/TITB.2010.2050592DOI Listing
November 2010

Antenatal allopurinol for reduction of birth asphyxia induced brain damage (ALLO-Trial); a randomized double blind placebo controlled multicenter study.

BMC Pregnancy Childbirth 2010 Feb 18;10. Epub 2010 Feb 18.

Perinatal Center, University Medical Center, Utrecht, the Netherlands.

Background: Hypoxic-ischaemic encephalopathy is associated with development of cerebral palsy and cognitive disability later in life and is therefore one of the fundamental problems in perinatal medicine. The xanthine-oxidase inhibitor allopurinol reduces the formation of free radicals, thereby limiting the amount of hypoxia-reperfusion damage. In case of suspected intra-uterine hypoxia, both animal and human studies suggest that maternal administration of allopurinol immediately prior to delivery reduces hypoxic-ischaemic encephalopathy.

Methods/design: The proposed trial is a randomized double blind placebo controlled multicenter study in pregnant women at term in whom the foetus is suspected of intra-uterine hypoxia.Allopurinol 500 mg IV or placebo will be administered antenatally to the pregnant woman when foetal hypoxia is suspected. Foetal distress is being diagnosed by the clinician as an abnormal or non-reassuring foetal heart rate trace, preferably accompanied by either significant ST-wave abnormalities (as detected by the STAN-monitor) or an abnormal foetal blood scalp sampling (pH < 7.20).Primary outcome measures are the amount of S100B (a marker for brain tissue damage) and the severity of oxidative stress (measured by isoprostane, neuroprostane, non protein bound iron and hypoxanthine), both measured in umbilical cord blood. Secondary outcome measures are neonatal mortality, serious composite neonatal morbidity and long-term neurological outcome. Furthermore pharmacokinetics and pharmacodynamics will be investigated.We expect an inclusion of 220 patients (110 per group) to be feasible in an inclusion period of two years. Given a suspected mean value of S100B of 1.05 ug/L (SD 0.37 ug/L) in the placebo group this trial has a power of 90% (alpha 0.05) to detect a mean value of S100B of 0.89 ug/L (SD 0.37 ug/L) in the 'allopurinol-treated' group (z-test2-sided). Analysis will be by intention to treat and it allows for one interim analysis.

Discussion: In this trial we aim to answer the question whether antenatal allopurinol administration reduces hypoxic-ischaemic encephalopathy in neonates exposed to foetal hypoxia.

Trial Registration Number: Clinical Trials, protocol registration system: NCT00189007.
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http://dx.doi.org/10.1186/1471-2393-10-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2834613PMC
February 2010

Cerebral MRI abnormalities in a premature infant with later confirmed congenital central hypoventilation syndrome.

Eur J Pediatr 2010 Jul 2;169(7):895-8. Epub 2009 Dec 2.

Department of Neonatology, Máxima Medical Centre, PO Box 7777, 5500 MB, Veldhoven, The Netherlands.

We present a premature infant with an inability to ventilate spontaneously during sleep periods. In addition, the patient showed general hypotonia. The child had a delayed passage of stool and increased anal muscle tone, indicating Hirschsprung's disease. The combination of these symptoms suggested congenital central hypoventilation syndrome, which was confirmed postmortem by DNA analysis showing a mutation in the PHOX2B gene. MRI of the brain showed damage to the white matter, including the internal capsula. This type of damage to the white matter has not been described before in a premature infant, who did not experience birth asphyxia.
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http://dx.doi.org/10.1007/s00431-009-1112-zDOI Listing
July 2010

Furosemide in preterm infants treated with indomethacin for patent ductus arteriosus.

Acta Paediatr 2009 May 2;98(5):797-803. Epub 2009 Feb 2.

Department of Neonatology, Máxima Medical Centre, Veldhoven, The Netherlands.

Objective: To evaluate the effect of furosemide on renal function and water balance in preterm infants treated with indomethacin (3 x 0.2 mg/kg at 12-h intervals) for symptomatic patent ductus arteriosus.

Patients And Methods: We performed a retrospective multi-centre double cohort study in preterm infants <32 weeks of gestational age. Thirty-two infants treated with furosemide (1 mg/kg i.v.) before each indomethacin dose (furosemide group) were matched with 32 infants with indomethacin treatment alone (control-group). Renal effects (urine output, weight gain, serum creatinine, sodium concentration) were registered.

Results: The study groups were comparable for gestational age, birth weight and day of therapy. Pretreatment differences were observed for urine output, weight and serum sodium. However, no differences were noticed in day-to-day urine output change or weight gain between the groups. A significant increase in serum creatinine concentration (50% vs. control, 18%; p < 0.05) and a concomitant significant decrease in serum sodium (-9 vs. control, -3 mmoL/L; p < 0.05) in the furosemide group was observed 72-96 h after starting therapy.

Conclusion: Furosemide before each indomethacin dose resulted in a significant increase in serum creatinine and hyponatremia, without increasing urine output.
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http://dx.doi.org/10.1111/j.1651-2227.2009.01224.xDOI Listing
May 2009

Feasibility of noninvasive continuous finger arterial blood pressure measurements in very young children, aged 0-4 years.

Pediatr Res 2008 Jun;63(6):691-6

Neonatal Intensive Care Unit, Máxima Medical Center, 5500 MB Veldhoven, The Netherlands.

Our goal was to study the feasibility of continuous noninvasive finger blood pressure (BP) monitoring in very young children, aged 0-4 y. To achieve this, we designed a set of small-sized finger cuffs based on the assessment of finger circumference. Finger arterial BP measured by a volume clamp device (Finapres technology) was compared with simultaneously measured intra-arterial BP in 15 very young children (median age, 5 mo; range, 0-48), admitted to the intensive care unit for vital monitoring. The finger cuff-derived BP waveforms showed good resemblance with the invasive arterial waveforms (mean root-mean-square error, 3 mm Hg). The correlation coefficient between both methods was 0.79 +/- 0.19 systolic and 0.74 +/- 0.24 diastolic. The correlation coefficient of beat-to-beat changes between both methods was 0.82 +/- 0.18 and 0.75 +/- 0.21, respectively. Three measurements were related to measurement errors (loose cuff application; wrong set-point). Excluding these erroneous measurements resulted in clinically acceptable measurement bias (-3.8 mm Hg) and 95% limits of agreement (-10.4 to + 2.8 mm Hg) of mean BP values. We conclude that continuous finger BP measurement is feasible in very young children. However, cuff application is critical, and the current set-point algorithm needs to be revised in very young children.
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http://dx.doi.org/10.1203/PDR.0b013e31816c8fe3DOI Listing
June 2008

Baroreceptor reflex sensitivity in human neonates: the effect of postmenstrual age.

J Physiol 2005 Oct 28;568(Pt 1):333-41. Epub 2005 Jul 28.

Máxima Medical Center, Neonatal Intensive Care Unit, PO Box 7777, 5500 MB Veldhoven, the Netherlands.

We performed a cross-sectional study in human infants to determine if indices of R-R interval variability, systolic blood pressure (SBP) variability, and baroreceptor reflex sensitivity change with postmenstrual age (PMA: gestational age+postnatal age). The electrocardiogram, arterial SBP and respiration were recorded in clinically stable infants (PMA, 28-42 weeks) in the quiet sleep state in the first days after birth. (Cross-)spectral analyses of R-R interval series and SBP series were performed to calculate the power of low-frequency (LF, indicating baroreceptor reflex activity, 0.04-0.15 Hz) and high-frequency (HF, indicating parasympathetic activity, individualized between the p-10 and p-90 values of respiratory frequency) fluctuations, and transfer function phase and gain. The mean R-R interval, and LF and HF spectral powers of R-R interval series increased with PMA. The mean SBP increased with PMA, but not the LF and HF spectral powers of SBP series. In the LF range, cross-spectral analysis showed high coherence values (>0.5) with a consistent negative phase shift between R-R interval and SBP, indicating a approximately 3 s lag in R-R interval changes in relation to SBP. Baroreceptor reflex sensitivity, calculated from LF transfer gain, increased significantly with PMA, from 5 (preterm) to 15 ms mmHg-1 (term). Baroreceptor reflex sensitivity correlated significantly with the (LF and) HF spectral powers of R-R interval series, but not with the LF and HF spectral powers of SBP series. The principal conclusions are that baroreceptor reflex sensitivity and spectral power in R-R interval series increase in parallel with PMA, suggesting a progressive vagal maturation with PMA.
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http://dx.doi.org/10.1113/jphysiol.2005.093641DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1474770PMC
October 2005

Early neonatal dexamethasone treatment for prevention of bronchopulmonary dysplasia. Randomised trial and meta-analysis evaluating the duration of dexamethasone therapy.

Eur J Pediatr 2005 Aug 28;164(8):472-81. Epub 2005 Apr 28.

Department of Paediatrics, University of Oulu, 5000, 90014 Oulu, Finland.

Unlabelled: The aim of the aborted trial was to determine whether the short early dexamethasone (DX) given after the birth improves the early outcome. We also reviewed the evidence (meta-analysis) to determine whether the duration of early DX treatment influences the early outcome, particularly in terms of bronchopulmonary dysplasia (BPD). The participants of the randomised multicentre, double-blinded placebo-controlled trial had a birth weight 500-999 g, gestation < or = 31.0 weeks, and respiratory failure by the age of 4 h. The infants received either four doses of DX (0.25 mg/kg at 12 h intervals) or placebo. The meta-analysis was performed to determine the beneficial and adverse effects of early short (<96 h duration) versus early prolonged (>96 h) DX treatment. The trial was discontinued after 109 infants had been enrolled. There was a non-significant improvement in the outcome (survival without BPD, severe intracranial haemorrhage or periventricular leukomalacia; RR 1.27; 95% CI 0.87-1.85). The risks for gastrointestinal perforation and hyperglycaemia tended to increase. A total of 15 trials were included in the meta-analysis: 10 involved prolonged (i.e. >96 h; 1594 infants) and five short interventions (1069 infants). Early prolonged DX decreased the RR for BPD to 0.72 (95% CI 0.61-0.87), whereas early short DX course did not significantly decrease the risk (RR 0.82; 95% CI 0.64-1.05). Gastrointestinal haemorrhages and perforations were significantly increased only in the early prolonged DX group.

Conclusion: The dosage and duration of early corticosteroid given to small premature infants influences the risk of the side-effects and the early outcome.
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http://dx.doi.org/10.1007/s00431-005-1645-8DOI Listing
August 2005

Activation of the inflammatory reaction within minutes after birth in ventilated preterm lambs with neonatal respiratory distress syndrome.

Biol Neonate 2004 21;86(1):1-5. Epub 2004 Jan 21.

Department of Pediatrics, Division of Biocompatibility, University of Groningen, Groningen, The Netherlands.

To study the activation of the inflammatory reaction within minutes after birth, we measured parameters of inflammation before and immediately after birth. To assess whether respiratory distress syndrome (RDS) or birth itself initiates activation, we compared preterm ventilated lambs with term nonventilated lambs. Preterm lambs were delivered by cesarean section at 132 days gestational age (term 145 days) and were ventilated by conventional ventilation (n = 9). Before clamping the cord, 5, 10 and 15 min after birth, blood was sampled from umbilical catheters. Term lambs (n = 9) were born spontaneously after 140-145 days gestational age. Immediately after birth, a venous umbilical catheter was inserted. Blood was sampled before the first breath and 5, 10, 15 and 20 min after birth while the lamb was breathing spontaneously. Blood was analyzed for AP50 (complement activation), number of polymorphonuclear leukocytes (PMNs) and beta-glucuronidase (released from activated PMNs). In preterm lambs, we found a decreased number of PMNs and increased levels of beta-glucuronidase already at 5 min after birth. In the term lambs, we found only a short-term mild decrease in PMNs and short-term increase in beta-glucuronidase. We conclude that systemic activation of the inflammatory reaction can be found in ventilated preterm lambs with RDS within 5 min after birth. This very early activation is mild, transient and less pronounced in term-born spontaneously breathing lambs compared with preterm, ventilated lambs with RDS.
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http://dx.doi.org/10.1159/000076366DOI Listing
January 2005

Antenatal glucocorticoids attenuate activation of the inflammatory reaction and clotting in preterm lambs.

Biol Neonate 2004 19;85(2):82-9. Epub 2003 Nov 19.

Department of Pediatrics, University Hospital Groningen, Groningen, The Netherlands.

Recently we have shown that activation of inflammatory reaction and clotting can be found immediately after delivery in preterm lambs ventilated for respiratory distress syndrome (RDS). To investigate whether antenatal glucocorticoids would attenuate postnatal activation of the inflammatory reaction and clotting, we studied ventilated preterm lambs delivered by cesarean section, 24 h after antenatal administration of betamethasone or placebo. Blood was sampled before clamping the cord, 5, 10, and 15 min after delivery, and 2-hourly afterwards. Blood was used to determine oxygenation index, alveolar - arterial partial O(2) difference (AaDO(2)), AP50 titer (see text), polymorphonuclear leukocytes (PMNs), beta-glucuronidase, thrombin inhibition, activated partial thromboplastin time, and clot lysis time. Bronchoalveolar lavage fluid was sampled before clamping the cord and 30 min and 1, 2, 4, 6 and 8 h after delivery and was analyzed for elastase, thrombin, and protein. After removal of the lungs, static compliance and water content of the lungs were determined. We found that betamethasone-treated lambs had lower oxygenation index and AaDO(2) than controls. At birth, PMN levels were higher, and the beta-glucuronidase level was lower after betamethasone treatment. PMNs and beta-glucuronidase did not change in betamethasone-treated lambs, in contrast to controls. Thrombin inhibition, activated partial thromboplastin time, and clot lysis time did not change in betamethasone-treated lambs, in contrast to controls. In both groups, elastase and protein levels in bronchoalveolar lavage fluid increased; the thrombin level increased in controls. The static compliance was better, and the water content of the lung was lower in the betamethasone-treated lambs. We conclude that early systemic activation of inflammatory reaction and clotting in preterm lambs with RDS are attenuated by antenatal betamethasone administration. Whether this is a direct effect of betamethasone on the inflammatory reaction or a result of a reduced ventilatory support because of less severe RDS after antenatal betamethasone treatment remains to be elucidated.
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http://dx.doi.org/10.1159/000074963DOI Listing
October 2004

SP-A-enriched surfactant for treatment of rat lung transplants with SP-A deficiency after storage and reperfusion.

Transplantation 2002 Feb;73(3):348-52

Department of Cardiopulmonary Surgery, Research Division, University Hospital Groningen, Groningen, The Netherlands.

Background: The function of pulmonary surfactant is affected by lung transplantation, contributing to impaired lung transplant function. A decreased amount of surfactant protein-A (SP-A) after reperfusion is believed to contribute to the impaired surfactant function. Surfactant treatment has been shown to improve lung transplant function, but the effect is variable. We investigated whether SP-A enrichment of surfactant improved the efficacy of surfactant treatment in lung transplantation.

Methods: Left and right lungs of Lewis rats, inflated with 50% O2, were stored for 20 hr at 8 degrees C. Surfactant in bronchoalveolar lavage fluid from right lungs was investigated after storage (n=6). Left lungs were transplanted into syngeneic recipients and treated with SP-A-deficient surfactant (n=6) or SP-A-enriched surfactant (n=6) just before reperfusion. Air was instilled into untreated lung transplants (n=6). Sham operated (n=4) and normal (n=8) animals served as controls. Lung function was measured during 1 hr of reperfusion; surfactant components in bronchoalveolar lavage fluid were measured after reperfusion.

Results: After storage the amount of SP-A decreased by 27%, whereas surfactant phospholipids changed minimally. After reperfusion a further decrease of SP-A was paralleled by profound changes in surfactant phospholipids. Lung transplant function, however, remained relatively good. After instillation of SP-A-enriched surfactant, PO2 values were reached that approximated sham control PO2 values, whereas after SP-A-deficient surfactant treatment, the PO2 values did not improve.

Conclusion: Enrichment of surfactant with SP-A for treatment of lung transplants improves the efficacy of surfactant treatment.
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http://dx.doi.org/10.1097/00007890-200202150-00006DOI Listing
February 2002
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