Minimally invasive surgical approach in children treated for oesophageal atresia is associated with attention problems at school age: a prospective cohort study.

The long-term neurodevelopment of children born with oesophageal atresia (OA) is unclear. Therefore, we assessed the neurocognitive domains and their predictors. Patients born with OA between February 2006 and December 2014, who were routinely seen at eight years as part of a structured prospective longitudinal follow-up program, were included. Main outcome measures were need for school support, performance in various neurocognitive domains and potential predictors of neurocognitive problems. We analysed data of 65 children with a mean (SD) age of 8.1 (0.2) years, of whom 89% with OA type C. Thirty-five (54%) surgical corrections were minimally invasive; the median (interquartile range) duration of exposure to anaesthetics in the first 24 months was 398 (296 - 710) minutes. Forty-four (68%) attended regular education without extra support and intelligence was within normal range (99-108). More than 50% had z-scores ≤ -2 on one or more neurocognitive domains, of which attention was the most frequently affected domain. The speed on the sustained attention task was significantly below normal (z-score -1.48 (2.12), p < .001), as was fluctuation of sustained attention (z-score -3.19 (3.80), p < .001). The minimally invasive approach and a lower socio-economic status (both p = 0.006) proved significant predictors for sustained attention problems in multivariable analyses.  Conclusion: Children who undergo minimally invasive surgery for OA correction are at risk for sustained attention problems at school age. Future studies unravelling the effects of perioperative events on neurodevelopment should lead to optimal surgical, anaesthesiological, and intensive care management in the neonatal period. What is Known: • School-aged children born with oesophageal atresia have normal intelligence but problems with sustained attention at eight years. What is New: • Oesophageal atresia patients, who undergo minimally invasive surgery or who have a background of lower socioeconomic status are at serious risk for sustained attention problems at school age. • Moreover, those who have been intubated for a longer period are at risk for stronger fluctuations in sustained attention.

Cardiopulmonary Morbidity in Adults Born With Congenital Diaphragmatic Hernia.

OBJECTIVES: Studies concerning cardiopulmonary outcomes of adults born with congenital diaphragmatic hernia (CDH) are sparse. Moreover, they don't include participants who have been treated with extracorporeal membrane oxygenation (ECMO) during the neonatal period. This study evaluated the cardiopulmonary morbidities in young adults born with CDH. METHODS: We assessed 68 participants between the ages of 18 and 30 years. The assessment included auxology assessment, lung function tests, pulmonary imaging, cardiopulmonary exercise testing, and echocardiography. RESULTS: Lung function parameters in the overall group were significantly worse than normal values. Mean (SD) scores postbronchodilator forced expiratory volume in 1 second were -2.91 (1.38) in the ECMO-treated and -1.20 (1.53) in the non-ECMO-treated participants. Chest computed tomography scans showed mild to moderate abnormal lung structure in all ECMO-treated participants, and to a lesser extent in non-ECMO treated participants. A recurrent diaphragmatic defect was observed in 77% of the ECMO-treated group and in 43% of the non-ECMO-treated group. Except for 2 cases with acute symptoms, no clinical problems were noted in cases of recurrence. Cardiopulmonary exercise testing revealed mean (SD) percentage predicted peak oxygen consumption per kilogram of 73 (14)% and 88 (16)% in ECMO-treated and non-ECMO-treated participants, respectively. The mean (SD) workload was normal in the non-ECMO-treated group (111 [25]% predicted); in the ECMO-treated group, it was 89 (23)%. Cardiac evaluation at rest revealed no signs of pulmonary hypertension. CONCLUSIONS: In young adults who survived treatment of CDH, significant pulmonary morbidity, reduced exercise capacity, and frequent hernia recurrence should be anticipated. Lifelong follow-up care, with the emphasis on prevention of further decline, is to be recommended.

Long-term neurodevelopment in children with resected congenital lung abnormalities.

To determine whether children who underwent resection of a congenital lung abnormality (CLA) are at higher risk for neurodevelopmental impairments than peers in the general population. The study population consisted of children born between 1999-2018 who underwent resection of a symptomatic CLA. Neurocognitive development (intelligence, memory, attention, visuospatial processing, executive functioning) and motor function of this population are monitored through our structured, prospective longitudinal follow-up program at the ages of 30 months, 5, 8, and 12 years. We compared study population scores with Dutch norm values using one-sample t-tests and one-sample binominal proportion tests. Forty-seven children were analyzed. The 8-year-olds showed significant impairments in sustained attention through the Dot Cancellation Test (mean z-scores -2.4; [-4.1; -0.8], p = 0.006 and -7.1; [-12.8; -1.4], p = 0.02 for execution speed and fluctuations respectively). Visuospatial memory was impaired at 8 years, though only in 1 out of 3 assessment tools (Rey Complex Figure Test z-scores (-1.0; [-1.5; -0.5], p < 0.001). Further neurocognitive outcomes were unimpaired at all tested ages. Regarding motor function outcomes, mean z-scores of total motor functioning were unimpaired across assessed ages. However, at 8 years, significantly more children than expected had definite motor problems (18% vs 5%, 95% CI [0.052; 0.403], p = 0.022).   Conclusion: This evaluation reveals impairment in some subtests of sustained attention, visuospatial memory and motor development. However, globally, normal neurodevelopmental outcomes were found throughout childhood. We recommend testing for neurodevelopmental impairments in children who underwent surgery for CLA only if associated morbidities are present or if caregivers express doubts about their daily functioning. What is Known: • In general, surgically managed CLA cases seldom suffer from long-term surgery-related morbidity and show favorable lung function. What is New: • Long-term neurocognitive and motor function outcome appear unimpaired within surgically managed CLA cases. We recommend testing for neurodevelopmental impairments in children who underwent surgery for CLA only if associated morbidities are present or if caregivers express doubts about their daily functioning.

Longitudinal Health Status and Quality of Life in Congenital Diaphragmatic Hernia.

OBJECTIVES: To longitudinally evaluate self-reported health status (HS) and quality of life (QoL) in 8- and 12-year-old survivors of congenital diaphragmatic hernia (CDH). We hypothesized that HS would improve with age-as associated health problems tend to decline-whereas QoL would decrease, as the children start to compare themselves with peers. METHODS: Self-reported HS and QoL of 133 children born between 1999 and 2013 who had joined our standardized follow-up program were routinely assessed at the ages of 8 and 12 with generic, internationally validated, standardized instruments. Longitudinal evaluation of total and subscale scores was performed using general linear model analyses. In addition, we compared these scores to sex- and age-specific normative data. RESULTS: Between ages 8 and 12, boys born with CDH perceived a decline in HS (mean difference -7.15, P < .001). Self-reported QoL did not change over time in both boys and girls. At both ages, HS was significantly lower than that of healthy peers (effect size = 0.71, P = .001 for boys, and effect size = 0.69, P = .003 for girls), whereas differences in QoL were small. CONCLUSIONS: Children born with CDH are at risk for declining HS between 8 and 12 years, but not QoL, compared with healthy peers. Given that children born with CDH tend to grow into deficits, our findings highlight the need for continued somatic and psychological assessments in adolescent and adult CDH survivors.

Neuropsychological outcome in survivors of congenital diaphragmatic hernia at 5 years of age, what does it tell?

Previous studies have frequently reported neurocognitive deficits in children born with congenital diaphragmatic hernia (CDH) at school age, which may contribute to academic difficulties. Yet, age at onset of these deficits is currently unknown. We evaluated neurocognitive skills with possible determinants in preschool children born with CDH. Eligible 5-year-old children born with CDH (2010-2015) who participated in our prospective structural follow-up program were included. We used the WPPSI-III to assess intelligence, subtests of the Kaufman-ABC for memory, and NEPSY-II to assess inhibition and attention. We included 63 children. Their test scores generally were within or significantly above normal range: total IQ = 103.4 (15.7) (p = 0.13); Verbal memory = 10.2 (2.8) (p = 0.61); Visuospatial memory = 11.4 (2.6) (p < 0.01); Inhibition = 10.5 (2.2), (p = 0.10). In univariable analyses, length of ICU-stay was negatively associated with IQ, and maximum vasoactive inotropic score and open repair were negatively associated with inhibition skills. In multivariable regression analysis, the latter association remained (B = 5.52, p = 0.04 (CI 0.32-10.72)).   Conclusions: In these tested 5-year-old children born with CDH, neuropsychological outcome was normal on average. While problems in 8-year-olds are common, we did not detect onset of these problems at age 5. Yet, we cannot rule out that this cohort had a relatively mild level of disease severity; therefore, conclusions should be interpreted with caution. However, given the growing-into-deficit hypothesis, meaning that deviant brain development in early life is revealed once higher cognitive brain functions are demanded, follow-up should be conducted up to school age, and preferably beyond. What is Known: • Children born with CDH are at risk for academic difficulties at school age. • Whether these difficulties can be detected already before school age is unknown. What is New: • At age 5 years, intelligence, inhibition, attention, and memory skills were all within normal range, or even above, in children with CDH. This is supportive of the growing-into-deficit hypothesis in this patient population. • Those who underwent open surgical correction had poorer inhibition skills than those who were corrected with minimal access surgery.

5q35 duplication syndrome: Narrowing the critical region on the distal side and further evidence of intrafamilial variability and expression.

The key features of patients with a microduplication 5q35.2q35.3 (including the NSD1 gene) are short stature, microcephaly, mild developmental delay, behavioral problems, digital anomalies and congenital anomalies of internal organs. This core phenotype can be viewed as the reversed phenotype of Sotos syndrome, which is caused by a microdeletion in the same chromosomal region or a pathogenic variant in the NSD1 gene, and includes tall stature and macrocephaly, developmental delay, and epilepsy. Here, we report on a patient and his mother, both with a 5q35.2q35.3 duplication, adding a fifth family to the recently published overview of 39 patients of Quintero-Rivera et al. Our patient had several congenital anomalies, intrauterine growth restriction with a persisting short stature, while his mother was only mildly affected with decreased growth parameters. In addition, he had hemophagogocytic lymphohistiocytosis (HLH) triggered by Haemophilus influenzae and was recently diagnosed with Ewing sarcoma. Our cases carry the smallest duplication published (ca 332 kb, arr[hg19] 5q35.2q35.3(176493106-176824785)x3) further narrowing the distal side of the critical region of the 5q35.2q35.3 duplication. Besides broadening the clinical phenotypic spectrum, our report indicates that the 5q35.2q35.3 microduplication also shows a large intra-familial variability and expression.

Parent-Reported Perceived Cognitive Functioning Identifies Cognitive Problems in Children Who Survived Neonatal Critical Illness.

Children with congenital anatomical foregut anomalies and children treated with neonatal extracorporeal membrane oxygenation (ECMO) are at risk for neurocognitive morbidities. We evaluated the association between the parent-reported pediatric perceived cognitive functioning (PedsPCF) questionnaire and the parent-reported behavior rating inventory of executive function (BRIEF) as well as neuropsychological assessments (NPA). We included 8-, 12- and 17-year-old participants who had joined a prospective follow-up program between 2017 and 2019. Self- and parental proxy-reported PedsPCF and proxy-reported BRIEF scores and their mutual association were evaluated. In total, 168 participants were included. Self- and proxy-reported PedsPCF scores were significantly below normal (mean (SD) z-score: −0.35 (0.88), p < 0.001; −0.36 (1.06), p < 0.001, respectively). Total BRIEF scores were significantly above normal (mean (SD) z-score 0.33 (0.98), p < 0.001). Proxy-reported PedsPCF scores and the Metacognition Index subscores of the BRIEF correlated strongly (τ = 0.551, p < 0.001). Self-reported PedsPCF scores were not associated with NPA test scores. Proxy-reported PedsPCF scores were positively associated with multiple NPA test scores, especially intelligence (R2 = 0.141). The proxy-reported PedsPCF revealed cognitive problems more often than the BRIEF in school-aged children who had survived neonatal critical illness. The proxy-reported PedsPCF may support clinical decision-making regarding the need for extensive neuropsychological assessments.

Persisting Motor Function Problems in School-Aged Survivors of Congenital Diaphragmatic Hernia.

Background and Objectives: Children born with congenital diaphragmatic hernia (CDH) and treated with extracorporeal membrane oxygenation (ECMO), are at risk for motor function impairment during childhood. We hypothesized that all children born with CDH are at risk for persistent motor function impairment, irrespective of ECMO-treatment. We longitudinally assessed these children's motor function. Methods: Children with CDH with and without ECMO-treatment, born 1999-2007, who joined our structural prospective follow-up program were assessed with the Movement Assessment Battery for Children (M-ABC) at 5, 8, 12 years. Z-scores were used in a general linear model for longitudinal analysis. Results: We included 55 children, of whom 25 had been treated with ECMO. Forty-three (78%) were evaluated at three ages. Estimated mean (95% CI) z-scores from the general linear model were -0.67 (-0.96 to -0.39) at 5 years of age, -0.35 (-0.65 to -0.05) at 8 years, and -0.46 (-0.76 to -0.17) at 12 years. The 5- and 8-years scores differed significantly (p = 0.02). Motor development was significantly below the norm in non-ECMO treated patients at five years; -0.44 (-0.83 to -0.05), and at all ages in the ECMO-treated-patients: -0.90 (-1.32 to -0.49), -0.45 (-0.90 to -0.02) and -0.75 (-1.2 to -0.34) at 5, 8, and 12 years, respectively. Length of hospital stay was negatively associated with estimated total z-score M-ABC (p = 0.004 multivariate analysis). Conclusion: School-age children born with CDH are at risk for motor function impairment, which persists in those who received ECMO-treatment. Especially for them long-term follow up is recommended.

Longitudinal Health Status and Quality of Life After Esophageal Atresia Repair.

OBJECTIVES: To longitudinally evaluate self-reported and proxy-reported health status (HS) and quality of life (QoL) of school-aged children born with esophageal atresia (EA). METHODS: We obtained Pediatric Quality of Life Inventory (HS) and DUX-25 (QoL) questionnaires from children born with EA between 1999 and 2011 at 8 and/or 12 years old. Children completed self-reports during neuropsychological assessments in a prospective longitudinal follow-up program. Parents filled out proxy-reports at home. Total and subscale scores were evaluated longitudinally and compared with sex-specific reference norms. RESULTS: In total, 110 participants (62% boys) were included. Self-reported HS improved significantly between 8 and 12 years for both boys (mean difference [md] 4.35, effect size [ES] 0.54, P = 0.009) and girls (md 3.26, ES 0.63, P = 0.004). Proxy-reported HS tended to improve over time, while self-reported and proxy-reported QoL tended to decline. Self-reported HS at 8 years was below normal for both boys (md -5.44, ES -0.35, P < 0.001) and girls (md -7.61, ES -0.32, P < 0.001). Girls' self-reported QoL was below normal at 8 (md -5.00, ES -0.18, P = 0.019) and 12 years (md -10.50, ES -0.26, P = 0.001). Parents reported normal HS at both ages, whereas they rated the QoL of their daughters below normal at 12 years (md -10.00, ES -0.16, P = 0.022). All above results are total scores. CONCLUSIONS: Self-reported and proxy-reported HS of children with EA improved between 8 and 12 years, while their QoL tended to decline. We recommend to consider HS and QoL as two separate concepts and to measure both simultaneously and longitudinally when evaluating the burden of disease.

Patient-Reported Outcome Measures and Clinical Outcomes in Children with Foregut Anomalies.

Increasing numbers of children and adults with chronic disease status highlight the need for a value-based healthcare system. Patient-reported outcome measures (PROMs) are essential to value-based healthcare, yet it remains unclear how they relate to clinical outcomes such as health and daily functioning. We aimed to assess the added value of self-reported PROMs for health status (HS) and quality of life (QoL) in the long-term follow-up of children with foregut anomalies. We evaluated data of PROMs for HS and/or QoL among eight-year-olds born with congenital diaphragmatic hernia (CDH), esophageal atresia (EA), or congenital lung malformations (CLM), collected within the infrastructure of a multidisciplinary, longitudinal follow-up program. Clinical outcomes were categorized into different outcome domains, and their relationships with self-reported HS and QoL were assessed through multivariable linear regression analyses. A total of 220 children completed HS and/or QoL self-reports. In children with CDH and EA, lower cognition was significantly associated with lower self-reported HS. Due to the low number of cases, multivariable linear regression analysis was not possible in children with CLM. HS, QoL, and clinical outcomes represent different aspects of a child's wellbeing and should be measured simultaneously to facilitate a more holistic approach to clinical decision making.

An Accidental Repetitive 10-Fold Overdose of Sildenafil in a Young Infant with Pulmonary Hypertension.

Sildenafil is a selective phosphodiesterase type-5 inhibitor that is increasingly used to treat pulmonary hypertension (PH) in neonates. Only little is known about the relation between the dose of sildenafil, plasma concentrations, and the degree of toxicity. Here, we present a young infant with congenital diaphragmatic hernia and PH who received an unintentional 10-fold overdose of oral sildenafil for 6 consecutive days. This overdose, compared to the therapeutic dose, resulted in increased plasma concentrations of sildenafil from 42 to 521 mcg/L and desmethylsildenafil from 81 to 393 mcg/L. However, the high exposure only led to diarrhea, without any other serious adverse events. This case describes the mild symptoms upon an overdose with the role of therapeutic drug monitoring to monitor exposure in relation to symptoms and therewith support clinical decision-making.

Congenital diaphragmatic hernia and exercise capacity, a longitudinal evaluation.

OBJECTIVE: Children with congenital diaphragmatic hernia (CDH) suffer from long-term pulmonary morbidity. Longitudinal data of exercise capacity in these children are lacking. We hypothesized that exercise capacity would be impaired in children with CDH and deteriorates over time. We evaluated exercise capacity and its determinants in CDH patients longitudinally until 12 years of age. DESIGN: Prospective longitudinal follow-up study in tertiary university hospital. PATIENTS: One hundred and fourteen children with CDH born between 1999 and 2012. METHODS: Exercise capacity was evaluated using the Bruce treadmill-protocol at the ages of 5, 8, and 12 years. Primary outcome parameter was standard deviation score (SDS) of maximal endurance time. Data were analyzed by using linear mixed models. RESULTS: A total of 107 children (30 treated with extracorporeal membrane oxygenation [ECMO]) performed 191 reliable exercise tests. At ages 5, 8, and 12 years, the mean (95%CI) SDS endurance time was -0.44 (-0.65 to -0.24); -1.01 (-1.23 to -0.78); -1.10 (-1.40 to -0.80), respectively, all less than zero (P < 0.001). Exercise capacity declined significantly over time irrespective of ECMO-treatment (5-12 years: non-ECMO P = 0.015; ECMO P = 0.006). Duration of initial hospital stay and diffusion capacity corrected for alveolar volume were associated with SDS endurance time (P < 0.001 and P = 0.039). CONCLUSIONS: In CDH patients exercise capacity deteriorates between 5 and 12 years of age, irrespective of ECMO-treatment. CDH patients may benefit from long-term assessments of exercise capacity with timely intervention.

The Importance of Parental Connectedness and Relationships With Healthcare Professionals in End-of-Life Care in the PICU.

OBJECTIVES: Support from healthcare professionals in a PICU is highly valuable for parents of dying children. The way they care for the patients and their families affects the parents' initial mourning process. This study explores what interaction with hospital staff is meaningful to parents in existential distress when their child is dying in the PICU. DESIGN: Qualitative interview study. SETTING: Level 3 PICU in the Erasmus University Medical Center-Sophia Children's Hospital, Rotterdam, and the Netherlands. SUBJECTS: Thirty-six parents of 20 children who had died in this unit 5 years previously. INTERVENTIONS: Parents participated in audio-recorded interviews in their own homes. The interviews were transcribed and analyzed using qualitative methods. MEASUREMENTS AND MAIN RESULTS: Parents' narratives of their child's end-of-life stage in the PICU bespeak experiences of estrangement, emotional distancing, and loneliness. Significant moments shared with hospital staff that remained valuable even after 5 years primarily involved personal connectedness, reflected in frequent informational updates, personal commitment of professionals, and interpersonal contact with doctors and nurses. CONCLUSIONS: Parents whose children died in the PICU value personal connectedness to doctors and nurses when coping with existential distress. Medical and nursing training programs should raise awareness of parents' need for contact in all interactions but especially in times of crisis and apprehension.

Assessment and significance of long-term outcomes in pediatric surgery.

Treatment modalities for newborns with anatomical congenital anomalies have greatly improved over the past decades, with a concomitant increase in survival. This review will briefly discuss specific long-term outcomes to illustrate, which domains deserve to be considered in long-term follow-up of patients with anatomical congenital anomalies. Apart from having disease-specific morbidities these children are at risk for impaired neurodevelopmental problems and school failure, which may affect participation in society in later life. There is every reason to offer them long-term multidisciplinary follow-up programs. We further provide an overview of the methodology of long-term follow-up, its significance and discuss ways to improve care for newborns with anatomical congenital anomalies from childhood into adulthood. Future initiatives should focus on transition of care, risk stratification, and multicenter collaboration.

Congenital Diaphragmatic Hernia and Growth to 12 Years.

OBJECTIVES: Growth problems are reported in patients with congenital diaphragmatic hernia during the first years of life. However, it is unknown if poor growth persists during childhood. We therefore evaluated growth of patients longitudinally until 12 years of age. METHODS: This prospective study included 172 patients (43 treated with extracorporeal membrane oxygenation [ECMO]) born from 1999 to 2014. Z scores of height-for-age (HFA), weight-for-height, and distance-to-target height were calculated at 6 months of age and at 1, 2, 5, 8, and 12 years of age. Data were analyzed by using general linear models. RESULTS: At 1 year of age, the mean weight-for-height z score had declined in ECMO (-1.30, 95% confidence interval: -1.62 to -0.97) and non-ECMO patients (-0.72, 95% confidence interval: -0.91 to -0.54; P < .05). Thereafter in ECMO patients, the mean HFA z score deteriorated between 1 (-0.43, 95% confidence interval: -0.73 to -0.13) and 5 years of age (-1.08, 95% confidence interval: -1.38 to -0.78; P < .01). In non-ECMO patients, the mean HFA z score deteriorated between 2 (-0.35, 95% confidence interval: -0.53 to -0.17) and 5 years of age (-0.56, 95% confidence interval: -0.75 to -0.37; P = .002). At 12 years of age, the mean HFA z score was still less than the norm in both groups: ECMO (-0.67, 95% confidence interval: -1.01 to -0.33) versus non-ECMO (-0.49, 95% confidence interval: -0.77 to -0.20; P < .01). Adjusting for target height improved the mean height z scores but did not bring them to normal range. CONCLUSIONS: Poor linear growth persisted at 12 years of age. The pattern of early deterioration of weight gain followed by a decline in linear growth is suggestive of inadequate nutrition during infancy. Therefore, nutritional assessment and intervention should be started early and should be continued during childhood.

Longitudinal evaluation of growth in oesophageal atresia patients up to 12†years.

OBJECTIVE: Previous studies reported diminished growth after oesophageal atresia (OA) repair. We evaluated long-term follow-up data on growth. METHODS: Longitudinal cohort study up to 12 years. Patients with OA, born 1999-2013, who participated in a longitudinal follow-up programme were included. Children with genetic syndromes associated with growth disorders were excluded. SD scores (SDS) for height-for-age (HFA), weight-for-height (WFH) and distance-to-target-height were calculated for routine visits (0.5/1/2/5/8/12 years). Linear mixed models were used to estimate SDS until 12 years of age and to evaluate explanatory factors for growth. RESULTS: We included 126/155 children (32% prematurely born, 20% small for gestational age), 32 reached the age of 12 years. Fundoplication surgery was performed in 24%. SDS-HFA was below normal up to 8 years but improved over these years (mean (SE) -0.48 (0.09), -0.31 (0.09) and -0.20 (0.13) at 0.5, 8 and 12 years). Scores improved after correction for target height (mean (SE) -0.29 (0.10), -0.17 (0.09) and -0.10 (0.14) at 0.5, 8 and 12 years). SDS-WFH was below normal from age 1-5 years (mean (SE) -0.53 (0.09), -0.24 (0.09) and 0.03 (0.14) at 1, 5 and 12 years). Low birth weight and fundoplication surgery were negatively associated with growth. CONCLUSIONS: The growth of patients with OA was below the reference norm during the first years of life, but normalised at 12 years. Large longitudinal cohort studies should evaluate if normal growth persists into adolescence. Early nutritional assessment with timely dietary intervention should be considered especially in those with low birth weight or following fundoplication surgery.

Neuropsychological Follow-up After Neonatal ECMO.

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.

Growing Up After Critical Illness: Verbal, Visual-Spatial, and Working Memory Problems in Neonatal Extracorporeal Membrane Oxygenation Survivors.

OBJECTIVES: To assess neuropsychologic outcome in 17- and 18-year-old neonatal extracorporeal membrane oxygenation survivors. DESIGN: A prospective longitudinal follow-up study. SETTING: Follow-up program at the Erasmus MC-Sophia Children's Hospital in Rotterdam, The Netherlands. PATIENTS: Thirty adolescents 17 or 18 years old, treated between 1991 and 1997, underwent neuropsychologic assessment. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Attention, memory, executive functioning, visual-spatial functions, social-emotional functioning, and behavior were assessed with validated instruments, and data were compared with reference data. Included predictors for analysis of adverse outcome were diagnosis, age at start extracorporeal membrane oxygenation, convulsions, and use of antiepileptics. Adolescents' performance (expressed as mean [SD] z score) was significantly lower than the norm on short-term and long-term verbal memory (z score = -1.40 [1.58], p = 0.016; z score = -1.54 [1.67], p = 0.010, respectively), visual-spatial memory (z score = -1.65 [1.37], p = 0.008; z score = -1.70 [1.23], p = 0.008, respectively), and working memory (32% vs 9% in the norm population). Parents reported more problems for their children regarding organization of materials (z score = -0.60 [0.90]; p = 0.03) and behavior evaluation (z score = -0.53 [0.88]; p = 0.05) on a questionnaire. Patients reported more withdrawn/depressed behavior (z score = -0.47 [0.54]; p = 0.02), somatic complaints (z score = -0.43 [0.48]; p = 0.03), and social problems (z score = -0.41 [0.46]; p = 0.04). Patients reported more positive feelings of self-esteem and an average health status. CONCLUSIONS: Adolescents treated with neonatal extracorporeal membrane oxygenation are at risk of verbal, visual-spatial, and working memory problems. Future research should focus on 1) the longitudinal outcome of specific neuropsychologic skills in adolescence and adulthood; 2) identifying risk factors of neuropsychologic dysfunction; 3) evaluating to what extent "severity of illness" is responsible for acquired brain injury; and 4) effects of timely cognitive rehabilitation.

Growth and development after oesophageal atresia surgery: Need for long-term multidisciplinary follow-up.

Survival rates in oesophageal atresia patients have reached over 90%. In long-term follow-up studies the focus has shifted from purely surgical or gastrointestinal evaluation to a multidisciplinary approach. We reviewed the literature on the long-term morbidity of these patients and discuss mainly issues of physical growth and neurodevelopment. We conclude that growth problems - both stunting and wasting - are frequently seen, but that sufficient longitudinal data are lacking. Therefore, it is unclear whether catch-up growth into adolescence and adulthood occurs. Data on determinants of growth retardation are also lacking in current literature. Studies on neurodevelopment beyond preschool age are scarce but oesophageal atresia patients seem at risk for academic problems and motor function delay. Many factors contribute to the susceptibility to growth and development problems and we propose a multidisciplinary follow-up schedule into adulthood future care which may help improve quality of life.

CKD and hypertension during long-term follow-up in children and adolescents previously treated with extracorporeal membrane oxygenation.

BACKGROUND AND OBJECTIVES: Many children receiving extracorporeal membrane oxygenation develop AKI. If AKI leads to permanent nephron loss, it may increase the risk of developing CKD. The prevalence of CKD and hypertension and its predictive factors during long-term follow-up of children and adolescents previously treated with neonatal extracorporeal membrane oxygenation were determined. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Between November of 2010 and February of 2014, neonatal survivors of extracorporeal membrane oxygenation who visited the prospective follow-up program at 1, 2, 5, 8, 12, and 18 years of age were screened for CKD and hypertension (BP≥95th percentile of reference values). CKD was suspected in children with either an eGFR<90 ml/min per 1.73 m(2) or proteinuria (urinary protein-to-creatinine ratio >0.50 for children ages ≤24 months and >0.20 at >24 months). The RIFLE classification (risk, injury, or failure as 150%, 200%, or 300% of serum creatinine reference values) was used to define AKI during extracorporeal membrane oxygenation without preemptive hemofiltration. RESULTS: Median follow-up of 169 screened participants was 8.2 years (interquartile range=5.2-12.1 years). Nine children had a lower eGFR, but all rates were >60 ml/min per 1.73 m(2). Proteinuria was observed in 20 children (median=0.26 mg protein/mg creatinine; interquartile range=0.23-0.32 mg protein/mg creatinine), and 32 children had hypertension. Only history of AKI was associated with CKD (P=0.004). Children with RIFLE scores injury and failure had 4.3 times higher odds of CKD signs or hypertension than those without AKI (95% confidence interval, 1.6 to 12.1; P=0.004). CONCLUSIONS: Altogether, 54 participants (32%) had at least one sign of CKD and/or hypertension. However, most values were marginally abnormal, with no immediate consequences for clinical care. Nevertheless, a prevalence of 32% clearly indicates that survivors of neonatal extracorporeal membrane oxygenation, especially those with AKI, are at risk of a more rapid decline of kidney function with increasing age. Therefore, screening for CKD development in adulthood is recommended.