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ObjectiveTo report the parent-reported behavioural outcomes of infants included in the Systemic Hydrocortisone To Prevent Bronchopulmonary Dysplasia in preterm infants study at 2 years’ corrected age (CA).DesignRandomised placebo-controlled trial.SettingDutch and Belgian neonatal intensive care units.PatientsInfants born InterventionInfants were randomly assigned to a 22-day course of systemic hydrocortisone (cumulative dose 72.5 mg/kg; n=182) or placebo (n=190).Main outcome measuresParent-reported behavioural outcomes at 2 years’ CA assessed with the Child Behavior Checklist (CBCL 1½−5).ResultsParents completed the CBCL of 183 (70% (183/262)) infants (hydrocortisone group, n=96; placebo group, n=87). Multiple imputation was used to account for missing data. Infants with critically elevated T-scores (>55) were found in 22.9%, 19.1% and 29.4% of infants for total, internalising and externalising problems, respectively; these scores were not significantly different between groups (mean difference −1.52 (95% CI −4.00 to 0.96), −2.40 (95% CI −4.99 to 0.20) and −0.81 (95% CI −3.40 to 1.77), respectively). In the subscales, we found a significantly lower T-score for anxiety problems in the hydrocortisone group (mean difference −1.26, 95% CI −2.41 to –0.12).ConclusionThis study found high rates of behaviour problems at 2 years’ CA following very preterm birth, but these problems were not associated with hydrocortisone treatment initiated between 7 and 14 days after birth in ventilated preterm infants.Trial registration numberNTR2768; EudraCT 2010-023777-19.

Objective: Perinatal mortality after previable prelabor rupture of membranes (previable PROM) might be underestimated as most studies exclude patients with poor prognosis, or solely include patients in tertiary-care centers. We aimed to report perinatal, neonatal and long-term outcomes in a consecutive series of women with pregnancies complicated by previable PROM. Study design: We conducted a prospective cohort study including women with singleton pregnancies and previable PROM ≤ 23+6 weeks gestational age (GA) from one tertiary hospital and eight affiliated secondary hospitals in the region of Amsterdam, the Netherlands (June 2012 until January 2016, PPROMEXIL-III cohort). Exclusion criteria were signs of active labor before onset of PROM or fetal structural anomalies visible at ultrasound. We assessed perinatal mortality. Furthermore, outcomes were maternal, perinatal, neonatal and long-term child characteristics. Results: We included 98 pregnancies with previable PROM. Twelve women (12.2%) opted for termination of pregnancy, resulting in 86 pregnancies included in further analyses. Median GA at PROM was 20+2 weeks (interquartile range (IQR) 17+6-22+0). Median GA at delivery was 22+6 weeks (IQR 20+1-26+4). Delivery within 1 week occurred in 38.4% of women and 60.4% delivered before 24 weeks GA (viability). Perinatal mortality occurred in 73.3% of pregnancies. 23/33 (69.7%) live-born neonates survived to discharge, representing 26.7% of total. None of the children died after discharge. Developmental data at two and/or five years of age was available for 13/23 children (i.e. all children born before 32 weeks of gestation), with 69.2% of children reporting a normal neurodevelopment. However, more than half of children reported respiratory problems. Conclusion: In women with previable PROM perinatal mortality was 73.3%, with a normal neurodevelopment in 69.2% of surviving children with follow-up data. Due to broad inclusion criteria, this cohort represents a population more generalizable to daily practice as compared to previous studies.

Objective To evaluate the long‐term outcomes of children born to women with a short cervix and otherwise low risk for preterm birth, after antenatal exposure to vaginal progesterone vs placebo. Methods This was a follow‐up study of the Triple P trial, which randomized 80 low‐risk women with a short cervix (≤ 30 mm) at 18–22 weeks' gestation to progesterone (n = 41) or placebo (n = 39). At 2 years of corrected age, children were invited for a neurodevelopmental assessment, using the Bayley Scales of Infant and Toddler Development, third edition (BSID‐III), and a neurological and physical examination by an assessor blinded to the allocated treatment. Parents filled out the Ages and Stages Questionnaire, the Child Behavior Checklist (CBCL) and a general‐health questionnaire. The main outcome of interest was mean BSID‐III cognitive and motor scores. Additionally, a composite score of mortality and abnormal developmental outcome, including BSID‐III ≤–1 SD, CBCL score in the clinical range and/or parental reported physical problems (at least two operations or at least two hospital admissions in the previous 2 years), was evaluated. Our sample size, dictated by the original sample of the Triple P trial, provided 80% power to detect a mean difference (MD) of 15 points (1 SD) between groups for the BSID‐III tests. Results Of the 80 children born to the randomized women, one in the progesterone group and two in the placebo group died in the neonatal period. Follow‐up data were obtained for 59/77 (77%) children and BSID‐III outcomes in 57 children (n = 28 in the progesterone group and n = 29 in the placebo group) born at a median gestational age of 38 + 6 weeks (interquartile range (IQR), 37 + 3 to 40 + 1 weeks) with a median birth weight of 3240 g (IQR, 2785–3620 g). In the progesterone vs placebo groups, mean BSID‐III cognitive development scores were 101.6 vs 105.0 (MD, –3.4 (95% CI, –9.3 to 2.6); P = 0.29) while mean motor scores were 102.4 vs 107.3 (MD, –4.9 (95% CI, –11.2 to 1.4); P = 0.13). No differences were seen between the two groups in physical (including genital and neurological examination), behavioral and health‐related outcomes. Conclusion In this sample of children born to low‐risk women with a short cervix at screening, no relevant differences in neurodevelopmental, behavioral, health‐related and physical outcomes were found between offspring exposed to vaginal progesterone and those exposed to placebo. © 2020 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Introduction: There is little evidence to guide the timing of delivery of women with early-onset severe preeclampsia. We hypothesize that immediate delivery is not inferior for neonatal outcome but reduces maternal complications compared with temporizing management. Material and methods: This Dutch multicenter open-label randomized clinical trial investigated non-inferiority for neonatal outcome of temporizing management as compared with immediate delivery (TOTEM NTR 2986) in women between 27+5 and 33+5 weeks of gestation admitted for early-onset severe preeclampsia with or without HELLP syndrome. In participants allocated to receive immediate delivery, either induction of labor or cesarean section was initiated at least 48 hours after admission. Primary outcomes were adverse perinatal outcome, defined as a composite of severe respiratory distress syndrome, bronchopulmonary dysplasia, culture proven sepsis, intraventricular hemorrhage grade 3 or worse, periventricular leukomalacia grade 2 or worse, necrotizing enterocolitis stage 2 or worse, and perinatal death. Major maternal complications were secondary outcomes. It was estimated 1130 women needed to be enrolled. Analysis was by intention-to-treat. Results: The trial was halted after 35 months because of slow recruitment. Between February 2011 and December 2013, a total of 56 women were randomized to immediate delivery (n = 26) or temporizing management (n = 30). Median gestational age at randomization was 30 weeks. Median prolongation of pregnancy was 2 days (interquartile range 1-3 days) in the temporizing management group. Mean birthweight was 1435 g after immediate delivery vs 1294 g after temporizing management (P =.14). The adverse perinatal outcome rate was 55% in the immediate delivery group vs 52% in the temporizing management group (relative risk 1.06; 95% confidence interval 0.67-1.70). In both groups there was one neonatal death and no maternal deaths. In the temporizing treatment group, one woman experienced pulmonary edema and one placental abruption. Analyses of only the singleton pregnancies did not result in other outcomes. Conclusions: Early termination of the trial precluded any conclusions for the main outcomes. We observed that temporizing management resulted in a modest prolongation of pregnancy without changes in perinatal and maternal outcome. Conducting a randomized study for this important research question did not prove feasible.

IntroductionLate preterm prelabour rupture of membranes (PROM between 34+0 and 36+6 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 analysisThe 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 disseminationThe 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 numberNL6623 (NTR6953).

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. Electronic supplementary material The online version of this article (10.1007/s00787-020-01561-0) contains supplementary material, which is available to authorized users.

A previous randomized controlled trial has suggested the effectiveness of a Dutch postdischarge responsive parenting program for very preterm (VPT) infants, indicating that nationwide implementation was justified. This paper describes the development and nationwide implementation of the intervention, known as the TOP program, which consisted of three phases. In the preparation phase (2006-2010), a theory of change and the structure of the TOP program were developed, and funding for phase two, based on a positive Business Case, was obtained. In the pilot implementation phase (2010-2014), intervention strategies were developed for a real-world setting, capacity and adoption were increased, systematic evaluations were incorporated, and sustained funding was obtained. In the full-implementation phase (2014-2019), all Dutch Healthcare Insurers reimbursed the TOP program, enabling VPT infants to participate in the program without charge. By 2018, the number of interventionists that provided the TOP program had increased from 37 to 91, and all level III hospitals and 65% of regional hospitals in the Netherlands referred VPT infants. Currently, the program reaches 70% of the Dutch target population and parental satisfaction with the TOP program is high. After a 12-year implementation period, the TOP program forms part of routine care in the Netherlands.Un previo ensayo controlado al azar ha sugerido la eficacia de un programa holandés sobre la crianza sensible para infantes muy prematuros (VPT) posterior al momento en que se les dio de alta, indicando que la implementación a lo largo de toda la nación era justificada. Este artículo describe el desarrollo y la implementación a nivel de toda la nación de la intervención, conocida como el programa ToP, el cual consistía de tres fases. En la fase de preparación (2006-2010), se desarrollaron una teoría de cambio y la estructura del programa ToP, y se obtuvieron los fondos para la fase dos, con base en un Caso de Negocios (BC) positivo. En la fase piloto de implementación (2010-2014), se desarrollaron estrategias de intervención para un escenario del mundo real, se aumentaron la capacidad y la adopción, se incorporaron evaluaciones sistemáticas y se obtuvieron fondos para mantener el programa. En la fase de implementación completa (2014-2019), todas las Aseguradoras Holandesas del Sector Salud reembolsaron el costo del programa ToP, permitiéndoles a los infantes VPT participar en el programa sin costo alguno. Para 2018, el número de practicantes de la intervención que prestaban el servicio del programa ToP había aumentado de 37 a 91, y todos los hospitales del nivel III y 65% de los hospitales regionales en Holanda refirieron los infantes VPT al programa. Actualmente, el programa llega a 70% de la población holandesa para la cual está destinado y la satisfacción de los padres con el programa ToP es alta. Después de un período de implementación de 12 años, el programa ToP forma parte del cuidado de salud rutinario en Holanda.Un essai contrôlé randomisé précédent a suggéré l'efficacité d'un programme hollandais de sensibilité de parentage après la sortie de l'hôpital pour les nourrissons grands prématurés (GP ici en français), indiquant qu'une mise en œuvre au niveau national était justifiée. Cet article décrit le développement et la mise en œuvre au niveau national de l'intervention, connue en tant que ToP program, qui a consisté en trois phases. Dans la phase de préparation (2006-2010), une théorie du changement et la structure du programme ToP a été développée, et le financement pour la phase deux, basée sur une Etude de Cas positive, a été sécurisé. Dans la phase pilote d'implémentation (2010-2014) des stratégies d'intervention ont été développées pour un contexte réel, la capacité et l'adoption ont été augmentées, les évaluations systématiques ont été incorporées, et un financement durable a été sécurisé. Dans la pleine phase de mise en œuvre (2014-1029), tous les Assurances Santé Hollandaises ont remboursé le programme ToP, permettant aux nourrissons GP de participer au programme sans coût. En 2018 le nombre de prestataires qui offraient le programme ToP a augmenté de 37 à 91, et tous les hôpitaux de niveau III ainsi que 65% des hôpitaux régionaux aux Pays Bas ont envoyé les nourrissons GP au programme. En ce moment le programme atteint 70% de la population cible hollandaise et la satisfaction parentale avec le programme ToP est élevée. Après une période de mise en œuvre de 12 ans le programme ToP fait partie des soins de routine aux Pays Bas.Entwicklung und landesweite Umsetzung eines Interventionsprogramms für Eltern von sehr frühgeborenen Kindern nach der Entlassung: das ToP-Programm Eine frühere randomisierte kontrollierte Studie hat die Wirksamkeit eines niederländischen Interventionsprogramms für Eltern von sehr frühgeborenen (very preterm; VPT) Kindern nach der Entlassung nahegelegt. Dies wies darauf hin, dass eine landesweite Umsetzung gerechtfertigt wäre. Die vorliegende Studie beschreibt die aus drei Phasen bestehende Entwicklung und landesweite Umsetzung dieser, ToP-Programm bekannten, Intervention. In der Vorbereitungsphase (2006-2010) wurden eine Veränderungstheorie und die Struktur des ToP-Programms entwickelt und eine Finanzierung der zweiten Phase auf der Grundlage eines positiven Geschäftsszenarios (Business Case; BC) ermöglicht. In der Pilotimplementierungsphase (2010-2014) wurden Interventionsstrategien für ein reales Umfeld entwickelt, Kapazität und Akzeptanz erhöht, systematische Evaluationen vorgenommen und eine nachhaltige Finanzierung realisiert. In der vollständigen Umsetzungsphase (2014-2019) haben alle niederländischen Krankenversicherungen das ToP-Programm erstattet, sodass VPT-Säuglinge kostenlos am Programm teilnehmen konnten. Bis 2018 ist die Zahl der Anbietenden des ToP-Programms von 37 auf 91 gestiegen und alle Krankenhäuser der Stufe III und 65% der regionalen Krankenhäuser in den Niederlanden überwiesen VPT-Säuglinge. Derzeit erreicht das Programm 70% der niederländischen Zielgruppe und die Zufriedenheit der Eltern mit dem ToP-Programm ist hoch. Nach einer 12-jährigen Umsetzungsphase ist das ToP-Programm Teil der Routineversorgung in den Niederlanden.在胎32週未満の早産児向け退院後応答的育児介入プログラム“ToPプログラム”の沿革と全国的な実施 先行無作為化比較研究は、オランダの在胎32週未満の早産(VPT)乳児のための退院後応答的育児プログラムの有効性を示唆しており、全国的な実施の合理性が示された。本論文では、3つのフェーズからなるToPプログラムと呼ばれる介入の開発と全国的な実施について述べる。準備フェーズ(2006-2010)では、変化の理論とToPプログラムの構造が開発され、正のビジネスケース(BC)に基づいてフェーズ2の資金が調達された。パイロット導入フェーズ(2010-2014)では、実際の環境に適した介入戦略が策定され、機能と採用件数が増加し、体系的な評価が組み込まれ、持続的な資金源が得られた。完全実施フェーズ(2014-2019)では、オランダの全ての医療保険会社がToPプログラムに払い戻しを行い、VPTの乳児が無償でプログラムに参加できるようなった。2018年までに、ToPプログラムを提供する介入者の数は37人から91人に増加し、オランダの全てのレベルIIIの病院と地域病院の65%がVPT乳児を紹介した。現在、プログラムはオランダの対象人口の70%に普及し、ToPプログラムに対する親の満足度は高い。実施開始後12年が経過し、ToPプログラムはオランダでは日常的なケアの一部となっている。 .此前的一项随机对照试验表明, 荷兰对极早产 (VPT) 婴儿的院后响应式育儿计划是有效的, 这表明在全国范围内实施是合理的。本文描述了干预措施的发展和在全国范围内的实施情况, 称为ToP计划, 分为三个阶段。在准备阶段 (2006-2010年) , 开发了变革理论和ToP计划的结构, 并基于积极的商业案例 (BC) 获得了第二阶段的资金支持。在试点实施阶段 (2010-2014年) , 针对现实环境制定了干预战略, 提高了业务能力和采用率, 纳入了系统评价, 并获得了持续的资金支持。在全面实施阶段 (2014-2019年) , 所有荷兰医疗保险公司都对ToP计划进行报销, 从而使VPT婴儿能够免费参与该计划。到2018年, 提供ToP计划的干预机构从37家增加到91家, 荷兰所有三级医院和65%的地区医院都将VPT婴儿纳入治疗范围。目前, 该计划覆盖了荷兰70%的目标人群, 并且父母对ToP项目的满意度很高。经过12年的实施期后, ToP计划已经成为荷兰常规护理的一部分。.تطوير وتنفيذ برنامج رعاية والدية ا لمرحلة ما بعد خروج الأطفال المبتسرين من المستشفى: برنامج ToP أشارت دراسة سابقة إلى فاعلية برنامج هولندي للرعاية الوالدية المستجيبة بعد خروج الرضع المبتسرين جداً (VPT) من المستشفى وأكدت على إمكانية تطبيقه على مستوى الدولة بشكل ناجح. تصف هذه الورقة تطوير وتنفيذ التدخل على مستوى الدولة، والمعروف باسم برنامج الـToP ، الذي يتكون من ثلاث مراحل. في مرحلة الإعداد (2006-2010)، تم تطوير نظرية التغيير وهيكل برنامج الـToP ، وتم الحصول على تمويل للمرحلة الثانية، بناء على وضعه التجاري الإيجابي (BC) وفي مرحلة التنفيذ التجريبي (2010-2014)، وضعت استراتيجيات للتدخل على أساس واقعي، وتم زيادة القدرات الاستيعابية والتبني ، واستخدام تقييمات منهجية، وبعد ذلك تم الحصول على تمويل مستدام. في مرحلة التنفيذ الكامل (2014-2019)، قامت جميع شركات التأمين الصحي الهولندية بسداد تكاليف برنامجToP ، مما مكن الرضع من المشاركة في البرنامج دون مقابل. وبحلول عام 2018، ارتفع عدد المتدخلين الذين قدموا برنامج الـToP من 37 إلى 91، كما أن جميع مستشفيات المستوى الثالث و65% من المستشفيات الإقليمية في هولندا أصبحت تقوم بتحويل الرضع من برنامج ToP ، وفي الوقت الجالي يصل البرنامج إلى 70٪ من السكان المستهدفين الهولنديين ورضا الوالدين عن برنامجToP مرتفع. بعد فترة تنفيذ مدتها 12 عاماً، يشكل برنامج الـToP جزءاً من الرعاية الروتينية في هولندا.

Introduction Severe early‐onset fetal growth restriction is an obstetric condition with significant risks of perinatal mortality, major and minor neonatal morbidity, and long‐term health sequelae. The prognosis of a fetus is influenced by the extent of prematurity and fetal weight. Clinical care is individually adjusted. In literature, survival rates vary and studies often only include live‐born neonates with missing rates of antenatal death. This systematic review aims to summarize the literature on mortality and morbidity. Material and methods A broad literature search was conducted in OVID MEDLINE from 2000 to 26 April 2019 to identify studies on fetal growth restriction and perinatal death. Studies were excluded when all included children were born before 2000 because (neonatal) health care has considerably improved since this period. Studies were included that described fetal growth restriction diagnosed before 32 weeks of gestation and antenatal mortality and neonatal mortality and/or morbidity as outcome. Quality of evidence was rated with the GRADE instrument. Results Of the 2604 publications identified, 25 studies, reporting 2895 pregnancies, were included in the systematic review. Overall risk of bias in most studies was judged as low. The quality of evidence was generally rated as very low to moderate, except for 3 large well‐designed randomized controlled trials. When combining all data on mortality, in 355 of 2895 pregnancies (12%) the fetus died antenatally, 192 died in the neonatal period (8% of live‐born neonates) and 2347 (81% of all pregnancies) children survived. Of the neonatal morbidities recorded, respiratory distress syndrome (34% of the live‐born neonates), retinopathy of prematurity (13%) and sepsis (30%) were most common. Of 476 children that underwent neurodevelopmental assessment, 58 (12% of surviving children, 9% of all pregnancies) suffered from cognitive impairment and/or cerebral palsy. Conclusions When combining the data of 25 included studies, survival in fetal growth restriction pregnancies, diagnosed before 32 weeks of gestation, was 81%. Neurodevelopmental impairment was assessed in a minority of surviving children. Individual prognostic counseling on the basis of these results is hampered by differences in patient and pregnancy characteristics within the included patient groups.

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.

Aim: This study determined whether cognitive outcomes differed between very preterm (VPT) and extremely preterm (EPT) children who were monolingual or multilingual when they reached the corrected ages of two and five years. Methods: The data were collected at the Emma Children's Hospital, Amsterdam, The Netherlands, as part of our national neonatal follow-up programme and comprised 325 VPT/EPT children born between January 1, 2007 and January 1, 2012. The study used the Third Editions of the Bayley Scales of Infant and Toddler Development and the Wechsler Preschool and Primary Scale of Intelligence. Results: We compared 234 monolingual children, 65 multilingual children who spoke Dutch and at least one foreign language at home and 26 multilingual children who didn't speak Dutch at home. The best performers on the cognitive scale at two years of age and the verbal subscales at five years of age were the monolingual children, followed by the children who spoke Dutch and at least one foreign language at home, then the children who only spoke foreign languages at home. Conclusion: In our study cohort from The Netherlands, multilingualism lowered the cognitive and verbal outcomes of VPT/EPT children at the corrected ages of two and five years.

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.

Objective: The objective of this study is to explore developmental outcomes at five years after early-onset fetal growth restriction (FGR). Study design: Retrospective data analysis of prospective follow-up of patients of three Dutch centres, who participated in a twenty centre European randomized controlled trial on timing of delivery in early-onset FGR. Developmental outcome of very preterm infants born after extreme FGR is assessed at (corrected) age of five. Results: Seventy-four very preterm FGR children underwent follow-up at the age of five. Mean gestational age at birth was 30 weeks and birth weight was 910 g, 7% had a Bayley score

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.

Background Perinatally chikungunya infected neonates have been reported to have high rates of post-infection neurologic sequelae, mainly cognitive problems. In older children and adults chikungunya does not appear to have sequelae, but data on postnatally infected infants are lacking. Methods We performed a prospective, non-controlled, observational study of infants infected before the age of 6 months with a severe chikungunya infection during the 2014–2015 epidemic in Curaçao, Dutch Antilles. Two years post-infection cognitive and motor - (BSID-III) and social emotional assessments (ITSEA) were performed. Results Of twenty-two infected infants, two died and two were lost to follow up. Eighteen children were seen at follow-up and included in the current study. Of these, 13 (72%) had abnormal scores on the BSID-III (cognitive/motor) or ITSEA. Conclusion In the first study aimed at postnatally infected infants, using an uncontrolled design, we observed a very high percentage of developmental problems. Further studies are needed to assess causality, however until these data are available preventive measure during outbreaks should also include young infants. Those that have been infected in early infancy should receive follow up.