Publications by authors named "Cornelieke S Aarnoudse-Moens"

21 Publications

  • Page 1 of 1

Long-term follow-up of children exposed in-utero to progesterone treatment for prevention of preterm birth: study protocol of the AMPHIA follow-up.

BMJ Open 2021 09 21;11(9):e053066. Epub 2021 Sep 21.

Department of Obstetrics and Gynaecology, Amsterdam Reproduction & Development, Amsterdam UMC Location AMC, Amsterdam, The Netherlands.

Introduction: Preterm birth is one of the main problems in obstetrics, and the most important cause of neonatal mortality, morbidity and neurodevelopmental impairment. Multiple gestation is an important risk factor for preterm birth, with up to 50% delivering before 37 weeks. Progesterone has a role in maintaining pregnancy and is frequently prescribed to prevent (recurrent) preterm birth and improve pregnancy outcomes in high-risk patients. However, little is known about its long-term effects in multiple gestations. The objective of this follow-up study is to assess long-term benefits and harms of prenatal exposure to progesterone treatment in multiple gestations on child development.

Methods And Analysis: This is a follow-up study of a multicentre, double-blind, placebo-controlled randomised trial (AMPHIA trial, ISRCTN40512715). Between 2006 and 2009 women with a multiple gestation were randomised at 16-20 weeks of gestation to weekly injections 250 mg 17α-hydroxyprogesterone caproate or placebo, until 36 weeks of gestation or delivery. The current long-term follow-up will assess all children (n=1355) born to mothers who participated in the AMPHIA trial, at 11-14 years of age, with internationally validated questionnaires, completed by themselves, their parents and their teachers.

Main Outcomes Are Child Cognition And Behaviour: Additional outcomes are death (perinatal and up to age 14), gender identity, educational performance and health-related problems. We will use intention-to-treat analyses comparing experimental and placebo group. To adjust for the correlation between twins, general linear mixed-effects models will be used.

Ethics And Dissemination: Amsterdam UMC MEC provided a waiver for the Medical Research Involving Human Subjects Act (W20_234#20.268). Results will be disseminated through peer-reviewed journals and summaries shared with stakeholders, patients and participants. This protocol is published before analysis of the results.

Trial Registration Number: NL8933.
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http://dx.doi.org/10.1136/bmjopen-2021-053066DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8458362PMC
September 2021

Child outcomes after induction of labour or expectant management in women with preterm prelabour rupture of membranes between 34 and 37 weeks of gestation: study protocol of the PPROMEXIL Follow-up trial. A long-term follow-up study of the randomised controlled trials PPROMEXIL and PPROMEXIL-2.

BMJ Open 2021 06 15;11(6):e046046. Epub 2021 Jun 15.

Department of Obstetrics and Gynaecology, Amsterdam Reproduction & Development, Amsterdam UMC Location AMC, Amsterdam, The Netherlands.

Introduction: Late preterm prelabour rupture of membranes (PROM between 34 and 36 weeks gestational age) is an important clinical dilemma. Previously, two large Dutch randomised controlled trials (RCTs) compared induction of labour (IoL) to expectant management (EM). Both trials showed that early delivery does not reduce the risk of neonatal sepsis as compared with EM, although prematurity-related risks might increase. An extensive, structured long-term follow-up of these children has never been performed.

Methods And Analysis: The PPROMEXIL Follow-up trial (NL6623 (NTR6953)) aims to assess long-term childhood outcomes of the PPROMEXIL (ISRCTN29313500) and PPROMEXIL-2 trial (ISRCTN05689407), two multicentre RCTs using the same protocol, conducted between 2007 and 2010 evaluating IoL versus EM in women with late preterm PROM. The PPROMEXIL Follow-up will analyse children of mothers with a singleton pregnancy (PPROMEXIL trial n=520, PPROMEXIL-2 trial n=191, total IoL n=359; total EM n=352). At 10-12 years of age all surviving children will be invited for a neurodevelopmental assessment using the Wechsler Intelligence Scale for Children-V, Color-Word Interference Test and the Movement Assessment Battery for Children-2. Parents will be asked to fill out questionnaires assessing behaviour, motor function, sensory processing, respiratory problems, general health and need for healthcare services. Teachers will fill out the Teacher Report Form and answer questions regarding school attainment. For all tests means with SDs will be compared, as well as predefined cut-off scores for abnormal outcome. Sensitivity analyses consisting of different imputation techniques will be used to deal with lost to follow-up.

Ethics And Dissemination: The study has been granted approval by the Medical Centre Amsterdam (MEC) of the AmsterdamUMC (MEC2016_217). Results will be disseminated through peer-reviewed journals and summaries shared with stakeholders. This protocol is published before analysis of the results.

Trial Registration Number: NL6623 (NTR6953).
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http://dx.doi.org/10.1136/bmjopen-2020-046046DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8208011PMC
June 2021

Executive function training in very preterm children: a randomized controlled trial.

Eur Child Adolesc Psychiatry 2021 May 26;30(5):785-797. Epub 2020 May 26.

Department of Neonatology, Emma Children's Hospital, Amsterdam UMC, University of Amsterdam, Meibergdreef 9, Amsterdam, The Netherlands.

Objective of the current study was to assess whether game-formatted executive function (EF) training, is effective in improving attention, EF and academic performance in very preterm and/or extremely low birthweight children aged 8-12 years. A multi-center, double-blind, placebo- and waitlist controlled randomized trial (NTR5365) in two academic hospitals in The Netherlands was performed. Eighty-five very preterm children with parent-rated attention problems on the Child Behavior Checklist were randomized to one of three treatment conditions: EF training, placebo training or waitlist condition. EF or placebo training was completed at home (6 weeks, 25 sessions of 30-45 min each). At baseline, 2 weeks after training or being on the waitlist, and five months after first follow-up visit, children underwent assessments of primary outcomes (parent and teacher ratings of attention) and secondary outcomes (parent and teacher ratings of daily-life EF, computerized EF tasks and academic performance). Linear mixed model analyses were performed for all outcome measures. There were no significant differences in improvement over time on parent- and teacher ratings of attention, parent- and teacher ratings of daily-life EF, computerized EF tasks, and academic performance (arithmetic and reading) between the EF training, placebo training and waitlist condition. In conclusion, game-formatted EF training does not improve attention, EF or academic performance in very preterm children with parent-rated attention problems.
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http://dx.doi.org/10.1007/s00787-020-01561-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7250540PMC
May 2021

Subtypes of behavioral functioning in 8-12 year old very preterm children.

Early Hum Dev 2020 03 7;142:104968. Epub 2020 Feb 7.

Emma Children's Hospital, Amsterdam UMC, University of Amsterdam, Neonatology, Meibergdreef 9, Amsterdam, the Netherlands.

Background: Very preterm children often have difficulties in behavioral functioning, but there is large heterogeneity in the severity of these difficulties and in the combination of the difficulties observed. Few studies so far addressed this heterogeneity by examining whether more homogeneous subtypes of behavioral functioning can be identified.

Aims: To identify behavioral subtypes in a group of very preterm children, examine whether such subtypes are related to neonatal medical complications and/or parental education level (to better understand origins) and to examine whether such subtypes are associated with IQ and neurocognitive deficits in attention and executive function (to study underlying mechanisms of dysfunction).

Study Design: Cross-sectional cohort study.

Subjects: 135 very preterm (gestational age < 30 weeks and/or birthweight < 1000 g) children aged 8-12 years.

Measures: Parent and teacher questionnaires covering a broad range of behavioral domains, parental education level, neonatal medical complications, short-form Wechsler Intelligence Scale for Children-III and performance-based attention and executive function measures.

Results: Cluster analysis indicated two behavioral subtypes: a subtype characterized by low behavioral problems (76% of children) and a subtype characterized by high behavioral problems across behavioral domains (24% of children). Lower parental education level, lower IQ and poorer verbal working memory, visuospatial working memory and inhibition were associated with the high problems subtype, but neonatal medical complications were not.

Conclusions: The majority of very preterm children was assigned to the low behavioral problems subtype. However, if problems do occur, they are wide-spread across behavioral domains and accompanied by problems in neurocognitive domains.
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http://dx.doi.org/10.1016/j.earlhumdev.2020.104968DOI Listing
March 2020

Eight-year-old very and extremely preterm children showed more difficulties in performance intelligence than verbal intelligence.

Acta Paediatr 2020 06 4;109(6):1175-1183. Epub 2019 Dec 4.

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

Aim: This study determined possible discrepancies between verbal IQ and performance IQ in 8-year-old very preterm (VPT) and extremely preterm (EPT) children, and examined associations between verbal IQ and performance IQ, and sociodemographic factors, perinatal factors, early cognitive outcomes and also with school achievement scores.

Methods: This prospective cohort study included 120 eight-year-old VPT/EPT children. Cognitive development was assessed at the ages of 2, 5 and 8 years. Eight years' school achievement results in arithmetic, reading and spelling were collected. Multiple regression analyses were performed to determine predictors of verbal IQ and performance IQ at the age of 8 years and to determine associations with school achievement scores.

Results: Mean performance IQ (89.8) was significantly lower than mean verbal IQ (99.4; Cohen's d = 0.59) at the age of 8 years. Gestational age (GA), small for GA status, and cognitive scores at the ages of 2 and 5 years significantly predicted verbal IQ and performance IQ at the age of 8 years. Performance IQ at age 8 years was an important predictor for arithmetic scores (β = 0.42).

Conclusion: Performance IQ was more strongly affected than verbal IQ in 8-year-old VPT/EPT children and was strongly related to mathematical difficulties.
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http://dx.doi.org/10.1111/apa.15095DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7317900PMC
June 2020

Effects of Executive Function Training on Attentional, Behavioral and Emotional Functioning and Self-Perceived Competence in Very Preterm Children: A Randomized Controlled Trial.

Front Psychol 2019 13;10:2100. Epub 2019 Sep 13.

Section of Clinical Neuropsychology, Vrije Universiteit Amsterdam, Amsterdam, Netherlands.

Objective: Very preterm children have poorer attentional, behavioral and emotional functioning than term-born children. Problems on these domains have been linked to poorer executive function (EF). This study examined effects of a game-formatted, comprehensive EF training on attentional, behavioral and emotional functioning and self-perceived competence in very preterm children.

Study Design: Eighty-five children participated in a multi-center, double-blind, placebo and waitlist-controlled randomized trial. Children were recruited from neonatal follow-up units of two academic medical centers in The Netherlands. Eligible for inclusion were 8-12 year old children born very preterm (<30 weeks of gestation) and/or with extremely low birthweight (<1000 g) with parent reported attention problems. Children were randomly assigned to one of three treatment arms: EF training, placebo training or waitlist. The EF and placebo training involved a 6 weeks, 25 (30-45 min) sessions training program. Attentional functioning (Attention Network Test), behavioral and emotional functioning (parent and teacher Strengths and Difficulties questionnaire) and self-perceived competence (Self-Perception Profile for Children) were assessed at baseline, at the end of the training program and 5 months after the training was finished. Data analyses involved linear mixed model analyses.

Results: Children in the EF training arm significantly improved on all training tasks over the course of the EF training program. Despite these improvements on the EF training tasks, there were no significant differences over time on any of the outcome measures between the three treatment arms, indicating that this computerized EF training program had no beneficial effects.

Conclusion: Although there were significant improvements in the EF training tasks, there was no generalization of these improvements to any of the outcome measures. Thus, our findings do not support the use of computerized EF training programs. Future research should investigate effectivity of more ecologically valid, real-world like EF training programs.
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http://dx.doi.org/10.3389/fpsyg.2019.02100DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6753219PMC
September 2019

Developmental outcomes of very preterm children with high parental education level.

Early Hum Dev 2019 06 28;133:11-17. Epub 2019 Apr 28.

Emma Children's Hospital, Amsterdam UMC, University of Amsterdam, Neonatology, Meibergdreef 9, Amsterdam, the Netherlands; Emma Children's Hospital, Amsterdam UMC, University of Amsterdam, Emma Neuroscience Group, Meibergdreef 9, Amsterdam, the Netherlands; Amsterdam UMC, Vrije Universiteit Amsterdam, Clinical Neuropsychology section, Van der Boechorststraat 7, 1081, BT, Amsterdam, Netherlands; Emma Children's Hospital, Amsterdam UMC, University of Amsterdam, Psychosocial Department, Meibergdreef 9, Amsterdam, the Netherlands.

Background: Compared to their term-born peers, children born very preterm are at risk for poorer cognitive, academic and behavioral outcomes, however this finding may have been confounded by lower parental education level in the very preterm children. Studies that compare very preterm and term-born children with comparable (high) parental education level are needed to assess the true effect of very preterm birth on outcomes.

Aims: To compare cognitive, academic and behavioral functioning in very preterm and term-born children of highly educated parents. To examine whether outcomes differ for children of whom one or both parents are highly educated.

Study Design: Cross-sectional study with a term-born comparison group.

Subjects: 113 very preterm children and 38 term-born children aged 8-12 years old, with highly educated parents.

Measures: Cognitive functioning (Intelligence Quotient), academic functioning (arithmetic facts and reading) and parent and teacher rated behavioral functioning (attention, executive function, hyperactivity, and emotional, conduct and peer problems). Parental education was considered high when children had two highly educated parents or one highly- and one middle educated parent.

Results: Very preterm children had significantly poorer cognitive (difference of 10 IQ points) and behavioral functioning than their term-born peers, but did not differ on academic functioning. Children with one highly educated parent performed poorer than children with two highly educated parents on most outcome measures.

Conclusions: Performance of very preterm children should be compared to term-born peers with parents having comparable educational levels for accurate assessment of outcomes. The number of highly educated parents also impacts outcomes.
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http://dx.doi.org/10.1016/j.earlhumdev.2019.04.010DOI Listing
June 2019

Executive function deficits in children born preterm or at low birthweight: a meta-analysis.

Dev Med Child Neurol 2019 09 3;61(9):1015-1024. Epub 2019 Apr 3.

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

Aim: To investigate the magnitude of executive function deficits and their dependency on gestational age, sex, age at assessment, and year of birth for children born preterm and/or at low birthweight.

Method: PubMed, PsychINFO, Web of Science, and ERIC were searched for studies reporting on executive functions in children born preterm/low birthweight and term controls born in 1990 and later, assessed at a mean age of 4 years or higher. Studies were included if five or more studies reported on the same executive function measures.

Results: Thirty-five studies (3360 children born preterm/low birthweight, 2812 controls) were included. Children born preterm/low birthweight performed 0.5 standardized mean difference (SMD) lower on working memory and cognitive flexibility and 0.4 SMD lower on inhibition. SMDs for these executive functions did not significantly differ from each other. Meta-regression showed that heterogeneity in SMDs for working memory and inhibition could not be explained by study differences in gestational age, sex, age at assessment, or year of birth.

Interpretation: Children born preterm/low birthweight since 1990 perform half a SMD below term-born peers on executive function, which does not seem to improve with more recent advances in medical care or with increasing age.

What This Paper Adds: Children born preterm/low birthweight perform below term-born children on core executive functions. Lower gestational age or male sex are not risk factors for poorer executive functions. Executive function difficulties in children born preterm/low birthweight remain stable across childhood. Executive function difficulties are similar for children born recently and children born in earlier eras.
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http://dx.doi.org/10.1111/dmcn.14213DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6850293PMC
September 2019

Duration of mechanical ventilation and neurodevelopment in preterm infants.

Arch Dis Child Fetal Neonatal Ed 2019 Nov 20;104(6):F631-F635. Epub 2019 Mar 20.

Neonatology, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands.

Objective: To investigate the association between invasive mechanical ventilation (IMV) duration and long-term neurodevelopmental outcomes in preterm infants in an era of restricted IMV.

Design: Retrospective cohort study.

Setting: Single neonatal intensive care unit in Amsterdam.

Patients: All ventilated patients with a gestational age between 24 and 30 weeks born between 2010 and 2015.

Main Outcome Measures: Neurodevelopmental impairment (NDI) at 24 months corrected age (CA). Data on patient characteristics, respiratory management, neonatal morbidities, mortality and bronchopulmonary dysplasia were collected. The relationship between IMV duration and NDI was determined by multivariate logistic regression analysis.

Results: During the study period, 368 admitted infants received IMV for a median duration of 2 days. Moderate and severe bronchopulmonary dysplasia was diagnosed in 33% of the infant. Multivariate regression analysis with adjustment for gestational age, small for gestational age and socioeconomic status showed a significant association between every day of IMV and NDI at 24 months CA (adjusted OR [aOR] 1.08, 95% CI 1.004 to 1.16, p=0.04). This association only reached borderline significance when also adjusting for severe neonatal morbidity (aOR 1.08, 95% CI 1.00 to 1.17, p=0.05).

Conclusion: Even in an era of restricted IMV, every additional day of IMV in preterm infants is strongly associated with an increased risk of NDI at 24 months CA. Limiting IMV should be an important focus in the treatment of preterm infants.
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http://dx.doi.org/10.1136/archdischild-2018-315993DOI Listing
November 2019

Visual perceptive skills account for very preterm children's mathematical difficulties in preschool.

Early Hum Dev 2019 02 27;129:11-15. Epub 2018 Dec 27.

Emma Children's Hospital, Amsterdam UMC, University of Amsterdam, Neonatology, Meibergdreef 9, Amsterdam, the Netherlands; Amsterdam UMC, University of Amsterdam & Vrije Universiteit Amsterdam, Emma Neuroscience Group at Emma Children's Hospital, Department of Pediatrics, Amsterdam Reproduction & Development, Amsterdam, the Netherlands; Amsterdam UMC, Vrije Universiteit Amsterdam, Clinical Neuropsychology Section, de Boelelaan 1117, Amsterdam, the Netherlands; Emma Children's Hospital, Amsterdam UMC, University of Amsterdam, Psychosocial Department, Meibergdreef 9, Amsterdam, the Netherlands.

Background: Already in preschool, very preterm (VP) children perform worse than term born-children on preschool mathematical skills tests. Strong associations have been found between preschool mathematical skills, cognition and visual-motor integration.

Aims: To compare VP children and their term-born peers on preschool mathematical achievement at the corrected age of five years, and determine whether cognitive, visual-perceptive, visual-motor, and motor-coordination skills, account for any significant differences observed.

Study Design: Single-center, consecutive cohort study with a term-born comparison group.

Subjects: 54 five-year-old VP children and 28 term-born comparison children.

Outcome Measures: Standardized test for preschool mathematical skills (Dutch pupil monitoring system), cognitive skills (Wechsler Preschool and Primary Scale for Intelligence - third edition), visual-perception, visual-motor integration, and motor-coordination (Beery Visual-Motor Integration test - sixth edition). Group differences were analyzed with ANCOVAs, adjusting for maternal education, preschool grade, and time of assessment. Sobel's mediation analyses tested for possible mediation effects.

Results: Preschool mathematical skills and visual perceptive skills were significantly lower in VP children than in term-born children (Cohen's d = 0.63, p = 0.01; Cohen's d = 0.84, p < 0.01, respectively). Sobel's test indicated a significant mediating effect of visual perceptive skills on the association between VP birth and preschool mathematical skills.

Conclusions: At preschool age, VP children have poorer preschool mathematical skills compared to term-born peers; deficits that were fully accounted for by poor visual perceptive skills. Our findings indicate the relevance of screening visual perceptive skills at preschool age, enabling timely identification of children at risk for mathematical difficulties.
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http://dx.doi.org/10.1016/j.earlhumdev.2018.12.018DOI Listing
February 2019

Maternal psychological distress after severe pregnancy hypertension was associated with increased child behavioural problems at the age of 12.

Acta Paediatr 2019 06 9;108(6):1061-1066. Epub 2019 Jan 9.

Department of Neonatology, Emma Children's Hospital, Academic Medical Center, Amsterdam, The Netherlands.

Aim: We examined the association between early maternal psychological distress after severe hypertensive disorders of pregnancy (HDP) and behavioural issues in their 12-year-old offspring.

Methods: This secondary analyses of a prospective mother-child birth cohort focused on 95 women with severe HDP and their singleton offspring. The mothers were recruited during pregnancy from 2000 to 2003 in Amsterdam, the Netherlands. Maternal distress at child term age and three months post-term was measured using the Symptom Checklist-90. The Child Behaviour Checklist for six years to 18 years was used to quantify social and attention problems in their offspring at 12 years of age. Perinatal and neonatal risk factors were also analysed.

Results: The children were born at a mean age of just under 32 weeks and 90% weighed below the 10th percentile. High psychological distress (score ≥133) affected 45% of the mothers at term age and 44% three months post-term. Child social problems were significantly associated with maternal distress at three months and were highest in cases of high maternal distress in combination with major neonatal morbidity. Child attention problems were associated with maternal anxiety at three months post-term.

Conclusion: Early maternal psychological distress after severe maternal HDP was associated with childhood behavioural issues at the age of 12.
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http://dx.doi.org/10.1111/apa.14676DOI Listing
June 2019

Executive Function Computerized Training in Very Preterm-Born Children: A Pilot Study.

Games Health J 2018 Jun 13;7(3):175-181. Epub 2018 Mar 13.

1 Department of Pediatrics, Emma Children's Hospital, Academic Medical Centre , Amsterdam, The Netherlands .

Objective: Attention problems are one of the most pronounced and documented consequences of very preterm birth (gestational age ≤32 weeks). However, up to now, there is no research published on suitable interventions at school age aimed to overcome these problems. Research in this population did show that executive functions (EFs) are strongly associated with inattention. BrainGame Brian is a newly developed computerized training, in which, in 25 training sessions, the core EFs, including working memory, impulse control, and cognitive flexibility, are trained. This pilot study aimed to examine the feasibility of studying BrainGame Brian in very preterm-born children with attention problems.

Design: Pilot feasibility intervention study with one baseline and one follow-up assessment.

Materials And Methods: Feasibility was measured by the participation rate, dropout rate, and user experiences with regard to effort, training characteristics, and recommendation to others. From a larger cohort study, 15 very preterm-born children at age 10 years with parent-reported attention problems on the Child Behavior Checklist/6-18 years were invited to participate in this pilot study. BrainGame Brian was performed for a period of 6 weeks. Training outcome measures included visual working memory, impulse control, cognitive flexibility, speed variability, and parent-rated attention, for which pre- and post-training differences were examined at the group level by the Wilcoxon signed-rank test as well as for each individual child separately by the reliable change index.

Results: Twelve of 15 children and their parents agreed to participate and 11 children successfully completed BrainGame Brian in the 6-week period. Parents were positive about training characteristics and lack of interference with schooling, but scored the effort as high. We found clinically significant changes in visual working memory and speed variability in post-training assessments.

Conclusion: BrainGame Brian is a feasible intervention for very preterm-born children with attention problems.
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http://dx.doi.org/10.1089/g4h.2017.0038DOI Listing
June 2018

Fetal Growth Restriction with Brain Sparing: Neurocognitive and Behavioral Outcomes at 12 Years of Age.

J Pediatr 2017 09 8;188:103-109.e2. Epub 2017 Jul 8.

Department of Pediatrics, Academic Medical Center, Amsterdam, The Netherlands.

Objective: To study neurocognitive functions and behavior in children with a history of fetal growth restriction (FGR) with brain sparing. We hypothesized that children with FGR would have poorer outcomes on these domains.

Study Design: Subjects were 12-year-old children with a history of FGR born to mothers with severe early-onset hypertensive pregnancy disorders (n = 96) compared with a normal functioning full term comparison group with a birth weight ≥2500 g (n = 32). Outcome measures were neurocognitive outcomes (ie, intelligence quotient, executive function, attention) and behavior.

Results: For the FGR group, the mean ratio of the pulsatility index for the umbilical artery/middle cerebral artery (UC-ratio = severity of brain sparing) was 1.42 ± 0.69. The mean gestational age was 31-6/7  ± 2-2/7 weeks. The mean birth weight was 1341  ± 454 g, and the mean birth weight ratio 0.68 ± 0.12. Neurocognitive outcomes were comparable between groups. Parents of children with FGR reported more social problems (mean T-score 56.6 ± 7.7; comparison 52.3 ± 4.3, P < .001, effect size = 1, 95% CI 0.52-1.46) and attention problems (mean T-score 57.3 ± 6.9; comparison 53.6 ± 4.2, P = .004, effect size = 0.88, 95% CI 0.42-1.33). UC-ratio was not associated with any of the outcomes, but low parental education and lower birth weight ratio were.

Conclusions: In this prospective follow-up study of 12-year-old children with a history of FGR and confirmed brain sparing, neurocognitive functions were comparable with the comparison group, but parent-reported social and attention problem scores were increased.
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http://dx.doi.org/10.1016/j.jpeds.2017.06.003DOI Listing
September 2017

Restricted Ventilation Associated with Reduced Neurodevelopmental Impairment in Preterm Infants.

Neonatology 2017 10;112(2):172-179. Epub 2017 Jun 10.

Department of Neonatology, Emma Children's Hospital, Academic Medical Center, Amsterdam, The Netherlands.

Background And Objective: Restrictive use of invasive mechanical ventilation (IMV) in preterm infants reduces the risk of bronchopulmonary dysplasia (BPD). Our objective was to determine its effect on neurodevelopmental impairment (NDI) at 24 months' corrected age (CA).

Methods: This retrospective single-center cohort study included all patients with a gestational age <30 weeks born in 2004/2005 (epoch 1) and 2010/2011 (epoch 2). In epoch 2, we introduced a policy of restriction on IMV and liberalized the use of respiratory stimulants in the delivery room and neonatal intensive care. Data on patient characteristics, respiratory management, short-term outcomes, mortality, BPD, and NDI at 24 months' CA were collected.

Results: Four hundred and four preterm infants were included. Compared to those in epoch 1, infants in epoch 2 were less likely to be intubated and the duration of IMV was shorter. Other noninvasive adjuvant therapies such as caffeine, doxapram, and nasal ventilation were more often used during epoch 2. There was a trend to less BPD in epoch 2 compared to epoch 1 (17 vs. 23%, adjusted OR = 0.75, 95% CI: 0.48, 1.16). Mortality did not change over time. The combined outcome death or NDI at 24 months' CA was significantly lower in epoch 2 compared to epoch 1 (24.7 vs. 33.9%, adjusted OR = 0.71, 95% CI: 0.53, 0.97).

Conclusions: Restricted use of IMV is feasible in preterm infants and might be associated with a reduced risk of the combined outcome death or NDI at 24 months' CA. Larger studies are needed to confirm these findings.
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http://dx.doi.org/10.1159/000471841DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5637296PMC
May 2018

Minor neurological dysfunction in five year old very preterm children is associated with lower processing speed.

Early Hum Dev 2016 12 8;103:55-60. Epub 2016 Aug 8.

Department of Neonatology, Emma Children's Hospital, Academic Medical Centre, Postbox 22660, 1100 DD, Amsterdam, The Netherlands.

Background: Minor neurological dysfunction (MND) is present in one quarter to one third of children born very preterm (VP). The more severe form, complex (c)-MND has been associated with learning disabilities, behavioural and motor problems.

Objective: To study the association between c-MND and neurocognitive and motor disabilities at age five in VP children without CP.

Methods: Ninety-four children born with gestational age<30weeks and/or a birth weight<1000g were assessed at five years corrected age. MND was classified according to Touwen. The Wechsler Preschool and Primary School Scale of Intelligence (WPPSI-III-NL) was used to measure intelligence. Simple reaction time, focused attention and visuomotor coordination were measured using the Amsterdam Neuropsychological Tasks, and working memory using a Digit Span Task. For motor skills the Movement Assessment Battery for children (M-ABC2) was used.

Results: Eighty-one percent was classified as 'normal' (no or simple (s-)-MND) and 19% as 'abnormal'(c-MND or mild CP). The abnormal group had a significantly lower processing speed quotient (PSQ), M-ABC percentile score and slower simple Reaction Time than the normal group. Verbal IQ, Performance IQ, working memory, focused attention and visuomotor coordination did not differ between groups. Exclusion of the mild CP cases (n=4) led to similar results.

Conclusions: Five year old VP children with c-MND have lower PSQ, slower reaction time, and poorer motor skills, than those without c-MND. Neurological examination should include identification of MND to help identify children at risk for neurocognitive disabilities.
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http://dx.doi.org/10.1016/j.earlhumdev.2016.07.002DOI Listing
December 2016

Consequences of Correcting Intelligence Quotient for Prematurity at Age 5 Years.

J Pediatr 2016 06 12;173:90-5. Epub 2016 Mar 12.

Department of Neonatology, Academic Medical Center, Amsterdam, The Netherlands.

Objectives: To determine the effects of correcting for prematurity on full scale IQ (FSIQ), verbal IQ (VIQ), performance IQ (PIQ), and processing speed quotient (PSQ) scores, and to investigate whether differences between corrected and uncorrected FSIQ are associated with gestational age (GA), FSIQ, and age at assessment.

Study Design: Single-center consecutive cohort study. Data were analyzed from 275 very preterm children (GA <30 weeks), born between January 2006 and December 2009 and assessed at 5 years corrected age as part of the neonatal long-term follow-up program, at the Emma Children's Hospital in Amsterdam, The Netherlands. Outcome measures were FSIQ, VIQ, PIQ, and PSQ, calculated for uncorrected and corrected age. Paired sample t tests, repeated measures ANOVA, and ANCOVA were performed to explore differences between corrected and uncorrected IQ.

Results: Differences between corrected and uncorrected FSIQ, VIQ, PIQ, and PSQ ranged from 0-15 IQ points. All corrected IQ scores were significantly higher than uncorrected IQ scores (all P values <.001). Differences were larger at lower GAs, for higher IQ scores, and if time of assessment lay near the starting point of a 3-month age band of the Wechsler Preschool and Primary Scale of Intelligence-Third Edition-Dutch Version.

Conclusions: Given the great variation observed in differences between corrected and uncorrected IQ scores, an international standard as to what age correction is appropriate should be pursued.
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http://dx.doi.org/10.1016/j.jpeds.2016.02.043DOI Listing
June 2016

Predicting extremely preterm children's school performance by transient abnormal neurology?

Dev Med Child Neurol 2015 Sep 12;57(9):794-5. Epub 2015 Jun 12.

Department of Pediatrics, Amsterdam Medical Centre, Amsterdam, the Netherlands.

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http://dx.doi.org/10.1111/dmcn.12833DOI Listing
September 2015

Predicting developmental outcomes in premature infants by term equivalent MRI: systematic review and meta-analysis.

Syst Rev 2015 May 17;4:71. Epub 2015 May 17.

Department of Neonatology (H3-147), Emma Children's Hospital, Academical Medical Center, PO Box 22660, 1100 DD, Amsterdam, The Netherlands.

Background: This study aims to determine the prognostic accuracy of term MRI in very preterm born (≤32 weeks) or low-birth-weight (≤1500 g) infants for long-term (>18 months) developmental outcomes.

Methods: We performed a systematic review searching Central, Medline, Embase, and PsycInfo. Two independent reviewers performed study selection, data extraction, and quality assessment. We documented sensitivity and specificity for three different MRI findings (white matter abnormalities (WMA), brain abnormality (BA), and diffuse excessive high signal intensity (DEHSI)), related to developmental outcomes including cerebral palsy (CP), visual and/or hearing problems, motor, neurocognitive, and behavioral function. Using bivariate meta-analysis, we estimated pooled sensitivity and specificity and plotted summary receiver operating characteristic (sROC) curves for different cut-offs of MRI.

Results: We included 20 papers published between 2000 and 2013. Quality of included studies varied. Pooled sensitivity and specificity values (95 % confidence interval (CI)) for prediction of CP combining the three different MRI findings (using normal/mild vs. moderate/severe cut-off) were 77 % (53 to 91 %) and 79 % (51 to 93 %), respectively. For prediction of motor function, the values were 72 % (52 to 86 %) and 62 % (29 to 87 %), respectively. Prognostic accuracy for visual and/or hearing problems, neurocognitive, and/or behavioral function was poor. sROC curves of the individual MRI findings showed that presence of WMA provided the best prognostic accuracy whereas DEHSI did not show any potential prognostic accuracy.

Conclusions: This study shows that presence of moderate/severe WMA on MRI around term equivalent age can predict CP and motor function in very preterm or low-birth-weight infants with moderate sensitivity and specificity. Its ability to predict other long-term outcomes such as neurocognitive and behavioral impairments is limited. Also, other white matter related tests as BA and DEHSI demonstrated limited prognostic value.

Systematic Review Registration: PROSPERO CRD42013006362.
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http://dx.doi.org/10.1186/s13643-015-0058-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4438620PMC
May 2015

The profile of executive function in very preterm children at 4 to 12 years.

Dev Med Child Neurol 2012 Mar 29;54(3):247-53. Epub 2011 Nov 29.

Division of Neonatology, Department of Pediatrics, Erasmus University Medical Centre, Sophia Children's Hospital, Rotterdam, Amsterdam, the Netherlands.

Aim: To examine executive functioning in very preterm (gestational age ≤30 wks) children at 4 to 12 years of age.

Method: Two-hundred very preterm (106 males, 94 females; mean gestational age 28.1wks, SD 1.4; mean age 8y 2mo, SD 2y 6mo) and 230 term children (106 males, 124 females; mean gestational age 39.9wks, SD 1.2; mean age 8y 4mo, SD 2y 3mo) without severe disabilities, born between 1996 and 2004, were assessed on an executive function battery comprising response inhibition, interference control, switching, verbal fluency, verbal and spatial working memory, and planning. Multiple regression analyses examined group differences while adjusting for effects of parental education, age, sex, and speed indices.

Results: Relative to children born at term, very preterm children had significant (p(s) <0.02; where p(s) represents p-values) deficits in verbal fluency (0.5 standardized mean differences [SMD]), response inhibition (0.4 SMD), planning (0.4 SMD), and verbal and spatial working memory (0.3 SMD), independent of slow and highly fluctuating processing speed. A significant group by age interaction indicated that group differences for response inhibition decreased between 4 and 12 years.

Interpretation: Very preterm birth is associated with a profile of affected and non-affected executive functions independent of impaired speed. Deficits are of small to moderate magnitude and persist over time, except for response inhibition for which very preterm children catch up with peers.
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http://dx.doi.org/10.1111/j.1469-8749.2011.04150.xDOI Listing
March 2012

Motor development in very preterm and very low-birth-weight children from birth to adolescence: a meta-analysis.

JAMA 2009 Nov;302(20):2235-42

Department of Clinical Neuropsychology, VU University Amsterdam, van der Boechorststraat 1, 1081 BT Amsterdam, the Netherlands.

Context: Infants who are very preterm (born < or = 32 weeks of gestation) and very low birth weight (VLBW) (weighing < or = 1500 g) are at risk for poor developmental outcomes. There is increasing evidence that very preterm birth and VLBW have a considerable effect on motor development, although findings are inconsistent.

Objective: To investigate the relationship between very preterm birth and VLBW and motor development.

Data Sources: The computerized databases EMBASE, PubMed, and Web of Knowledge were used to search for English-language peer-reviewed articles published between January 1992 and August 2009.

Study Selection: Studies were included if they reported motor scores of very preterm and VLBW children without congenital anomalies using 1 of 3 established and widely used motor tests: the Bayley Scales of Infant Development II (BSID-II), the Movement Assessment Battery for Children (MABC), and the Bruininks-Oseretsky Test of Motor Proficiency (BOTMP). Forty-one articles were identified, encompassing 9653 children.

Results: In comparison with term-born peers, very preterm and VLBW children obtained significantly lower scores on all 3 motor tests: BSID-II: d = -0.88 (95% confidence interval [CI], -0.96 to -0.80; P < .001), MABC: d = -0.65 (95% CI, -0.70 to -0.60; P < .001), and BOTMP: d = -0.57 (95% CI, -0.68 to -0.46; P < .001). Whereas motor outcomes on the BSID-II show a catch-up effect in the first years of development (r = 0.50, P = .01), the results on the MABC demonstrate a nonsignificantly greater deficit with increasing age during elementary school and early adolescence (r = -0.59, P = .07).

Conclusion: Being born preterm or VLBW is associated with significant motor impairment persisting throughout childhood.
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http://dx.doi.org/10.1001/jama.2009.1708DOI Listing
November 2009

Executive function in very preterm children at early school age.

J Abnorm Child Psychol 2009 Oct;37(7):981-93

Department of Pediatrics, Division of Neonatology, Erasmus University Medical Centre Sophia Children's Hospital Rotterdam, Rotterdam, The Netherlands.

We examined whether very preterm (< or =30 weeks gestation) children at early school age have impairments in executive function (EF) independent of IQ and processing speed, and whether demographic and neonatal risk factors were associated with EF impairments. A consecutive sample of 50 children (27 boys and 23 girls) born very preterm (mean age = 5.9 years, SD = 0.4, mean gestational age = 28.0 weeks, SD = 1.4) was compared to a sample of 50 age-matched full-term controls (23 girls and 27 boys, mean age = 6.0 years, SD = 0.6) with respect to performance on a comprehensive EF battery, assessing the domains of inhibition, working memory, switching, verbal fluency, and concept generation. The very preterm group demonstrated poor performance compared to the controls on all EF domains, even after partialing out the effects of IQ. Processing speed was marginally related to EF. Analyses with demographic and neonatal risk factors showed maternal education and gestational age to be related to EF. This study adds to the emerging body of literature showing that very preterm birth is associated with EF impairments.
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http://dx.doi.org/10.1007/s10802-009-9327-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2734253PMC
October 2009
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