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1. Fecal amine metabolite analysis before onset of severe necrotizing enterocolitis in preterm infants

Author

Deianova, N., El Hassani, S.E., Struijs, E.A., Jansen, E.E.W., Bakkali, A., van de Wiel, M.A., de Boode, W.P., Hulzebos, C.V., van Kaam, A.H., Kramer, B.W., D'Haens, E., Vijlbrief, D.C., van Weissenbruch, M.M., de Jonge, W.J., Benninga, M.A., Niemarkt, H.J., de Boer, N.K.H., de Meij, T.G.J., Neonatology, ARD - Amsterdam Reproduction and Development, Gastroenterology and Hepatology, Tytgat Institute for Liver and Intestinal Research, AGEM - Amsterdam Gastroenterology Endocrinology Metabolism, Paediatric Gastroenterology, Pediatrics, Amsterdam Neuroscience - Cellular & Molecular Mechanisms, Amsterdam Gastroenterology Endocrinology Metabolism, Laboratory Medicine, Epidemiology and Data Science, APH - Methodology, Amsterdam Reproduction & Development (AR&D), Gastroenterology and hepatology, Center for Liver, Digestive and Metabolic Diseases (CLDM), Reproductive Origins of Adult Health and Disease (ROAHD), RS: GROW - R4 - Reproductive and Perinatal Medicine, RS: MHeNs - R3 - Neuroscience, Kindergeneeskunde, and MUMC+: MA Medische Staf Kindergeneeskunde (9)

Subjects
BIRTH-WEIGHT INFANTS, Multidisciplinary, IMPACT, Lysine, Vascular damage Radboud Institute for Health Sciences [Radboudumc 16], GUT MICROBIOTA, Infant, Newborn, Infant, Infant, Newborn, Diseases, AGE, Enterocolitis, Necrotizing, Ethanolamines, Case-Control Studies, Humans, Amines, Isoleucine, Infant, Premature
Abstract

Contains fulltext : 283142.pdf (Publisher’s version ) (Open Access) Infants developing necrotizing enterocolitis (NEC) have a different metabolomic profile compared to controls. The potential of specific metabolomics, i.e. amino acids and amino alcohols (AAA), as early diagnostic biomarkers for NEC is largely unexplored. In this multicenter prospective case-control study, longitudinally collected fecal samples from preterm infants (born

Published
2022

3. High variability and low irradiance of phototherapy devices in Dutch NICUs

Author

Imhoff, D.E. van, Hulzebos, C.V., Heide, M. van der, Belt, V.W. van den, Vreman, H.J., Dijk, P.H., Liem, K.D., Faculteit Medische Wetenschappen/UMCG, Center for Liver, Digestive and Metabolic Diseases (CLDM), Reproductive Origins of Adult Health and Disease (ROAHD), Kindergeneeskunde, and RS: GROW - School for Oncology and Reproduction

Subjects
Pediatrics, medicine.medical_specialty, High variability, Irradiance, Total serum bilirubin, Child health, Intensive care, Intensive Care Units, Neonatal, Statistics, medicine, Fiber Optic Technology, Humans, Neonatal health, Prospective Studies, Radiometry, Netherlands, HYPERBILIRUBINEMIA, Practice patterns, business.industry, Infant, Newborn, Obstetrics and Gynecology, Reproducibility of Results, Professional Practice, General Medicine, Functional imaging [IGMD 1], Phototherapy, Multicenter study, NEONATAL JAUNDICE, Pediatrics, Perinatology and Child Health, Hyperbilirubinemia, Neonatal, business
Abstract

Item does not contain fulltext OBJECTIVE: To evaluate phototherapy practices by measuring the irradiance levels of phototherapy (PT) devices. DESIGN: Prospective study. SETTING: Tertiary neonatal intensive care units. PATIENTS: None. INTERVENTIONS: Irradiance levels of PT devices used in the 10 Dutch Neonatal Intensive Care Units (NICUs) were measured according to the local PT practice patterns. The irradiance levels of all overhead and fibre-optic PT devices were measured with a radiometer using an infant silhouette model. RESULTS: Eight different PT devices were used in the 10 NICUs; five were overhead devices and three fibre-optic pads. The median (range) irradiance level for overhead PT devices was 9.7 (4.3-32.6) microW/cm(2)/nm and for fibre-optic pads 6.8 (0.8-15.6) microW/cm(2)/nm. Approximately 50% of PT devices failed to meet the minimal recommended irradiance level of 10 microW/cm(2)/nm. Maximal irradiance levels for overhead PT spot lights were inversely related to the distance between device and infant model (R2=0.33). The distances ranged from 37 cm to 65 cm. CONCLUSIONS: PT devices in the Dutch NICUs show considerable variability with often too low irradiance levels. These results indicate that suboptimal PT is frequently applied and may even be ineffective towards reducing total serum bilirubin levels. These results underline the need for greater awareness among all healthcare workers towards the requirements for effective PT including measurements of irradiance and distance. 01 maart 2013

Published
2013

4. The Bilirubin Albumin Ratio in the Management of Hyperbilirubinemia in Preterm Infants to Improve Neurodevelopmental Outcome: A Randomized Controlled Trial - BARTrial

Author

Hulzebos, C.V., Dijk, P.H., Imhoff, D.E. van, Bos, A.F., Lopriore, E., Offringa, M., Ruiter, S.A.J., Braeckel, K.N.J.A. van, Krabbe, P.F.M., Quik, E.H., Toledo-Eppinga, L. van, Nuytemans, D.H.G.M., Wassenaer-Leemhuis, A.G. van, Benders, M.J.N., Korbeeck-van Hof, K.K.M., Lingen, R.A. van, Jebbink, L.J.M.G., Liem, D., Mansvelt, P., Buijs, J., Govaert, P., Vliet, I. van, Mulder, T.L.M., Wolfs, C., Fetter, W.P.F., Laarman, C., BARTrial Study Grp, Klinische Genetica, RS: GROW - Developmental Biology, RS: GROW - R4 - Reproductive and Perinatal Medicine, Other departments, Neonatology, Other Research, Public Health, Neurology, Pediatrics, Pediatric surgery, ICaR - Circulation and metabolism, Developmental and behavioural disorders in education and care: assessment and intervention, Methods in Medicines evaluation & Outcomes research (M2O), Center for Liver, Digestive and Metabolic Diseases (CLDM), and Reproductive Origins of Adult Health and Disease (ROAHD)

Subjects
Male, Pediatrics, Vascular damage Radboud Institute for Health Sciences [Radboudumc 16], lcsh:Medicine, Developmental and Pediatric Neurology, Bayley Scales of Infant Development, law.invention, chemistry.chemical_compound, Child Development, Randomized controlled trial, law, Medicine and Health Sciences, Birth Weight, LOW-BIRTH-WEIGHT, Prospective Studies, lcsh:Science, Prospective cohort study, PREMATURE-INFANTS, Multidisciplinary, Liver Diseases, ASSOCIATION, Neurology, Research Design, Gestation, Pediatric Gastroenterology, Female, Hyperbilirubinemia, Neonatal, medicine.symptom, Infant, Premature, Research Article, medicine.medical_specialty, KERNICTERUS, Clinical Research Design, Bilirubin, Birth weight, Gastroenterology and Hepatology, Research and Analysis Methods, Diagnostic Medicine, medicine, Humans, Liver Disease and Pregnancy, Serum Albumin, PHOTOTHERAPY, business.industry, lcsh:R, Infant, Newborn, JAUNDICED NEWBORNS, medicine.disease, Low birth weight, chemistry, NEUROTOXICITY, Kernicterus, SERUM BILIRUBIN, lcsh:Q, Neonatology, business
Abstract

Contains fulltext : 136978.pdf (Publisher’s version ) (Open Access) BACKGROUND AND OBJECTIVE: High bilirubin/albumin (B/A) ratios increase the risk of bilirubin neurotoxicity. The B/A ratio may be a valuable measure, in addition to the total serum bilirubin (TSB), in the management of hyperbilirubinemia. We aimed to assess whether the additional use of B/A ratios in the management of hyperbilirubinemia in preterm infants improved neurodevelopmental outcome. METHODS: In a prospective, randomized controlled trial, 615 preterm infants of 32 weeks' gestation or less were randomly assigned to treatment based on either B/A ratio and TSB thresholds (consensus-based), whichever threshold was crossed first, or on the TSB thresholds only. The primary outcome was neurodevelopment at 18 to 24 months' corrected age as assessed with the Bayley Scales of Infant Development III by investigators unaware of treatment allocation. Secondary outcomes included complications of preterm birth and death. RESULTS: Composite motor (100 +/- 13 vs. 101 +/- 12) and cognitive (101 +/- 12 vs. 101 +/- 11) scores did not differ between the B/A ratio and TSB groups. Demographic characteristics, maximal TSB levels, B/A ratios, and other secondary outcomes were similar. The rates of death and/or severe neurodevelopmental impairment for the B/A ratio versus TSB groups were 15.4% versus 15.5% (P = 1.0) and 2.8% versus 1.4% (P = 0.62) for birth weights 1000 g. CONCLUSIONS: The additional use of B/A ratio in the management of hyperbilirubinemia in preterm infants did not improve their neurodevelopmental outcome. TRIAL REGISTRATION: Controlled-Trials.com ISRCTN74465643.

Published
2014

5. Evaluation of Treatment Thresholds for Unconjugated Hyperbilirubinemia in Preterm Infants: Effects on Serum Bilirubin and on Hearing Loss?

Author

Hulzebos, C.V., Dommelen, P. van, Verkerk, P.H., Dijk, P.H., and Straaten, H.L.M. van

Subjects
Health, LS - Life Style CH - Child Health, Healthy for Life, Healthy Living, BSS - Behavioural and Societal Sciences, Human
Abstract

Background:Severe unconjugated hyperbilirubinemia may cause deafness. In the Netherlands, 25% lower total serum bilirubin (TSB) treatment thresholds were recently implemented for preterm infants.Objective:To determine the rate of hearing loss in jaundiced preterms treated at high or at low TSB thresholds.Design/Methods:In this retrospective study conducted at two neonatal intensive care units in the Netherlands, we included preterms (gestational age 35 dB).Results:There were 479 patients in the high and 144 in the low threshold group. Both groups had similar gestational ages (29.5 weeks) and birth weights (1300 g). Mean and mean peak TSB levels were significantly lower after the implementation of the novel thresholds: 152±43 μmol/L and 212±52 μmol/L versus 131±37 μmol/L and 188±46 μmol/L for the high versus low thresholds, respectively (P

Published
2013

6. Measurements of neonatal bilirubin and albumin concentrations: a need for improvement and quality control

Author

Imhoff, D.E. van, Dijk, P.H., Weykamp, C.W., Cobbaert, C.M., Hulzebos, C.V., Liem, K.D., Kindergeneeskunde, RS: GROW - School for Oncology and Reproduction, Center for Liver, Digestive and Metabolic Diseases (CLDM), and Reproductive Origins of Adult Health and Disease (ROAHD)

Subjects
Quality Control, Albumin concentrations, Pediatrics, medicine.medical_specialty, Bilirubin, INFANTS, chemistry.chemical_compound, Albumin . Bilirubin . Unconjugated hyperbilirubinemia . Neonates, Neonatal Screening, Albumins, Intensive Care Units, Neonatal, Intensive care, MANAGEMENT, Humans, Medicine, Pediatrics, Perinatology, and Child Health, GESTATION, Netherlands, HYPERBILIRUBINEMIA, Original Paper, Chromatography, business.industry, Albumin, Infant, Newborn, Reproducibility of Results, Neonates, Functional imaging [IGMD 1], Jaundice, PERFORMANCE, Human serum albumin, Quality Improvement, Albumin Measurement, Bilirubin concentration, VARIABILITY, chemistry, JAUNDICE, Pediatrics, Perinatology and Child Health, Unconjugated hyperbilirubinemia, medicine.symptom, business, medicine.drug
Abstract

Item does not contain fulltext Accurate and precise bilirubin and albumin measurements are essential for proper management of jaundiced neonates. Data hereon are lacking for Dutch laboratories. We aimed to determine variability of measurements of bilirubin and albumin concentrations typical for (preterm) neonates. Aqueous, human serum albumin-based samples with different concentrations of bilirubin (100, 200, 300, 400, and 500 mumol/L) and albumin (0, 10, 15, 20, 25, and 30 g/L) were sent to laboratories of all Dutch neonatal intensive care units (n = 10). Bilirubin and albumin recoveries of the specimens were measured using locally available routine analytical methods. The mean, standard deviation, and coefficients of variations (CV) were calculated per sample. Bilirubin concentrations were underestimated in the absence of albumin (maximal CV 26.0%). When the albumin concentration was 10 or 20 g/L, the bilirubin concentrations of the samples were overestimated (maximal CV 14.1% and 9.2%, respectively). Variability increased with higher weighed-in bilirubin concentrations. Measured albumin levels were ~10% lower than albumin levels of manufactured samples. Bilirubin concentration did not influence albumin measurements. The maximal CV was 6.8%. In conclusion, interlaboratory variability of bilirubin and albumin measurements is high. Recalibration and introduction of a specific quality assessment scheme for neonatal samples is recommended to ensure exchangeability of bilirubin and albumin measurements among laboratories and to control the observed large variability.

Published
2011

7. Uniform treatment thresholds for hyperbilirubinemia in preterm infants: background and synopsis of a national guideline

Author

Imhoff, D.E. van, Dijk, P.H., Hulzebos, C.V., Liem, K.D., Center for Liver, Digestive and Metabolic Diseases (CLDM), Reproductive Origins of Adult Health and Disease (ROAHD), Kindergeneeskunde, and RS: GROW - School for Oncology and Reproduction

Subjects
Pediatrics, medicine.medical_specialty, Neonatal intensive care unit, KERNICTERUS, Birth weight, Exchange Transfusion, Whole Blood, Infant, Premature, Diseases, Guidelines, CONSERVATIVE PHOTOTHERAPY, Risk Factors, Intensive care, Intensive Care Units, Neonatal, medicine, Birth Weight, Humans, LOW-BIRTH-WEIGHT, PREMATURE-INFANTS, Hyperbilirubinemia, Netherlands, Asphyxia, OUTCOMES, business.industry, Infant, Newborn, Obstetrics and Gynecology, Gestational age, Preterm infants, Guideline, Functional imaging [IGMD 1], ASSOCIATION, Phototherapy, medicine.disease, RANDOMIZED-TRIAL, Treatment, Low birth weight, NEONATAL JAUNDICE, Pediatrics, Perinatology and Child Health, Practice Guidelines as Topic, Kernicterus, SERUM BILIRUBIN, medicine.symptom, Hyperbilirubinemia, Neonatal, business, Infant, Premature, NEWBORN
Abstract

Background: To prevent severe hyperbilirubinemia and bilirubin neurotoxicity, the American Academy of Pediatrics' management guideline for hyperbilirubinemia in near term infants is used worldwide. A leading guideline for jaundiced preterm infants is lacking whereas the risk on severe hyperbilirubinemia is high in these infants. Our aim was to define uniform treatment thresholds for jaundiced preterm infants. In this article we present the history and a synopsis of this novel national guideline.Study Design: A survey on guidelines for hyperbilirubinemia in preterm infants was sent to all Dutch Neonatal Intensive Care Units (NICUs). After comparison with international guidelines, a new consensus-based guideline was developed.Results: Treatment thresholds of all 10 NICUs were based on Total Serum Bilirubin (TSB) and related to birth weight (n = 9) and gestational age (n = 1). NICUs used age-specific (n = 6) or fixed (n = 4) TSB-thresholds resulting in a large range of thresholds (maximal 170 mu mol/L for phototherapy and 125 mu mol/L for exchange transfusion). Acidosis, asphyxia, sepsis, active hemolysis and intraventricular hemorrhage were the most frequently used risk factors. Consensus was agreed upon TSB-based treatment thresholds, categorized in 5 birth weight groups and divided in high and low risk infants.Conclusion: There was no standardized care for jaundiced preterm infants in the Netherlands. In addition to the internationally used guideline for (near) term infants, a novel "consensus based" guideline for preterm infants with a gestational age of less than 35 weeks has been developed and implemented in the Netherlands. This guideline is approved and recommended by the Dutch Society of Pediatrics. (C) 2011 Elsevier Ireland Ltd. All rights reserved.

Published
2011

11. Cytokines patterns in newborn infants with late onset sepsis.

Author

Lusyati, S., Hulzebos, C.V., Zandvoort, J., Sukandar, H., and Sauer, P.J.J.

Subjects
*CYTOKINES, *NEONATAL diseases, *SEPSIS, *CHEMOKINES, *CHILDREN'S hospitals
Abstract

BACKGROUND: Cytokines might be helpful to diagnose late onset sepsis (LOS) in newborn infants. Many studies on cytokines did not discriminate culture-proven from clinically-suspected sepsis; however, such differentiation is clinically useful. OBJECTIVES: To evaluate the feasibility to differentiate among culture-proven LOS, clinical LOS and controls using a battery of cytokines. STUDY DESIGN: This prospective study was conducted at the NICU of Harapan-Kita Women and Children's Hospital, Jakarta-Indonesia. Three groups of infants with postnatal age >72 hours of age were enrolled in the study: culture-proven sepsis group (PS) (n = 18), clinical sepsis group (CS) (n = 25) and control group (n = 34). A battery of 25 cytokines was measured in each infant five times: at enrollment, after 4 hrs, 12 hrs, 24 hrs, and 48 hrs using Invitrogen-immunoassays-Luminex™100. RESULTS: There were no significant differences in gestational age or mode of delivery among the three groups. IL-1β, IL-2r, IL-6, IL-8, IL-10 and MIP-1a were significantly higher at all measurement points in group PS compared to controls. IL-13 was lower at all measurement moments in group CS compared to controls, IL-12 was lower and IP-10 higher between 0 and 24 hrs. IL-1Ra, IL-6, IL-8, IL-13, IL-15, TNFα, MIP-1a and MIP-1b were higher at all the measurement moments in group PS compared to group CS. The ROC curves show that IL-6, IL-8, IL-15, MIP-1a, MIP-1b and TNFα have a sensitivity and specificity between 80 and 85% during the first 24-48 hours after the onset of infection. IL-6, IL-15, MIP-1a, MIP-1b and TNFα showed the best likelihood ratios. CONCLUSIONS: IL-6, IL8, IL 15, MIP-1a, MIP-1b and TNFα are potentially good markers for detecting a proven LOS. In case these cytokines are not elevated in sick infants, other causes than an infection have to be identified. [ABSTRACT FROM AUTHOR]

Published
2013
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12. Hypoalbuminemia in Donors with Twin-Twin Transfusion Syndrome.

Author

Verbeek, L., Middeldorp, J.M., Hulzebos, C.V., Oepkes, D., Walther, F.J., and Lopriore, E.

Subjects
FETOFETAL transfusion, ALBUMINS, FETOSCOPY, LASER surgery, GESTATIONAL age, CASE-control method
Abstract

Objective: To estimate the differences in albumin levels between donors and recipients with twin-twin transfusion syndrome (TTTS). Methods: We performed a matched case-control study including twin pairs with TTTS treated conservatively (conservative group) or with fetoscopic laser surgery (laser group) and analyzed the albumin levels at birth in donor and recipient twins. Results: We included 18 twin pairs in the conservative group and 36 control twin pairs (laser group), matched for gestational age at birth. Median albumin levels in donor twins in the conservative group were significantly lower than in recipient twins, 25.0 versus 33.0 g/l, respectively (p = 0.001). In the laser group, albumin levels in donors and recipients were similar, 32.0 versus 32.0 g/l, respectively (p = 0.633). Hypoalbuminemia (albumin level <20 g/l) occurred in 22% (4/18) of donor twins in the conservative group. Conclusions: Hypoalbuminemia occurs frequently in donor twins with TTTS treated conservatively. In TTTS treated with laser, donor twins have similar and normal albumin levels compared to recipients, confirming a successfully performed fetoscopic laser procedure. Copyright © 2012 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Published
2013
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13. Progressive facial hemiatrophy: a complex disorder not only affecting the face. A report in a monozygotic male twin pair.

Author

Hulzebos, C.V., deVries, T.W., Armbrust, W., Sauer, P.J.J., and Kerstjens-Frederikse, W.S.

Subjects
*DISEASES in twins, *AUTOIMMUNE diseases, *HUMAN skin color, *JUVENILE diseases, *PEDIATRICS
Abstract

Progressive facial hemiatrophy (PFH) is a ubiquitous disease, characterized by hyperpigmentation of the skin followed by unilateral craniofacial atrophy of subcutaneous tissues, including fat, muscle and bone. Hereditary factors have been postulated to be involved in the aetiology of PFH. Yet, the occurrence of PFH in one of two identical male twins reported here makes this possibility unlikely. PFH usually occurs in the first two decades of life, and the clinical presentation resembles linear scleroderma. PFH may be complicated by autoimmune, neurological, ocular and dental disorders. Management of PFH comprises a long term follow-up of somatic disorders, and prevention of psychological problems. Treatment of PFH is symptomatic and consists of plastic surgery after the disease activity has stopped. Conclusion: The occurrence of PFH in one of a monozygotic twin pair suggests that genetic factors are not involved in its aetiology. Early diagnosis of PFH and accurate follow-up is essential to disclose the occurrence of complications. [ABSTRACT FROM AUTHOR]

Published
2004
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14. Splenic epithelial cysts and splenomegaly: diagnosis and management

Author

Hulzebos, C.V, Leemans, R, Halma, C, and de Vries, T.W

Abstract

Splenomegaly is a common problem. In the absence of systemic illness or malignancy splenic cysts must be considered, especially the epithelial variety. For large cysts total splenectomy has long been recommended. Recognition of the risk of an overwhelming postsplenectomy infection (OPSI), especially in children, has led to spleen conserving surgery. We describe the use of an absorbable Vicryl® net after partial splenectomy with total cystectomy in the management of splenic epitelial cysts.

Published
1998
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16. Optimising neonatal management of haemolytic disease of the foetus and newborn

Author

Ree, I.M.C., Lopriore, E., Haas, M. de, Klink, J.M.M. van, Pas, A.B. te, Reiss, I.K.M., Tiblad, E., Hulzebos, C.V., and Leiden University

Subjects
Alloimmunisation, Haemolysis, Anaemia, Hyperbilirubinaemia, Neonatology, Haemolytic disease of the foetus and newborn, Haematology
Abstract

Haemolytic disease of the foetus and newborn (HDFN) is a condition in which the red blood cells of the foetus and the newborn child are destructed due to maternal alloantibodies. This can lead to anaemia already in early pregnancy. In case of severe anaemia, it can be necessary to perform one or more blood transfusions to the anaemic foetus, so called intrauterine transfusions (IUTs). This thesis evaluates the current therapy for HDFN and describes exogenous erythropoietin as potential new therapeutic agent to treat anaemia. It also gives starting points to individualise the treatment of these children in the future, as predictive values were identified for a more severe neonatal disease course. In addition to short-term outcomes measures after birth, the long-term effects of IUTs were also critically evaluated to optimise the treatment of HDFN.

Published
2022

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