Publications by authors named "Koen F M Joosten"

113 Publications

Evaluation of the OSA treatment protocol in syndromic craniosynostosis during the first 6 years of life.

J Plast Reconstr Aesthet Surg 2021 Mar 28. Epub 2021 Mar 28.

Department of Plastic Surgery, Sophia Children's Hospital - Erasmus Medical Center, Rotterdam, Netherlands.

Introduction: Obstructive sleep apnea (OSA) is frequently present in patients with syndromic craniosynostosis. The aim of this study is to determine the long-term effectiveness of our OSA treatment protocol in our tertiary center in a cohort of children with syndromic craniosynostosis.

Methods: Children with syndromic craniosynostosis born between January 2005 and December 2013 were eligible for inclusion (n = 114). Data from ambulatory and inhospital polysomnographies were used. The obstructive-apnea/hypopnea index was used for OSA classification.

Results: Polysomnographies were performed in 83 patients. Mild OSA was diagnosed in 19, moderate in six, and severe in seven children. Of the 32 patients with OSA, 12 patients (37.5%) initially received expectant care of which OSA resolved spontaneously in nine without recurrence. Twenty patients were surgically treated. Adenotonsillectomy (ATE) had a 90% success rate with no OSA recurrence. Monobloc surgery was performed in four patients with mild OSA, although not OSA-indicated. Monobloc was performed for moderate or severe OSA in six patients, in four patients in combination with ATE and with mandibular distraction in one. Monobloc surgery for moderate or severe OSA had a 100% success rate in treating OSA and decannulation.

Conclusion: Expectant care is often sufficient to resolve mild OSA in patients with syndromic craniosynostosis, and should also be considered in patients with moderate OSA with close follow-up. ATE has an important role in the OSA treatment protocol. Monobloc surgery, combined with mandibular distraction on indication, is effective in resolving moderate to severe OSA with a stable long-term result.
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http://dx.doi.org/10.1016/j.bjps.2021.03.033DOI Listing
March 2021

Evaluation of Nutrient Intake and Food Consumption among Dutch Toddlers.

Nutrients 2021 May 1;13(5). Epub 2021 May 1.

National Institute for Public Health and the Environment, 3720 BA Bilthoven, The Netherlands.

Improving dietary habits at a young age could prevent adverse health outcomes. The aim was to gain insight into the adequacy of the dietary intake of Dutch toddlers, which may provide valuable information for preventive measures. Data obtained from the Dutch National Food Consumption Survey 2012-2016 were used, which included 672 children aged one to three years. Habitual intakes of nutrients were evaluated according to recommendations set by the Dutch Health Council. Specific food groups were evaluated according to the Dutch food-based dietary guidelines. For most nutrients, intakes were estimated to be adequate. High intakes were found for saturated fatty acids, retinol, iodine, copper, zinc, and sodium. No statement could be provided on the adequacy of intakes of alpha-linoleic acids, N-3 fish fatty acids, fiber, and iron. 74% of the toddlers used dietary supplements, and 59% used vitamin D supplements specifically. Total median intakes of vegetables, bread, and milk products were sufficient. Consumption of bread, potatoes and cereals, milk products, fats, and drinks consisted largely of unhealthy products. Consumption of unfavorable products may have been the cause of the observed high and low intakes of several nutrients. Shifting towards a healthier diet that is more in line with the guidelines may positively affect the dietary intake of Dutch toddlers and prevent negative health impacts, also later in life.
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http://dx.doi.org/10.3390/nu13051531DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8147311PMC
May 2021

Objective measurements for upper airway obstruction in infants with Robin sequence: what are we measuring? A systematic review.

J Clin Sleep Med 2021 May 7. Epub 2021 May 7.

Department of Plastic and Reconstructive Surgery, Amsterdam University Medical Centre, location AMC & VU, Emma Children's Hospital, Amsterdam, The Netherlands.

Study Objectives: Identifying optimal treatment for infants with Robin sequence (RS) is challenging due to substantial variability in the presentation of upper airway obstruction (UAO) in this population. Objective assessments of UAO and treatments are not standardized. A systematic review of objective measures of UAO was conducted as step towards evidence based clinical decision making for RS.

Methods: A literature search was performed in Pubmed and Embase databases (1990-2020) following PRISMA-guidelines. Articles reporting on RS and UAO-treatment were included if the following objective measures were studied: oximetry, polysomnography and blood gas. Quality was appraised by methodological index for non-randomized studies (MINORS, range:0-24).

Results: A total of 91 articles met inclusion criteria. Mean MINORS-score was 7.1 (range:3-14). Polysomnography was most frequently used (76%) followed by oximetry (20%) and blood gas (11%). Sleep position of the infant was reported in 35% of studies, with supine position most frequently, and monitoring time in 42%, including overnight recordings in more than half. Of 71 studies that evaluated UAO-interventions, the majority used polysomnography (90%), of which 61% did not specify the polysomnography technique. Reported polysomnography metrics included oxygen saturation (61%), apnea-hypopnea index (52%), carbon dioxide levels (31%), obstructive-apnea-hypopnea index (27%), and oxygen-desaturation-index (16%). Only 42 studies reported indications for UAO-intervention, with oximetry and polysomnography thresholds used equally (both 40%). In total, 34 distinct indications for treatment were identified.

Conclusions: This systematic review demonstrates a lack of standardization, interpretation and reporting of assessment and treatment indications for UAO in RS. An international, multidisciplinary consensus protocol is needed to guide clinicians on optimal UAO assessment in RS.
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http://dx.doi.org/10.5664/jcsm.9394DOI Listing
May 2021

A bibliometric overview of craniosynostosis research development.

Eur J Med Genet 2021 Jun 16;64(6):104224. Epub 2021 Apr 16.

Erasmus MC, University Medical Center Rotterdam, Department of Plastic, Reconstructive Surgery, and Hand Surgery, the Netherlands.

This article reviews the development of research in the field of craniosynostosis from a bibliometric standpoint. Craniosynostosis is a malformation occurring during the early development of the skull, when one or more of the sutures close too early, causing problems with normal brain and skull growth. Research in this field has developed from early clinical case descriptions, to genetic discoveries responsible for the occurring malformations and onwards to developing sophisticated surgical treatment. In this article we describe these developments, zoom in on publication trends and characteristics and visualize developing networks and topic shifts in this research field.
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http://dx.doi.org/10.1016/j.ejmg.2021.104224DOI Listing
June 2021

Supplementation of vitamins, trace elements and electrolytes in the PEPaNIC Randomised Controlled Trial: Composition and preparation of the prescription.

Clin Nutr ESPEN 2021 Apr 5;42:244-251. Epub 2021 Feb 5.

Intensive Care, Department of Paediatrics and Paediatric Surgery, Erasmus Medical Centre - Sophia Children's Hospital, Rotterdam, the Netherlands. Electronic address:

Background And Aims: Following the results of the paediatric early versus late parenteral nutrition in critical illness (PEPaNIC) multicentre, randomised, controlled trial, the new ESPGHAN/ESPEN/ESPR/CSPEN and ESPNIC guidelines recommend to consider withholding parenteral macronutrients for 1 week, while providing micronutrients, in critically ill children if enteral nutrition is insufficient. Critically ill children are suspected to be vulnerable to micronutrient deficiencies due to inadequate enteral nutrition, increased body's demands and excessive losses. Hitherto, micronutrient requirements in PICU are estimated based on recommended daily intakes for healthy children and expert opinion. We aimed to provide an overview of the current practice of micronutrient administration and practical considerations in the three participating centres of the PEPaNIC study, and compare these therapies with the recommendations in the new ESPGHAN/ESPEN/ESPR/CSPEN guidelines.

Methods: We describe the current composition and preparation of the prescribed parenteral micronutrients (consisting of vitamins, trace elements and electrolytes) in the three centres (Leuven, Rotterdam and Edmonton) that participated in the PEPaNIC RCT, and compare this per micronutrient with the ESPGHAN/ESPEN/ESPR/CSPEN guidelines recommendations.

Results: The three centres use a different micronutrient supplementation protocol during the first week of critical illness in children, with substantial differences regarding the amounts administered. Leuven administers commercial vitamins, trace elements and electrolytes in separate infusions both in 4 h. Rotterdam provides commercial vitamins and trace elements simultaneously via 8-h infusion and electrolytes continuously over 24 h. Lastly, Edmonton administers commercial vitamins and institutionally prepared trace elements solutions in 1 h and electrolytes on demand. Comparison with the ESPGHAN/ESPEN/ESPR/CSPEN guidelines yields in differences between the recommendations and the administered amounts, which are most substantial for vitamins.

Conclusion: The practice of intravenous micronutrient administration differs substantially between the three PEPaNIC centres and in comparison with the current guideline recommendations. This deviation is at least partially explained by the inability to provide all recommended amounts with the currently available commercial products and by the lack of strong evidence supporting these recommendations.
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http://dx.doi.org/10.1016/j.clnesp.2021.01.028DOI Listing
April 2021

Early weight gain trajectories and body composition in infancy in infants born very preterm.

Pediatr Obes 2021 Jun 17;16(6):e12752. Epub 2020 Nov 17.

Department of Pediatrics, Division of Neonatology, Erasmus MC-Sophia's Children's Hospital, Rotterdam, The Netherlands.

Background: Concerns are raised about the influence of rapid growth on excessive fat mass (FM) gain in early life and later cardiometabolic health of infants born preterm.

Objectives: To study the association between postnatal weight gain trajectories and body composition in infancy in infants born very preterm.

Methods: In infants born <30 weeks gestation, we evaluated associations between weight Z-score trajectories for three consecutive timeframes (NICU stay, level-II hospital stay and at home) and body composition, measured at 2 and 6 months corrected age by air-displacement plethysmography.

Results: Of 120 infants included, median gestational age at birth was 27 (interquartile range 26 ;28 ) and birth weight 1015 g (801;1250). The majority of infants did not make up for their initial loss of weight Z-score, but growth and later body composition were within term reference values. Weight gain during NICU stay was not associated with fat mass (absolute, %FM or FM index) in infancy. Weight gain during NICU and level II hospital stay was weakly associated with higher absolute lean mass (LM), but not after adjustment for length (LM index). Weight gain in the level-II hospital was positively associated with fat mass parameters at 2 months but not at 6 months. Strongest associations were found between weight gain at home and body composition (at both time points), especially fat mass.

Conclusions: Weight gain in different timeframes after preterm birth is associated with distinct parameters of body composition in infancy, with weight gain at home being most strongly related to fat mass.
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http://dx.doi.org/10.1111/ijpo.12752DOI Listing
June 2021

Early visuospatial attention and processing and related neurodevelopmental outcome at 2 years in children born very preterm.

Pediatr Res 2020 Oct 18. Epub 2020 Oct 18.

Vestibular and Oculomotor Research Group, Department of Neuroscience, Erasmus MC, Rotterdam, The Netherlands.

Background: The ability to perceive and process visuospatial information is a condition for broader neurodevelopment. We examined the association of early visuospatial attention and processing with later neurodevelopmental outcome in very preterm infants.

Methods: Visuospatial attention and processing was assessed in 209 children (<30 weeks gestation) using an easy applicable eye tracking-based paradigm at 1 and 2 years. Average reaction times to fixation (RTF) on specific visual stimuli were calculated, representing time needed for overall attention (Cartoon stimuli) and processing (Motion and Form stimuli). Associations between RTFs and various measures of development at 2 years including cognitive and motor development (Bayley Scales of Infant and Toddler Development-Third edition; Bayley-III), language (Lexi test) and behavior (Child Behavior Checklist) were examined.

Results: At 1 year, 100 ms slower Cartoon and Motion RTFs were associated with lower cognitive Bayley-III scores (-4.4 points, 95%CI: -7.4; -1.5 and -1.0 points, -1.8; -0.2, respectively). A 100 ms slower Cartoon RTF was associated with a 3.5 (-6.6; -0.5) point decrease in motor Bayley-III score.

Conclusions: Visuospatial attention and motion processing at 1 year is predictive of overall cognitive and motor development 1 year later. The nonverbal eye tracking-based test can assist in early detection of preterm children at risk of adverse neurodevelopment.

Impact: Visuospatial attention and processing at 1 year corrected age is predictive for overall cognitive and motor development 1 year later in preterm infants.First study to relate early visuospatial attention and processing with later neurodevelopmental outcome in preterm children.Early detection of preterm children at risk of adverse neurodevelopment, which allows for more timely interventions.
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http://dx.doi.org/10.1038/s41390-020-01206-7DOI Listing
October 2020

Circadian Variation in Human Milk Composition, a Systematic Review.

Nutrients 2020 Aug 4;12(8). Epub 2020 Aug 4.

Department of Pediatrics-Division Neonatology, Erasmus MC University Hospital-Sophia Children's Hospital, P.O. Box 2060, 3000 CB Rotterdam, The Netherlands.

Background: Breastfeeding is considered the most optimal mode of feeding for neonates and mothers. Human milk changes over the course of lactation in order to perfectly suit the infant's nutritional and immunological needs. Its composition also varies throughout the day. Circadian fluctuations in some bioactive components are suggested to transfer chronobiological information from mother to child to assist the development of the biological clock. This review aims to give a complete overview of studies examining human milk components found to exhibit circadian variation in their concentration.

Methods: We included studies assessing the concentration of a specific human milk component more than once in 24 h. Study characteristics, including gestational age, lactational stage, sampling strategy, analytical method, and outcome were extracted. Methodological quality was graded using a modified Newcastle-Ottawa Scale (NOS).

Results: A total of 83 reports assessing the circadian variation in the concentration of 71 human milk components were included. Heterogeneity among studies was high. The methodological quality varied widely. Significant circadian variation is found in tryptophan, fats, triacylglycerol, cholesterol, iron, melatonin, cortisol, and cortisone. This may play a role in the child's growth and development in terms of the biological clock.
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http://dx.doi.org/10.3390/nu12082328DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7468880PMC
August 2020

Surviving Sepsis Campaign International Guidelines for the Management of Septic Shock and Sepsis-Associated Organ Dysfunction in Children.

Pediatr Crit Care Med 2020 02;21(2):e52-e106

Radboud University Medical Centre, Nijmegen, The Netherlands.

Objectives: To develop evidence-based recommendations for clinicians caring for children (including infants, school-aged children, and adolescents) with septic shock and other sepsis-associated organ dysfunction.

Design: A panel of 49 international experts, representing 12 international organizations, as well as three methodologists and three public members was convened. Panel members assembled at key international meetings (for those panel members attending the conference), and a stand-alone meeting was held for all panel members in November 2018. A formal conflict-of-interest policy was developed at the onset of the process and enforced throughout. Teleconferences and electronic-based discussion among the chairs, co-chairs, methodologists, and group heads, as well as within subgroups, served as an integral part of the guideline development process.

Methods: The panel consisted of six subgroups: recognition and management of infection, hemodynamics and resuscitation, ventilation, endocrine and metabolic therapies, adjunctive therapies, and research priorities. We conducted a systematic review for each Population, Intervention, Control, and Outcomes question to identify the best available evidence, statistically summarized the evidence, and then assessed the quality of evidence using the Grading of Recommendations Assessment, Development, and Evaluation approach. We used the evidence-to-decision framework to formulate recommendations as strong or weak, or as a best practice statement. In addition, "in our practice" statements were included when evidence was inconclusive to issue a recommendation, but the panel felt that some guidance based on practice patterns may be appropriate.

Results: The panel provided 77 statements on the management and resuscitation of children with septic shock and other sepsis-associated organ dysfunction. Overall, six were strong recommendations, 52 were weak recommendations, and nine were best-practice statements. For 13 questions, no recommendations could be made; but, for 10 of these, "in our practice" statements were provided. In addition, 49 research priorities were identified.

Conclusions: A large cohort of international experts was able to achieve consensus regarding many recommendations for the best care of children with sepsis, acknowledging that most aspects of care had relatively low quality of evidence resulting in the frequent issuance of weak recommendations. Despite this challenge, these recommendations regarding the management of children with septic shock and other sepsis-associated organ dysfunction provide a foundation for consistent care to improve outcomes and inform future research.
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http://dx.doi.org/10.1097/PCC.0000000000002198DOI Listing
February 2020

Surviving sepsis campaign international guidelines for the management of septic shock and sepsis-associated organ dysfunction in children.

Intensive Care Med 2020 02;46(Suppl 1):10-67

Radboud University Medical Centre, Nijmegen, The Netherlands.

Objectives: To develop evidence-based recommendations for clinicians caring for children (including infants, school-aged children, and adolescents) with septic shock and other sepsis-associated organ dysfunction.

Design: A panel of 49 international experts, representing 12 international organizations, as well as three methodologists and three public members was convened. Panel members assembled at key international meetings (for those panel members attending the conference), and a stand-alone meeting was held for all panel members in November 2018. A formal conflict-of-interest policy was developed at the onset of the process and enforced throughout. Teleconferences and electronic-based discussion among the chairs, co-chairs, methodologists, and group heads, as well as within subgroups, served as an integral part of the guideline development process.

Methods: The panel consisted of six subgroups: recognition and management of infection, hemodynamics and resuscitation, ventilation, endocrine and metabolic therapies, adjunctive therapies, and research priorities. We conducted a systematic review for each Population, Intervention, Control, and Outcomes question to identify the best available evidence, statistically summarized the evidence, and then assessed the quality of evidence using the Grading of Recommendations Assessment, Development, and Evaluation approach. We used the evidence-to-decision framework to formulate recommendations as strong or weak, or as a best practice statement. In addition, "in our practice" statements were included when evidence was inconclusive to issue a recommendation, but the panel felt that some guidance based on practice patterns may be appropriate.

Results: The panel provided 77 statements on the management and resuscitation of children with septic shock and other sepsis-associated organ dysfunction. Overall, six were strong recommendations, 49 were weak recommendations, and nine were best-practice statements. For 13 questions, no recommendations could be made; but, for 10 of these, "in our practice" statements were provided. In addition, 52 research priorities were identified.

Conclusions: A large cohort of international experts was able to achieve consensus regarding many recommendations for the best care of children with sepsis, acknowledging that most aspects of care had relatively low quality of evidence resulting in the frequent issuance of weak recommendations. Despite this challenge, these recommendations regarding the management of children with septic shock and other sepsis-associated organ dysfunction provide a foundation for consistent care to improve outcomes and inform future research.
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http://dx.doi.org/10.1007/s00134-019-05878-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7095013PMC
February 2020

Dural sinus volume in children with syndromic craniosynostosis and intracranial hypertension.

J Neurosurg Pediatr 2020 Jan 31:1-8. Epub 2020 Jan 31.

Departments of1Plastic and Reconstructive Surgery, and Hand Surgery.

Objective: Intracranial hypertension is a major concern in children with syndromic craniosynostosis (sCS). Cerebral venous hypertension caused by cerebral venous outflow obstruction is believed to contribute to intracranial hypertension. The authors therefore hypothesized that cerebral venous volume would be increased in those children with sCS and intracranial hypertension.

Methods: In a case series of 105 children with sCS, of whom 32 had intracranial hypertension, cerebral MRI techniques were used to quantify the volume of the superior sagittal sinus, straight sinus (StrS), and both transverse sinuses.

Results: Linear regression showed that total cerebral venous volume increased by 580.8 mm3 per cm increase in occipitofrontal head circumference (p < 0.001). No significant difference was found between the intracranial hypertension group and the nonintracranial hypertension group (p = 0.470). Multivariate ANOVA showed increased StrS volume (as a proportion of total volume) in the intracranial hypertension group (8.5% vs 5.1% in the nonintracranial hypertension group, p < 0.001). Multivariate logistic regression showed that a 100-mm3 increase in StrS volume is associated with increased odds of having intracranial hypertension by 60% (OR 1.60, 95% CI 1.24-2.08).

Conclusions: Although intracranial hypertension was not associated with total cerebral venous volume increase, it was associated with an isolated increase in StrS volume. Hence, it is unlikely that general cerebral venous outflow obstruction is the mechanism of intracranial hypertension in sCS. Rather, these findings indicate either a central cerebral vulnerability to intracranial hypertension or a mechanism involving venous blood redistribution.
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http://dx.doi.org/10.3171/2019.12.PEDS19562DOI Listing
January 2020

Cerebral blood flow in children with syndromic craniosynostosis: cohort arterial spin labeling studies.

J Neurosurg Pediatr 2019 Dec 27:1-11. Epub 2019 Dec 27.

1Department of Plastic and Reconstructive Surgery and Hand Surgery, Dutch Craniofacial Center.

Objective: In comparison with the general population, children with syndromic craniosynostosis (sCS) have abnormal cerebral venous anatomy and are more likely to develop intracranial hypertension. To date, little is known about the postnatal development change in cerebral blood flow (CBF) in sCS. The aim of this study was to determine CBF in patients with sCS, and compare findings with control subjects.

Methods: A prospective cohort study of patients with sCS using MRI and arterial spin labeling (ASL) determined regional CBF patterns in comparison with a convenience sample of control subjects with identical MRI/ASL assessments in whom the imaging showed no cerebral/neurological pathology. Patients with SCS and control subjects were stratified into four age categories and compared using CBF measurements from four brain lobes, the cerebellum, supratentorial cortex, and white matter. In a subgroup of patients with sCS the authors also compared longitudinal pre- to postoperative CBF changes.

Results: Seventy-six patients with sCS (35 female [46.1%] and 41 male [53.9%]), with a mean age of 4.5 years (range 0.2-19.2 years), were compared with 86 control subjects (38 female [44.2%] and 48 male [55.8%]), with a mean age of 6.4 years (range 0.1-17.8 years). Untreated sCS patients < 1 year old had lower CBF than control subjects. In older age categories, CBF normalized to values observed in controls. Graphical analyses of CBF by age showed that the normally expected peak in CBF during childhood, noted at 4 years of age in control subjects, occurred at 5-6 years of age in patients with sCS. Patients with longitudinal pre- to postoperative CBF measurements showed significant increases in CBF after surgery.

Conclusions: Untreated patients with sCS < 1 year old have lower CBF than control subjects. Following vault expansion, and with age, CBF in these patients normalizes to that of control subjects, but the usual physiological peak in CBF in childhood occurs later than expected.
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http://dx.doi.org/10.3171/2019.10.PEDS19150DOI Listing
December 2019

Improvement in Sleep Architecture is associated with the Indication of Surgery in Syndromic Craniosynostosis.

Plast Reconstr Surg Glob Open 2019 Sep 10;7(9):e2419. Epub 2019 Sep 10.

Department of Plastic and Reconstructive Surgery, and Hand Surgery, Erasmus MC, Rotterdam, the Netherlands.

Children with syndromic craniosynostosis (sCS) often suffer from obstructive sleep apnea (OSA) and intracranial hypertension (ICH). Both OSA and ICH might disrupt sleep architecture. However, it is unclear how surgically treating OSA or ICH affects sleep architecture. The aim of this study was twofold: to explore the usefulness of sleep architecture analysis in detecting disturbed sleep and to determine whether surgical treatment can improve it.

Methods: Eighty-three children with sCS and 35 control subjects, who had undergone a polysomnography (PSG), were included. Linear-mixed models showed the effects of OSA and ICH on sleep architecture parameters. In a subset of 19 patients, linear regression models illustrated the effects of OSA-indicated and ICH-indicated surgery on pre-to-postoperative changes.

Results: An increase in obstructive-apnea/hypopnea index (oAHI) was significantly associated with an increase in N2-sleep, arousal index, and respiratory-arousal index and a decrease in REM-sleep, N3-sleep, sleep efficiency, and sleep quality. ICH and having sCS were not related to any change in sleep architecture. OSA-indicated surgery significantly increased the total sleep time and sleep efficiency and decreased the arousal index and respiratory-arousal index. ICH-indicated surgery significantly decreased REM-sleep, N1-sleep, sleep efficiency, and sleep quality.

Conclusions: For routine detection of disturbed sleep in individual subjects, PSG-assessed sleep architecture is currently not useful. OSA does disrupt sleep architecture, but ICH does not. OSA-indicated surgery improves sleep architecture, which stresses the importance of treating OSA to assure adequate sleep. ICH-indicated surgery affects sleep architecture, although it is not clear whether this is a positive or negative effect.
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http://dx.doi.org/10.1097/GOX.0000000000002419DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6799402PMC
September 2019

Muenke syndrome: long-term outcome of a syndrome-specific treatment protocol.

J Neurosurg Pediatr 2019 Jul 19:1-8. Epub 2019 Jul 19.

Departments of1Plastic and Reconstructive Surgery and Hand Surgery, Dutch Craniofacial Center, and.

Objective: The authors evaluated the long-term outcome of their treatment protocol for Muenke syndrome, which includes a single craniofacial procedure.

Methods: This was a prospective observational cohort study of Muenke syndrome patients who underwent surgery for craniosynostosis within the first year of life. Symptoms and determinants of intracranial hypertension were evaluated by longitudinal monitoring of the presence of papilledema (fundoscopy), obstructive sleep apnea (OSA; with polysomnography), cerebellar tonsillar herniation (MRI studies), ventricular size (MRI and CT studies), and skull growth (occipital frontal head circumference [OFC]). Other evaluated factors included hearing, speech, and ophthalmological outcomes.

Results: The study included 38 patients; 36 patients underwent fronto-supraorbital advancement. The median age at last follow-up was 13.2 years (range 1.3-24.4 years). Three patients had papilledema, which was related to ophthalmological disorders in 2 patients. Three patients had mild OSA. Three patients had a Chiari I malformation, and tonsillar descent < 5 mm was present in 6 patients. Tonsillar position was unrelated to papilledema, ventricular size, or restricted skull growth. Ten patients had ventriculomegaly, and the OFC growth curve deflected in 3 patients. Twenty-two patients had hearing loss. Refraction anomalies were diagnosed in 14/15 patients measured at ≥ 8 years of age.

Conclusions: Patients with Muenke syndrome treated with a single fronto-supraorbital advancement in their first year of life rarely develop signs of intracranial hypertension, in accordance with the very low prevalence of its causative factors (OSA, hydrocephalus, and restricted skull growth). This illustrates that there is no need for a routine second craniofacial procedure. Patient follow-up should focus on visual assessment and speech and hearing outcomes.
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http://dx.doi.org/10.3171/2019.5.PEDS1969DOI Listing
July 2019

International survey of De-implementation of initiating parenteral nutrition early in Paediatric intensive care units.

BMC Health Serv Res 2019 Jun 13;19(1):379. Epub 2019 Jun 13.

Department of Paediatrics and Paediatric Surgery, Erasmus MC - Sophia Children's Hospital, University Medical Centre Rotterdam, Wytemaweg 80, 3015, CN, Rotterdam, The Netherlands.

Background: Initiating parenteral nutrition (PN) within 24 h in critically ill children is inferior to withholding PN during the first week, as was found in the PEPaNIC study. The aims of this study were to investigate de-implementation of early initiation of PN at PICUs worldwide, and to identify factors influencing de-implementation.

Methods: A cross-sectional online survey was conducted (May - October 2017), consisting of 41 questions addressing current PN practices, the degree of de-implementation, and factors affecting de-implementation.

Results: We analysed 81 responses from 39 countries. Of these 81 respondents, 53 (65%) were aware of the findings of the PEPaNIC study, and 43 (53%) have read the article. In these 43 PICUs, PN was completely withheld during the first week in 10 PICUs, of which 5 already withheld PN (12%), and 5 de-implemented early initiation of PN (12%). Partial de-implementation was reported by 17 (40%) and no de-implementation by 16 (37%). Higher de-implementation rates were observed when the interpreted level of evidence and grade of recommendation of PEPaNIC was high. Predominant reasons for retaining early initiation of PN were concerns on withholding amino acids, the safety in undernourished children and neonates, and the long-term consequences. Furthermore, the respondents were waiting for updated guidelines.

Conclusions: One year after the publication of the PEPaNIC trial, only two-thirds of the respondents was aware of the study results. Within this group, early initiation of PN was de-implemented completely in 12% of the PICUs, while 40% asserted partial de-implementation. Increasing the awareness, addressing the intervention-specific questions and more frequently revising international guidelines might help to accelerate de-implementation of ineffective, unproven or harmful healthcare.
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http://dx.doi.org/10.1186/s12913-019-4223-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6567488PMC
June 2019

Swallowing problems in children with a tracheostomy tube.

Int J Pediatr Otorhinolaryngol 2019 Sep 16;124:30-33. Epub 2019 May 16.

Department of Pediatrics, Pediatric Intensive Care Unit, Erasmus Medical Center, Sophia Children's Hospital, Rotterdam, the Netherlands.

Introduction: Swallowing problems in children with a tracheostomy tube seem to be a common problem, although exact prevalence is not known. The aim of this study is to identify the prevalence and type of swallowing problems in children with a tracheostomy tube.

Methods: We retrospectively included 44 children having a tracheostomy tube at Erasmus MC-Sophia Children's hospital. Assessment by a specialized speech and language therapist, the Modified Evans Blue Dye test, Video Fluoroscopic Swallowing Study and a Fiber-optic Endoscopic Evaluation of Swallowing were reviewed with regard to the different phases of swallowing, in particular signs of aspiration.

Results: In our cohort, 31 (70%) children with a tracheostomy tube presented with problems in the oral and/or the pharyngeal phase of swallowing. Overall 19 (43%) children aspirated.

Conclusions: The majority of children with a tracheostomy tube have swallowing problems in the different swallowing phases with a high risk for aspiration.
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http://dx.doi.org/10.1016/j.ijporl.2019.05.003DOI Listing
September 2019

Sleep-related breathing disorders in young adults with Prader-Willi syndrome: a placebo-controlled, cross-over GH trial.

J Clin Endocrinol Metab 2019 Apr 18. Epub 2019 Apr 18.

Dutch Growth Research Foundation, Rotterdam, The Netherlands.

Context: Sleep-related breathing disorders (SRBD) are common in people with Prader-Willi syndrome (PWS). Young adults with PWS benefit from GH continuation after adult height by maintaining the improved body composition obtained during childhood. There are, however, no studies about the effects of GH on SRBD in young adults with PWS who were treated with GH during childhood.

Objective: To investigate the effects of GH versus placebo on SRBD in young adults with PWS who were treated with GH during childhood and had attained adult height.

Design: 2-year, randomized, double-blind, placebo-controlled, cross-over GH-study in 27 young adults with PWS, stratified for gender and BMI.

Setting: Dutch PWS Reference Center.

Intervention: Cross-over intervention with GH (0.67 mg/m2/day) and placebo, both during one year.

Main Outcome Measures: Apnea hypopnea index (AHI), obstructive apnea index (OAI), central apnea index (CAI), measured by polysomnography.

Results: Compared to placebo, GH treatment did not increase AHI, CAI or OAI (p>0.35). The effect of GH versus placebo was neither different between men and women, nor between patients with a deletion or mUPD/ICD. After 2 years, there was no difference in AHI, CAI or OAI compared to baseline (p>0.18). Two patients (7%) fulfilled the criteria of obstructive sleep apnea (OSA), regardless of GH or placebo.

Conclusions: GH compared to placebo does not cause a significant increase in AHI, CAI or OAI in adults with PWS who were treated with GH during childhood and have attained adult height. Our findings are reassuring and prove that GH can be safely administered.
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http://dx.doi.org/10.1210/jc.2019-00391DOI Listing
April 2019

Outcomes of Delaying Parenteral Nutrition for 1 Week vs Initiation Within 24 Hours Among Undernourished Children in Pediatric Intensive Care: A Subanalysis of the PEPaNIC Randomized Clinical Trial.

JAMA Netw Open 2018 09 7;1(5):e182668. Epub 2018 Sep 7.

Department of Pediatrics and Pediatric Surgery, Intensive Care Unit, Erasmus MC-Sophia Children's Hospital, University Medical Center Rotterdam, Rotterdam, the Netherlands.

Importance: Undernourishment has been associated with poor outcomes of critical illness in children. The effects of withholding parenteral nutrition (PN) for 1 week in undernourished critically ill children are unknown.

Objective: To assess the outcome effects of withholding PN for 1 week in undernourished critically ill children.

Design, Setting, And Participants: This is a subanalysis of the randomized clinical trial Pediatric Early vs Late Parenteral Nutrition in Intensive Care Unit (PEPaNIC; N = 1440), which focused on the subgroup of pediatric intensive care unit (PICU) patients identified as undernourished on admission. Children included in the PEPaNIC trial were enrolled between June 18, 2012, and July 27, 2015. Undernourishment was defined as weight-for-age z score less than -2 in children younger than 1 year, and body mass index-for-age z score less than -2 in children 1 year or older. Data analysis was conducted from August 3, 2017, to July 6, 2018.

Interventions: Patients were randomized to initiation of supplemental PN within 24 hours (early PN) or after 1 week (late PN) when enteral nutrition was insufficient.

Main Outcomes And Measures: Primary end points were risk of new infections acquired in the PICU and time to live PICU discharge, assessed via multivariable logistic regression and Cox proportional hazard analyses, adjusted for risk factors.

Results: A total of 289 of 1440 children (20.1%), term newborn to age 17 years, were identified as undernourished, of whom 150 of 717 patients (20.9%) were in the late PN group and 139 of 723 patients (19.2%) were in the early PN group. On admission, characteristics were similar among the treatment groups. Mean (SD) weight z scores were -3.33 (1.18) in the late PN group and -3.21 (1.09) in the early PN group. Compared with well-nourished PICU patients, undernourishment on admission was associated with lower likelihood of an earlier live PICU discharge (adjusted hazard ratio, 0.86; 95% CI, 0.75-0.99; P = .03). Among undernourished PICU patients, late PN reduced the risk of new infections by 11.0% (adjusted odds ratio, 0.39; 95% CI, 0.19-0.78; P = .01), and shortened the duration of PICU stay by a median of 2 days (earlier live PICU discharge: adjusted hazard ratio, 1.37; 95% CI, 1.06-1.75; P = .01). The safety outcomes mortality, incidence of hypoglycemia during the first week, and incidence of weight deterioration during PICU stay were similar between the treatment groups.

Conclusions And Relevance: In undernourished critically ill children, withholding PN for 1 week was clinically superior to early PN.

Trial Registration: ClinicalTrials.gov Identifier: NCT01536275.
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http://dx.doi.org/10.1001/jamanetworkopen.2018.2668DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6324499PMC
September 2018

Nutritional support in the recovery phase of critically ill children.

Curr Opin Clin Nutr Metab Care 2019 03;22(2):152-158

Paediatric Intensive Care, Department of Paediatrics and Paediatric Surgery, Erasmus MC - Sophia Children's Hospital, Rotterdam, the Netherlands.

Purpose Of Review: The metabolic stress response of a critically ill child evolves over time and thus it seems reasonable that nutritional requirements change during their course of illness as well. This review proposes strategies and considerations for nutritional support during the recovery phase to gain optimal (catch-up) growth with preservation of lean body mass.

Recent Findings: Critical illness impairs nutritional status, muscle mass and function, and neurocognition, but early and high intakes of artificial nutrition during the acute phase cannot resolve this. Although (parenteral) nutrient restriction during the acute phase appears to be beneficial, persistent nutrient restriction, when the metabolic stress response resolves, has short-term and long-term detrimental consequences. Requirements increase markedly during the recovery phase to enable recovery and catch-up growth. Such large amounts of intake demand for alternate approach, especially when intestinal problems constitute a barrier for full enteral feeding. As part of the nutritional recovery, mobilization and exercise are essential to achieve catch-up growth with an optimal body composition.

Summary: During the recovery phase of paediatric critical illness (catch-up) growth and muscle recovery require nutritional intakes at least two times the resting energy expenditure.
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http://dx.doi.org/10.1097/MCO.0000000000000549DOI Listing
March 2019

Phthalate and alternative plasticizers in indwelling medical devices in pediatric intensive care units.

J Hazard Mater 2019 02 1;363:64-72. Epub 2018 Oct 1.

Toxicological Centre, University of Antwerp, Wilrijk, Belgium. Electronic address:

The present study aimed to identify plasticizers present in indwelling plastic medical devices commonly used in the pediatric intensive care unit (PICU). We have analyzed a wide range of medical devices (n = 97) daily used in the PICUs of two academic hospitals in Belgium and the Netherlands. Identified compounds varied between the samples. Most of the indwelling medical devices and essential accessories were found to actively leach phthalates and alternative plasticizers. Results indicated that DEHP was predominantly present as plasticizer (60 of 97 samples), followed by bis(2-ethylhexyl) adipate (DEHA, 32 of 97), bis(2-ethylhexyl) terephthalate (DEHT, 24 of 97), tris(2-ethylhexyl) trimellitate (TOTM, 20 of 97), and tributyl-O-acetyl citrate (ATBC, 10 of 97). Other plasticizers, such as di-isononyl-cyclohexane-1,2-dicarboxylate (DINCH, 2 of 97), di-isononyl phthalate (DiNP, 4 of 97), di(2-propylheptyl) phthalate (DPHP, 4 of 97) and di-isodecyl phthalate (DiDP, 2 of 97) were detected in < 5% of the investigated samples. Several devices contained multiple plasticizers, e.g. devices containing TOTM contained also DEHP and DEHT. Our data indicate that PICU patients are exposed to a wide range of plasticizers, including the controversial DEHP. Future studies should investigate the exposure to APs in children staying in the PICU and the possible health effects thereof.
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http://dx.doi.org/10.1016/j.jhazmat.2018.09.087DOI Listing
February 2019

Early versus late parenteral nutrition in critically ill, term neonates: a preplanned secondary subgroup analysis of the PEPaNIC multicentre, randomised controlled trial.

Lancet Child Adolesc Health 2018 07 11;2(7):505-515. Epub 2018 May 11.

Intensive Care Unit, Department of Paediatrics and Paediatric Surgery, Erasmus Medical Centre, Sophia Children's Hospital, Rotterdam, Netherlands. Electronic address:

Background: Previous randomised studies showed that withholding parenteral nutrition for 1 week of critical illness was superior to early initiation (<24-48 h) of parenteral nutrition in children and adults. However, neonates are considered more susceptible to macronutrient deficits. We investigated the effect of withholding parenteral nutrition for 1 week in critically ill, term neonates.

Methods: We previously did a randomised, controlled study (PEPaNIC) of children aged up to 17 years admitted to paediatric intensive-care units (ICUs) in three hospitals in Belgium, Canada, and the Netherlands randomly assigned (1:1) to either standard care of parenteral nutrition initiated early within 24 h of admission to an ICU or late parenteral nutrition (where supplemental parenteral nutrition was withheld for 1 week after admission to the ICU). In this preplanned, secondary subanalysis of PEPaNIC, we looked at data from critically ill, term neonate participants (gestational age ≥37 weeks) aged up to 28 days (studied in overlapping age groups of ≤4 weeks, ≤1 week, and <1 day-ie, age at admission). In both the early parenteral nutrition and late parenteral nutrition groups, enteral nutrition was initiated as soon as possible and increased according to local protocols. Outcome assessors and investigators not directly involved in the paediatric ICU were not informed of treatment allocation. The primary endpoints were incidence of new infections and duration of paediatric ICU dependency (quantified as the number of days in the paediatric ICU and likelihood of earlier live discharge from the ICU), analysed based on intention to treat. Multivariable analyses were adjusted for the following risk factors: centre, Paediatric Logistic Organ Dysfunction score, Paediatric Index of Mortality 2 score, diagnosis group, and weight-for-age Z scores on admission. Secondary safety outcomes were mortality (at 90 days, during the intervention, in the paediatric ICU, and in the hospital) and hypoglycaemic incidents during the intervention. All patients in the respective groups were included in the safety analysis.

Findings: Between June 18, 2012, and July 27, 2015, we included 209 participants in this substudy, 145 of whom were aged up to and including 1 week and 45 aged younger than 1 day. In neonates aged up to and including 4 weeks, late parenteral nutrition increased the likelihood of earlier live discharge from the paediatric ICU compared with early parenteral nutrition (adjusted hazard ratio [HR] 1·61, 95% CI 1·19-2·20; p=0·0021) but did not affect the risk of infection. The risk of infection in neonates aged up to and including 1 week and younger than 1 day was lower with late parenteral nutrition than with early parenteral nutrition (adjusted odds ratios [OR] 0·36, 95% CI 0·15-0·83, p=0·017; and 0·10, 0·01-0·64, p=0·015, respectively). For neonates aged up to and including 1 week, the likelihood of an earlier live discharge from the ICU was higher with late parenteral nutrition (adjusted HR 1·69, 95% CI 1·16-2·46; p=0·0063). For neonates younger than 1 day, adjusted HR was 1·95 (95% CI 0·93-4·12; p=0·078). Mortality at all studied timepoints was similar between the groups for all ages; however, in neonates aged up to and including 4 weeks and aged up to and including 1 week, the risk of hypoglycaemia was higher with late parenteral nutrition (23% vs 14%; adjusted OR 3·05, 95% CI 1·27-7·35, p=0·013; and 24% vs 14%; 3·57, 1·23-10·45, p=0·019, respectively.

Interpretation: In critically ill, term neonates, withholding parenteral nutrition for 1 week was clinically superior to standard care of initiating parenteral nutrition within 24 h for short-term outcomes. However, withholding parenteral nutrition for 1 week significantly increased the risk of developing hypoglycaemia, which necessitates long-term follow-up of these children before late parenteral nutrition can be confidently recommended for this vulnerable patient group.

Funding: Flemish Agency for Innovation through Science and Technology, Methusalem-Programme Flemish Government, European Research Council, Fonds NutsOhra, Stichting Agis-Zorginnovatie, and the Sophia Research-Foundation.
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http://dx.doi.org/10.1016/S2352-4642(18)30131-7DOI Listing
July 2018

Electrocardiographic variables in children with syndromic craniosynostosis and primary snoring to mild obstructive sleep apnea: significance of identifying respiratory arrhythmia during sleep.

Sleep Med 2018 05 14;45:1-6. Epub 2017 Nov 14.

Erasmus MC - Sophia Children's Hospital, University Medical Center Rotterdam, Pediatric Intensive Care Unit, Wytemaweg 80, 3015 CN Rotterdam, The Netherlands.

Background: In the spectrum of children with symptomatic sleep disordered breathing (SDB), some individuals - such as those with upper airway resistance syndrome (UARS) - do not have abnormalities on polysomnography (PSG). In this study we have assessed whether assessment of respiratory arrhythmia (RA) and heart rate variability (HRV) analysis helps in management of children with syndromic craniosynostosis and none-to-mild obstructive sleep apnea (OSA).

Methods: Prospective cohort study in children aged 1-18 years old with syndromic craniosynostosis. Children were selected for HRV analysis from the ECG if their obstructive apnea-hypopnea index (oAHI) was between zero and five per hour (ie, oAHI ≤5/hour). Subjects were divided into groups based on the presence or absence of respiratory arrhythmia (with or without RA respectively) using the electrocardiogram (ECG). The main analysis included studying the relationship between RA and HRV, symptoms, interventions, and sleep architecture.

Results: We identified 42 patients with, at worst, mild OSA. We found higher parasympathetic control and higher total power in children with RA during the non-rapid eye movement (non-REM) sleep. Children with RA also have a relatively higher percentage of paradoxical breathing during non-REM sleep (P = 0.042). Intracranial hypertension was distributed equally between groups. Last, RA patients showed increased parasympathetic activity that further increased in non-REM sleep.

Conclusion: In syndromic craniosynostosis cases with SDB and PSG showing oAHI ≤5/hour, the presence of RA may indicate subsequent need for treatment interventions, and a trend toward higher occurrence of clinical symptoms. ECG analyses of HRV variables in subjects with RA demonstrate increased parasympathetic activity and total power. Such findings may add to the diagnosis of apparently asymptomatic children.
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http://dx.doi.org/10.1016/j.sleep.2017.09.036DOI Listing
May 2018

Effects of glucocorticoids on serum amino acid levels during cardiac surgery in children.

Clin Nutr ESPEN 2018 02 10;23:212-216. Epub 2017 Oct 10.

Intensive Care and Department of Pediatric Surgery, Erasmus MC - Sophia Children's Hospital, Rotterdam, Netherlands.

Background And Aims: Children undergoing cardiac surgery with cardio pulmonary bypass often receive glucocorticoids to reduce the systemic inflammatory response. Glucocorticoids stimulate protein breakdown and increase amino acid availability. We studied whether glucocorticoid treatment influences the availability of amino acids, specifically those involved in the nitric oxide pathway.

Methods: We prospectively studied 49 children with congenital heart disease undergoing cardiac surgery. Serum cortisol and amino acid levels were measured in arterial blood sampled before surgery (t = -5 min), directly after surgery (t = 0 h) and at t = 12 h and t = 24 h after surgery. Serum cortisol and amino acid levels were compared between children who had received glucocorticoids (G+) and children who had not (G-).

Results: Of 49 patients included ((49% male, age 1.7 (0.5-8.7) y)), 33 (67%) received glucocorticoids. Baseline characteristics were not different between groups, except a higher weighted inotropic score in the G+ group. At t = 0 h, serum cortisol levels in the G+ group were significantly higher than in the G- group (7218 vs. 660 nmol/L; (p < 0.05)), but not different at the other time points. The levels of plasma amino acids had dropped after surgery. Compared to the G- group, in the G+ group the total amount of amino acids was significantly higher at t = 12 and t = 24; citrulline levels were higher at t = 12 and t = 24; and glutamine and arginine levels were higher at t = 12.

Conclusions: Glucocorticoid treatment during cardiac surgery in children preserves serum amino acid levels post-surgery. The preservation of glutamine, citrulline and arginine levels might have a beneficial effect on the related NO metabolism.
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http://dx.doi.org/10.1016/j.clnesp.2017.09.012DOI Listing
February 2018

Evaluation of Swallow Function in Patients with Craniofacial Microsomia: A Retrospective Study.

Dysphagia 2018 Apr 4;33(2):234-242. Epub 2017 Nov 4.

Department of Plastic and Oral Surgery, Boston Children's Hospital, Boston, USA.

Craniofacial microsomia (CFM) is characterized by underdevelopment of the structures derived from the first and second pharyngeal arches resulting in aesthetic, psychological, and functional problems including feeding and swallowing difficulties. The aim of this study is to gain more insight into swallowing difficulties in patients with CFM. A retrospective study was conducted in the population of patients diagnosed with CFM at three major craniofacial units. Patients with feeding difficulties and those who underwent video fluoroscopic swallow (VFS) studies were included for further analyses. The outcome of the VFS-studies was reviewed with regard to the four phases of swallowing. In our cohort, 13.5% of the 755 patients were diagnosed with swallowing difficulties. The outcome of the VFS-studies of 42 patients showed difficulties in the oral and pharyngeal phases with both thin and thick liquids. Patients with more severe mandibular hypoplasia showed more difficulties to form an appropriate bolus compared to patients who were less severely affected. This is the first study to document swallowing problems in patients with CFM. Difficulties were seen in both the oral and pharyngeal phases. We recommend routine screening for swallowing issues by a speech and language therapist in all patients with CFM and to obtain a VFS-study in patients with a type III mandible.
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http://dx.doi.org/10.1007/s00455-017-9851-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5866261PMC
April 2018

First week weight dip and reaching growth targets in early life in preterm infants.

Clin Nutr 2018 10 31;37(5):1526-1533. Epub 2017 Aug 31.

Department of Pediatrics, Division of Neonatology, Erasmus MC - Sophia Children's Hospital, Wytemaweg 80, 3015 CN Rotterdam, The Netherlands. Electronic address:

Background & Aims: Aggressive parenteral nutritional practices were implemented in clinical practice over a decade ago to prevent early growth retardation in preterm infants. We aimed to study adherence to current nutritional recommendations in a population of very preterm infants, and to evaluate growth in early life.

Methods: Preterm infants (gestational age <30 weeks and birth weight <1500 g) were included in a prospective observational cohort study. Data on parenteral and enteral intake were collected on days 1-7, 14, 21 and 28 (d28) of life. Growth data were collected at birth, at moment of maximal weight loss (dip), and either at discharge from the neonatal intensive care unit or at d28, whichever came first. Nutritional intakes were compared to recommendations of current guidelines. The target growth rate was 15-20 g/kg/d.

Results: Fifty-nine infants (63% male) were included. Median gestational age was 27 3/7 (interquartile range 25 6/7;28 4/7), and birth weight was 920 g (720;1200). Median macronutrient intakes were within or above the targets on all study days, but energy targets were not met before day 5. Median growth rates were 9.5 and 18.1 g/kg/d, when calculated from respectively birth and dip to discharge/d28. Eight (14%) versus 46 (78%) infants met the growth targets, when evaluated from respectively birth and dip to discharge/d28.

Conclusions: In this cohort, only energy intake up to day 5 was lower than recommended. Growth targets were achieved in the majority of the infants, but only when evaluated from dip onward, not from birth.
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http://dx.doi.org/10.1016/j.clnu.2017.08.023DOI Listing
October 2018

Letter to the Editor. Raised intracranial pressure and cognitive delay in craniosynostosis.

J Neurosurg Pediatr 2017 11 18;20(5):498-502. Epub 2017 Aug 18.

Harvard Medical School and Boston Children's Hospital, Boston, MA.

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http://dx.doi.org/10.3171/2017.3.PEDS17118DOI Listing
November 2017

Congenital Diaphragmatic Hernia and Growth to 12 Years.

Pediatrics 2017 Aug 14;140(2). Epub 2017 Jul 14.

Intensive Care and Department of Pediatric Surgery, Erasmus Medical Center-Sophia Children's Hospital, Rotterdam, Netherlands;and.

Objectives: Growth problems are reported in patients with congenital diaphragmatic hernia during the first years of life. However, it is unknown if poor growth persists during childhood. We therefore evaluated growth of patients longitudinally until 12 years of age.

Methods: This prospective study included 172 patients (43 treated with extracorporeal membrane oxygenation [ECMO]) born from 1999 to 2014. scores of height-for-age (HFA), weight-for-height, and distance-to-target height were calculated at 6 months of age and at 1, 2, 5, 8, and 12 years of age. Data were analyzed by using general linear models.

Results: At 1 year of age, the mean weight-for-height score had declined in ECMO (-1.30, 95% confidence interval: -1.62 to -0.97) and non-ECMO patients (-0.72, 95% confidence interval: -0.91 to -0.54; < .05). Thereafter in ECMO patients, the mean HFA score deteriorated between 1 (-0.43, 95% confidence interval: -0.73 to -0.13) and 5 years of age (-1.08, 95% confidence interval: -1.38 to -0.78; < .01). In non-ECMO patients, the mean HFA score deteriorated between 2 (-0.35, 95% confidence interval: -0.53 to -0.17) and 5 years of age (-0.56, 95% confidence interval: -0.75 to -0.37; = .002). At 12 years of age, the mean HFA score was still less than the norm in both groups: ECMO (-0.67, 95% confidence interval: -1.01 to -0.33) versus non-ECMO (-0.49, 95% confidence interval: -0.77 to -0.20; < .01). Adjusting for target height improved the mean height scores but did not bring them to normal range.

Conclusions: Poor linear growth persisted at 12 years of age. The pattern of early deterioration of weight gain followed by a decline in linear growth is suggestive of inadequate nutrition during infancy. Therefore, nutritional assessment and intervention should be started early and should be continued during childhood.
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http://dx.doi.org/10.1542/peds.2016-3659DOI Listing
August 2017