Publications by authors named "Arno F van Heijst"

64 Publications

Follow-up after very preterm birth in Europe.

Arch Dis Child Fetal Neonatal Ed 2021 Feb 10. Epub 2021 Feb 10.

Université de Paris, CRESS, Obstetrical Perinatal and Pediatric Epidemiology Research Team, EPOPé, INSERM, INRA, F-75004 Paris, France.

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http://dx.doi.org/10.1136/archdischild-2020-320823DOI Listing
February 2021

Survival and causes of death in extremely preterm infants in the Netherlands.

Arch Dis Child Fetal Neonatal Ed 2020 11 6. Epub 2020 Nov 6.

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

Objective: In the Netherlands, the threshold for offering active treatment for spontaneous birth was lowered from 25 to 24 weeks' gestation in 2010. This study aimed to evaluate the impact of guideline implementation on survival and causes and timing of death in the years following implementation.

Design: National cohort study, using data from the Netherlands Perinatal Registry.

Patients: The study population included all 3312 stillborn and live born infants with a gestational age (GA) between 24 and 26 weeks born between January 2011 and December 2017. Infants with the same GA born between January 2007 and December 2009 (N=1400) were used as the reference group.

Main Outcome Measures: Survival to discharge, as well as cause and timing of death.

Results: After guideline implementation, there was a significant increase in neonatal intensive care unit (NICU) admission rate for live born infants born at 24 weeks' GA (27%-69%, p<0.001), resulting in increased survival to discharge in 24-week live born infants (13%-34%, p<0.001). Top three causes of in-hospital mortality were necrotising enterocolitis (28%), respiratory distress syndrome (19%) and intraventricular haemorrhage (17%). A significant decrease in cause of death either complicated or caused by respiratory insufficiency was seen over time (34% in 2011-2014 to 23% in 2015-2017, p=0.006).

Conclusions: Implementation of the 2010 guideline resulted as expected in increased NICU admissions rate and postnatal survival of infants born at 24 weeks' GA. In the years after implementation, a shift in cause of death was seen from respiratory insufficiency towards necrotising enterocolitis and sepsis.
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http://dx.doi.org/10.1136/archdischild-2020-318978DOI Listing
November 2020

Validation of an Instrument for Real-Time Assessment of Neonatal Intubation Skills: A Randomized Controlled Simulation Study.

Am J Perinatol 2020 Sep 8. Epub 2020 Sep 8.

Department of Neonatology, Radboud University Medical Center Amalia Children's Hospital, Nijmegen, The Netherlands.

Objective:  This study aimed to evaluate the construct validity and reliability of real-time assessment of a previously developed neonatal intubation scoring instrument (NISI).

Study Design:  We performed a randomized controlled simulation study at a simulation-based research and training facility. Twenty-four clinicians experienced in neonatal intubation ("experts") and 11 medical students ("novices") performed two identical elective intubations on a neonatal patient simulator. Subjects were randomly assigned to either the intervention group, receiving predefined feedback between the two intubations, or the control group, receiving no feedback. Using the previously developed NISI, all intubations were assessed, both in real time and remotely on video. Construct validity was evaluated by (1) comparing the intubation performances, expressed as percentage scores, with and without feedback, and (2) correlating the intubation performances with the subjects' level of experience. The intrarater reliability, expressed as intraclass correlation coefficient (ICC), of real-time assessment compared with video-based assessment was determined.

Results:  The intervention group contained 18 subjects, the control group 17. Background characteristics and baseline intubation scores were comparable in both groups. The median (IQR) change in percentage scores between the first and second intubation was significantly different between the intervention and control group (11.6% [4.7-22.8%] vs. 1.4% [0.0-5.7%], respectively;  = 0.013). The 95% CI for this 10.2% difference was 2.2 to 21.4%. The subjects' experience level correlated significantly with their percentage scores (Spearman's  = 0.70; 0.01). ICC's were 0.95 (95% CI: 0.89-0.97) and 0.94 (95% CI: 0.89-0.97) for the first and second intubation, respectively.

Conclusion:  Our NISI has construct validity and is reliable for real-time assessment.

Key Points: · Our neonatal intubation scoring instrument has construct validity.. · Our instrument can be reliably employed to assess neonatal intubation skills directly in real time.. · It is suitable for formative assessment, i.e., providing direct feedback during procedural training..
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http://dx.doi.org/10.1055/s-0040-1715530DOI Listing
September 2020

Increase in treatment of retinopathy of prematurity in the Netherlands from 2010 to 2017.

Acta Ophthalmol 2021 Feb 23;99(1):97-103. Epub 2020 Jul 23.

Leiden University Medical Center, Leiden, Netherlands.

Purpose: Compare patients treated for Retinopathy of Prematurity (ROP) in two consecutive periods.

Methods: Retrospective inventory of anonymized neonatal and ophthalmological data of all patients treated for ROP from 2010 to 2017 in the Netherlands, subdivided in period (P)1: 1-1-2010 to 31-3-2013 and P2: 1-4-2013 to 31-12-2016. Treatment characteristics, adherence to early treatment for ROP (ETROP) criteria, outcome of treatment and changes in neonatal parameters and policy of care were compared.

Results: Overall 196 infants were included, 57 infants (113 eyes) in P1 and 139 (275 eyes) in P2, indicating a 2.1-fold increase in ROP treatment. No differences were found in mean gestational age (GA) (25.9 ± 1.7 versus 26.0 ± 1.7 weeks, p = 0.711), mean birth weight (791 ± 311 versus 764 ± 204 grams, p = 0.967) and other neonatal risk factors for ROP. In P2, the number of premature infants born <25 weeks increased by factor 1.23 and higher oxygen saturation levels were aimed at in most centres. At treatment decision, 59.6% (P1) versus 83.5% (P2) (p = 0.263) infants were classified as Type 1 ROP (ETROP classification). Infants were treated with laser photocoagulation (98 versus 96%) and intravitreal bevacizumab (2 versus 4%). Retreatment was necessary in 10 versus 21 (p = 0.160). Retinal detachment developed in 6 versus 13 infants (p = 0.791) of which 2 versus 6 bilateral (p = 0.599).

Conclusion: In period 2, the number of infants treated according to the ETROP criteria (Type 1) increased, the number of ROP treatments, retinal detachments and retreatments doubled and the absolute number of retinal detachments increased. Neonatal data did not provide a decisive explanation, although changes in neonatal policy were reported.
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http://dx.doi.org/10.1111/aos.14501DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7891652PMC
February 2021

Neonatal resuscitation guideline adherence: simulation study and framework for improvement.

Eur J Pediatr 2020 Nov 29;179(11):1813-1822. Epub 2020 May 29.

Department of Neonatology, Amalia Children's Hospital, Radboud Institute for Health Sciences (RIHS), Radboud University Medical Center, P.O. Box 9101, 6500 HB, Nijmegen, the Netherlands.

We wanted to assess newborn life support (NLS) knowledge and guideline adherence, and provide strategies to improve (neonatal) resuscitation guideline adherence. Pediatricians completed 17 multiple-choice questions (MCQ). They performed a simulated NLS scenario, using a high-fidelity manikin. The literature was systematically searched for publications regarding guideline adherence. Forty-six pediatricians participated: 45 completed the MCQ, 34 performed the scenario. Seventy-one percent (median, IQR 56-82) of the MCQ were answered correctly. Fifty-six percent performed inflation breaths ≤ 60 s, 24% delivered inflation breaths of 2-3 s, and 85% used adequate inspiratory pressures. Airway patency was ensured 83% (IQR 76-92) of the time. Median events/min, compression rate, and percentage of effective compressions were 138/min (IQR 130-145), 120/min (IQR 114-120), and 38% (IQR 24-48), respectively. Other adherence percentages were temperature management 50%, auscultation of initial heart rate 100%, pulse oximeter use 94%, oxygen increase 74%, and correct epinephrine dose 82%. Ten publications were identified and used for our framework. The framework may inspire clinicians, educators, researchers, and guideline developers in their attempt to improve resuscitation guideline adherence. It contains many feasible strategies to enhance professionals' knowledge, skills, self-efficacy, and team performance, as well as recommendations regarding equipment, environment, and guideline development/dissemination.Conclusion: NLS guideline adherence among pediatricians needs improvement. Our framework is meant to promote resuscitation guideline adherence. What is Known: • Inadequate newborn life support (NLS) may contribute to (long-term) pulmonary and cerebral damage. • Video-based assessment of neonatal resuscitations has shown that deviations from the NLS guideline occur frequently; this assessment method has its audiovisual shortcomings. What is New: • The resuscitation quality metrics provided by our high-fidelity manikin suggest that the adherence of Dutch general pediatricians to the NLS guideline is suboptimal. • We constructed a comprehensive framework, containing multiple strategies to improve (neonatal) resuscitation guideline adherence.
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http://dx.doi.org/10.1007/s00431-020-03693-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7547969PMC
November 2020

Validation of a Prediction Rule for Mortality in Congenital Diaphragmatic Hernia.

Pediatrics 2020 04 5;145(4). Epub 2020 Mar 5.

Intensive Care and Departments of Pediatric Surgery.

Background: Congenital diaphragmatic hernia (CDH) is a rare congenital anomaly with a mortality of ∼27%. The Congenital Diaphragmatic Hernia Study Group (CDHSG) developed a simple postnatal clinical prediction rule to predict mortality in newborns with CDH. Our aim for this study is to externally validate the CDHSG rule in the European population and to improve its prediction of mortality by adding prenatal variables.

Methods: We performed a European multicenter retrospective cohort study and included all newborns diagnosed with unilateral CDH who were born between 2008 and 2015. Newborns born from November 2011 onward were included for the external validation of the rule ( = 343). To improve the prediction rule, we included all patients born between 2008 and 2015 ( = 620) with prenatally diagnosed CDH and collected pre- and postnatal variables. We build a logistic regression model and performed bootstrap resampling and computed calibration plots.

Results: With our validation data set, the CDHSG rule had an area under the curve of 79.0%, revealing a fair predictive performance. For the new prediction rule, prenatal herniation of the liver was added, and absent 5-minute Apgar score was taken out. The new prediction rule revealed good calibration, and with an area under the curve of 84.6%, it had good discriminative abilities.

Conclusions: In this study, we externally validated the CDHSG rule for the European population, which revealed fair predictive performance. The modified rule, with prenatal liver herniation as an additional variable, appears to further improve the model's ability to predict mortality in a population of patients with prenatally diagnosed CDH.
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http://dx.doi.org/10.1542/peds.2019-2379DOI Listing
April 2020

Improvement of exercise capacity following neonatal respiratory failure: A randomized controlled trial.

Scand J Med Sci Sports 2020 Apr 15;30(4):662-671. Epub 2019 Dec 15.

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

Exercise capacity deteriorates in school-aged children born with major anatomical foregut anomalies and/or treated with extracorporeal membrane oxygenation. The aim of the present study was to evaluate whether exercise capacity can be improved in the short term and long term in children born with anatomical foregut anomalies and/or treated with extracorporeal membrane oxygenation. Therefore, we evaluated two different interventions in this single-blinded randomized controlled trial. Forty participants were randomly assigned to group A: standardized anaerobic high-intensity interval training plus online lifestyle coaching program, B: online lifestyle coaching program only, or C: standard of care. Inclusion criteria were as follows: score ≤-1 standard deviation (SD) on the Bruce protocol. Exercise capacity was assessed at baseline (T0), after 3 months (T1), and after 12 months (T2). Exercise capacity improved over time: mean (SD) standard deviation score (SDS) endurance time: T0 -1.91 (0.73); T1 -1.35 (0.94); T2 -1.20 (1.03): both P < .001. No significant differences in maximal endurance time were found at T1 (group A-C: estimated mean difference (SDS): 0.06 P = .802; group B-C: -0.17 P = .733) or T2 (group A-C: -0.13 P = .635; group B-C: -0.18 P = .587). Exercise capacity improved significantly over time, irrespective of the study arm. Not only residual morbidities may be responsible for reduced exercise capacity. Parental awareness of reduced exercise capacity rather than specific interventions may have contributed. Monitoring of exercise tolerance and providing counseling on lifestyle factors that improve physical activity should be part of routine care, and aftercare should be offered on an individual basis.
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http://dx.doi.org/10.1111/sms.13604DOI Listing
April 2020

Validation of an Assessment Instrument for Pediatric Basic Life Support.

Pediatr Emerg Care 2019 Jul 15. Epub 2019 Jul 15.

Pediatrics, Radboud University Medical Center Amalia Children's Hospital, Nijmegen, the Netherlands.

Objectives: To develop a valid and reliable instrument for the assessment of pediatric basic life support (PBLS).

Methods: An assessment instrument for PBLS was developed, based on 3 existing scoring systems and the European Resuscitation Council PBLS guideline. We tested if experienced PBLS instructors performed better than medical students on a standard PBLS examination on a low-fidelity pediatric manikin (construct validity). To pass the examination, 15 penalty points or less were required. The examinations were videotaped. One researcher assessed all videos once, and approximately half of them twice (intrarater reliability). A second researcher independently assessed part of the videos (interrater reliability). The time needed to assess 1 examination was determined.

Results: Face and content validity were established, because PBLS experts reached consensus on the instrument and because the instrument incorporated all items of the European Resuscitation Council algorithm. Of the 157 medical students that were scored, 98 (62.4%) passed the examination. Fourteen PBLS instructors were scored; all passed (100%). Pass rate (62.4% vs 100%) and median penalty points (15 [interquartile range, 10-22.5] vs 7.5 [interquartile range, 1.25-10]) were significantly different between students and instructors (P = 0.005 and <0.001, respectively). Reassessment demonstrated a κ for intrarater reliability of 0.62 (95% confidence interval, 0.45-0.81) (substantial agreement); κ for interrater reliability was 0.51 (95% confidence interval, 0.09-0.93) (moderate agreement). It took approximately 3 minutes to assess 1 videotaped examination.

Conclusions: Our instrument for the (video-based) assessment of PBLS is valid and sufficiently reliable. It is also designed to be practical, time-efficient, and applicable in various settings, including resource limited.
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http://dx.doi.org/10.1097/PEC.0000000000001899DOI Listing
July 2019

Training-induced white matter microstructure changes in survivors of neonatal critical illness: A randomized controlled trial.

Dev Cogn Neurosci 2019 08 27;38:100678. Epub 2019 Jun 27.

Department of Child and Adolescent Psychiatry/Psychology, Erasmus MC-Sophia Children's Hospital, 3015 CN Rotterdam, the Netherlands; Department of Radiology and Nuclear Medicine, Erasmus MC, 3015 CN Rotterdam, the Netherlands. Electronic address:

In a nationwide randomized controlled trial, white matter microstructure was assessed before and immediately after Cogmed Working-Memory Training (CWMT) in school-age neonatal critical illness survivors. Eligible participants were survivors (8-12 years) with an IQ ≥ 80 and a z-score of ≤ -1.5 on (working)memory test at first assessment. Diffusion Tensor Imaging was used to assess white matter microstructure. Associations between any training-induced changes and improved neuropsychological outcome immediately and one year post-CWMT were evaluated as well. The trial was conducted between October 2014-June 2017 at Erasmus MC-Sophia, Rotterdam, Netherlands. Researchers involved were blinded to group allocation. Participants were randomized to CWMT(n = 14) or no-intervention(n = 20). All children completed the CWMT. Global fractional anisotropy(FA) increased significantly post-CWMT compared to no-intervention(estimated-coefficient = .007, p = .015). Increased FA(estimated coefficient = .009, p = .033) and decreased mean diffusivity(estimated-coefficient = -.010, p = .018) were found in the left superior longitudinal fasciculus(SFL) post-CWMT compared no-intervention. Children after CWMT who improved with >1SD on verbal working-memory had significantly higher FA in the left SLF post-CWMT(n = 6; improvement = .408 ± .01) than children without this improvement post-CWMT(n = 6; no-improvement = .384 ± .02), F(1,12) = 6.22, p = .041, η = .47. No other structure-function relationships were found post-CWMT. Our findings demonstrate that white matter microstructure and associated cognitive outcomes are malleable by CWMT in survivors of neonatal critical illness.
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http://dx.doi.org/10.1016/j.dcn.2019.100678DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6969347PMC
August 2019

Development of Nationwide Recommendations to Support Prenatal Counseling in Extreme Prematurity.

Pediatrics 2019 06;143(6)

Departments of Neonatology and Pediatrics and.

Objectives: To develop a nationwide, evidence-based framework to support prenatal counseling in extreme prematurity, focusing on organization, decision-making, content, and style aspects.

Methods: A nationwide multicenter RAND-modified Delphi method study was performed between November 2016 and December 2017 in the Netherlands. Firstly, recommendations were extracted from literature and previous studies. Secondly, an expert panel ( = 21) with experienced parents, obstetricians, and neonatologists rated the recommendations on importance for inclusion in the framework. Thirdly, ratings were discussed in a consensus meeting. The final set of recommendations was approved and transformed into a framework.

Results: A total of 101 recommendations on organization, decision-making, content, and style were included in the framework, including tools to support personalization. The most important recommendations regarding organization were to have both parents involved in the counseling with both the neonatologist and obstetrician. The shared decision-making model was recommended for deciding between active support and comfort care. Main recommendations regarding content of conversation were explanation of treatment options, information on survival, risk of permanent consequences, impossibility to predict an individual course, possibility for multiple future decision moments, and a discussion on parental values and standards. It was considered important to avoid jargon, check understanding, and provide a summary. The expert panel, patient organization, and national professional associations (gynecology and pediatrics) approved the framework.

Conclusions: A nationwide, evidence-based framework for prenatal counseling in extreme prematurity was developed. It contains recommendations and tools for personalization in the domains of organization, decision-making, content, and style of prenatal counseling.
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http://dx.doi.org/10.1542/peds.2018-3253DOI Listing
June 2019

Effect of Hydrocortisone Therapy Initiated 7 to 14 Days After Birth on Mortality or Bronchopulmonary Dysplasia Among Very Preterm Infants Receiving Mechanical Ventilation: A Randomized Clinical Trial.

JAMA 2019 01;321(4):354-363

Department of Neonatology, Emma Children's Hospital, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands.

Importance: Dexamethasone initiated after the first week of life reduces the rate of death or bronchopulmonary dysplasia (BPD) but may cause long-term adverse effects in very preterm infants. Hydrocortisone is increasingly used as an alternative, but evidence supporting its efficacy and safety is lacking.

Objective: To assess the effect of hydrocortisone initiated between 7 and 14 days after birth on death or BPD in very preterm infants.

Design, Setting, And Participants: Double-blind, placebo-controlled randomized trial conducted in 19 neonatal intensive care units in the Netherlands and Belgium from November 15, 2011, to December 23, 2016, among preterm infants with a gestational age of less than 30 weeks and/or birth weight of less than 1250 g who were ventilator dependent between 7 and 14 days of life, with follow-up to hospital discharge ending December 12, 2017.

Interventions: Infants were randomly assigned to receive a 22-day course of systemic hydrocortisone (cumulative dose, 72.5 mg/kg) (n = 182) or placebo (n = 190).

Main Outcomes And Measures: The primary outcome was a composite of death or BPD assessed at 36 weeks' postmenstrual age. Twenty-nine secondary outcomes were analyzed up to hospital discharge, including death and BPD at 36 weeks' postmenstrual age.

Results: Among 372 patients randomized (mean gestational age, 26 weeks; 55% male), 371 completed the trial; parents withdrew consent for 1 child treated with hydrocortisone. Death or BPD occurred in 128 of 181 infants (70.7%) randomized to hydrocortisone and in 140 of 190 infants (73.7%) randomized to placebo (adjusted risk difference, -3.6% [95% CI, -12.7% to 5.4%]; adjusted odds ratio, 0.87 [95% CI, 0.54-1.38]; P = .54). Of 29 secondary outcomes, 8 showed significant differences, including death at 36 weeks' postmenstrual age (15.5% with hydrocortisone vs 23.7% with placebo; risk difference, -8.2% [95% CI, -16.2% to -0.1%]; odds ratio, 0.59 [95% CI, 0.35-0.995]; P = .048). Twenty-one outcomes showed nonsignificant differences, including BPD (55.2% with hydrocortisone vs 50.0% with placebo; risk difference, 5.2% [95% CI, -4.9% to 15.2%]; odds ratio, 1.24 [95% CI, 0.82-1.86]; P = .31). Hyperglycemia requiring insulin therapy was the only adverse effect reported more often in the hydrocortisone group (18.2%) than in the placebo group (7.9%).

Conclusions And Relevance: Among mechanically ventilated very preterm infants, administration of hydrocortisone between 7 and 14 days after birth, compared with placebo, did not improve the composite outcome of death or BPD at 36 weeks' postmenstrual age. These findings do not support the use of hydrocortisone for this indication.

Trial Registration: Netherlands National Trial Register Identifier: NTR2768.
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http://dx.doi.org/10.1001/jama.2018.21443DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6439762PMC
January 2019

Uncontrolled maternal chronic respiratory diseases in pregnancy: A new potential risk factor suggested to be associated with anorectal malformations in offspring.

Birth Defects Res 2019 01 19;111(2):62-69. Epub 2018 Dec 19.

Department for Health Evidence, Radboud Institute for Health Sciences, Radboud university medical center (Radboudumc), Nijmegen, The Netherlands.

Background: Chronic respiratory diseases and use of antiasthmatic medication during pregnancy may both play a role in the etiology of congenital anorectal malformations (ARM). However, it is unclear, whether the medication use or the underlying condition would be responsible. Therefore, our aim was to unravel the role of maternal chronic respiratory diseases from that of antiasthmatic medication in the etiology of ARM.

Methods: We obtained 412 ARM patients and 2,137 population-based controls from the Dutch AGORA data- and biobank. We used maternal questionnaires and follow-up telephone interviews to obtain information on chronic respiratory diseases, antiasthmatic medication use, and potential confounders. Multivariable logistic regression analyses were performed to estimate odds ratios (ORs) with 95% confidence intervals (95% CI).

Results: We observed higher risk estimates among women with chronic respiratory diseases with and without medication use (1.4 [0.8-2.7] and 2.0 [0.8-5.0]), both in comparison to women without a chronic respiratory disease and without medication use. Furthermore, increased ORs of ARM were found for women using rescue medication (2.4 [0.8-7.3]) or a combination of maintenance and rescue medication (2.5 [0.9-6.7]). In addition, increased risk estimates were observed for women having nonallergic triggers (2.5 [1.0-6.3]) or experiencing exacerbations during the periconceptional period (3.5 [1.4-8.6]).

Conclusions: Although the 95% CIs of most associations include the null value, the risk estimates all point towards an association between uncontrolled chronic respiratory disease, instead of antiasthmatic medication use, with ARM in offspring. Further in-depth studies towards mechanisms of this newly identified risk factor are warranted.
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http://dx.doi.org/10.1002/bdr2.1429DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7380291PMC
January 2019

Appraisal of a scoring instrument for training and testing neonatal intubation skills.

Arch Dis Child Fetal Neonatal Ed 2019 Sep 1;104(5):F521-F527. Epub 2018 Dec 1.

Department of Neonatology, Amalia Children's Hospital, Radboud University Medical Center, Nijmegen, The Netherlands.

Objective: To determine the validity, reliability, feasibility and applicability of a neonatal intubation scoring instrument.

Design: Prospective observational study.

Setting: Simulation-based research and training centre (Center for Advanced Pediatric and Perinatal Education), California, USA.

Subjects: Forty clinicians qualified for neonatal intubation.

Interventions: Videotaped elective intubations on a neonatal patient simulator were scored by two independent raters. One rater scored the intubations twice. We scored the preparation of equipment and premedication, intubation performance, tube position/fixation, communication, number of attempts, duration and successfulness of the procedure.

Main Outcome Measures: Intraclass correlation coefficients (ICC) were calculated for intrarater and inter-rater reliability. Kappa coefficients for individual items and mean kappa coefficients for all items combined were calculated. Construct validity was assessed with one-way analysis of variance using the hypothesis that experienced clinicians score higher than less experienced clinicians. The approximate time to score one intubation and the instrument's applicability in another setting were evaluated.

Results: ICCs for intrarater and inter-rater reliability were 0.99 (95% CI 0.98 to 0.99) and 0.89 (95% CI 0.35 to 0.96), and mean kappa coefficients were 0.93 (95% CI 0.85 to 1.01) and 0.71 (95% CI 0.56 to 0.92), respectively. There were no differences between the more and less experienced clinicians regarding preparation, performance, communication and total scores. The experienced group scored higher only on tube position/fixation (p0.02). Scoring one intubation took approximately 15 min. Our instrument, developed in The Netherlands, could be readily applied in the USA.

Conclusions: Our scoring instrument for simulated neonatal intubations appears to be reliable, feasible and applicable in another centre. Construct validity could not be established.
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http://dx.doi.org/10.1136/archdischild-2018-315221DOI Listing
September 2019

Early treatment versus expectative management of patent ductus arteriosus in preterm infants: a multicentre, randomised, non-inferiority trial in Europe (BeNeDuctus trial).

BMC Pediatr 2018 08 4;18(1):262. Epub 2018 Aug 4.

Department of Paediatrics, Division of Neonatology, Radboud university medical centre Nijmegen, Radboud Institute for Health Sciences, Amalia Children's Hospital, Internal postal code 804, Geert Grooteplein Zuid 10, 6525, GA, Nijmegen, The Netherlands.

Background: Much controversy exists about the optimal management of a patent ductus arteriosus (PDA) in preterm infants, especially in those born at a gestational age (GA) less than 28 weeks. No causal relationship has been proven between a (haemodynamically significant) PDA and neonatal complications related to pulmonary hyperperfusion and/or systemic hypoperfusion. Although studies show conflicting results, a common understanding is that medical or surgical treatment of a PDA does not seem to reduce the risk of major neonatal morbidities and mortality. As the PDA might have closed spontaneously, treated children are potentially exposed to iatrogenic adverse effects. A conservative approach is gaining interest worldwide, although convincing evidence to support its use is lacking.

Methods: This multicentre, randomised, non-inferiority trial is conducted in neonatal intensive care units. The study population consists of preterm infants (GA < 28 weeks) with an echocardiographic-confirmed PDA with a transductal diameter > 1.5 mm. Early treatment (between 24 and 72 h postnatal age) with the cyclooxygenase inhibitor (COXi) ibuprofen (IBU) is compared with an expectative management (no intervention intended to close a PDA). The primary outcome is the composite of mortality, and/or necrotising enterocolitis (NEC) Bell stage ≥ IIa, and/or bronchopulmonary dysplasia (BPD) defined as the need for supplemental oxygen, all at a postmenstrual age (PMA) of 36 weeks. Secondary outcome parameters are short term sequelae of cardiovascular failure, comorbidity and adverse events assessed during hospitalization and long-term neurodevelopmental outcome assessed at a corrected age of 2 years. Consequences regarding health economics are evaluated by cost effectiveness analysis and budget impact analysis.

Discussion: As a conservative approach is gaining interest, we investigate whether in preterm infants, born at a GA less than 28 weeks, with a PDA an expectative management is non-inferior to early treatment with IBU regarding to the composite outcome of mortality and/or NEC and/or BPD at a PMA of 36 weeks.

Trial Registration: This trial is registered with the Dutch Trial Register NTR5479 (registered on 19 October 2015), the registry sponsored by the United States National Library of Medicine Clinicaltrials.gov NCT02884219 (registered May 2016) and the European Clinical Trials Database EudraCT 2017-001376-28 .
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http://dx.doi.org/10.1186/s12887-018-1215-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6090763PMC
August 2018

Improving Long-Term Outcomes After Extracorporeal Membrane Oxygenation: From Observational Follow-Up Programs Toward Risk Stratification.

Front Pediatr 2018 26;6:177. Epub 2018 Jun 26.

Department of Neonatology, Amalia Children's Hospital, Radboud University Medical Center, Nijmegen, Netherlands.

Since the introduction of extracorporeal membrane oxygenation (ECMO), more neonates and children with cardiorespiratory failure survive. Interest has therefore shifted from reduction of mortality toward evaluation of long-term outcomes and prevention of morbidity. This review addresses the changes in ECMO population and the ECMO-treatment that may affect long-term outcomes, the diagnostic modalities to evaluate neurological morbidities and their contributions to prognostication of long-term outcomes. Most follow-up data have only become available from observational follow-up programs in neonatal ECMO-survivors. The main topics are discussed in this review. Recommendations for long-term follow up depend on the presence of neurological comorbidity, the nature and extent of the underlying disease, and the indication for ECMO. Follow up should preferably be offered as standard of care, and in an interdisciplinary, structured and standardized way. This permits evaluation of outcome data and effect of interventions. We propose a standardized approach and recommend that multiple domains should be evaluated during long-term follow up of neonates and children who needed extracorporeal life support.
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http://dx.doi.org/10.3389/fped.2018.00177DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6036288PMC
June 2018

Evaluation of bone mineralization in former preterm born children: Phalangeal quantitative ultrasound cannot replace dual-energy X-ray absorptiometry.

Bone Rep 2018 Jun 28;8:38-45. Epub 2018 Jan 28.

Department of Pediatrics, Subdivision of Neonatology, Radboudumc Amalia Children's Hospital, Radboud University Medical Center, Nijmegen, The Netherlands.

Background: Preterm infants are at risk of impaired bone health in later life. Dual-energy X-ray absorptiometry-scan (DXA) is the gold standard to determine bone mineralization. Phalangeal quantitative ultrasound (pQUS) is an alternative technique that is inexpensive, easy to use and radiation-free. The aim of this study was to investigate whether both techniques reveal equivalent results.

Materials And Methods: Sixty former preterm infants (31 boys; 29 girls) received a DXA and pQUS at age 9 to 10 years. DXA measured bone mineral content (BMC) and bone mineral density (BMD) for total body and lumbar spine (L1-4), while pQUS measured the amplitude dependent speed of sound (AD-SoS) and bone transit time (BTT) at metacarpals II-IV providing continuous values and -scores based on age and sex. Four statistical methods evaluated the association between both techniques: Pearson's correlation coefficients, partial correlation coefficients adjusted for gestational age, height and BMI, Bland-Altman analysis and cross tabulation.

Results: Both techniques showed a statistically significant weak correlation for continuous values as well as -scores (0.291-0.462, p < 0.05). Boys had significant and relatively high correlations (0.468-0.585, p < 0.05). In comparison, the correlations for girls were not significant. Correlation coefficients further decreased while calculating the partial correlations. The Bland-Altman plots showed poor agreement. Sensitivity ranged from 33% to 92% and specificity from 16% to 68%. Positive and negative predictive values ranged from 4% to 38% and 82% to 97%, respectively.

Conclusions: We found statistically significant weak correlations and poor agreement between DXA and pQUS measurements. DXA is not equivalent to pQUS and therefore not replaceable by this technique in former preterm born children at the age of 9 to 10 years.
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http://dx.doi.org/10.1016/j.bonr.2018.01.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6019963PMC
June 2018

Defining outcomes following congenital diaphragmatic hernia using standardised clinical assessment and management plan (SCAMP) methodology within the CDH EURO consortium.

Pediatr Res 2018 08 29;84(2):181-189. Epub 2018 May 29.

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

Treatment modalities for neonates born with congenital diaphragmatic hernia (CDH) have greatly improved in recent times with a concomitant increase in survival. In 2008, CDH EURO consortium, a collaboration of a large volume of CDH centers in Western Europe, was established with a goal to standardize management and facilitate multicenter research. However, limited knowledge on long-term outcomes restricts the identification of optimal care pathways for CDH survivors in adolescence and adulthood. This review aimed to evaluate the current practice of long-term follow-up within the CDH EURO consortium centers, and to review the literature on long-term outcomes published from 2000 onward. Apart from having disease-specific morbidities, children with CDH are at risk for impaired neurodevelopmental problems and failure of educational attainments which may affect participation in society and the quality of life in later years. Thus, there is every reason to offer them long-term multidisciplinary follow-up programs. We discuss a proposed collaborative project using standardized clinical assessment and management plan (SCAMP) methodology to obtain uniform and standardized follow-up of CDH patients at an international level.
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http://dx.doi.org/10.1038/s41390-018-0063-3DOI Listing
August 2018

Neonatal Hemodynamics: From Developmental Physiology to Comprehensive Monitoring.

Front Pediatr 2018 5;6:87. Epub 2018 Apr 5.

Department of Perinatology (Neonatology), Amalia Children's Hospital, Radboud Institute for Health Sciences, Radboud University Medical Center, Nijmegen, Netherlands.

Maintenance of neonatal circulatory homeostasis is a real challenge, due to the complex physiology during postnatal transition and the inherent immaturity of the cardiovascular system and other relevant organs. It is known that abnormal cardiovascular function during the neonatal period is associated with increased risk of severe morbidity and mortality. Understanding the functional and structural characteristics of the neonatal circulation is, therefore, essential, as therapeutic hemodynamic interventions should be based on the assumed underlying (patho)physiology. The clinical assessment of systemic blood flow (SBF) by indirect parameters, such as blood pressure, capillary refill time, heart rate, urine output, and central-peripheral temperature difference is inaccurate. As blood pressure is no surrogate for SBF, information on cardiac output and systemic vascular resistance should be obtained in combination with an evaluation of end organ perfusion. Accurate and reliable hemodynamic monitoring systems are required to detect inadequate tissue perfusion and oxygenation at an early stage before this result in irreversible damage. Also, the hemodynamic response to the initiated treatment should be re-evaluated regularly as changes in cardiovascular function can occur quickly. New insights in the understanding of neonatal cardiovascular physiology are reviewed and several methods for current and future neonatal hemodynamic monitoring are discussed.
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http://dx.doi.org/10.3389/fped.2018.00087DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5895966PMC
April 2018

Working Memory Training Following Neonatal Critical Illness: A Randomized Controlled Trial.

Crit Care Med 2018 07;46(7):1158-1166

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

Objectives: To test the immediate and long-term effectiveness of Cogmed Working Memory Training following extracorporeal membrane oxygenation and/or congenital diaphragmatic hernia.

Design: A nationwide randomized controlled trial assessing neuropsychologic outcome immediately and 1 year post Cogmed Working Memory Training, conducted between October 2014 and June 2017. Researchers involved in the follow-up assessments were blinded to group allocation.

Setting: Erasmus MC-Sophia Children's Hospital, Rotterdam, and Radboud University Medical Center, Nijmegen, the Netherlands.

Patients: Eligible participants were neonatal extracorporeal membrane oxygenation and/or congenital diaphragmatic hernia survivors (8-12 yr) with an intelligence quotient greater than or equal to 80 and a z score less than or equal to -1.5 on at least one (working) memory test at first assessment.

Interventions: Cogmed Working Memory Training, comprising 25 45-minute training sessions for 5 consecutive weeks at home.

Measurements And Main Results: Participants were randomized to Cogmed Working Memory Training (n = 19) or no intervention (n = 24) (two dropped out after T0). Verbal working memory (estimated coefficient = 0.87; p = 0.002) and visuospatial working memory (estimated coefficient=0.96, p = 0.003) significantly improved at T1 post Cogmed Working Memory Training but was similar between groups at T2 (verbal, p = 0.902; visuospatial, p = 0.416). Improvements were found at T2 on long-term visuospatial memory following Cogmed Working Memory Training (estimated coefficient = 0.95; p = 0.003). Greater improvements in this domain at T2 following Cogmed Working Memory Training were associated with better self-rated school functioning (r = 0.541; p = 0.031) and parent-rated attention (r = 0.672; p = 0.006).

Conclusions: Working memory improvements after Cogmed Working Memory Training disappeared 1 year post training in neonatal extracorporeal membrane oxygenation and/or congenital diaphragmatic hernia survivors. Gains in visuospatial memory persisted 1 year post intervention. Cogmed Working Memory Training may be beneficial for survivors with visuospatial memory deficits.
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http://dx.doi.org/10.1097/CCM.0000000000003151DOI Listing
July 2018

Growth and Bone Mineralization of Very Preterm Infants at Term Corrected Age in Relation to Different Nutritional Intakes in the Early Postnatal Period.

Nutrients 2017 Dec 2;9(12). Epub 2017 Dec 2.

Department of Paediatrics, Subdivision of Neonatology, Radboudumc Amalia Children's Hospital, Radboud University Medical Center, P.O. Box 9101, Internal Postal Code 804, 6500 HB Nijmegen, The Netherlands.

Preterm infants often have a reduced bone mineral content (BMC) with increased risk of metabolic bone disease. After birth it is difficult to supply calcium (Ca) and phosphorus (P) comparable to the high fetal accretion rate. It is not known whether high supplementation of minerals in the early postnatal period improves growth and bone mineralization. The aim of this study was to evaluate growth and bone mineralization at term corrected age (TCA) in very and extremely preterm infants who received different enteral Ca and P intakes during the first 10 days of life. Infants ( = 109) with birth weights below 1500 g were randomly assigned to one of three groups that differed in the nutritional protocols delivered until day 10: Group A, mother's own milk (MOM) and donor milk (unfortified); Group B, MOM (unfortified) and preterm formula; Group C, MOM (start fortification >50 mL/day) and preterm formula. Due to the earlier commencement of fortification, Group C received higher intakes of calcium and phosphorus and protein ( < 0.001) until day 10. At TCA weight, length, BMC and bone mineral density (BMD), measured by dual-X-ray absorptiometry, were not different between the groups. Nutritional intake of P was positively associated with length (β; (95% confidence interval (CI): 0.20 (0.001; 0.393); -value = 0.048), whereas Ca intake was negatively associated with BMC (-1.94 (-2.78; -1.09); -value < 0.001). A small interaction between Ca and P intake was only found for BMD (0.003 (0.00002; 0.00006); -value = 0.036). The volume of human milk per kg provided during the first 10 days was positively associated with BMC (β; (95% CI): 0.013 (0.002; 0.023); < 0.017). Higher intakes of Ca and P during the first 10 days, as provided in this study, did not improve bone mineralization at term corrected age.
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http://dx.doi.org/10.3390/nu9121318DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5748768PMC
December 2017

Neurodevelopmental Outcome in Relation to Treatment of Patent Ductus Arteriosus.

JAMA Pediatr 2017 10;171(10):1018

Subdivision of Neonatology, Department of Pediatrics, Radboudumc Amalia Children's Hospital, Radboud University Medical Center, Nijmegen, the Netherlands.

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http://dx.doi.org/10.1001/jamapediatrics.2017.2612DOI Listing
October 2017

Neurobiologic Correlates of Attention and Memory Deficits Following Critical Illness in Early Life.

Crit Care Med 2017 Oct;45(10):1742-1750

1Intensive Care and Department of Pediatric Surgery, Erasmus MC-Sophia Children's Hospital, Rotterdam, The Netherlands. 2Department of Child and Adolescent Psychiatry/Psychology, Erasmus MC-Sophia Children's Hospital, Rotterdam, The Netherlands. 3Department of Radiology and Nuclear Medicine, Erasmus MC-Sophia Children's Hospital, Rotterdam, The Netherlands. 4Department of Neonatology, Radboud University Medical Center, Nijmegen, The Netherlands.

Objectives: Survivors of critical illness in early life are at risk of long-term-memory and attention impairments. However, their neurobiologic substrates remain largely unknown.

Design: A prospective follow-up study.

Setting: Erasmus MC-Sophia Children's Hospital, Rotterdam, the Netherlands.

Patients: Thirty-eight school-age (8-12 yr) survivors of neonatal extracorporeal membrane oxygenation and/or congenital diaphragmatic hernia with an intelligence quotient greater than or equal to 80 and a below average score (z score ≤ -1.5) on one or more memory tests.

Interventions: None.

Measurements And Main Results: Intelligence, attention, memory, executive functioning, and visuospatial processing were assessed and compared with reference data. White matter microstructure and hippocampal volume were assessed using diffusion tensor imaging and structural MRI, respectively. Global fractional anisotropy was positively associated with selective attention (β = 0.53; p = 0.030) and sustained attention (β = 0.48; p = 0.018). Mean diffusivity in the left parahippocampal region of the cingulum was negatively associated with visuospatial memory, both immediate (β = -0.48; p = 0.030) and delayed recall (β = -0.47; p = 0.030). Mean diffusivity in the parahippocampal region of the cingulum was negatively associated with verbal memory delayed recall (left: β = -0.52, p = 0.021; right: β = -0.52, p = 0.021). Hippocampal volume was positively associated with verbal memory delayed recall (left: β = 0.44, p = 0.037; right: β = 0.67, p = 0.012). Extracorporeal membrane oxygenation treatment or extracorporeal membrane oxygenation type did not influence the structure-function relationships.

Conclusions: Our findings indicate specific neurobiologic correlates of attention and memory deficits in school-age survivors of neonatal extracorporeal membrane oxygenation and congenital diaphragmatic hernia. A better understanding of the neurobiology following critical illness, both in early and in adult life, may lead to earlier identification of patients at risk for impaired neuropsychological outcome with the use of neurobiologic markers.
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http://dx.doi.org/10.1097/CCM.0000000000002553DOI Listing
October 2017

The validity of the observed-to-expected lung-to-head ratio in congenital diaphragmatic hernia in an era of standardized neonatal treatment; a multicenter study.

Prenat Diagn 2017 Jul 1;37(7):658-665. Epub 2017 Jun 1.

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

Objective: To assess the predictive value of observed-to-expected lung-to-head ratio (O/E LHR) for survival and chronic lung disease (CLD) in survivors of left-sided congenital diaphragmatic hernia (CDH) in an era of standardized neonatal treatment, and to evaluate the predictive value of the O/E LHR trajectory for survival.

Methods: This retrospective cohort study was performed in two high-volume CDH centers in the Netherlands in prenatally detected, isolated left-sided CDH patients born between 2008 and 2014. O/E LHR and liver position were determined using 2D-ultrasonography at three time points during gestation from 19 weeks onwards. Ultrasound measurements were performed on stored ultrasound data by one single experienced operator blinded to postnatal outcome.

Results: Of the 122 included cases, 77.9% survived of whom 38.9% developed CLD. A significant association was found between the first measured O/E LHR and survival and development of CLD in survivors. Prenatal liver position did not have additional predictive value. No significant association was found between the trajectory of the O/E LHR and survival.

Conclusion: In an era of standardized neonatal treatment for neonates with CDH, the first measured O/E LHR per patient significantly predicts survival and development of CLD in survivors in isolated left-sided CDH infants. © 2017 The Authors. Prenatal Diagnosis published by John Wiley & Sons, Ltd.
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http://dx.doi.org/10.1002/pd.5062DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5518227PMC
July 2017

Early-onset preeclampsia is associated with perinatal mortality and severe neonatal morbidity.

J Matern Fetal Neonatal Med 2017 Dec 23;30(23):2789-2794. Epub 2017 Feb 23.

a Department of Obstetrics and Gynecology , Radboud University Medical Centre, Nijmegen , the Netherlands.

Objective: To evaluate neonatal outcomes of pregnancies complicated by early-onset preeclampsia (PE) and compare these outcomes to those of gestational age matched neonates born to mothers whose pregnancy was not complicated by early-onset PE.

Methods: We analyzed the outcome in 97 neonates born to mothers with early-onset PE (24-32 weeks amenorrhea at diagnosis) and compared it to that of 680 gestational age-matched neonates born between 25-36 weeks due to other etiologies and admitted to the Neonatal Intensive Care Unit (NICU) of a tertiary referral hospital in the Netherlands. We used Chi-square test, Wilcoxon test, and logistic regression analyses.

Results: Neonates born to PE mothers had a higher perinatal mortality (13% vs. 7%, p = 0.03) and infant mortality (16% vs. 9%, p= 0.03), a 20% lower birth weight (1150 vs. 1430 g, p<0.001), were more often SGA (22% vs. 9%, p < 0.001) and had more neonatal complications as compared to neonates born to mothers without PE.

Conclusions: Overall adverse perinatal outcome is significantly worse in neonates born to mothers with early-onset PE. The effect of early-onset PE on perinatal mortality seems partially due to SGA. Whether these differences are due to uteroplacental factors or intrinsic neonatal factors remains to be elucidated.
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http://dx.doi.org/10.1080/14767058.2016.1263295DOI Listing
December 2017

Neuropsychological Follow-up After Neonatal ECMO.

Pediatrics 2016 11 6;138(5). Epub 2016 Oct 6.

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

Objective: To assess the longitudinal development of intelligence and its relation to school performance in a nationwide cohort of neonatal extracorporeal membrane oxygenation (ECMO) survivors and evaluate predictors of outcome at 8 years of age.

Methods: Repeated measurements assessed intelligence of neonatal ECMO survivors at 2, 5, and 8 years (n = 178) with the use of validated, standardized instruments. Selective attention (n = 148) and type of education were evaluated in the 8-year-olds.

Results: Intelligence remained stable and average across development (mean ± SD IQ: at 2 years, 102 ± 18; at 5 years, 100 ± 17; and at 8 years, 99 ± 17 [P = .15]). Children attending regular education without the need for help (n = 101; mean z score: -1.50 ± 1.93) performed significantly better on the selective attention task compared with those children who needed extra help (n = 65; mean z score: -2.54 ± 3.18) or those attending special education (n = 13; mean z score: -4.14 ± 3.63) (P = .03). However, only children attending special education had below-average intelligence (mean IQ: 76 ± 15), compared with average intelligence for those attending regular education, both with help (mean IQ: 95 ± 15) and without help (mean IQ: 105 ± 16). Compared with children with other diagnoses, children with congenital diaphragmatic hernia (CDH) scored significantly lower on both IQ (CDH, mean IQ: 93 ± 20; meconium aspiration syndrome, mean IQ: 100 ± 15; other diagnoses, mean IQ: 100 ± 19 [P = .04]) and selective attention (CDH, mean z score: -3.48 ± 3.46; meconium aspiration syndrome, mean z score: -1.60 ± 2.13; other diagnoses, mean z score: -1.65 ± 2.39 [P = .002]).

Conclusions: For the majority of neonatal ECMO survivors, intelligence testing alone did not identify those at risk for academic problems. We propose internationally standardized follow-up protocols that focus on long-term, problem-oriented neuropsychological assessment.
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http://dx.doi.org/10.1542/peds.2016-1313DOI Listing
November 2016

Changes in Biochemical Parameters of the Calcium-Phosphorus Homeostasis in Relation to Nutritional Intake in Very-Low-Birth-Weight Infants.

Nutrients 2016 Nov 29;8(12). Epub 2016 Nov 29.

Department of Paediatrics, Subdivision of Neonatology, Radboudumc Amalia Children's Hospital, Radboud University Medical Center, Nijmegen 6500HB, The Netherlands.

Preterm infants are at significant risk to develop reduced bone mineralization based on inadequate supply of calcium and phosphorus (Ca-P). Biochemical parameters can be used to evaluate the nutritional intake. The direct effect of nutritional intake on changes in biochemical parameters has not been studied. Our objective was to evaluate the effect of Ca-P supplementation on biochemical markers as serum (s)/urinary (u) Ca and P; alkaline phosphatase (ALP); tubular reabsorption of P (TrP); and urinary ratios for Ca/creatinin (creat) and P/creatinin in Very-Low-Birth-Weight infants on Postnatal Days 1, 3, 5, 7, 10, and 14. This observational study compared two groups with High ( = 30) and Low ( = 40) intake of Ca-P. Birth weight: median (IRQ) 948 (772-1225) vs. 939 (776-1163) grams; and gestational age: 28.2 (26.5-29.6) vs. 27.8 (26.1-29.4) weeks. Daily median concentrations of biochemical parameter were not different between the groups but linear regression mixed model analyses showed that Ca intake increased the uCa and TrP ( = 0.04) and decreased ALP ( = 0.00). Phosphorus intake increased sP, uP and uP/creat ratio and ALP ( ≤ 0.02) and caused decrease in TrP ( = 0.00). Protein intake decreased sP ( = 0.000), while low gestational age and male gender increased renal excretion of P ( < 0.03). Standardized repeated measurements showed that biochemical parameters were affected by nutritional intake, gestational age and gender.
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http://dx.doi.org/10.3390/nu8120764DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5188419PMC
November 2016

Risk and relevance of open lung biopsy in pediatric ECMO patients: the Dutch experience.

J Pediatr Surg 2017 Mar 14;52(3):405-409. Epub 2016 Nov 14.

Division of Neonatology, Department of Pediatrics, Radboudumc-Amalia Children's Hospital, Nijmegen, The Netherlands.

Background: Open lung biopsy can help differentiate between reversible and irreversible lung disease and may guide therapy. To assess the risk-benefit ratio of this procedure in pediatric extracorporeal membrane oxygenation (ECMO) patients, we reviewed data of all patients who underwent an open lung biopsy during ECMO in one of the two pediatric ECMO centers in a nationwide study in the Netherlands.

Results: In nineteen neonatal and six pediatric patients (0-15.5years), twenty-five open lung biopsies were performed during the study period. In 13 patients (52%), a classifying diagnosis of underlying lung disease could be made. In another nine patients (36%), specific pathological abnormalities were described. In three patients (12%), only nonspecific abnormalities were described. The histological results led to withdrawal of ECMO treatment in 6 neonates with alveolar capillary dysplasia/misalignment of pulmonary veins (24%) and in another 6 patients, corticosteroids were started (24%). All patients survived the biopsy procedure. Hemorrhagic complications were rare.

Conclusion: An open lung biopsy during an ECMO run in neonates and children is a safe procedure with a minimum risk for blood loss and biopsy-related death. It can be very useful in diagnosing the underlying pathology and can guide cessation of ECMO treatment and thereby avoid continuation of futile treatment, especially in neonatal patients.

Level Of Evidence: III.

Type Of Study: Diagnostic study.
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http://dx.doi.org/10.1016/j.jpedsurg.2016.11.031DOI Listing
March 2017

The early postnatal nutritional intake of preterm infants affected neurodevelopmental outcomes differently in boys and girls at 24 months.

Acta Paediatr 2017 Feb 12;106(2):242-249. Epub 2016 Dec 12.

Department of Paediatrics, Subdivision of Neonatology, Radboudumc Amalia Children's Hospital, Radboud university medical center, Nijmegen, The Netherlands.

Aim: This study assessed whether increased amino acid and energy intake in preterm infants during the first week of life was associated with improved neurodevelopment at the corrected age (CA) of 24 months.

Methods: We evaluated preterm infants from two consecutive cohorts in 2004 (Cohort 1) and 2005 (Cohort 2) with different nutritional intakes in the Netherlands. Nutritional intake and growth were recorded until week 5 and after discharge. Neurodevelopment was determined using the Bayley Scales of Infant Development - Second Edition at a CA of 24 months.

Results: Compared to Cohort 1 (n = 56), Cohort 2 (n = 56) received higher nutritional intake during week 1 (p < 0.001). The weight gain in Cohort 2 was higher until week 5, especially among boys (p < 0.002). The mean Mental Developmental Index (MDI) scores did not differ, but Cohort 2 was associated with an increased chance of having an MDI ≥ 85, with an odds ratio of 6.4 and 95% confidence interval (CI) of 1.5-27.4, among all girls with a higher protein intake (5.3, 1.2-23.3). The Psychomotor Developmental Index increased with increasing nutritional intake, especially among boys (β-coefficient 3.1, 95% CI 0.2-6.0).

Conclusion: Higher nutritional intake was associated with different improvements in growth and neurodevelopment in boys and girls.
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http://dx.doi.org/10.1111/apa.13669DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5248638PMC
February 2017

Outcome of isolated gastroschisis; an international study, systematic review and meta-analysis.

Early Hum Dev 2016 12 27;103:209-218. Epub 2016 Oct 27.

University Medical Center Utrecht, Division Woman and Baby, Department of Obstetrics, Utrecht, The Netherlands.. Electronic address:

Objective: To determine outcome of children born with isolated gastroschisis (no extra-gastrointestinal congenital abnormalities).

Study Design: International cohort study and meta-analysis.

Primary Outcome: time to full enteral feeding (TFEF); secondary outcomes: Duration of mechanical ventilation, length of stay (LOS), mortality and differences in outcome between simple and complex gastroschisis (complex; born with bowel atresia, volvulus, perforation or necrosis). To compare the cohort study results with literature three databases were searched. Studies were eligible for inclusion if cases were born in developed countries with isolated gastroschisis after 1990, number of cases >20 and TFEF was reported.

Results: The cohort study included 204 liveborn cases of isolated gastroschisis. The TFEF, median duration of ventilation and LOS was, 26days (range 6-515), 2days (range 0-90) and 33days (range 11-515), respectively. Overall mortality was 10.8%. TFEF and LOS were significantly longer (P<0.0001) and mortality was fourfold higher in the complex group. Seventeen studies, amongst the current study, were included for further meta-analysis comprising a total of 1652 patients. Mean TFEF was 35.3±4.4days, length of ventilation was 5.5±2.0days, LOS was 46.4±5.2days and mortality risk was 0.06 [0.04-0.07 95%CI]. Outcome of simple and complex gastroschisis was described in five studies. TFEF, ventilation time, LOS were significant longer and mortality rate was 3.64 [1.95-6.83 95%CI] times higher in complex cases.

Conclusions: These results give a good indication of the expected TFEF, ventilation time and LOS and mortality risk in children born with isolated gastroschisis, although ranges remain wide. This study shows the importance of dividing gastroschisis into simple and complex for the prediction of outcome.
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http://dx.doi.org/10.1016/j.earlhumdev.2016.10.002DOI Listing
December 2016

Detection and quantification of left-to-right shunting using transpulmonary ultrasound dilution (TPUD): a validation study in neonatal lambs.

J Perinat Med 2016 Oct;44(8):925-932

Objectives: We investigated the accuracy of left-to-right shunt detection using transpulmonary ultrasound dilution (TPUD) and compared the agreement between pulmonary over systemic blood flow (Qp/Qs) ratio measured by TPUD [Qp/Qs(tpud)] and ultrasonic flow probes [Qp/Qs(ufp)].

Methods: Seven newborn lambs under general anesthesia were connected to the TPUD monitor (COstatus™) after insertion of arterial and central venous catheters. A Gore-Tex® shunt, inserted between the descending aorta and left pulmonary artery, was intermittently opened and closed while cardiac output was varied by blood withdrawals. Flow probes were placed around the main pulmonary artery (Qufp) and the descending aorta proximal (Qpre) and distal (Qpost) to the shunt insertion. Qp/Qs(ufp) was calculated as (Qufp+Qpre-Qpost)/Qufp.

Results: Seventy-two paired measurement sessions were analyzed. Shunts were detected by TPUD with a positive predictive value of 86%, a negative predictive value of 100%, a sensitivity of 100% and a specificity of 83%. The Bland-Altman analysis comparing Qp/Qs(tpud) and Qp/Qs(ufp) showed an overall mean bias (SD) of 0.1 (0.3), limits of agreement (LOA) of ±0.6 and a percentage error of 34.8%.

Conclusions: The qualitative diagnostic accuracy of TPUD for shunt detection is high. Modification of the algorithm seems required as shunt quantification by TPUD is accurate, but not yet very precise.
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http://dx.doi.org/10.1515/jpm-2015-0310DOI Listing
October 2016